MX2008007019A

MX2008007019A - Fused heterocyclic compound

Info

Publication number: MX2008007019A
Application number: MX/A/2008/007019A
Authority: MX
Inventors: Banno Hiroshi; Miwa Kazuhiro; Seto Masaki; Ishikawa Yomoyasu; Kawakita Youichi
Original assignee: Banno Hiroshi; Ishikawa Tomoyasu; Kawakita Youichi; Miwa Kazuhiro; Seto Masaki; Takeda Pharmaceutical Company Limited
Priority date: 2005-12-02
Filing date: 2008-05-30
Publication date: 2008-09-02

Abstract

The present invention provides a compound represented by the formula:wherein R1ais a hydrogen atom, R2ais a C1-6alkyl group substituted by a group represented by-NR6a-CO-(CH2)n-SO2-optionally halogenated C1-4alkyl wherein n is an integer of 1 to 4, R6ais a hydrogen atom or a C1-4alkyl group, and -(CH2)n- is optionally substituted by C1-4alkyl, R3ais a hydrogen atom or a C1-6alkyl group, R4ais a halogen atom or a C1-6alkyl group, R5ais a halogen atom or a C1-6alkyl group, and Xais a hydrogen atom or a halogen atom, or a salt thereof. The compound of the present invention has a superior tyrosine kinase inhibitory action, is highly safe, and is sufficiently satisfactory as a pharmaceutical product.

Description

FUSED HETEROCICLIC COMPOUND FIELD OF THE INVENTION The present invention relates to a fused pyrimidine compound with inhibitory activity of growth factor tyrosine kinase receptor, which is useful for the prevention or treatment of cancer, one of its production methods its use . BACKGROUND OF THE INVENTION The cell growth factor and growth factor receptor gene is called a protooncogene and plays a key role in human tumor pathology. The family of epithelial cell growth factor receptors (erbB) includes EGFR, HER2, HER3 and HER4, which are tyrosine kinases of the type I receptor. These erbB families are expressed in various cell groups and play a role in the control of growth and cell differentiation and control of the suppression of cell death (suppression of apoptosis). For example, it is empirically known that the high expression of EGFR and HER2, and the homeostatic activation of receptors transforms the cells. It is also known that elevated expression and simultaneous expression of each of these receptors are factors of poor prognosis in various cancer patients. These receptors bind to many peptide ligands such as EGF, TGFa and the like, and the binding of Ref. 191841 the ligands favor homo- or heterodimerization of the receptors. This induces kinase activity by autophosphorylation or transphosphorylation of the receptors, and causes activation of the downstream signaling pathway (MAPK, Akt) through a protein bound to a particular phosphorylated tyrosine residue. This is the mechanism of receptor activity of the aforementioned cell growth, differentiation, suppression of cell death and the like, which are considered responsible for the high expression of receptors in cancer and malignant degeneration of cancer due to the topical increase in the concentration of ligand . Many malignancies are associated with elevated expression of EGFR or HER2. For example, there may be mentioned breast cancer (20-30%), ovarian cancer (20-40%), non-small cell lung cancer (30-60%), colorectal cancer (40-80%), cancer of prostate (10-60%), bladder cancer (30-60%), kidney cancer (20-40%) and the like. In addition, receptor expression and prognosis are correlated, and receptor expression is a poor prognostic factor in breast cancer, non-small cell lung cancer and the like. In recent years, the clinical use of a humanized anti-HER2 antibody (Trastuzumab) against HER2 with high expression in breast cancer, the clinical study of antibody Anti-EGFR and clinical studies of several inhibitors of low molecular weight enzyme receptors have shown a potential of these drugs against HER2 or EGFR for therapeutic drugs against cancer. Although these drugs show an inhibitory action of tumor growth in clinical and non-clinical studies, it is known that they induce the inhibition of the activity of enzyme receptors and the suppression of the downstream signaling path. Accordingly, an EGFR or HER2 kinase inhibitor compound, or inhibitor of EGFR or HER2 kinase activation is effective as a therapeutic drug against cancer. As a compound that inhibits the type of receptor tyrosine kinases represented by HER2 / EGFR kinase, fused heterocyclic compounds are known (eg W097 / 13771, WO98 / 02437, WO00 / 44728), quinazoline derivatives (for example, WO02 / 02552). , WO01 / 98277, WO03 / 049740, WO03 / 050108), thienopyrimidine derivatives (e.g., WO03 / 053446), aromatic azole derivatives (e.g., WO98 / 03648, WO01 / 77107, WO03 / 031442) and the like; however, until now there is no inhibitory substance of HER2 kinase that has been marketed as a therapeutic drug against cancer. Regarding the pyrrolo [3, 2-d] pyrimidine derivatives, the following compounds are known as compounds with cell growth inhibitory activity (Khim.-Farm.

Zh., 1982, 16, 1338-1343; Collect. Czech Chem. Commun As the compound with tyrosine kinase receptor inhibitory activity, the following pyrrolo [3,2-d] pyrimidine derivative is known (WO96 / 40142, W098 / 23613).

In addition, with respect to pyrazolo [, 3-d] pyrimidine derivatives, 3, 5, 7-trisubstituted pyrazolo [, 3-d] pyrimidine derivatives are known as compounds with inhibitory action of CDK, an inhibitory action of cell growth is known and / or an action inducing apoptosis (EP-A-1348707), and 3-isopropylpyrazolo [4, 3-d] pyrimidine derivatives are known as compounds with inhibitory activity of CDK1 / cyclin B (Bioorganic & Medicinal Chemistry Letters, 2003, 13, 2989-2992). Further, the synthesis of 3-methylpyrazolo [4, 3-d] pyrimidine derivatives (The Journal of Organic Chemistry, 1956, 21, 833-836) has been reported.

BRIEF DESCRIPTION OF THE INVENTION The present invention is directed to providing a compound with superior inhibitory action of tyrosine kinase, of low toxicity and highly safe as a pharmaceutical product. The present inventors have conducted intensive studies in an attempt to solve the aforementioned problems and found that the compounds represented by the following formulas (Ia) - (Ih) and their salts have a superior inhibitory action of tyrosine kinase. Other studies resulted in the termination of the present invention. Accordingly, the present invention relates to the following. [la] A compound represented by the formula wherein R, 1a is a hydrogen atom, R, 2 < a is an alkyl group of C? _6 substituted with a a group represented by C ?4 alkyl optionally halogenated with -NR6a-CO- (CH2) n-S02- wherein n is an integer from 1 to 4, R6a is a hydrogen atom or an alkyl group of C ?4, and - (CH2) n- is optionally substituted with C? -4 alkyl, R3a is a hydrogen atom or an alkyl group of Ci- 6, R 4a is a halogen atom or an alkyl group of Cl-6, R5a is a halogen atom or an alkyl group of C? -6, and Xa is a hydrogen atom or a halogen atom, or a salt thereof, with the proviso that N- [2- (4 - ([3-chloro-4- (3- chlorophenoxy) phenyl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2- (methylsulfonyl) acetamide. [2a] The compound of the aforementioned point [la], wherein Xa is a hydrogen atom. [3a] The compound of the above-mentioned point [2a], wherein Rla is a hydrogen atom, R2a is an alkyl group of C? -6 substituted with a group represented by -NR6aa-CO- CR7aR8a-S02-C alquilo_4 alkyl wherein R6aa is a hydrogen atom or a methyl group, R7a and R8a are the same or different and each is a hydrogen atom or a methyl group, R3a is a hydrogen atom, R4a is a chlorine atom or a methyl group, and R5a is a fluorine atom, a chlorine atom or a methyl group. [4a] The compound of point [3a] mentioned above, wherein R7a and R8a are methyl groups. [5a] A compound selected from the following: N- [2- (4- { [3-chloro-4- (3-chlorophenoxy) phenyl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2-methy1-2- (methylsulfonyl) propanamide, N- [2- (4- ([3-chloro-4- (3-chlorophenoxy) phenyl] amino.}. -5H- pyrrolo [3, 2-d] pyrimidin-5-yl) ethyl] -2- (ethylsulfonyl) acetamide, N- [2- (4- { [3-chloro-4- (3-chlorophenoxy) phenyl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -N , 2-dimethy1-2- (methylsulfonyl) propanamide, N- [2- (4- { [3-chloro-4- (3-methylphenoxy) phenyl] amino}. -5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethyl] -2- (methylsulfonyl) acetamide, N- [2- (4- { [3-chloro-4- (3-fluorophenoxy) phenyl] amino.} - 5H- pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2- (methylsulfonyl) acetamide, and N- [2- (4- { [4- (3-chlorophenoxy) -3-methylphenyl] araino .}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2-methy1-2- (methylsulfonyl) propanamide, or one of its salts, or one of its hydrates. [6a] A prodrug of the compound of the aforementioned point [la]. [7a] A method of producing the compound of the aforementioned point [la] or a salt thereof, which comprises reacting a compound represented by the formula: where La is a leaving group, and the other symbols are as defined previously, or one of its salts and a compound represented by the formula: where Ga is a hydrogen atom or a metal atom, and the other symbols are as defined previously, or one of their salts. [8a] A pharmaceutical agent comprising the compound of the aforementioned point [la] or one of its salts or one of its prodrugs. [9a] The pharmaceutical agent of the aforementioned point [8a], which is a tyrosine kinase inhibitor. [10a] The pharmaceutical agent of the aforementioned point [8a], which is an agent for the prevention or treatment of cancer. [lia] The above-mentioned pharmaceutical agent [10a], wherein the cancer is breast cancer, ovarian cancer, colorectal cancer, gastric cancer, esophageal cancer, prostate cancer, lung cancer, pancreatic cancer or cancer of kidney. [12a] A method for the prevention or treatment of cancer in a mammal, comprising the administration of an effective amount of the compound of the above-mentioned point [la] or a salt thereof or one of its prodrugs, to the mammal. [13a] Use of the compound of the aforementioned point [la] or one of its salts or one of its prodrugs, for the production of an agent for the prevention or treatment of cancer. [Ib] A co-formula represented by the formula: (Ib) wherein Wb is C (Rlb) or N, ring Ab is an optionally substituted pipdma ring, Xlb is -NR3b-Ylb-, -O-, -S-, -SO-, -S02- or -CHR3b- wherein R3b is a hydrogen atom or an optionally substituted aliphatic hydrocarbon group, or R3b is optionally attached to the carbon atom in the pyridine ring so that the Ab ring forms an optionally substituted ring structure, and Ylb is a bond, or an alkylene of C? -4 u -O- (alkylene of C? -) -, each of which is optionally substituted, and Rlb is a hydrogen atom, a halogen atom, or an optionally substituted group attached through an atom carbon, a nitrogen atom or an oxygen atom, R2b is a hydrogen atom, or an optionally substituted group attached through a carbon atom or a sulfur atom, or Rlb and R2b, or R2b and R3b are joined optionally to form an optionally substituted ring structure, or one of its salts. [2b] The compound of the aforementioned point [Ib], which is a compound represented by the formula: wherein ring A is a pyridine ring also optionally substituted, ring Bb is an aryl group of Cd-? optionally substituted, and the other symbols are as defined previously. [3b] The compound of the aforementioned point [2b], wherein Rlb is a hydrogen atom, a halogen atom, a cyano group or an optionally halogenated C?-6 alkyl group, R 2b is an alkyl group of C?? -6 substituted with substituents selected from the group consisting of (i) -NR5ba-CO- (CH2) ni-S02-C? -4 alkyl wherein R6ba is a hydrogen atom or a methyl group, nor is a whole number from 1 to 4, and - (CH2) n? _ is optionally substituted with C? _ alkyl, (ii) -NR6bb-C0- (CH2) n2-OH wherein R6bb is a hydrogen atom or a methyl group, n2 is an integer from 1 to 4, and - (CH2) n2- is optionally substituted with C? _4 alkyl, (iii) -0- (CH2) n3-OH wherein n3 is an integer from 1 to 4, and - (CH2) n3- is optionally substituted with C? -4 alkyl, and (iv) hydroxy, R3b is a hydrogen atom, the Ab ring is a pyridine ring optionally substituted with substituents selected from the group consisting of halogen and methyl, and the ring Bb is a phenyl group optionally substituted with substituents selected from the group consisting of C? -6 alkyl optionally halogenated, optionally halogenated C? -6 alkoxy, C? -6-carbamoyl alkyl and halogen. [4b] The compound of the aforementioned point [2b], wherein the Ab ring is a pyridine ring optionally substituted with halogen, and the Bb ring is a phenyl group optionally substituted at the 3 position by substituents selected from the group consisting of alkyl of optionally halogenated C? _6, optionally halogenated C? -6 alkoxy, alkyl of C? -6-carbamoyl and halogen. [5b] A compound selected from the following: 2-. { 2- [4 - ((5-chloro-6- [3- (trifluoromethyl) phenoxy] pyridin-3-yl} amino) -5H-pyrrolo [3,2- d] pyrimidin-5-yl] ethoxy} Ethanol, N-. { 2- [4- ( { 5-Chloro-6- [3- (trifluoromethyl) phenoxy] pyridin-3-yl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide, N-. { 2- [4- ((5-chloro-6- [3- (trifluoromethyl) phenoxy] pyridin-3-yl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -3-hydroxy-3-methylbutanamide, N- (2- [4 - ((5-chloro-6- [3- (trifluorornetoxy) phenoxy] pyridin-3-yl} amino) -5H-pyrrolo [ 3,2-d] pyrimidin-5-yl] ethyl.} -2- (methylsulfonyl) acetamide, and N- (tert-butyl) -3- [(3-chloro-5- { [5- ( 2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. Pyridin-2-yl) oxy] benzamide, or one of its salts. [6b] A prodrug of the point compound [Ib] mentioned above [7b] A method of producing the compound of the aforementioned point [Ib] or a salt thereof, which comprises reacting a compound represented by the formula where L is a leaving group, and the other symbols are as defined previously, or one of its salts and a compound represented by the formula where G is a hydrogen atom or a metal atom, and the other symbols are as defined previously, or one of their salts. [8b] A pharmaceutical agent comprising the compound of the aforementioned point [Ib] or one of its salts or one of its prodrugs. [9b] The pharmaceutical agent of the aforementioned point [8b], which is a tyrosine kinase inhibitor. [10b] The pharmaceutical agent of the aforementioned point [8b], which is an agent for the prevention or treatment of cancer. [11b] The pharmaceutical agent of the aforementioned point [10b], wherein the cancer is breast cancer, ovarian cancer, colorectal cancer, gastric cancer, esophageal cancer, prostate cancer, lung cancer, pancreatic cancer or cancer of kidney. [12b] A method for the prevention or treatment of cancer in a mammal, comprising administering an effective amount of the compound of item [Ib] above mentioned or one of its salts or one of its prodrugs, to the mammal. [13b] Use of the above-mentioned compound [Ib] or one of its salts or one of its prodrugs, for the production of an agent for the prevention or treatment of cancer. [14b] The compound of the aforementioned point [Ib], which is a compound represented by the formula: where each symbol is as defined previously. [lc] A compound represented by the formula: wherein R, 1c is a hydrogen atom, or a group optionally substituted, attached through a carbon atom, a nitrogen atom or an oxygen atom, R 2c is an optionally substituted group attached through a carbon atom or a sulfur atom, or R cc and R 2c, or R 2c and R 3c optionally attached to form an optionally substituted ring structure, R3c is a hydrogen atom or an optionally substituted aliphatic hydrocarbon group, or R3c is optionally attached to the carbon atom in the adjacent Benzene ring to form an optionally substituted ring structure, the Ac ring is an optionally substituted benzene ring, R5c is (i) an optionally substituted amino group, (ii) an optionally substituted carbamoyl group, (iii) an optionally substituted ureido group, (iv) an optionally substituted sulfamoyl group, (v) an optionally substituted heterocyclic group, (vi) an optionally substituted C 2-6 alkoxy group, (vii) an optionally substituted aminomethyl group, (viii) an optionally substituted carbamoylmethyl group, (ix) an optionally substituted alkylsulfonyl group, or (x) a cyano group, and the Bc ring is an aryl group of C6-? or a C5-8 cycloalkyl group, each of which is also optionally substituted in addition to R5c, or a salt thereof, with the proviso that N- (tert-butyl) -4- [2- hydrochloride is excluded. chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3, 2-d] pyrimidin-4-yl} amino) phenoxy] benzamide, 4- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl}. amino) phenoxy] -N- (2,2-dimethylpropyl) benzamide, 3- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4) -yl] amino.}. phenoxy) benzonitrile, 3- [2-chloro-4- ((5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl .}. amino) phenoxy] benzonitrile, 3- [2-chloro-4- (6,7-dihydro-9H-pyrimido [4 ', 5 Y 4, 5] pyrrolohydrochloride [2, lc] [1,4 ] oxazin-4-ylamino) phenoxy] benzonitrile, and (2E) -N- [(2E) -3- (4 { [3-chloro-4- (3-cyanophenoxy) phenyl] amino.} - 5-methyl-5H-pyrrolo [3,2-d] pyrimidin-6-yl) prop-2-en-l-yl] -A- (dimethylamino) but-2-enamide. [2c] The compound of the point [ lc] mentioned above, where Rlc is a hydrogen atom. [3c] A compound selected from the following: 2- (2- [4- (. {3-Chloro-4- [3- (1, 3-thiazol-5-yl) phenoxy] phenyl} amino} -5H-pyrrolo [3, 2-d] pyrimidin-5-yl] ethoxy.] Ethanol, N- (tert-butyl) -3- [2-chloro-4- ((5- [2- (2- hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl.}. amino) phenoxy] benzamide, 3- [2-chloro-4- (. {5- [2- (2- hydroxyethoxy) ethyl] -5H-pyrrolo [3, 2-d] pyrimidin-4-yl.}. amino) phenoxy] -N- (2-hydroxy-1, 1-dimethylethyl) benzamide, N- (tert-butyl) -3- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. Phenoxy) benzamide, N- (3 - {2-chloro-4- [(6-cyano-5-methyl-5H-pyrrolo [3,2-d] pyrimidin-4-yl) amino] phenoxy] phenyl) cyclopropanecarboxamide, N- (ter -butyl) -5- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. phenoxy) -2- fluorobenzamide, N-. { 2- [4- ( { 3-Chloro-4- [3- (dimethylamino) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -3-hydroxy-3-methylbutanamide, N-. { 2- [4- ( { 3-Chloro-4- [3- (dimethylamino) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (Rethylsulfonyl) acetamide, N- (tert-butyl) -2- [3- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. phenoxy) phenyl] acetamide, N-. { 2- [4- ( { 3-Chloro-4- [3- (cyclopropylmethoxy) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide, N- (2- [4- (. {3-chloro-4- [3- (2,2-dimethylpropoxy) phenoxy] phenyl} amino) -5H-pyrrolo [3 , 2-d] pyrimidin-5-yl] ethyl.} -2- (methylsulfonyl) acetamide, 2- (methylsulfonyl) -N- { 2- [4- (. {3-meti1-4- [ 3- (2,2,2-trifluoroethoxy) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl.} Acetamide, 2- [4 - ((3 -chloro-4- [3- (isopropylsulfonyl) phenoxy] phenyl]. amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethanol, and N- [2- (4-. [3-chloro-4- (3-cyanophenoxy) phenyl] amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2- (methylsulfonyl) acetamide, or one of its salts [4c] A prodrug of the above-mentioned compound [lc]. [5c] A method of producing the compound of the aforementioned point [Ic] or a salt thereof, which comprises reacting a compound represented by the formula: Ole) where Lc is a leaving group, and the other symbols are as defined previously, or one of its salts and a compound represented by the formula: wherein Gc is a hydrogen atom or a metal atom, and the other symbols are as previously defined, or one of their salts. [6c] A pharmaceutical agent comprising the compound of the aforementioned point [Ic] or one of its salts or one of its prodrugs. [7c] The pharmaceutical agent of the aforementioned point [6c], which is a tyrosine kinase inhibitor. [8c] The pharmaceutical agent of item [6c] mentioned above, which is an agent for the prevention or treatment of cancer. [9c] The pharmaceutical agent of the aforementioned point [8c], wherein the cancer is breast cancer, ovarian cancer, colorectal cancer, gastric cancer, esophageal cancer, prostate cancer, lung cancer, pancreatic cancer or cancer of kidney. [10c] A method for the prevention or treatment of cancer in a mammal, comprising the administration of an effective amount of the compound of the aforementioned point [Ic] or one of its salts or one of its prodrugs, to the mammal. [11c] Use of the compound of the aforementioned point [Ic] or one of its salts or one of its prodrugs, for the production of an agent for the prevention or treatment of cancer. [12c] The compound of the above-mentioned point [lc], which is a compound represented by the formula: where each symbol is as defined previously. [13c] The compound of the above-mentioned point [lc], which is a compound represented by the formula: wherein the Bc ring is a phenyl group or a cyclohexyl group, each of which is also optionally substituted in addition to R5c, and the other symbols are corao defined above. [14c] The compound of point [lc] mentioned above, wherein R2c is an alkyl group of C6-6 optionally substituted with substituents selected from the group consisting of (i) C4-4 alkyl optionally halogenated with -NR6c-CO- (CH2) n-S02-, (ii) - NR6c-C0- (CH2) n-OH, (iii) -0- (CH2) n-OH, (iv) hydroxy, (v) -NR6c-CO-alkyl of C? -4, (vi) -O- C? -4 alkyl, (vii) -S-C? _4 alkyl, (viii) -S02-C? _ alkyl, and (ix) amino wherein n is an integer from 1 to 4, R? c is a hydrogen atom or an alkyl group of C? _4, and - (CH2) n- is optionally substituted with C? _o alkyl. [15c] The compound of the point [lc] mentioned above, wherein Rlc is a hydrogen atom or a cyano group, R2c is an alkyl group of C6-6 optionally substituted with substituents selected from the group consisting of (i) C6 alkyl - optionally halogenated with -NR6c-CO- (CH2) n-S02-, (ii) -NR6c-CO - (CH2) n-OH, (iii) -0- (CH2) n-OH, (iv) hydroxy, (v) -NR6c-CO-C-4 alkyl, (vi) -O-C-alkyl ? 4, (vii) -S-C? -4 alkyl, (viii) -S? 2-C? _4 alkyl, and (ix) amino wherein n is an integer from 1 to 4, R6c is a hydrogen atom or an alkyl group of C? _4, and - (CH2) n- is optionally substituted by C? _ alkyl, R3c is a hydrogen atom or an alkyl group of the Ac ring is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl, R5c is (i) an amino group, (ii) a monoalkyl group of C? -6-amino, (iii) a dialkyl group of C? -6-amino, (iv) an optionally halogenated C? _6-amino alkanoyl group, (v) a C? -6-amino-hydroxy alkanoyl group, (vi) an alkanoyl group of C? -6-amino with hydroxy and halogen, ( vii) a C3_7-C6-aminoalkanoyl cycloalkyl group, (viii) an alkanoyl group of C6-amino with C3-7 cycloalkyl and halogen, (ix) an alkylsulfonyl group of C? 6-C-alkanoyl? 6-amino, (x) a C3-7-carbonyl-amino cycloalkyl group, (xi) a C? -6-carbonyl-amino alkoxy group, (xii) a carbamoyl group, (xiii) an alkyl group of C ? -6-carbamoyl optionally halogenated, (xiv) a hydroxy-alkyl group of C? _6-carbamoyl, (xv) a C? -6-alkoxy group of C? -6-carbamoyl, (xvi) an aryl group of C6-? 4-C? -6-carbamoyl-alkyl, (xvii) a C2-6-carbamoyl-alkynyl group, (xviii) a piperidyl-C1-6-carbamoyl-alkyl group, (xix) a morpholinylanyl-alkyl group of C? _6-carbamoyl, (xx) a C3-7-carbamoyl cycloalkyl group optionally substituted by C?-6 alkyl or C 2-6 alkynyl r (xxi) a 5- or 6-membered cyclic amino-carbonyl group optionally containing an oxygen atom, (xxii) a ureido group, (xxiii) a C? -6-ureido alkyl group, (xxiv) a C3-7-ureido cycloalkyl group, (xxv) a 5- to 8-membered heterocyclyl-ureido group containing, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, (xxvi) a sulfamoyl group optionally substituted with C? -6 alkyl, (xxvii) a 5- to 8-membered heterocyclic group containing, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, which is optionally substituted with substituents selected from the group consisting of group consisting of optionally halogenated C? -6 alkyl already C6-6-carbonyl lcoxy, (xxviii) a C2-6 alkoxy group optionally substituted with substituents selected from the group consisting of C3-7 cycloalkyl, halogen, C6-6 alkoxy and C6-6-carbamoyl alkyl , (xxix) a carbamoylmethyl group optionally substituted with C? -6 alkyl, (xxx) an aminomethyl group optionally substituted with C? -6-carbonyl alkyl, (xxxi) a C? -6-sulfonyl alkyl group optionally containing C3-7 cycloalkyl or halogen, or (xxxii) a cyano group, and the Bc ring is an aryl group of Cß-? or a C5-8 cycloalkyl group, each of which is also optionally substituted, in addition to R5c, with substituents selected from the group consisting of optionally halogenated C1-6 alkyl and halogen. [16c] The above-mentioned point [lc] or point [12c] compound, wherein R5c is an amino group optionally substituted with substituents selected from the group consisting of (i) C? -6 alkyl, (ii) alkanoyl optionally halogenated C1-6, (iii) C6-hydroxy alkanoyl, (iv) C5-5 alkanoyl having hydroxy and halogen, (v) C 3-7 cycloalkyl C 1-6 alkanoyl, (vi) C? -6 alkanoyl having C 3-7 cycloalkyl and halogen, (vii) C? -6-sulfonyl-C 1-6 alkanoyl 6, (viii) C3_7-carbonyl cycloalkyl, and (ix) C6-6-carbonyl alkoxy, the Bc ring is an aryl group of C6-? or a C5_8 cycloalkyl group, each of which is also optionally substituted, in addition to R5c, with substituents selected from the group consisting of optionally halogenated C? -6 alkyl and halogen, Rlc is a hydrogen atom, R2c is a C? -6 alkyl group substituted with substituents selected from the group consisting of (i) C? - alkyl optionally halogenated with -NR6c-C0- (CH2) n-S02, (ii) -NR6c-CO- (CH2) n-OH, (iii) -0- (CH2) n-OH, (iv) hydroxy, (v) -NR6c-CO-C de -4 alkyl, (vi) -O-C ?4 alkyl, ( vii) -S-alkyl of C? -4, (viii) -S? 2 ~ C? - alkyl, and (ix) amino wherein n is an integer of 1 a, R6c is a hydrogen atom or a alkyl group of C? _4, and - (CH2) n- is optionally substituted with C? -4 alkyl, R3c is a hydrogen atom or an alkyl group of ie, and the Ac ring is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl. [17c] The compound of point [lc] or of the aforementioned point [12c], wherein R5c is a carbamoyl group optionally substituted with substituents selected from the group consisting of (i) optionally halogenated C? -6 alkyl, (ii) ) C6-C6-hydroxy-alkyl, (iii) C6-C6-alkoxy of C6-6, (iv) C6-C4-C4 alkyl-C6-6 alkyl, (v) C2_6-alkynyl, vi) piperidyl-C? -6 alkyl, (vii) morpholinyl-C? -6 alkyl, and (viii) C3-7 cycloalkyl optionally substituted with C? -6 alkyl or C2-b alkynyl, the ring Bc is an aryl group of C6-? 4 or a cycloalkyl group of C5-8, each of which is also optionally substituted, in addition to R5c, with substituents selected from the group consisting of optionally halogenated C1-6 alkyl and halogen , Rlc is a hydrogen atom, R 2c is a C ?_6 alkyl group substituted with substituents selected from the group consisting of (i) C? _ Alkyl optionally halogenated with -NRc-CO- (CH2) n-S02-, (ii) -NR6c-CO- (CH2) n-OH, (iii) -0- (CH2) n-OH, (iv) hydroxy, (v) -NR6c-CO-alkyl of C? _4, (vi) -O-alkyl of C? _4, (vii) -S-alkyl of C? -4, (viii) -S? 2-alkyl of C? _4, and (ix) amino wherein n is an integer of 1 to 4, Rdc is a hydrogen atom or an alkyl group of C? -4, and - (CH2) n_ is optionally substituted with C? _ alkyl, R3c is a hydrogen atom or an alkyl group of C? -, 5, and the Ac ring is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl. [18c] The above-mentioned point [lc] or point [12c] compound, wherein R5c is a ureido group optionally substituted with substituents selected from the group consisting of (i) C? -6 alkyl, (ii) cycloalkyl of C3_7, and (iii) 5- to 8-membered heterocyclic group containing, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group consisting of one atom nitrogen, an oxygen atom and a sulfur atom, the Bc ring is an aryl group of C6-? 4 or a cycloalkyl group of C5-a, each of which is also optionally substituted, in addition to R5c, with selected substituents of the group consisting of optionally halogenated C ?_6 alkyl and halogen, Rlc is a hydrogen atom, R 2c is a C?-6 alkyl group substituted with substituents selected from the group consisting of (i) C? alkyl - optionally halogenated with - NRf > c-CO- (CH2) n-S02-, (ii) -NR6c-C0- (CH2) n-OH, (iii) -0- (CH2) n-OH, (iv) hydroxy, (v) -NR6c -CO-C alquilo-alkyl, (vi) -O-C? -4 alkyl, (vii) -S-C alquilo4 alkyl, (viii) -S02-C? -4 alkyl, and (ix) ) amino, wherein n is an integer from 1 to 4, R6c is a hydrogen atom or an alkyl group of C? _4, and - (CH) n_ is optionally substituted with C? _ alkyl, R3c is an atom of hydrogen or an alkyl group of C? -6, and the Ac ring is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl. [19c] The compound of point [lc] or of point [12c] mentioned above, wherein R5c is a sulfamoyl group optionally substituted with C? -6 alkyl, the Bc ring is an aryl group of Ce-? or a C5-8 cycloalkyl group, each of which is also optionally substituted, in addition to R5c, with substituents selected from the group consisting of optionally halogenated C1-6alkyl and halogen, Rlc is a hydrogen atom, R2c is a C ?_6 alkyl group substituted with substituents selected from the group consisting of (i) C? - alkyl optionally halogenated with -NR6c-CO- (CH2) n-S02-, (ii) -NR6c-CO- (CH2) n-OH, (iii) -0- (CH2) n-OH, (iv) hydroxy, (v) - NR6c-CO-C de4 alkyl, (vi) -O-C? -4 alkyl, (vii) -S-C? -4 alkyl, (viii) -S? 2-C ?4 alkyl, and (ix) amino where n is an integer from 1 to 4, R6c is a hydrogen atom or an alkyl group of C? _, and - (CH2) n_ is optionally substituted with C? - alkyl, R3c is a hydrogen atom or a C? -6 alkyl group, and the Ac ring is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl. [20c] The compound of point [lc] or of the above-mentioned point [12c], wherein R5c is a 5- to 8-membered heterocyclic group containing, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group consisting of in a nitrogen atom, an oxygen atom and a sulfur atom, which is optionally substituted with substituents selected from the group consisting of optionally halogenated C? -6 alkyl and C? -6-carbonyl clcoxy, the Bc ring is an aryl group of Cd-? or a C5-8 cycloalkyl group, each of which is also optionally substituted, in addition to R5c, with substituents selected from the group consisting of optionally halogenated C? -6 alkyl and halogen, RIc is a hydrogen atom, R2c is a C ?_6 alkyl group substituted with substituents selected from the group consisting of (i) C? _ alkyl optionally halogenated with - NR6c-CO- (CH2) n-S02-, (ii) -NR6c-CO- (CH2) n-OH, (iii) -0- (CH2) n-OH, (iv) hydroxy, (v) -NR6c -CO-C de4 alkyl, (vi) -O-C ?4 alkyl, (vii) -S-C alquilo4 alkyl, (viii) -S02-C? -4 alkyl, and (ix) amino, wherein n is an integer from 1 to 4, R6c is a hydrogen atom or an alkyl group of C? -4, and - (CH2) n- is optionally substituted with C? - alkyl, R3c is a hydrogen atom or an alkyl group of C? -6, and the Ac ring is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl. [21c] The compound of any of the points [16c | a [20c] mentioned above, wherein R2c is a C6_6 alkyl group substituted with its tuent selected from the group consisting of (i) -NH-CO-CR7cR8c-S02-C alquilo_4 alkyl wherein R7c and R8c are the same or different and each is a hydrogen atom or an alkyl group of C? -4, (ii) -NR6cb-CO- (CH2) n2-OH wherein n2 is an integer of 1 a, R6cb is a hydrogen atom or an alkyl group of C? _4, and - (CH2) n2- is optionally substituted with C? _ alkyl, (iii) -0- ( CH2) n3-OH where n3 is an integer from 1 to 4, and - (CH2) n3_ is optionally substituted with C? _4 alkyl, (iv) hydroxy, (v) -NR6c-CO-a C? -4, (vi) -O-C? - alkyl, (vii) -S-C? _ Alkyl, (viii) -S02-C? _4 alkyl, and (ix) amino. [22c] The compound of the above-mentioned point [lc] or point [12c], wherein R2c is an alkyl group of C?-6 substituted with a group represented by C? _ Alkyl optionally halogenated with -NR6ca-CO- (CH2) n? -S02- wherein neither is an integer of 1 a, R6ca is a hydrogen atom or an alkyl group of C? _, And - (CH2) n? - is optionally substituted with alkyl of C? -, Rlc is a hydrogen atom, R3c is a hydrogen atom, the Ac ring is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl, R5c is (i) an amino group optionally (a) monosubstituted with C? _6 alkanoyl optionally having C? _6-sulfonyl alkyl, or (b) mono- or disubstituted with C? -6 alkyl, (ii) a optionally substituted carbamoyl group with C? -6 alkyl, (iii) a 5- to 8-membered heterocyclic group containing, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen and a sulfur atom, which is optionally substituted with optionally halogenated C? -6 alkyl(iv) a C2_6 alkoxy group optionally substituted with C3_7 cycloalkyl, halogen, C6_6 alkoxy or C6_6 carbamoyl alkoxy, (v) an aminomethyl group optionally substituted with C6_6 alkyl -carbonyl, (vi) a C? -6-sulfonyl alkyl group optionally substituted by C3-7 cycloalkyl, or (vii) a cyano group, and the Bc ring is an aryl group of C? -? also optionally substituted, in addition to R5c, with substituents selected from the group consisting of optionally halogenated C? -6 alkyl and halogen. [23c] The compound of point [22c] before mentioned, wherein R2c is an alkyl group of C? -6 substituted with a group represented by -NH-CO-CR7cR8c-S02-Cx-4 alkyl wherein R7c and R8c are the same or different and each is an hydrogen or an alkyl group of C? _4. [24c] The compound of point [lc] or of the above-mentioned point [12c], wherein R2c is an alkyl group of C6 -6 substituted with a group represented by -NR6cb-CO- (CH2) n2-0H wherein n2 is an integer from 1 to 4, R6c is a hydrogen atom or an alkyl group of C? -, and - (CH2) n2_ is optionally substituted with C? _ alkyl, Rlc is a hydrogen atom, R3c is a hydrogen atom, the Ac ring is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl, R5c is (i) an amino group optionally (a) monosubstituted with C? _6 alkanoyl which optionally has hydroxy, or (b) mono- or disubstituted with C? _6 alkyl, (ii) a carbamoyl group optionally substituted with C? _6 alkyl, (iii) a 5- to 8-membered heterocyclic group containing, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, which is optionally substituted with optionally halogenated C?-alkyl, (iv) a C 2-6 alkoxy group optionally substituted with cycloalkyl C3-7, halogen, C? -6 alkoxy or C? _6-carbaraoyl alkyl, (v) an aminomethyl group optionally substituted with C? -6-carbonyl alkyl, (vi) an alkyl group of C? _6- sulfonyl optionally substituted with C3-7 cycloalkyl, or (vii) a cyano group, and ring Bc is an aryl group of Ce-? 4 also optionally substituted, in addition to R5c, with substituents selected from the group consisting of C-alkyl ? -6 optionally halogenated and halogen. [25c] The compound of the aforementioned point [24c], wherein R2c is an alkyl group of C? -6 substituted with a group represented by -NH-CO-CH2-CR9cR10c-OH wherein R9c and R10c are the same or different and each is an alkyl group of C? -. [26c] The compound of point [lc] or point [12c] mentioned above, wherein R2c is an alkyl group of C? -6 substituted with a group represented by -0- (CH2) n-0H wherein n3 is an integer from 1 to 4, and - (CH2) n3- is optionally substituted with alkyl of C? _, Rlc is a hydrogen atom, R3c is a hydrogen atom, the Ac ring is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl, R5c is (i) an amino group, (ii) an alkyl group of C? -6-amino, ( iii) an alkanoyl group of C? -6-amino optionally has Logenated, (iv) a hydroxy-alkanoyl group of C? _6-amino, (v) an alkanoyl group of C? -6-amino with hydroxy and ha-ogen (vi) a C3-7 cycloalkyl-C6-amino-alkanoyl group, (vii) an alkanoyl group of C6-amino with C3-7 cycloalkyl and halogen, (viii) a cycloalkyl group of C-7-carbonyl-amino, (ix) a C?-6-carbonyl-amino alkoxy group, (x) a carbamoyl group, (xi) an optionally halogenated C?-6-carbamoyl alkyl group, (xii) a hydroxy alkyl group of C? -6-carbamoyl, (xiii) a C? -6 alkoxy group of C? -6 carbamoyl alkyl, (xiv) a C3-7-carbamoyl cycloalkyl group, (xv) a ureido group, (xvi) a C? -6-ureido alkyl group, (xvii) a C3_7-ureido cycloalkyl group, (xviii) a 5- to 8-membered heterocyclyl-ureido group containing, in addition to carbon atoms, 1 to 3 hetero atoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, (xix) a 5- or 6-membered cyclic amino-carbonyl group optionally containing one atom of oxygen, (xx) a 5- to 8-membered heterocyclic group containing, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, which is optionally substituted with optionally halogenated C? _6 alkyl or C? -6-carbonyl alkoxy, (xxi) a C2_6 alkoxy group optionally logenated, (xx ii) a C ?_6_sulfonyl alkyl group, or (xxiii) a cyano group, and the Bc ring is an optionally substituted C6-? 4 aryl group, in addition to R5c, with substituents selected from the group consisting of optionally halogenated C? -6 alkyl and halogen. [27c] The compound of point [lc] or of the above-mentioned point [12c], wherein R2c is an alkyl group of C? -6 substituted with hydroxy, Rlc is a hydrogen atom, R3c is a hydrogen atom, Ac ring is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl, R5c is (i) an amino group optionally (a) monosubstituted with C? -6 alkanoyl optionally having hydroxy, or (b) mono - or disubstituted with C? _6 alkyl, (ii) a carbamoyl group optionally substituted with optionally halogenated C? -6 alkyl, (iii) a C3-7 cycloalkyl-carbamoyl group optionally substituted with C? _6 alkyl or alkynyl of C2_6, (iv) an aryl group of C6-? 4-C? -6-carbamoyl-alkyl, (v) a hydroxy-C-6-carbamoyl-alkyl group, (vi) a morpholinyl-alkyl group of Cx-g-carbamoyl, (vii) a C2_6-carbamoyl alkynyl group, (viii) a carbamoylmethyl group optionally substituted with C? -6 alkyl, (ix) a C2_6 alkoxy group optionally substituted with C7 cycloalkyl, halogen, C? _6 alkoxy or C? _6-carbamoyl alkyl, (x ) an aminomethyl group optionally substituted with C? -6-carbonyl alkoxy, or (xi) a C? _6-sulfonyl alkyl group optionally substituted with C3_7 cycloalkyl, and the Bc ring is an aryl group of C6-? 4 also optionally substituted, in addition to R5c, with substituents selected from the group consisting of optionally halogenated C? _6 alkyl and halogen. [28c] The compound of the above-mentioned point [lc] or point [12c], wherein Rlc is a cyano group or an optionally halogenated C? -6 alkyl group, R2c is (i) an alkyl group of C? _6 , or (ii) an alkyl group of C6-6 substituted with substituents selected from the group consisting of (a) C4-4 alkyl optionally halogenated with -NR6c-CO- (CH2) n-S02-, (b) - NR6c-CO- (CH2) n-OH, (c) -0- (CH2) n-OH, and (d) hydroxy, wherein n is an integer from 1 to 4, R6c is a hydrogen atom or an alkyl group of C? _4, and - (CH2) n- is optionally substituted with C? -4 alkyl, R3c is a hydrogen atom or an alkyl group of the Ac ring is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl, R5c is (i) an amino group, (ii) a C? -6-amino alkyl group, (iii) an alkanoyl group of optionally halogenated C? -6-amino, (iv) a hydroxy-alkanoyl group of C? -6-amino, (v) an alkanoyl group of C? -6-amino with hydroxy and halogen, (vi) a cycloalkyl group of C-7-C6-amino-alkanoyl, (vii) an alkanoyl group of C6-amino with C3-7 cycloalkyl and halogen, (viii) an alkylsulfonyl group of C6-6-C-alkanoyl ? 6-amino, (ix) a C3-7-carbonyl-amino cycloalkyl group, (x) a C? -6-carbonyl-amino alkoxy group, (xi) a carbamoyl group, (xii) an optionally halogenated C? -6-carbamoyl alkyl group, (xiii) a C? _6-carbamoyl hydroxy-alkyl group, (xiv) a C? -6- alkoxy group C6-6-camobamoyl alkyl, (xv) a C3-7-carbamoyl cycloalkyl group, (xvi) a 5- or 6-membered cyclic amino-carbonyl group optionally containing an oxygen atom, (xvii) a ureido group , (xviii) a C? -6-ureido alkyl group, (xix) a C3-7-ureido cycloalkyl group, (xx) a 5- to 8-membered heterocyclic-ureido group containing, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, (xxi) a sulfamoyl group optionally substituted with a C? _6 ylkyl, or (xxii) a heterocyclic group of 5 a 8 members containing, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, which is optionally substituted with substituents selected from the group consisting of optionally halogenated C? -6 alkyl and C? -6-carbonyl alkoxy, and the Bc ring is an aryl group of C6-? or a C5-8 cycloalkyl group, each of which is also optionally substituted, in addition to R5c, with substituents selected from the group consisting of optionally halogenated C ?_6 alkyl and halogen. [29c] The compound of any of the aforementioned points [14c] to [20c] and [28c], wherein the Bc ring is a phenyl group or a cyclohexyl group, each of which is also optionally substituted, in addition to R5c, with substituents selected from the group consisting of optionally halogenated C ?_6 alkyl and halogen, and is substituted with R 5c at the meta position of the phenyl group or the β-position of the cyclohexyl group. [30c] The compound of any of the aforementioned points [22c] to [27c], wherein the Bc ring is a phenyl group also optionally substituted, in addition to R5c, with substituents selected from the group consisting of C? Alkyl? 6 optionally halogenated and halogen, which phenyl is substituted with R 5c at the meta position of the phenyl group. [Id] A compound represented by the formula: wherein R, l ± du is a hydrogen atom, or an optionally substituted group attached through a carbon atom, a nitrogen atom or an oxygen atom, R 2 d is an optionally substituted group attached through a hydrogen atom. carbon or a sulfur atom, or Rld and R2d, or R2d and R3d are optionally attached to form an optionally substituted ring structure, R3d is a hydrogen atom or an optionally substituted aliphatic hydrocarbon group, or R3d is optionally attached to the carbon in the adjacent benzene ring to form an optionally substituted ring structure, the Ad ring is an optionally substituted benzene ring, Zd is an optionally substituted C? -3 alkylene, the Bd ring is an optionally substituted heterocyclic group, or a its salts, on the condition that they are excluded - [(4- {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} -5H-pyrrolo [3,2-d] pyrimidin-5-yl) methyl] -2 ethyl-furoate, 5 - [(4 - ([3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino]} -5H-pyrrolo [3,2-d] pyrimidin-5-yl) methyl] -2- furancarboxylic, 2- [2- (4- ([3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino.}. -5H-pyrrolo [3,2-d] pyrimidine-5 -yl) ethoxy] ethanol, and N- [2- (4- ([3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino.}. -5H-pyrrolo [3,2-d] pyrimidine- 5-yl) ethyl] -2- (Rethylsulfonyl) acetamide. [2d] The compound of the aforementioned point [Id], which is a compound represented by the formula: wherein R4d is an acyl group or an optionally substituted ureido group, the Bd ring is a piperidyl group also optionally substituted in addition to R4d, and the other symbols are as defined above. [3d] A compound selected from the following: 4-. { [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyr: rolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] methyl} piperidin-1-tert-butyl carboxylate, and 4- [(2-chloro-4- ([5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino]. phenoxy) methyl] piperidine-1-carboxylic acid tert-butyl ester, or one of its salts. [4d] A prodrug of the compound of the above-mentioned point [Id]. [5d] A method of producing the compound of item [Id] aforementioned or a salt thereof, which comprises reacting a compound represented by the formula: where L is a leaving group, and the other symbols are as defined above, or one of its salts and a compound represented by the formula: where Gd is a hydrogen atom or a metal atom, and the other symbols are as defined with anteriority, or one of its salts. [6d] A pharmaceutical agent comprising the compound of the aforementioned point [Id] or one of its salts or anus of its prodrugs. [7d] The pharmaceutical agent of the aforementioned point [6d], which is a tyrosine kinase inhibitor. [8d] The pharmaceutical agent of point [6d] mentioned above, which is an agent for the prevention or treatment of cancer. [9d] The pharmaceutical agent of the aforementioned point [8d], wherein the cancer is breast cancer, ovarian cancer, colorectal cancer, gastric cancer, esophageal cancer, prostate cancer, lung cancer, pancreatic cancer or cancer of kidney. [0100] A method for the prevention or treatment of cancer in a mammal, comprising administering an effective amount of the compound of the above-mentioned point [Id] or one of its salts or one of its prodrugs, to the mammal. [lid] Use of the compound of the aforementioned point [Id] or one of its salts or one of its prodrugs, for the production of an agent for the prevention or treatment of cancer. [12d] The compound of the point [Id] mentioned above, which is a compound represented by the formula: where each symbol is as defined previously. [13d] The compound of the above-mentioned point [2d], wherein Rld is a hydrogen atom, a cyano group or an optionally halogenated C? _6 alkyl group, R2d is (i) an alkyl group of C? _6, or (ii) a C6_6 alkyl group substituted with substituents selected from the group consisting of (a) C4_4 alkyl optionally halogenated with -NR6d-CO- (CH2) n-S02-, (b) -NR6d-CO - (CH2) n-OH, (c) -0- (CH2) n-OH, and (d) hydroxy, wherein n is an integer from 1 to 4, R6d is a hydrogen atom or an alkyl group of C? _4, and - (CH2) n- is optionally substituted with C? _ Alkyl, R, 3d is a hydrogen atom or an alkyl group of If the ring A is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl, Zd is methylene, the ring Bd 'is a piperidyl group, and Rd is an alkoxy group of C? -6- carbonyl, a Cs-s-carbonyl cycloalkyl group, a C? -6-ureido alkyl group or a Cs-s-ureido cycloalkyl group. [14d] The compound of the aforementioned point [2d], wherein R 3d is a hydrogen atom, and the Ad ring is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl. [le] A compound represented by the formula: where Rle is a hydrogen atom, a group optionally substituted by attached through a carbon atom, a nitrogen atom or an oxygen atom, R2e is an optionally substituted group attached through a carbon atom or a sulfur atom, or Rle and R2e, or R2e and R3e optionally attached to form an optionally substituted ring structure, R3e is a hydrogen atom or an optionally substituted aliphatic hydrocarbon group, or R3e is optionally attached to the carbon atom in the adjacent Benzene ring to form an optionally substituted ring structure, the Ae ring is an optionally substituted benzene ring, R5e is (i) a linear alkyl group substituted with optionally substituted heterocyclic group, (ii) a linear alkyl group substituted with optionally substituted imino, (iii) a linear alkyl group substituted by optionally substituted aryl , which is optionally halogenated or hydroxylated, (iv) a branched alkyl group optionally substituted uido, (v) an optionally substituted alkenyl group, (vi) a hydroxy group substituted with optionally substituted aryl, (vii) a hydroxy group substituted with alkyl of C? _ 6, (viii) a hydroxy group substituted with halogenated C 2-6 alkyl, (ix) a halogenated C 2-6 alkyl group, (x) an optionally substituted cycloalkyl group, or (xi) a C? -6 alkyl group -carbonyl optionally substituted with optionally substituted aryl, and ring B is an aryl group of Ce-? also optionally substituted adipose of R5e, or a salt thereof, with the proviso that 2- (2- (4- [(3-chloro-4-. {4- [3- (1H-imidazole)] dihydrochloride is excluded. - 1-yl) propyl] phenoxy] phenyl) amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl.} Ethoxy) ethanol, 2- (2-. {4- [( 3-chloro-4- (4- [4- (lH-1, 2, 3-triazol-1-yl) butyl] phenoxy] phenyl) amino] -5H-pyrrolo [3,2-d] pyrimidine - 5-yl.} Ethoxy) ethanol, and l-. {3- [2-chloro-4- ((5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] ] pyrimidin-4-yl.}. amino) phenoxy] phenyl.} ethanone. [2e] The compound of the aforementioned point [le], wherein the "linear alkyl group substituted with optionally substituted heterocyclic group" for R5e is ( i) a methyl group substituted with group optionally substituted heterocyclic, or (ii) a linear alkyl group substituted with substituted heterocyclic group. [3e] A compound selected from the following: 2- [4- ( { 3-Chloro-4- [3- (1, 1-difluoroethyl) phenoxy] phenyl} amino) -5H-pyrrolo [3, 2-d] pyrimidin-5-l] ethanol, O-ethyl oxime of (1Z) -1-. { 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3, 2-d] pyrimidin-4-ylamino) phenoxy] phenyl} -2, 2-dimethylpropan-l-one, l-. { 3- [2-chloro-4- ((5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] phenyl}. -2, 2-dimethylpropan-1-ol, 1- [3- (2-chloro-4. {[[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] ] amino.}. phenoxy) phenyl] -3,3-dimethylbutan-1-one, N- (2- { 4- [(3-methyl-4 -. {3- [(1E) -3- methylbut-1-en-1-yl] phenoxyphenyl) amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl.} ethyl) -2- (disthylsulfonyl) acetamide, and N-. {2 - [4- ( { 3-Chloro-4- [3- (1-cyanocyclopropyl) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl. -2- (methylsulfonyl) acetamide, or one of its salts. [4e] A prodrug of the above-mentioned compound [le]. [5e] A method of producing the compound of aforementioned point [I] or a salt thereof, which comprises reacting a compound represented by the formula: where Le is a leaving group, and the other symbols are as defined previously, or one of its salts and a compound represented by the formula: where Ge is a hydrogen atom or a metal atom, and the other symbols are as defined previously, or one of their salts. [6e] A pharmaceutical agent comprising the above-mentioned compound [le] or one of its salts or one of its prodrugs. [7e] The pharmaceutical agent of the aforementioned point [6e], which is a tyrosine kinase inhibitor. [8e] The pharmaceutical agent of point [6e] before mentioned, which is an agent for the prevention or treatment of cancer. [9e] The pharmaceutical agent of the aforementioned point [8e], wherein the cancer is breast cancer, ovarian cancer, colorectal cancer, gastric cancer, esophageal cancer, prostate cancer, lung cancer, pancreatic cancer or cancer of kidney. [10A] A method for the prevention or treatment of cancer in a mammal, comprising administering an effective amount of the compound of the aforementioned site [I] or one of its salts or one of its prodrugs, to the mammal. [lie] Use of the above-mentioned compound [le] or one of its salts or one of its prodrugs, for the production of an agent for the prevention or treatment of cancer. [12e] The compound of the aforementioned point [le], which is a compound represented by the formula: where each symbol is as defined previously. [13e] The compound of the aforementioned point [le], wherein Rle is a hydrogen atom, a cyano group or an optionally halogenated C? _6 alkyl group, R2e is (i) a C? _6 alkyl group, or (ii) a C? _6 alkyl group substituted with substituents selected from the group consisting of (a) -NR6e-CO- (CH2) n-S02-optionally halogenated C? -4 alkyl, (b) -NR6e-CO- (CH2) n-0H, (c) -0 - (CH2) n-0H, and (d) hydroxy, wherein n is an integer from 1 to 4, R6e is a hydrogen atom or an alkyl group of Cx-4, and - (CH2) n- is optionally substituted with C? _4 alkyl, R3e is a hydrogen atom, the ring Ae is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl, R5e is (i) an alkyl group of C6-6 heterocyclyl- linear of to 8 members containing, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, and optionally having C? -6 alkyl, (ii) a linear C? -6 alkyl group substituted with hydroxyimino or C? -6-imino alkoxy, (iii) a linear C? _6 alkyl group substituted with Cd-? aryl. , which is also optionally halogenated or hydroxylated, (iv) an optionally halogenated branched C3_6 alkyl group, (v) a C2-6 alkenyl group, (vi) a hydroxyl group substituted with Cd-? aryl. (vii) a hydroxy group substituted with C 1 alkyl? 6, (viii) a hydroxy group substituted with halogenated C 2-6 alkyl, (ix) a halogenated C 2-6 alkyl group, (x) a C 3-7 cycloalkyl group optionally substituted with cyano or carbamoyl, or (xi) an alkyl group of C6-carbonyl optionally substituted with phenyl, and the ring Be is an aryl group of C6-? also optionally substituted, in addition to R5e, with substituents selected from the group consisting of optionally halogenated C 1-6 alkyl and halogen. [14e] The compound of the aforementioned point [13e], wherein the "heterocyclyl-linear C 5-6 alkyl group containing 5 to 8 members, in addition to carbon, 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, and optionally having C? _6"alkyl for R5e is (i) a heterocyclylmethyl group of to 8 members it contains, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, and optionally having C? -6 alkyl, or (ii) an alkyl group of C? -6 heterocyclyl-linear of 5 to 8 members containing, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, and having alkyl of C? _6. [lf] A compound represented by the formula: wherein Rlf is a hydrogen atom, or an optionally substituted group attached through a carbon atom, a nitrogen atom or an oxygen atom, R2f is an optionally substituted group attached through a carbon atom or a sulfur atom, or Rlf and R2f, or R2f and R3f are optionally attached to form an optionally substituted ring structure, R3f is a hydrogen atom or a group optionally substituted aliphatic hydrocarbon, or R3f is optionally bonded to the carbon atom in the adjacent Benzene ring to form an optionally substituted ring structure, the Af ring is an optionally substituted benzene ring, the Bf ring is a piperidyl group also optionally substituted in addition to R4f, and R4f is (i) an optionally substituted C6-6 alkyl group, or (ii) an optionally substituted C5-8 cycloalkyl group, or a salt thereof. [2f] The compound of the aforementioned point [lf], wherein Rlf is a hydrogen atom, a cyano group or an optionally halogenated C ?_6 alkyl group, R 2f is (i) an alkyl group of C?-6, or (ii) a C? -6 alkyl group substituted with substituents selected from the group consisting of (a) C? _4 alkyl optionally halogenated with -NRdf-C0- (CH2) n-S02-, (b) -NR6f-CO- (CH2) n-OH, (c) -0- (CH2) n-OH, and (d) hydroxy, wherein n is an integer from 1 to 4, R6f is a hydrogen atom or an alkyl group of C? -, and - (CH2) n_ is optionally substituted with C1-4 alkyl, R3f is a hydrogen atom or an alkyl group from ring Af is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl, the ring Bf is a piperidyl group, and R f is (i) an optionally substituted C? -6 alkyl group, or (ii) ) an optionally substituted C5_8 cycloalkyl group. [3f] The compound of the above-mentioned point [lf], wherein R3f is a hydrogen atom, and the Af ring is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl. [4f] A prodrug of the compound of point [lf] mentioned above. [5f] A method of producing the compound of aforementioned point [If] or one of its salts, which comprises reacting a compound represented by the formula: where L is a leaving group, and the other symbols are as defined above, or one of its salts and a compound represented by the formula: where GS is a hydrogen atom or a metal atom, and the other symbols are as previously defined, or one of their salts. [6f] A pharmaceutical agent comprising the compound of the aforementioned point [lf] or one of its salts or one of its prodrugs. [7f] The pharmaceutical agent of the aforesaid point [6f], which is a tyrosine kinase inhibitor. [8f] The pharmaceutical agent of point [6f] before mentioned, which is an agent for the prevention or treatment of cancer. [9f] The pharmaceutical agent of the aforementioned point [8f], wherein the cancer is breast cancer, ovarian cancer, colorectal cancer, gastric cancer, esophageal cancer, prostate cancer, lung cancer, pancreatic cancer or cancer of kidney. [IOF] A method for the prevention or treatment of cancer in a mammal, comprising administering an effective amount of the compound of the aforementioned site [I] or one of its salts or one of its prodrugs, to the mammal. [llf] Use of the above-mentioned compound [lf] or one of its salts or one of its prodrugs, for the production of an agent for the prevention or treatment of cancer. [12f] The compound of the above-mentioned point [lf], which is a compound represented by the formula: where each symbol is as defined with anteriority. [Ig] A compound represented by the formula: wherein Wg is C (Rlg) or N, ring A9 is an optionally substituted benzene ring, the ring Bg is a heterocycle with optionally substituted nitrogen content, Xlg is -NR3g-Ylg-, -O-, -S-, -SO-, -S02- or -CHR3g- wherein R3g is a hydrogen atom or an optionally substituted aliphatic hydrocarbon group, or R3g is optionally bonded to the carbon atom in the Benzene ring for the Ag ring to form an optionally substituted ring structure, and Ylg is a bond, or an alkylene of C? -4u -O - (alkylene of C? _) -, each of which is optionally substituted, and Rlg is a hydrogen atom, a halogen atom, or an optionally substituted group attached through a carbon atom, a nitrogen atom or an atom of oxygen, R2g is a hydrogen atom, or an optionally substituted group attached through a carbon atom or a sulfur atom, or Rlg and R2g, or R2g and R3g are optionally attached to form an optionally substituted ring structure, or one of its salts. [2g] The compound of the aforementioned point [lg], which is a compound represented by the formula: wherein R4g is an optionally substituted hydrocarbon group, ring Bg is a heterocycle with 5 or 6 membered nitrogen also optionally substituted in addition to R4g, and the other symbols are as defined above. [3g] The compound of the aforementioned point [2g], wherein Rlg is a hydrogen atom, a halogen atom, a cyano group or an optionally halogenated C? -6 alkyl group, R2g is a hydrogen atom or a alkyl group of C6-6 optionally substituted, R3g is a hydrogen atom or an alkyl group of R 4g is (i) an optionally substituted C6-? 4-alkyl group of C6-, (ii) an optionally substituted heterocyclyl-C-8 alkyl group, (iii) an alkyl group of CX-e, or ( iv) an optionally substituted C6_? 4 aryl group. [4g] The compound of the aforementioned point [2g], wherein Rlg is a hydrogen atom, a halogen atom, a cyano group or an optionally halogenated C? -6 alkyl group, R2g is (i) an hydrogen, (ii) an alkyl group of C? _6, or (iii) an alkyl group of C? g substituted with substituents selected from the group consisting of (a) -0- (CH2) n-OH, (b) - NR5g-CO- (CH2) n-OH, (c) -NR5g-C0- (CH2) n-S02-optionally halogenated C? _4 alkyl, (d) hydroxy, and (e) amino wherein n is a number integer from 1 to 4, R5g is a hydrogen atom or an alkyl group of C? _4, and - (CH2) n- is optionally substituted with C 1 alkyl, R 3 g is a hydrogen atom or an alkyl group of Cl- 6 / It is the formula R4g is (i) an aryl group of C6-? 4-C 1 -alkyl optionally substituted with substituents selected from the group consisting of halogen, C? _6-carbamoyl alkyl and C? -6 haloalkoxy, (ii) an optionally substituted heterocyclyl-C-8 alkyl group; or (iii) an optionally substituted Cd-4-aryl group. [5g] A compound selected from the following: N- [2- (4- { [1- (3-fluorobenzyl) -lH-indazol-5-yl] amino.}. -5H-pyrrolo [3,2 -d] pyrimidin-5-yl) ethyl] -2- (methylsulfonyl) acetamide, N- [2- (4- { [1- (3-fluorobenzyl) -lH-indol-5-yl] amino.} .5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -3-hydroxy-3-methylbutanamide, N- (tert-butyl) -3- [(5- { [5- ( 2-hydroxyethyl) -5H-pyrrolo [3, 2-d] pyrimidin-yl] amino.} - lH-indole-1- il) methyl] benzamide, N- (tert-butyl) -3 - [(5- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino}-lH-indazol-1-yl) methyl] benzamide, and N- (tert-butyl) -6 - [(5- ([5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.} - lH-indol-l-yl) methyl] pyridine-2-carboxamide, or one of its salts. [6g] A prodrug of the compound of the above-mentioned point [lg]. [7g ] A method of producing the above-mentioned compound [lg] or a salt thereof, which comprises reacting a compound represented by the formula: where Lg is a leaving group, and the other symbols are as previously defined, or one of their salts and a compound represented by the formula: where Gg is a hydrogen atom or an atom of metal, and the other symbols are as defined previously, or one of their salts. [8g] A pharmaceutical agent comprising the compound of the aforementioned point [Ig] or one of its salts or one of its prodrugs. [9g] The pharmaceutical agent of the aforementioned point [8g], which is a tyrosine kinase inhibitor. [10g] The pharmaceutical agent of the aforementioned point [8g], which is an agent for the prevention or treatment of cancer. [llg] The pharmaceutical agent of the aforementioned point [lOg], wherein the cancer is breast cancer, ovarian cancer, colorectal cancer, gastric cancer, esophageal cancer, prostate cancer, lung cancer, pancreatic cancer or kidney cancer. [12g] A method for the prevention or treatment of cancer in a mammal, comprising the administration of an effective amount of the compound of the aforementioned point [Ig] or one of its salts or one of its prodrugs, to the mammal. [13g] Use of the above-mentioned point compound [Ig] or one of its salts or one of its prodrugs, for the production of an agent for the prevention or treatment of cancer. [lh] A compound represented by the formula: wherein Rlh is a halogen atom or a halogenated C? -6 alkyl group, R2h is a hydrogen atom, or an optionally substituted group attached through a carbon atom or a sulfur atom, or Rlh and R2h, or R2h and R3h are bonded to form an optionally substituted ring structure, R3h is a hydrogen atom or an optionally substituted aliphatic hydrocarbon group, or R3h is optionally attached to the carbon atom in the adjacent Benzene ring to form a ring structure optionally substituted, Zh is a bond or an alkylene of optionally substituted C? -3, the ring Ah is an optionally substituted benzene ring, and the ring Bh is (i) an aryl group of C6-? 4 optionally substituted, (ii) an optionally substituted heterocyclic group, or (iii) an optionally substituted C5-8 cycloalkyl group, or a salt thereof. [2h] The compound of point [lh] mentioned above, which is a compound represented by the formula: wherein R5h is (i) an optionally substituted amino group, (ii) an optionally substituted carbamoyl group, (iii) an optionally substituted ureido group, (iv) an optionally substituted sulfamoyl group, (v) an optionally substituted heterocyclic group,. vi, an optionally substituted hydrocarbon group, [vii) a halogen atom, or [viii) an optionally substituted carboxyl group, and the ring Bh 'is (i) an aryl group of C6-? 4, (ii) a heterocyclic group, or (iii) a cycloalkyl group of C5-s, each of which is also optionally substituted in addition to R5h, and the other symbols are as previously defined. [3h] A compound selected from the following: N- (3- (2-chloro-4- [(6-chloro-5-methyl-5H-pyrrolo [3,2-d] pyrimidin-4-yl) amino] phenoxyphenyl) cyclopropanecarboxamide, 6-chloro-N- (3-chloro-4- [3- (trifluoromethyl) phenoxy] phenyl] -5-methy1-5H-pyrrolo [3,2-d] pyrimidin-4-amino, N- [3- (2-Chloro-4. {[6-chloro-5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-yl] amino] phenoxy) phenyl ] cyclopropanecarboxamide, and N- (tert-butyl) -3- (2-chloro-4- { [6-chloro-5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4] -yl] amino.}. phenoxy) benzamide, or one of its salts. [4h] A prodrug of the compound of the above-mentioned point [lh]. [5h] A method of producing the compound of the aforementioned point [lh] or a of its salts, which comprises reacting a compound represented by the formula: where L is a leaving group, and the other symbols are as previously defined, or one of their salts and a co-formula represented by the formula: where G is a hydrogen atom or a metal atom, and the other symbols are as defined previously, or one of their salts. [6h] A pharmaceutical agent comprising the above-mentioned compound [lh] or one of its salts or one of its prodrugs. [7h] The pharmaceutical agent of the aforementioned point [6h], which is a tyrosine kinase inhibitor. [8h] The pharmaceutical agent of the aforementioned point [6h], which is an agent for the prevention or treatment of cancer. [9h] The pharmaceutical agent of the aforementioned point [8h], wherein the cancer is breast cancer, ovarian cancer, colorectal cancer, gastric cancer, esophageal cancer, prostate cancer, lung cancer, pancreatic cancer or cancer of kidney. [010] A method for the prevention or treatment of cancer in a mammal, comprising the administration of an effective amount of the compound of the above-mentioned point [Ih] or one of its salts or one of its prodrugs, to the mammal. [llh] Use of the above-mentioned compound [lh] or one of its salts or one of its prodrugs, for the production of an agent for the prevention or treatment of cancer. [12h] The compound of point [lh] mentioned above, which is a compound represented by the formula: where each symbol is corao was previously defined. [13h] The compound of the aforementioned point [2h], wherein Rlh is a halogen atom or an optionally halogenated C-6 alkyl group, R 2 h is (i) a hydrogen atom, (ii) an alkyl group of C ? -6, or (iii) a C? -6 alkyl group substituted with substituents selected from the group consisting of (a) -0- (CH2) n-OH, (b) -NR6h-CO- (CH2) n -OH, (c) -NR6h-C0- (CH2) n-S02-optionally halogenated C? _4 alkyl, and (d) hydroxy, wherein n is an integer from 1 to 4, R6h is a hydrogen atom or an alkyl group of C? -4, and - (CH2) n- is optionally substituted with C4 alkyl, R3h is a hydrogen atom or an alkyl group of Zh is a bond or methylene, the ring Ah is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl, R5h is (i) an amino group, (ii) an alkyl group of C? -6-amino, (iii) an optionally halogenated C? -6-amino alkanoyl group, (iv) a hydroxy-alkanoyl group of C? -6-amino, (v) a alkanoyl group of C? -6-amino with hydroxy and halogen, (vi) a C3-7 cycloalkyl-C6-amino-amino alkanoyl group, (vii) an alkanoyl group of C? -6-amino with cycloalkyl of C3-7 and halogen, (viii) an alkylsulfonyl group of C6-alkanoyl of C6-6 arnino, (ix) a cycloalkyl group of C3-7-carbonyl-amino, (x) an alkoxy group of C6-6 -carbonyl-amino, (xi) a carbamoyl group, (xii) an optionally halogenated C? -6-carbamoyl alkyl group, (xiii) a hydroxy-C? _6-carbamoyl alkyl group, (xiv) an alkoxy group of C6-C6-carbamoyl alkyl, (xv) a C3-7-carbamoyl cycloalkyl group, (xvi) a 5- or 6-membered cyclic amino-carbonyl group optionally containing an oxygen atom, (xvii) a ureido group, (xviii) a C? -6-ureido alkyl group, (xix) a C3-7-ureido cycloalkyl group, (xx) a 5- to 8-membered heterocyclyl-ureido group containing, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, (xxi) a sulfamoyl group optionally substituted by C? _6 alkyl, (xxii) a 5- to 8-membered heterocyclic group containing, in addition to carbon atoms, 1 to 3 selected heteroatoms of the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, which is optionally substituted with substituents selected from the group consisting of optionally halogenated C_6 alkyl and C? -6-carbonyl alkoxy, (xxiii) an optionally halogenated C? -6 alkyl group, (xxiv) a C? -6-carbonyl alkoxy group, (xxv) a halogen atom, or (xxvi) a carboxyl group, and the Bh 'ring is a phenyl group , a pyridyl group or a piperidyl group, each of which is also optionally substituted besides R 5h. Each symbol used in the present specification is described in detail below. In the present specification, unless specify otherwise, as "halogen atom" (and "halogen" in substituent), fluorine atom, chlorine atom, bromine atom and iodine atom may be mentioned. In the present specification, unless otherwise specified, as "alkyl group", there may be mentioned a straight or branched chain alkyl group with 1 to 10 (eg, 1 to 10, 1 to 8, 1 to 6, 2). to 6, 1 to 4) carbon atoms, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, 1-ethylpropyl, hexyl, isohexyl, 1, 1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 2-ethylbutyl, heptyl, octyl, nonyl, decyl and the like. In the present specification, unless otherwise specified, as "alkyl group of C? _? O", there may be mentioned, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl , pentyl, isopentyl, neopentyl, 1-ethylpropyl, hexyl, isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3,3-dimethylbutyl, 2-ethylbutyl, heptyl, octyl, nonyl, decyl and the like. In the present specification, unless otherwise specified, as "C? -8 alkyl group", there may be mentioned, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, 1-ethylpropyl, hexyl, isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3, 3-dimethylbutyl, 2-ethylbutyl, heptyl, octyl and the like. In the present specification, unless otherwise specified, as "Ci-V alkyl group, there may be mentioned, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, 1-ethylpropyl, hexyl, isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3, 3-dimethylbutyl, 2-ethylbutyl, and the like In the present specification, unless otherwise specified, as " C2_6 alkyl group, there may be mentioned, for example, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, 1-ethylpropyl, hexyl, isohexyl, 1,1-dimethylbutyl , 2, 2-dimethylbutyl, 3, 3-dimethylbutyl, 2-ethylbutyl, and the like In the present specification, unless otherwise specified, such as "C? _4 alkyl group", there may be mentioned, for example, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl and the like In the present specification, unless otherwise specified Otherwise, as an "alkenyl group", there can be mentioned an alkenyl group with 2 to 10 (for example, 2 to 10, 2 to 8, 2 to 6, 2 to 4) carbon atoms, for example, ethenyl, 1-propenyl, 2-propenyl, 2-methyl-1-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 3-methyl-2-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4- pentenyl, 4-methyl-3-pentenyl, 1-hexenyl, 3-hexenyl, 5-hexenyl, 1-heptenyl, 1-octenyl and the like. In the present specification, unless otherwise specified, "C2-alkenyl group" or "Y" may be mentioned, for example, ethenyl, 1-propenyl, 2-propenyl, 2-methyl-1-propenyl, 1-butenyl , 2-butenyl, 3-butenyl, 3-methyl-2-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 4-methyl-3-pentenyl, 1-hexenyl, 3-hexenyl, -hexenyl, 1-heptenyl, 1-octenyl and the like In the present specification, unless otherwise specified, as "C2-s'V alkenyl group there may be mentioned, for example, ethenyl, 1-propenyl, 2-propenyl , 2-methyl-1-propenyl, 1-butenyl, 2-butenyl, 3-butenyl, 3-methyl-2-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 4-methyl-3 -pentenyl, 1-hexenyl, 3-hexenyl, 5-hexenyl, 1-heptenyl, 1-octenyl and the like. In the present specification, unless otherwise specified, as "C2-6 alkenyl group" there may be mentioned, for example, ethenyl, 1-propenyl, 2-propenyl, 2-methyl-1-propenyl, 1-butenyl, -butenyl, 3-butenyl, 3-methyl-2-butenyl, 1-pentenyl, 2-pentenyl, 3-pentenyl, 4-pentenyl, 4-methyl-3-pentenyl, 1-hexenyl, 3-hexenyl, 5- hexenyl and the like. In the present specification, unless otherwise specified, as "C2- alkenyl group" there can be mentioned, for example, ethenyl, 1-propenyl, 2-propenyl, 2-methyl-1-propenyl, 1-butenyl, 2- butenyl, 3-butenyl and the like. In the present specification, unless otherwise specified, as "alkynyl group" there may be mentioned an alkynyl group of Con 2 to 10 (eg, 2 to 10, 2 to 8, 2 to 6, 2 to 4) carbon, for example, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-hexynyl, 2-hexynyl , 3-hexynyl, 4-hexynyl, 5-hexynyl, 1-heptynyl, 1-octynyl and the like. In the present specification, unless otherwise specified, there may be mentioned, for example, "C2-alkynyl group" or "ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl". , 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 1-heptynyl, 1-octynyl and the like. In the present specification, unless otherwise specified, as "C2-8 alkynyl group" there may be mentioned, for example, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentinyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl, 1-heptynyl, 1-octynyl and the like. In the present specification, unless otherwise specified, as "C2-6 alkynyl group" there may be mentioned, for example, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1-pentynyl, 2-pentynyl, 3-pentynyl, 4-pentynyl, 1-hexynyl, 2-hexynyl, 3-hexynyl, 4-hexynyl, 5-hexynyl and the like. In the present specification, unless otherwise specified, as "C2-4 alkynyl group" there can be mentioned, for example, ethynyl, 1-propynyl, 2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl and Similar. In the present specification, unless otherwise specified, as "cycloalkyl group" there may be mentioned a cycloalkyl group of Con 3 to 10 (eg, 3 to 10, 3 to 8, 3 to 7, 3 to 6, 5 a 8) carbon atoms, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclo [2, 2, 1] heptyl, bicyclo [2, 2, 2] octyl, bicyclo [3.2, l] octyl , bicyclo [3.2.2] nonyl, bicyclo [3.3, l] nonyl, bicyclo [4.2, l] nonyl, bicyclo [, 3, 1] decyl, adamantyl and the like. In the present specification, unless otherwise specified, as "cycloalkyl group of C3-? 0" is they may mention, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclo [2.2, 1] heptyl, bicyclo [2.2.2] octyl, bicyclo [3.2, 1] octyl, bicyclo [ 3,2,2] nonyl, bicyclo [3, 3, 1] nonyl, bicyclo [4, 2, 1] nonyl, bicyclo [4, 3, 1] decyl, adamantyl and the like. In the present specification, unless otherwise specified, as "C3-8 cycloalkyl group" there may be mentioned, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl, bicyclo [2.2, 1] heptyl, bicyclo [2,2,2] octyl, bicyclo [3, 2, 1] octyl and the like. In the present specification, unless otherwise specified, as "C3-7 cycloalkyl group" there can be mentioned, for example, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cycloheptyl and the like. In the present specification, unless otherwise specified, as "C5-8 cycloalkyl group" there may be mentioned, for example, cyclopentyl, cyclohexyl, cycloheptyl, cyclooctyl and the like. In the present specification, unless otherwise specified, as "cycloalkenyl group" there can be mentioned a cycloalkenyl group of With 3 to 10 carbon atoms, for example, 2-cyclopenten-1-yl, 3-cyclopenten-1-yl , 2-cyclohexen-1-yl, 3-cyclohexen-1-yl and the like.

In the present specification, unless otherwise specified, as "C3-0 cycloalkenyl group" there can be mentioned, for example, 2-cyclopenten-1-yl, 3-cyclopenten-1-yl, 2-cyclohexen-1- ilo, 3-cyclohexen-1-yl and the like. In the present specification, unless otherwise specified, as "cycloalkdienyl group" there can be mentioned a cycloalkadienyl group with 4 to 10 carbon atoms, for example, 2,4-cyclopentadien-1-yl, 2,4-cyclohexadienyl- 1-yl, 2, 5-cyclohexadien-1-yl and the like. In the present specification, unless otherwise specified, as "C4-10 cycloalkalienyl group" there can be mentioned, for example, 2-cyclopentadien-1-yl, 2,4-cyclohexadien-1-yl, 2, 5- cyclohexadiene-1-yl and the like. In the present specification, unless otherwise specified, the term "aryl group" comprises a monocyclic aryl group and a fused polycyclic aryl group. As the "aryl group" there can be mentioned an aryl group of Con 6 to 18 (for example, 6 to 18, 6 to 14, 6 to 10) carbon atoms, for example, phenyl, naphthyl, anthryl, phenanthryl, acenaphthyl, biphenylyl and similar. In the present specification, unless otherwise specified, "aryl group of Ce-xs" may be mentioned, for example, phenyl, naphthyl, anthryl, phenanthryl, acenaphthyl, biphenylyl, and the like.

In the present specification, unless otherwise specified, "aryl group of Cd-4" may be mentioned, for example, phenyl, naphthyl, anthryl, phenanthryl, acenaphthyl, biphenylyl, and the like. In the present specification, unless otherwise specified, "aryl group of C6-?" Or "can be mentioned, for example, phenyl, naphthyl and the like. In the present specification, unless otherwise specified, as "aralkyl group" there can be mentioned an aralkyl group of With 7 to 16 carbon atoms, for example, benzyl, phenethyl, phenylpropyl, naphthylmethyl, biphenylylmethyl and the like. In the present specification, unless otherwise specified, "aralkyl group of C7-X6" may be mentioned, for example, benzyl, phenethyl, phenylpropyl, naphthylmethyl, biphenylylmethyl and the like. In the present specification, unless otherwise specified, as "alkanoyl group" there may be mentioned an alkanoyl group of from 1 to 7 (for example, 1 to 7, 1 to 6) carbon atoms, for example, formyl, alkyl C6-carbonyl (eg, acetyl, propionyl, butyryl, valeryl, pivaloyl) and the like. In the present specification, unless otherwise specified, as "alkanoyl group of C? _6" there may be mentioned, for example, formyl, C-6 alkyl. carbonyl (for example, acetyl, propionyl, butyryl, valeryl, pivaloyl) and the like. In the present specification, unless otherwise specified, as "alkoxy group" there can be mentioned alkoxy group of Con 1 to 6 (for example, 1 to 6, 2 to 6, 1 to 4) carbon atoms, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, n-pentyloxy, n-hexyloxy and the like. In the present specification, unless otherwise specified, as "Cx-e alkoxy group" there can be mentioned, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, n-pentyloxy, n-hexyloxy and the like. In the present specification, unless otherwise specified, as "C-6 alkoxy group" there may be mentioned, for example, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy, n-pentyloxy, n- hexyloxy and the like. In the present specification, unless otherwise specified, "C? -4 alkoxy group" may be mentioned, for example, methoxy, ethoxy, n-propoxy, isopropoxy, n-butoxy, tert-butoxy and the like. In the present specification, unless otherwise specified, as "alkylene" there may be mentioned an alkylene of Con 1 to 4 (eg, 1 to 4, 1 to 3) carbon atoms, for example, -CH 2 -, - CH2CH2-, _ (CH2) 3-, - (CH2) 4-, CH (CH3) -, -C (CH3) 2-, -CH (CH3) CH2-, -CH2CH (CH3) -, -C (CH3 ) 2CH2-, - CH2C (CH3) 2- and the like. In the present specification, unless otherwise specified, as "C? -4 alkylene" there may be mentioned, for example, -CH2-, -CH2CH2-, - (CH2) 3-, - (CH2) 4-, -CH (CH3) -, -C (CH3) 2-, -CH (CH3) CH2-, -CH2CH (CH3) -, -C (CH3) 2CH2-, -CH2C (CH3) 2- and the like. In the present specification, unless otherwise specified, as "alkylene of C? _3" there may be mentioned, for example, -CH2-, -CH2CH2-, - (CH2) 3-, - (CH2) 4-, - CH (CH3) -, -C (CH3) 2-, -CH (CH3) CH2-, -CH2CH (CH3) - and the like. In the present specification, unless otherwise specified, as "hydrocarbon group" of the "optionally substituted hydrocarbon group" there can be mentioned, for example, an alkyl group, an alkenyl group, an alkynyl group, a cycloalkyl group, a cycloalkenyl group , a cycloalkadienyl group, an aryl group, an aralkyl group, an arylalkenyl group, a cycloalkyl-alkyl group and the like. Of these, an alkyl group of C-10, a C2-? Alkenyl group or an alkynyl group of C2-xcw a cycloalkyl group of C-? Or a cycloalkenyl group of C-? Or a cycloalkdienyl group C4_ ?, an aryl group of Cg-? 4, an aralkyl group of C7-16, an arylalkenyl group of C? -3, a cycloalkyl group of C-? or-C? _6 alkyl and the like. The cycloalkyl group of C3-? 0, cycloalkenyl group of C3-X0 and cycloalkdienyl group of C4-? Or aforementioned are each optionally condensed with a Benzene ring, and as such may be mentioned a fused ring group, for example, indanyl, dihydronaphthyl, tetrahydronaphthyl, fluorenyl and the like. In addition, as the aforementioned hydrocarbon group, there may also be cited a crosslinked hydrocarbon group such as norbornyl, adamantyl and the like, and others. As the arylalkenyl group of Cs-β3 there may be mentioned, for example, styryl and the like. As the C3-α- or C-6-alkylcycloalkyl group, there can be mentioned, for example, cyclopropylmethyl, cyclohexylmethyl and the like. The abovementioned C alquilo _? 0 alkyl, C2-, C o- al o alkenyl and C alqu-? Alkynyl group, which are exemplified as the "hydrocarbon group", each optionally has 1 to 3 substituents in positions replaceable As such substituents there may be mentioned, for example, (1) a cycloalkyl group of C3-X0 (for example, cyclopropyl, cyclohexyl) optionally substituted with 1 to 3 substituents selected from the group consisting of halogen; hydroxy; carboxyl; sulfo; cyano; azido; nitro; nitrous; optionally halogenated C? -4 alkyl; optionally halogenated C2_4 alkenyl; optionally halogenated C2_4 alkynyl; C7 cycloalkyl; C6-4 aryl; aralkyl of C7-16; formyl; optionally halogenated C? _6-carbonyl alkyl; optionally halogenated C6-carbonyl alkoxy; optionally halogenated C? -6-sulfonyl alkyl; carbamoyl; carbamoyl mono- or disubstituted with optionally halogenated C? -6 alkyl; mono- or di-aryl of C6-? 4-carbamoyl; thiocarbamoyl optionally mono- or disubstituted with optionally halogenated C? -6 alkyl; ureido optionally mono- or disubstituted with optionally halogenated C? -6 alkyl; pono- or di-aryl of C6-? 4-ureido; sulfamoyl optionally mono- or disubstituted with optionally halogenated C? -6 alkyl; optionally halogenated C-6 alkoxy; optionally halogenated C2-6 alkenyloxy; C3-10 cycloalkyloxy; C7-X6 aralkyloxy; Cd-β4 aryloxy; C? -6-carbonyloxy alkyl; C3_ [alpha] o-C6-C6 alkoxy, C6-6 alkylsulfonyloxy, mercapto, optionally halogenated C6-6 alkylthio, C7_16 aralkylthio, C6_4alkaryl, C6_6 alkylsulfinyl, oxo; C 1 -3 alkylenedioxy (for example, methylenedioxy, ethylenedioxy); hydroxyaryano optionally substituted with C 6 -6 alkyl, and the like (substituent group S): (2) an aryl group of C 6 - 4 (for example, phenyl, naphthyl) optionally substituted with 1 to 3 substituents selected from the substituent group S; (3) a heterocyclic group optionally substituted with 1 to 3 substituents selected from the substituent group S; (4) an amino group optionally substituted with 1 or 2 substituents selected from the group consisting of C? -6 alkyl optionally substituted with substituents selected from the group consisting of halogen, hydroxy, C3_7 cycloalkyl, C? -6 alkyl sulfonyl, C6-6 alkoxy and the like; C2-4 alkenyl optionally halogenated; optionally halogenated C2-4 alkynyl; C3-7 cycloalkyl; C6-? 4 aryl, "C7-6 aralkyl, 4- to 7-membered heterocyclic group (preferably 5 or 6 membered) (eg, non-aromatic heterocyclic group such as morpholinyl and the like) which contains, as a constituent atom of the ring, in addition to carbon atoms, 1 to 4 heteroatoms selected from the group consisting of an oxygen atom, a sulfur atom and a nitrogen atom; formyl; C? -6-carbonyl alkyl optionally substituted with substituents selected from the group consisting of halogen, hydroxy, C3_7 cycloalkyl, C6-6-sulfonyl alkyl, C6-6 alkoxy and the like; C6-6-carbonyl alkoxy; C6-4-carbonyl aryl (eg, benzoyl); C7-16 aralkylcarbonyl (e.g., benzylcarbonyl, phenethylcarbonyl); C3-7-carbonyl cycloalkyl; C? -6-carbamoyl alkyl (e.g., methylaminocarbonyl, ethylaminocarbonyl); C6-i4-carbamoyl aryl (e.g., phenylaminocarbonyl, 1-naphthylaminocarbonyl, 2-naphthylaminocarbonyl); C7_6-carbamoyl aralkyl (e.g., benzylaminocarbonyl); C 1-6 alkylsulfonyl (for example, methylsulfonyl, ethylsulfonyl, isopropylsulfonyl); C6-? 4 arylsulfonyl (for example, benzenesulfonyl, toluenesulfonyl, 1-naphthalenesulfonyl, 2-naphthalenesulfonyl); C7-? 6 aralkylsulfonyl (for example, benzylsulfonyl); and the like (substituent group T); (5) an amidino group; (6) an optionally formyl or halogenated C -6-carbonyl alkyl group; (7) an optionally halogenated C?-E-carbonyl alkoxy group; (8) an optionally halogenated C? -6 alkylsulfonyl (eg, methylsulfonyl); (9) a carbamoyl group optionally substituted with 1 or 2 substituents selected from the substituent group T; (10) an optionally mono- or disubstituted thiocarbamoyl group with optionally halogenated C alquilo alkyl group (11) a ureido group optionally substituted with 1 or 2 substituents selected from the substituent group T; (12) a sulfamoyl group optionally substituted with 1 or 2 substituents selected from the substituent group T; (13) a carboxyl group; (14) a hydroxy group; (15) a C? -6 alkoxy group optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, carboxyl, C-g alkoxy and C? -6-carbonyl alkoxy; (16) an optionally halogenated C2_6 alkenyloxy group (e.g., ethenyloxy); (17) a cycloalkyloxy group of C3-X0 (for example, cyclohexyloxy); (18) an aralkyloxy group of C7-X6 (for example, benzyloxy); (19) an aryloxy group of C6-? (for example, phenyloxy, naphthyloxy); (20) an alkyl group of C6-6-carbonyloxy (for example, acetyloxy, tert-butylcarbonyloxy); (21) a mercapto group; (22) an optionally halogenated C? -6 alkyl group (eg, methylthio, ethylthio); (23) an aralkylthio group of C7-6 (for example, benzylthio); (24) an arylthio group of Cg-i4 (for example, phenylthio, naphthylthio); (25) a sulfo group; (26) a cyano group; (27) an azido group; (28) a nitro group; (29) a nitrous group; (30) a halogen atom; (31) an alkylsulfinyl group of C? -6 (for example, methylsulfinyl); (32) an oxo group; (33) a C3-10 cycloalkyl-C6-6 alkoxy group (e.g., cyclopropylmethoxy); (34) an alkylene dioxy group C? -3 (for example, methylenedioxy, ethylenedioxy); (35) a hydroxyimino group optionally substituted with C? -6 alkyl, "and the like (substituent group U). number of substituents is not less than 2, the respective substituents may be the same or different. The cycloalkyl group of C3-X0, cycloalkenyl group of C3-X0, cycloalkalienyl group C4-10, aryl group of C6-? 4, aralkyl group of C7-16, aryl group of Cs-13-alkenyl and cycloalkyl group of C3- The aforementioned C 1 -C 6 -alkyl, which are listed by way of example as the "hydrocarbon group", each optionally have 1 to 3 substituents in substitutable positions. As such substituents there may be mentioned, for example, (1) a substituent selected from the substituent group U; (2) an alkyl C de-α group or optionally substituted with 1 to 3 substituents selected from the substituent group U; (3) a C2-? O alkenyl group (eg, ethenyl, 1-propenyl) optionally substituted with 1 to 3 substituents selected from the substituent group U; (4) an aralkyl group of C7-? 6 (for example, benzyl) optionally substituted with 1 to 3 substituents selected from the substituent group U; and the like (substituent group V). When the number of substituents is not less than 2, the respective substituents may be the same or different.

In the present specification, unless otherwise specified, as "heterocyclic group" of the "optionally substituted heterocyclic group" there may be mentioned an aromatic heterocyclic group and a non-aromatic heterocyclic group. As the aromatic heterocyclic group, there can be mentioned, for example, a 4 to 7 membered monocyclic aromatic heterocyclic group (preferably 5 or 6 membered) containing, as ring constituent atom In addition to carbon atoms, 1 to 4 heteroatoms selected from the group consisting of group consisting of an oxygen atom, a sulfur atom and a nitrogen atom and a fused aromatic heterocyclic group. As the fused aromatic heterocyclic group there can be mentioned, for example, a group derived from a fused ring in which a ring corresponding to such monocyclic aromatic heterocyclic group of 4 to 7 members, and 1 or 2 rings selected from the group consisting of 5 or 6 membered ring containing 1 or 2 nitrogen atoms, a 5 membered ring containing a sulfur atom, a Benzene ring and the like. As preferred examples of the aromatic heterocyclic group there may be mentioned monocyclic aromatic heterocyclic groups such as furyl (e.g., 2-furyl, 3-furyl), thienyl (e.g., 2-thienyl, 3-thienyl), pyridyl (e.g., 2-pyridyl, 3-pyridyl, 4-pyridyl), pyrimidinyl (e.g. , 2-pyrimidinyl, 4-pyrimidinyl, 5-pyriraidinyl, 6-pyrimidinyl), pyridazinyl (e.g., 3-pyridazinyl, 4-pyridazinyl), pyrazinyl (e.g., 2-pyrazinyl), pyrrolyl (e.g., 1-pyrrolyl) , 2-pyrrolyl, 3-pyrrolyl), imidazolyl (for example, 1-imidazolyl, 2-imidazolyl, 4-imidazolyl, 5-imidazolyl), pyrazolyl (e.g., 1-pyrazolyl, 3-pyrazolyl, 4-pyrazolyl), thiazolyl (e.g., 2-thiazolyl, 4-thiazolyl, 5-thiazolyl), isothiazolyl (e.g., 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl), oxazolyl (e.g., 2-oxazolyl, 4-oxazolyl, -oxazolyl), isoxazolyl (e.g., 3-isoxazolyl, 4-isoxazolyl, 5-isoxazolyl), oxadiazolyl (e.g., 1,2,4-oxadiazol-5-yl, 1,3,4-oxadiazol-2-yl) ), thiadiazolyl (for example, 1,3,4-thiadiazol-2-yl), triazolyl (per axis) mplo, 1,2,4-triazol-1-yl, 1, 2,4-triazol-3-yl, 1, 2, 3-triazol-1-yl, 1, 2, 3-triazol-2-yl, 1, 2, 3-triazol-4-yl), tetrazolyl (for example, tetrazol-1-yl, tetrazol-5-yl), triazinyl (for example, 1,2,4-triazin-1-yl, 1, 2,4-triazin-3-yl) and the like; fused aromatic heterocyclic groups such as quinolyl (for example, 2-quinolyl, 3-quinolyl, 4-quinolyl, 6-quinolyl), isoquinolyl (eg, 3-isoquinolyl), quinazolyl (eg, 2-quinazolyl, 4-quinazolyl), quinoxalyl (eg, 2-quinoxalyl, 6-quinoxalyl), benzofuryl (eg example, 2-benzofuryl, 3-benzofuryl), benzothienyl (e.g., 2-benzothienyl, 3-benzothienyl), benzoxazolyl (e.g., 2-benzoxazolyl), benzisoxazolyl (e.g., 7-benzisoxazolyl), benzothiazolyl (e.g. 2-benzothiazolyl), benzimidazolyl (for example, benzimidazol-1-yl, benzimidazol-2-yl, benzimidazol-5-yl), benzotriazolyl (for example, 1H-1, 2, 3-benzotriazol-5-yl), indolyl (for example, indol-1-yl, indole-2-yl, indole-3-yl, indole-5-yl), indazolyl (e.g., lH-indazol-3-yl), pyrrolopyrazinyl (e.g. pyrrolo [2, 3-b] pyrazin-2-yl, lH-pyrrolo [2, 3-b] pyrazin-6-yl), imidazopyridinyl (e.g., 1H-imidazo [4, 5-b] pyridin-2-) ilo, 1H-imidazo [4, 5-c] pyridin-2-yl, 2H-imidazo [1, 2-a] pyridin-3-yl), imidazopyrazinyl (by e Example, lH-imidazo [4, 5-b] pyrazin-2-yl), pyrazolopyridinyl (e.g., lH-pyrazolo [, 3-c] pyridin-3-yl), pyrazolothienyl (e.g., 2H-pyrazolo [3 , 4-b] thiophen-2-yl), pyrazolotriazinyl (e.g., pyrazolo [5, 1-c] [1, 2,] triazin-3-yl) and the like; and similar. As the non-aromatic heterocyclic group there may be mentioned, for example, a non-aromatic heterocyclic group 4 to 7 membered monocyclics (preferably 5 or 6 membered) containing, as ring constituent atom In addition to carbon atoms, 1 to 4 heteroatoms selected from the group consisting of an oxygen atom, a sulfur atom and a nitrogen atom and a non-aromatic heterocyclic fused group. As the fused non-aromatic heterocyclic group there can be mentioned, for example, a group derived from a fused ring in which a ring corresponding to such a monocyclic non-aromatic heterocyclic group of 4 to 7 members, and 1 or 2 rings selected from the group consisting of in a 5 or 6 membered ring containing 1 or 2 nitrogen atoms, a 5 membered ring containing a sulfur atom, a benzene ring and the like, and others. Preferred examples of non-aromatic heterocyclic group may be mentioned non-aromatic monocyclic heterocyclic groups such as oxetanyl (e.g., 2-oxetanyl, 3-oxetanyl), pyrrolidinyl (e.g. 1-pyrrolidinyl, 2-pyrrolidinyl), piperidinyl ( example, piperidino, 2-piperidinyl, 3-piperidinyl, 4-piperidinyl), morpholinyl (eg morpholino), thiomorpholinyl (e.g., thiomorpholino), piperazinyl (e.g. 1-piperazinyl, 2-piperazinyl, 3-piperazinyl) , hexamethyleneiminyl (by eg yl hexamethyleneimin-1), oxazolidinyl (e.g., oxazolidin-2-yl), thiazolidinyl (e.g., thiazolidin-2-yl), imidazolidinyl (e.g., imidazolidin-2-yl, imidazolidin-3-yl) , oxazolinyl (e.g., oxazolin-2-yl), thiazolinyl (e.g., thiazolin-2-yl), imidazolinyl (e.g., imidazolin-2-yl, imidazolin-3-yl), dioxolyl (e.g., 1, 3-dioxol-4-yl), dioxolanyl (e.g., 1,3-dioxolan-4-yl), dihydrooxadiazolyl (e.g., 4,5-dihydro-l, 2,4-oxadiazol-3-yl), -tioxo-l, 3-oxazolidin-5-yl, pyranyl (e.g., 4-pyranyl), tetrahydropyranyl (e.g., 2-tetrahydropyranyl, 3-tetrahydropyranyl, 4-tetrahydropyranyl), thiopyranyl (e.g., 4-thiopyranyl) , tetrahydrothiopyranyl (e.g., 2-tetrahydrothiopyranyl, 3-tetrahydrothiopyranyl, 4-tetrahydrothiopyranyl), 1-oxidotetrahydrothiopyranyl (e.g., l-oxidotetrahydrothiopyran-4-yl), 1,1-dioxidotetrahydrothiopyranyl (e.g., 1,1-dioxidotetrahydrothiopy) RAN-4-yl), tetrahydrofuryl (e.g., tetrahydrofuran-3-yl, 2-tetrahydrofuran-), pyrazolidinyl (e.g., pyrazolidin-1-yl, pyrazolidin-3-yl), pyrazolinyl (e.g., pirazolin- 1-yl), tetrahydropyrimidinyl (e.g., tetrahydropyrimidin-1-yl), dihydrotriazolyl (e.g., 2,3-dihydro-lH-l, 2,3-triazol-1-yl), tetrahydrotriazolyl (e.g., 2, 3,4,5-tetrahydro-lH-1,2,3-triazol-1-yl) and the like; Non-aromatic heterocyclic groups fused such as dihydroindolyl (e.g., 2, 3-dihydro-lH-indol-1-yl), dihydroisoindolyl (e.g., 1, 3-dihydro-yl 2H-isoindol-2-), dihydrobenzofuranyl (by example, 2,3-dihydro-l-benzofuran-5-yl), dihydrobenzodioxinyl (e.g., 2,3-dihydro-l, 4-benzodioxinyl), dihydrobenzodioxepinyl (e.g., 3,4-dihydro-2H-l, 5-benzodioxepinyl), tetrahydrobenzofuranyl (for example, 4, 5, 6, 7-tetrahydro-l-benzofuran-3-yl), chromenyl (for example, 4H-chromen-2-yl, 2H-chromen-3-yl) , dihydroquinolinyl (eg, 1,2-dihydroquinolin-4-yl), tetrahydroquinolinyl (e.g., 1,2,3,4-tetrahydroquinolin-4-yl), dihydroisoquinolinyl (e.g., 1,2-dihydroisoquinolin-4-) ilo), tetrahydroisoquinolinyl (e.g., 1,2,3,4-tetrahydroisoquinolin-4-yl), dihydrophthalazinyl (e.g., 1,4-dihydrophthalazin-4-yl) and the like. The "heterocyclic group" of the "optionally substituted heterocyclic group" optionally has 1 to 3 substituents in substitutable positions. Substituents selected from substituent group V may be mentioned, for example, as such substituents. When the number of substituents is not less than 2, the respective substituents may be the same or different.

In the present specification, unless otherwise specified, as "aliphatic hydrocarbon group" of the "optionally substituted aliphatic hydrocarbon group" there can be mentioned a linear or branched aliphatic hydrocarbon group having 1 to 10 carbon atoms (preferably 1 to 8 carbon atoms). As the "aliphatic hydrocarbon group" there may be mentioned, for example, an alkyl group of C? -10, a C2-? Or alkenyl group, an alkynyl group of C2-? O and a cycloalkyl group of C3-X0 (each group is like was defined earlier). The "aliphatic hydrocarbon group" is optionally substituted with substituents selected from substituent group V, in particular, 1 to 3 substituents selected from the group consisting of halogen, hydroxy, C? -4 alkoxy, C? -4-carbonyl alkyl, carboxy, C? -4-carbonyl alkoxy, cyano, carbamoyl, sulfamoyl, nitro, amino, C? -4-carbonylamino alkyl, C? -4-carbonylamino alkoxy and C? -4-sulfonylamino alkyl. When the number of substituents is not less than 2, the respective substituents may be the same or different. In the present specification, unless otherwise specified, as "acyl group" there may be mentioned, for example, -COR? L, -CO-OR? L, -S02RY1, -SOR? L, -PO (OR? L ) (OR? 2) (where R? And R? 2 are the same or different and each is a hydrogen atom, a hydrocarbon group optionally substituted, or an optionally substituted heterocyclic group), and the like. In the present specification, unless otherwise specified, the "amino group" of the "optionally substituted amino group", the "carbamoyl group" of the "optionally substituted carbamoyl group", the "ureido group" of the "optionally substituted ureido group" and the "sulfamoyl group" of the "optionally substituted sulfamoyl group" optionally have 1 or 2 substituents in substitutable positions. As such substituents there may be mentioned, for example, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, an acyl group and the like. Of these, 1 or 2 substituents selected from the substituent group T are preferred. When the number of substituents is not less than 2, the respective substituents may be the same or different. When the aforementioned nitrogen atom constituting the amino group, carbamoyl group, ureido group or sulfamoyl group is substituted with two substituents, these substituents can be combined, together with the adjacent nitrogen atom, a nitrogen-containing heterocycle. As "nitrogen-containing heterocycle" there may be mentioned, for example, a 3 to 8-membered heterocycle with nitrogen containing, as ring constituent atom, in addition to carbon atoms, at least one carbon atom. nitrogen and also optionally contains one or two heteroatoms selected from the group consisting of an oxygen atom, a sulfur atom and a nitrogen atom. As preferred examples of the nitrogen-containing heterocycle, there may be mentioned a 5- or 6-membered cyclic amine optionally containing an oxygen atom (eg, 1-pyrrolidine, piperidine, 1-piperazine, morpholine). In the present specification, unless otherwise specified, the "imino group" of the "optionally substituted imino group" optionally has 1 or 2 substituents in substitutable positions. As such substituents there may be mentioned, for example, an optionally substituted hydrocarbon group, an optionally substituted heterocyclic group, an acyl group and the like. Of these, substituents selected from the substituent group T are preferred. When the number of substituents is not less than 2, the respective substituents may be the same or different. In the present specification, unless otherwise specified, as "optionally substituted group attached through a carbon atom, a nitrogen atom or an oxygen atom", there may be mentioned a group represented by the formula: -Xx- Rx, an amino group and a hydroxy group. In the aforementioned formula, Xx is a link, -NRY- (where R? Is a hydrogen atom or an alkyl group of C? -6) or -0-. In the aforementioned formula, Rx is a cyano group, or an alkyl group of C? _8, a C2-8 alkenyl group, a C2_8 alkynyl group, a carbamoyl group, a C? -8-carbonyl alkyl group, a C3_8 cycloalkyl group, an aryl group of C6-? 8, an aryl group of C6-? s-C? -4 alkyl, an aryl group of C6-? 8_carbonyl, an aryl group of C6-? 8-alkyl of C 4 -carbonyl, a heterocyclic group, a heterocyclyl-C 4 alkyl group, a heterocyclylcarbonyl group or a heterocyclyl C 4 alkylcarbonyl group, each of which is optionally substituted. In the above-mentioned formula, the "C? -8 alkyl group", "C2_8 alkenyl group", "C? -8 alkynyl group", "carbamoyl group", "C? -8-carbonyl alkyl group", "C3-8 cycloalkyl group", "aryl group of Ce-is'V" aryl group of C6-? 8 ~ algyl of C-4"," aryl group of C6-i8_carbonyl "," aryl group of C6- ? 8-C? -4 -carbonyl alkyl, "" heterocyclic group, "" heterocyclyl-C? -4 alkyl group, "" heterocyclylcarbonyl group "and" heterocyclyl-C4-carbonyl group "for Rx are optionally substituted with one or more (preferably 1 to 5, more preferably 1 to 3) substituents selected, for example, from the following group (substituent group X) (a) a halogen atom, (b) an oxo group, (c) an optionally halogenated C? -4 alkyl group, (d) group - (CH2) m-Qx, (e) C? - alkyl group optionally halogenated with - (CH2) m -Zlx-, (f) group - (CH2) m-Zlx-cycloalkyl of C3-8, (g) group - (CH2) m -Z2x- (CH2) n-Qx, (h) alkyl group of C? - 4 optionally halogenated with - (CH2) m -Z2x- (CH2) n -Zlx-, (i) group - (CH2) m -Z2x- (CH2) n-Zlx- cycloalkyl of C3-s, (j) group - (CH2) optionally substituted heterocyclic m-Zlx (preferably, the heterocyclic group is a 5- to 8-membered heterocyclic group containing 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and an oxygen atom; sulfur optionally oxidized), (k) group - (CH2) m- Z2x-C4-4 alkoxy, and (1) group - (CH2) m- Z2x- (CH2) n- Zlx- (CH2) n- Zlx -alkyl of C? -4 - R? it is preferably a hydrogen or methyl atom, with particular preference a hydrogen atom. In the aforementioned formula, m is an integer from 0 to 4, n is an integer from 1 to 4, Qx is hydroxy, carboxy, cyano, nitro, -NRlxR2x, -CONRlxR2x or -S02NRlxR2x, Zlx is -O-, -CO-, -C (OH) R3x-, -C (= N-OR3x) -, -S- , -SO-, -S02-, -N (COR3x) -, -N (C02R4x) -, -N (S02R4x) -, -CO-O-, -O-CO-, -CO-NR3 -, -NR3x -CO-, -NR3x-C02-, -NR3x-CO-NH-, -NR3x-S02- or -NR3x-C (= NH) -NH-, Z2x is -O-, -CO-, -C (OH ) R3x-, -C (= N-OR3x) -, -S-, -SO-, -S02-, -NR3x-, -N (COR3x) -, -N (C02R4x) -, -N (S02R x) -, -CO-O-, -O-CO-, -CO-NR3x-, -NR3x-CO-, -NR3x-C02-, -NR3x-CO-NH-, -NR3x-C (= NH) -NH -, -NR3x-S02- or -S02-NR3x-. In the aforementioned formula, - (CH2) m- and (CH2) n- are optionally substituted with one or more (preferably 1 to 5, more preferably 1 to 3) substituents selected, for example, from the group consisting of halogen, optionally halogenated C ?4 alkyl and hydroxy, and when mon is not less than 2, a subgroup -CH2CH2- of - (CH2) m- or - (CH2) n- is optionally replaced by -CH = CH-o -C = C-. In the aforementioned formula, R1x and R2x are the same or different and each is a hydrogen atom or an alkyl of C4-4, or R1x and R2x optionally join to form a ring together with the nitrogen atom. In the aforementioned formula, R x is a hydrogen atom or a C 4 alkyl, and R 4 x is a C 4 alkyl. When Rlx and R2x are joined to form a ring together with the nitrogen atom, as the nitrogen-containing heterocycle, there can be mentioned, for example, saturated or unsaturated (preferably saturated) 3 to 8-membered (preferably 5 or 6 membered) aliphatic heterocyclic groups such as azetidine, pyrrolidine, piperidine, homopiperidine, heptamethyleneimine, morpholine, thiomorpholine, piperazine, homopiperazine and the like. In the present specification, unless otherwise specified, as "optionally substituted group attached through a carbon atom or a sulfur atom" there may be mentioned an alkyl group of C? _8, a C2-8 alkenyl group, an C2-8 alkynyl group, a carbamoyl group, a C? -8-carbonyl alkyl group, a C? -8-thio alkyl group, a C? -8-sulfonyl alkyl group, a C3- cycloalkyl group 8, an aryl group of Cd-is, an aryl group of C6-8 ~ algyl of C_4, an aryl group of C6-? 8_carbonyl, an aryl group of C6-? 8-C? -4-carbonyl alkyl, an aryl group of C6-? 8_thio, an aryl group of Cd-xs-sulfonyl, a heterocyclic group, a heterocyclyl-C? _ alkyl group, a heterocyclylcarbonyl group, a heterocyclyl-C? -4-carbonyl group , a heterocyclylthio group and a heterocyclyl-C de -4 -thio alkyl group, each of which is optionally substituted, and the like. The "C-8 alkyl group", "C2-8'V alkenyl group" C2-8 alkynyl group "," carbamoyl group "," alkyl group " of C? -8-carbonyl "," alkyl group of C? -8"," alkylsulfonyl group of C? _8"," C3-8 cycloalkyl group "," aryl group of C6-i8'V "aryl group of C6-? 8-C? -4 alkyl, "aryl group of C6-? 8-carbonyl", "aryl group of C6-? 8-alkyl of C? _4-carbonyl", "arylthio group of C6-? 8"," C6-? 8 arylsulfonyl group "," heterocyclic group "," heterocyclyl-C-4 alkyl group "," heterocyclylcarbonyl group "," heterocyclyl-C-4-carbonyl group "," "heterocyclylthio group" and "C4-4 heterocyclyl-alkylthio group" are optionally substituted with one or more (preferably 1 to 5, more preferably 1 to 3) substituents selected, for example, from substituent group X. DETAILED DESCRIPTION OF THE INVENTION [compound (la)] The present invention provides a compound represented by the formula (Ia) or a salt thereof (in the present specification, now more abbreviated sometimes as where each symbol is as defined with anteriority R2a is preferably an alkyl group of C6-6 (in particular, an ethyl group) substituted with a group represented by the formula "-NR6aa-CO-CR7aR8a-S02-C4-4 alkyl". In the formula, R6aa is a hydrogen atom or a methyl group, and R7a and R8a are the same or different and each is a hydrogen atom or a methyl group. R7a and R8a are preferably methyl groups. R 3a is preferably a hydrogen atom. As the "halogen atom" for R 4a, a chlorine atom is preferred. As the "Cx-e alkyl group" for R 4a, a methyl group is preferred. R 4a is preferably a chlorine atom or a methyl group. As the "halogen atom" for R5a, a fluorine atom and a chlorine atom are preferred. As the "Cx-e alkyl group" for R5a, a methyl group is preferred. R5a is preferably a fluorine atom, a chlorine atom or a methyl group. Corao "halogen atom" for Xa, a fluorine atom is preferred. Xa is preferably a hydrogen atom or a fluorine atom, more preferably a hydrogen atom. As a preferred embodiment of the compound (la), the compound (la) can be mentioned wherein R a is a hydrogen atom, R 2a is an alkyl group of C 6 -6 (in particular, an ethyl group) substituted with a group represented by -NR 6 aaa-CO-CR 7 a R 8 a-S 0 2 -alkyl of C 0 -4 wherein R 6 a is a hydrogen atom or a methyl group, R7a and R8a are the same or different and each is a hydrogen atom or a methyl group, R3a is a hydrogen atom, R4a is a chlorine atom or a methyl group, R5a is a fluorine atom, a chlorine atom or a methyl group, and Xa is a hydrogen atom or fluorine atom (preferably, a hydrogen atom). As the most preferred embodiment of the compound (la), the co-moiety (la) in which Rla is a hydrogen atom can be mentioned, R2a is an alkyl group of C? _6 (in particular, an ethyl group) substituted with a group represented by -NR6aa-CO-CR7aR8a-S02-C4-4 alkyl wherein R6aa is a hydrogen atom or a methyl group, R7a and R8a are methyl groups, R3a is a hydrogen atom, R4a is a chlorine atom or a methyl group, R5a is a fluorine atom, a chlorine atom or a methyl group, and Xa is a hydrogen atom or fluorine atom (preferably a hydrogen atom). As the compound, there can be mentioned, with particular preference, N- [2- (4- ([3-chloro-4- (3-chlorophenoxy) phenyl] amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2-methyl-2- (methylsulfonyl) propanamide, N- [2- (4- { [3-chloro-4- (3-chlorophenoxy) phenyl] amino.} - 5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2- (ethylsulfonyl) acetamide, N- [2- (4- ([3-chloro-4- (3-chlorophenoxy) phenyl] amino] .}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -N, 2-dimethyl-2- (methylsulfonyl) propanamide, N- [2- (4- { [3- chloro-4- (3-methylphenoxy) phenyl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2- (methylsulfonyl) acetamide, N- [2- (4- { [3-Chloro-4- (3-fluorophenoxy) phenyl] amino.} - 5 H -pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2- (methylsulfonyl) acetamide, and N - [2- (4- { [4- (3-chlorophenoxy) -3-methylphenyl] amino.}. -5H-pyrrolo [3, 2-d] pyrimidin-5-yl) ethyl] -2-methy1 -2- (methylsulfonyl) propanamide, and its salts and hydrates. [Compound (Ib)] The present invention also provides n a compound represented by the formula (Ib) or one of its salts (in the present specification, now more abbreviated sometimes as "compound (Ib)"). where each symbol is as defined previously. In the aforementioned formula (Ib), the "pyridine ring" of the "optionally substituted pyridine ring" for the Ab ring is optionally substituted, for example, by a group represented by the formula: -Y2b-Bb '. Y2b is a bond, -O-, -O- (alkylene of C? _3) -, -NRzb- (wherein Rzb is a hydrogen atom or an alkyl group of C? -6), or -S-, and Bb 'is an aryl group of Cg-? 8 (preferably an aryl group of Ce-? 4, more preferably a phenyl group), a heterocyclic group (preferably a heterocyclic group of 5 or 6 members, with higher preferably a pipdyl group or a pipepdyl group), a C3-8 cycloalkyl group (preferably a cyclohexyl group), a carbamoyl group, a ureido group, an aryl group of C6-? 8carbonyl or an aryl group of C6 -? 8-carbon alkyl, each of which is optionally substituted.

Y2b is preferably a bond, -0- or -0CH2-, more preferably -0- or -0CH2-, with particular preference -0-. The "aplo group of C6-? 8", "heterocyclic group", "C3-8 cycloalkyl group", "carbamoyl group", "ureido group", "apl group of C6_? 8-carbon? Lo" and "group aryl of C6-i8_ alkyl of C? -4-carbon? lo "of" group aplo of C6-18, heterocyclic group, cycloalkyl group of C3_8, carbamoyl group, ureido group, apl group of C6-? 8 ~ carbon? lo or aryl group of Cβ-xa-C? -4-carbonyl alkyl, each of which is optionally substituted "for Bb each optionally having 1 to 5 same or different substituents in any substitutable position. As substituents, substituents similar to those of substituent group V mentioned above can be mentioned. Of these, optionally halogenated C 1-6 alkyl, optionally halogenated C? -6 alkoxy, C? -6-carbamoyl and halogen alkyl are preferred. Bb is preferably an optionally substituted C 1 -4 group of C 1 -s, more preferably a phenyl group optionally substituted with substituents selected from the group consisting of optionally halogenated C 1 -6 alkyl, optionally halogenated C 6 -alkoxy, alkyl C6-carbamoyl and halogen (preferably a phenyl group optionally substituted with substituents selected from the group consisting of optionally halogenated C? -6 alkyl, optionally halogenated C? -6 alkoxy, and C? -6-carbamoyl alkyl), particularly preferably a phenyl group optionally substituted in the 3-position by selected substituents of the group consisting of optionally halogenated C? _6 alkyl, optionally halogenated C-6 alkoxy, C? -6-carbamoyl alkyl and halogen (preferably, a phenyl group optionally substituted in the 3-position by substituents selected from the group consists of optionally halogenated C? -6 alkyl, optionally halogenated C? _6 alkoxy, and C? -6-carbamoyl alkyl). The "pyridine ring" of the "optionally substituted pyridine ring" for the Ab ring optionally also has, in addition to the group represented by the formula: -Y2b-Bb, 1 to 3 same or different substituents in any substitutable position. As substituents, substituents similar to those of substituent group V mentioned above can be mentioned. Of these, halogen and methyl are preferred. The ring Ab is preferably an optionally substituted pyridine ring, in addition to the group represented by the formula: -Y2b-Bb ', with substituents selected from the group consisting of halogen and methyl, more preferably a pyridine ring also optionally substituted, in addition to the group represented by the formula: -Y2b-Bb ', by halogen. As the "aliphatic hydrocarbon group" of the "optionally substituted aliphatic hydrocarbon group" for R3b, an alkyl group of C6-6 is preferred. "C? -4" alkylene and "-0- (C? -4 al alkylene) -" of the "C al _4 alkylene or -0- (C? -4 al alkylene) -, each of which is optionally substituted "for Ylb are optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, hydroxy, C? _4 alkoxy, C? -4-carbonyl, carboxy, C alco alco alkoxy 4-carbonyl, cyano, carbamoyl, sulfamoyl, nitro, amino, C 4 -carbonylamino alkyl, C 4 -4 -carbonylamino alkoxy and C 4 -4 -sulfonylamino alkyl. Xlb is preferably -NR 3b- In the formula, R3b is preferably a hydrogen atom or an alkyl group of C-6, more preferably a hydrogen atom, b is preferably C (Rlb), as an "optionally substituted group attached through an atom". of carbon, a nitrogen atom or an oxygen atom "for Rlb, a cyano group and an optionally substituted C? -8 alkyl group are preferred. As the C? -a alkyl group, an alkyl group of C? As substituents for the alkyl group, substituents similar to those of the group may be mentioned. substituent X mentioned above. Of these, halogen is preferred. R1 is preferably a hydrogen atom, a halogen atom, a cyano group or an optionally halogenated C6-6 alkyl group, more preferably a hydrogen atom. As "optionally substituted group attached through a carbon atom or a sulfur atom" for R2b, an optionally substituted C? _ _ Alkyl group is preferred. As the C? -8 alkyl group, an alkyl group of C? 6- As substituents for the alkyl group, substituents similar to those of the aforementioned substituent group X can be used, preferably substituents selected from the group consisting of (i) -NR6ba-CO- (CH2) ni-S02-alkyl of C? -4 wherein R6ba is a hydrogen atom or a methyl group, nor is an integer from 1 to 4, and - (CH2) nl- is optionally substituted with C? -4 alkyl, (ii) -NR6bb -CO- (CH2) n2-OH wherein R6b is a hydrogen atom or a methyl group, n2 is an integer from 1 to 4, and - (CH2) n2- is optionally substituted with C? _4 alkyl, ( iii) -0- (CH2) n3-OH where n3 is an integer from 1 to 4, and - (CH2) n3- is optionally substituted with C? _ Alkyl, and (iv) hydroxy. As the "ring structure" of the "optionally substituted ring structure" formed by R3b attached to the carbon atom in the pyridine ring for the Ab ring, a heterocycle containing saturated or unsaturated (preferably saturated) nitrogen of 4 may be mentioned. to 8 members (with a preference of 5 or 6 members). Specifically, where each symbol is as defined previously, is, for example, and similar. The "ring structure" optionally has 1 to 5 (preferably 1 to 3, more preferably 1 or 2), equal or different substituents in any substitutable position. As substituents, substituents similar to those of substituent group V mentioned above can be mentioned. R1b and R2b are optionally linked together to form an optionally substituted ring structure. As "ring structure", there may be mentioned a saturated or unsaturated heterocycle (preferably saturated) of 4 to 8 members (preferably 5 to 7 members). As "ring structure" of the "optionally substituted ring structure" formed by Rlb and R2b linked together can be mentioned, for example, where each symbol is as defined previously, and similar. R2b and R3b are optionally linked together to form an optionally substituted ring structure. Corao "ring structure", we can mention a heterocycle saturated or unsaturated (preferably saturated) from 4 to 8 members (preferably from 5 to 7 members). As "ring structure" of the "optionally substituted ring structure" formed by R2b and R3b bonded together can be mentioned, for example, where each symbol is as defined previously, and similar. The "ring structure" of the "optionally substituted ring structure" formed by R1 and R2b, or R2b and R3b optionally has 1 to 5 (preferably 1 to 3, more preferably 1 or 2), substituents the same or different in any replaceable position. As substituents, substituents similar to those of substituent group V mentioned above can be mentioned. When Wb is C (Rlb), the compound (Ib) is represented by the following formula (IbA): (IDA) where each symbol is as defined previously. When Wb is N, the compound (Ib) is represented by the following formula (IbB) or (IbC): (IbB) (IbC) where each symbol is as defined previously. In the aforementioned formula, the partial structural formula it is preferably where each symbol is as defined previously. As specific examples, there can be mentioned a compound represented by the following formula (IbY or one of its salts (in the present specification, now more abbreviated sometimes as "compound (Ib ')"): where each symbol is as defined previously. [compound (Iba)] As a preferred embodiment of compound (Ib), there can be mentioned a compound represented by the following formula (Iba) or a salt thereof (in the present specification, now more abbreviated sometimes as "compound ( I was going)"): wherein ring A is an optionally substituted pyridine ring, ring Bb is an optionally substituted C 1 -C 14 aryl group, and the other symbols are as defined above. In the aforementioned formula (Iba), the "pyridine ring" of the "also optionally substituted pyridine ring" for the ring Ab 'optionally also has, in addition to the group represented by the formula: -0-Bb, 1 to 3 substituents or different in any substitutable position. As substituents, substituents similar to those of substituent group V mentioned above can be mentioned. Of these, halogen and methyl are preferred. The Ab ring is preferably an optionally substituted pyridine ring, in addition to the group represented by the formula: -0-Bb, with substituents selected from the group consisting of halogen and methyl, more preferably an optionally substituted pyridine ring, in addition to the group represented by the formula: -0-Bb, by halogen. The "aryl group of C6-? 4" of the "optionally substituted C 6-14 aryl group" for ring Bb optionally has 1 to 5 same or different substituents in any substitutable position. As substituents, substituents similar to those of substituent group V mentioned above can be mentioned. Of these, optionally halogenated C? -6 alkyl, optionally halogenated C? _6 alkoxy, C? -6-carbamoyl alkyl and halogen are preferred. The Bb ring is preferably a phenyl group optionally substituted with substituents selected from the group consisting of optionally halogenated C? -6 alkyl, optionally halogenated C? -6 alkoxy, C? _6-carbamoyl alkyl and halogen (preferably a phenyl group optionally substituted with substituents selected from the group consisting of optionally halogenated C? _6 alkyl, optionally halogenated C? -6 alkoxy and C? -6-carbamoyl alkyl), more preferably a phenyl group optionally substituted at the position 3 by substituents selected from the group consisting of optionally halogenated C? -6 alkyl, optionally halogenated C? _6 alkoxy, C? -6-carbamoyl alkyl, and halogen (preferably, a phenyl group optionally substituted at the 3-position by Substituents selected from the group consists of optionally halogenated C? -6 alkyl, optionally halogenated C] .- 6 alkoxy, and C? -6-carbamoyl alkyl). As the most preferred embodiment of the compound (Ib), the co-tax (Iba) can be mentioned wherein the aforementioned formula (Iba) Rlb is a hydrogen atom, a halogen atom, a cyano group or an alkyl group of C? _6 optionally halogenated, R2 is an alkyl group of C6 -6 substituted with substituents selected from the group consisting of (i) -NR6ba-CO- (CH2) n? -S02-C? -4 alkyl wherein R6ba is an atom of hydrogen or a methyl group, nor is it an integer from 1 to 4, and - (CH2) n? - is optionally substituted by C? -4 alkyl, (ii) -NR6bb-CO- (CH2) n2-OH wherein R6bb is a hydrogen atom or a methyl group, n2 is an integer from 1 to 4, and - (CH2) n2- is optionally substituted with C? -4 alkyl, (iii) -0- (CH2) n3-OH wherein n3 is an integer from 1 to 4, and - (CH) n3- is optionally substituted with C? -4 alkyl, and (iv) hydroxy, R3b is a hydrogen atom, the Ab ring is a pyridine ring optionally substituted with its tituyentes selected from the group it consists of halogen and methyl, and the ring Bb is a phenyl group optionally substituted with substituents selected from the group consisting of optionally halogenated C? -6 alkyl, optionally halogenated C? -6 alkoxy, C? _6-carbamoyl alkyl and halogen. As another preferred embodiment of the compound (Ib), the compound (Iba) may be mentioned wherein the aforesaid formula (Iba) may be mentioned, the ring Ab is a pyridine ring optionally substituted with halogen, and the ring Bb is a phenyl group optionally substituted in the 3-position by substituents selected from the group consisting of optionally halogenated C? -6 alkyl, optionally halogenated C? _6 alkoxy, C? -6-carbamoyl and halogen. As the compound (Ib), 2- with particular preference can be mentioned. { 2- [4 - ((5-chloro-6- [3- (trifluoromethyl) phenoxy] pyridin-3-yl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethoxy} ethanol, N- { 2- [4- ( { 5-chloro-6- [3- (trifluoromethyl) phenoxy] pyridin-3-yl} amino) -5H-pyrrolo [3,2 -d] pyrimidin-5-yl] ethyl.} -2- (methylsulfonyl) acetamide, N- (2- [4- (. {5-chloro-6- [3- (trifluoromethyl) phenoxy] pyridin-3-yl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -3-hydroxy-3-methylbutanamide, N-. { 2- [4- ( { 5-Chloro-6- [3- (trifluoromethoxy) phenoxy] pyridin-3-yl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide, and N- (tert-butyl) -3- [(3-chloro-5- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidine -4-yl] amino.}. Pyridin-2-yl) oxy] benzamide, and their salts. [compound (le)] The present invention also provides a compound represented by the formula (le) or a salt thereof (in the present specification, now abbreviated sometimes as "compound (le)"). where each symbol is as defined previously. In the aforementioned formula (le), as the "optionally substituted group attached through a carbon atom, a nitrogen atom or an oxygen atom" to Rlc, a cyano group and an optionally substituted C?-Β alkyl group are preferred. As an alkyl group of C? -s, an alkyl group of C? _6 is preferred. As substituents for the alkyl group, substituents similar to those of the aforementioned substituent group X can be mentioned. Of these, halogen is preferred. R1c is preferably a hydrogen atom, a cyano group or an optionally halogenated C6-6 alkyl group, more preferably a hydrogen atom or a cyano group, particularly preferably a hydrogen atom. As "optionally substituted group attached through a carbon atom or a sulfur atom" for R2c, an optionally substituted C?-S alkyl group is preferred.

As the C? _g alkyl group, an alkyl group of Cx-6 is preferred. As substituents for the alkyl group, substituents similar to those of the aforementioned substituent group X can be used, preferably substituents selected from the group consisting of ( i) C? -4 alkyl optionally halogenated with -NR6c-CO- (CH2) n-S02-, (ii) -NR6c-C0- (CH2) n -OH, (iii) -0- (CH2) n- OH, (iv) hydroxy, (v) -NR6c-CO-alkyl of C? _4, (vi) -O-alkyl of C? _4, (vii) -S-alkyl of C? _4, (viii) -S02-alkyl of C? -4, and (ix) amino wherein n is an integer from 1 to 4, R6c is a hydrogen atom or an alkyl group of C? _, and - (CH2) n_ is optionally substituted with alkyl of C? _4, and more preferably, substituents selected from the group consisting of (i) -NH-CO-CR7cR8c-S02-C? _4 alkyl wherein R7c and R8c are the same or different and each is a hydrogen atom or an alkyl group of C? _4, (ii) -NR6cb-CO- (CH2) n2-OH wherein n2 is an integer from 1 to 4, R6cb is a hydrogen atom or an alkyl group of C? -4 , and - (CH2) n2 ~ is optionally substituted with C? _4 alkyl, (iii) -0- (CH2) n3-OH where n3 is an integer from 1 to 4, - (CH2) n3-is optionally substituted with C ?4 alkyl, (iv) hydroxy, (v) -NR6c-CO-C ?4 alkyl, (vi) -O-C? -4 alkyl, (vii) -S-C alkyl? -4, (viii) -S02-C 1 -4 alkyl, and (ix) amino. As the "aliphatic hydrocarbon group" of the "optionally substituted aliphatic hydrocarbon group" for R3c, an alkyl group of C6-6 is preferred. R3c is preferably a hydrogen atom or an alkyl group of C6-6, more preferably a hydrogen atom. As "ring structure" of the "optionally substituted ring structure" formed by R3c attached to the carbon atom in the adjacent Benzene ring can be mentioned a heterocycle containing saturated or unsaturated (preferably saturated) nitrogen of 4 to 8 members (with preference of 5 or 6 members). Specifically, where each symbol is as defined previously, is, for example, and similar The "ring structure" optionally has 1 to 5 (preferably 1 to 3, more preferably 1 or 2), equal or different substituents in any substitutable position. As substituents, substituents similar to those of substituent group V mentioned above can be mentioned. R c and R > 2c are optionally joined together to form an optionally substituted ring structure. As "ring structure" can be mentioned a saturated or unsaturated heterocycle (preferably saturated) of 4 to 8 members (preferably 5 to 7 members). As "ring structure" of the "optionally substituted ring structure" formed by Rlc and R2c bonded together can be mentioned, for example, where each symbol is as defined previously, and similar. R2c and R3c are optionally linked together to form an optionally substituted ring structure. As "ring structure" can be mentioned a saturated or unsaturated heterocycle (preferably saturated) of 4 to 8 members (preferably from 5 to 7 members). As "ring structure" of the "optionally substituted ring structure" formed by R2c and R3c bonded together there may be mentioned, for example, where each symbol is as defined previously, and similar. The "ring structure" of the "optionally substituted ring structure" formed by Rlc and R2c, or R2c and R3c optionally has 1 to 5 (preferably 1 to 3, more preferably 1 or 2), substituents the same or different in any replaceable position. As substituents, substituents similar to those of substituent group V mentioned above can be mentioned. The "Benzene ring" of the "optionally substituted Benzene ring" for the Ac ring optionally has 1 to 3 identical or different substituents in any substitutable position. As substituents, substituents similar to those of substituent group V mentioned above can be mentioned. Of these, halogen and methyl are preferred.

The Ac ring is preferably a the Benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl. As "optionally substituted amino group" for R 5c, an amino group, a mono- or di-C 1 -6-amino alkyl group, an optionally halogenated C 1 _6-amino alkanoyl group, a hydroxy-alkanoyl group of C? -6-amino, an alkanoyl group of C? -6-amino with hydroxy and halogen, a C3-7 cycloalkyl-C6-amino-alkanoyl group, an alkanoyl group of C? -6-amino with C3-7 cycloalkyl and halogen, an alkylsulfonyl group of C6-6-alkanoyl of C6- amino, a cycloalkyl group of C3-7-carbonyl-amino and an alkoxy group of C6-6-carbonyl-amino. As the "optionally substituted carbamoyl group" for R5c, a carbamoyl group, an optionally halogenated C? -6-carbamoyl alkyl group, a hydroxy-C6 alkylcarbamoyl group, a C? -6-oxy-alkyl group of C? -6carbamoyl, an aryl group of C6-? 4-C6-6-carbamoyl-alkyl, a C2-6 alkynyl-carbamoyl group, a piperidyl-C6-carbamoyl-alkyl group, a morpholinyl-alkyl group of C? _6-carbamoyl, a C3_7-carbamoyl cycloalkyl group optionally substituted by C? _6 alkyl or C2_6 alkynyl, and a 5- or 6-membered cyclic carbonyl group optionally containing an oxygen atom. As an "optionally substituted ureido group" for R5c, a ureido group, a C? -6-ureido alkyl group, a C3-7-ureido cycloalkyl group, and a 5- to 8-membered heterocyclyl-ureido group containing, in addition to carbon atoms, is preferred. to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom. As the "optionally substituted sulfamoyl group" for R5c, a sulfamoyl group optionally substituted with C6 alkyl is preferred. As "optionally substituted heterocyclic group" for R5c, a 5- to 8-membered heterocyclic group containing, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, which is optionally substituted with substituents selected from the group consisting of C? -6 alkyl optionally halogenated and C6-6-carbonyl alkoxy. As "optionally substituted C2-6 alkoxy group" for R5c, a C2-6 alkoxy group optionally substituted with substituents selected from the group consisting of C3-7 cycloalkyl, halogen, C6-6 alkoxy and alkyl C? -6-carbamoyl. As "optionally substituted aminomethyl group" for R5c, an aminomethyl group optionally substituted with C6-6-carbonyl alkyl is preferred.

As the "optionally substituted carbamoylmethyl group" for R5c, a carbamoylmethyl group optionally substituted with C? -6 alkyl is preferred. As "optionally substituted alkylsulfonyl group" for R5c, a C?-6-sulfonyl alkyl group optionally containing C3-7 cycloalkyl or halogen is preferred. As "aryl group of C6-? 4" of the "also optionally substituted C6-? 4 aryl group" for the ring Bc, a phenyl group is preferred. As the "C5-8 cycloalkyl group" of the "C5-8 cycloalkyl group also optionally substituted" for the Bc ring, a cyclohexyl group is preferred. The "aryl group of C6-? 4" of the "also aryl group of C6-i4 optionally substituted" for the ring Bc and the "cycloalkyl group of of the "C5_8 cycloalkyl group also optionally substituted" for the Bc ring, each optionally has, in addition to R5c, 1 to 5 same or different substituents in any substitutable position. As substituents, substituents similar to those of substituent group V mentioned above can be mentioned. Of these, optionally halogenated C? _6 alkyl and halogen are preferred. In the aforementioned formula, the partial structural formula it is preferably where each symbol is as defined previously. As specific examples, there may be mentioned a compound represented by the following formula (le ') or a salt thereof (in the present specification, now more abbreviated sometimes as "compound (le')"), and may be mentioned a compound represented by the following formula (le '') or one of its salts (in the present specification, now more abbreviated sometimes as "compound (le '')"): [compound (le ')] where each symbol is as defined previously. [composed (le '')] wherein the ring Bc 'is a phenyl group or a cyclohexyl group, each of which is also optionally substituted in addition to R5c, and the other symbols are as defined above. As the preferred embodiment of compound (le), there may be mentioned the compound (le) wherein R2c is a C6_6 alkyl group optionally substituted with substituents selected from the group consisting of (i) optionally halogenated C? _4 alkyl with - NR6c-CO- (CH2) n-S02-, (ii) -NR6c-CO- (CH2) n-OH, (iii) -0- (CH2) n-OH, (iv) hydroxy, (v) -NR6c -CO-C? -4 alkyl, (vi) -O-C de _4 alkyl, (vii) -S-Ci -4 alqu alkyl, (viii) -S? 2-Ci? Alkylo- 4, and (ix) amino wherein n is an integer from 1 to 4, R6c is a hydrogen atom or an alkyl group of C? _4, and - (CH) n- is optionally substituted with C? -4 alkyl. As another preferred embodiment of the compound (le), there may be mentioned the compound (le) wherein Rlc is a hydrogen atom or a cyano group, R 2c is an alkyl group of C 6 -6 optionally substituted with substituents selected from the group consisting of in (i) C ?4 alkyl optionally halogenated with -NR6c-CO- (CH2) n-S02-, (ii) -NR6c-C0- (CH2) n -OH, (iii) -0- (CH2) n -OH, (iv) hydroxy, (v) -NR6c-CO-C de -4 alkyl, (vi) -O-C? -4 alkyl, (vii) -S-C? -4 alkyl, ( viii) -S02-C alquilo4 alkyl, and (ix) amino wherein n is an integer from 1 to 4, R6c is a hydrogen atom or an alkyl group of C ?-, and - (CH2) n_ is optionally substituted with C? -4 alkyl, R3c is a hydrogen atom or an alkyl group of C? _6, the Ac ring is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl, R5c is (i) an amino group, (ii) a monoalkyl group of C? _6-amino, (iii) a dialkyl group of C? -6-amino, (iv) an optionally halogenated C? -6-amino alkanoyl group, (v) a C? -6-amino-hydroxy alkanoyl group, (vi) an alkanoyl group of C? -6 -amino with hydroxy and halogen, (vii) a C-7-alkanoyl C-6-amino-cycloalkyl group, (viii) an alkanoyl group of C? -6-amino with C3-7 cycloalkyl and halogen, ( ix) an alkylsulfonyl group of C? _6-C6_6-amino alkanoyl, (x) a C3-7-carbonyl-amino cycloalkyl group, (xi) a C? -6-carbonyl-amino alkoxy group, (xii) a carbamoyl group, (xiii) an optionally halogenated C? -6-carbamoyl alkyl group, (xiv) a C? -6-carbamoyl hydroxy-alkyl group, (xv) a C? -6 alkoxy group -alkyl of C? _6- carbamoyl, (xvi) an aryl group of C6-? 4-alkyl of C? -6-carbamoyl, (xvii) a C2-6 alkynyl carbamoyl group, (xviii) a piperidyl-alkyl group of C? _6-carbamoyl, (xix) a morpholinyl-alkyl group of C? -6-carbamoyl, (xx) a C7-carbamoyl cycloalkyl group optionally substituted by C6-6 alkyl or C2-6 alkynyl, (xxi) a 5- or 6-membered cyclic amino-carbonyl group optionally containing an oxygen atom, ( xxii) a ureido group, (xxiii) a C? -6-ureido alkyl group, (xxiv) a C3-7-ureido cycloalkyl group, (xxv) a 5- to 8-membered heterocyclic-ureido group containing, in addition of carbon atoms, 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, (xxvi) a sulfamoyl group optionally substituted with C? -6 alkyl, (xxvii) a 5- to 8-membered heterocyclic group containing, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, which is optionally substituted with substituents selected from the group consisting of optionally halogenated C?-d alkyl and C ?6-carbonyl alkoxy, (xxviii) a C 2-6 alkoxy group optionally substituted with substituents selected from the group consisting of C3_7 cycloalkyl , halogen, C? -6 alkoxy and C? _5-carbamoyl alkyl, (xxix) a carbamoylmethyl group optionally substituted with C? _6 alkyl, (xxx) an aminomethyl group optionally substituted with C? -6-carbonyl alkyl , (xxxi) a C? _6-sulfonyl alkyl group optionally containing C3-7 cycloalkyl or halogen, or (xxxii) a cyano group, and the Bc ring is an aryl group of C6-? 4 or a cycloalkyl group of C5-8, each of which is also optionally substituted, in addition to R5c, with substituents selected from the group consisting of optionally halogenated C? -6 alkyl and halogen. As another preferred embodiment of the compound (le), there may be mentioned the compound (le) wherein R5c is an amino group optionally substituted with substituents selected from the group consisting of (i) C? -6 alkyl, (ii) alkanoyl C? -6 optionally halogenated, (iii) C6-hydroxy alkanoyl, (iv) C6-6 alkanoyl having hydroxy and halogen, (v) C3-7 cycloalkyl-C6-6 alkanoyl, (vi) C6-6 alkanoyl having C3_7 cycloalkyl and halogen, (vii) C6-6-sulfonyl-alkanoyl-C6 alkanoyl , (viii) C3-7-carbonyl cycloalkyl, and (ix) C6-6-carbonyl alkoxy, the Bc ring is an aryl group of C6-? 4 or a cycloalkyl group of C5-8, each of which is also optionally substituted, in addition to R 5c, with substituents selected from the group consisting of optionally halogenated C?-βalkyl and halogen, Rlc is a hydrogen atom, R 2c is a C?-6 alkyl group substituted with selected substituents of the group consisting of (i) C 1 -4 alkyl optionally halogenated with -NR 6c-CO- (CH 2) n-S 0 2-, (ii) -NR 6c -CO- (CH 2) n-OH, (iii) -0- (CH2) n-OH, (iv) hydroxy, (v) -NR6c-CO-C-4 alkyl, (vi) -O-C4 alkyl, (vii) -S-C-4 alkyl , (viii) -S02-alkyl of C? _4, and (x) amino wherein n is an integer from 1 to 4, R6c is a hydrogen atom or an alkyl group of C? _4, and - (CH2) n- is optionally substituted with C? -4 alkyl, R3c is a hydrogen atom or an alkyl group of Ci-e, and the Ac ring is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl. In the aforementioned embodiment, more preferably, R 2c is a C 6 -6 alkyl group substituted with substituents selected from the group consisting of (i) -NH-CO-CR 7 c R 8 c-S 0 2 -alkyl-C 4 alkyl wherein R 7c and R8c are the same or different and each is a hydrogen atom or an alkyl group of C? _, (Ii) -NR6cb-CO- (CH2) n2-OH where n2 is an integer from 1 to 4, R6cb is a hydrogen atom or an alkyl group of C? _4, and - (CH2) n2- is optionally substituted with C? _4 alkyl, (iii) -0- (CH2) n3-OH wherein n3 is an integer 1 to 4, and - (CH2) n3- is optionally substituted with C? -4 alkyl, (iv) hydroxy, (v) -NR6c-CO-C? _4 alkyl, (vi) -O-C alkyl ?-4, (vii) -S-alkyl of C? -4, (viii) -S0 -alike that of C? _4, and (ix) amino. As another preferred embodiment of the compound (le), there may be mentioned the compound (le) wherein R5c is a carbamoyl group optionally substituted with substituents selected from the group consisting of (i) optionally halogenated C? -6 alkyl, (ii) hydroxy-C-6 alkyl, (iii) C6-6 alkyloxy-C6-6alkyl, (iv) C6-6alkaryl-C6-6alkyl, (v) C2-6alkynyl (vi) piperidyl-C6-6alkyl (vii) morpholinyl-C6-6alkyl, and (viii) C3-7cycloalkyl optionally substituted with C6-6alkyl or C2-alkynyl, the ring Bc is an aryl group of Cd-? 4 or a cycloalkyl group of C5_8? each of which is also optionally substituted, in addition to R5c, with substituents selected from the group consisting of optionally halogenated C?-alkyl and halogen, Rlc is a hydrogen atom, R 2c is a C?-6 alkyl group substituted with substituents selected from the group consisting of (i) optionally halogenated C? _4 alkyl with - NR6c-CO- (CH2) n-S02-, (ii) -NR6c-CO- (CH2) n-OH, (iii) -0- (CH2) n-OH, (iv) hydroxy, (v) -NR6c -CO-C de4 alkyl, (vi) -O-C ?4 alkyl, (vii) -S-C alquilo4 alkyl, (viii) -S02-C ?4 alkyl, and (ix) amino , wherein n is an integer from 1 to 4, R6c is a hydrogen atom or an alkyl group of C? _4, and - (CH2) n- is optionally substituted with C? _4 alkyl, R3c is a hydrogen or an alkyl group of C? -6, and the Ac ring is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl. In the aforementioned embodiment, more preferably, R2c is an alkyl group of C6-6 substituted with substituents selected from the group consisting of (i) -NH-C0-CR7cR8c-S02-alkyl of C? _4 wherein R7c and R8c are the same or different and each is a hydrogen atom or an alkyl group of C? -4, (ii) -NR6cb-C0- (CH2) n2-OH wherein n2 is an integer from 1 to 4, R6cb is a hydrogen atom or an alkyl group of C? -4, and - (CH2) n2? is optionally substituted with C? -4 alkyl, (iii) -0- (CH2) n3-OH where n3 is a whole number of 1 a, and - (CH2) n3- is optionally substituted with C ?4 alkyl, (iv) hydroxy, (v) -NR6c-C0-C ?4 alkyl, (vi) -O-C alkyl? _4, (vii) -S-C de -4 alkyl, (viii) -S02-C? -4 alkyl, and (ix) amino. As another preferred embodiment of the compound (le), there may be mentioned the compound (le) wherein R5c is a ureido group optionally substituted with substituents selected from the group consisting of (i) C? -6 alkyl, (ii) cycloalkyl of C3-7, and (iii) 5- to 8-membered heterocyclic group containing, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, Bc ring is an aryl group of Cß-? or a C5-8 cycloalkyl group, each of which is also optionally substituted, in addition to R5c, with substituents selected from the group consisting of C? -6 alkyl optionally halogenated and halogen, Rlc is a hydrogen atom, R 2c is a C ?_6 alkyl group substituted with substituents selected from the group consisting of (i) C? _4 alkyl optionally halogenated with -NR6c-CO- (CH2) n-S02-, (ii) -NR6c-CO- (CH2) n-OH, (iii) -0- (CH2) n-OH, (iv) hydroxy, (v) - NR6c-CO-C4-4alkyl, (vi) -O-C4-4alkyl, (vii) -S-C4-4alkyl, (viii) -S02-C4-4alkyl, and (ix) amino wherein n is an integer from 1 to 4, R6c is a hydrogen atom or an alkyl group of C? _4, and - (CH2) n- is optionally substituted with C? -4 alkyl, R3c is a hydrogen atom or an alkyl group of C -6, and the Ac ring is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl. In the aforementioned embodiment, more preferably, R2c is an alkyl group of C6-6 substituted with substituents selected from the group consisting of (i) -NH-CO-CR7cR8c-S02-C? -4 alkyl wherein R7c and R8c are the same or different and each is a hydrogen atom or an alkyl group of C? -4, (ii) -NR6cb -CO- (CH2) n2-OH wherein n2 is an integer of 1 a, R6cb is a hydrogen atom or an alkyl group of C? -, and - (CH2) n2 ~ is optionally substituted with alkyl of C? _4, (iii) -0- (CH2) n3-OH wherein n3 is an integer from 1 to 4, and - (CH2) n3- is optionally substituted with C? -4 alkyl, (iv) hydroxy, ( v) -NR6c-CO-alkyl of C? _4, (vi) -O-alkyl of C? -4, (vii) -S-alkyl of C? -4, (viii) -S02-C? 4, and (ix) amino. As another preferred embodiment of the compound (le), the compound (le) wherein R5c is a sulfamoyl group optionally substituted with C? -6 alkyl, the Bc ring is an aryl group of C6-? or a C5-8 cycloalkyl group, each of which is also optionally substituted, in addition to R5c, with substituents selected from the group consisting of optionally halogenated C?-C alquiloalkyl and halogen, Rlc is a hydrogen atom, R 2c is a C? -6 alkyl group substituted with substituents selected from the group consisting of (i) C? -4 alkyl optionally halogenated with -NR6c-CO- (CH2) n-S02- , (ii) -NR6c-C0- (CH2) n-0H, (iii) -0- (CH2) n-OH, (iv) hydroxy, (v) -NR6c-CO-a lqui lo of C? _4, (vi) -O-alkylo of C? -4, (vii) -Sa lqui lo of C? _4, (viii) -S02-alkyl of C? _4, and (ix) amino where n is a number integer from 1 to 4, R6c is a hydrogen atom or an alkyl group of C? -4, and - (CH2) n- is optionally substituted with C? _4 alkyl, R3c is a hydrogen atom or an alkyl group of C? -6, and the Ac ring is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl. In the aforementioned embodiment, more preferably, R 2c is a C?-6 alkyl group substituted with substituents selected from the group consisting of (i) -NH-CO-CR7cR8c-S02-C alquilo -4 alkyl wherein R7c and R8c are the same or different and each is a hydrogen atom or an alkyl group of C? -4, (ii) -NR6cb-CO- (CH2Y2-OH where n2 is an integer from 1 to 4 , R6cb is a hydrogen atom or an alkyl group of C? _4, and - (CH2) n2_ is optionally substituted with C? _4 alkyl, (iii) -0- (CH2) n3-OH where n3 is a number integer from 1 to 4, and - (CH2) n3- is optionally substituted with C? -4 alkyl, (iv) hydroxy, (v) -NR6c-CO-C? _4 alkyl, (vi) -O-alkyl of C? -4, (vii) -S-C? -4 alkyl, (viii) -S02-C? _4 alkyl, and (ix) amino.As another preferred embodiment of the compound (le), it can be mentioned the compound (le) wherein R5c is a 5- to 8-membered heterocyclic group containing, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom , which is optionally substituted with substituents selected from the group consisting of With C? -6 optionally halogenated and C? -6-carbonyl alkoxy, ring Bc is an aryl group of C6-? 4 or a group C5-8 cycloalkyl, each of which is also optionally substituted, in addition to R5c, with substituents selected from the group consisting of optionally halogenated C y_6 alkyl and halogen, Rlc is a hydrogen atom, R2c is an alkyl group of C? -6 substituted with substituents selected from the group consisting of (i) C? -4 alkyl optionally halogenated with -NR6c-CO- (CH2) n-S02-, (ii) -NR6c-CO- (CH2) n-OH, (iii) -0- (CH2) n-OH, (iv) hydroxy, (v) -NR6c-CO-C? -4 alkyl, (vi) -O-C? _ alkyl, ( vii) -S-alkyl of C? _4, (viii) -S02-alkyl of C? _4, and (ix) amino wherein n is an integer from 1 to 4, R6c is a hydrogen atom or an alkyl group of C? -4, and - (CH2) n_ is optionally substituted with C? _4 alkyl, R3c is a hydrogen atom or a C? -6 alkyl group, and the Ac ring is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl.

In the aforementioned embodiment, more preferably, R 2c is an alkyl group of C-6 substituted with substituents selected from the group consisting of (i) -NH-CO-CR7cR8c-S02-alkyl of C? _4 wherein R7c and R8c they are the same or different and each is a hydrogen atom or an alkyl group of C? _4, (ii) -NR6cb-CO- (CH2) n2-0H where n2 is an integer from 1 to 4, R6cb is a hydrogen atom or an alkyl group of C? -4, and - (CH2) n2- is optionally substituted with C? -4 alkyl, (iii) -0- (CH2) n3-OH where n3 is a whole number from 1 to, and - (CH2) n3- is optionally substituted with C? -4 alkyl, (iv) hydroxy, (v) -NR6c-CO-C? _4 alkyl, (vi) -O-C alkyl ? 4, (vii) -S-alkyl of C? _4, (viii) -S02-C? -4 alkyl, and (ix) amino. As another preferred embodiment of the compound (le), there may be mentioned the compound (le) wherein R2c is a C6_6 alkyl group substituted with a group represented by C4_4alkyl optionally halogenated with -NR6ca-CO- (CH2 ) n? -S02- where neither is an integer from 1 to 4, R5ca is a hydrogen atom or an alkyl group of C? _4, and - (CH2) nl- is optionally substituted by C? -4 alkyl, Rlc is a hydrogen atom, R3c is a hydrogen atom, the Ac ring is a ring benzene optionally substituted with substituents selected from the group consisting of halogen and methyl, R5c is (i) an amino group optionally (a) monosubstituted with C? -6 alkanoyl optionally having C? _6-sulfonyl alkyl, or (b) mono- or di-substituted with C? -6 alkyl, (ii) a carbamoyl group optionally substituted with C? -6 alkyl, (iii) a 5- to 8-membered heterocyclic group containing, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, which is optionally substituted with optionally halogenated C? -6 alkyl, (iv) a C2-6 alkoxy group optionally substituted with C3_7 cycloalkyl, halogen, C? _6 alkoxy or C? -6- alkyl carbamoyl, (v) an aminomethyl group optionally substituted with C? _g-carbonyl alkyl, (vi) a C? _6-sulfonyl alkyl group optionally substituted with C3-7 cycloalkyl, or (vii) a cyano group, and the Bc ring is an aryl group of C-? also optionally substituted, in addition to R5c, with substituents selected from the group consisting of optionally halogenated C? -6 alkyl and halogen. In the aforementioned embodiment, more preferably, R2c is an alkyl group of C6 -6 substituted with a group represented by '-NH-CO-CR7cR8c-S02-C? -4 alkyl wherein R7c and R8c are the same or different and each is a hydrogen atom or an alkyl group of C? _4. As another preferred embodiment of the compound (le), there may be mentioned the compound (le) wherein R2c is a C6_6 alkyl group substituted with a group represented by -NR6cb-CO- (CH2) n2-OH wherein n2 is an integer from 1 to 4, R6c is a hydrogen atom or an alkyl group of C? _4, and - (CH2) n2_ is optionally substituted with C? -4 alkyl, Rlc is a hydrogen atom, R3c is a hydrogen atom, the Ac ring is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl, R5c is (i) an amino group optionally (a) monosubstituted with C ?_6 alkanoyl optionally having hydroxy, or (b) mono- or disubstituted with C ?_6 alkyl, (ii) a carbamoyl group optionally substituted with C alquilo alkyl? -6, (iii) a 5- to 8-membered heterocyclic group containing, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, which is optionally substituted with optionally halogenated C? -6 alkyl, (iv) a C2-6 alkoxy group optionally substituted with C3_7 cycloalkyl, halogen, C-6 alkoxy or C? -6-carbamoyl alkyl, (v) a an aminomethyl group optionally substituted with C? _6-carbonyl alkyl, (vi) a C? -6-sulfonyl alkyl group optionally substituted with C3_7 cycloalkyl, or (vii) a cyano group, and the Bc ring is an aryl group of C6-? 4 also optionally substituted, adera of R5c, with substituents selected from the group which consists of optionally halogenated C? -6 alkyl and halogen. In the aforementioned modality, with greater preference, R c is an alkyl group of C6-6 substituted with a group represented by -NH-CO-CH2-CR9cR10c-OH wherein R9c and R10c are the same or different and each is an alkyl group of C? -4. As another preferred embodiment of the compound (le), the compound (le) can be mentioned wherein R2c is a C6_6 alkyl group substituted with a group represented by -0- (CH2) n3-0H wherein n3 is a number integer from 1 to 4, and - (CH2) n3- is optionally substituted with C? -4 alkyl, Rlc is a hydrogen atom, R3c is a hydrogen atom, the Ac ring is a benzene ring optionally substituted with selected substituents of the group consisting of halogen and methyl, R5c is (i) an amino group, (ii) an alkyl group of C? -d-amino, (iii) an optionally halogenated C? -6-amino alkanoyl group, (iv) a hydroxy-C alca-5-amino alkanoyl group, (v) a C?-6-amino-alkanoyl group with hydroxy and halogen, (vi) a C3_7-C alca-e-amino alkanoyl cycloalkyl group, (vii) a C?-6-amino alkanoyl group with C 3-7 cycloalkyl and halogen, (viii) a C 3-7 cycloalkylcarbonyl amino group, (ix) a C?-6-carbonyl alkoxy group araino, (x) a carbamoyl group, (xi) an optionally halogenated C? -6-carbamoyl alkyl group, (xii) a hydroxy-C? -6-carbamoyl alkyl group, (xiii) an alkoxy group of C? -6-C6-carbamoyl-alkyl, (xiv) a C3-7-carbamoyl cycloalkyl group, (xv) a ureido group, (xvi) a C? -6-ureido alkyl group, (xvii) a C3-7-ureido cycloalkyl group, (xviii) a 5- to 8-membered heterocyclyl-ureido group containing, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, (xix) a 5- or 6-membered cyclic amino-carbonyl group optionally containing an oxygen atom, (xx) a 5- to 8-membered heterocyclic group containing, in addition to carbon atoms, 1 to 3 selected heteroatoms of the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, which is optionally substituted with optionally halogenated alkyl of C? -6 or C? -6-carbonyl alkoxy, (xxi) an optionally halogenated C2-6 alkoxy group, (xxii) a C? -6-sulfonyl alkyl group, or (xxiii) a cyano group, and the Bc ring is an optionally substituted C6-? 4 aryl group, in addition to R c, with substituents selected from the group consisting of optionally halogenated C? -6 alkyl and halogen. As another preferred embodiment of the compound (le), there may be mentioned the compound (le) wherein R2c is a C6_6 alkyl group substituted with hydroxy, Rlc is a hydrogen atom, R3c is a hydrogen atom, the ring Ac is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl, R5c is (i) an amino group optionally (a) monosubstituted with C?-6 alkanoyl optionally having hydroxy, or (b) mono- or disubstituted with C? -6 alkyl, (ii) a carbamoyl group optionally substituted with optionally halogenated C-6 alkyl, (iii) a C3_7-carbamoyl cycloalkyl group optionally substituted with C? -6 alkyl or C2-6 alkynyl, (iv) a C6-? 4-alkyl group of C? -6-carbamoyl, (v) a hydroxy-C6-alkylcarbamoyl group, ( vi) a morpholinyl-alkyl group of C6-6 carbamoyl, (vii) a C2_6-carbamoyl alkynyl group, (viii) a carbamoylmethyl group optionally substituted with C6_6 alkyl, (ix) a C2_6 alkoxy group optionally substituted with C3_7 cycloalkyl, halogen, C? -6 alkoxy or C? -6-carbamoyl alkyl, (x) an aminomethyl group optionally substituted with C? _6-carbonyl alkoxy, or (xi) an alkyl group of C6-sulfonyl optionally substituted with C3_7 cycloalkyl, and ring Bc is an optionally substituted C6-? 4 aryl group, in addition to R5c, with substituents selected from the group consisting of optionally halogenated C6-6 alkyl and halogen . As another preferred embodiment of the compound (le), there may be mentioned the compound (le) wherein Rlc is a cyano group or an optionally halogenated C? -6 alkyl group, R2c is (i) an alkyl group of C? _6, or (ii) an alkyl group of C6-6 substituted with substituents selected from the group consisting of (a) C? -4 alquiloalkyl optionally halogenated with -NR6c-CO- (CH2) n-S02-, (b) -NR6c-C0- (CH2) n-OH, (c) -0- (CH2) n-OH, and (d) hydroxy, wherein n is an integer from 1 to 4, R6c is a hydrogen atom or an alkyl group of C? -4, and - (CH2) n - is optionally substituted with C 4 alkyl, R 3c is a hydrogen atom or an alkyl group of the Ac ring is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl, R5c is (i) an amino group, (ii) an alkyl group of C? -g-amino, (iii) an alkanoyl group Optionally halogenated C6-amino, (iv) a C6-amino -6-alkanoyl group, (v) a C6-amino-alkanoyl group with hydroxy and halogen, (vi) a C3-cycloalkyl group 7-C6-amino-alkanoyl, (vii) a C6-amino-alkanoyl group with cycloalkyl of C3_7 and halogen, (viii) an alkylsulfonyl C? -6-alkanoyl C? -6-amino group, (ix) a C3-7-carbonyl-amino cycloalkyl group, (x) a C? -6 alkoxy group -carbonyl-amino, (xi) a carbamoyl group, (xii) an optionally halogenated C? -6-carbamoyl alkyl group, (xiii) a hydroxy-C? _6-carbamoyl alkyl group, (xiv) an alkoxy group of C.sub.6 -C.sub.6 -carbamoyl alkyl, (xv) a C3_7-carbamoyl cycloalkyl group, (xvi) a 5- or 6-membered cyclic amino-carbonyl group optionally containing an oxygen atom, (xvii) a ureido group, (xviii) a C? -5-ureido alkyl group, (xix) a C3_7-ureido cycloalkyl group, (xx) a 5- to 8-membered heterocyclyl-ureido group containing, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, (xxi) a sulfamoyl group optionally substituted with C? -6 alkyl, or (xxii) a heterocyclic group of to 8 member s that contains, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, which is optionally substituted with substituents selected from the group consisting of optionally halogenated C? _6 alkyl and C? -6-carbonyl alkoxy, and the Bc ring is an aryl group of Cd-? 4 or a cycloalkyl group of C5-8, each of which is also optionally substituted, in addition to R5c, with substituents selected from the group consisting of C? -6 alkyl optionally halogenated and halogen. Of the above-mentioned preferred embodiments of the compound (le), a compound corresponding to the compound (le ") is particularly preferred. That is, in particular (i) a compound wherein the Bc ring is a phenyl group or a cyclohexyl group, each of which is also optionally substituted, in addition to R5c, with substituents selected from the group consisting of C? -6 optionally halogenated and halogen, and is substituted with R5c at the meta position of the phenyl group or the β position of the cyclohexyl group, and (ii) a compound wherein the Bc ring is a phenyl group also optionally substituted, in addition to R5c, with substituents selected from the group consisting of optionally halogenated C? -6 alkyl and halogen, whose phenyl is substituted with R5c at the meta position of the phenyl group. As a compound (le), it can be mentioned, with particular preference, 2-. { 2- [4- ((3-chloro-4- [3- (1, 3-thiazol-5-yl) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5- il] ethoxy.} ethanol, N- (tert-butyl) -3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3, 2- d] pyrimidin-4-yl.}. amino) phenoxy] benzamide, 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2- d] pyrimidin-4-yl.}. amino) phenoxy] -N- (2-hydroxy-1, 1-dimethylethyl) benzamide, N- (tert-butyl) -3- (2-chloro-4- ([5 - (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. Phenoxy) benzamide, N- (3- (2-chloro-4- [(6-cyano-5 methyl-5H-pyrrolo [3,2-d] pyrimidin-4-yl) amino] phenoxy] phenyl) cyclopropanecarboxamide, N- (tert-butyl) -5- (2-chloro-4- { [ 5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. Phenoxy) -2-fluorobenzamide, N-. { 2- [4- ((3-chloro-4- [3- (dimethylamino) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl.} -3 -hydroxy-3-methylbutanamide, N- (2- [4- (. {3-chloro-4- [3- (dimethylamino) phenoxy] phenyl} amino) -5H-pyrrolo [3, 2-d] pyrimidin-5-yl] ethyl.} -2- (methylsulfonyl) acetamide, N- (tert-butyl) -2- [3- (2-chloro-4- { [5- (2-hydroxyethyl) - 5H-pyrrolo [3,2-d] pyriraidin-4-yl] amino} phenoxy) phenyl] acetamide, N-. { 2- [4- ( { 3-Chloro-4- [3- (cyclopropylmethoxy) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide, N-. { 2- [4- ((3-chloro-4- [3- (2,2-dimethylpropoxy) phenoxy] phenyl] amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide, 2- (methylsulfonyl) -N- { 2- [4- (. {3-methyl-4- [3- (2,2,2-trifluoroethoxy) phenoxy] phenyl.}. amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl.}. acetamide, 2- [4- (. {3-chloro-4- [3- (isopropylsulfonyl) phenoxy] phenyl.} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethanol, and N- [2- (4- { [3-chloro-4- (3-cyanophenoxy) ) phenyl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2- (methylsulfonyl) acetamide, and its salts. [compound (Id)] The present invention also provides a compound represented by the formula (Id) or one of its salts (in the present specification, now more abbreviated sometimes as "compound (Id)"). where each symbol is as defined previously. In the aforementioned formula (Id), as the "optionally substituted group bonded through a carbon atom, a nitrogen atom or an oxygen atom" for Rld, a cyano group and an alkyl group of C? _8 are preferred. optionally substituted. As the C? _8 alkyl group, an alkyl group of C? _6 is preferred. As substituents for the alkyl group, substituents similar to those of the aforementioned substituent group X can be mentioned. Of these, halogen is preferred. Rld is preferably a hydrogen atom, a cyano group or an optionally halogenated C? -6 alkyl group, more preferably a hydrogen atom. As "optionally substituted group attached through a carbon atom or a sulfur atom" for R2d, an optionally substituted C? _ _ Alkyl group is preferred.

As the C? -e alkyl group, an alkyl group of C? 6- As substituents for the alkyl group, substituents similar to those of the aforementioned substituent group X can be used, preferably substituents selected from the group consisting of (a) C4 alkyl optionally halogenated with -NR6d-C0- (CH2 ) n-S02-, (b) -NR6d-CO- (CH2) n-OH, (c) -0- (CH2) n-OH, and (d) hydroxy wherein n is an integer from 1 to 4 , R6d is a hydrogen atom or an alkyl group of C? _4, and - (CH2) n- is optionally substituted with C? _4 alkyl. Corao "aliphatic hydrocarbon group" of the "optionally substituted aliphatic hydrocarbon group" for R3d, a C 1-6 alkyl group is preferably R3d is preferably a hydrogen atom or a C? -6 alkyl group, more preferably a hydrogen atom. As "ring structure" of the "optionally substituted ring structure" formed by R3d attached to the carbon atom in the adjacent Benzene ring, there can be mentioned a saturated or unsaturated (preferably saturated) nitrogen heterocycle of 4 to 8 members ( with preference of 5 or 6 members; Specifically, where each symbol is as defined previously, is, for example, and similar. The "ring structure" optionally has 1 to 5 (preferably 1 to 3, more preferably 1 or 2), equal or different substituents in any substitutable position. As substituents, substituents similar to those of substituent group V mentioned above can be mentioned. Rld and R2d are optionally linked together to form an optionally substituted ring structure. As "ring structure", there may be mentioned a saturated or unsaturated heterocycle (preferably saturated) of 4 to 8 members (preferably 5 to 7 members). As "ring structure" of the "optionally substituted ring structure" formed by Rld and R2d attached to each other there may be mentioned, for example, priority, and similar. R2d and R3d are optionally linked together to form an optionally substituted ring structure. As "ring structure" can be mentioned a saturated or unsaturated heterocycle (preferably saturated) of 4 to 8 members (preferably 5 to 7 members). As "ring structure" of the "optionally substituted ring structure" formed by R2d and R > 3d joined together can be mentioned, for example, where each symbol is as defined previously, and similar. The "ring structure" of the "optionally substituted ring structure" formed by Rld and R2d, or R2d and R3d optionally has 1 to 5 (preferably 1 to 3, more preferably 1 or 2), same or different substituents in any substitutable position. As substituents, substituents similar to those of substituent group V mentioned above can be mentioned. The "Benzene ring" of the "optionally substituted Benzene ring" for the Ad ring optionally has 1 to 3 same or different substituents in any substitutable position. As substituents, substituents similar to those of substituent group V mentioned above can be mentioned. Of these, halogen and methyl are preferred. The Ad ring is preferably a Benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl, more preferably a the Benzene ring optionally substituted with halogen. As the "heterocyclic group" of the "optionally substituted heterocyclic group" for the Bd ring, a 5- or 6-membered monocyclic heterocyclic group is preferred, and a piperidyl group is still more preferred. The "heterocyclic group" of the "optionally substituted heterocyclic group" for the Bd ring optionally has 1 to 5 same or different substituents in any substitutable position. As substituents, there may be mentioned acyl and substituents similar to those of the aforementioned substituent group V. Of these, acyl is preferred and optionally substituted ureido, and C?-6-carbonyl alkoxy, C5_8-carbonyl cycloalkyl, C?-6-ureido alkyl and Cs-8-ureido cycloalkyl are still preferred. The Bd ring is preferably a heterocyclic group (preferably a 5- or 6-membered monocyclic heterocyclic group, more preferably a piperidyl group) optionally substituted with optionally substituted acyl or ureido, more preferably a heterocyclic group (preferably a heterocyclic group). 5- or 6-membered monocyclic heterocyclic group, more preferably, a piperidyl group) optionally substituted with C6-6-carbonyl alkoxy, C5_8-carbonyl cycloalkyl, C6_6-ureido alkyl or C5_8-ureido cycloalkyl. As "C? _3 alkylene" of "optionally substituted C? _3 alkylene" for Zd, methylene is preferred. The "C al alkylene" of the "optionally substituted C al3 alkylene" for Zd is optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, hydroxy, C? -4 alkoxy, C alquilo? Alkyl; 4-carbonyl, carboxy, C? -4-carbonyl alkoxy, cyano, carbamoyl, sulfamoyl, nitro, amino, C? _4-carbonylamino alkyl, C? -4-carbonylamino alkoxy and C? _4-sulfonylamino alkyl. In the aforementioned formula, the partial structural formula it is preferably where each symbol is as defined previously. As specific examples, a compound represented by the following formula (Id ') or a salt thereof (in the present specification, now more abbreviated sometimes as "compound (Id')") can be mentioned: [compound ( Id ')] where each symbol is as defined previously. As a preferred embodiment of compound (Id), a co-formula represented by the following formula (Ida) or one of its salts (in the present specification, now more abbreviated sometimes as 'compound (Ida; [compound (Ida)] wherein R, 4d is an acyl group or an optionally substituted ureido group, the Bd ring is a piperidyl group also optionally substituted in addition to Rd, and the other symbols are as defined above. In the aforementioned formula (Ida), as the "acyl group" for R4d, a C6-6-carbonyl alkoxy group and a C5_8-carbonyl cycloalkyl group are preferable. In the aforementioned formula (Ida), as the "optionally substituted ureido group" for R4d, a C ?_6-ureido alkyl group and a Cs-8-ureido cycloalkyl group are preferred. The "piperidyl group" of the "also optionally substituted piperidyl group" for the Bd 'ring optionally has, in addition to Rd, 1 to 5 same or different substituents in any substitutable position. As substituents, substituents similar to those of substituent group V mentioned above may be mentioned. As the most preferred embodiment of the compound (Id), the compound (Ida) may be mentioned wherein, in the aforementioned formula (Ida), R 1 is a hydrogen atom, a cyano group or an optionally halogenated C 1-6 alkyl group, R2 is (i) an alkyl group of C? _6, or (ii) an alkyl group of C? -? substituted with substituents selected from the group consisting of (a) C? -4 alquiloalkyl optionally halogenated with -NR6d-C0- (CH2) n-S02-, (b) -NR6d-CO- (CH2) n-0H, ( c) -0- (CH2) n-0H, and (d) hydroxy, wherein n is an integer from 1 to 4, R6d is a hydrogen atom or an alkyl group of C? -4, and - (CH ) n_ is optionally substituted with C? -4 alkyl, R3d is a hydrogen atom or an alkyl group of C? -6, the Ad ring is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl, Zd is methylene, the Bd 'ring is a piperidyl group, and R4d is a C? _6-carbonyl alkoxy group, a C5_8-carbonyl cycloalkyl group, a C? -6-ureido alkyl group or a Cs-a cycloalkyl group -ureido. As another preferred embodiment of compound (Id), there may be mentioned the compound (Ida) wherein the aforementioned formula (Ida), R3d is a hydrogen atom, and the Ad ring is a benzene ring optionally substituted with selected substituents of the group consisting of halogen and methyl. As a compound (Id), there can be mentioned with particular preference, 4-. { [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] methyl} tert-butyl piperidine-1-carboxylate, and 4- [(2-chloro-4. {[[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino] .) phenoxy) methyl] piperidine-1-carboxylate of tert-butyl, and their salts. [compound (le)] The present invention also provides a compound represented by the formula (le) or a salt thereof (in the present specification, now more abbreviated sometimes as "compound (le)"). where each symbol is as defined previously. In the aforementioned formula (le), as the "optionally substituted group bonded through a carbon atom, a nitrogen atom or an oxygen atom" for Rle, a cyano group and an alkyl group of C? 8 optionally substituted. As the C? -8 alkyl group, an alkyl group of C? _6 is preferred. As substituents for the alkyl group, substituents similar to those of the aforementioned substituent group X can be mentioned. Of these, halogen is preferred. Rle is preferably a hydrogen atom, a cyano group or an optionally halogenated C? -6 alkyl group, more preferably a hydrogen atom or a cyano group, with particular preference a hydrogen atom. As an "optionally substituted group attached through of a carbon atom or a sulfur atom "for R2e, an optionally substituted C? -8 alkyl group is preferred.As an alkyl group of C? _8, an alkyl group of C? 6- Substituents similar to those of substituent group X mentioned above can be used as substituents for the alkyl group, preferably, substituents selected from the group consisting of (a) C? -4 alkyl optionally halogenated with -NR5e-CO- (CH2) n-S02-, (b) -NR6e-CO- (CH2) n-OH , (c) -0- (CH2) n-OH, and (d) hydroxy, wherein n is an integer from 1 to 4, R6e is a hydrogen atom or an alkyl group of C? _4, and - ( CH2) n- is optionally substituted with C? _4 alkyl. As the "aliphatic hydrocarbon group" of the "optionally substituted aliphatic hydrocarbon group" for R3e, an alkyl group of C6-6 is preferred. R3e is preferably a hydrogen atom or an alkyl group of C6-6, more preferably a hydrogen atom. As "ring structure" of the "optionally substituted ring structure" formed by R3e attached to the carbon atom in the adjacent Benzene ring, it can be mention a heterocycle containing saturated or unsaturated nitrogen (preferably saturated) of 4 to 8 members (preferably 5 or 6 members). Specifically, where each symbol is as defined previously, is, for example, and similar. The "ring structure" optionally has 1 to 5 (preferably 1 to 3, more preferably 1 or 2), equal or different substituents in any substitutable position. As substituents, substituents similar to those of substituent group V mentioned above can be mentioned. Rle and R2e are optionally linked together to form an optionally substituted ring structure. As "ring structure", there may be mentioned a saturated or unsaturated heterocycle (preferably saturated) of 4 to 8 members (preferably 5 to 7 members). As "ring structure" of the "structure of the optionally substituted ring "formed by Rle and R2e joined together can be mentioned, for example, where each symbol is as defined previously, and similar. R2e and R3e are optionally linked together to form an optionally substituted ring structure. As "ring structure", there may be mentioned a saturated or unsaturated heterocycle (preferably saturated) of 4 to 8 members (preferably 5 to 7 members). As "ring structure" of the "optionally substituted ring structure" formed by R2e and R3e linked together there may be mentioned, for example, where each symbol is as defined previously, and similar. The "ring structure" of the "structure of the optionally substituted ring "formed by Rle and R2e, or R2e and R3e optionally has 1 to 5 (preferably 1 to 3, more preferably 1 or 2), same or different substituents in any substitutable position. Substituents, substituents may be mentioned similar to those of substituent group V mentioned above The "Benzene ring" of the "optionally substituted Benzene ring" for the Ae ring optionally has 1 to 3 substituents same or different in any substitutable position As substituents, similar substituents may be mentioned those of the above-mentioned substituent group V. Of these, halogen and methyl are preferred The ring Ae is preferably a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl.As a linear alkyl group on R5e, can be mentioned a linear alkyl group with 1 to 10 (preferably 1 to 8, more preferably 1 to 6) carbon atoms. Clyphically, methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl and decyl may be mentioned. As the branched alkyl group in R5e, there can be mentioned a branched alkyl group with 3 to 10 (preferably 3 to 8, more preferably 3 to 6) carbon atoms. Specifically, isopropyl may be mentioned, isobutyl, sec-butyl, tert-butyl, isopentyl, neopentyl, 1-ethylpropyl, isohexyl, 1,1-dimethylbutyl, 2,2-dimethylbutyl, 3, 3-dimethylbutyl, 2-ethylbutyl, and the like. As a substituent for the "aryl" of the "linear alkyl group substituted by optionally substituted aryl, which is also optionally halogenated or hydroxylated", "hydroxy group substituted by optionally substituted aryl" and "C alqu-6-carbonyl alkyl group optionally substituted with optionally substituted aryl "for R5e, substituents similar to those of substituent group V mentioned above may be mentioned. As a substituent of "optionally substituted branched alkyl group", "optionally substituted alkenyl group" and "optionally substituted cycloalkyl group" for R5e, substituents similar to those of substituent group U mentioned above may be mentioned. As "linear alkyl group substituted with optionally substituted heterocyclic group" for R5e, a heterocyclyl-linear C 5-6 alkyl group containing 5 to 8 members containing, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group consisting of in a nitrogen atom, an oxygen atom and a sulfur atom, and optionally having C? _6 alkyl- As "linear alkyl group substituted with optionally substituted imino" for R5e, a group is preferred linear C? _6 alkyl substituted with hydroxyimino or C? -6-imino alkoxy. As "linear alkyl group substituted by optionally substituted aryl, which is also optionally halogenated or hydroxylated" for R5e, a linear C6-6 alkyl group substituted by C6-? 4 aryl, which is also optionally halogenated or hydroxylated, is preferred. As the "optionally substituted branched alkyl group" for R5e, an optionally halogenated branched C3-6 alkyl group is preferred. As the "optionally substituted alkenyl group" for R5e, a C2-6 alkenyl group is preferred. As "hydroxy group substituted with optionally substituted aryl" for R5e, a hydroxy group substituted with C6_14 aryl is preferred. As "halogenated C2_6 alkyl" of the "halogenated C2-6 alkyl substituted hydroxy group" for R5e and "halogenated C2-6 alkyl group" for R5e, there can be mentioned ethyl, propyl, isopropyl, butyl, isobutyl, t- butyl, pentyl, isopentyl, neopentyl, hexyl and the like, each of which is halogenated. Of these, halogenated ethyl is preferred. As "optionally substituted cycloalkyl group" for R5e, a C3-7 cycloalkyl group optionally substituted with cyano or carbamoyl is preferred.

As "C?-C6-alkylcarbonyl group optionally substituted by optionally substituted aryl" for R5e, C?-C6-carbonyl alkyl group optionally substituted by phenyl is preferred. As "linear alkyl group substituted with optionally substituted heterocyclic group" for R5e, preferred are (i) a methyl group substituted with optionally substituted heterocyclic group, and (ii) a linear alkyl group substituted with substituted heterocyclic group. The "aryl group of C6-? 4" of the "also optionally substituted Cd-? 4 aryl group" for the ring Be optionally has, in addition to R5c, 1 to 3 identical or different substituents in any substitutable position. As substituents, substituents similar to those of substituent group V mentioned above can be mentioned. Of these, optionally halogenated C?-6 alkyl and halogen are preferred. The Be ring is preferably an aryl group of C6-? 4 (preferably, a phenyl group) also optionally substituted, in addition to R5e, with substituents selected from the group consisting of optionally halogenated C? -6 alkyl and halogen. In the aforementioned formula, the partial structural formula it is preferably where each symbol is as defined previously. As specific examples, a compound represented by the following formula (le ') or a salt thereof (in the present specification, now more abbreviated sometimes as "compound (le')") can be mentioned: [compound ( you')] where each symbol is as defined previously. As a preferred embodiment of compound (le), the compound (le) in which Rle is a hydrogen atom, a cyano group or an optionally halogenated C ?_6 alkyl group, R2e is (i) an alkyl group of C can be mentioned. ? -6, or (ii) an alkyl group of C? _6 substituted with substituents selected from the group consisting of (a) C? -4 alkyl optionally halogenated with -NR6e-CO- (CH2) n-S02-, (b) -NR6e-CO- (CH2) n-OH, (c) -0- (CH2) n-OH, and (d) hydroxy, wherein n is an integer from 1 to 4, R6e is a hydrogen atom or an alkyl group of C? -4, and - (CH2) n - is optionally substituted with C? -4alkyl, R3e is a hydrogen atom, the ring Ae is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl, R5e is (i) an alkyl group of C ? -6 heterocyclyl-linear to 8 members containing, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, and optionally having C? -6 alkyl, ( ii) a linear C C_6 alkyl group substituted with hydroxyimino or C?-6-imino alkoxy, (iii) a linear C C-6 alkyl group substituted with aryl of Ce-i 4, which is also optionally halogenated or hydroxylated , (iv) a branched C3_6 alkyl group optionally halogenated, (v) a C2_6 alkenyl group, (vi) a hydroxy group substituted with aryl of Cß-? , (vii) a hydroxy group substituted with C? _6 alkyl, (viii) a hydroxy group substituted with halogenated C2-6 alkyl, (ix) a halogenated C2-6 alkyl group, (x) a cycloalkyl group of C3 -7 optionally substituted with cyano or carbamoyl, or (xi) a C? -6-carbonyl alkyl group optionally substituted with phenyl, and the Be ring is an aryl group of Ce-? 4 also optionally substituted, in addition to R5e, with substituents selected from the group consisting of optionally halogenated C? -6 alkyl and halogen. In the aforementioned preferred embodiment of the compound (le), a compound is preferred wherein the "5- to 8-membered heterocyclyl-linear C-6 alkyl group contains, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group which consists of a nitrogen atom, an oxygen atom and a sulfur atom, and which optionally has Cx-e alkyl "for R5e is (i) a 5- to 8-membered heterocyclic-methyl group containing, in addition to atoms of carbon, 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, and optionally having C? -6 alkyl, or (ii) a heterocyclyl-linear C? -6 alkyl group of 5 to 8 members containing, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, and having C? -6 alkyl. As the compound (le), there can be mentioned, with particular preference, 2- [4- (. {3-chloro-4- [3- (1,1-difluoroethyl) phenoxy] phenyl} amino) -5H- pyrrolo [3, 2-d] pyrimidin-5-yl] ethanol, O-ethyl oxime of (1Z) -1-. { 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] phenyl} -2, 2-dimethylpropan-l-one, l-. { 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] phenyl} -2,2-dimethylpropan-1-ol, 1- [3- (2-chloro-4. {[[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] ] amino.}. phenoxy) phenyl] -3,3-dimethylbutan-1-one, N- (2- { 4- [(3-methyl-4- { 3- [(1 E) -3-methylbut-l-en-1-yl] phenoxyphenyl) amino] -5H-pyrrolo [3 , 2-d] pyrimidin-5-yl.} Ethyl) -2- (methylsulfonyl) acetamide, and N-. { 2- [4- ( { 3-chloro-4- [3- (l- cyanocyclopropyl) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (Methylsulfonyl) acetamide, and its salts. [compound (If)] The present invention also provides a compound represented by the formula (If) or a salt thereof (in the present specification, now more abbreviated sometimes as "compound (If)"). where each symbol is as defined previously. In the aforementioned formula (If), as the "optionally substituted group bonded through a carbon atom, a nitrogen atom or an oxygen atom" for Rlf, a cyano group and an alkyl group of C? 8 optionally substituted. For an alkyl group of C? _8, an alkyl group of C? -6 is preferred. As substituents for the alkyl group, substituents similar to those of the group may be mentioned substituent X mentioned above. Of these, halogen is preferred. Rlf is preferably a hydrogen atom, a cyano group or an optionally halogenated C? -6 alkyl group, more preferably a hydrogen atom or a cyano group, particularly preferably a hydrogen atom. As "optionally substituted group attached through a carbon atom or a sulfur atom" for R2f, an optionally substituted C? _ _ Alkyl group is preferred.

As the C? -8 alkyl group, an alkyl group of C? 6- As substituents for the alkyl group, substituents similar to those of the aforementioned substituent group X can be used, preferably substituents selected from the group consisting of (a) C? -4 alquilo alkyl optionally halogenated with -NR6f-CO- (CH2) n-S02-, (b) -NR6f-CO- (CH2) n-OH, (c) -O- (CH2) n-OH, and (d) hydroxy, wherein n is an integer 1 to 4, R6f is a hydrogen atom or an alkyl group of C? -4, and - (CH2) n- is optionally substituted with C? _4 alkyl. As "aliphatic hydrocarbon group" of the "groupoptionally substituted aliphatic hydrocarbon "for R3f, an alkyl group of C6-6 is preferred, R3f is preferably a hydrogen atom or a C-6 alkyl group, more preferably a hydrogen atom. "optionally substituted ring structure" formed by R3f attached to the carbon atom in the adjacent Benzene ring, there can be mentioned a saturated or unsaturated (preferably saturated) nitrogen heterocycle of 4 to 8 members (preferably 5 or 6 members) Specifically, where each symbol is as defined previously, is, for example, and similar. The "ring structure" optionally has 1 to (preferably 1 to 3, more preferably 1 or 2), equal or different substituents in any substitutable position. As substituents, it can be mentioned substituents similar to those of substituent group V mentioned above. Rlf and R2f are optionally linked together to form an optionally substituted ring structure. As "ring structure", there may be mentioned a saturated or unsaturated heterocycle (preferably saturated) of 4 to 8 members (preferably 5 to 7 members). As "ring structure" of the "optionally substituted ring structure" formed by R.sub.lf and R.sub.2f linked together can be mentioned, for example, priority, and similar. R and R > 3f are optionally joined together to form an optionally substituted ring structure. As "ring structure" can be mentioned a saturated or unsaturated heterocycle (preferably saturated) of 4 to 8 members (preferably 5 to 7 members). As "ring structure" of the "optionally substituted ring structure" formed by R2f and R3f linked together can be mentioned, for example, where each symbol is as defined previously, and similar. The "ring structure" of the "optionally substituted ring structure" formed by Rlf and R2f, or R2f and R3f optionally has 1 to 5 (preferably 1 to 3, more preferably 1 or 2), substituents the same or different in any replaceable position. As substituents, substituents similar to those of substituent group V mentioned above can be mentioned. The "Benzene ring" of the "optionally substituted Benzene ring" for the Af ring optionally has 1 to 3 same or different substituents in any substitutable position. As substituents, substituents similar to those of substituent group V mentioned above can be mentioned. Of these, halogen and methyl are preferred. The Af ring is preferably a Benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl. The "piperidyl group" of the "piperidyl group also optionally substituted "for ring B optionally has, in addition to R4f, 1 to 3 same or different substituents in any substitutable position As substituents, substituents similar to those of substituent group V mentioned above may be mentioned. -6"of the" optionally substituted Cx-e alkyl group "for R4f optionally has 1 to 5 same or different substituents in any substitutable position As substituents, substituents similar to those of the aforementioned substituent group U may be mentioned. C5_8"cycloalkyl" of the "optionally substituted cycloalkyl group Cs-8" for Rf optionally has 1 to 5 same or different substituents in any substitutable position As substituents, substituents similar to those of substituent group V mentioned above can be mentioned. mentioned above, the partial structural formula where each symbol is as defined previously.

As specific examples, there may be mentioned a compound represented by the following formula (IP) or a salt thereof (in the present specification, now more abbreviated sometimes as "compound (IP)"): [compound (If ' )] where each symbol is as defined previously. As the preferred embodiment of compound (If), there can be mentioned the compound (If) wherein Rlf is a hydrogen atom, a cyano group or an optionally halogenated C ?_6 alkyl group, R²f is (i) an alkyl group of C ? -6, or (ii) a C? _6 alkyl group substituted with substituents selected from the group consisting of (a) C? -4 alkyl optionally halogenated with -NR6f-CO- (CH2) n-S02-, ( b) -NR6f-C0- (CH2) n-0H, (c) -0- (CH2) n-OH, and (d) hydroxy wherein n is an integer from 1 to 4, R6f is a hydrogen atom or an alkyl group of C? -4, and - (CH2) n- is optionally substituted with C? -4 alkyl, R3f is a hydrogen atom or an alkyl group of Cyclohexane is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl, ring Bf is a piperidyl group, and R 4f is (i) an optionally substituted C 1 _6 alkyl group, or ( ii) an optionally substituted C5-8 cycloalkyl group. As another preferred embodiment of the compound (If), there may be mentioned the compound (If) wherein R3f is a hydrogen atom, and the Af ring is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl. [compound (Ig)] The present invention also provides a compound represented by the formula (Ig) or a salt thereof (in the present specification, now more abbreviated sometimes as "compound (Ig)"). where each symbol is as defined previously. In the formula (Ig), the "Benzene ring" of the "optionally substituted Benzene ring" for ring A9 optionally has 1 to 3 identical or different substituents in any substitutable position. As substituents, substituents similar to those of substituent group V mentioned above can be mentioned. As "nitrogen-containing heterocycle" of the "heterocycle with optionally substituted nitrogen content" for the Bg ring, there may be mentioned, for example, a 3- to 8-membered aromatic heterocycle (preferably 5 or 6 membered) or an aliphatic heterocycle unsaturated (preferably saturated). Of these, preferably 3- to 8-membered (preferably 5 or 6 membered) aliphatic heterocyclic groups can be used, saturated or unsaturated (preferably saturated) such as azetidine, pyrrolidine, piperidine, homopiperidine, heptamethyleneimine, morpholine, thiomorpholine, piperazine, homopiperazine and the like, and others. The "nitrogen-containing heterocycle" optionally has 1 to 5 same or different substituents in any substitutable position. As a substituent, substituents similar to those of substituent group V mentioned above can be mentioned. As the "aliphatic hydrocarbon group" of the "optionally substituted aliphatic hydrocarbon group" for R3g, an alkyl group of C6-6 is preferred. The "alkylene of C-4" and "-0- (C? -4 alkylene) -" of the "alkylene of C? -44-O- (C? -4 alkylene) -, each of which optionally substituted, "for Ylg are optionally substituted with 1 to 3 substituents selected from halogen, hydroxy, C? -4 alkoxy, C? -4-carbonyl, carboxy, C? -4-carbonyl alkoxy, cyano, carbamoyl, sulfamoyl, nitro, amino, C? _4-carbonylamino alkyl, C? -4-carbonylamino alkoxy and C? -4-sulfonylamino alkyl. Xlg is preferably -NR3g-. In the formula, R3g is preferably a hydrogen atom or an alkyl group of C6-6, more preferably a hydrogen atom. Wg is preferably C (Rlg). As an "optionally substituted group attached through of a carbon atom, a nitrogen atom or an oxygen atom "for Rlg, a cyano group and an optionally substituted C ?_8 alkyl group are preferred.As an alkyl group of C ?_8, an alkyl group of C is preferred. As substituents for the alkyl group, substituents similar to those of the aforementioned substituent group X can be mentioned, of which, halogen is preferred, R 1 is preferably a hydrogen atom, a halogen atom, a cyano group or an optionally halogenated C? _g alkyl group, more preferably a hydrogen atom. As an "optionally substituted group bonded through a carbon atom or a sulfur atom" for R2g, an optionally optional C? _8 alkyl group is preferred. replaced.

As the C? _8 alkyl group, an alkyl group of C? 6- As substituents for the alkyl group, substituents similar to those of the aforementioned substituent group X can be used, preferably substituents selected from the group consisting of (a) -0- (CH2) n-OH, (b) - NR5g-CO- (CH2) n-OH, (c) C4-4 alkyl optionally halogenated with -NR5g-CO- (CH2) n-S02-, (d) hydroxy, and (e) amino wherein n is an integer from 1 to 4, R5g is a hydrogen atom or an alkyl group of C? _4, and - (CH2) n_ is optionally substituted with C-alkyl. ?_4. As "ring structure" of the "optionally substituted ring structure" formed by R3g attached to the carbon atom in the Benzene ring for the Ag ring, a heterocycle containing saturated or unsaturated (preferably saturated) nitrogen of 4 to 8 members (with a preference of 5 or 6 members). Specifically, where each symbol is as defined previously, is, for example, The "ring structure" optionally has 1 to 5 (preferably 1 to 3, more preferably 1 or 2), equal or different substituents in any substitutable position. As substituents, substituents similar to those of substituent group V mentioned above can be mentioned. Rlg and R2g are optionally linked together to form an optionally substituted ring structure. As "ring structure" can be mentioned a saturated or unsaturated heterocycle (preferably saturated) of 4 to 8 members (preferably 5 to 7 members). As "ring structure" of the "optionally substituted ring structure" formed by Rlg and R2g bonded together can be mentioned, for example, where each symbol is as it was previously defined, and similar. R2g and R3g are optionally linked together to form an optionally substituted ring structure. As "ring structure", there may be mentioned a saturated or unsaturated heterocycle (preferably saturated) of 4 to 8 members (preferably 5 to 7 members).

As "ring structure" of the "optionally substituted ring structure" coated by R2g and R3g bonded together can be mentioned, for example, where each symbol is as defined previously, and similar. The "ring structure" of the "optionally substituted ring structure" formed by Rlg and R2g, or R2g and R3g optionally has 1 to 5 (preferably 1 to 3, more preferably 1 or 2), substituents the same or different in any replaceable position. As substituents, substituents similar to those of substituent group V mentioned above can be mentioned. When g is C (Rlg), the compound (Ig) is represented by the following formula (IgA): (igA) where each symbol is as defined previously. When Wg is N, the compound (Ig) is represented by the following formula (IgB) or (IgC): (IgB) 9c) where each symbol is as defined previously. [compound (Iga)] As a preferred embodiment of compound (Ig), there may be mentioned a compound represented by the following formula (Iga) or a salt thereof (in the present specification, now more abbreviated sometimes as "compound (Iga)"): wherein Rg is an optionally substituted hydrocarbon group, the ring Bg is a heterocycle with 5- or 6-membered nitrogen content also optionally substituted in addition to R4g, and the other symbols are corao defined above. In the aforementioned formula (Iga), as "heterocycle with 5- or 6-membered nitrogen content" of "also optionally substituted heterocycle with 5 or 6 membered nitrogen content" for ring Bg ', a "heterocycle" may be mentioned containing nitrogen "of 5 or 6 members of the" nitrogen-containing heterocycle "of the" heterocycle with optionally substituted nitrogen content "for the Bg ring. R4g is preferably (i) an optionally substituted C6-? 4-alkyl group of C? _8 alkyl, (ii) an optionally substituted heterocyclyl-C- -8 alkyl group, (iii) an alkyl group of C? -8, or (iv) an optionally substituted aryl group of Ce-? 4, more preferably (i) a C6-14 aryl group of C? -8 alkyl optionally substituted with substituents selected from the group consisting of halogen, C? -6-carbamoyl alkyl and C? -6 haloalkoxy, (ii) a heterocyclyl-alkyl group of C? _8 optionally substituted, or (iii) an optionally substituted C6-? 4 aryl group. The "aryl group C6-? 4-alkyl of C? -8" of the "optionally substituted aryl group C6-? 4-C? _8" alkyl for R4g, "heterocyclyl-C? _8 alkyl group" of the "optionally substituted heterocyclyl-C? _8 alkyl group" for R4g and "C6 aryl group" -? 4"of the" optionally substituted C6-? 4 aryl group "for R4g optionally have 1 to 5 same or different substituents in any substitutable position. As substituents, substituents similar to those of substituent group V mentioned above can be mentioned. In the aforementioned formula, the partial structural formula it is preferably where each symbol is as defined previously. As a preferred embodiment of compound (Ig), the compound (Iga) can be mentioned wherein, in the aforementioned formula (Iga), Rlg is a hydrogen atom, a halogen atom, a cyano group or an alkyl group of C ? -6 optionally halogenated, R2g is a hydrogen atom or an optionally substituted C? -6 alkyl group, R3g is a hydrogen atom or an alkyl group of R4g is (i) an optionally substituted C6-? 4-alkyl group of C? _8 alkyl, (ii) an optionally substituted heterocyclyl-C8 alkyl group, (iii) an alkyl group of C? _ 8, or ( iv) an optionally substituted aryl group of Ce-14. As another preferred embodiment of compound (Ig), compound (Iga) wherein, in the aforementioned formula (Iga), Rlg is a hydrogen atom, a halogen atom, a cyano group or an alkyl group of C? -6 optionally halogenated, R2g is (i) a hydrogen atom, (ii) an alkyl group of C? _6, or (iii) a C? _6 alkyl group substituted with substituents selected from the group consisting of (a) - O- (CH2) n-OH, (b) -NR5g-CO- (CH2) n-OH, (c) C4-4 alkyl optionally halogenated with -NR5g-CO- (CH2) n-S02-, ( d) hydroxy, and (e) amino wherein n is an integer from 1 to 4, R5g is a hydrogen atom or an alkyl group of C? _4, and - (CH2) n- is optionally substituted with C? -4 alkyl, R3g is an hydrogen or an alkyl group of C? -6, It is the formula Rg is (i) an aryl C6-x4-C?-8 alkyl optionally substituted with substituents selected from the group consisting of halogen, C?-6-carbamoyl alkyl and C? _6 haloalkoxy, (ii) a group optionally substituted C 1 -8-heterocyclyl alkyl, or (iii) an optionally substituted C 4 -aryl aryl group. As the compound (Ig), N- [2- (4-. {[1- (3-fluorobenzyl) -lH-indazol-5-yl] amino] -5H-pyrrolo [3] can be mentioned particularly preferably. , 2-d] pyrimidin-5-yl) ethyl] -2- (methylsulfonyl) acetamide, N- [2- (4- { [1- (3-fluorobenzyl) -lH-indol-5-yl] amino] .}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -3-hydroxy-3-methylbutanamide, N- (tert-butyl) -3- [(5- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyriraidin-4-yl] amino.}.-LH-indole -l-yl) methyl] benzamide, N- (tert-butyl) -3- [(5- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl) ] amino.}. - lH-indazol-1-yl) methyl] benzamide, and N- (tert-butyl) -6- [(5 { [5- (2-hydroxyethyl) -5H-pyrrolo [3 , 2-d] pyrimidin-4-yl] amino.} - lH-indol-1-yl) methyl] pyridine-2-carboxamide, and their salts. [compound (Ih)] The present invention also provides a compound represented by the formula (Ih) or a salt thereof (in the present specification, now more abbreviated sometimes as "compound (Ih)"). where each symbol is as defined previously. In the aforementioned formula (Ih), as the "group optionally substituted alkyl bonded through a carbon atom or a sulfur atom "for R2h, an optionally substituted C? -8 alkyl group is preferred.As C? -8 alkyl group, an alkyl group of C? 6. As substituents for the alkyl group, substituents similar to those of the aforementioned substituent group X can be used, preferably substituents selected from the group consisting of (a) -0- (CH2) n-0H, (b) - NR5g-CO- (CH2) n-OH, (c) C? -4 alkyl optionally halogenated with -NR5g-CO- (CH2) n-S02-, and (d) hydroxy, wherein n is an integer from 1 to 4, Rdh is a hydrogen atom or an alkyl group of C? -4, and - (CH2) n- is optionally substituted with alkyl of C? _4. As the "aliphatic hydrocarbon group" of the "optionally substituted aliphatic hydrocarbon group" for R3h, an alkyl group of C6-6 is preferred. R3h is preferably a hydrogen atom or an alkyl group of C6-6, more preferably a hydrogen atom. As "ring structure" of the "optionally substituted ring structure" formed by R 3h attached to the carbon atom in the adjacent Benzene ring, it can be mention a heterocycle containing saturated or unsaturated nitrogen (preferably saturated) of 4 to 8 members (preferably 5 or 6 members). Specifically, where each symbol is as defined previously, is, for example, and similar. The "ring structure" optionally has 1 to 5 (preferably 1 to 3, more preferably 1 or 2), equal or different substituents in any substitutable position. As substituents, substituents similar to those of substituent group V mentioned above can be mentioned. Rlh and R2h are optionally linked together to form an optionally substituted ring structure. As "ring structure", there may be mentioned a saturated or unsaturated heterocycle (preferably saturated) of 4 to 8 members (preferably 5 to 7 members). As "ring structure" of the "structure of the optionally substituted ring "formed by Rlh and R2h joined together can be mentioned, for example, where each symbol is as it was previously defined, and similar. R2h and R3h are optionally linked together to form an optionally substituted ring structure. As "ring structure" can be mentioned a saturated or unsaturated heterocycle (preferably saturated) of 4 to 8 members (preferably 5 to 7 members). As "ring structure" of the "optionally substituted ring structure" formed by R2 and R3h bonded together there may be mentioned, for example, where each symbol is as previously defined, and similar. The "ring structure" of the "optionally substituted ring structure" formed by Rlh and R2h, or R2h and R3h optionally has 1 to 5 (preferably 1 to 3, more preferably 1 or 2), equal or different substituents in any substitutable position. As substituents, substituents similar to those of substituent group V mentioned above can be mentioned. The "Benzene ring" of the "optionally substituted Benzene ring" for the ring Ah optionally has 1 to 3 same or different substituents in any substitutable position. As substituents, substituents similar to those of substituent group V mentioned above can be mentioned. Of these, halogen and methyl are preferred. The ring Ah is preferably a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl. As "C? -3 alkylene" of "optionally substituted C? _3 alkylene" for Zh, methylene is preferred. The "C al _3 alkylene" of the "optionally substituted C al -3 alkylene" for Zh is optionally substituted with 1 to 3 substituents selected from the group consisting of halogen, hydroxy, C? -4 alkoxy, C alquilo? Alkyl; -4-carbonyl, carboxy, C? -4-carbonyl alkoxy, cyano, carbamoyl, sulfamoyl, nitro, amino, C? -4-carbonylamino alkyl, C? -4-carbonylamino alkoxy and C? _4- alkyl sulfonylamino.

As "aryl group of C6-? 4" of the "optionally substituted C6-? 4 aryl group" for the Bh ring, a phenyl group is preferred. As the "heterocyclic group" of the "optionally substituted heterocyclic group" for the Bh ring, a pyridyl group and a piperidyl group are preferred. As the "C5-8 cycloalkyl group" of the "C5_8 optionally substituted cycloalkyl group" for the Bh ring, a cyclohexyl group is preferred. The "aryl group of C6-? 4" of the "aryl group of Ce-? 4 optionally substituted" for the ring Bh, the "heterocyclic group" of the "optionally substituted heterocyclic group" for the ring Bh and the "cycloalkyl group of C5 -s "of the" optionally substituted C5_8 cycloalkyl group "for the Bh ring optionally have 1 to 5 same or different substituents in any substitutable position. As substituents, substituents similar to those of substituent group V mentioned above can be mentioned. In the aforementioned formula, the partial structural formula it is preferably where each symbol is as defined with anteriority. As specific examples, there may be mentioned a compound represented by the following formula (Ih ') or a salt thereof (in the present specification, now more abbreviated sometimes as "compound (Ih')"): [compound ( Ih ')] where each symbol is as defined previously. As the preferred embodiment of compound (Ih), there can be mentioned a compound represented by the following formula (Iha) or a salt thereof (in the present specification, now more abbreviated sometimes as "compound (Iha)"): R5h is (i) an optionally substituted amino group, (ii) an optionally substituted carbamoyl group, (iii) an optionally substituted ureido group, (iv) an optionally substituted sulfamoyl group, (v) an optionally substituted heterocyclic group,, v? an optionally substituted hydrocarbon group; vii) a halogen atom, or viii) an optionally substituted carboxyl group, and ring B is (i) an aryl group of Ce-i4, (ii) a heterocyclic group, or (iii) ) a C5_8 cycloalkyl group, each of which is also optionally substituted in addition to R5h, and the other symbols are as defined with anteriority. In the aforementioned formula (Iha), as the "optionally substituted amino group" for R5h, an amino group, a C? -g-amino alkyl group, an optionally halogenated C? _6-amino alkanoyl group, a group are preferred hydroxy-alkanoyl C6-amino, a C6-6-amino-alkanoyl group with hydroxy and halogen, a C3-7 cycloalkyl-C6-amino-alkanoyl group, a C6-6-araino alkanoyl group with C3-7 cycloalkyl and halogen, an alkylsulfonyl C6-6-alkanoyl C6-amino group, a C3-7 cycloalkyl-carbonyl-amino group and a C6-6-carbonyl-amino alkoxy group. As "optionally substituted carbamoyl group" for R5h, a carbamoyl group, an optionally halogenated C? -6-carbamoyl alkyl group, a hydroxy-C? -6-carbamoyl alkyl group, a C? _6- alkoxy group, are preferred. C6-6-carbamoyl-alkyl, a C3-7-carbamoyl cycloalkyl group, and a 5- or 6-membered cyclic amino-carbonyl group optionally containing an oxygen atom. As "optionally substituted ureido group" for R5h, a ureido group, a C6_6-ureido alkyl group, a C-7-ureido cycloalkyl group, and a 5- to 8-membered heterocyclyl-ureido group containing, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom.

As the "optionally substituted sulfamoyl group" for R5h, a sulfamoyl group optionally substituted by C6-6 alkyl is preferred. As the "optionally substituted heterocyclic group" for R5h, a 5- to 8-membered heterocyclic group containing, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and an oxygen atom is preferred. sulfur atom, which is optionally substituted with substituents selected from the group consisting of optionally halogenated C? _6 alkyl and C? -6-carbonyl alkoxy. As the "optionally substituted hydrocarbon group" for R5h, an optionally halogenated C6-6 alkyl group and a C6-6-carbonyl alkoxy group are preferred. As the "optionally substituted carboxyl group" for R5h, a carboxyl group is preferred. In the aforementioned formula (Iha), as the "aryl group of C6_? 4" of the "optionally substituted C6-? 4 aryl group" for the Bh 'ring, a phenyl group is preferred. As the "heterocyclic group" of the "optionally substituted heterocyclic group" for the Bh 'ring, a pyridyl group and a piperidyl group are preferred. As the "C5-8 cycloalkyl group" of the "C5-8 optionally substituted cycloalkyl group" for the Bh 'ring, a cyclohexyl group is preferred.

The "aryl group of C6-? 4" of the "optionally substituted C6-? 4 aryl group" for the Bh ring, the "heterocyclic group" of the "optionally substituted heterocyclic group" for the Bh 'ring and the "C5_8 cycloalkyl group" of the "optionally substituted C5_8 cycloalkyl group" for the Bh ring optionally have, in addition to R5h, 1 to 5 substituents same or different in any replaceable position. As substituents, substituents similar to those of substituent group V mentioned above can be mentioned. The ring Bh is preferably a phenyl group, a pyridyl group or a piperidyl group, each of which is also optionally substituted in addition to R5h. As the most preferred embodiment of the compound (Ih), the compound (Iha) can be mentioned wherein, in the aforementioned formula (Iha), Rlh is a halogen atom or an optionally halogenated C? -6 alkyl group, R2h is (i) a hydrogen atom, (ii) an alkyl group of C? -6, or (iii) a C? -6 alkyl group substituted with substituents selected from the group consisting of (a) -0- (CH2) n-OH, (b) -NR6h-CO- (CH2) n-OH, (c) C ?4 alkyl optionally halogenated with -NR6h-CO- (CH2) n-S02-, and (d) hydroxy, wherein n is an integer from 1 to 4, R6h is a hydrogen atom or a alkyl group of C? _4, and - (CH2) n- is optionally substituted with C? -4 alkyl, R3h is a hydrogen atom or an alkyl group of Cx 1-6, is a bond or methylene, the ring Ah is a benzene ring optionally substituted with substituents selected from the group consisting of halogen and methyl, R5h is (i) an amino group, (ii) an alkyl group of C ? -6-amino, (iii) an optionally halogenated C? _6-amino alkanoyl group, (iv) a C? -6-amino-hydroxy alkanoyl group, (v) a C? _6-amino alkanoyl group with hydroxy and halogen (vi) a C3-7 cycloalkyl-C6-6-amino-alkanoyl group, (vii) an alkanoyl C6-amino group with C3-7 cycloalkyl and halogen, (viii) an alkylsulfonyl group C6-6 -alcanoil C? -6- amino, (ix) a C3-7-carbonyl-amino cycloalkyl group, (x) a C? -6-carbonyl-amino alkoxy group, (xi) a carbamoyl group, (xii) an alkyl group of C? 6-carbamoyl optionally halogenated, (xiii) a hydroxy-C6-6-carbamoyl alkyl group, (xiv) a C6-6 alkoxy-C6-6-carbamoyl-alkyl group, (xv) a C3- cycloalkyl group 7-carbamoyl, (xvi) a 5- or 6-membered cyclic amino-carbonyl group optionally containing an oxygen atom, (xvii) a ureido group, (xviii) a C? -6-ureido alkyl group, (xix) a C3_7-ureido cycloalkyl group, (xx) a 5- to 8-membered heterocyclyl-ureido group containing, in addition to carbon atoms, 1 to 3 heteroatoms selected from the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, (xxi) a sulfamoyl group optionally substituted with C? -6 alkyl, (xxii) a 5- to 8-membered heterocyclic group containing, in addition to carbon atoms, 1 to 3 heteroatoms selected two of the group consisting of a nitrogen atom, an oxygen atom and a sulfur atom, which is optionally substituted with substituents selected from the group consisting of optionally halogenated C? -6 alkyl and C? _6-carbonyl alkoxy, (xxiii) an optionally halogenated C? _6 alkyl group, (xxiv) a C? 6-carbonyl, (xxv) a halogen atom, or (xxvi) a carboxyl group, and the Bh 'ring is a phenyl group, a pyridyl group or a piperidyl group, each of which is also optionally substituted in addition to R5h . As the compound (Ih), there can be mentioned, with particular preference, N- (3- {2-chloro-4- [(6-chloro-5-methyl-5H-pyrrolo [3,2-d] pyrimidine) 4-yl) amino] phenoxy] phenyl) cyclopropanecarboxamide, 6-chloro-N-. { 3-Chloro-4- [3- (trifluoromethyl) phenoxy] phenyl} -5-methyl-5H-pyrrolo [3,2-d] pyrimidin-4-amine, N- [3- (2-chloro-4- { [6-chloro-5- (2-hydroxyethyl) -5H -pyrrolo [3, 2-d] pyrimidin-4-yl] amino.}. phenoxy) phenyl] cyclopropanecarboxamide, and N- (tert-butyl) -3- (2-chloro-4- { [6-chloro -5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. Phenoxy) benzamide, and salts thereof.

As salts of the compounds represented by the formulas, there may be mentioned, for example, metal salts, ammonium salts, salts with organic base, salts with inorganic acid, salts with organic acid, salts with basic or acidic amino acid and the like. As preferred examples of the metal salt, there may be mentioned, for example, alkali metal salts such as sodium salt, potassium salt and the like; alkaline earth metal salts such as calcium salt, magnesium salt, barium salt and the like; aluminum salt and the like. As preferred examples of salts with organic base, there may be mentioned, for example, salts with trimethylamine, triethylamine, pyridine, picoline, 2,6-lutidine, ethanolamine, diethanolamine, triethanolamine, tromethamine [tris (hydroxymethyl) methylamine], t-butylamine , cyclohexylamine, dicyclohexylamine, N, N'-dibenzylethylenediamine and the like. As preferred examples of salts with inorganic acid, there may be mentioned, for example, salts with hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid, and the like. As preferred examples of salts with organic acid, there may be mentioned, for example, salts with formic acid, acetic acid, trifluoroacetic acid, acid italic, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, mellic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid and the like. As preferred examples of salts with basic amino acid, there may be mentioned, for example, salts with arginine, lysine, ornithine and the like. As preferred examples of the salts with acidic amino acid, there may be mentioned, for example, salts with aspartic acid, glutamic acid and the like. Of these, pharmaceutically acceptable salts are preferred. When a compound contains an acid functional group, there may be mentioned, for example, inorganic salts such as alkali metal salts (eg, sodium salt, potassium salt etc.), alkaline earth metal salts (for example, calcium salt, magnesium salt, barium salt etc.) and the like, ammonium salt and the like. And when a compound contains a basic functional group, there can be mentioned, for example, salts with inorganic acid such as hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, phosphoric acid and the like, and salts with organic acid such as acetic acid, italic acid, fumaric acid, oxalic acid, tartaric acid, maleic acid, citric acid, succinic acid, methanesulfonic acid, benzenesulfonic acid, p-toluenesulfonic acid and the like.

[Production methods] From now on, the production methods of the compounds (la) to (Ih) of the present invention are explained. [Production method A] The compound (Ia) of the present invention can be obtained, for example, by the method indicated in the following reaction scheme or an analogous method and the like. where each symbol is as defined previously. Each compound in the following reaction schemes includes salts, and such salts can be used, for example, those similar to the salts of the compound (la) and the like. The compound obtained in each step can be used as a reaction mixture or a crude product in the next reaction. In addition, the compound can be isolated from a reaction mixture according to a conventional method, and can be easily purified through a separation medium such as recrystallization, distillation, chromatography and the like. The schematic reaction formulas are indicated below, where each symbol of the compounds is as defined above. The compound (Ia) of the present invention can be produced, for example, by reacting a compound represented by the formula: where La is a leaving group, and the other symbols are as defined previously, or one of its salts and a compound represented by the formula: where Ga is a hydrogen atom or an atom of metal, and the other symbols are as defined previously, or one of their salts. Ga is primarily a hydrogen atom, but may be an alkali metal such as lithium, sodium, potassium, cesium and the like, or an alkaline earth metal such as magnesium, calcium and the like. The compound (Illa) or a salt thereof is preferably used in an amount of 1-5 equivalents, preferably 1-2 equivalents, based on the compound (Ha) and the reaction is preferably carried out in a solvent.

Further, a base or an ammonium salt may be used in an amount of about 1-10 equivalents, preferably 1-2 equivalents. In the aforementioned formula, as the leaving group for La, a halogen atom such as chlorine, bromine, iodine and the like, a group represented by the formula: -S (0) Rz wherein k is an integer of 0, 1 or 2, and Rz is a lower C ?4 alkyl group such as methyl, ethyl, propyl and the like, an aryl group of Cg-o such as phenyl, tolyl and the like, or a group represented by the formula: -ORz where Rz is as previously defined, and similar. As a solvent in the aforesaid reaction, there can be mentioned, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, 1-methy1-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. As a base in the aforesaid reaction, an inorganic base, an organic base and the like can be used. Specifically, for example, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, pyridine, N, N-dimethylaminopyridine, sodium methoxide, sodium, sodium ethoxide, potassium t-butoxide, sodium hydride, sodium amide, diazabicycloundecene (DBU) and the like. As the ammonium salt in the aforesaid reaction, pyridine hydrochloride, pyridine hydrobromide, pyridinium p-toluenesulfonate, quinoline hydrochloride, isoquinoline hydrochloride, pyrimidine hydrochloride, pyrazine hydrochloride, triazine hydrochloride, trimethylamine hydrochloride can be used. , triethylamine hydrochloride, hydrochloride N-ethyldiisopropylamine and the like. The aforesaid reaction can be carried out under cooling, at room temperature or under heating (about 40-200 ° C, preferably about 40-160 ° C), and the reaction time is, in general, about 1- 30 h, preferably about 1-20 h, more preferably about 1-10 h. A compound within the scope of the present invention can also be produced by means of application known per se in the compound obtained from the present invention for the introduction of substituents and conversion of functional groups. For the conversion of substituents, a known conventional method can be used. For example, conversion to the carboxy group can be mentioned by hydrolysis of the ester, conversion to the carbamoyl group by amidation of the carboxy group, conversion to the hydroxymethyl group by reduction of the carboxy group, conversion to the alcoholic compound by reduction or alkylation of the carbonyl group , reductive amination of the carbonyl group, oximation of the carbonyl group, acylation of the amino group, alkylation of the amino group, substitution and amination of the active halogen by amine, alkylation of the hydroxy group, substitution and amination of the hydroxy group and the like. When a reactive substituent causes a non-objective reaction is present during the introduction of substituents and the conversion of the functional groups, a protective group is first introduced if necessary into the reactive substituent by a known means, and the protecting group is removed by a means known per se after the reaction of the object, the compound also being able to be produced within the scope of the present invention. The compound (la), which is a product of the reaction, can be prepared as a single compound or as a mixture. The compound (Ia) of the present invention thus obtained can be subjected to a medium known per se, such as solvent extraction, concentration, neutralization, filtration, crystallization, recrystallization, column chromatography, high performance liquid chromatography and the like, while that the object compound can be isolated and purified with high purity from a reaction mixture. As the starting compound (Illa) of this production method, a commercially available one is used or it can be produced by a means known per se. The starting compound (Ha) of this production method can be prepared, for example, by a method indicated in the following reaction scheme. Here, the compounds (Ilaa), (Ilab), (Ilac) and (liad) are comprised in the compound (Ha). wherein Lla and L2a are halogen atoms, Rz is as defined above, and t is an integer of 1 or 2. As the method Aa, the compound (Ilaa) can be produced by reacting the compound (IVa) with an agent halogenant As a Ba method, the compound (IVa) is reacted with a thionating agent to give the compound (Va), which is then reacted with a compound represented by RzL2a in the presence of a base to give the compound (Ilab), which then it is subjected to an oxidation reaction to give the compound (Ilac). As the Ca method, the compound (Ilaa) is reacted with a compound represented by RzOH in the presence of a base to give the compound (liad). As the halogenating agent in Method Aa, for example, about 1-100 equivalents of phosphorus oxychloride, phosphorus pentachloride, phosphorus trichloride, thionyl chloride, sulfuryl chloride, tribromide can be used. of phosphorus and the like. In this case, the reaction can be carried out in the presence of a base such as diethylaniline, dimethylaniline, pyridine and the like. While the reaction can be carried out without a solvent, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like can be used as the reaction solvent; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetonitrile, ethyl acetate and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. As the thionant agent used in the production step from the compound (IVa) in the compound (Va) in the Ba method, for example, about 1-5 equivalents of a Lawesson reagent, phosphorus pentasulfide and the like can be used. . As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; and others. The The reaction is carried out at room temperature or under heating, and the reaction time is, in general, about 1-20 h, preferably about 1-10 h. As RzL2a in the production step from the compound (Va) in the compound (Ilab) in the Ba Method, for example, about 1-5 equivalents of methyl iodide, benzyl chloride, benzyl bromide and the like can be used , and as the base, there can be used, for example, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, pyridine, N, N- dimethylaminopyridine, sodium methoxide, sodium ethoxide, potassium t-butoxide, sodium hydride, sodium amide, diazabicycloundecene (DBU) and the like. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent of them and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. As an oxidizing agent in the production step from the compound (Ilab) in the compound (Ilac) in the Ba Method, there can be used, for example, m-chloroperbenzoic acid, hydrogen peroxide, peracetic acid, t-butyl hydroperoxide, potassium peroxysulfate, potassium permanganate, sodium perborate, sodium periodate, sodium hypochlorite, halogen and the like. When the compound (Ilac) is produced where t = l, the oxidizing agent is used in about 1-1.5 equivalents based on the compound (Ilab), and when the compound (Ilac) is produced where t = 2, it employs in approximately 2-3 equivalents referred to the compound (Ilab). The reaction solvent is not particularly limited, as long as it does not react with the oxidizing agent and, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like can be used.; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acids carboxylic acids such as acetic acid, trifluoroacetic acid and the like; acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethyl sulfoxide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. As RzOH in the production step from the compound (Ilaa) in the compound (liad) in the Ca method, for example, about 1-10 equivalents of methanol, ethanol, phenol and the like can be used, and as a base, for example, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, pyridine, N, N-dimethylaminopyridine, sodium methoxide can be used. , sodium ethoxide, potassium t-butoxide, sodium hydride, sodium amide, diazabicycloundecene (DBU) and the like. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N- dimethylacetamide, l-methyl-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. On the other hand, the compound (IVa) can be produced, for example, by means of a method indicated by the following formula: wherein R, 1 ± 0uaa is an alkyl group of C? _4, and the other symbols are as defined above. That is, the compound (Via) is reacted with about 1-4 equivalents of formamidine or one of its salts to give the compound (IVa). As the reaction solvent, for example, alcohols such as methanol, ethanol, isopropanol, t-butanol and the like can be used; halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, 1-methy1-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. The compound (Ha) can also be prepared, for example, by means of a method indicated by the following formula: where L 3jaa is a halogen atom, and the other symbols are as previously defined. For the production step from the compound (Vlla) in the compound (Villa) in this method, a general knowledge reaction can be carried out in the form of a Sonogashira reaction or an analogous reaction and, in general, the compound (Villa) can be produced by reacting the compound (Vlla) with about 1-3 equivalents of a compound represented by the formula: in the presence of a base, approximately 0.01-1 equivalents of a palladium and copper iodide catalyst. As the base there can be used, for example, triethylamine, N-ethyldiisopropylamine, diisopropylamine, pyridine, N, N-dimethylaminopyridine, diazabicycloundecene (DBU), sodium carbonate, potassium carbonate, sodium acid carbonate, potassium hydrogen carbonate and the like. As palladium catalyst can be used, for example, dichlorobis (triphenylphosphine) palladium (II), palladium on carbon, palladium (II) diacetate, bis (benzonitrile) dichloropalladium (II) and the like. This reaction can be carried out in the co-presence of a tertiary phosphine compound such as triphenylphosphine, tributylphosphine and the like as a ligand. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like can be used, for example.; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent of them and the like. This reaction is carried out at room temperature or under heating, and the reaction time is generally about 1-50 h, preferably about 1-20 h. For the production stage from the compound (Villa) In the compound (Ha) in this method, a cyclization reaction is generally carried out in the presence of about 1-3 equivalents of base or about 0.01-1 equivalents of copper iodide to give the compound (Ha) . As a base, for example, potassium t-butoxide, sodium t-butoxide, cesium t-butoxide, sodium ethoxide, potassium hydride, sodium hydride, cesium hydroxide, sodium hydroxide, potassium hydroxide can be used. , sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, diisopropylamine, pyridine, N, N-dimethylaminopyridine, diazabicycloundecene (DBU) and the like. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane and the like; acetone, acetonitrile, ethyl acetate, N, N- dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out at low temperature, at room temperature or under heating, and the reaction time is generally about 1-50 h, preferably about 1-20 h. According to the type of substituent of the starting compound (Ha), a starting compound (Ha) with a different substituent can be produced by conversion of the substituent, as a starting material, from a co-formula produced by means of the production method before mentioned. For the conversion of the substituent, a known general method can be employed. For example, conversion to the carbamoyl group by ester hydrolysis and amidation, conversion to hydroxymethyl group by reduction of the carboxy group, conversion to the alcohol compound by reduction or alkylation of the carbonyl group, reductive amination of the carbonyl group, carbonyl group oximation, acylation of the amino group, alkylation of the amino group, substitution and amination of the active halogen by amine, alkylation of the hydroxy group, substitution and amination of the hydroxy group and the like. When a reactive substituent that causes a non-objective reaction is present during the introduction of substituents and the conversion of the functional groups, before introducing a protective group, if necessary, into the reactive substituent by means known per se, and the protective group is removed by a known means after the object reaction, and the starting compound (Ha) can also be produced. [Production method B] The compound (Ib) of the present invention can be obtained, for example, by the method indicated by the following reaction schemes or an analogous method and the like. where each symbol is as defined previously. Each compound in the following reaction schemes includes salts, and such salts can be used, for example, those similar to the salts of the compound (Ib) and the like. The compound obtained in each step can be used as a reaction mixture or as a crude product in the next reaction. In addition, the compound can be isolated from a reaction mixture according to a conventional method, and can be easily purified through a separation medium such as recrystallization, distillation, chromatography and the like. The schematic reaction formulas are indicated below, where each symbol of the compounds is as defined above. The compound (Ib) of the present invention can be produced, for example, by reacting a compound represented by the formula: where L is a leaving group, and the other symbols are as defined above, or one of its salts and a compound represented by the formula: where Gb is a hydrogen atom or a metal atom, and the other symbols are as previously defined, or one of their salts.

When Xlb is -NR3b-Ylb-, -0- or -S-, Gb is primarily a hydrogen atom, but may be an alkali metal such as lithium, sodium, potassium, cesium and the like, or an alkaline earth metal such as magnesium , calcium and the like. When Xlb is -CHR3b-, Gb can be a metal such as lithium, halogenated magnesium, copper, zinc and the like. The compound (IHb) or a salt thereof is preferably used in an amount of 1-5 equivalents, preferably 1-2 equivalents, based on the compound (Hb) and the reaction is preferably carried out in a solvent. In addition, a base or an ammonium salt may be used in an amount of about 1-10 equivalents, preferably 1-2 equivalents. In the aforementioned formula, as a leaving group for Lb, a halogen atom such as chlorine, bromine, iodine and the like, a group represented by the formula: -S (0) kRz wherein k is an integer of 0, 1 or 2, and Rz is a lower (C? 4) alkyl group such as methyl, ethyl, propyl and the like, a C6-10 aryl group such as phenyl, tolyl and the like, or a group represented by the formula : -ORz where Rz is as defined previously, and similar. As a solvent in the aforesaid reaction, there can be mentioned, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, 1-methy1-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. As a base in the aforesaid reaction, an inorganic base, an organic base and the like can be used. Specifically, for example, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, pyridine, N, N-dimethylaminopyridine, sodium methoxide, sodium, sodium ethoxide, potassium t-butoxide, sodium hydride, sodium amide, diazabicycloundecene (DBU) and the like. As the ammonium salt in the aforesaid reaction, pyridine hydrochloride, pyridine hydrobromide, pyridinium p-toluenesulfonate, quinoline hydrochloride, isoquinoline hydrochloride, pyrimidine hydrochloride, pyrazine hydrochloride, triazine hydrochloride, trimethylamine hydrochloride can be used. , triethylamine hydrochloride, hydrochloride N-ethyldiisopropylamine and the like. The aforesaid reaction can be carried out under cooling, at room temperature or under heating (about 40-200 ° C, preferably about 40-160 ° C), and the reaction time is, in general, about 1- 30 h, preferably about 1-20 h, more preferably about 1-10 h. The compound (Ib) wherein Xlb is -SO- or -S02- can be produced by subjecting the compound (Ib) wherein Xlb is -S-, to an oxidation reaction. As an oxidizing agent in the production step, there can be used, for example, m-chloroperbenzoic acid, hydrogen peroxide, peracetic acid, t-butyl hydroperoxide, potassium peroxysulfate, potassium permanganate, sodium perborate, sodium periodate, sodium hypochlorite, halogen and the like. When the compound (Ib) is produced wherein Xlb is -SO-, the oxidizing agent is used in about 1-1.5 equivalents based on the starting compound, and when the compound (Ib) is produced wherein Xlb is -S02 -, it is used in approximately 2-3 equivalents based on the starting compound. The reaction solvent is not particularly limited, as long as it does not react with the oxidizing agent and, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2- can be used.dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; carboxylic acids such as acetic acid, trifluoroacetic acid and the like; acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethyl sulfoxide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. A compound within the scope of the present invention can also be produced by means of application known per se in the compound obtained (Ib) of the present invention for the introduction of substituents and conversion of functional groups. For the conversion of substituents, a known conventional method can be used. For example, conversion to the carboxy group can be mentioned by hydrolysis of the ester, conversion to the carbamoyl group by amidation of the carboxy group, conversion to the hydroxymethyl group by reduction of the carboxy group, conversion to the alcoholic compound by reduction or alkylation of the carbonyl group , reductive amination of the carbonyl group, carbonyl group oximation, amino group acylation, alkylation of the amino group, substitution and amination of the active halogen by amine, alkylation of the hydroxy group, substitution and amination of the hydroxy group and the like. When a reactive substituent which causes a non-objective reaction is present during the introduction of substituents and the conversion of the functional groups, a protecting group is introduced beforehand in the reactive substituent if necessary by means known per se, and the protective group is It is removed by a means known per se after the reaction of the object, and the compound can also be produced within the scope of the present invention. The compound (Ib), which is a product of the reaction, can be prepared as a single compound or as a mixture. The compound (Ib) of the present invention thus obtained can be subjected to a medium known per se, such as solvent extraction, concentration, neutralization, filtration, crystallization, recrystallization, column chromatography, high performance liquid chromatography and the like, while that the object compound can be isolated and purified with high purity from a reaction mixture. As the starting compound (IHb) of this production method, a commercially available one is used or it can be produced by a means known per se. The starting compound (Hb) of this method of Production can be prepared, for example, by a method indicated in the following reaction scheme. Here, the compounds (liba), (Hbb), (Hbc), (Hbd) and (libe) are included in the compound (Hb). wherein Llb and L2b are halogen atoms, Rz is as defined above, and t is an integer of 1 or 2. As the Ab method, the compound (liba) can be produced by reacting the compound (IVb) with an agent halogenant As a Bb method, the compound (IVb) is reacted with a thionating agent to give the compound (Vb), which is then reacted with a compound represented by RzL2b in the presence of a base to give the compound (Hbb), which is then subjected to an oxidation reaction to give the compound (Hbc). As the Cb method, the compound (liba) is reacted with a compound represented by RzOH in presence of a base to give the compound (Hbd). As the halogenating agent in Method Ab, there can be used, for example, about 1-100 equivalents of phosphorus oxychloride, phosphorus pentachloride, phosphorus trichloride, thionyl chloride, sulfuryl chloride, phosphorus tribromide and the like. In this case, the reaction can be carried out in the presence of a base such as diethylaniline, dimethylaniline, pyridine and the like. While the reaction can be carried out without a solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like can be used as the reaction solvent.; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetonitrile, ethyl acetate and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. As the thionant agent used in the production step from the compound (IVb) in the compound (Vb) in the Method Bb, for example, approximately 1-5 equivalents of a Lawesson reagent, phosphorus pentasulfide and the like can be used. . As a reaction solvent, they can be using, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; and others. The reaction is carried out at room temperature or under heating, and the reaction time is, in general, about 1-20 h, preferably about 1-10 h. As RzL2b in the production step from the compound (Vb) in the compound (Hbb) in the Method Bb, for example, about 1-5 equivalents of methyl iodide, benzyl chloride, benzyl bromide and the like can be used , and as the base, there can be used, for example, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, pyridine, N, N- dimethylaminopyridine, sodium methoxide, sodium ethoxide, potassium t-butoxide, sodium hydride, sodium amide, diazabicycloundecene (DBU) and the like. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitop, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-met-l-2-pyrroiidone, dimethylsulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, of about 1-20 h, preferably about 1-10 h. As an oxidizing agent in the production step of the compound (Hbb) in the compound (Hbc) in Method Bb, there can be used, for example, m-chloroperbenzoic acid, hydrogen peroxide, peracetic acid, t-butyl hydroperoxide , potassium peroxysulfate, potassium permanganate, sodium perborate, sodium periodate, sodium hypochlocite, halogen and the like. When the compound (Hbc) is produced where t = l, the oxidizing agent is used in about 1-1.5 equivalents based on the compound (Hbb), and when the compound (Hbc) is produced where t = 2, it employs in approximately 2-3 equivalents referred to the compound (Hbb). The reaction solvent is not particularly limited, as long as it does not react with the oxidizing agent and, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; carboxylic acids such as acetic acid, trifluoroacetic acid and the like; acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethyl sulfoxide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. As RzOH in the production step from the compound (liba) in the compound (Hbd) in Method Cb, for example, about 1-10 equivalents of methanol, ethanol, phenol and the like can be used, and as a base, for example, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, pyridine, N, N-dimethylaminopyridine, sodium methoxide can be used. , sodium ethoxide, potassium t-butoxide, sodium hydride, sodium amide, diazabicycloundecene (DBU) and the like. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, for example, can be used, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethisulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. On the other hand, the compound (IVb) can be produced, for example, by means of a method indicated by the following formula: wherein R10b is an alkyl group of C? _4, and the other symbols are as defined above. That is, the compound (VIb) is reacted with about 1-4 equivalents of formamidine or one of its salts to give the co-tax (IVb). As the reaction solvent, alcohols such as methanol, for example, can be used. ethanol, isopropanol, t-butanol and the like; halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, 1-methy1-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. When b is C (Rlb), the compound (libe) can also be prepared, for example, by a method indicated by the following formula: where L 3b is a halogen atom, and the other symbols are as defined above. For the production stage from the compound (VHb) in the compound (HIVb) in this method, a general knowledge reaction can be carried out in the form of a Sonogashira reaction or an analogous reaction and, in general, the compound (HIVb) can be produced by reacting the compound (VHb) with about 1-3 equivalents of a compound represented by the formula: R 1 b- ^ in the presence of a base, approximately 0.01-1 equivalents of a palladium and copper iodide catalyst. As the base there can be used, for example, triethylamine, N-ethyldiisopropylamine, diisopropylamine, pyridine, N, N-dimethylaminopyridine, diazabicycloundecene (DBU), sodium carbonate, potassium carbonate, sodium acid carbonate, potassium hydrogen carbonate and the like. As the palladium catalyst, dichlorobis (triphenylphosphine) palladium (II), palladium on carbon, palladium (II) diacetate, bis (benzonitrile) dichloropalladium (II) and the like can be used, for example. This reaction can be carried out in the co-presence of a tertiary phosphine compound such as triphenylphosphine, tributylphosphine and the like as a ligand. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as ether diethyl, tetrahydrofuran, dioxane, 1,2-dimethoxyethane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethisulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. This reaction is carried out at room temperature or under heating, and the reaction time is generally about 1-50 h, preferably about 1-20 h. For the production stage from the compound (HIVb) in the compound (libe) in this method, a cyclization reaction is generally carried out in the presence of about 1-3 equivalents of base or about 0.01-1 equivalents of copper iodide to give the compound (libe). As a base, for example, potassium t-butoxide, sodium t-butoxide, cesium t-butoxide, sodium ethoxide, potassium hydride, sodium hydride, cesium hydroxide, sodium hydroxide, potassium hydroxide can be used. , sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, diisopropylamine, pyridine, N, N-dimethylaminopyridine, diazabicycloundecene (DBU) and the like. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like can be used, for example.; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out at low temperature, at room temperature or under heating, and the reaction time is generally about 1-50 h, preferably about 1-20 h. Depending on the type of substituent of the starting compound (Hb), a starting compound (Hb) with a different substituent can be produced by conversion of the substituent, as a starting material, from a compound produced by means of the production method before mentioned. For the conversion of the substituent, a known general method can be employed. For example, conversion to the carbamoyl group by ester hydrolysis and amidation, conversion to hydroxymethyl group by reduction of the carboxy group, conversion to the alcohol compound by reduction or alkylation of the carbonyl group, reductive amination of the carbonyl group, carbonyl group oximation, acylation of the amino group, alkylation of the amino group, substitution and amination of the active halogen by amine, alkylation of the hydroxy group, substitution and amination of the hydroxy group and the like. When a reactive substituent which causes a non-objective reaction is present during the introduction of substituents and the conversion of the functional groups, a protecting group is introduced beforehand in the reactive substituent if necessary by a known means, and the protective group is it can be removed by a medium known per se after the object reaction, and the starting compound (Hb) can also be produced. [Production method C] The compound (le) of the present invention can be obtained, for example, by the method indicated in the following reaction scheme or an analogous method and the like. where each symbol is as defined previously. Each compound in the following reaction schemes includes salts, and such salts can be used, for example, those similar to salts of the compound (le) and similar. The compound obtained in each step can be used as a reaction mixture or as a crude product in the next reaction. In addition, the compound can be isolated from a reaction mixture according to a conventional method, and can be easily purified through a separation medium such as recrystallization, distillation, chromatography and the like. The schematic reaction formulas are indicated below, where each symbol of the compounds is as defined above. The compound (le) of the present invention can be produced, for example, by reacting a compound represented by the formula: where Lc is a leaving group, and the other symbols are as defined previously, or one of its salts and a compound represented by the formula: wherein Gc is a hydrogen atom or a metal atom, and the other symbols are as previously defined, or one of their salts. Gc is primarily a hydrogen atom, but may be an alkali metal such as lithium, sodium, potassium, cesium and the like, or an alkaline earth metal such as magnesium, calcium and the like. The compound (HIc) or a salt thereof is preferably used in an amount of 1-5 equivalents, preferably 1-2 equivalents, based on the compound (He) and the reaction is preferably carried out in a solvent. In addition, a base or an ammonium salt may be used in an amount of about 1-10 equivalents, preferably 1-2 equivalents. In the aforementioned formula, as a leaving group for Lc, a halogen atom such as chlorine, bromine, iodine and the like can be used, a group represented by the formula: -S (OYRz where k is an integer of 0, 1 or 2, and Rz is a lower (C? 4) alkyl group such as methyl, ethyl, propyl and the like, an aryl group of Ce-xo such as phenyl, tolyl and the like, or a group represented by the formula: ORz where Rz is as previously defined, and similar.

As the solvent in the aforesaid reaction, there can be mentioned, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethisulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. As a base in the aforesaid reaction, an inorganic base, an organic base and the like can be used. Specifically, for example, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, pyridine, N, N-dimethylaminopyridine, sodium methoxide, sodium, sodium ethoxide, potassium t-butoxide, sodium hydride, sodium amide, diazabicycloundecene (DBU) and the like. As the ammonium salt in the aforesaid reaction, pyridine hydrochloride, pyridine hydrobromide, pyridinium p-toluenesulfonate, quinoline hydrochloride, isoquinoline hydrochloride, pyrimidine hydrochloride, can be used, pyrazine hydrochloride, triazine hydrochloride, trimethylamine hydrochloride, triethylamine hydrochloride, N-ethi Idiisopropylamine hydrochloride and the like. The aforesaid reaction can be carried out under cooling, at room temperature or under heating (about 40-200 ° C, preferably about 40-160 ° C), and the reaction time is, in general, about 1 hour. -30 h, preferably about 1-20 h, more preferably about 1-10 h. A compound within the scope of the present invention can also be produced by means of application known per se in the compound obtained (le) of the present invention for the introduction of substituents and conversion of functional groups. For the conversion of substituents, a known conventional method can be used. For example, conversion to the carboxy group can be mentioned by hydrolysis of the ester, conversion to the carbamoyl group by amidation of the carboxy group, conversion to the hydroxymethyl group by reduction of the carboxy group, conversion to the alcoholic compound by reduction or alkylation of the carbonyl group , reductive amination of the carbonyl group, oximation of the carbonyl group, acylation of the amino group, alkylation of the amino group, substitution and amination of the active halogen by amine, alkylation of the hydroxy group, substitution and amination of the hydroxy group and the like. When a reactive substituent which causes a non-objective reaction is present during the introduction of substituents and the conversion of the functional groups, a protective group is introduced beforehand into the reactive substituent if necessary by a known means, and the protective group is It is removed by a means known per se after the reaction of the object, and the compound can also be produced within the scope of the present invention. The compound (le), which is a product of the reaction, can be prepared as a single compound or as a mixture. The compound (le) of the present invention thus obtained can be subjected to a medium known per se, such as solvent extraction, concentration, neutralization, filtration, crystallization, recrystallization, column chromatography, high performance liquid chromatography and the like, while that the object compound can be isolated and purified with high purity from a reaction mixture. As the starting compound (lile) of this production method, a commercially available one is used or it can be produced by a means known per se. The starting compound (He) of this production method can be prepared, for example, by a method indicated in the following reaction scheme. Here, the compounds (Hca), (Hcb), (Hcc) and (Hcd) are included in the compound (He). wherein Llc and L2c are halogen atoms, Rz is as defined above, and t is an integer of 1 or 2. As the Ac method, the compound (Ilca) can be produced by reacting the compound (IVc) with an agent halogenant As a Be method, the compound (IVc) is reacted with a thionating agent to give the compound (Ve), which is then reacted with a compound represented by RzL2c in the presence of a base to give the compound (Hcb), which then it is subjected to an oxidation reaction to give the compound (Hcc). As the Ce method, the compound (Ilca) is reacted with a compound represented by RzOH in the presence of a base to give the compound (Hcd). As the halogenating agent in the Ac Method, for example, approximately 1-100 equivalents of phosphorus oxychloride, phosphorus pentachloride, phosphorus trichloride, thionyl chloride, sulfuryl chloride, phosphorus tribromide and the like. In this case, the reaction can be carried out: carried out in the presence of a base such as diethyloliline, dimethylaniline, pyridine and the like. While the reaction can be carried out without a solvent, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like can be used as the reaction solvent; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetonitrile, ethyl acetate and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. As the thionant agent used in the production step from the compound (IVc) in the compound (Ve) in the Be Method, for example, about 1-5 equivalents of a Lawesson reagent, phosphorus pentasulfide and the like can be used. . As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; and others. The reaction is carried out at room temperature or under heating, and the reaction time is, in general, about 1-20 h, preferably about 1-10 h. As RzL2c in the production step from the compound (Ve) in the compound (Hcb) in the Be Method, for example, about 1-5 equivalents of methyl iodide, benzyl chloride, benzyl bromide and the like can be used , and as the base, there can be used, for example, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, pyridine, N, N- dimethylaminopyridine, sodium methoxide, sodium ethoxide, potassium t-butoxide, sodium hydride, sodium amide, diazabicycloundecene (DBU) and the like. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N- dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. As an oxidizing agent in the production step from the compound (Hcb) in the compound (Hcc) in the Be Method, there can be used, for example, m-chloroperbenzoic acid, hydrogen peroxide, peracetic acid, t-butyl hydroperoxide, potassium peroxysulfate, potassium permanganate, sodium perborate, sodium periodate, sodium hypochlorite, halogen and the like. When the compound (IIcc) is produced where t = l, the oxidizing agent is used in about 1-1.5 equivalents based on the compound (Hcb), and when the compound (Hcc) is produced where t = 2, it employs in approximately 2-3 equivalents referred to the compound (Hcb). The reaction solvent is not particularly limited, as long as it does not react with the oxidizing agent and, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like can be used.; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; carboxylic acids such as acetic acid, trifluoroacetic acid and the like; acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethyl sulfoxide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. As Rz0H in the production step from the compound (Hca) in the compound (Hcd) in the Ce Method, for example, approximately 1-10 equivalents of methanol, ethanol, phenol and the like can be used, and as a base, for example, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, pyridine, N, N-dimethylaminopyridine, sodium methoxide can be used. , sodium ethoxide, potassium t-butoxide, sodium hydride, sodium amide, diazabicycloundecene (DBU) and the like. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as ether diethyl, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethisulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. On the other hand, the compound (IVc) can be produced, for example, by means of a method indicated by the following formula: wherein R, 10c is an alkyl group of C? -4, and the other symbols are as defined above. That is, the compound (VIc) is reacted with about 1-4 equivalents of formamidine or one of its salts to give the compound (IVc). As the reaction solvent, for example, alcohols such as methanol, ethanol, isopropanol, t-butanol and the like can be used; halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetranhydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, 1-meth i 1-2 -pyrrolidone, dimethisulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. The compound (He) can also be prepared, for example, by means of a method indicated by the following formula: where L 3c is a halogen atom, and the other symbols are as defined above. For the production step from the compound (HCV) in the compound (HIVc) in this method, a general knowledge reaction can be carried out in the form of a Sonogashira reaction or an analogous reaction and, in general, the compound (VIIIc) can be produced by reacting the compound (HCV) with about 1-3 equivalents of a compound represented by the formula: R1C- ^ in the presence of a base, approximately 0.01-1 equivalents of a palladium and copper iodide catalyst. As a base there can be used, for example, triethylamine, N-ethyldiisopropylamine, diisopropylamine, pyridine, N, N-dimethylaminopyridine, diazabicycloundecene (DBU), sodium carbonate, potassium carbonate., sodium hydrogen carbonate, potassium hydrogen carbonate and the like. As the palladium catalyst, dichlorobis (triphenylphosphine) palladium (II), palladium on carbon, palladium (II) diacetate, bis (benzonitrile) dichloropalladium (II) and the like can be used, for example. This reaction can be carried out in the co-presence of a tertiary phosphine compound such as triphenylphosphine, tributylphosphine and the like as a ligand. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like can be used, for example.; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent of them and the like. This reaction is carried out at room temperature or under heating, and the reaction time is generally about 1-50 h, preferably about 1-20 h. For the production stage from the compound (HIVc) in the compound (He) in this method, a cyclization reaction is generally carried out in the presence of about 1-3 equivalents of base or about 0.01-1 equivalents of copper iodide to give the compound ( 11c). As a base, for example, potassium t-butoxide, sodium t-butoxide, cesium t-butoxide, sodium ethoxide, potassium hydride, sodium hydride, cesium hydroxide, sodium hydroxide, potassium hydroxide can be used. , sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, diisopropylamine, pyridine, N, N-dimethylaminopyridine, diazabicycloundecene (DBU) and the like. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane and the like; acetone, acetonitrile, ethyl acetate, N, N- dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out at low temperature, at room temperature or under heating, and the reaction time is generally about 1-50 h, preferably about 1-20 h. Depending on the type of substituent of the starting compound (lie), a starting co-tax (lie) with a different substituent can be produced by conversion of the substituent, as a starting material, from a compound produced by means of the production method before mentioned. For the conversion of the substituent, a known general method can be employed. For example, conversion to the carbamoyl group by ester hydrolysis and amidation, conversion to hydroxymethyl group by reduction of the carboxy group, conversion to the alcohol compound by reduction or alkylation of the carbonyl group, reductive amination of the carbonyl group, carbonyl group oximation, acylation of the amino group, alkylation of the amino group, substitution and amination of the active halogen by amine, alkylation of the hydroxy group, substitution and amination of the hydroxy group and the like. When a reactive substituent that causes a non-objective reaction is present during the introduction of substituents and the conversion of the functional groups, before introducing a protective group, if necessary, into the reactive substituent by means known per se, and the protecting group is removed by a medium known per se after the subject reaction, and the starting compound (He) can also be produced. The starting compound (He) of this production method can also be produced, for example, by means of a method using the compound (HcY, as indicated by the following reaction scheme: (He ') dfc) where each symbol is as defined previously. In this method, the compound (He ') in the anion is generally converted by removing a proton from the compound (He') using a base which is then reacted with a cation having Rlc to give the compound (He). As the base, for example, n-butyl lithium, s-butyl lithium, t-butyl lithium, lithium t-butoxide, lithium diisopropylamide and the like can be used. As reagent for generating the cation, for example, p-toluenesulfonyl chloride, benzenesulfonyl bromide, p-toluenesulfonyl cyanide, S- (trifluoromethyl) dibenzothiophenium trifluoromethanesulfonate, can be used, N, N-dimethylformamide and the like. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like can be used, for example.; ethers such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane and the like, a mixed solvent thereof and the like. The aforesaid reaction can be carried out under cooling, preferably about no more than -20 ° C, and the reaction time is generally about 15 min-50 h, preferably about 30 min-4 h. [Production method D] The compound (Id) of the present invention can be obtained, for example, by the method indicated in the following reaction scheme or an analogous method and the like. where each symbol is as defined previously. Each compound in the following reaction schemes includes salts, and as such salts can be used, for example, those similar to salts of the compound (Id) and similar. The compound obtained in each step can be used as a reaction mixture or as a crude product in the next reaction. In addition, the compound can be isolated from a reaction mixture according to a conventional method, and can be easily purified through a separation medium such as recrystallization, distillation, chromatography and the like. The schematic reaction formulas are indicated below, where each symbol of the compounds is as defined above. The compound (Id) of the present invention can be produced, for example, by reacting a compound represented by the formula: where L is a leaving group, and the other symbols are as previously defined, or one of their salts and a co-formula represented by the formula: where G is a hydrogen atom or a metal atom, and the other symbols are as defined previously, or one of their salts. Gd is primarily a hydrogen atom, but may be an alkali metal such as lithium, sodium, potassium, cesium and the like, or an alkaline earth metal such as magnesium, calcium and the like. The compound (IHd) or a salt thereof is preferably used in an amount of 1-5 equivalents, preferably 1-2 equivalents, based on the compound (Hd) and the reaction is preferably carried out in a solvent. In addition, a base or an ammonium salt may be used in an amount of about 1-10 equivalents, preferably 1-2 equivalents. In the aforementioned formula, as a leaving group for Ld, a halogen atom such as chlorine, bromine, iodine and the like, a group represented by the formula: -S (0) kRz wherein k is an integer of 0, 1 or 2, and Rz is a lower alkyl (C? _4) group such as methyl, ethyl, propyl and the like, an aryl group of Ce-xo such as phenyl, tolyl and the like, or a group represented by the formula: -0Rz wherein Rz is as defined above, and the like. As the solvent in the aforesaid reaction, there can be mentioned, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, 1-methy1-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. As a base in the aforesaid reaction, an inorganic base, an organic base and the like can be used. Specifically, for example, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, pyridine, N, N-dimethylaminopyridine, sodium methoxide, sodium, sodium ethoxide, potassium t-butoxide, sodium hydride, sodium amide, diazabicycloundecene (DBU) and the like.

As the ammonium salt in the aforesaid reaction, pyridine hydrochloride, pyridine hydrobromide, pyridinium p-toluenesulfonate, quinoline hydrochloride, isoquinoline hydrochloride, pyrimidine hydrochloride, pyrazine hydrochloride, triazine hydrochloride, trimethylamine hydrochloride can be used. , triethylamine hydrochloride, N-ethyldiisopropylamine hydrochloride and the like. The aforesaid reaction can be carried out under cooling, at room temperature or under heating (about 40-200 ° C, preferably about 40-160 ° C), and the reaction time is, in general, about 1- 30 h, preferably about 1-20 h, more preferably about 1-10 h. A compound within the scope of the present invention can also be produced by means of application known per se in the compound obtained (Id) of the present invention for the introduction of substituents and conversion of functional groups. For the conversion of substituents, a known conventional method can be used. For example, conversion to the carboxy group can be mentioned by hydrolysis of the ester, conversion to the carbamoyl group by amidation of the carboxy group, conversion to the hydroxymethyl group by reduction of the carboxy group, conversion to the alcoholic compound by reduction or alkylation of the group carbonyl, reductive amination of the carbonyl group, oximation of the carbonyl group, acylation of the amino group, alkylation of the amino group, substitution and amination of the active halogen by amine, alkylation of the hydroxy group, substitution and amination of the hydroxy group and the like. When a reactive substituent which causes a non-objective reaction is present during the introduction of substituents and the conversion of the functional groups, a protecting group is introduced beforehand in the reactive substituent if necessary by means known per se, and the protective group is It is removed by a means known per se after the reaction of the object, and the compound can also be produced within the scope of the present invention. The compound (Id), which is a product of the reaction, can be prepared as a single compound or as a mixture. The compound (Id) of the present invention thus obtained can be subjected to a medium known per se, such as solvent extraction, concentration, neutralization, filtration, crystallization, recrystallization, column chromatography, high performance liquid chromatography and the like, while that the object compound can be isolated and purified with high purity from a reaction mixture. As the starting compound (IHd) of this production method, one is commercially available or can be used produce by a means known per se. The starting compound (lid) of this production method can be prepared, for example, by a method indicated in the following reaction scheme. Here, the compounds (Hda), (Hdb), (Ildc) and (Hdd) are comprised in the compound (Hd). wherein Lld and L2 are halogen atoms, Rz is as defined above, and t is an integer of 1 or 2. As Ad method, the compound (Hda) can be produced by reacting the compound (IVd) with an agent halogenant As a Bd method, the compound (IVd) is reacted with a thionating agent to give the compound (Vd), which is then reacted with a compound represented by RL2d in the presence of a base to give the compound (Hdb), which then it is subjected to an oxidation reaction to give the compound (Ildc). As a Cd method, the compound (Hda) it is reacted with a compound represented by RzOH in the presence of a base to give the compound (Hdd). As the halogenating agent in the Ad Method, there can be used, for example, about 1-100 equivalents of phosphorus oxychloride, phosphorus pentachloride, phosphorus trichloride, thionyl chloride, sulfuryl chloride, phosphorus tribromide and the like. In this case, the reaction can be carried out in the presence of a base such as diethylaniline, diraethylaniline, pyridine and the like. While the reaction can be carried out without a solvent, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like can be used as the reaction solvent; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetonitrile, ethyl acetate and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. As the thionant agent used in the production step from the compound (IVd) in the compound (Vd) in the Bd Method, for example, approximately 1-5 equivalents of a Lawesson reagent, pentasulfide phosphorus and the like. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like can be used, for example; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; and others. The reaction is carried out at room temperature or under heating, and the reaction time is, in general, about 1-20 h, preferably about 1-10 h. As RzL2d in the production step from the compound (Vd) in the compound (Ildb) in the Bd Method, for example, about 1-5 equivalents of methyl iodide, benzyl chloride, benzyl bromide and the like can be used , and as the base, there can be used, for example, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, pyridine, N, N- dimethylaminopyridine, sodium methoxide, sodium ethoxide, potassium t-butoxide, sodium hydride, sodium amide, diazabicycloundecene (DBU) and the like. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like can be used, for example.; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, 1-methyl-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time is, in general, about 1-20 h, preferably about 1-10 h. As an oxidizing agent in the production step from the compound (Ildb) in the compound (Ildc) in the Bd Method, there can be used, for example, m-chloroperbenzoic acid, hydrogen peroxide, peracetic acid, t-butyl hydroperoxide , potassium peroxysulfate, potassium permanganate, sodium perborate, sodium periodate, sodium hypochlorite, halogen and the like. When the compound (Hdc) is produced where t = l, the oxidizing agent is used in about 1-1.5 equivalents based on the compound (Hdb), and when the compound (Hdc) is produced where t = 2, it employs in approximately 2-3 equivalents referred to the compound (Hdb). The reaction solvent is not particularly limited, as long as it does not react with the oxidizing agent and, for example, hydrocarbons can be used halogenated such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; carboxylic acids such as acetic acid, trifluoroacetic acid and the like; acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethyl sulfoxide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. As RzOH in the production step from the compound (Hda) in the compound (Hdd) in the Cd Method, for example, approximately 1-10 equivalents of methanol, ethanol, phenol and the like can be used, and as a base, for example, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, pyridine, N, N-dimethylaminopyridine, sodium methoxide can be used. , sodium ethoxide, potassium t-butoxide, sodium hydride, sodium amide, diazabicycloundecene (DBU) and the like. As a reaction solvent, they can be used, example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-diraethylacetamide, l-methyl-2-pyrrolidone, dimethisulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. On the other hand, the compound (IVd) can be produced, for example, by means of a method indicated by the following formula: wherein R, 10d is an alkyl group of C? -4, and the other symbols are as defined above. That is, the compound (Vid) is reacted with about 1-4 equivalents of formamidine or one of its salts to give the compound (IVd). As the reaction solvent, alcohols such as methanol, for example, can be used. ethanol, isopropanol, t-butanol and the like; halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, 1-methy1-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. The compound (lid) can also be prepared, for example, by means of a method indicated by the following formula: where L 3d is a halogen atom, and the other symbols are as previously defined. For the production stage from the compound (VHd) in the compound (HIVd) in this method, you can carry out a general knowledge reaction in the form of a Sonogashira reaction or an analogous reaction and, in general, the compound (HIVd) can be produced by reacting the compound (VHd) with about 1-3 equivalents of a compound represented by the formula: R1d- in the presence of a base, approximately 0.01-1 equivalents of a palladium and copper iodide catalyst. As the base, for example, tpetilamma, N-ethyldiisopropylamine, dnsopropylamine, pyridine, N, N-dimetham, lammopyridine, diazabicycloundecene (DBU), sodium carbonate, potassium carbonate, sodium acid carbonate, potassium carbonate and Similar. As palatant catalyst there can be used, for example, dicloi bis (tpphenylphosphine) palladium (II), palladium on carbon, palladium (II) diacetate, bis (benzonitop) dichloropalladium (II) and the like. This reaction can be carried out in the co-presence of a tertiary phosphine compound such as tp-phenylphosphine, tris-phosphine and the like as a ligand. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-d-chloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as ether diethyl, tetrahydrofuran, dioxane, 1,2-dimethoxyethane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrroLidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. This reaction is carried out at room temperature or under heating, and the reaction time is generally about 1-50 h, preferably about 1-20 h. For the production step from the compound (HIVd) in the compound (Hd) in this method, a cyclization reaction is generally carried out in the presence of about 1-3 equivalents of base or about 0.01-1 equivalents of copper iodide to give the compound (Hd). As a base, for example, potassium t-butoxide, sodium t-butoxide, cesium t-butoxide, sodium ethoxide, potassium hydride, sodium hydride, cesium hydroxide, sodium hydroxide, potassium hydroxide can be used. , sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, diisopropylamine, pyridine, N, N-dimethylaminopyridine, diazabicycloundecene (DBU) and the like. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethisulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out at low temperature, at room temperature or under heating, and the reaction time is generally about 1-50 h, preferably about 1-20 h. According to the type of substituent of the starting compound (Hd), According to the type of substituent of the starting compound a starting compound (Hd) with a different substituent by conversion of the substituent, as starting material, from a compound produced by means of the aforementioned production method. For the conversion of the substituent, a known general method can be employed. For example, conversion to the carbamoyl group by ester hydrolysis and amidation, conversion to hydroxymethyl group by reduction of the carboxy group, conversion to the alcohol compound by reduction or alkylation of the carbonyl group, reductive amination of the carbonyl group, carbonyl group oximation, acylation of the amino group, alkylation of the amino group, substitution and amination of the active halogen by amine, alkylation of the hydroxy group, substitution and amination of the hydroxy group and the like. When a reactive substituent which causes a non-objective reaction is present during the introduction of substituents and the conversion of the functional groups, a protecting group is introduced beforehand in the reactive substituent if necessary by means known per se, and the protective group is it is removed by a known means after the object reaction, and the starting compound (Hd) can also be produced. [Production method E] The compound (le) of the present invention can be obtained, for example, by the method indicated in the following reaction scheme or an analogous method and the like where each symbol is as defined previously. Each compound in the following reaction schemes includes salts, and such salts can be used, for example, those similar to the salts of the compound (le) and the like.

The compound obtained in each step can be used as a reaction mixture or as a crude product in the next reaction. In addition, the compound can be isolated from a reaction mixture according to a conventional method, and can be easily purified through a separation medium such as recrystallization, distillation, chromatography and the like. The schematic reaction formulas are indicated below, where each symbol of the compounds is as defined above. The compound (le) of the present invention can be produced, for example, by reacting a compound represented by the formula: where Le is a leaving group, and the other symbols are as defined previously, or one of its salts and a compound represented by the formula: (lile) where Ge is a hydrogen atom or a metal atom, and the other symbols are as defined by anterj opdad, or one of its salts. Ge is primarily a hydrogen atom, but may be an alkali metal such as lithium, sodium, potassium, cesium and the like, or an alkaline earth metal such as magnesium, calcium and the like. The compound (lile) or a salt thereof is preferably used in an amount of 1-5 equivalents, preferably 1-2 equivalents, based on the compound (He) and the reaction is preferably carried out in a solvent. In addition, a base or an ammonium salt may be used in an amount of about 1-10 equivalents, preferably 1-2 equivalents. In the aforementioned formula, as a leaving group for Le, a halogen atom such as chlorine, bromine, iodine and the like can be used, a group represented by the formula: -S (0) kRz wherein k is an integer of 0, 1 or 2, and Rz is a lower (C? -4) alkyl group such as methyl, ethyl, propyl and the like, a C6-10 aryl group such as phenyl, tolyl and the like, or a group represented by the formula: -0Rz where Rz is as previously defined, and similar. As a solvent in the aforesaid reaction, they may mention, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, 1-methyl-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. As a base in the aforesaid reaction, an inorganic base, an organic base and the like can be used. Specifically, for example, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, pyridine, N, N-dimethylaminopyridine, methoxide can be used. sodium, sodium ethoxide, potassium t-butoxide, sodium hydride, sodium amide, diazabicycloundecene (DBU) and the like. As ammonium salt in the aforesaid reaction, pyridine hydrochloride, pyridine hydrobromide, pyridinium p-toluenesulfonate, quinoline hydrochloride, isoquinoline hydrochloride, pyrimidine hydrochloride, pyrazine hydrochloride, triazine hydrochloride, hydrochloride can be used of trimethylamine, triethylamine hydrochloride, N-ethyldiisopropylamine hydrochloride and the like. The aforesaid reaction can be carried out under cooling, at room temperature or under heating (about 40-200 ° C, preferably about 40-160 ° C), and the reaction time is, in general, about 1- 30 h, preferably about 1-20 h, more preferably about 1-10 h. A compound within the scope of the present invention can also be produced by means of application known per se in the compound obtained (le) of the present invention for the introduction of substituents and conversion of functional groups. For the conversion of substituents, a known conventional method can be used. For example, conversion to the carboxy group can be mentioned by hydrolysis of the ester, conversion to the carbamoyl group by amidation of the carboxy group, conversion to the hydroxymethyl group by reduction of the carboxy group, conversion to the alcoholic compound by reduction or alkylation of the carbonyl group , reductive amination of the carbonyl group, oximation of the carbonyl group, acylation of the amino group, alkylation of the amino group, substitution and amination of the active halogen by amine, alkylation of the hydroxy group, substitution and amination of the hydroxy group and the like. When a Reactive substituent which causes a non-objective reaction is present during the introduction of substituents and the conversion of the functional groups, a protective group is first introduced if necessary into the reactive substituent by a known means, and the protective group is removed by a medium known per se after the reaction of the object, the compound also being able to be produced within the scope of the present invention. The compound (le), which is a product of the reaction, can be prepared as a single compound or as a mixture. The compound (le) of the present invention thus obtained can be subjected to a medium known per se, such as solvent extraction, concentration, neutralization, filtration, crystallization, recrystallization, column chromatography, high performance liquid chromatography and the like, while that the object compound can be isolated and purified with high purity from a reaction mixture. As the starting compound (lile) of this production method, a commercially available one is used or it can be produced by a means known per se. The starting compound (He) of this production method can be prepared, for example, by a method indicated in the following reaction scheme. Here, the compounds (Hea), (Heb), (Ilec) and (Hed) are included in the compound (He¡ where Lle and L2e are halogen atoms, Rz is as defined above, and t is an integer of 1 or 2. As the Ae method, the compound (Hea) can be produced by reacting the compound (IVe) with an agent halogenant As a Be method, the compound (IVe) is reacted with a thionating agent to give the compound (Ve), which is then reacted with a compound represented by PzL2e in the presence of a base to give the compound (Heb), which is then subjected to an oxidation reaction to give the compound (Hec). As a Ce method, the compound (Hea) is reacted with a compound represented by RzOH in the presence of a base to give the compound (Hed). As a halogenating agent in the Ae method, for example, approximately 1-100 equivalents of phosphorus oxychloride, phosphorus pentachloride, trichloride phosphorus, thionyl chloride, sulfuryl chloride, phosphorus tribromide and the like. In this case, the reaction can be carried out in the presence of a base such as diethylaniline, dimethylaniline, pyridine and the like. While the reaction can be carried out without a solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like can be used as the reaction solvent.; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetonitrile, ethyl acetate and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. As the thionant agent used in the production step from the compound (IVe) in the compound (Ve) in the Be Method, for example, about 1-5 equivalents of a Lawesson reagent, phosphorus pentasulfide and the like can be used. . As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as ether diethyl, tetrahydrofuran, dioxane and the like; and others. The reaction is carried out at room temperature or under heating, and the reaction time is, in general, about 1-20 h, preferably about 1-10 h. As RzL2e in the production step from the compound (Ve) in the compound (Heb) in the Be Method, for example, about 1-5 equivalents of methyl iodide, benzyl chloride, benzyl bromide and the like can be used , and as the base, there can be used, for example, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, pyridine, N, N- dimethylaminopyridine, sodium methoxide, sodium ethoxide, potassium t-butoxide, sodium hydride, sodium amide, diazabicycloundecene (DBU) and the like. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2- Pyrrhus! idone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, of about 1-20 h, preferably about 1-10 h. As the oxidizing agent in the production step from the compound (Heb) in the compound (Hec) in the Be Method, there can be used, for example, m-chloroperbenzoic acid, hydrogen peroxide, peracetic acid, t-butyl hydroperoxide , potassium peroxysulfate, potassium permanganate, sodium perborate, sodium periodate, sodium hypochlorite, halogen and the like. When the compound (Hec) is produced where t = 1, the oxidizing agent is used in about 1-1.5 equivalents based on the compound (Heb), and when the compound (Hec) is produced where t = 2, it employs in approximately 2-3 equivalents referred to the compound (Heb). The reaction solvent is not particularly limited, as long as it does not react with the oxidizing agent and, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as ether diethyl, tetrahydrofuran, dioxane and the like; carboxylic acids such as acetic acid, trifluoroacetic acid and the like; acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetaramide, l-methyl-2-pyrrolidone, dimethyl sulfoxide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. As Rz0H in the production step from the compound (Hea) in the compound (Hed) in the Ce Method, for example, approximately 1-10 equivalents of methanol, ethanol, phenol and the like can be used, and as a base, for example, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, pyridine, N, N-dimethylaminopyridine, sodium methoxide can be used. , sodium ethoxide, potassium t-butoxide, sodium hydride, sodium amide, diazabicycloundecene (DBU) and the like. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. On the other hand, the compound (IVe) can be produced, for example, by means of a method indicated by the following formula: wherein R, 10e is an alkyl group of C? -, and the other symbols are as defined above. That is, the compound (VIe) is reacted with about 1-4 equivalents of formamidine or one of its salts to give the compound (IVe). As the reaction solvent, for example, alcohols such as methanol, ethanol, isopropanol, t-butanol and the like can be used; halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, 1-methy1-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. The compound (He) can also be prepared, for example, by means of a method indicated by the following formula: where L3e is a halogen atom, and the other symbols are as previously defined. For the production step from the compound (VHe) in the compound (HIVe) in this method, a general knowledge reaction can be carried out in the form of a Sonogashira reaction or an analogous reaction and, in general, the compound (HIVe) can be produced by reacting the co-tax (VHe) with about 1-3 equivalents of a compound represented by the formula: R1e- = in the presence of a base, approximately 0.01-1 equivalents of a palladium and copper iodide catalyst. As the base, for example, triethylamine, N-ethyldiisopropylamine, diisopropylamine, pyridine, N, N-dimethylaminopyridine, diazabicycloundecene (DBU), sodium carbonate, potassium carbonate, sodium acid carbonate, potassium hydrogen carbonate and the like can be used. . As the palladium catalyst, dichlorobis (triphenylphosphine) palladium (II), palladium on carbon, palladium (II) diacetate, bis (benzonitrile) dichloropalladium (II) and the like can be used, for example. This reaction can be carried out in the co-presence of a tertiary phosphine compound such as triphenylphosphine, tributylphosphine and the like as a ligand. For reaction solvent, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent of them and the like. This reaction is carried out at room temperature or under heating, and the reaction time is generally about 1-50 h, preferably about 1-20 h. For the production stage from the compound (HIVe) in the compound (He) in this method, a cyclization reaction is generally carried out in the presence of about 1-3 equivalents of base or about 0.01-1 equivalents of copper iodide to give the compound ( He) As a base you can use, for example, potassium t-butoxide, sodium t-butoxide, cesium t-butoxide, sodium ethoxide, potassium hydride, sodium hydride, cesium hydroxide, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium acid carbonate, potassium acid carbonate, triethylamine, N-ethyldiisopropylamine, diisopropylamine, pyridine, N, N-dimethylaminopyridine, diazabicycloundecene (DBU) and the like. For the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like can be used, for example.; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane and the like; acetone, acetonitrile, ethyl acetate, N, N- dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out at low temperature, at room temperature or under heating, and the reaction time is generally about 1-50 h, preferably about 1-20 h. Depending on the type of substituent of the starting compound (He), a starting compound (He) with a different substituent can be produced by conversion of the substituent, as a starting material, from a compound produced by means of the production method before mentioned. For the conversion of the substituent, a known general method can be employed. For example, conversion to the carbamoyl group by ester hydrolysis and amidation, conversion to hydroxymethyl group by reduction of the carboxy group, conversion to the alcohol compound by reduction or alkylation of the carbonyl group, reductive amination of the carbonyl group, carbonyl group oximation, acylation of the amino group, alkylation of the amino group, substitution and amination of the active halogen by amine, alkylation of the hydroxy group, substitution and amination of the hydroxy group and the like. When a reactive substituent that causes a non-objective reaction is present during the introduction of substituents and the conversion of the functional groups, before introducing a protective group, if necessary, into the reactive substituent by means known per se, and the protecting group is removed by a medium known per se after the object reaction, and the starting compound (He) can also be produced. [Production method F] The compound (If) of the present invention can be obtained, for example, by the method indicated in the following reaction scheme or an analogous method and the like. where each symbol is as defined previously. Each compound in the following reaction schemes includes salts, and such salts can be used, for example, those similar to the salts of the compound (If) and the like. The compound obtained in each step can be used as a reaction mixture or as a crude product in the next reaction. In addition, the compound can be isolated from a reaction mixture according to a conventional method, and it can be easily purified through a separation medium such as recrystallization, distillation, chromatography and the like. The schematic reaction formulas are indicated below, wherein each symbol of the compounds is as previously defined. The compound (If) of the present invention can be produced, for example, by reacting a compound represented by the formula: where L is a leaving group, and the other symbols are as defined above, or one of its salts and a compound represented by the formula: where G is a hydrogen atom or a metal atom, and the other symbols are as defined previously, or one of their salts.

Gf is primarily a hydrogen atom, but may be an alkali metal such as lithium, sodium, potassium, cesium and the like, or an alkaline earth metal such as magnesium, calcium and the like. The compound (IHf) or a salt thereof is preferably used in an amount of 1-5 equivalents, preferably 1-2 equivalents, based on the compound (Hf) and the reaction is preferably carried out in a solvent. In addition, a base or an ammonium salt may be used in an amount of about 1-10 equivalents, preferably 1-2 equivalents. In the aforementioned formula, as a leaving group for L £, a halogen atom such as chlorine, bromine, iodine and the like, a group represented by the formula: -S (0) kRz wherein k is a whole number can be used of 0, 1 or 2, and Rz is a lower alkyl group (C? _4) such as methyl, ethyl, propyl and the like, an aryl group of C6-? or such as phenyl, tolyl and the like, or a group depicted by the formula: -ORz where Rz is as previously defined, and similar. As the solvent in the aforesaid reaction, there can be mentioned, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, 1-methyl 1-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. As a base in the aforesaid reaction, an inorganic base, an organic base and the like can be used. Specifically, for example, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, pyridine, N, N-dimethylaminopyridine, methoxide can be used. sodium, sodium ethoxide, potassium t-butoxide, sodium hydride, sodium amide, diazabicycloundecene (DBU) and the like. As the ammonium salt in the aforesaid reaction, pyridine hydrochloride, pyridine hydrobromide, pyridinium p-toluenesulfonate, quinoline hydrochloride, isoquinoline hydrochloride, pyrimidine hydrochloride, pyrazine hydrochloride, triazine hydrochloride, trimethylamine hydrochloride can be used. , triethylamine hydrochloride, N-ethyl] diisopropylamine hydrochloride and the like. The aforesaid reaction can be carried out under cooling, at room temperature or under heating (about 40-200 ° C, preferably about 40-160 ° C), and the reaction time is, in general, about 1-30 h, preferably about 1-20 h, more preferably about 1-10 h. A compound within the scope of the present invention can also be produced by means of application known per se in the obtained compound (If) of the present invention for the introduction of substituents and conversion of functional groups. For the conversion of substituents, a known conventional method can be used. For example, conversion to the carboxy group can be mentioned by hydrolysis of the ester, conversion to the carbamoyl group by amidation of the carboxy group, conversion to the hydroxymethyl group by reduction of the carboxy group, conversion to the alcoholic compound by reduction or alkylation of the carbonyl group , reductive amination of the carbonyl group, oximation of the carbonyl group, acylation of the amino group, alkylation of the amino group, substitution and amination of the active halogen by amine, alkylation of the hydroxy group, substitution and amination of the hydroxy group and the like. When a reactive substituent which causes a non-objective reaction is present during the introduction of substituents and the conversion of the functional groups, a protecting group is introduced beforehand if necessary in the reactive substituent by a means known per se, and the protecting group is removed by a means known per se after the reaction of the object, and the compound can also be produced within the scope of the present invention. The compound (If), which is a product of the reaction, can be prepared as a single compound or as a mixture. The compound (If) of the present invention thus obtained can be subjected to a known medium, such as solvent extraction, concentration, neutralization, filtration, crystallization, recrystallization, column chromatography, high performance liquid chromatography and the like, while that the object compound can be isolated and purified with high purity from a reaction mixture. As the starting compound (IHf) of this production method, a commercially available one is used or it can be produced by a means known per se. The starting compound (Hf) of this production method can be prepared, for example, by a method indicated in the following reaction scheme. Here, the compounds (Ufa), (Hfb), (Ufe) and (Hfd) are comprised in the compound (Hf). wherein Llf and L2f are halogen atoms, Rz is as defined above, and t is an integer of 1 or 2. As the Af method, the compound (Ufa) can be produced by reacting the compound (IVf) with an agent halogenant As a Bf method, the compound (IVf) is reacted with a thionating agent to give the compound (Vf), which is then reacted with a compound represented by RzL2f in the presence of a base to give the compound (Hfb), which is then subjected to an oxidation reaction to give the compound (Ufe). As the Cf method, the compound (Ufa) is reacted with a compound represented by RzOH in the presence of a base to give the compound (Hfd). As the halogenating agent in the Af Method, for example, approximately 1-100 equivalents of phosphorus oxychloride, phosphorus pentachloride, trichloride phosphorus, thionyl chloride, sulfuryl chloride, phosphorus tribromide and the like. In this case, the reaction can be carried out in the presence of a base such as diethylaniline, dimethylaniline, pyridine and the like. While the reaction can be carried out without a solvent, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like can be used as the reaction solvent; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetonitrile, ethyl acetate and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. As the thionant agent used in the production step from the compound (IVf) in the compound (Vf) in the Bf Method, for example, about 1-5 equivalents of a Lawesson reagent, phosphorus pentasulfide and the like can be used. . As the reaction solvent, halogenated hydrocarbons such as corao dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like can be used, for example; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as ether diethyl, tetrahydrofuran, dioxane and the like; and others. The reaction is carried out at room temperature or under heating, and the reaction time is, in general, about 1-20 h, preferably about 1-10 h. Corao RzL2f in the production step from compound (Vf) in compound (Hfb) in Method Bf, for example, about 1-5 equivalents of methyl iodide, benzyl chloride, benzyl bromide and the like can be used , and as the base, there can be used, for example, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, pyridine, N, N- dimethylaminopyridine, sodium methoxide, sodium ethoxide, potassium t-butoxide, sodium hydride, sodium amide, diazabicycloundecene (DBU) and the like. As a reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like can be used; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2- pyrrolidone, dimethisulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. As an oxidizing agent in the production step from the compound (Hfb) in the compound (Hfc) in Method Bf, there can be used, for example, m-chloroperbenzoic acid, hydrogen peroxide, peracetic acid, t-butyl hydroperoxide , potassium peroxysulfate, potassium permanganate, sodium perborate, sodium periodate, sodium hypochlorite, halogen and the like. When the compound (Hfc) is produced where t = 1, the oxidizing agent is used in about 1-1.5 equivalents based on the compound (Hfb), and when the compound (Ufe) is produced where t = 2, it employs in approximately 2-3 equivalents referred to the compound (Hfb). The reaction solvent is not particularly limited, as long as it does not react with the oxidizing agent and, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like can be used.; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as ether diethyl, tetrahydrofuran, dioxane and the like; carboxylic acids such as acetic acid, trifluoroacetic acid and the like; acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethyl sulfoxide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. As RzOH in the production step from the compound (Ufa) in the compound (Hfd) in the Cf Method, for example, about 1-10 equivalents of methanol, ethanol, phenol and the like can be used, and as a base, for example, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, pyridine, N, N-dimethylaminopyridine, sodium methoxide can be used. , sodium ethoxide, potassium t-butoxide, sodium hydride, sodium amide, diazabicycloundecene (DBU) and the like. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. On the other hand, the compound (IVf) can be produced, for example, by means of a method indicated by the following formula: wherein R, 1 ± 0ufr is an alkyl group of C_4, and the other symbols are as defined above. That is, the compound (Vlf) is reacted with about 1-4 equivalents of formamidine or one of its salts to give the compound (IVf). As the reaction solvent, for example, alcohols such as methanol, ethanol, isopropanol, t-butanol and the like can be used; halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethisulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. The compound (Hf) can also be prepared, for example, by means of a method indicated by the following formula: where L 3 f is a halogen atom, and the other symbols are as previously defined. For the production step from the compound (VHf) in the compound (HIVf) in this method, a general knowledge reaction can be carried out in the form of a Sonogashira reaction or an analogous reaction and, in general, the compound (HIVf) can be produced by reacting the compound (VHf) with about 1-3 equivalents of a compound represented by the formula R1f- = in the presence of a base, approximately 0.01-1 equivalents of a palladium and copper iodide catalyst. As the base there can be used, for example, triethylamine, N-ethyldiisopropylamine, diisopropylamine, pyridine, N, N-dimethylaminopyridine, diazabicycloundecene (DBU), sodium carbonate, potassium carbonate, sodium acid carbonate, potassium hydrogen carbonate and the like. As palladium catalyst can be used, for example, dichlorobis (triphenylphosphine) palladium (II), palladium on carbon, palladium (II) diacetate, bis (benzonitrile) dichloropalladium (II) and the like. This reaction can be carried out in the co-presence of a tertiary phosphine compound such as triphenylphosphine, tributylphosphine and the like as a ligand. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like can be used, for example.; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethyl Lformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent of them and the like. This reaction is carried out at room temperature or under heating, and the reaction time is generally about 1-50 h, preferably about 1-20 h. For the production stage from the compound (HIVf) in the compound (Hf) in this method, a cyclization reaction is generally carried out in the presence of about 1-3 equivalents of base or about 0.01-1 equivalents of copper iodide to give the compound ( Ilf). As a base, for example, potassium t-butoxide, sodium t-butoxide, cesium t-butoxide, sodium ethoxide, potassium hydride, sodium hydride, cesium hydroxide, sodium hydroxide, potassium hydroxide can be used. , sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, diisopropylamine, pyridine, N, N-dimethylaminopyridine, diazabicycloundecene (DBU) and the like. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane and the like; acetone, acetonitrile, ethyl acetate, N, N- dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out at low temperature, at room temperature or under heating, and the reaction time is generally about 1-50 h, preferably about 1-20 h. According to the type of substituent of the starting compound (Hf), a starting compound (Hf) with a different substituent can be produced by conversion of the substituent, as a starting material, from a compound produced by means of the production method before mentioned. For the conversion of the substituent, a known general method can be employed. For example, conversion to the carbamoyl group by ester hydrolysis and amidation, conversion to hydroxymethyl group by reduction of the carboxy group, conversion to the alcohol compound by reduction or alkylation of the carbonyl group, reductive amination of the carbonyl group, carbonyl group oximation, acylation of the amino group, alkylation of the amino group, substitution and amination of the active halogen by amine, alkylation of the hydroxy group, substitution and amination of the hydroxy group and the like. When a reactive substituent that causes a non-objective reaction is present during the introduction of substituents and the conversion of the functional groups, before introducing a protective group, if necessary, into the reactive substituent by means known per se, and the protecting group is removed by a known means after the object reaction, and the starting compound (Hf) can also be produced. [Production method G] The compound (Ig) of the present invention can be obtained, for example, by the method indicated in the following reaction scheme or an analogous method and the like. where each symbol is as defined previously. Each compound in the following reaction schemes includes salts, and such salts can be used, for example, those similar to the salts of the compound (Ig) and the like. The compound obtained in each step can be used as a reaction mixture or as a crude product in the next reaction. In addition, the compound can be isolated from a reaction mixture according to a conventional method, and can be easily purified through a separation medium such as recrystallization, distillation, chromatography and the like. The schematic reaction formulas are indicated below, wherein each symbol of the compounds is as previously defined. The compound (Ig) of the present invention can be produced, for example, by reacting a compound represented by the formula: where Lg is a leaving group, and the other symbols are as previously defined, or one of their salts and a compound represented by the formula: where Gg is a hydrogen atom or a metal atom, and the other symbols are as defined above, or one of its salts. When Xig is _NR3g_? Ig -0- -s-, g is primarily a hydrogen atom, but may be an alkali metal such as lithium, sodium, potassium, cesium and the like, or an alkaline earth metal such as magnesium, calcium and the like . When Xlg is -CHR3g-, Gg can be a metal such as lithium, halogenated magnesium, copper, zinc and the like. The compound (IHg) or a salt thereof is preferably used in an amount of 1-5 equivalents, preferably 1-2 equivalents, based on the compound (Ilg) and the reaction is preferably carried out in a solvent. In addition, a base or an ammonium salt may be used in an amount of about 1-10 equivalents, preferably 1-2 equivalents. In the aforementioned formula, as a leaving group for Lg, a halogen atom such as chlorine, bromine, iodine and the like, a group represented by the formula: -S (0) kRz wherein k is an integer of 0, 1 or 2, and Rz is a lower (C? -4) alkyl group such as methyl, ethyl, propyl and the like, an aryl group of Ce-1 such as phenyl, tolyl and the like, or a group represented by formula: -0RZ where Rz is as previously defined, and similar. As a solvent in the aforesaid reaction, they may mention, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-d-chloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, 1-met Ll-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. As a base in the aforesaid reaction, an inorganic base, an organic base and the like can be used. Specifically, sodium hydroxide, potassium hydroxide, sodium carbonate, LO potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, pyridine, N, N-dimethylaramine, methoxide may be used, for example. sodium, sodium ethoxide, potassium t-butoxide, sodium hydride, sodium amide, diazabicycloundecene (DBU) and the like. As an ammonium salt in the aforesaid reaction, pipdma hydrochloride, pyridine hydrobromide, pyridmium p-toluenesulfonate, qumol a hydrochloride, isoqumolm hydrochloride, pyrimidine hydrochloride, pyrazine hydrochloride, triazma hydrochloride, hydrochloride may be used. of trimethylamine, triethylamine hydrochloride, N-ethyldiisopropylamine hydrochloride and the like. The aforesaid reaction can be carried out under cooling, at room temperature or under heating (about 40-200 ° C, preferably about 40-160 ° C), and the reaction time is, in general, about 1- 30 h, preferably about 1-20 h, more preferably about 1-10 h. The compound (Ig) wherein Xlg is -SO- or -S02- can be produced by subjecting the compound (Ig) wherein Xlg is -S-, to an oxidation reaction. As an oxidizing agent in the production step, there can be used, for example, m-chloroperbenzoic acid, hydrogen peroxide, peracetic acid, t-butyl hydroperoxide, potassium peroxysulfate, potassium permanganate, sodium perborate, sodium periodate, sodium hypochlorite, halogen and the like. When the compound (Ig) is produced in which Xlg is -SO-, the oxidizing agent is used in about 1-1.5 equivalents based on the starting compound, and when the compound (Ig) is produced wherein Xlg is -S02 -, it is used in approximately 2-3 equivalents based on the starting compound. The reaction solvent is not particularly limited, as long as it does not react with the oxidizing agent and, for example, halogenated hydrocarbons such as as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; carboxylic acids such as acetic acid, trifluoroacetic acid and the like; acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethyl sulfoxide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. A compound within the scope of the present invention can also be produced by known application means in the obtained compound (Ig) of the present invention for the introduction of substituents and conversion of functional groups. For the conversion of substituents, a known conventional method can be used. For example, conversion to the carboxy group can be mentioned by hydrolysis of the ester, conversion to the carbamoyl group by amidation of the carboxy group, conversion to the hydroxymethyl group by reduction of the carboxy group, conversion to the alcoholic compound by reduction or alkylation of the carbonyl group , reductive amination of the carbonyl group, oximation of the carbonyl group, acylation of the amino group, alkylation of the amino group, substitution and amination of the active halogen by amine, alkylation of the hydroxy group, substitution and amination of the hydroxy group and the like. When a reactive substituent which causes a non-objective reaction is present during the introduction of substituents and the conversion of the functional groups, a protecting group is introduced beforehand in the reactive substituent if necessary by means known per se, and the protective group is It is removed by a means known per se after the reaction of the object, and the compound can also be produced within the scope of the present invention. The compound (Ig), which is a product of the reaction, can be prepared as a single compound or as a mixture. The compound (Ig) of the present invention thus obtained can be subjected to a medium known per se, such as solvent extraction, concentration, neutralization, filtration, crystallization, recrystallization, column chromatography, high performance liquid chromatography and the like, while that the object compound can be isolated and purified with high purity from a reaction mixture. As the starting compound (IHg) of this production method, a commercially available one is used or it can be produced by a means known per se.

The starting compound (Ilg) of this production method can be prepared, for example, by a method indicated in the following reaction scheme. Here, the compounds (liga), (Hgb), (Hgc), (Hgd) and (Hge) are comprised in the compound (Ilg). wherein Llg and L2g are halogen atoms, Rz is as defined above, and t is an integer of 1 or 2. As an Ag method, the compound (link) can be produced by reacting the compound (IVg) with an agent halogenant As a Bg method, the compound (IVg) is reacted with a thionating agent to give the compound (Vg), which is then reacted with a compound represented by RzL2g in the presence of a base to give the compound (Hgb), which is then subjected to an oxidation reaction to give the compound (Hgc). As a Cg method, the compound (league) it is reacted with a compound represented by ROH in the presence of a base to give the compound (Hgd). As the halogenating agent in the Ag Method, there can be used, for example, about 1-100 equivalents of phosphorus oxychloride, phosphorus pentachloride, phosphorus trichloride, thionyl chloride, sulfuryl chloride, phosphorus tribromide and the like. In this case, the reaction can be carried out in the presence of a base such as diethylaniline, dimethylaniline, pyridine and the like. While the reaction can be carried out without a solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like can be used as the reaction solvent.; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetonitrile, ethyl acetate and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. As the thionant agent used in the production step from the compound (IVg) in the compound (Vg) in Method Bg, there can be used, for example, about 1-5 equivalents of a Lawesson reagent, pentasulfide phosphorus and the like. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; and others. The reaction is carried out at room temperature or under heating, and the reaction time is, in general, about 1-20 h, preferably about 1-10 n. As RzL2g in the production step from the compound (Vg) in the compound (Hgb) in the Bg Method, for example, about 1-5 equivalents of methyl iodide, benzyl chloride, benzyl bromide and the like can be used , and as a base, there can be used, for example, sodium aroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, pyridine, N, N- dimethylaminopyridine, sodium methoxide, sodium ethoxide, potassium t-butoxide, sodium hydride, sodium amide, diazabicycloundecene (DBU) and the like. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrroiidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, of about 1-20 h, preferably about 1-10 h. As oxidizing agent in the production step from the compound (Hgb) in the compound (Hgc) in the Method Bg, there can be used, for example, m-chloroperbenzoic acid, hydrogen peroxide, peracetic acid, t-butyl hydroperoxide , potassium peroxysulfate, potassium permanganate, sodium perborate, sodium periodate, sodium hypochlorite, halogen and the like. When the compound (Hgc) is produced where t = 1, the oxidizing agent is used in about 1-1.5 equivalents based on the compound (Hgb), and when the compound (Hgc) is produced where t = 2, It is used in approximately 2-3 equivalents based on the compound (Hgb). The reaction solvent is not particularly limited, as long as it does not react with the oxidizing agent and, for example, hydrocarbons can be used halogenated such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; carboxylic acids such as acetic acid, trifluoroacetic acid and the like; acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethyl sulfoxide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. As RzOH in the production step from the compound (ligate) in the compound (Hgd) in the Cg Method, for example, about 1-10 equivalents of methanol, ethanol, phenol and the like can be used, and as a base, for example, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, pyridine, N, N-dimethylaminopyridine, sodium methoxide can be used. , sodium ethoxide, potassium t-butoxide, sodium hydride, sodium amide, diazabicycloundecene (DBU) and the like. As a reaction solvent, they can be used, example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethisulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. On the other hand, the compound (IVg) can be produced, for example, by means of a method indicated by the following formula: wherein R10g is an alkyl group of C? _4, and the other symbols are as defined above. That is, the compound (VIg) is reacted with about 1-4 equivalents of formamidine or one of its salts to give the compound (IVg). As the reaction solvent, alcohols such as methanol, for example, can be used. ethanol, isopropanol, t-butanol and the like; halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethisulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. When g is C (Rlg), the compound (Hge) can also be prepared, for example, by a method indicated by the following formula: where L3g is a halogen atom, and the other symbols are as previously defined. For the production stage from the compound (VHg) in the compound (HIVg) in this method, a general knowledge reaction can be carried out in the form of a Sonogashira reaction or an analogous reaction and, in general, the compound (HIVg) can be produced by reacting the compound (VHg) with about 1-3 equivalents of a compound represented by the formula: R 1 ^ in the presence of a base , about 0.01-1 equivalents of a palladium and copper iodide catalyst. As the base there can be used, for example, triethylamine, N-ethyldiisopropylamine, diisopropylamine, pyridine, N, N-dimethylaminopyridine, diazabicycloundecene (DBU), sodium carbonate, potassium carbonate, sodium acid carbonate, potassium hydrogen carbonate and the like. As the palladium catalyst, dichlorobis (triphenylphosphine) palladium (II), palladium on carbon, palladium (II) diacetate, bis (benzonitrile) dichloropalladium (II) and the like can be used, for example. This reaction can be carried out in the co-presence of a tertiary phosphine compound such as triphenylphosphine, tributylphosphine and the like as a ligand. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as ether diethyl, tetrahydrofuran, dioxane, 1,2-dimethoxyethane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethisulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. This reaction is carried out at room temperature or under heating, and the reaction time is generally about 1-50 h, preferably about 1-20 h. For the production step from the compound (HIVs) in the compound (Ilge) in this method, a cyclization reaction is generally carried out in the presence of about 1-3 equivalents of base or about 0.01-1 equivalents of copper iodide to give the compound (Hge). As a base, for example, potassium t-butoxide, sodium t-butoxide, cesium t-butoxide, sodium ethoxide, potassium hydride, sodium hydride, cesium hydroxide, sodium hydroxide, potassium hydroxide can be used. , sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, diisopropylamine, pyridine, N, N-dimethylaminopyridine, diazabicycloundecene (DBU) and the like. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like can be used, for example.; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanoi, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethisulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out at low temperature, at room temperature or under heating, and the reaction time is generally about 1-50 h, preferably about 1-20 h. According to the type of substituent of the starting compound (Hg), a starting compound (Ilg) with a different substitution by conversion of the substituent, as a starting material, from a compound produced by means of the aforementioned production method. For the conversion of the substituent, a known general method can be employed. For example, conversion to the carbamoyl group by ester hydrolysis and amidation, conversion to hydroxymethyl group by reduction of the carboxy group, conversion to the alcohol compound by reduction or alkylation of the carbonyl group, reductive amination of the carbonyl group, carbonyl group oximation, acylation of the amino group, alkylation of the amino group, substitution and amination of the active halogen by amine, alkylation of the hydroxy group, substitution and amination of the hydroxy group and the like. When a reactive substituent which causes a non-objective reaction is present during the introduction of substituents and the conversion of the functional groups, a protective group is introduced beforehand into the reactive substituent by a means known per se, and the protective group is it eliminates by a means known per se after the object reaction, and can also produce the starting compound (Hg). [Production method H] The compound (Ih) of the present invention can be obtained, for example, by the method indicated in the following reaction scheme or an analogous method and the like. where each symbol is as previously defined. Each compound in the following reaction schemes includes salts, and such salts can be used, for example, those similar to salts of the compound (Ih) and similar. The compound obtained in each step can be used as a reaction mixture or as a crude product in the next reaction. In addition, the compound can be isolated from a reaction mixture according to a conventional method, and can be easily purified through a separation medium such as recrystallization, distillation, chromatography and the like. The schematic reaction formulas are indicated below, wherein each symbol of the compounds is as previously defined. The compound (Ih) of the present invention can be produced, for example, by reacting a compound represented by the formula: where L is a leaving group, and the other symbols are as defined above, or one of its salts and a compound represented by the formula: (lllh) where Gh is a hydrogen atom or a metal atom, and the other symbols are as defined previously, or one of their salts. Gh is primarily a hydrogen atom, but may be an alkali metal such as lithium, sodium, potassium, cesium and the like, or an alkaline earth metal such as magnesium, calcium and the like. The compound (Illh) or a salt thereof is preferably used in an amount of 1-5 equivalents, preferably 1-2 equivalents, based on the compound (Ilh) and the reaction is preferably carried out in a solvent. In addition, a base or an ammonium salt may be used in an amount of about 1-10 equivalents, preferably 1-2 equivalents. In the aforementioned formula, as a leaving group for Lh, a halogen atom such as chlorine, bromine, iodine and the like, a group represented by the formula: -S (0) kRz wherein k is an integer of 0, 1 or 2, and Rz is a lower (C? -4) alkyl group such as methyl, ethyl, propyl and the like, an aryl group of C6-? Or such as phenyl, tolyl and the like, or a group represented by the formula: -ORz where Rz is as previously defined, and similar.

As the solvent in the aforesaid reaction, there can be mentioned, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, 1-methyl 1-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. As a base in the aforesaid reaction, an inorganic base, an organic base and the like can be used. Specifically, for example, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, pyridine, N, N-dimethylaminopyridine, sodium methoxide, sodium, sodium ethoxide, potassium t-butoxide, sodium hydride, sodium amide, diazabicycloundecene (DBU) and the like. As the ammonium salt in the aforesaid reaction, pyridine hydrochloride, pyridine hydrobromide, pyridinium p-toluenesulfonate, quinoline hydrochloride, isoquinoline hydrochloride, pyrimidine hydrochloride, can be used, pyrazam hydrochloride, triazma hydrochloride, tr-Lmethylamine hydrochloride, triethylamine hydrochloride, N-ethidinesopropylamine hydrochloride and the like. The aforesaid reaction can be carried out under cooling, at room temperature or under heating (about 40-200 ° C, preferably about 40-160 ° C), and the reaction time is, in general, about 1. -30 h, preferably about 1-20 h, more preferably about 1-10 h. A compound within the scope of the present invention can also be produced by means of application known per se in the compound obtained (Ih) of the present invention for the introduction of substituents and conversion of functional groups. For the conversion of substituents, a known conventional method can be used. For example, conversion to the carboxy group can be mentioned by hydrolysis of the ester, conversion to the carbamoyl group by amidation of the carboxy group, conversion to the hydroethyl imethyl group by reduction of the carboxy group, conversion to the alcoholic compound by reduction or alkylation of the group carbonyl, reductive amination of the carbonyl group, oximation of the carbonyl group, acylation of the amino group, alkylation of the ammo group, substitution and ammation of the active halogen by amine, alkylation of the hydroxy group, substitution and amination of the hydroxy group and the like. When a reactive substituent which causes a non-objective reaction is present during the introduction of substituents and the conversion of the functional groups, a protective group is introduced beforehand into the reactive substituent if necessary by a known means, and the protective group is It is removed by a means known per se after the reaction of the object, and the compound can also be produced within the scope of the present invention. The compound (Ih), which is a product of the reaction, can be prepared as a single co-pay or as a mixture. The compound (Ih) of the present invention thus obtained can be subjected to a medium known per se, such as solvent extraction, concentration, neutralization, filtration, crystallization, recrystallization, column chromatography, high performance liquid chromatography and the like, while that the object compound can be isolated and purified with high purity from a reaction mixture. As the starting compound (IHh) of this production method, a commercially available one is used or it can be produced by a means known per se. The starting compound (Hh) of this production method can be prepared, for example, by a method indicated in the following reaction scheme. Here, the compounds (Hha), (Hhb), (Hhc) and (Hhd) are included in the compound (Hh). wherein Llh and L2h are halogen atoms, Rz is as defined above, and t is an integer of 1 or 2. As the Ah method, the compound (lina) can be produced by ting the compound (IVh) with an agent halogenant As a Bh method, the compound (IVh) is ted with a thionating agent to give the compound (Vh), which is then ted with a compound represented by RzL2h in the presence of a base to give the compound (Hhb), which then it is subjected to an oxidation tion to give the compound (Hhc). As a method Ch, the compound (Hha) is ted with a compound represented by RzOH in the presence of a base to give the compound (Hhd). As a halogenating agent in the Ah method, it can be using, for example, about 1-100 equivalents of phosphorus oxychloride, phosphorus pentachloride, phosphorus trichloride, thionyl chloride, sulfuryl chloride, phosphorus tribromide and the like. In this case, the tion can be carried out in the presence of a base such as diethylaniline, dimethylaniline, pyridine and the like. While the tion can be carried out without a solvent, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like can be used as the tion solvent; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetonitrile, ethyl acetate and the like. The tion is carried out under cooling, at room temperature or under heating, and the tion time varies, in general, from about 1-20 h, preferably about 1-10 h. As the thionant agent used in the production step from the compound (IVh) in the compound (Vh) in the Bh Method, for example, about 1-5 equivalents of a Lawesson ent, phosphorus pentasulfide and the like can be used. . As the tion solvent, halogenated hydrocarbons, such as dichloromethane, chloroform, carbon tetrachloride, 1,2-, can be used, for example. dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; and others. The tion is carried out at room temperature or under heating, and the tion time is, in general, about 1-20 h, preferably about 1-10 h. As RzL2h in the production step from the compound (Vh) in the compound (Hhb) in the Bh Method, for example, about 1-5 equivalents of methyl iodide, benzyl chloride, benzyl bromide and the like can be used , and as the base, there can be used, for example, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, pyridine, N, N- dimethylaminopyridine, sodium methoxide, sodium ethoxide, potassium t-butoxide, sodium hydride, sodium amide, diazabicycloundecene (DBU) and the like. For tion solvent, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethisulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The tion is carried out under cooling, at room temperature or under heating, and the tion time varies, in general, from about 1-20 h, preferably about 1-10 h. As an oxidizing agent in the production step from the compound (Hhb) in the compound (Hhc) in the Bh Method, there can be used, for example, m-chloroperbenzoic acid, hydrogen peroxide, peracetic acid, t-butyl hydroperoxide, potassium peroxysulfate, potassium permanganate, sodium perborate, sodium periodate, sodium hypochlorite, halogen and the like. When the compound (Hhc) is produced where t = l, the oxidizing agent is used in about 1-1.5 equivalents relative to the compound (Hhb), and when the compound (Hhc) is produced where t = 2, used in approximately 2-3 equivalents referred to the compound (Hhb). The reaction solvent is not particularly limited, as long as it does not react with the oxidizing agent and, for example, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like can be used.; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; carboxylic acids such as acetic acid, trifluoroacetic acid and the like; acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethyl sulfoxide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. As RzOH in the production step from the compound (lina) in the compound (Hhd) in the Ch Method, for example, about 1-10 equivalents of methanol, ethanol, phenol and the like can be used, and as a base, sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldi isopropylamine, pyridine, N, N-dimethylaminopyridine, sodium methoxide may be used, for example. sodium, sodium ethoxide, potassium t-butoxide, sodium hydride, sodium amide, diazabicycloundecene (DBU) and the like. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethisulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. On the other hand, the compound (IVh) can be produced, for example, by means of a method indicated by the following formula: wherein R, 1? 0? hn is an alkyl group of C? -4, and the other symbols are as defined above. That is, the compound (VIh) is reacted with about 1-4 equivalents of formamidine or one of its salts to give the compound (IVh). As the reaction solvent, for example, alcohols such as methanol, ethanol, isopropanol, t-butanol and the like can be used; halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out under cooling, at room temperature or under heating, and the reaction time varies, in general, from about 1-20 h, preferably about 1-10 h. The compound (Hh) can also be prepared, for example, by means of a method indicated by the following formula: where L 3h is a halogen atom, and the other symbols are as previously defined. For the production stage from the compound (VHh) in the compound (HIVh) in this method, a general knowledge reaction can be carried out in the form of a Sonogashira reaction or an analogous reaction and, in general, the compound (HIVh) can be produced by reacting the compound (VHh) with approximately 1-3 equivalents of a compound represented by the formula: R1h- ^ in the presence of a base, approximately 0.01-1 equivalents of a palladium and copper iodide catalyst. As a base, for example, triethylamine, N-ethyldiisopropylamine, diisopropylamine, pyridine, N, N-dimethylaminopyridine, diazabicycloundecene (DBU) may be used., sodium carbonate, potassium carbonate, sodium acid carbonate, potassium hydrogen carbonate and the like. As the palladium catalyst, dichlorobis (triphenylphone) palladium (II), palladium on carbon, palladium (II) diacetate, bis (benzonitrile) dichloropalladium (II) and the like can be used, for example. This reaction can be carried out in the co-presence of a tertiary phone compound such as triphenylphone, tributylphone and the like as a ligand. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like can be used, for example.; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-methyl-2- pyrrolidone, dimethisulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. This reaction is carried out at room temperature or under heating, and the reaction time is generally about 1-50 h, preferably about 1-20 h. For the production step from the compound (HIVh) in the compound (Hh) in this method, a cyclization reaction is generally carried out in the presence of about 1-3 equivalents of base or about 0.01-1 equivalents of copper iodide to give the compound (H H). As a base, for example, potassium t-butoxide, sodium t-butoxide, cesium t-butoxide, sodium ethoxide, potassium hydride, sodium hydride, cesium hydroxide, sodium hydroxide, potassium hydroxide can be used. , sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, triethylamine, N-ethyldiisopropylamine, diisopropylamine, pyridine, N, N-dimethylaminopyridine, diazabicycloundecene (DBU) and the like. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; alcohols such as methanol, ethanol, isopropanol, t-butanol and the like; ethers such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane and the like; acetone, acetonitrile, ethyl acetate, N, N-dimethylformamide, N, N-dimethylacetamide, l-phenyl-2-pyrrolidone, dimethyl sulfoxide, hexamethylphosphoramide, water or a mixed solvent thereof and the like. The reaction is carried out at low temperature, at room temperature or under heating, and the reaction time is generally about 1-50 h, preferably about 1-20 h. According to the type of substituent of the starting compound (Hh), a starting compound (Ilh) with a different substituent by conversion of the substituent, as a starting material, from a compound produced by means of the aforementioned production method. For the conversion of the substituent, a known general method can be employed. For example, conversion to the carbamoyl group by ester hydrolysis and amidation, conversion to hydroxymethyl group by reduction of the carboxy group, conversion to the alcohol compound by reduction or alkylation of the carbonyl group, reductive amination of the carbonyl group, carbonyl group oximation, acylation of the amino group, alkylation of the amino group, substitution and amination of the active halogen by amine, alkylation of the hydroxy group, substitution and amination of the hydroxy group and the like. When a reactive substituent that causes a non-objective reaction is present during the introduction of substituents and the conversion of the functional groups, a protecting group is introduced beforehand in the reactive substituent by a known means, if necessary, and the protective group is eliminated by means known per se after the object reaction, and can also produce the starting compound (Ilh). The starting compound (Hh) of this production method can also be produced, for example, by means of a method using the compound (IlhP), as indicated by the following reaction scheme: where each symbol is as defined previously. In this method, the compound (Hh ') in the anion is generally converted by removing a proton from the compound (Hh') using a base which is then reacted with a cation having Rlh to give the compound (Hh). As the base, for example, n-butyl lithium, s-butyl lithium, t-butyl lithium, lithium t-butoxide, lithium diisopropylamide and the like can be used. As reagent for generating the cation, for example, p-toluenesulfonyl chloride, benzenesulfonyl bromide, p-toluenesulfonyl cyanide, can be used, S- (trifluoromethyl) dibenzothiophenium trifluoromethanesulfonate, N, N-dimethylformamide and the like. As the reaction solvent, halogenated hydrocarbons such as dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane and the like can be used, for example.; ethers such as diethyl ether, tetrahydrofuran, dioxane, 1,2-dimethoxyethane and the like, a mixed solvent thereof and the like. The aforesaid reaction can be carried out under cooling, preferably about no more than -20 ° C, and the reaction time is generally about 15 min-50 h, preferably about 30 min-4 h. The compounds (Ia) - (Ih) thus obtained can be isolated and purified by a separation medium known per se, such as concentration, concentration under reduced pressure, extraction of the solvent, crystallization, recrystallization, phase transfer, chromatography and the like. . If the compounds (Ia) - (Ih) are obtained in free form, they can be converted into a desired salt by means of a method known per se or a modification thereof; on the contrary, if the compounds (Ia) - (Ih) are obtained as a salt, they can be converted into a free form or another desired salt by means of a method known per se or a modification thereof. When the compounds (Ia) - (Ih) have isomers such as optical isomer, stereoisomer, positional isomer, rotation isomer and the like, and any isomer and mixtures are comprised in compound (Ia) - (Ih). For example, when the compounds (Ia) - (Ih) have an optical isomer, an optical isomer separated from the racemate is also comprised in the compound (Ia) - (Ih). These isomers can be obtained as independent products by means of synthesis or separation (concentration, solvent extraction, column chromatography, recrystallization and the like) known per se. The compounds (Ia) - (Ih) can be a crystal, and both an individual crystal and mixtures of crystals are comprised in the compound (Ia) - (Ih). The crystals can be produced by crystallization according to known crystallization methods. The compounds (Ia) - (Ih) can be a solvate (for example, hydrate, etc.) or a non-solvate, and both are comprised in the compound (Ia) - (Ih). A compound labeled with an isotope (for example, 3H, 1C, 35S, 125I and the like) is also included in the compound (Ia) - (Ih). A prodrug of the compounds (Ia) - (Ih) or their salts (hereinafter referred to as compound (Ia) - (Ih)) means a compound that is converted to the compounds (Ia) - (Ih) with a reaction due to an enzyme, an acid gastric, etc. in the physiological condition in the living organism, that is, a compound that is converted into the compounds (Ia) - (Ih) with oxidation, reduction, hydrolysis, etc. due to an enzyme; a compound that is converted into the compounds (Ia) - (Ih) by hydrolysis, etc. due to gastric acid, etc. A prodrug for the compounds (Ia) - (Ih) can be a compound obtained by subjecting an amino group in the compounds (Ia) - (Ih) to an acylation, alkylation or phosphorylation (for example, a compound obtained by subjecting a group amino in the compounds (Ia) - (Ih) to an eicosanoylation, alanylation, pentylaminocarbonylation, (5-methyl-2-oxo-l, 3-dioxolen-4-yl) methoxycarbonylation, tetrahydrofuranoylation, pyrrolidylmethylation, pivaloyloxymethylation or tert-butylation); a compound obtained by subjecting a hydroxy group in the compounds (Ia) - (Ih) to an acylation, alkylation, phosphorylation or boration (for example, a compound obtained by subjecting a hydroxy group in the compounds (Ia) - (Ih) to acetylation, palmitoylation, propanoylation, pivaloylation, succinylation, fumalation, alanylation or dimethylaminomethylcarbonylation); a compound obtained by subjecting a carboxyl group in the compounds (Ia) - (Ih) to an esterification or amidation (for example, a compound obtained by subjecting a carboxyl group in the compounds (Ia) - (Ih) to an ethylesterification, phenylsterification , carboxymethyl esterification, dimethylaminathomethyl ester, pivaloyloxymethyl ester, ethoxycarbonyloxyethyl ester, phthalidyl ester, (5-methyl-2-oxo-1,3-dioxolen-4-yl) methyl ester, cyclohexyloxycarbonyletheterification or methylamidation) and the like. Any of these compounds can be produced from the compounds (Ia) - (Ih) by means of a method known per se. A prodrug for the compounds (Ia) - (Ih) can also be one which is converted to the compounds (Ia) - (Ih) in a physiological condition, for example those described in IYAKUHIN not KAIHATSU (Developraent of Pharmaceuticals), Vol. 7, Design of Molecules, p, 163-198, Published by HIROKAWA SHOTEN (1990). The compounds (Ia) - (Ih) of the present invention, or one of its salts or one of its prodrugs (hereinafter referred to as the compound of the present invention) possess tyrosine kinase inhibitory activity and can be used for the prophylaxis or treatment of tyrosine kinase dependent diseases in mammals. Tyrosine kinase dependent diseases include diseases characterized by increased cell proliferation due to the abnormal activity of the tyrosine kinase enzyme. Particularly, the compound of the present invention specifically inhibits HER2 kinase and / or EGFR kinase and consequently it is also useful as a therapeutic agent to suppress the growth of cancer expressing HER2 and / or EGFR kinase. In addition, the compound of the present invention is useful as a preventive agent for preventing hormone-dependent cancer and the transition from hormone-dependent cancer to hormone-independent cancer. In addition, the compound of the present invention is useful as a pharmaceutical agent since it shows low toxicity (eg, acute toxicity, chronic toxicity, genetic toxicity, reproductive toxicity, cardiotoxicity, drug interaction, carcinogenicity and the like), high solubility in water, and is superior in stability, pharmacokinetics (absorption, distribution, metabolism, excretion and the like) and expression of efficacy. Accordingly, the compound of the present invention can be used as a safe agent for the prophylaxis or treatment of diseases due to the proliferation of abnormal cells such as various malignancies (particularly, breast cancer (e.g., invasive ductal carcinoma, ductal cancer). m if you, inflammatory breast cancer, etc.), prostate cancer (eg, hormone-dependent prostate cancer, non-hormone-dependent prostate cancer, etc.), pancreatic cancer (eg, pancreatic duct cancer) , etc.), gastric cancer (eg, papillary adenocarcinoma, adenocarcinoma mucosa, adenopavimentous carcinoma, etc.), lung cancer (eg, non-small cell lung cancer, small cell lung cancer, malignant mesothelioma, etc.), colorectal cancer (eg, familial colorectal cancer, cancer non-hereditary polyps colorectal, gastrointestinal stromal tumor, etc.), colon cancer (eg, gastrointestinal stromal tumor, etc.), rectal cancer (eg, gastrointestinal stromal tumor, etc.), esophageal cancer, duodenum cancer, tongue cancer, pharyngeal cancer (eg, nasopharyngeal carcinoma, oropharyngeal cancer, hypopharyngeal cancer, etc.), salivary gland cancer, brain tumor (eg, pineal astrocytoma, pilocytic astrocytoma, diffuse astrocytoma, astrocytoma) anaplastic, etc.), neurinoma, non-small cell lung cancer, small cell lung cancer, liver cancer (eg, primary liver cancer, cancer of the liver, extrahepatic bile duct, etc.), kidney cancer (eg, renal cell carcinoma, renal pelvis and ureter, transitional cell cancer, etc.), cancer of the bile duct, cancer of the body of the uterus, endometrial carcinoma, cancer of the cervix, ovarian cancer (eg, ovarian epithelial cell tumor, extragonadal germ cells, ovarian germ cell tumor, low malignant potential ovarian tumor, etc.), bladder cancer, urethral cancer, skin cancer (eg, ocular melanoma, Merkel cell carcinoma, etc.), hemangioma, malignant lymphoma, malignant melanoma, thyroid cancer (eg, thyroid marrow carcinoma, etc.), parathyroid cancer, cancer nasal cavity, paranasal sinus cancer, bone tumors (for example, osteosarcoma, Ewing's tumor, uterine sarcoma, soft tissue sarcoma, etc.), vascular fibroma, retinoblastoma, penile cancer, solid childhood cancer, sarcoma of Kaposi, Kaposi sarcoma derived from AIDS, maxillary tumor, fibrous histiocytoma, leiomyosarcoma, rhabdomyosarcoma, leukemia (for example, acute myeloid leukemia, acute lymphoblastic leukemia, etc.) etc.), atherosclerosis, angiogenesis (eg, angiogenesis associated with growth of solid malignancies and sarcoma, angiogenesis associated with tumor metastasis, angiogenesis associated with diabetic retinopathy, etc.), and viral diseases (HIV infection, etc.). Tyrosine kinase-dependent diseases also include cardiovascular diseases associated with abnormal activity of the tyrosine kinase enzyme. Accordingly, the compound of the present invention can be used as an agent for prophylaxis or treatment of cardiovascular diseases such as restenosis. The compound of the present invention is useful as an antineoplastic agent for the prophylaxis or treatment of cancer, especially breast cancer, ovarian cancer, colorectal cancer, gastric cancer, esophageal cancer, prostate cancer, lung cancer, pancreatic cancer, kidney cancer and the like. The compound of the present invention shows low toxicity and can be used as a pharmaceutical agent as such, or as a pharmaceutical composition mixed with a commonly known pharmaceutically acceptable carrier, etc. in mammals (for example, humans, horses, cattle, dogs, cats, rats, mice, rabbits, pigs, monkeys and the like). In addition to the compound of the present invention, said pharmaceutical composition may contain other active ingredients, for example, the following hormonal therapeutic agents, antineoplastic agents (e.g., chemotherapeutic agents, immunotherapeutic agents, or pharmaceutical agents that inhibit the action of cell growth factors or cell growth factor receptor), and the like. As a pharmaceutical agent for mammals such as humans, the compound of the present invention can be administered orally, for example, in the form of tablets, capsules (including soft capsules and microcapsules), powders, granules and the like, or parenterally in the form of injections, suppositories, granules and the like. The examples of "administration route "parenteral" include intravenous, intramuscular, subcutaneous, intratissular, intranasal, intradermal, instillation, intracerebral, intrarectal, intravaginal, intraperitoneal, intratumoral, tumor juxtaposition, and administration directly to the lesion The dose of the compound of the present invention varies according to the route of administration, symptoms, etc. For example, when administered orally as an antineoplastic agent to a patient (body weight 40 to 80 kg) with breast cancer or prostate cancer, the dose is, for example, 0.5 at 100 mg / kg of body weight per day, preferably 1 to 50 mg / kg of body weight per day, and more preferably 1 to 25 mg / kg of body weight per day.This amount can be administered once or in 2 to 3 divided portions per day The compound of the present invention can be administered safely orally or parenterally (eg, topical, rectal, intravenous, etc.) as a single agent. ico, or a pharmaceutical composition containing a pharmacologically acceptable carrier according to a conventional method (eg, a method described in Japanese Pharmacopoeia etc.), for example a tablet (including tablet coated by sugar, film-coated tablet), powder , granule, capsule, liquid, emulsion, suspension, injection, suppository, preparation sustained release, patches and the like. And (1) the administration of an effective amount of a compound of the present invention and (2) a combination of 1 to 3 selected from the group consisting of (i) administering an effective amount of other anticancer agents, (ii) administering an effective amount of hormonal therapeutic agents and (iii) non-pharmacological therapy can prevent and / or treat cancer more effectively. As non-pharmacological therapeutics, for example, surgery, radiotherapy, gene therapy, thermotherapy, cryotherapy, laser cauterization and the like are examples and two or more of them can be combined. For example, the compound of the present invention can be administered to the same subject simultaneously with hormonal therapeutic agents, antineoplastic agents (eg, chemotherapeutic agents, immunotherapeutic agents, or pharmaceutical agents that inhibit the action of cell growth factors or factor receptor receptors). cell growth) (hereinafter referred to as concomitant drug). Although the compound of the present invention exhibits excellent anticancer action, even when used as a single agent, its effect may be increased by using it in combination with one or more of the concomitant drug (s) mentioned above (co-administration of agents multiple).

As examples of the "hormonal therapeutic agents" there may be mentioned fosfestrol, diethylstilbestrol, chlorotrianisen, medroxyprogesterone acetate, megestrol acetate, chlormadinone acetate, cyproterone acetate, danazol, dienogest, asoprisnil, allystrenol, gestrinone, nomegestrol, tadenan, meparticin, raloxifene, ormeloxifene, levormeloxifen, antiestrogens (e.g., tamoxifen citrate, toremifene citrate, and the like), down-regulator of ER (e.g., fulvestrant, and the like), human menopause gonadotropin, follicle-stimulating hormone, pill preparations, mepitiostane, testrolactone, aminoglutethimide, LH-RH agonists (eg, goserelin acetate, buserelin, leuprorelin, and the like), droloxifene, epithioestanol, ethinylestradiol sulfonate, aromatase inhibitors (e.g., fadrozole hydrochloride, anastrozole, retrozol, exemestane, vorozole, formestane, and the like), antiandrogens (e.g., flutamide, bicart amide, nilutamide, and the like), 5a-reductase inhibitors (e.g., finasteride, dutasteride, epristeride, and the like), adrenocorticotrophic hormone drugs (e.g., dexamethasone, prednisolone, betamethasone, triamcinolone, and the like), synthesis inhibitors of androgens (eg, abiraterone, and the like), retinoids, and drugs that slow down the metabolism of retinoids (eg, liarozole, and the like), etc., and LH-RH agonists (e.g., goserelma acetate, buserelin, leuprorelin) are preferred. As examples of "chemotherapeutic agents" there may be mentioned alkylating agents, antimetabolites, anticancer antibiotics, antimicrobial agents derived from plants, and the like. As examples of "alkylating agents" there may be mentioned nitrogen mustard, nitrogenated mustard N-oxide hydrochloride, chlorambutyl, cyclophosphamide, phosphamide, thiotepa, carbocuone, improsulfan tosylate, busulfan, nimustma hydrochloride, mitobronitol, melphalan, dacarbazm, ranimustma, sodium phosphate estramustma, trietJ lenemelamma, carmustma, lomustine, streptozocin, pipobroman, etoglucid, carboplatmo, cisplatmo, mibopl atino, nedaplatin, oxaliplatmo, altretamma, ambamustma hydrochloride dibrospidium, foteraustina, prednimustma, pumitepa, ribomustma, temozolomide, treosulfan, trofosfamide , estimalámero of zmostat a, adozelesma, cistemustma, bizelesma, and the like. As examples of "antimetabolites" there may be mentioned mercaptopurma, pbosideo of 6-mercaptopurma, thio osin, methotrexate, enocitabma, cytarabma, cyclobarma octofosphate, ancitab hydrochloride, 5-FU drugs (eg, fluorouracil, tegafur, UFT, doxifluridma). , carmofur, galocitabine, emitefur, and the like), aminopterin, calcitic leucovorin, tabloid, butocin, calcium folinate, calcium levofolinate, cladribine, emitefur, fludarabine, gemcitabine, hydroxycarbamide, pentostatin, piritrexime, idoxuridine, mitoguazone, thiazophrine, ambamustine, and the like. As examples of "anticancer antibiotics", there may be mentioned actinomycin-D, actinomycin-C, mitomycin-C, chromomycin-A3, bleomycin hydrochloride, bleomycin sulfate, peplomycin sulfate, daunorubicin hydrochloride, doxorubicin hydrochloride, aclarubicin hydrochloride , pirarubicin hydrochloride, epirubicin hydrochloride, neocarzinostatin, mithramycin, sarcomycin, carzinophilin, mitotane, zorrubicin hydrochloride, mitoxantrone hydrochloride, idarubicin hydrochloride, and the like. As examples of "anticancer agents derived from plants", there may be mentioned etoposide, etoposide phosphate, vinblastine sulfate, vincristine sulfate, vindesine sulfate, teniposide, paclitaxel (Taxol (trademark)), docetaxel, vinorelbine, and the like. As examples of "immunotherapeutic agents (BRM)", there may be mentioned picibanil, crestin, sizofirano, lentinan, ubenimex, interferons, interleukins, macrophage colony stimulating factor, colonies of granulocytes, erythropoietin, lymphotoxin, BCG vaccine, Corineba cteri um parvum, levamisole, K polysaccharide, procodazole, and the like. As "growth factor" of said "pharmaceutical agents inhibiting the action of cell growth factors or cell growth factor receptors", we can mention any substance that favors cell proliferation, which are usually peptides with a molecular weight of more than 20,000, capable of exhibiting its activity at low concentrations by binding to a receptor, including (1) EGF (epidermal growth factor) or substances possessing substantially the same activity [eg, EGF, heregulin, and the like], (2) insulin or substances that possess substantially the same activity [eg, insulin, IGF (growth factor simil insulin) -1, IGF-2, and the like], (3) FGF (fibroblast growth factor) or substances that substantially possess the same activity [eg, FGF acid, basic FGF, KGF (keratinocyte growth factor), FGF-10, and the like], (4) other cell growth factors [eg, CSF (f colony stimulating agent), EPO (erythropoietin), IL-2 (interleukin-2), NGF (nerve growth factor), PDGF (platelet-derived growth factor), TGFβ (ß-transforming growth factor), HGF ( hepatocyte growth factor), VEGF (factor of vascular endothelial growth), and the like], and the like. As examples of "growth factor receptors", there may be mentioned any receptor capable of binding to the aforementioned growth factors, including EGF receptor, heregulin receptor (HER2), insulin receptor, IGF receptor, receptor FGF-1 or receptor of FGF-2, and the like. As examples of "pharmaceutical agents inhibiting the action of cell growth factor", there may be mentioned HER2 antibody (trastuzumab (Herceptin (trademark)), imatinib mesylate, antibody ZD1839 or EGFR (cetuximab (Erbitux (trademark)) ) etc.), antibody to VEGF (eg, bevacizumab (Avastin (trademark))), VEGFR antibody, VEGFR inhibitor, EGFR inhibitor (gefitinib (Iressa (trademark)), erlotinib (Tarceva (brand name)) etc.) and similar. In addition to the aforementioned drugs, L-asparaginase, aceglatone, procarbazine hydrochloride, protoporphyrin-cobalt complex salt, mercuric-sodium hematoporphyrin, topoisomerase I inhibitors (eg, irinotecan, topotecan, and the like), inhibitors can be used. of topoisomerase II (eg, sobuzoxane, and the like), inducers of differentiation (eg, retinoid, vitamin D, and the like), angiogenesis inhibitors (eg, example, thalidomide, SU11248, and the like), α-blockers (e.g., tamsulosin hydrochloride, naftopidil, urapidil, alfuzosin, terazosin, prazosin, silodosin, and the like), serine / threonine kinase inhibitor, endothelin receptor antagonist ( for example, atrasentan, and the like), proteasome inhibitor (e.g., bortezomib, and the like), Hsp 90 inhibitor (e.g., 17 -AAG, and the like), spironolactone, minoxidil, lla-hydroxyprogesterone, suppressive agent of the inhibition / metastasis of bone resorption (eg, zoledronic acid, alendronic acid, pamidronic acid, etidronic acid, ibandronic acid, clodronic acid) and the like. Of the aforementioned as a concomitant drug, LH-RH agonist (e.g., goserelin acetate, buserelin, leuprorelin, and the like), HER2 antibody (trastuzumab (Herceptin (trademark)), EGFR antibody (cetuximab) are preferred. (Erbitux) (trademark) etc.), EGFR inhibitor (erlotinib (Tarceva) (trademark), gefitinib (Iressa (trademark)) etc.), VEGFR inhibitory agent or chemotherapeutic agent (paclitaxel (Taxol (brand name) ) etc.) Particularly, trastuzumab (Herceptin (trademark)), cetuximab (Erbitux (trademark)), erlotinib (Tarceva) (trademark)), gefitinib (Iressa (trademark)), paclitaxel (Taxol ( brand commercial)) and similar. In combination with the compound of the present invention and the concomitant drug, the time of administration of the compound of the present invention and the concomitant drug is not restricted, and the compound of the present invention and concomitant drug can be administered to the subject of administration simultaneously, or can be administered at different times. The dose of the concomitant drug can be determined according to the amount of administration for clinical use, and can be appropriately selected according to the subject of administration, the route of administration, the disease, the combination and the like. The mode of administration of the compound of the present invention and the concomitant drug is not particularly restricted, and it is sufficient to combine the compound of the present invention and the concomitant drug in the administration. Examples of modes of such administration include the following methods: (1) The compound of the present invention and the concomitant drug are simultaneously produced to give a single preparation administered. (2) The compound of the present invention and the concomitant drug are produced separately to give two types of preparations that are administered simultaneously by the same route of administration. administration. (3) The compound of the present invention and the concomitant drug are produced separately to give two types of preparations that are administered by the same route of administration, but at different times. (4) The compound of the present invention and the concomitant drug are produced separately to give two types of preparations that are administered simultaneously by different routes of administration. (5) The compound of the present invention and the concomitant drug are produced separately to give two types of preparations which are administered by different routes of administration, at different times (for example, the compound of the present invention and the concomitant drug is administered in that order, or in reverse order). Examples The present invention is explained in detail by way of the following Examples, Formulation Examples and Experimental Examples, but do not limit the present invention. Examples The present invention is explained below in detail with reference to Examples, Preparation Examples and Experimental Examples, which are not constructed as limiting.

Example A-l Production of N- [2- (4- { [3-chloro-4- (3-chlorophenoxy) phenyl] amino} -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2-methy1-2- (methylsulfonyl) propanamide To a solution of 5- (2-aminoethyl) -N- [3-chloro-4- (3-chlorophenoxy) phenyl] -5H-pyrrolo dihydrochloride [3, 2- d] pyrimidin-4-amine (487 mg), 2-methyl-2- (methyl sulfonyl) propanoic acid (249 mg) and 1-hydroxybenzotriazole (225 mg) in N, N-dimethylformamide (5.0 ml) were added triethylamine (0.69 ml) and l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (316 mg) under ice-cooling, and the mixture was stirred at room temperature for 15 h. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: methanol = 100: 0-> 90: 10) and then recrystallized from ethyl acetate / ether diisopropyl to give the title compound (419 mg) in form of colorless crystals. XH-NMR (CDCl3) d: 1.70 (6H, s), 2.93 (3H, s), 3.60- 3.80 (2H, m), 4.40-4.60 (2H, m), 6.46 (1H, d, J = 2.8 Hz ), 6. 85-7.00 (2H, m), 7.00-7.15 (2H, m), 7.15-7.30 (2H, m), 7.30-7.40 (1H, m), 7.85-7.95 (1H, m), 8.00-8.05 (1H , m), 8.36 (1H, br s), 8.54 (1H, s). Example A-2 Production of N- [2- (4- { [3-chloro-4- (3-chlorophenoxy) phenyl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) eti 1 ] -2- (methylsulfonyl) propanamide To a solution of 5- (2-aminoethyl) -N- [3-chloro-4- (3-chlorophenoxy) phenyl] -5H-pyrrolo dihydrochloride [3, 2-d] pyrimidin-4-amine (200 mg), 2-chloropropanoic acid (67 mg) and 1-hydroxybenzotriazole (90 mg) in N, N-dimethylformamide (4.0 ml) were added triethylamine (0.29 ml) and hydrochloride of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (126 mg) under ice-cooling, and the mixture was stirred at room temperature for 17 h. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over magnesium sulfate anhydrous. After concentrating under reduced pressure, the residue was dissolved in N, N-dimethylformamide (2 ml), sodium metansulfinic acid (420 mg) and pyridine (0.40 ml) were added, and the mixture was stirred at 70 ° C for 2 hours. days. After cooling to room temperature, water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: meianol 100: 0-95: 5) and then recrystallized from ethyl acetate / diisopropyl ether to give the title compound (97 mg) as colorless crystals. XH-NMR (CDC13) d: 1.71 (3H, d, J = 7.2 Hz), 2.98 (3H, s), 3.65-3.75 (2H, m), 3.81 (1H, q, J = 7.2 Hz), 4.45- 4.55 (2H, m), 6.61 (1H, d, J = 3.3 Hz), 6.85-6.90 (1H, m), 6.90-6.95 (1H, m), 7.00-7.10 (2H, m), 7.20-7.30 ( 1H, m), 7.30-7.40 (1H, m), 7.75-7.85 (1H, m), 7.97 (1H, d, J = 2.4 Hz), 8.28 (1H, s), 8.51 (1H, s). Example A-3 Production of N- [2- (4- ([3-chloro-4- (3-chlorophenoxy) phenyl] amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2 - (isopropylsulfonyl) acetamide (i) Production of N- [2- (4- { [3-chloro-4- (3-chlorophenoxy) phenyl] amino.}. -5H-pyrrolo [3, 2-d] pyrimidin-5-yl) eti 1] -2- (isopropylthio) acetamide To a solution of 5- (2-aminoethyl) -N- [3-chloro-4- (3-chlorophenoxy) phenyl] -5H-pyrrolohydrochloride. [3, 2-d] pyrimidin-4-amine (300 mg), chloroacetic acid (87 mg) and 1-hydroxybenzotriazole (135 mg) in N, N-dimethylformamide (5.0 ml) were added triethylamine (0.43 ml) and hydrochloride of 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (189 mg) under ice-cooling, and the mixture was stirred at room temperature for 18 h, water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate.After concentrating under reduced pressure, the residue was dissolved in N, dimethylformamide (2 ml) / tetrahydrofuran (4 ml), sodium propan-2-thiolate (605 mg) was added, and the mixture was stirred at room temperature for 6 h. Aqueous sodium bicarbonate was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by gel column chromatography of silica (eluent, ethyl acetate: methanol = 100: 0- »95: 5) to give the title compound (201 mg) as a white powder. XH-NMR (CDC13) d: 1.24 (6H, d, J = 6.9 Hz), 2.80-2.90 (1H, ra), 3.33 (2H, s), 3.60-3.70 (2H, m), 4.45-4.55 (2H , m), 6.62 (1H, d, J = 3.3 Hz), 6.85-6.90 (1H, m), 6.95-7.00 (1H, rn), 7.00-7.05 (1H, m), 7.07 (1H, d, J = 8.7 Hz), 7.20-7.30 (2H, m), 7.40-7.50 (1H, m), 7.73 (1H, dd , J = 2.4, 8.7 Hz), 8.05 (1H, d, J = 2.4 Hz), 8.51 (1H, s). (ü) Production of N- [2- (4- ([3-chloro-4- (3-chlorophenoxy) phenyl] amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl ] -2- (isopropylsulfonyl) acetamide To a solution of N- [2- (4- { [3-chloro-4- (3-chlorophenoxy) phenyl] amino.}. -5H-pyrrolo [3, 2- d] pyrimidin-5-yl) ethyl] -2- (isopropylthio) acetamide in methanol (6 ml) / water (1.5 ml) was added monopersulphated OXONE® compound (339 mg), and the mixture was stirred at room temperature for 21 h. Water was added to the reaction mixture and the mixture was extracted with dichloromethane. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from dichloromethane / raetanol / diisopropyl ether to give the title co-tax (173 mg) as pale yellow crystals. XH-NMR (DMSO-d6) d: 1.23 (6H, d, J = 6.9 Hz), 3.40- 3. 65 (3H, m), 4.03 (2H, s), 4.50-4.70 (2H, m), 6.58 (1H, s), 6.90-6.95 (1H, m), 6.99 (1H, s), 7.15-7.25 ( 1H, m), 7.30 (1H, d, J = 8.7 Hz), 7.40-7.50 (1H, ra), 7.65-7.75 (1H, m), 7.79 (1H, s), 7.92 (1H, s), 8.53 (1H, s), 8.70-8.80 (1H, ra), 9.28 1H, br s) Example A-4 Production of N- [2- (4- { [3-chloro-4- (3-chlorophenoxy) phenyl] amino} -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2- (ethylsulphonyl) acetamide (i) Production of N- [2- (4- ([3-chloro-4- (3-chlorophenoxy) phenyl] amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2- (ethylthio) acetamide When using 5- (2-aminoethyl) -N- [3-chloro-4- (3-chlorophenoxy) phenyl] -5H-pyrrolo dihydrochloride [3, 2-d] pyrimidin-4-amine (200 mg), ethylthioacetic acid (99 mg), 1-hydroxybenzotriazole (123 mg), triethylamine (0.57 ml), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride ( 173 mg) and N, N-dimethylformamide (4.0 ml) and in the same manner as in Example Al, the title compound (186 mg) was obtained as a white powder.

XH-NMR (CDCl3) d: 1.24 (3H, t, J = 7.5 Hz), 2.52 (2H, q, J = 7.5 Hz), 3.32 (2H, s), 3.60-3.70 (2H, m), 4.45- 4.55 (2H, m), 6.62 (1H, d, J = 3.0 Hz), 6.88 (1H, d, J = 8.1 Hz), 6.95-7.00 (1H, m), 7.00-7.10 (2H, m), 7.15 -7.25 (1H, m), 7.40-7.50 (1H, m), 7.70-7.80 (1H, m), 8.05-8.10 (1H, m), 8.50 (1H, e), 8.51 (1H, s). (ii) Production of N- [2- (4. {[[3-chloro-4- (3-chlorophenoxy) phenyl] amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl. ) ethyl] -2- (ethylsulfonyl) acetamide When using N- [2- (4- ([3-chloro-4- (3-chlorophenoxy) phenyl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2- (ethylthio) acetamide (180 mg), compound OXONE® monopersulfated (322 mg) and methanol (6 ml) / water (1.2 ml) and in the same manner as in Example A -3 (ii), the title compound (149 mg) was obtained as colorless crystals XH-NMR (DMSO-d6) d: 1.21 (3H, t, J = 7.2 Hz), 3.22 (2H, q, J = 7.2 Hz), 3.45-3.55 (2H, m), 4.03 (2H, s), 4.55-4.65 (2H, m), 6.55-6.60 (1H, m), 6.90-6.95 (1H, m), 6.99 (1H, s), 7.15-7.20 (1H, m), 7.29 (1H, d, J = 8.7 Hz), 7.41 (1H, t, J = 8.2 Hz), 7.65-7.75 (1H, m), 7.75- 7.80 (1H, m), 7.93 (1H, s), 8.52 (1H, s), 8.72 (1H, br s), 9.22 (1H, br s).

Example A-5 Production of N- [2- (4. {[[3-chloro-4- (3-chlorophenoxy) phenyl] amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl) eti 1 ] -N-methy1-2- (methylsulfonyl) acetamide (i) Production of [2- (4- ([3-chloro-4- (3-chlorophenoxy) phenyl] amino.}. -5H-pyrrolo [3,2] -d] pyrimidin-5-yl) eti 1] tert-butyl methylcarbamate A mixture of [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] methylcarbamate ter Butyl (2.56 g), 3-chloro-4- (3-chlorophenoxy) aniline (2.51 g) and isopropyl alcohol (25 ml) were stirred at 80 ° C. for 18 h after cooling to room temperature, the mixture was stirred for 5 h The precipitate was collected by filtration, and washed with diisopropyl ether to give the title co-tax (3.72 g) as a white powder XH-NMR (CDC13) d: 1.52 (9H, s), 3.01 ( 3H, s), 3.50-3.60 (2H, ra), 4.40-4.50 (2H, m), 6.60 (1H, d, J = 3.0 Hz), 6.85-6.95 (1H, m), 6.95-7.00 (1H, m), 7.00-7.05 (1H, m), 7.07 (1H, d, J = 9.0 Hz), 7.15-7.25 (2H, m), 7.90 (1H, d, J = 9. 0 Hz), 8.01 (1H, br s), 8.52 (1H, s), 8.83 (1H, s). (n) Production of N- [3-chloro-4- (3-chlorophenoxy?) phenyl] -5- [2- (methylamino) ethyl] -5H-pyrrol [3, 2-d] -phenylhydrochloride ? d? n-4-am? na A mixture of [2- (4- ([3-chloro-4- (3-chloroenoxi) phenyl] amino.}. -5H-pyrrolo [3,2-d] ] p? r? m? d? n-5-yl) et 1] tert-butyl methylcarbamate (3.72 g) and 10% hydrochloric acid (w / w) / methanol (30 ml) was stirred at 65 ° C The reaction mixture was concentrated under reduced pressure, and the precipitate was collected by filtration, and washed with diethyl ether to give the title compound (2.70 g) as pale yellow crystals. NMR (DMSO-d6) d: 2.50-2.60 (3H, m), 3.30-3.50 (2H, m), 5.00-5.20 (2H, m), 6.75 (1H, d, J = 3.0 Hz), 6.90-7.00 (1H, m), 7.02 (1H, s), 7.21 (1H, d, J = 7.8 Hz), 7.32 (1H, cl, J = 8.7 Hz), 7.44 (1H, t, J = 8.1 Hz), 7.66 (1H, d, J = 8.7 Hz), 7.93 (1H, s), 8.07 (1H, d, J = 3.0 Hz), 8.73 (1H, s), 9.10-9.30 (2H, m), 10.17 (1H, br s). (m) Production of N- [2- (4- { [3-chloro-4- (3-chlor ofenoxi) phenyl] amino} -5H-pyrrolo [3,2-d] p? R? M? D? N-5-yl) ethyl] -N-met? L-2- (methylsulfonyl) acetamide When using N- [3 dihydrochloride] -chloro-4- (3-chlorophenoxy) phenyl] -5- [2- (methylamino) ethyl] -5H-pyrrolo [3, 2-d] p? pm? dm-4 -amma (200 rag), methylated acid sulfite ontic lacetico (83 mg), L-hydroxybenzotriazole (87 mg), triethylamine (0.28 ml), l-et? l-3- (3-d? met? lammopropyl) hydrochloride) carbodnide (123 mg) and N, N-dimethylformamide (5.0 ml) and in the same manner as in Example A-1, the title compound (164 mg) was obtained as colorless crystals. XH-NMR (CDC13) d: 3.17 (3H, s), 3.33 (3H, s), 3.70-3.85 (2H, m), 4.17 (2H, s), 4.45-4.55 (2H, m), 6.63 (1H , d, J = 3.0 Hz), 6.85-6.95 (2H, m), 7.00-7.10 (2H, m), 7.20-7.30 (2H, m), 7.82 (1H, dd, J = 2.7 Hz, 9.0 Hz), 7.92 (1H, d, J = 2. 7 Hz), 8.44 (1H, s), 8.52 (1H, s). Example A-6 Production of 2- (tert-butylsulfonyl) -N- [2- (4- ([3-chloro-4- (3-chlorophenoxy) phenyl] amino.}. -5H-pyrrolo [3,2-d] pyrimidine- 5-yl) ethyl] acetamide (i) Production of 2- (tert-butylthio) -N- [2- (4- ([3-chloro-4- (3-chlorophenoxy) phenyl] amino] -5H- pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] acetamide To a solution of 5- (2-aminoethyl) -N- [3-chloro-4- (3-chlorophenoxy) phenyl] -5H- dihydrochloride pyrrolo [3,2-d] pyrimidin-4-amine (200 mg), chloroacetic acid (58 rag) and 1-hydroxybenzotriazole (90 mg) in N, N-dimethylformamide (4.0 ml) were added triethylamine (0.29 ml) and 1-ethyl-hydrochloride 3- (3-dimethylaminopropyl) carbodiimide (126 mg) under ice-cooling, and the mixture was stirred at room temperature for 4 h. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was dissolved in N, N-dimethylformamide (2 ml) / tetrahydrofuran (4 ml), 2-methylpropane-2-thiolate sodium (511 mg) was added, and the mixture was stirred at room temperature. room temperature for 2 h. Aqueous sodium bicarbonate was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: methanol = 100: 0- »95: 5) to give the title compound (159 mg) in the form of a white powder. XH-NMR (CDC13) d: 1.30 (9H, s), 3.33 (2H, s), 3.60-3.70 (2H, m), 4.40-4.50 (2H, m), 6.61 (1H, d, J = 3.3 Hz ), 6.85-6.90 (1H, m), 6.95-7.00 (1H, m), 7.00-7.05 (1H, m), 7.07 (1H, d, J = 9.0 Hz), 7.15-7.25 (2H, m), 7.45-7.55 (1H, ra), 7.73 (1H, dd, J = 3.0 Hz, 9.0 Hz), 8.06 (1H, d, J = 2.7 Hz), 8.51 (1H, s), 8.56 (1H, s). (ii) Production of 2- (tert-butylsulfonyl) -N- [2- (4. {[[3-chloro-4- (3-chlorophenoxy) phenyl] amino] -5H-pyrrolo [3, 2] - d] pyrimidin-5-yl) ethyl] acetamide Using 2- (tert-butylthio) -N- [2- (4. {[[3-chloro-4- (3-chlorophenoxy) phenyl] amino]. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] acetamide (159 mg), compound OXONE® monopersulfated (269 mg) and methanol (5 ml) / water (1.5 ml) and in the same manner that in Example A-3 (ii), the title compound (99 mg) was obtained in the form of pale yellow crystals. XH-NMR (95% CDCl3 + 5% DMSO-d6) d: 1.43 (9H, s), 3.50-3.70 (2H, m), 4.00 (2H, s), 4.60-4.70 (2H, m), 6.60 ( 1H, d, J = 3.0 Hz), 6.85-6.95 (2H, m), 7.05-7.15 (2H, m), 7.31 (1H, t, J = 8.1 Hz), 7.60-7.70 (2H, m), 7.92 (1H, s), 8.49 (1H, s), 8.80-8.90 (1H, m), 9.30-9.50 (1H, m). Example A-7 Production of N- [2- (4- { [3-chloro-4- (3-chlorophenoxy) phenyl] amino} -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -N, 2-dimethy1-2- (methylsulfonyl) propanamide To a solution of N- [3-chloro-4- (3-chlorophenoxy) phenyl] -5- [2- (methylamino) ethyl] -5H-pyrrolo dihydrochloride [3,2-d] pyrimidin-4-amine (200 mg) and 2-methyl-2- (methylsulfonyl) propanoic acid (100 mg) in N, N-dimethylformamide (5.0 ml) were added tpetilamma (0.28 ml) and diethyl cyanophosphonate (0.097 ml) under cooling with ice, and the mixture was stirred at room temperature for 25 h. Aqueous sodium bicarbonate was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: methanol = 100: 0-90: 10) and then recrystallized from ethyl acetate / dnsopropyl ether to give the title compound (94 mg) as pale yellow crystals. ^ -NMR (CDC13) d: 1.85 (6H, s), 2.97 (3H, s), 3.47 (3H, s), 3.70-3.80 (2H, m), 4.40-4.50 (2H, m), 6.63 (1H , d, J = 3.6 Hz), 6.85-6.95 (2H, m), 7.00-7.05 (1H, m), 7.06 (1H, d, J = 8.7 Hz), 7.20-7.30 (2H, m), 7.90- 8.00 (1H, m), 8.01 (1H, d, J = 2.4 Hz), 8.52 (1H, s), 8.69 (1H, br s). Example A-8 Prod [3-chloro-4- (3-methylphenoxy) phenyl] ammo} -5H-pyrrolo [3,2-d] p? R? M? D? N-5-yl) ethyl] -2-methy1-2- (methylsulfonyl) propanami (i) Production of 5- (2-aminoethyl) -N- [3-chloro-4- (3-methylphenoxy) phenyl] -5H-pyrrolo [3,2-d] pyrimidin-4-amine dihydrochloride A mixture of [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (594 mg), 3-chloro-4- (3-methylphenoxy) aniline (467) mg) and isopropyl alcohol (10 ml) was stirred at 80 ° C for 6 h. Aqueous sodium carbonate aqueous solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and the obtained residue was purified by silica gel column chromatography (eluent, ethyl acetate: hexane = 50: 50-> 100: 0). The object fractions were concentrated under reduced pressure. To a solution of the residue in methanol (10 ml) was added concentrated hydrochloric acid (3 ml), and the mixture was stirred at room temperature overnight and also at 60 ° C for 3 h. The reaction mixture was concentrated under reduced pressure. Isopropyl alcohol and toluene were added to the residue, and the mixture was concentrated under reduced pressure. Methanol was added to the residue, and the mixture was concentrated under reduced pressure. Isopropyl alcohol and diisopropyl ether were added to the residue, and the precipitated solid was collected by filtration to give the title compound (805 mg) as a yellow powder pale. XH-NMR (DMSO-d5) d: 2.31 (3H, s), 3.23-3.37 (2H, m), . 04 (2H, t, J = 6.2 Hz), 6.72-6.80 (2H, m), 6.83 (1H, m), 6.98 (1H, d, J = 7.5 Hz), 7.18 (1H, d, J = 8.9 Hz ), 7.29 (1H, t, J = 7.8 Hz), 7.59 (1H, dd, J = 8.8, 2.5 Hz), 7.87 (1H, d, J = 2. 5 Hz), 8.07 (1H, d, J = 3.2 Hz), 8.35 (3H, br s), 8.73 (1H, s), 10.15 (1H, br s). (ii) Production of N- [2- (4- ([3-chloro-4- (3-methylphenoxy) phenyl] amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl) eti 1] -2-methy1-2- (methylsulfonyl) propanamide A mixture of 5- (2-aminoethyl) -N- [3-chloro-4- (3-methylphenoxy) phenyl] -5H-pyrrolo dihydrochloride [3.2 -d] pyrimidin-4-amine (140 mg), 2-methyl-2- (methylsulfonyl) propanoic acid (75 mg), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (86 mg), 1- hydroxybenzotriazole (69 mg), triethylamine (0.100 ml) and N, N-dimethylformamide (3 ml) was stirred at room temperature overnight, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate.The solvent was evaporated under reduced pressure and the residue obtained was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100-> 20: 80.) The object fractions were concentrated at reduced pressure. The residue is crystallized from ethyl acetate-diisopropyl ether to give the title compound (155 mg) as a white powder. XH-NMR (CDCl3) d: 1.69 (6H, s), 2.33 (3H, s), 2.93 (3H, s), 3.61-3.74 (2H, m), 4.41-4.51 (2H, m), 6.61 (1H , d, J = 3.3 Hz), 6.75-6.84 (2H, m), 6.89 (1H, d, J = 7.7 Hz), 7.02 (1H, d, J = 8.8 Hz), 7.16-7.24 (2H, m) , 7.34 (1H, t, J = 5.8 Hz), 7.80 (1H, dd, J = 8.8 Hz, 2.5 Hz), 7.97 (1H, d, J = 2.5 Hz), 8.31 (1H, br s), 8.51 ( 1H, s). Example A-9 Production of N- [2- (4- ([3-chloro-4- (3-methylphenoxy) phenyl] amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2 - (methylsulfonyl) acetamide A mixture of 5- (2-aminoethyl) -N- [3-chloro-4- (3-methylphenoxy) phenyl] -5H-pyrrolo [3,2-d] pyrimidin-4-amine dihydrochloride (140 mg), methylsulfonylacetic acid (62 mg), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (86 mg), 1-hydroxybenzotriazole (69 rag), triethylamine (0.100 ml) and N, N-dimethylformamide (3 ml) was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The The organic layer was washed successively with water and saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100- >); 15: 85). The object fractions were concentrated under reduced pressure. The residue was crystallized from ethyl acetate-diisopropyl ether to give the title compound (147 mg) as a white powder. XH-NMR (CDC13) d: 2.33 (3H, s), 3.13 (3H, s), 3.63-3.76 (2H, m), 3.70 (2H, s), 4.41-4.53 (2H, ra), 6.58 (1H , d, J = 3.3 Hz), 6.75-6.84 (2H, m), 6.90 (1H, d, J = 7.4 Hz), 7.01 (1H, d, J = 8.7 Hz), 7.16-7.24 (2H, m) , 7.55-7.64 (1H, m), 7.69 (1H, dd, J = 8.7, 2.7 Hz), 7.89 (1H, d, J = 2.7 Hz), 8.14 (ÍH, 'br s), 8.48 (1H, s ). -chloro-4- (3-fluorophenoxy) phenyl] amino} -5H-pyrrolo [3, 2-d] pyrimidin-5-yl) ethyl] -2-methy1-2- (methylsulfonyl) propanamide (i) Production of 5- (2-aminoethyl) dihydrochloride - N- [3-chloro-4- (3-fluorophenoxy) phenyl] -5H-pyrrolo [3,2-d] pyrimidin-4-amine A mixture of [2- (4-chloro-5H-pyrrolo [3, 2 -d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (594 mg), 3-chloro-4- (3-fluorophenoxy) aniline (475 mg) and isopropyl alcohol (10 ml) was stirred at 80 ° C. for 6 h. An aqueous solution of sodium acid carbonate was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue obtained was subjected to chromatography on silica gel column (eluent, ethyl acetate: hexane = 50: 50 → 100: 0). The object fractions were concentrated under reduced pressure. Methanol (10 ml), tetrahydrofuran (1 ml) and concentrated hydrochloric acid (3 ml) were added to the residue, and the mixture was stirred at room temperature overnight and then stirred at 60 ° C for 3 h. The reaction mixture was concentrated under reduced pressure. Isopropyl alcohol and toluene were added to the residue, and the mixture was concentrated under reduced pressure. Methanol was added to the residue, and the mixture was concentrated under reduced pressure. Isopropyl alcohol and diisopropyl ether were added to the residue and the precipitated solid was collected by filtration to give the title compound (809 mg) as a pale yellow powder.

XH-NMR (DMSO-d6) d: 3.22-3.39 (2H, m), 5.09 (2H, t, J = 6.3 Hz), 6.73-6.82 (2H, m), 6.83-6.92 (1H, m), 6.96-7.05 (1H, m), 7.31 (1H, d, J = 8.9 Hz), 7.39-7.51 (1H, m), 7.66 (1H, dd, J = 2.4 Hz, 8.9 Hz), 7.93 (1H, d, J = 2.4 Hz), 8.10 (1H, d, J = 3.2 Hz), 8.42 (3H, br s), 8.74 (1H, s), 10.30 (1H, br s). (ii) Production of N- [2- (4- { [3-chloro-4- (3-fluorophenoxy) phenyl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl. ) eti 1] -2-methy1-2- (methylsulfonyl) propanamide A mixture of 5- (2-aminoethyl) -N- [3-chloro-4- (3-fluorophenoxy) phenyl] -5H-pyrrolo dihydrochloride [3] , 2-d] pyrimidin-4-amine (141 mg), 2-methyl-2- (methylsulfonyl) propanoic acid (75 mg), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (86 mg) , 1-hydroxybenzotriazole (69 mg), triethylamine (0.100 ml) and N, N-dimethylformamide (3 ml) was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100-> 20: 80). The object fractions were concentrated under reduced pressure. The residue was crystallized from ethyl acetate-diisopropyl ether to give the title compound (161 mg) as a white powder. XH-NMR (CDCl3) d: 1.70 (6H, s), 2.93 (3H, s), 3.63-3.74 (2H, m), 4.42-4.53 (2H, m), 6.63 (1H, d, J = 3.3 Hz ), 6.64-6.71 (1H, m), 6.74-6.82 (2H, m), 7.09 (1H, d, J = 8.9 Hz), 7.19-7.32 (2H, m), 7.37 (1H, t, J = 5.8 Hz), 7.88 (1H, dd, J = 2.7 Hz, 8.9 Hz), 8.02 (1H, d, J = 2.7 Hz), 8.36 (1H, br s), 8.53 (1H, s). Example A-ll Production of N- [2- (4- ([3-chloro-4- (3-fluorcfenox?) Phen? L] amino) -5H-pyrrolo [3,2-d] p? Pm? D? N -5-yl) ethyl] -2- (methylsulfonyl) acetamide A mixture of 5- (2-ammoetyl) -N- [3-chloro-4- (3-fluorophenoxy) phenyl] -5H-p dihydrochloride? rrolo [3,2-d] pyrimid-4-amma (141 mg), methylsulfonylacetic acid (62 mg), l-et? l-3- (3-d? met? lammopropyl) hydrochloride) carbodnide (86 mg), 1-hydroxybenzotrol azol (69 mg), triethylamine (0.100 ml) and N, N-dimethylformamide (3 ml) were stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed successively with water and Saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100-> 15: 85). The object fractions were concentrated under reduced pressure. The residue was crystallized from ethyl acetate-diisopropyl ether to give the title compound (146 mg) as a white powder. XH-NMR (CDC13) d: 3.14 (3H, s), 3.64-3.76 (2H, m), 3.98 (2H, s), 4.43-4.54 (2H, m), 6.59 (1H, d, J = 3.3 Hz ), 6. 63-6.70 (1H, m), 6.73-6.82 (2H, m), 7.08 (1H, d, J = 8.9 Hz), 7.18-7.31 (2H, m), 7.57-7.65 (1H, m), 7.75 (1H, dd, J = 2. 5 Hz, 8.9 Hz), 7.93 (1H, d, J = 2.5 Hz), 8.19 (1H, br s), 49 (1H, s; Example A-12 Production of N- [2- (4- { [4- (3-chlorophenoxy) -3-methylphenyl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] - 2-methyl-2- (methylsulfonyl) propanamide (i) Production of [2- (4- { [4- (3-chlorophenoxy) -3-methylphenyl] amino.}. -5H-pyrrolo [3,2-] d] pyrimidin-5- il) eti 1] tert-butyl carbamate A solution of tert-butyl [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] carbamate (1.0 g) and 3 methyl-4- [3-chlorophenoxy] aniline (1.18 g) in isopropyl alcohol (10 ml) was stirred at 80 ° C for 12 h. Aqueous sodium bicarbonate was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by chromatography on silica gel column (eluent, hexane: ethyl acetate = 8: 2- ^ ethyl acetate) to give the title compound (1.7 g) in the form of colorless crystals. XH-NMR (CDC13) d: 1.47 (9H, s), 2.20 (3H, s), 3.48 (2H, m), 4.45 (2H, m), 5.16 (1H, m), 6.57 (1H, d, J = 3 Hz), 6.80-7.00 (4H, m), 7.10-7.30 (2H, m), 7.68 (2H, m), 8.40 (1H, br s), 8.49 (1H, s). (ii) Production of 5- (2-aminoethyl) -N- [4- (3-chlorophenoxy) -3-methylphenyl] -5H-pyrrolo [3,2-d] pyrimidin-4-amine dihydrochloride A mixture of [2- (4- { [4- (3-Chlorophenoxy) -3-methylphenyl] amino} -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (1.6 g), 2N hydrochloric acid (23 ml) and tetrahydrofuran (46 ml) was stirred at 60 ° C for 20 h. The solvent was evaporated under reduced pressure, ethanol, and the mixture was then concentrated. The resulting crystals were collected by filtration. The crystals were washed with isopropyl ether to give the title compound (1.35 g) as a pale yellow powder. XH-NMR (DMSO-d6) d: 2.19 (3H, s), 3.30 (2H, m), 5.04 (2H, m), 6.72 (1H, d, J = 3 Hz), 6.80-7.00 (2H, m ), 7.08 (1H, d, J = 9 Hz), 7.16 (1H, dd, J = 2 Hz, 8 Hz), 7.30-7.50 (2H, m), 7.54 (1H, m), 8.06 (1H, m ), 8.40 (3H, br s), 8.68 (1H, s), 10.00 (1H, br s). (iii) Production of N- [2- (4- ([4- (3-chlorophenoxy) -3-methylphenyl] amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2-methyl-2- (methylsulfonyl) propanamide A mixture of 5- (2-aminoethyl) -N- [4- (3-chlorophenoxy) -3-methylphenyl] -5H-pyrrolo dihydrochloride [3,2-d] pyrimidin-4-amine (167 mg), 2-methyl-2- (methylsulfonyl) propanoic acid (89 rag), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (103 mg), 1-hydroxybenzotriazole (72.5) mg), triethylamine (0.15 ml) and N, N-dimethylformamide (6.9 ml) was stirred at room temperature for 16 h, water was added to the reaction mixture and the mixture was extracted with ethyl acetate. successively with water and saturated brine, and dried over anhydrous magnesium sulfate.After concentrating under reduced pressure, the residue was separated and purified by column chromatography on silica gel (eluent, ethyl acetate-> ethyl acetate: methanol = 85:15) to give the title compound (179 mg) as an incolpable crystal > ros. XH-NMR (DMSO-d6) d: 1.42 (6H, s), 2.14 (3H, s), 2.96 (3H, s), 3.47 (2H, q, J = 6 Hz), 4.56 (2H, t, J = 6 Hz), 6.45 (1H, d, J = 3 Hz), 6.80-6.90 (2H, m), 7.02 (1H, d, J = 9 Hz), 7.11 (1H, dd, J = 1 Hz, 8 Hz), 7.37 (1H, t, J = 8 Hz), 7.52 (1H, d, J = 3 Hz), 7.58 (2H, m), 8.20 (1H, t, J = 6 Hz), 8.28 (1H, e), 8.49 (1H, br s). Example A-13 Production of N- [2- (4- { [4- (3-chlorophenoxy) -3-methylphenyl] amino} -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] - 2- (Methylsulfonyl) acetamide A mixture of 5- (2-aminoethyl) -N- [4- (3-chlorophenoxy) -3-methylphenyl] -5H-pyrrolo [3,2-d] pyrimidin-4-amine dihydrochloride (167 mg), methylsulfonylacetic acid (74 mg), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (103 mg), 1-hydroxybenzotriazole (72.5 mg), triethylamine (0.15 ml) and N, N-dimethylformamide (6.9 ml) was stirred at temperature environment for 16 h. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate -> ethyl acetate: methanol = 85:15) to give the title compound (177 mg) in the form of colorless crystals. XH-NMR (DMSO-d6) d: 2.13 (3H, s), 3.09 (3H, s), 3.45 (2H, q, J = 6 Hz), 4.05 (2H, s), 4.55 (2H, t, J = 6 Hz), 6.46 (1H, cl, J = 3 Hz), 6.80-6.95 (2H, m), 7.00 (1H, d, J = 9 Hz), 7.11 (1H, m), 7.37 (1H, t , J = 8 Hz), 7.56 (3H, m), 8.28 (1H, s), 8.52 (1H, br s), 8.66 (1H, m). Example A-14 Production of N- [2- (4- { [4- (3-chlorophenoxy) -3-methylphenyl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] - 2- (Rethylsulfonyl) propanamide A mixture of 5- (2-aminoethyl) -N- [4- (3-chlorophenoxy) -3-methylphenyl] -5H-pyrrolo [3,2-d] pyrimidine dihydrochloride 4-amine (192 mg), 2-chloropropanoic acid (0.057 ml), l-ethyl-3- (3-diraethylaminopropyl) carbodiimide hydrochloride (126 mg), 1-hydroxybenzotriazole (90 rag), triethylamine (0.29 ml) and N, N-dimethylformamide (4 ml) was stirred at room temperature for 16 h. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate-ethyl acetate: methanol = 90:10), and the fraction containing 2-chloro- N- [2- (4- { [4- (3-chlorophenoxy) -3-methylphenyl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] propanamide was concentrated at reduced pressure. The residue was dissolved in N, N-dimethylformamide (4 ml) and pyridine (0.4 ml), sodium methansulfinic acid (420 mg) was added and the mixture was stirred at 70 ° C for 2 days. After cooling to room temperature, water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate -> ethyl acetate: methanol = 85:15) to give the title co-tax (116 mg) in the form of crystals colorless XH-NMR (DMSO-d6) d: 1.36 (3H, d, J = 7 Hz), 2.13 (3H, s), 2.95 (3H, s), 3.50 (2H, m), 3.82 (1H, m), 4.53 (2H, m), 6. 46 (1H, d, J = 3 Hz), 6.80-6.90 (2H, m), 7.01 (1H, d, J = 9 Hz), 7.10 (1H, d, J = 8 Hz), 7.37 (1H, t , J = 8 Hz), 7.57 (3H, m), 8.28 (1H, s), 8.49 (1H, br s), 8.59 (1H, t, J = 6 Hz). Example A-15 Production of N- [2- (4 - ([3-chloro-4- (3-chlorophenoxy) phenyl] amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl p-toluenesulfonate) ethyl] -2-methy1-2- (methylsulfonyl) propanamide Ethyl acetate (200 ml) and ethanol (70 ml) were added to N- [2- (4- { [3-chloro-4- (3- chlorophenoxy) phenyl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2-methy1-2- (methylsulfonyl) propanamide (9.0 g), the mixture was dissolved by heating 65 ° C, and p-toluenesulfonic acid monohydrate (3.04 g) was added.The mixture was allowed to stand at room temperature under light protection for 23 h and the resulting crystals were collected by filtration.The crystals were washed with a small amount of water. ethyl acetate and diisopropyl ether to give the title compound (11.5 g) in the form of colorless crystals. XH-NMR (DMSO-de) d: 1.40 (6H, s), 2.28 (3H, s), 2.93 (3H, s), 3.50-3.60 (2H, m), 4.65-4.75 (2H, m), 6.65 (1H, d, J = 3.0 Hz), 6.90-7.00 (1H, m), 7.00-7.05 (1H, m), 7.10 (2H, d, J = 7.8 Hz), 7.20-7.25 (1H, m), 7.35 (1H, d, J = 9.0 Hz), 7.40-7.50 (3H, m), 7.60-7.70 (1H, m), 7.89 (1H, d, J = 3.0 Hz), 7.91 (1H, d, J = 1.8 Hz), 8.15-8.25 (1H, m), 8.74 (1H, s), 9.80 (1H, br s). Elemental analysis for C 32 H 33 Cl 2 N 5 O 7 S 2 Calculated: C, 52. 32; H, 4 53; N, 9 53 Experimental: C, 52.35; H, 4.54; N, 9.49. P. f. 217-218 ° C. Example A-16 Production of N- [2- (4. {[[3-chloro-4- (3-chlorophenoxy) phenyl] amino] -5H-pyrrolo [3,2-d] pyrimidin-5-p-toluenesulfonate il) ethyl] -2-phenyl-2- (distylsulfonyl) propanamide monohydrate Acetone (20 ml) was added to N- [2- (4- ([3-chloro-4- (3-chlorophenoxy) phenyl] amino]. .5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2-methyl-2- (methylsulfonyl) propanamide (500 mg), and the The mixture was dissolved by heating to 40 ° C, and p-toluenesulfonic acid monohydrate (168 mg) was added. The mixture was allowed to stand at room temperature under light protection for 4 days, and concentrated under reduced pressure. Ethyl acetate (12 ml) and ethanol (4 ml) were added to the residue, and the mixture was dissolved by heating to 60 ° C. The mixture was allowed to stand at room temperature for 17 h under light protection, and the resulting crystals were collected by filtration. The crystals were washed with diisopropyl ether to give the title compound (543 mg) as colorless crystals. XH-NMR (DMSO-d6) d: 1.40 (6H, s), 2.29 (3H, s), 2.93 (3H, s), 3.50-3.60 (2H, m), 4.65-4.75 (2H, m), 6.65 (1H, d, J = 3.0 Hz), 6.90-7.00 (1H, m), 7.00-7.05 (1H, m), 7.10 (2H, d, J = 7.8 Hz), 7.20-7.25 (1H, m), 7.35 (1H, d, J = 9.0 Hz), 7. 40-7.50 (3H, m), 7.67 (1H, dd, J = 2.4 Hz, 9.0 Hz), 7.88 (1H, d, J = 3.0 Hz), 7.92 (1H, d, J = 2.4 Hz), 8.15-8.25 (1H, m), 8.73 (1H, s), 9.76 (1H, br s). Elemental analysis for C32H33Cl2N507S2"1.0H2O Calculated: C, 51.06; H, 4.69; N, 9.30 Experimental: C, 50.49; H, 4.52; N, 9.23, P., 216-217 ° C.

Example A-17 Production of N- [2- (4. {[[3-chloro-4- (3-chlorophenoxy) phenyl] amino]} -5H-pyrrolo [3,2-d] pyrimidin-5-yl benzenesulfonate) ethyl] -2-methy1-2- (methylsulfonyl) propanamide monohydrate A N- [2- (4- ([3-chloro-4- (3-chlorophenoxy) phenyl] amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2- methyl-2- (methylsulfonyl) propanamide (400 mg) were added ethyl acetate (12 ml) and ethanol (4 ml), and the mixture was dissolved by heating at 60 ° C, and benzenesulfonic acid monohydrate (132 rag) was added The mixture was allowed to stand at room temperature for 17 h under light protection and concentrated under reduced pressure, and ethyl acetate (10 ml) was added to the residue.The mixture was allowed to stand at room temperature for 17 h under protection The crystals were washed with diisopropyl ether to give the title compound (447 mg) as colorless crystals, 2 H-NMR (DMSO-d 6) d: 1.41 (6H, s), 2.93 (3H, s), 3. 50-3.60 (2H, m), 4.65-4.75 (2H, m), 6.65 (1H, d, J = 3.0 Hz), 6.95-7.00 (1H, m), 7.00-7.05 (1H, m), 7.20- 7.25 (1H, m), 7.25-7.35 (3H, m), 7.35 (1H, d, J = 8.4 Hz), 7.45 (1H, t, J = 8.4 Hz), 7.55-7.65 (2H, m), 7.67 (1H, dd, J = 2.4, 8.7 Hz), 7.88 (1H, d, J = 3.0 Hz), 7.93 (1H, d, J = 2.4 Hz), 8.20-8.25 (1H, m), 8.73 (1H, s), 9.74 (1H, br s). Elemental analysis for C3iH31Cl2N507S2- 1.0H2O Calculated: C, 50.41; H, 4.50; N, 9.48. Experimental: C, 50.53; H, 4.43; N, 9.48. P. f. 142-144 ° C. Example A-18 Production of N- [2- (- { [3-chloro-4- (3-chlorophenoxy) phenyl] amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl hydrochloride ] -2-methyl-2- (methylsulfonyl) propanamide Acetone (20 ml) was added to N- [2- (4- ([3-chloro-4- (3-chlorophenoxy) phenyl] amino] -5H- pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2-methyl-2- (methylsulfonyl) propanamide (400 mg), and the mixture was dissolved by heating at 40 ° C. A chloride solution was added. of hydrogen 4 N / ethyl acetate (0.196 ml) The mixture was allowed to stand at room temperature during 4 days under light protection, and the resulting crystals were collected by filtration. The crystals were washed with clisopropyl ether to give the title compound (401 mg) as pale yellow crystals. XH-NMR (DMS0-d6) d: 1.40 (6H, s), 2.93 (3H, s), 3. 50-3.65 (2H, ra), 4.4.70-4.80 (2H, m), 6.65 (1H, d, J = 3.0 Hz), 6.90-7.00 (1H, m), 7.00-7.05 (1H, m), 7.20-7.25 (1H, m), 7.35 (1H, d, J = 8.7 Hz), 7.45 (1H, t, J = 8.1 Hz), 7.68 (1H, dd, J = 2.4 Hz, 8.7 Hz), 7.89 ( 1H, d, J = 3.0 Hz), 7.94 (1H, d, J = 2.4 Hz), 8.20-8.30 (1H, m), 8.73 (1H, s), 9.89 (1H, br Elemental analysis for C25H26Cl3N5O4S Calculated: C, 50.13; H, 4.38; N, 11.69. Experimental: C, 49.70; H, 4.41; N, 11.4¡ P. f. 194-195 ° C. Example A-19 Production of N- (2- (4- ((3-chloro-4- (-fluoro-3-methylphenoxy) phenyl) amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl) - 2- (methylsulfonyl) acetamide A mixture of tert-butyl [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] carbamate (1.00 g), 3-chloro-4- (4-fluoro- 3-methylphenoxy) aniline (1.51 g) and isopropyl alcohol (10 ml) was stirred at 80 ° C for 12 h. Aqueous sodium bicarbonate was added to the reaction mixture under cooling with ice and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The residue was separated and purified by column chromatography on silica gel (eluent, ethyl acetate: hexane = 60: 40-> 100: 0) to give a crude product (1.52 g). The obtained crude product (150 mg) was dissolved in tetrahydrofuran (22.2 ml). A solution of 4 N hydrogen chloride / ethyl acetate (11.5 ml) was added, and the mixture was stirred at 70 ° C for 20 h. The solvent was evaporated under reduced pressure, ethanol was added, and the mixture was then concentrated. Diisopropyl ether was added, and the precipitated powder was collected by filtration. A mixture of the obtained powder, methylsulfonylacetic acid (74 mg), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (103 mg), 1-hydroxybenzotriazole (72 mg), triethylamine (0.15 ml) and N, N- dimethylformamide (7.0 ml) was stirred at room temperature for 16 h. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine and dried over magnesium sulfate. After concentrating under pressure reduced, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate -> ethyl acetate: methanol = 90:10) and crystallized from diisopropyl ether to give the title compound (116 mg ) in the form of colorless crystals. XH-NMR (DMSO-d6) d: 2.22 (3H, s), 3.10 (3H, s), 3.46 (2H, q, J = 6.0 Hz), 4.04 (2H, s), 4.55 (2H, t, J = 6.0 Hz), 6.49-7.17 (5H, m), 7.61-7.93 (3H, m), 8.33 (1H, s), 8.65-8.66 (2H, m). Example B-l Production of 2- (2- [4- ((5-chloro-6- [3- (trifluoromethyl) phenoxy] pyridin-3-yl} amino) -5H-pyrrolo [3,2-d] pyrimidine-5 -yl] ethoxy.} ethanol (i) Production of 3-chloro-5-nitro-2- [3- (trifluoromethyl) phenoxy] pyridine Under an argon atmosphere, it was added to a solution of 3- (trifluoromethyl) phenol (0.42 g) in tetrahydrofuran (8.0 ml) sodium hydride (60% dispersion in mineral oil, 0.11 g) under ice cooling.After stirring under ice cooling for 1 h, it was added 2. 3-di chloro-5-nitropyridine (0.50 g). After stirring at room temperature for 2.5 h, water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by chromatography on a silica gel column (eluent, hexane: ethyl acetate = 9: 1-> 3: 1) to give the title compound (746). mg) in the form of a colorless oil. XH-NMR (CDC13) d: 7.35-7.43 (1H, m), 7.45-7.51 (1H, m), 7.55-7.65 (1H, ra), 8.61 (1H, d, J = 2.7 Hz), 8.88 (1H , d, J = 2.7 Hz). (ii) Production of 5-chloro-6- [3- (trifluoromethyl) phenoxy] pyridin-3-amine A mixture of 3-chloro-5-nitro-2- [3- (trifluoromethyl) phenoxy] pyridine (746 mg) , reduced iron (0.65 g), calcium chloride (0.13 g) and 15% ethanol with water content (23 ml) was stirred at 80 ° C for 8 h. The solid was removed by filtration, and the filtrate was concentrated under reduced pressure. Water was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by column chromatography on silica gel (eluent, hexane: ethyl acetate = 4: 1- >; 1: 1) for give the title compound (290 mg) as a brown oil. XH-NMR (CDCl 3) d: 3.65 (2H, br s), 7.20 (1H, d, J = 2.9 Hz), 7.22-7.26 (1H, m), 7.27-7.32 (1H, m), 7.37-7.40 ( 1H, m), 7.44-7.50 (1H, m), 7.59 (1H, d, J = 2.9 Hz). (iii) Production of 2- (2- [4- (. {5-chloro-6- [3- (trifluoromethyl) phenoxy] pyridin-3-yl} amino) -5H-pyrrolo [3,2- d] pyrimidin-5-yl] ethoxy.] ethanol A solution of 2- [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethoxy] ethyl benzoate (100 mg ) and 5-chloro-6- [3- (trifluoromethyl) phenoxy] pyridin-3-amine (100 mg) in isopropyl alcohol (2.0 ml) was stirred at 80 [deg.] C. for 16 h. Aqueous sodium bicarbonate was added to the The mixture was extracted with ethyl acetate.The organic layer was washed with saturated brine and dried over magnesium sulfate.After concentrating under reduced pressure, the residue was separated and purified by gel column chromatography. silica (eluant, ethyl acetate: hexane = 1: 1- ^ ethyl acetate) to give 2- {2- {4- (. {5-chloro-6- [3- (trifluoromethyl) benzoate} phenoxy] pyridin-3-yl.} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethoxy.] ethyl (130 mg) in the form of a colorless amorphous. Benzoate 2- (2- [4- (. { 5-Chloro-6- [3- (trifluoromethyl) phenoxy] pyridin-3-yl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethoxy} ethyl (130 mg) in alcohol Isopropyl-tetrahydrofuran (3 ml-2 ml) was added 1N aqueous solution of sodium hydroxide (0.5 ml) at room temperature and the mixture was stirred for 3 h. The reaction mixture was diluted with ethyl acetate, and the organic layer was washed with saturated brine and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate-> ethyl acetate: methanol = 9: 1) to give the title compound (72 mg) in the form of colorless crystals. XH-NMR (CDC13) d: 3.69-3.80 (4H, m), 4.00-4.04 (2H, m), 4.54-4.59 (2H, m), 6.65 (1H, d, J = 3.3 Hz), 7.23 (1H , d, J = 3.3 Hz), 7.31-7.36 (1H, m), 7.40-7.55 (3H, m), 8.24 (1H, d, J = 2.7 Hz), 8.47 (1H, d, J = 2.7 Hz) , 8.51 (1H, s), 8.83 (1H, s). Example B-2 Production of N- (2- [4- (. {5-chloro-6- [3- (trifluoromethyl) phenoxy] pyridin-3-yl} amino) -5H-pyrrolo [3,2-d] pyrimidine -5-yl] ethyl.} -2- (methylsulfonyl) acetamide (i) Production of (2- [4- ((5-chloro-6- [3- (trifluoromethyl) phenoxy] pyridin-3-yl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} tert-butyl carbamate A solution of tert-butyl [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] carbamate (189 mg) and 5-chloro-6- [3- (trifluoromethyl) phenoxy] pyridin-3-amine (184 mg) in isopropyl alcohol (4.0 ml) was stirred at 80 ° C for 20 h. Aqueous sodium bicarbonate was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by column chromatography on silica gel (eluent, hexane: ethyl acetate 1: 1-> ethyl acetate) to give the title compound (257 mg) in the form of a pale yellow solid. XH-NMR (CDC13) d: 1.49 (9H, s), 3.43-4.54 (2H, m), 4. 40-4.51 (2H, m), 5.05-5.15 (1H, m), 6.60 (1H, d, J = 3.0 Hz), 7.19 (1H, d, J = 3.0 Hz), 7.33-7.39 (1H, rn) , 7.41-7.53 (3H, m), 8.39 (1H, d, J = 2.4 Hz), 8.47 (1H, s), 8.64 (1H, d, J = 2.4 Hz), 8.79 (1H, s). (ii) Production of 5- (2-aminoethyl) -N- trichlorohydrate. { 5-Chloro-6- [3- (trifluoromethyl) phenoxy] pyridin-3-yl} -5H-pyrrolo [3,2-d] pyrimidin-4-amine To a solution of. { 2- [4- ( { 5-Chloro-β- [3- (trifluoromethyl) phenoxy] pyridin-3-yl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} tert-butyl carbamate (257 mg) in tetrahydrofuran (10 ml) was added 2 N hydrochloric acid (5.0 ml) at room temperature, and the mixture was stirred at 60 ° C for 20 h. After concentrating under reduced pressure, ethanol was added to the residue, and the mixture became concentrated again. The precipitated solid was collected by filtration and the solid was washed with diisopropyl ether to give the title compound (220 mg) as a pale yellow solid. XH-NMR (DMSO-d6) d: 3.23-3.37 (2H, m), 4.95-5.08 (2H, m), 6.74 (1H, d, J = 2.7 Hz), 7.56 (1H, d, J = 8.4 Hz ), 7.64-7.74 (3H, m), 8.06 (1H, br s), 8.23-8.45 (5H, m), 8.71 (1H, e), 10.15 (1H, br s). (iii) Production of N-. { 2- [4- ( { 5-Chloro-6- [3- (trifluoromethyl) phenoxy] pyridin-3-yl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide A mixture of 5- (2-aminoethyl) -N- trichlorohydrate. { 5-Chloro-6- [3- (trifluoromethyl) phenoxy] pyridin-3-yl} -5H-pyrrolo [3,2-d] pyrimidin-4-amine (95 mg), methylsulfonylacetic acid (47 mg), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (98 mg), 1-hydroxybenzotriazole (78 mg) and triethylamine (0.12 ml) in N, N-dimethylformamide (5.0 ml) was stirred at room temperature for 14 h. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by column chromatography on silica gel (eluent, ethyl acetate → ethyl acetate: methanol = 85:15) to give the title compound (86 mg) in the form of colorless crystals. XH-NMR (CDC13) d: 3.10 (3H, s), 3.62-3.78 (2H, m), 3.98 (2H, s), 4.41-4.53 (2H, m), 6.63 (1H, d, J = 3.0 Hz ), 7.21 (1H, d, J = 3.0 Hz), 7.29-7.55 (5H, m), 8.41-8.50 (4H, m Example B-3 Production of N- (2- [4- (. {5-chloro-6- [3- (trifluoromethyl) phenoxy] pyridin-3-yl} amino) -5H-pyrrolo [3,2-d] pyrimidine -5-yl] ethyl.}. -3-hydroxy-3-methylbutanamide When using 5- (2-aminoethyl) -N- (5-chloro-6- [3- (trifluoromethyl) phenoxy] pyridin-3-trichlorohydrate. il.}. -5H-pyrrolo [3,2-d] pyrimidin-4-amine (95 mg), 3-hydroxy-3-methylbutanoic acid (46 mg), l-ethyl-3- (3-dimethylareneopropyl hydrochloride carbodiiramide (98 mg), 1-hydroxybenzotriazole (78 mg), triethylamine (0.12 ml) and N, N-dimethylformamide (5.0 ml) and in the same manner as in the Example B-2 (iii), the title compound (73 mg) was obtained as colorless crystals. XH-NMR (CDCl 3) d: 1.33 (6H, s), 2.36-2.43 (1H, m), 2. 48 (2H, s), 3.55-3.66 (2H, m), 4.41-4.50 (2H, m), 6.60 (1H, d, J = 3.0 Hz), 7.18-7.22 (2H, m), 7.34-7.39 ( 1H, m), 7.42- 7.53 (3H, m), 8.44 (1H, d, J = 2.4 Hz), 8.47 (1H, s), 8.54 (1H, d, J = 2.4 Hz), 8.97 (1H, s). Example B-4 Production of 2- [4- ((5-chloro-6- [3- (trifluoromethoxy) phenoxy] pyridin-3-yl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethanol (i) Production of 3-chloro-5-nitro-2- [3- (trifluoromethoxy) phenoxy] pyridine Under an argon atmosphere, when using 3- (trifluoromethoxy) phenol (0.93 g), 2,3-dichloro-5- nitropyridine (1.0 g), sodium hydride (60% dispersion in mineral oil, 0.23 g) and tetrahydrofuran (10 ml) and in the same manner as in Example Bl (i), the title compound was obtained (1.57 g). ) in the form of a pale yellow oil XH-NMR (CDCl3) d: 7.06-7.22 (3H, m), 7.49 (1H, t, J = 8.3 Hz), 8.59 (1H, d, J = 2.4 Hz), 8.88 (1H, d, J = 2.4 Hz). (ii) Production of 5-chloro-6- [3- (trifluororatoethoxy) phenoxy] pyridin-3-amine When using 3-chloro-5-nitro-2- [3- (trifluoromethoxy) phenoxy] pyridine (1.57 g), reduced iron (1.31 g), calcium chloride (0.26 g) and 15% ethanol with water content (50 ml) and in the same manner as in Example Bl (ii), the title compound was obtained (1.23 g). ) in the form of an orange oil. XH-NMR (CDC13) d: 3.65 (2H, br s), 6.91-7.02 (3H, m), 7.18 (1H, d, J = 2.7 Hz), 7.35 (1H, t, J = 8.1 Hz), 7.59 (1H, cl, J = 2.7 Hz). (iii) Production of 2- [4- (. {5-chloro-6- [3- (trifluoromethoxy) phenoxy] pyridin-3-yl} amino) -5H-pyrrolo [3,2-d] pyrimidine -5-yl] ethanol A solution of benzoate of 2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl (100 mg) and 5-chloro-6- [3- ( trifluoromethoxy) phenoxy] pyridin-3-amine (101 mg) in isopropyl alcohol (2.0 ml) was stirred at 80 ° C for 2 days. The reaction mixture was cooled to room temperature, 1 N aqueous solution of sodium hydroxide (1.0 ml) was added. The reaction mixture was stirred at room temperature for 4 h, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and Saturated brine, and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by column chromatography (eluent, ethyl acetate-> ethyl acetate: methanol = 9: 1) to give the title compound (112 mg) as colorless crystals. XH-NMR (CDC13) d: 4.11-4.19 (2H, m), 4.39-4.45 (2H, m), 4.83-4.99 (1H, ra), 6.31 (1H, d, J = 3.3 Hz), 7.02-7.10 (4H, m), 7.36-7.42 (1H, m), 8.17 (1H, d, J = 2.7 Hz), 8.31 (1H, e), 8.34 (1H, d, J = 2.7 Hz), 9.44 (1H, s). Example B-5 Production of N-. { 2- [4- ( { 5-chloro-6- [3- (trifluoromethoxy) phenoxy] pyridin-3-yl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide (i) Production of. { 2- [4- ( { 5-Chloro-6- [3- (trifluoromethoxy) phenoxy] pyridin-3-yl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} tert-butyl carbamate When using [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (300 mg), 5-chloro-6- [ 3- (trifluoromethoxy) phenoxy] pyridin-3-amine (308 mg) and isopropyl alcohol (3.0 ml) and in the same manner as in Example B-2 (i), the title compound (372 mg) was obtained as colorless crystals. XH-NMR (CDCl3) d: 1.49 (9H, s), 3.45-3.53 (2H, ra), 4. 43-4.49 (2H, m), 5.10 (1H, t, J = 5.4 Hz), 6.60 (1H, d, J = 3.0 Hz), 7.02-7.12 (3H, m), 7.18 (1H, d, J = 3.0 Hz), 7.36- 7.42 (1H, m), 8.38 (1H, d, J = 2.4 Hz), 8.47 (1H, s), 8.65 (1H, el, J = 2.4 Hz), 8.77 (1H, br s). (ii) Production of 5- (2-aminoethyl) -N- (5-chloro-6- [3- (trifluoromethoxy) phenoxy] pyridin-3-yl] -5H-pyrrolo trichlorohydrate [3,2-d] ] pyrimidin-4-amine When using (2- [4- (. {5-chloro-6- [3- (trifluoromethoxy) phenoxy] pyridin-3-yl} amino) -5H-pyrrolo [3,2 -d] pyrimidin-5-yl] ethyl.} tert-butyl carbamate (350 mg), 2N hydrochloric acid (5.0 ral) and tetrahydrofuran (10 ml) and in the same manner as in Example B-2 ( ii), the title compound (294 mg) was obtained in the form of pale yellow crystals XH-NMR (DMSO-d6) d: 3.20-3.34 (2H, m), 4.91-5.03 (2H, m), 6.66-6.76 (1H, m), 7.20-7.32 (3H, m), 7.59 (1H, t, J = 8.1 Hz), 8.01 (1H, br s), 8.12-8.37 (5H, m), 8.68 (1H , br s), 9.94-10.06 (1H, m). (iii) Production of N-. {2- 2- [4- ( { 5-Chloro-6- [3- (trifluoromethoxy) phenoxy] pyridine-3 -yl.}. amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl.} -2- (methylsulfonyl) acetamide When using 5- (2-aminoethyl) -N- trichlorohydrate { 5- chloro-6- [3- (trifluoromethoxy) phenoxy] pyridin-3-yl} -5H-pyrrolo [3,2-d] pyrimidin-4-amine (90 mg), methylsulfonylacetic acid (43 mg), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (90 mg), monohydrate 1-hydroxybenzotriazole (72 mg), triethylamine (0.12 ml) and N, N-dimethylformamide (5.0 ml) and in the same manner as in Example B-2 (iii), the title compound (59 mg) was obtained in the form of pale yellow crystals. XH-NMR (CDC13) d: 3.10 (3H, s), 3.64-3.75 (2H, m), 3.98 (2H, s), 4.43-4.53 (2H, m), 6.62 (1H, d, J = 3.0 Hz ), 7.03-7.13 (3H, m), 7.15-7.23 (2H, m), 7.41 (1H, t, J = 8.4 Hz), 8.42 (1H, s), 8.44-8.47 (2H, m), 8.49 ( 1H, s). Example B-6 Production of 2- (2- [4- (. {5-chloro-6- [3- (trifluoromethoxy) phenoxy] pyridin-3-yl} amino) -5H-pyrrolo [3,2-d] pyrimidine -5-yl] ethoxy.} Ethanol When using 2- [2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethoxy] ethyl benzoate (100 mg), 5- chloro-6- [3- (trifluoromethoxy) phenoxy] pyridin-3-amine (80 mg), isopropyl alcohol (2.0 ml) and 1 N aqueous sodium hydroxide solution (1.0 ml) and in the same manner as in Example B-4 (iii), the title compound (71 mg) was obtained in the form of Pale yellow crystals. XH-NMR (CDCl3) d: 1.77 (1H, br s), 3.66-3.80 (4H, ra), 4.01 (2H, t, J = 4.5 Hz), 4.56 (2H, t, J = 4.5 Hz), 6.64 (1H, d, J = 3.3 Hz), 7.01-7.09 (3H, m), 7.22 (1H, d, J = 3.3 Hz), 7.36-7.42 (1H, m), 8.25 (1H, d, J = 2.7 Hz), 8-.47 (1H, d, J == 2.7 Hz), 8.49 (1H, s), 8.83 (1H, s). Example B-7 Production of N- (tert-butyl) -3- [(3-chloro-5- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino} pyridin-2-yl) oxy] benzamide (i) Production of methyl 3- [(3-chloro-5-nitropyridin-2-yl) oxy] oxy] benzoate When using methyl 3-hydroxybenzoate (0.83 g), 2.3 Dichloro-5-nitropyridine (1.0 g), sodium hydride (60% dispersion in mineral oil, 0.24 g) and tetrahydrofuran (10 ml) and in the same manner as in Example Bl (i), the compound was obtained of the title (1.61 g) in the form of a colorless oil. XH-NMR (CDCl3) d: 3.93 (3H, s), 7.37-7.41 (1H, m), 7. 52-7.57 (1H, m), 7.84-7.86 (1H, m), 7.98-8.02 (1H, ra), 8.58 (1H, d, J = 2.7 Hz), 8.86 (1H, d, J = 2.7 Hz). (ii) Production of 3- [(3-chloro-5- nitropyridin-2-yl) oxy] benzoic acid To a solution of methyl 3- [(3-chloro-5-nitropyridin-2-yl) oxy] benzoate (1.61 g) in isopropyl alcohol (20 ml) and tetrahydrofuran (10 ml ) 1 N aqueous solution of sodium hydroxide (6.0 ml) was added at room temperature. After stirring at room temperature for 24 h, 1N hydrochloric acid (6.0 ml) was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over magnesium sulfate. After concentrating at reduced pressure, the resulting crystals were collected by filtration. The crystals were washed with diisopropyl ether to give the title compound (0.62 g) as colorless crystals. XH-NMR (CDC13) d: 7.42-7.48 (2H, m), 7.57-7.63 (1H, m), 7.90-7.94 (1H, m), 8.06-8.08 (1H, m), 8.60-8.61 (1H, m), 8.88 (1H, d, J = 2.4 Hz). (iii) Production of N- (tert-butyl) -3 - [(3-chloro-5-nitropyridin-2-yl) oxy] benzamide To a solution of 3- [(3-chloro-5-nitropyridin- 2 -l) oxy] benzoic acid (0.62 g) and N, N-dimethylformamide (0.1 ml) in tetrahydrofuran (12 ml) was added thionyl chloride (0.23 ml) at room temperature. After stirring at room temperature for 2 h, the mixture was concentrated under reduced pressure. A solution of the residue in tetrahydrofuran (10 ml) was added dropwise to a solution of tert-butylamine (0.3 g) and triethylamine (0.89 ml) in tetrahydrofuran (5.0 ml) at 0 ° C. After stirring at room temperature for 20 h, water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by column chromatography (eluent, hexane: ethyl acetate = 9: 1-> 2: 1) to give the title compound (0.61 g) as a pale yellow solid. XH-NMR (CDC13) d: 1.47 (9H, s), 5.93 (1H, br s), 7.28-7.32 (1H, m), 7.52 (1H, t, J = 8.0 Hz), 7.57 (1H, t, J = 2.1 Hz), 7.62-7.65 (1H, m), 8.59 (1H, d, J = 2.4 Hz), 8.87 (1H, d, J = 2.4 Hz). (iv) Production of 3- [(5-amino-3-chloropyridin-2-yl) oxy] -N- (tert-butyl) benzamide When using N- (tert-butyl) -3- [(3-chloro- 5-nitropyridin-2-yl) oxy] benzamide (570 mg), reduced iron (0.46 g), calcium chloride (90 mg) and 15% ethanol with water content (17 ml) and in the same manner as in Example Bl (ii), the title compound (373 rag) was obtained as pale yellow crystals. XH-NMR (CDCl3) d: 1.45 (9H, s), 3.63 (2H, br s), 5.91 (1H, br s), 7.15-7.19 (2H, m), 7.36-7.47 (3H, m), 7.56 (1H, d, J = 2.7 Hz). (v) Production of N- (tert-butyl) -3- [(3-chloro-5- { [5- (2-hydrox? et? l) -5H-pyrrolo [3.2 -d] p? r? m? dm-4-yl] am mo.} p? r? d? n-2-? l) oxy] enzamide When using benzoate of 2- (4-chloro-5H-p) [3, 2-d] pyre Lm? d? n-5-? l) ethyl (80 mg), 3- [(5-ammo-3-chlorop? r? dm-2-yl) ox L] -N- (tert-butyl) benzamide (85 mg), isopropyl alcohol (2.0 ml) and 1 N aqueous solution of sodium hydroxide (1.0 ml) and in the same manner as in Example B-4 (m), obtained the title compound (78 mg) as colorless crystals. XH-NMR (CDC13) d: 1.49 (9H, s), 4.11 (2H, t, J = 4.5 Hz), 4.41 (2H, t, J = 4.5 Hz), 5.44-5.56 (1H, m), 5.98 (1H, s), 6.30 (1H, d, J = 3.0 Hz), 7.06 (1H, d, J = 3.0 Hz), 7.20- 7.28 YH, m), 7.37-7.43 (1H, m), 7.46-7.50 (2H, m), 8.09 (1H, d, J = 2.7 Hz), 8.28 (1H, s), 8.31 (1H, d, J = 2.7 Hz), 9.57 (1H, s). Example C-1 Production of 2-. { 2- [4- ( { 3-chloro-4- [3- (2-met? L-lH-? M? Dazol-1-? L) phenoxy] phenyl}. Amn.) -5H- pyrrolo [3,2-d] pyrimidin-5-l] ethoxy} ethanol (i) Production of 1- [3- (2-chloro-4-nitrophenoxy) phenyl] -2-methyl-1H-imidazole To a solution of 3- (2-methyl-1H-imidazol-1-yl) phenol ( 1.10 g) and 3-chloro-4-fluoronitrobenzene (1.28 g) in N, N-dimethylformamide (10 ml) was added potassium carbonate (1.31 g) and the mixture was stirred at room temperature for 18 h. Brine was added to the reaction mixture under cooling with ice, and the mixture was extracted with ethyl acetate twice, and the organic layer was dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: methanol = 100: 0-> 95: 5) to give the title compound (1.86 g) in the form of a pale yellow oil. XH-NMR (CDC13) d: 2.40 (3H, s), 7.00-7.25 (6H, m), 7. 54 (1H, t, J = 8.2 Hz), 8.12 (1H, dd, J = 2.7, 9.0 Hz), 8.41 (1H, d, J = 2.4 Hz). (ii) Production of 3-chloro-4- [3- (2-methyl-lH-imidazol-1-yl) phenoxy] aniline To a solution of 1- [3- (2-chloro-4-nitrophenoxy) phenyl] -2-methyl-lH-imidazole (1.86 g) in ethyl acetate (30 ml) / methanol (2 ml) was added 5% activated carbon-platinum (0.37 g) under a nitrogen atmosphere. The reaction mixture was stirred under an atmosphere of hydrogen at room temperature for 3.5 h, the platinum-carbon activated was filtered, and the filtrate was concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: hexane = 60: 40-> 100: 0) to give the title compound (1.26 g) as colorless crystals. XH-NMR (CDC13) d: 2.34 (3H, s), 3.73 (2H, br s), 6.58 (1H, dd, J = 2.7, 8.7 Hz), 6.74 (1H, t, J = 2.1 Hz), 6.79 HH, d, J = 2.4 Hz), 6.9-7.05 ( 5H, m), 7.37 (1H, t, J = 8.1 Hz). (iii) Production of 2- (2- [4- ((3-chloro-4- [3- (2-methyl-lH-imidazol-1-yl) phenoxy] phenyl}. amino) -5H-pyrrolo [ 3,2-d] pyrimidin-5-yl] ethoxy.} Ethanol A mixture of 2- [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethoxy] benzoate] ethyl (207 mg), 3-chloro-4- [3- (2-methyl-1H-imidazol-1-yl) phenoxy] aniline (180 mg), 1-methyl-2-pyrrolidone (4.0 ml) and hydrochloride pyridine (139 mg) was stirred at 120 ° C for 17 h, aqueous sodium bicarbonate was added to the reaction mixture and the mixture was extracted with ethyl acetate.The organic layer was washed with brine and dried over magnesium sulfate. Anhydrous After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: methanol = 100: 0-> 95: 5). 1 N of sodium hydroxide (2.6 ml) and tetrahydrofuran (5 ml) and the The mixture was stirred at room temperature for 3 days. The reaction mixture was neutralized with 1N hydrochloric acid, and aqueous sodium bicarbonate and brine were added. The mixture was extracted with ethyl acetate and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by column chromatography on silica gel (eluent, ethyl acetate: methanol = 100: 0-> 95: 5) and the solid obtained was collected by filtration and washed with diisopropyl ether to give the title compound (158 mg) as a white powder. XH-NMR (CDC13) d: 2.35 (3H, s), 3.70-3.75 (2H, m), 3.75-3.85 (2H, m), 4.02 (2H, t, J = 4.4 Hz), 4.57 (2H, t , J = 4.4 Hz), 6.64 (1H, d, J = 3.0 Hz), 6.80-6.85 (1H, ra), 6.95-7.05 (4H, m), 7.11 (2H, d, J = 9.0 Hz), 7.22 (1H, d, J = 3.6 Hz), 7.40 (1H, t, J = 8.4 Hz), 7.64 (1H, dd, J = 2.4, 9.0 Hz), 7.90 (1H, d, J = 2.4 Hz), 8.53 (1H, s), 8.82 (1H, s). Example C-2 [3- (1, 3-oxazol-5-yl) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethoxy} ethanol (i) Production of 5- [3- (benzyloxy) phenyl] -1,3-oxazole To a solution of 3- (benzyloxy) benzaldehyde (2.12 g) and p-toluenesulfonylmethyl isocyanide (1.95 g) in methanol (40 ml) was added potassium carbonate (1.66 g) under ice-cooling, and the mixture was stirred at room temperature for 20 min. and refluxed for 1 h. After concentrating under reduced pressure, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: hexane = 20: 80-> 50:50) to give the title compound (2.04 g) as a white powder. XH-NMR (CDC13) d: 5.12 (2H, s), 6.90-7.00 (1H, m), 7.25-7.50 (9H, m), 7.91 (1H, s). (ii) Production of 3- (1, 3-oxazol-5-yl) phenol To a solution of 5- [3- (benzyloxy) phenyl] -1,3-oxazole (2.01 g) in raetanol (10 ml) / tetrahydrofuran (10 ml) was added palladium-activated carbon 10% (0.40 g) and the mixture was stirred under an atmosphere of hydrogen at room temperature for 5 h. Palladium activated carbon was filtered, and the filtrate was concentrated under reduced pressure. The precipitate was washed with diisopropyl ether and hexane to give the title compound (1.25 g) as pale gray crystals.

XH-NMR (95% CDCl3 + 5% DMSO-d6) d: 6.80-6.90 (1H, m), 7.10-7.20 (2H, m), 7.24 (1H, t, J = 8.0 Hz), 7.31 (1H, s), 7.94 (1H, s), 9.13 (1H, s). (iii) Production of 5- [3- (2-chloro-4-nitrophenoxy) phenyl] -1,3-oxazole To a solution of 3- (1,3-oxazol-5-yl) phenol (1.20 g) and 3-chloro-4-fluoronitrobenzene (1.45 g) in N, N-dimethylformamide (10 ml) was added potassium carbonate (1.54 g) and the mixture was stirred at room temperature for 18 h. To the reaction mixture was added brine under cooling with ice, and the mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was recrystallized from ethyl acetate / diisopropyl ether / hexane to give the title compound (2.00 g) as pale yellow crystals. XH-NMR (CDC13) d: 6.96 (1H, t, J = 9.0 Hz), 7.00-7.10 (1H, m), 7.35-7.45 (2H, m), 7.45-7.60 (2H, m), 7.93 (1H , s), 8.08 (1H, dd, J = 3.0 Hz, 9.0 Hz), 8.40 (1H, d, J = 3.0 Hz). (iv) Production of 3-chloro-4- [3- (1, 3-oxazol-5-yl) phenoxy] aniline When using 5- [3- (2-chloro-4-nitrophenoxy) phenyl] -1, 3 -oxazole (1.95 g), 5% activated carbon platinum (0.33 g) and ethyl acetate (30 ml) / raetanol (5 ml) and in the same manner that in Example C-1 (ii), the title compound (1.80 g) was obtained in the form of pale yellow crystals. XH-NMR (95% CDCl3 + 5% DMSO-d6) d: 6.8-6.9 (2H, m), 6.95-7.05 (2H, m), 7.15-7.2 (2H, m), 7.3-7.4 (3H, m ), 7.91 (1H, s), 8.09 (1H, s). (v) Production of 2-. { 2- [4- ( { 3-chloro-4- [3- (1, 3-oxazol-5-yl) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethoxy} ethanol A mixture of 2- [2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethoxy] ethyl benzoate (346 mg), 3-chloro-4- [3- ( 1,3-oxazol-5-yl) phenoxy] aniline (344 mg) and isopropyl alcohol (10 ml) was stirred at 80 ° C for 18 h. Aqueous sodium bicarbonate was added to the reaction mixture under cooling with ice and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: methanol = 100: 0-> g.; 95: 5). Aqueous 1 N aqueous solution of sodium hydroxide (0.8 ml) and tetrahydrofuran (4.0 ml) were added to the obtained compound, and the mixture was stirred at room temperature for 2 days. The reaction mixture was neutralized with 1N hydrochloric acid, and aqueous sodium bicarbonate and brine were added. The mixture was extracted with ethyl acetate, and the extract was dried over anhydrous magnesium sulfate. After concentrating At reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: methanol = 100: 0- »95: 5) to give the title compound (26 mg) as a pale yellow powder. XH-NMR (CDC13) d: 3.70-3.75 (2H, m), 3.75-3.85 (2H, m), 4.03 (2H, t, J = 4.5 Hz), 4.58 (2H, t, J = 4.5 Hz), 6.64 (1H, c, J = 3.0 Hz), 6.90-6.95 (1H, m), 7.08 (1H, d, J = 9.0 Hz), 7.22 (1H, d, J = 3.3 Hz), 7.25-7.30 (1H, m), 7.30-7.40 (3H, m), 7.61 (1H, dd, J = 2.4 Hz, 9.0 Hz), 7.89 (2H, d, J = 2.1 Hz), 8.53 (1H, s), 8.78 (1H, s). Example C-3 Production of 2-. { 2- [4- ((3-chloro-4- [3- (1, 3-thiazol-5-yl) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidine-Sil] ethoxy.} ethanol (i) Production of 5- [3- (2-chloro-4-nitrophenoxy) phenyl] -1,3-thiazole When using 3- (1, 3-thiazol-5-yl) phenol (343 mg), 3-chloro-4-fluoronitrobenzene (429 mg), potassium carbonate (401 mg) and N, N-dimethylformamide (5.0 ml) and in the same manner as in Example C-1 (i), was obtained the title compound (624 mg) in the form of a colorless oil. XH-NMR (CDCl3) d: 6.96 (1H, t, J = 9.3 Hz), 7.00-7.10 (1H, m), 7.30-7.35 (1H, m), 7.50-7.55 (2H, m), 8.07 (1H , d, J == 2.7 Hz), 8.10-8.15 (1H, m), 8.41 (1H, d, J = 2.4 Hz), 8.79 (1H, d, J = 0.6 Hz). (ii) Production of 2- (2- [4- ((3-chloro-4- [3- (1, 3-thiazol-5-yl) phenoxy] phenyl} amino) -5H-pyrrolo [3, 2-d] pyrimidin-5-yl] ethoxy.] Ethanol A mixture of the compound obtained using 5- [3- (2-chloro-4-nitrophenoxy) phenyl] -1,3-thiazole (624 rag), platinum- 5% activated carbon (312 mg) and ethyl acetate (10 ml) and in the same manner as in Example Cl (ii), 2- [2- (4-chloro-5H-pyrrolo [3,2] benzoate -d] pyrimidin-5-yl) ethoxy] ethyl (450 mg) and isopropyl alcohol (10 ml) was stirred at 80 ° C for 20 h, aqueous sodium bicarbonate was added to the reaction mixture under cooling with ice, and the mixture was extracted with ethyl acetate.The organic layer was washed with brine and dried over anhydrous magnesium sulfate.The residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: methanol = 100 : 0-> 95: 5.) To the obtained compound, 1 N aqueous solution of sodium hydroxide (2.2 ml) and tetrahydrofur were added. anion (5 ml) and the mixture was stirred at room temperature for 2 days. The reaction mixture was neutralized with 1N hydrochloric acid, and aqueous sodium bicarbonate and brine were added. The The mixture was extracted with ethyl acetate and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: methanol = 100: 0-> 95: 5) and then washed with diisopropyl ether to give the compound of the title (63.5 mg) in the form of a pale yellow powder. XH-NMR (CDC13) d: 3.70-3.85 (4H, m), 4.00-4.10 (2H, m), 4.50-4.60 (2H, m), 6.64 (1H, d, J = 3.0 Hz), 6.85-6.95 (1H, rn), 7.08 (1H, d, J = 8.7 Hz), 7.20-7.40 (4H, m), 7.61 (1H, dd, J = 2.4, 8.7 Hz), 7.90 (1H, d, J = 2.4 Hz), 8.06 (1H, s), 8.53 (1H, s), 8.75 (1H, s), 8.78 (1H, s).

Production of 2-. { 2- [4- ( { 3-chloro-4- [3- (4-methyl-l, 3-oxazol-2-yl) phenoxy] phenyl} amino) -5H-pyrrolo [3, 2- d] pyrimidin-5-yl] ethoxy} ethanol (i) Production of 2- (3-Rethoxyphenyl) -4-methyl-l, 3-oxazole A suspension of 3-methoxybenzamide (4.91 g) and chloroacetone (3.61 g) in toluene (30 ml) was stirred at 110 ° C. C for 2 days. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed successively with aqueous sodium bicarbonate and brine, and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: hexane = 10: 90 → 30: 70) to give the title compound (1.54 g) in shape of a yellow oil. XH-NMR (CDC13) d: 2.25 (3H, s), 3.88 (3H, s), 6.95-7.05 (1H, m), 7.35 (1H, t, J = 8.0 Hz), 7.40-7.45 (1H, m), 7.50-7.65 (2H, m). (ii) Production of 3- (4-methyl-l, 3-oxazol-2-yl) phenol A solution (10 ml) of 2- (3-methoxyphenyl) -4-methyl-1,3-oxazole (1.54 g) ) in 48% hydrobromic acid was heated to reflux for 24 h. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with aqueous sodium bicarbonate and brine, and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: hexane = 10: 90-> g.; 40: 60) to give the title compound (1.14 g) as a white powder. XH-NMR (CDCl 3) d: 2.24 (3H, s), 6.09 (1H, br s), 6.90-7.00 (1H, m), 7.30 (1H, t, J = 8.0 Hz), 7.40-7.45 (1H, m), 7.50-7.60 (2H, m). (iii) Production of 2- [3- (2-chloro-4-nitrophenoxy) phenyl] -4-methyl-l, 3-oxazole When using 3- (4-methyl-l, 3-oxazol-2-yl) phenol (1.09 g), 3-chloro-4-fluoronitrobenzene (1.21 g), potassium carbonate (1.29 g) and N, N-dimethylformamide (10 ml) and in the same manner as in Example C-1 (i), the title compound was obtained (1.86 g) in the form of a pale yellow oil. XH-NMR (CDC13) d: 2.38 (3H, s), 6.94 (1H, t, J = 9.2 Hz), 7.10-7.20 (1H, m), 7.40-7.45 (1H, ra), 7.53 (1H, t , J = 8.0 Hz), 7.70-7.75 (1H, m), 7.85-7.95 (1H, m), 8.07 (1H, dd, J = 2.6, 9.2 Hz), 8.40 (1H, d, J = 2.6 Hz) . (iv) Production of 3-chloro-4- [3- (4-methyl-l, 3-oxazol-2-yl) phenoxy] aniline When using 2- [3- (2-chloro-4-nitrophenoxy) phenyl] -4-methyl-1,3-oxazole (1.86 g), 5% activated carbon-platinum (0.31 g) and ethyl acetate (20 ml) and in the same manner as in Example Cl (ii), was obtained the title compound (0.41 g) as a colorless oil. XH-NMR (CDCI3) d: 2.23 (3H, s), 3.69 (2H, br s), 6. 58 (1H, dd, J = 2.7 Hz, 9.0 Hz), 6.80 (1H, d, J = 3.0 Hz), 6.96 (1H, d, J = 6.9 Hz), 6.95-7.00 (1H, m), 7.36 ( 1H, t, J = 8.0 Hz), 7.35-7.40 (1H, m), 7.50-7.55 (1H, m), 7.70-7.75 (1H, m). (v) Production of 2- (2- [4- ( { 3-chloro-4- [3- (4-methyl- 1,3-oxazol-2-yl) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethoxy} ethanol When using 2- [2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethoxy] ethyl benzoate (392 mg), 3-chloro-4- [3- (4 methyl-1, 3-oxazol-2-yl) phenoxy] aniline (410 mg) and isopropyl alcohol (10 ml), the reaction was carried out in the same manner as in Example C-2 (v). Then, the obtained compound was reacted in the same manner as in Example C-2 (v) and 1 N aqueous solution of sodium hydroxide (4.7 ml) and tetrahydrofuran (10 ml) was used to give the title compound ( 371 mg) in the form of a white powder. iH-NMR (CDC13) d: 2.21 (3H, s), 3.65-3.85 (4H, m), 4.02 (2H, t, J = 4.4 Hz), 4.57 (2H, t, J = 4.4 Hz), 6.62 ( 1H, d, J = 3.2 Hz), 7.05-7.15 (2H, m), 7.20 (1H, d, J = 3.0 Hz), 7.30-7.45 (2H, m), 7.50-7.55 (1H, m), 7.62 (1H, dd, J = 2.6 Hz, 8.8 Hz), 7.70-7.75 (1H, m), 7.90 (1H, d, J = 2.6 Hz), 8.52 (1H, s), 8.79 (1H, s). Example C-5 Production of 2-. { 2- [4- ( { 4- [3- (4-tert-Butyl-l, 3-oxazol-2-yl) phenoxy] -3-chlorophenyl} amino) -5H-pyrrolo [3, 2 -d] pyrimidin-5-yl] ethoxy} ethanol (i) Production of 4-tert-butyl-2- (3-methoxyphenyl) -1,3-oxazole When using 3-methoxybenzamide (1.51 g), 1-bromopinacolone (2.15 g) and toluene (10 ml) and the In the same manner as in Example C-4 (i), the title compound (2.01 g) was obtained in the form of a pale yellow oil. XH-NMR (CDC13) d: 1.32 (9H, s), 3.88 (3H, s), 6.96 (1H, dd, J = 2.6 Hz, 8.4 Hz), 7.30-7.40 (2H, m), 7.55-7.65 ( 2H, m). (ii) Production of 3- (4-tert-butyl-l, 3-oxazol-2-yl) phenol When using 4-tert-butyl-2- (3-methoxyphenyl) -1, 3-oxazole (2.01 g) and 48% hydrobromic acid (10 ml) and in the same manner as in Example C-4 (ii), the title compound (0.62 g) was obtained as a pale yellow powder. XH-NMR (CDCl3) d: 1.31 (9H, s), 5.20-5.50 (1H, ra), 6.90 (1H, dd, J = 1.8 Hz, 8.0 Hz), 7.31 (1H, d, J = 7.6 Hz) , 7.36 (1H, s), 7.45-7.55 (1H, m), 7.58 (1H, d, J = 7.2 Hz). (iii) Production of 4-tert-butyl-2- [3- (2-chloro-4-nitrophenoxy) phenyl] -1,3-oxazole When using 3- (4-tert-butyl-l, 3-oxazole- 2-yl) phenol (1.48 g), 3-chloro-4-fluoronitrobenzene (1.26 g), potassium carbonate (1.41 g) and N, N-diraethylformamide (12 ml) and the same so that in Example C-1 (i), the title compound (2.13 g) was obtained in the form of a white powder. XH-NMR (CDCl 3) d: 1.31 (9H, s), 6.92 (1H, t, J = 9.3 Hz), 7.10-7.20 (1H, m), 7.37 (1H, s), 7.51 (1H, t, J = 8.1 Hz), 7.75-7.80 (1H, m), 7.94 (1H, t, J = 7.8 Hz), 8.06 (1H, dd, J = 2.7 Hz, 9.3 Hz), 8.40 (1H, d, J = 2.7 Hz). (iv) Production of 4- [3- (4-tert-butyl-l, 3-oxazol-2-yl) fer.oxi] -3-chloroaniline When using 4-tert-butyl-2- [3- (2 -chloro-4-nitrophenoxy) phenyl] -1,3-oxazole (1.12 g), 5% activated carbon-platinum (0.19 g) and ethyl acetate (20 ml) / methanol (4 ml) and in the same manner that in Example Cl (ii), the title compound (985 mg) was obtained as a colorless oil. XH-NMR (CDCl 3) d: 1.30 (9H, s), 3.68 (2H, br s), 6. 58 (1H, dd, J = 2.6, 8.4 Hz), 6.80 (1H, d, J = 2.6 Hz), 6.85-6.95 (2H, m), 7.33 (2H, t, J = 8.4 Hz), 7.55-7.60 (1H, m), 7.70-7.75 (1H, m). (v) Production of 2-. { 2- [4- ( { 4- [3- (4-tert-Butyl-l, 3-oxazol-2-yl) phenoxy] -3-chlorophenyl} amino) -5H-pyrrolo [3, 2 -d] pyrimidin-5-yl] ethoxy} ethanol When using 2- [2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethoxy] ethyl benzoate (444 rag), 4- [3- (4-tert-butyl -l, 3-oxazol-2-yl) phenoxy] -3-chloroaniline (660 mg) and isopropyl alcohol (10 ml), the reaction was carried out therefrom as in Example C-2 (v). Then, the obtained compound was reacted in the same manner as in Example C-2 (v) and 1N aqueous solution of sodium hydroxide (6.0 ml) and tetrahydrofuran (12 ml) was used to give the title compound ( 316 mg) in the form of a white powder. ^ -RMN (CDC13) d: 1.30 (9H, s), 3.70-3.80 (4H, m), 4.02 (2H, t, J = 4.2 Hz), 4.56 (2H, t, J = 4.2 Hz), 6.62 ( 1H, d, J = 3.3 Hz), 7.00 (1H, dd, J = 2.4 Hz, 8.4 Hz), 7.05 (1H, d, J = 8.7 Hz), 7.20 (1H, d, J = 3.3 Hz), 7.34 (1H, s), 7.37 (1H, t, J = 7.8 Hz), 7.59 (1H, dd, J = 2.4 Hz, 9.0 Hz), 7.60-7.65 (1H, m), 7.75 (1H, d, J = 7.8 Hz), 7.89 (1H, d, J = 2.7 Hz), 8.51 (1H, s), 8.77 (1H, s). Example C-6 Production of 2-. { 2- [4- ((4- [3- (4-tert-butyl-l, 3-thiazol-2-yl) phenoxy] -3-chlorophenyl} amino) -5H-pyrrolo [3,2-d ] pyrimidin-5-yl] ethoxy.} ethanol (i) Production of 3-methoxybenzenecarbothioamide A mixture of 3-methoxybenzonitrile (9.32 g), 0.0-diethyldithiophosphate (11.85 ml) and 4 N hydrochloric acid (70 ml) it was stirred at room temperature for 20 h. The precipitate was collected by filtration, and washed with ethyl acetate and liisopropyl ether to give the title compound (8.51 g) as a pale green powder. XH-NMR (CDC13) d: 3.27 (2H, br s), 3.89 (3H, s), 7. 10-7.20 (1H, m), 7.36 (1H, t, J = 7.8 Hz), 7.40-7.50 (1H, m), 7.50-7.60 (1H, m). (ii) Production of 4-tert-butyl-2- (3-methoxyphenyl) -1,3-thiazole A solution of 3-methoxybenzenecarbothioamide (4.18 g) and 1-bromopinacolone (4.48 g) in ethanol (50 ml) was stirred at room temperature for 1 h. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed successively with aqueous sodium bicarbonate and brine, and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: hexane = 0: 100-> 10: 90) to give the title compound (4.91 g). ) in a colorless oil foil. XH-NMR (CDCl 3) d: 1.39 (9H, s), 3.88 (3H, s), 6.88 (1H, s), 6.90-7.00 (1H, m), 7.32 (1H, t, J = 8.1 Hz), 7.50-7.60 (2H, m). (iii) Production of 3- (4-tert-butyl-l, 3-thiazol-2-yl) phenol When using 4-tert-butyl-2- (3-methoxyphenyl) -1,3-thiazole (4.91 g) and 48% hydrobromic acid (30 ml) and in the same manner as in Example C-4 (ii) , the title compound (3.59 g) was obtained as a colorless oil. XH-NMR (CDC13) d: 1.40 (9H, s), 5.08 (1H, s), 6.80-6.85 (1H, m), 6.89 (1H, s), 7.28 (1H, t, J = 8.0 Hz), 7.45-7.55 (2H, m). (iv) Production of 4-tert-butyl-2- [3- (2-chloro-4-nitrophenoxy) phenyl] -1,3-thiazole When using 3- (4-tert-butyl-l, 3-thiazole- 2-yl) phenol (3.13 g), 3-chloro-4-fluoronitrobenzene (2.48 g), potassium carbonate (2.78 g) and N, N-dimethylformamide (24 ral) and in the same manner as in Example C- 1 (i), the title compound (1.49 g) was obtained as a pale yellow oil. XH-NMR (CDCl3) d: 1.38 (9H, s), 6.93 (2H, t, J = 4.6 Hz), 7.05-7.15 (1H, m), 7.49 (1H, t, J = 8.0 Hz), 7.75- 7.80 (1H, m), 7.80-7.90 (1H, m), 8.06 (1H, dd, J = 2.6, 8.8 Hz), 8.40 (1H, d, J = 2.6 Hz). (v) Production of 4- [3- (4-tert-butyl-l, 3-thiazol-2-yl) phenoxy] -3-chloroaniline When using 4-tert-butyl-2- [3- (2-chloro -4-nitrophenoxy) phenyl] -1,3-thiazole (1.49 g), 5% activated carbon-platinum (0.25 g) and ethyl acetate (10 ml) and in the same manner as in Example Cl (ii) , the compound of the title (1.37 g) in the form of a pale yellow oil. XH-NMR (CDCl3) d: 1.38 (9H, s), 3.68 (2H, br s), 6.58 (1H, dd, J = 2.8, 8.6 Hz), 6.80-6.95 (4H, m), 7.30 (1H, t, J = 8.1 Hz), 7.55-7.65 (2H, m). (vi) Production of 2-. { 2- [4- ( { 4- [3- (4-tert-butyl-l, 3-thiazol-2-yl) phenoxy] -3-chlorophenyl} amino) -5H-pyrrolo [3,2 -d] pyriraidin-5-yl] ethoxy} ethanol When using 2- [2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethoxy] ethyl benzoate (277 mg), 4- [3- (4-tert-butyl -l, 3-thiazol-2-yl) phenoxy] -3-chloroaniline (359 mg) and isopropyl alcohol (5.0 ml), the reaction was carried out in the same manner as in Example C-2 (v). Then, the obtained compound was reacted in the same manner as in Example C-2 (v) and 1 N aqueous solution of sodium hydroxide (3.7 ral) and tetrahydrofuran (7.5 ml) was used to give the title compound ( 163 mg) in the form of a white powder. XH-NMR (CDCl3) d: 1.39 (9H, s), 3.70-3.80 (4H, ra), 4. 02 (2H, t, J = 4.5 Hz), 4.57 (2H, t, J = 4.5 Hz), 6.63 (1H, d, J = 3.3 Hz), 6.89 (1H, s), 6.92 (1H, d, J = 2.4 Hz), 7.05 (1H, d, J = 9.0 Hz), 7.21 (1H, d, J = 3.0 Hz), 7.34 (1H, t, J = 8.4 Hz), 7.58 (1H, dd, J = 2.4 Hz, 8.7 Hz), 7.65-7.70 (2H, m), 7.89 (1H, d, J = 2.4 Hz), 8.52 (1H, s), 8.75 ( 1H, s).

Example C-7 Production of 2- (2- { - [(3-chloro-4- (3- [4- (trifluoromethyl) -1,3-thiazol-2-yl] phenoxy] phenyl) amino] -5H- pyrrolo [3, 2-d] pyrimidin-5-yl.} ethoxy) ethanol (i) Production of 2- (3-methoxyphenyl) -4- (trifluoromethyl) -1,3-thiazole When using 3-methoxybenzenecarbothioamide (4.18) g), 3-bromo-1,1, 1-trifluoroacetone (4.77 g) and ethanol (50 ral) and in the same manner as in Example C-6 (ii), the title compound (4.29 g) was obtained in the form of a pale yellow oil XH-NMR (CDC13) d: 3.90 (3H, s), 6.95-7.05 (1H, m), 7.37 (1H, d, J = 8.2 Hz), 7.50-7.60 (2H, m), 7.73 (1H, d, J = 1.0 Hz) (ii) Production of 3- [4- (trifluoromethyl) -1,3-thiazol-2-yl] phenol When using 2- (3-methoxyphenyl) - 4- (trifluoromethyl) -1,3-thiazole (4.23 g) and 48% hydrobromic acid (30 ml) and in the same manner as in Ejeraplo C-4 (ii), the compound of the title (4.61 g) in the form of a yellow oil. XH-NMR (CDCl3) d: 5.10-5.50 (1H, m), 6.90-7.00 (1H, m), 7.33 (1H, t, J = 8.1 Hz), 7.50-7.60 (2H, m), 7.73 (1H , s). (iii) Production of 2- [3- (2-chloro-4-nitrophenoxy) phenyl] -A- (trifluoromethyl) -1,3-thiazole When using 3- [4- (trifluoromethyl) -1,3-thiazole- 2-yl] phenol (4.00 g), 3-chloro-4-fluoronitrobenzene (3.01 g), potassium carbonate (3.38 g) and N, N-dimethylformamide (20 ml) and in the same manner as in Example C- 1 (i), the title compound (4.82 g) was obtained as a pale yellow powder. XH-NMR (CDCl 3) d: 6.96 (1H, t, J = 9.0 Hz), 7.15-7.25 (1H, m), 7.55 (1H, t, J = 8.1 Hz), 7.75-7.80 (2H, m), 7.85 (1H, t, J = 8.1 Hz), 8.09 (1H, dd, J = 2.7 Hz, 9.0 Hz), 8.41 (1H, d, J = 2.7 Hz). (iv) Production of 3-chloro-4- (3- [4- (trifluoromethyl) -1,3-thiazol-2-yl] phenoxy]. aniline When using 2- [3- (2-chloro-4- nitrophenoxy) phenyl] -4- (trifluoromethyl) -1,3-thiazole (2.00 g), 5% activated carbon-platinum (0.33 g) and ethyl acetate (15 ml) and in the same manner as in Example Cl (ii), the title compound (1.87 g) was obtained as a colorless oil: XH-NMR (CDCl 3) d: 3.70 (2H, br s), 6.59 (1H, dd, J = 2.7 Hz, 8.7 Hz ), 6.81 (1H, d, J = 2.7 Hz), 6.94 (2H, d, J = 8. 7 Hz), 7.36 (1H, t, J = 8.1 Hz), 7.50-7.55 (1H, m), 7.63 (1H, d, J = 7.5 Hz), 7.73 (1H, s). (v) Production of 2- (2-. {4- [(3-chloro-4-. {3- [4- (trifluoromethyl) -1,3-thiazol-2-yl] phenoxy] phenyl ) amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl.} ethoxy) ethanol When using 2- [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin benzoate] -5-yl) ethoxy] ethyl (262 mg), 3-chloro-4-. { 3- [4- (trifluoromethyl) -1,3-thiazol-2-yl] phenoxy} aniline (338 mg) and isopropyl alcohol (5.0 ml), the reaction was carried out in the same manner as in Example C-2 (v). Then, the obtained compound was reacted in the same manner as in Example C-2 (v) and 1 N aqueous solution of sodium hydroxide (3.4 ml) and tetrahydrofuran (7 ml) was used to give the title compound ( 173 mg) in the form of a white powder. XH-NMR (CDC13) d: 3.70-3.85 (4H, m), 4.02 (2H, t, J = 4.5 Hz), 4.57 (2H, t, J = 4.5 Hz), 6.63 (1H, d, J = 3.3 Hz), 7.00-7.10 (1H, m), 7.08 (1H, d, J = 8.7 Hz), 7.21 (1H, d, J = 3.0 Hz), 7.39 (1H, t, J = 8.0 Hz), 7.6-7.65 (2H, m), 7.67 (1H, d, J = 7.8 Hz), 7.74 (1H, s ), 7.91 (1H, d, J = 2.7 Hz), 8.52 (1H, s), 8.79 (1H, s).

Example C-8 Production of N- (2- (4- [(3-chloro-4-. {3- [4- (trifluoromethyl) -1,3-thiazol-2-yl] phenoxy] phenyl) amino] -5H -pyrrolo [3,2-d] pyrimidin-5-yl.} ethyl) -2- (methylsulfonyl) acetamide (i) Production of (2- { - [(3-chloro-4- (3- [ 4- (Trifluoromethyl) -1,3-thiazol-2-yl] phenoxy] phenyl) amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl.} Ethyl) tert-butyl carbamate A mixture of tert-butyl [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] carbamate (1.01 g), 3-chloro-4-. {3- [4- (trifluoromethyl) -1,3-thiazol-2-yl] phenoxy] aniline (1.51 g) and isopropyl alcohol (10 ml) was stirred at 80 ° C. for 12 h. Aqueous sodium bicarbonate was added while cooling with ice, and the mixture was extracted with ethyl acetate.The organic layer was washed with brine and dried over anhydrous magnesium sulfate.After concentrating under reduced pressure, the residue was separated and purified by column chromatography on silica gel (e luyente, ethyl acetate: hexane = 60: 40- > 100: 0). The solid obtained was collected by filtration, washed with ether dnsopropyl and hexane to give the title compound (1.88 g) as a white powder. XH-NMR (CDCl3) d: 1.50 (9H, s), 3.45-3.55 (2H, m), 4.45-4.55 (2H, m), 5.05-5.15 (1H, m), 6.61 (1H, d, J = 1.5 Hz), 7.00-7.10 (2H, m), 7.18 (1H, d, J = 2.1 Hz), 7.40 (1H, t, J = 8.5 Hz), 7.65 (1H, s), 7.68 (1H, d, J = 7.5 Hz), 7.74 (1H, 3), 7.89 (1H, d, J = 9.0 Hz), 8.03 (1H, s), 8.51 (1H, s), 8.61 (1H, br s). (11) Production of 5- (2-aminoethyl) -N- (3-chloro-4- (3- [4- (tnfluoromethyl) -1,3-t-azol-2-yl] phenoxy dihydrochloride} fen?) -5H-pyrrolo [3,2-d] p? r? m? dm-4-am? na A mixture of (2- {4- [(3-chloro-4)} - (3- [4- (tpf1-uoromethyl) -1,3-t-azole-2-? L] phenoxy?}. Phenol) amino] -5H-pyrrolo [3,2-d] p? R ? m? dm-5-? l.) ethyl) tert-butyl carbamate (1.70 g) and 10% hydrochloric acid (w / w) / methanol (12 ml) was stirred at 65 ° C for 4 h. The reaction mixture was concentrated under reduced pressure, and the precipitate was collected by filtration, and washed with diethyl ether to give the title compound (1.53 g) as pale yellow crystals XH-NMR (DMSO-d6 ) d: 3.25-3.35 (2H, m), 5.00-5.10 (2H, ra), 6.75 (1H, d, J = 3.3 Hz), 7.17 (1H, dd, J = 2.4, 8.1 Hz), 7.35 (1H , d, J = 8.7 Hz), 7.5-7.7 (3H, m), 7.78 (1H, d, J = 7.8 Hz), 7.93 (1H, d, J = 2.4 Hz), 8.07 (1H, d, J = 3.0 Hz), 8.20-8.40 (3H, m), 8.61 (1H, s), 8.72 (1H, s), 10.10 (1H, br s). (iii) Production of N- (2- {4- [(3-chloro-4- (3- [4- (trifluoromethyl) -1,3-thiazol-2-yl] phenoxy} phenyl) amino ] -5H-pyrrolo [3,2-d] pyrimidin-5-yl.} Ethyl) -2- (methylsulfonyl) acetamide To a solution of 5- (2-aminoethyl) -N- (3-chloro-) dihydrochloride 4- { 3- [4- (trifluoromethyl) -1,3-thiazol-2-yl] phenoxy] phenyl) -5H-pyrrolo [3,2-d] pyrimidin-4-amine (200 mg) , methylsulfonylacetic acid (69 mg) and 1-hydroxybenzotriazole (75 mg) in N, N-dimethylformamide (5.0 ml) were added triethylamine (0.23 ml) and l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (105 mg ) under cooling with ice, and the mixture was stirred at room temperature for 6 h.Water was added to the reaction mixture and the mixture was extracted with ethyl acetate.The organic layer was washed with brine and dried over magnesium sulfate. Anhydrous After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluted nte, ethyl acetate: methanol = 100: 0- > 95: 5) and then recrystallized from ethyl acetate / diisopropyl ether to give the title compound (179 mg) as colorless crystals. XH-NMR (CDC13) d: 3.12 (3H, s), 3.65-3.75 (2H, m), 3.98 (2H, s), 4.45-4.55 (2H, m), 6.60-6.65 (1H, m), 7.08 (2H, d, J = 9.0 Hz), 7.21 (1H, d, J = 3.0 Hz), 7.25-7.30 (2H, m), 7.42 (1H, t, J = 8.0 Hz), 7.65-7.75 (2H, ra), 7.75 (1H, s), 7. 95 (1H, s), 8.20 (1H, s), 8.51 (1H, s; Example C-9) Production of N- (tert-butyl) -3- [2-chloro-4- ((5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2- d] pyrimidin-4-yl} amino) phenoxy] benzamide (i) Production of diphenylmethyl 3-hydroxybenzoate To a solution of 3-hydroxybenzoic acid (2.76 g) in acetone (40 ml) was added diphenyldiazomethane (3.88 g) under ice-cooling, and the mixture it was stirred at room temperature overnight The reaction mixture was concentrated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, ethyl acetate: hexane = 15: 85-> 35:65 The object fractions were concentrated under reduced pressure to give the title compound (5.16 g) as a pale yellow oil XH-NMR (CDC13) d: 5.13 (1H, s), 7.03-7.08 (1H , m), 7.10 (1H, s), 7.25-7.46 (11H, m), 7.58-7.62 (1H, m), 7.70-7.76 (1H, m). (ii) Production of diphenylmethyl 3- (2-chloro-4-nitrophenoxy) benzoate A mixture of 2-chloro-1-fluoro-4-nitrobenzene (2.81 g), diphenylmethyl 3-hydroxybenzoate (5.16 g), carbonate potassium (3.32 g) and N, N-dimethylformamide (50 ml) was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure, water was added and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, diisopropyl ether was added to the obtained residue, and the precipitated solide was collected by filtration to give the title compound (6.93 g) as a colorless powder. XH-NMR (CDC13) d: 6.90 (1H, d, J = 9.3 Hz), 7.12 (1H, s), 7.27-7.46 (11H, m), 7.55 (1H, t, J = 8.0 Hz), 7.82 ( 1H, m), 8.02-8.11 (2H, m), 8.40 (1H, d, J = 2.7 Hz). (iii) Production of diphenylmethyl 3- (4-amino-2-chlorophenoxy) benzoate To diphenylmethyl 3- (2-chloro-4-nitrophenoxy) benzoate (4.60 g) were added ethyl acetate (80 ml) and platinum- 5% activated carbon (50 mg) and the mixture was stirred under an atmosphere of hydrogen at room temperature for 5 h. The catalyst was filtered, the filtrate was concentrated and the residue obtained was subjected to silica gel column chromatography (eluent, ethyl acetate: hexane = : 80- > 40: 60), and column chromatography on silica gel (eluent, ethyl acetate: hexane = 15: 85- »35: 65). The object fractions were concentrated under reduced pressure to give the title compound (3.58 g) as a colorless solid. ^ -RMN (CDC13) d: 3.69 (2H, br s), 6.57 (1H, dd, J = 2.7 Hz, 8.6 Hz), 6.79 (1H, d, J = 2.7 Hz), 6.91 (1H, d, J = 8.6 Hz), 7.04-7.10 (2H, m), 7.26-7.44 (11H, m), 7.62-7.65 (1H, m), 7.78-7.83 (1H, m). (iv) Production of 3- hydrochloride. { 4 - [(5- { 2- [2- (benzoyloxy) ethoxy] ethyl} -5H-pyrrolo [3,2-d] pyrimidin-4-yl) amino] -2-chlorophenoxy} benzoic A mixture of 2- [2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethoxy] ethyl benzoate (1.04 g), 3- (4-amino-2-chlorophenoxy) ) diphenylmethyl benzoate (1.29 g) and isopropyl alcohol (20 ml) was stirred at 80 ° C overnight. An aqueous solution of sodium acid carbonate was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, ethyl acetate: hexane = 50: 50-> 100: 0). The object fractions were concentrated under reduced pressure. To the residue were added trifluoroacetic acid (10 ml) and anisole (10 ml) and the mixture was stirred at room temperature for 4 h. The reaction mixture was concentrated under reduced pressure. A solution of 4 N hydrogen chloride / ethyl acetate was added to the residue, and the mixture was concentrated under reduced pressure. Ethyl acetate and acetonitrile were added to the residue and the precipitated solid was collected by filtration to give the title compound (1.24 g) as a white powder. XH-NMR (DMSO-d6) d: 3.76-3.83 (2H, m), 3.91 (2H, t, J = 4.7 Hz), 4.27-4.33 (2H, m), 4.89 (2H, ra), 6.60-6.64 (1H, m), 7.22 (1H, d, J = 8.8 Hz), 7.26-7.75 (10H, m), 7.91 (1H, d, J = 2.5 Hz), 8.01 (1H, d, J = 3.0 Hz), 8.64 (1H, s), 9.91 (1H, m). (v) Production of N- (tert-butyl) -3- [2-chloro-4- ((5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4 -yl.}. amino) phenoxy] benzamide A mixture of 3- {4- [(5- {2- [2- (benzoyloxy) ethoxy] ethyl} -5H-pyrrolo [3] hydrochloride. , 2-d] pyrimidin-4-yl) amino] -2-chlorophenoxy.} Benzoic acid (183 mg), tert-butylamine (0.038 ml), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (69 mg), 1-hydroxybenzotriazole (55 mg), triethylamine (0.050 ml) and N, N-dimethylformamide (3 ml) was stirred at room temperature overnight, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate.The acetate layer of ethyl was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100-> 10: 90). The object fractions were concentrated under reduced pressure. To the residue were added methanol (5 ml), tetrahydrofuran (1 ml) and 1 N aqueous sodium hydroxide solution (0.6 ml) and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue obtained was subjected to silica gel column chromatography (eluent, raetanol: ethyl acetate = 0: 100-> 10: 90). The object fractions were concentrated under reduced pressure. The residue was crystallized from ethyl acetate-diethyl ether to give the title compound (106 mg) as white crystals. XH-NMR (CDC13) d: 1.45 (9H, s), 2.36 (1H, br s), 3.69-3.81 (4H, m), 3.99-4.05 (2H, m), 4.53-4.60 (2H, m), 5.96 (1H, br s), 6.61 (1H, d, J = 3.0 Hz), 7.03 (1H, d, J = 8.8 Hz), 7. 05-7.12 (1H, m), 7.21 (1H, d, J = 3.0 Hz), 7.27-7.37 (3H, m), 7.57 (1H, dd, J = 2.5 Hz, 8.8 Hz), 7.91 (1H, d , J = 2.5 Hz), 8.51 (1H, s), 8.79 (1H, br s).

Production of 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] -N- (2, 2-dimethylpropyl) benzamide When using 3-hydrochloride. { 4- [(5- (2- [2 - (benzyloxy) ethoxy] ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl) amino] -2-chlorophenoxy} benzoic acid (183) mg), neopentylamine (0.042 ml), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (69 mg), 1-hydroxybenzotriazole (55 mg), triethylamine (0.050 ml), N, N-dimethylformamide (3 ml ), methanol (5 ml), tetrahydrofuran (1 ml) and 1 N aqueous solution of sodium hydroxide (0.6 ml) and in the same manner as in Example C-9 (v), the title compound was obtained (116 mg) in the form of white crystals, XH-NMR (CDC13) d: 0.97 (9H, s), 2.30 (1H, br s), 3. 25 (2H, d, J = 6.3 Hz), 3.69-3.81 (4H, m), 3.99-4.05 (2H, m), 4.53-4.60 (2H, m), 6.14-6.26 (1H, ra), 6.61 ( 1H, d, J = 3.3 Hz), 7.04 (1H, d, J = 8.8 Hz), 7.06-7.12 (1H, m), 7.21 (1H, d, J = 3.3 Hz), 7.32-7.44 (3H, m ), 7.57 (1H, dd, J = 2.5 Hz, 8.8 Hz), 7.90 (1H, d, J = 2.5 Hz), 8.51 (1H, s), 8.79 (1H, br s).

Production of 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] -N- (2,2,2-trifluoroethyl) benzamide When using 3- (4- [(5- {2- [2- (benzoyloxy) ethoxy] ethyl} -5H-pyrrolo [3] hydrochloride , 2-d] pyrimidin-4-yl) amino] -2-chlorophenoxy.} Benzoic acid (183 mg), 2,2,2-trifluoroethylaraine (0.029 ml), l-ethyl-3- (3-dimethylaminopropyl hydrochloride carbodiimide (69 mg), 1-hydroxybenzotriazole (55 mg), triethylamine (0.050 ml), N, N-dimethylformamide (3 ml), methanol (5 ml), tetrahydrofuran (1 ml) and 1 N aqueous hydroxide solution. sodium (0.6 ml) and in the same manner as in Example C-9 (v), the title compound (125 mg) was obtained as white crystals: XH-NMR (CDC13) d: 2.11 (1H, br s), 3.70-3.82 (4H, m), 3.99-4.17 (4H, m), 4.54-4.62 (2H, m), 6.61 (1H, d, J = 3.0 Hz), 6.67-6.78 (1H, m), 7.03 (1H, d, J = 8.8 Hz), 7.14-7.20 (1H, m), 7.21 (1H, d, J = 3.0 Hz), 7.33 (1H, ra), 7.40 (1H, t, J = 8.0 Hz), 7.46-7.51 (1H, m), 7.55 (1H, dd, J = 8.8, 2.6 Hz), 7.88 (1H, d, J = 2.6 Hz), 8.46 (1H, s), 8.78 ( 1H, br s).

Example C-12 Production of 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-yl]. Amino) phenoxy] benzamide To a solution of 3- hydrochloride. { 4 - [(5- { 2- [2- (benzoyloxy) ethoxy] ethyl} -5H-pyrrolo [3,2-d] pyrimidin-4-yl) amino] -2-chlorophenoxy} Benzoic acid (183 mg) in N, N-dimethylformamide (3 ml) was added triethylamine (0.050 ml) and 1,1 '-carbonylbis (lH-imidazole) (58 mg) and the mixture was stirred at room temperature for 0.5 h. 7 N ammonia / methanol (0.086 ml) was added and the mixture was stirred at room temperature for 4 h. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100- >).; 15: 85). The object fractions were concentrated under reduced pressure. To the residue were added methanol (5 ml), tetrahydrofuran (1 ml) and 1 N aqueous hydroxide solution. sodium (0.6 ml) and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100-> 15: 85). The object fractions were concentrated under reduced pressure. The residue was crystallized from ethanol-ethyl acetate to give the title compound (95 mg) as white crystals. XH-NMR (DMSO-d6) d: 3.49 (4H, m), 3.84 (2H, t, J = 4.4 Hz), 4.65 (2H, t, J = 4.4 Hz), 4.72 (1H, t, J = 4.4 Hz), 6.52 (1H, d, J = 2.7 Hz), 7.08-7.15 (1H, m), 7.21 (1H, d, J = 8.7 Hz), 7.36-7.50 (3H, ra), 7.58-7.72 (3H , m), 7.98-8.08 (2H, m), 8.35 (1H, s), 8.97 (1H, br s). Example C-13 Production of 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] -N-methylbenzamide By using 3- (4- [(5- (2- [2- (benzyloxy) ethoxy] ethyl] - 5 H -pyrrolo [3,2-d] pyrimidin-4-yl) amino] -2-hydrochloride -chlorophenoxy.} benzoic acid (183 mg), N, N-dimethylformamide (3 ml), triethylamine (0.050 ral), 1,1'-carbonylbis (lH-imidazole) (58 mg), 2 M methylamine / tetrahydrofuran (0.30) ml), methanol (5 ml), tetrahydrofuran (1 ml) and 1 N aqueous solution of sodium hydroxide (0.6 ml) and in the same manner as in Example C-12, the title compound (114 mg) was obtained. in the form of white crystals XH-MN (DMSO-d6) d: 2.76 (3H, d, J = 4.5 Hz), 3.50 (4H, m), 3.84 (2H, t, J = 4.4 Hz), 4.65 (2H , t, J = 4.4 Hz), 4.72 (1H, t, J = 4.5 Hz), 6.52 (1H, d, J = 3.0 Hz), 7.07-7.15 (1H, m), 7.20 (1H, d, J = 8.7 Hz), 7.34 (1H, m), 7.46 (1H, t, J = 7.8 Hz), 7.52-7.60 (1H, ra), 7.61-7.73 (2H, m), 8.01 (1H, d, J = 2.7 Hz), 8.35 (1H, s), 8.44-8.53 (1H, m), 8.97 (1H, br Production of 2- (2- [4- (. {3-Chloro-4- [3- (piperidin-1-ylcarbonyl) phenoxy] phenyl} amino) -5H-pyrrolo hydrochloride [3, 2-d ] pyrimidin-5-yl] ethoxy.} ethanol By using 3- (4- [(5- {2- [2- (benzoyloxy) ethoxy] ethyl} -5H-pyrrolo [3,2- d] pyrimidin-4-yl) amino] hydrochloride] -2-chlorophenoxy.} Benzoic acid (183 mg), N, N-dimethylformamide (3 ml), triethylamine (0.050 ml), 1,1'-carbonylbis (lH-imidazole) (58 mg), piperidine (0.059 ml) ), methanol (5 ml), tetrahydrofuran (1 ml) and 1 N aqueous solution of sodium hydroxide (0.6 ml) and in the same manner as in Example C-12, 2- (2- [4- ( (3-Chloro-4- [3- (piperidin-1-ylearbonyl) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethoxy} ethanol. it was dissolved in ethyl acetate-ethanol and 1N hydrogen chloride solution / ethyl acetate (0.3 ml) was added.The solvent was evaporated under reduced pressure and the residue obtained was crystallized from ethanol-ethyl acetate to give the compound of the title (126 mg) as white crystals XH-NMR (DMSO-d6) d: 1.34-1.68 (6H, m), 3.15-3.75 (8H, m), 3.84 (2H, t, J = 4.5 Hz ), 4.81 (2H, m), 6.70 (1H, d, J = 3.0 Hz), 6.86 (1H, m), 7.04-7.10 (1H, m), 7.12 (1H, d, J = 7.7 Hz), 7.31 (1H, d, J = 8.8 Hz ), 7.44-7.51 (1H, ra), 7.64 (1H, dd, J = 2.5 Hz, 8.8 Hz), 7.97 (1H, d, J = 2.5 Hz), 8.02 (1H, d, J = 3.3 Hz), 8.74 (1H, s), 9.90 (1H, br s).

Production of 2- hydrochloride. { 2- [4- ( { 3-chloro-4- [3- (morpholin-disubbonyl) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethoxy } ethanol When using 3- (4- [(5- (2- [2- (benzoyloxy) ethoxy] ethyl] -5H-pyrrolo [3,2- d] pyrimidin-4-yl) amino] - hydrochloride 2-Chlorophenoxy.} Benzoic acid (183 mg), morpholine (0.031 ml), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (69 mg), 1-hydroxybenzotriazole (55 mg), triethylamine (0.050 ml) , N, N-dimethylformamide (3 ml), methanol (5 ml), tetrahydrofuran (1 ml) and 1 N aqueous sodium hydroxide solution (0.6 ml) and in the same manner as in Example C-9 (v) , 2- (2- [4- (. {3-chloro-4- [3- (morpholin-4-ylcarbonyl) phenoxy] phenyl} amino) -5H-pyrrolo [3, 2-d] was obtained pyrimidin-5-yl] ethoxy.] ethanol The compound was dissolved in ethyl acetate-ethanol, and 1N hydrogen chloride solution / ethyl acetate (0.3 ml) was added.The solvent was evaporated under reduced pressure and The residue obtained was crystallized from ethanol-ethyl acetate to give the title compound (116 mg) as white crystals.

XH-NMR (DMSO-d6) d: 3.20-3.80 (12H, m), 3.85 (2H, t, J = 4.4 Hz), 4.81 (2H, t, J = 4.4 Hz), 6.70 (1H, d, J = 3.0 Hz), 6.94 (1H, m), 7.05-7.12 (1H, m), 7.15-7.21 (1H, m), 7.30 (1H, d, J = 8.8 Hz), 7.45-7.53 (1H, m) , 7.64 (1H, dd, J = 2.5 Hz, 8.8 Hz), 7.97 (1H, d, J = 2.5 Hz), 8.02 (1H, d, J = 3.3 Hz), 8.74 (1H, s), 9.90 (1H , br s).

Production of 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] -N- (2-methoxyethyl) benzamide When using 3-hydrochloride. { 4- [(5- (2- [2- (benzoyloxy) ethoxy] ethyl] -5H-pyrrolo [3,2- d] pyrimidin-4-yl) amino] -2-chlorophenoxy} benzoic acid (183) mg), 2-methoxyethylamine (0.031 ml), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (69 mg, 1-hydroxybenzotriazole (55 mg), triethylamine (0.050 ml), N, N-dimethylformamide (3 mg) ml), methanol (5 ml), tetrahydrofuran (1 ml) and 1 N aqueous solution of sodium hydroxide (0.6 ml) and in the same manner as in Example C-9 (v), the title compound was obtained ( 134 mg) in the form of white crystals XH-NMR (CDC13) d: 2.07-2.31 (1H, m), 3.38 (3H, s), 3. 51-3.66 (4H, ra), 3.69-3.81 (4H, ra), 3.99-4.05 (2H, m), 4.54-4.60 (2H, m), 6.51-6.59 (1H, ra), 6.62 (1H, d) , J = 3.3 Hz), 7.04 (1H, d, J = 8.8 Hz), 7.08-7.13 (1H, m), 7.21 (1H, d, J = 3.3 Hz), 7.31-7.46 (3H, m), 7.58 (1H, dd, J = 8.8, 2.8 Hz), 7.90 (1H, d, J = 2.8 Hz), 8.51 (1H, s), 8.78 (1H, br s). Example C-17 Production of 3- [2-chloro-4- ((5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] -N - (3, 3, 3-trifluoropropyl) benzamide When using 3- (4- [(5- {2- [2- (benzoyloxy) ethoxy] ethyl} -5H-pyrroloic acid hydrochloride [3, 2 -d] pyrimidin-4-yl) amino] -2-chlorophenoxy] benzoic acid (183 mg), 3,3,3-trifluoropropylamine hydrochloride (53 mg), l-ethyl-3- (3-dimethylaminopropyl hydrochloride carbodiimide (69 mg), 1-hydroxybenzotriazole (55 mg), triethylamine (0.092 ml), N, N-dimethylformamide (3 ml), methanol (5 ml), tetrahydrofuran (1 ml) and 1 N aqueous solution of hydroxide sodium (0.6 ml) and in the same manner as in Example C-9 (v), the title compound (150 mg) was obtained as white crystals XH-NMR (CDC13) d: 2.08 (1H, br s), 2.37-2.54 (2H, m), 3.64-3.83 (6H, m), 3.99-4.06 (2H, m), 4.55-4.61 (2H, m), 6. 48-6.58 (1H, m), 6.62 (1H, d, J = 3.2 Hz), 7.04 (1H, d, J = 9. 0 Hz), 7.11-7.17 (1H, m), 7.22 (1H, d, J = 3.2 Hz), 7.27 (1H, m), 7.34-7.45 (2H, ra), 7.57 (1H, dd, J = 2.5 Hz, 9.0 Hz), 7.89 (1H, d, J = 2.5 Hz), 8.50 (1H, s), 8.78 (1H, br s).

Production of 3- [2-chloro-4- ((5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] -N -isopropylbenzamide When using 3- {4- [(5- {2- [2- (benzoyloxy) ethoxy] ethyl} -5H-pyrrolo [3,2-d] pyrimidin-4-hydrochloride il) amino] -2-chlorophenoxy [benzoic (183 mg), isopropylamine (0.031 ml), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (69 mg), 1-hydroxybenzotriazole (55 mg), triethylamine ( 0.050 ml), N, N-dimethylformamide (3 ml), methanol (5 ml), tetrahydrofuran (1 ml) and 1 N aqueous solution of sodium hydroxide (0.6 ml) and in the same manner as in Example C-9 (v), the title compound (125 mg) was obtained as white crystals XH-NMR (CDC13) d: 1.25 (6H, d, J = 6.6 Hz), 2.13-2.37 (1H, m), 3.69-3.81 (4H, m), 3.99-4.05 (2H, m), 4.18-4.31 (1H, m), 4.53-4.60 (2H, m), 5.92-6.02 (1H, m) , 6.62 (1H, d, J = 3.0 Hz), 7.03 (1H, d, J = 8.8 Hz), 7.06-7.12 (1H, m), 7.21 (1H, d, J = 3.0 Hz), 7.30-7.42 (3H, m), 7.56 (1H, dd, J = 2.8 Hz, 8.8 Hz), 7.90 (1H, d, J = 2.8 Hz), 8.50 (1H, s), 8.78 (1H, br s).

Production of 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] -N-cyclopropylbenzamide When using 3-hydrochloride. { 4- [(5- { 2- [2- (benzoyloxy) ethoxy] ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl) amino] -2-chlorophenoxy} benzoic acid (183 mg), cyclopropylamine (0.025 ml), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (69 mg), 1-hydroxybenzotriazole (55 mg), triethylamine (0.050 ml), N, N-dimethylformamide (3 ml), methanol (5 ml), tetrahydrofuran (1 ml) and 1 N aqueous solution of sodium hydroxide (0.6 ml) and in the same manner as in Example C-9 (v), the compound of title (118 mg) in the form of white crystals. XH-NMR (DMSO-d6) d: 0.52-0.73 (4H, m), 2.76-2.87 (1H, m), 3.49 (4H, m), 3.84 (2H, t, J = 4.6 Hz), 4.65 (2H, t, J = 4.6 Hz), 4.72 (1H, t, J = 4.6 Hz), 6.52 (1H, d, J = 3.2 Hz), 7.06-7.12 (1H, m), 7.19 (1H, d, J = 8.9 Hz), 7.35 (1H, m), 7.44 (1H, t, J = 7.8 Hz) , 7.52-7.58 (1H, ra), 7.64 (1H, dd, J = 8.9, 2.5 Hz), 7.69 (1H, d, J = 3.2 Hz), 8.00 (1H, d, J = 2.5 Hz), 8.34 ( 1H, s), 8.49 (1H, d, J = 4.1 Hz), 8.97 (1H, br s). Example C-20 Production of 3- [2-chloro-4- ((5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] -N - (1,1-dimethylpropyl) benzamide When using 3- {4- [[5- {2- [2- (benzoyloxy) ethoxy] ethyl} -5H-pyrrolo [3, 2] hydrochloride. -d] pyrimidin-4-yl) amino] -2-chlorophenoxy.} benzoic acid (183 mg), tert-amylamine (0.042 ml), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (69 mg) , 1-hydroxybenzotriazole (55 rag), triethylamine (0.050 ml), N, N-dimethylformamide (3 ml), methanol (5 ml), tetrahydrofuran (1 ml) and 1 N aqueous solution of sodium hydroxide (0.6 ml) and in the same manner as in Example C-9 (v), the title compound (135 mg) was obtained as white crystals.

XH-NMR (CDCl3) d: 0.90 (3H, t, J = 7.5 Hz), 1.40 (6H, s), 1..83 (2H, q, J = 7.5 Hz), 3.70-3.80 (4H, m) , 3.99-4.05 (2H, m), 4.54-4.60 (2H, ra), 5.84 (1H, br s), 6.63 (1H, d, J = 3.2 Hz), 7.02-7.12 (2H, m), 7.21 ( 1H, d, J = 3.2 Hz), 7.28-7.39 (3H, m), 7.58 (1H, dd, J = 8.8, 2.7 Hz), 7.91 (1H, d, J = 2.7 Hz), 8.51 (1H, s ), 8.79 (1H, br s). Example C-21 Production of 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] -N- (2-hydroxy-1,1-dimethylethyl) benzamide When using 3- (4- [(5- {2- [2- (benzoyloxy) ethoxy] ethyl} -5H-pyrroloic acid hydrochloride [3, 2-d] pyrimidin-4-yl) amino] -2-chlorophenoxy.} Benzoic acid (183 mg), 2-amino-2-methyl-1-propanol (0.034 ml), l-ethyl hydrochloride 3- (3-dimethylaminopropyl) carbodiimide (69 mg), 1-hydroxybenzotriazole (55 mg), triethylamine (0.050 ml), N, N-dimethylformamide (3 ml), methanol (5 ml), tetrahydrofuran (1 ml) and solution aqueous 1 N sodium hydroxide (0.6 ml) and in the same manner as in Example C-9 (v), the title compound (106 mg) was obtained as white crystals.

XH-NMR (CDCl 3) d: 1.40 (6H, s), 3.67 (2H, s), 3.69-3.81 (4H, m), 3.98-4.05 (2H, m), 4.54-4.60 (2H, m), 6.23 (1H, br s), 6.62 (1H, d, J = 3.0 Hz), 7.04 (1H, d, J = 8.8 Hz), 7.08-7.15 (1H, m), 7.21 (1H, d, J = 3.0 Hz ), 7.28 (1H, m), 7.32-7.40 (2H, m), 7.57 (1H, dd, J = 2.5 Hz, 8.8 Hz), 7.90 (1H, d, J = 2.5 Hz), 8.49 (1H, s ), 8.80 (1H, br s). Example C-22 Production of N- (tert-butyl) -3- (2-chloro-4- ([5- (2. {[[(Methylsulfonyl) acetyl] amino]} ethyl) -5H-pyrrolo hydrochloride [3, 2-d] pyrimidin-4-yl] amino.}. Phenoxy) benzamide (i) Production of 3- {4- [(5- {2- [(tert-butoxycarbonyl) amino] ethyl}. -5H-pyrrolo [3,2-d] pyrimidin-4-yl) amino] -2-chlorophenoxy.] Methyl benzoate A fraction of [2- (4-chloro-5H-pyrrolo [3, 2-d] tert-butyl pyrimidin-5-yl) ethyl] carbamate (2.08 g), methyl 3- (4-amino-2-chlorophenoxy) benzoate (1.94 g) and isopropyl alcohol (20 ml) was stirred at 80 ° C for overnight, aqueous sodium carbonate aqueous solution was added to the reaction mixture and the mixture was extracted with ethyl acetate.The ethyl acetate layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, ethyl acetate: hexane = 50: 50-> 100: 0). The object fractions were concentrated under reduced pressure. Ethyl acetate and diisopropyl ether were added to the residue, and the precipitated solid was collected by filtration to give the title compound (3.26 g) as a white powder. XH-NMR (CDC13) d: 1.50 (9H, s), 3.44-3.54 (2H, m), 3.90 (3H, s), 4.43-4.53 (2H, m), 5.12 (1H, t, J = 5.6 Hz ), 6.60 (1H, d, J = 3.2 Hz), 7.05 (1H, d, J = 8.9 Hz), 7.16-7.22 (2H, m), 7.39 (1H, t, J = 8.0 Hz), 7.63 (1H , m), 7.74-7.78 (1H, m), 7.89 (1H, dd, J = 2.7 Hz, 8.9 Hz), 8.03 (1H, d, J = 2.7 Hz), 8.52 (1H, s), 8.61 (1H, br s). (ii) Acid production 3-. { 4- [(5- (2- [(tert-butoxycarbonyl) amino] ethyl] -5H-pyrrolo [3,2-d] pyrimidin-yl) amino] -2-chlorophenoxy.} Benzoic A 3- {.4 - [(5-. {2- [(tert-butoxycarbonyl) amino] ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl) amino] -2-chlorophenoxy. The methyl benzoate (2.96 g) was added with methanol (50 ml), tetrahydrofuran (10 ml) and 1 N aqueous sodium hydroxide solution (11 ml) and the mixture was stirred at 60 ° C overnight. Concentrate under reduced pressure, water and acetic acid (0.63 ml) were added, and the mixture was extracted with ethyl acetate.The organic layer was washed with brine Saturated and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue obtained was crystallized from methanol-acetonitrile-diethyl ether to give the title compound (2.58 g) as white crystals. ^ -RN (DMSO-d6) d: 1.32 (9H, s), 3.22-3.32 (2H, m), 4.51 (2H, t, J = 6.2 Hz), 6.49 (1H, d, J = 3.0 Hz), 7.10-7.20 (1H, rn), 7.24-7.34 (3H, m), 7.52 (1H, t, J = 8.0 Hz), 7.61 (1H, ra), 7.67 (1H, d, J = 7.7 Hz), 7.75 -7.84 (1H, m), 7.97 (1H, m), 8.33 (1H, s), 8.66 (1H, br s). (iii) Production of 3- (4. {[[5- (2-aminoethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino] -2-chlorophenoxy dihydrochloride] - N- (tert-butyl) benzamide A mixture of 3- (4- [(5- {2- [(tert-butoxycarbonyl) amino] ethyl} -5H-pyrrolo [3,2-d] pyrimidine -4-yl) amino] -2-chlorophenoxy.} Benzoic acid (524 mg), tert-butylamine (0.126 ml), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (230 mg), 1-hydroxybenzotriazole (184 mg) and N, N-dimethylformamide (10 ml) was stirred at room temperature overnight, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate.The organic layer was washed with saturated brine. and dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure and the residue obtained was subjected to silica gel column chromatography. (eluent, ethyl acetate: hexane = 50: 50-> 100: 0). The object fractions were concentrated under reduced pressure. To the residue were added ethanol (2 ml) and 4 N hydrogen chloride solution / ethyl acetate (2 ml) and the mixture was stirred at room temperature overnight. Ethyl acetate was added to the reaction mixture, and the precipitated solid was collected by filtration to give the title compound (427 mg) as a pale yellow powder. XH-NMR (DMSO-d6) d: 1.36 (9H, s), 3.23-3.37 (2H, m), 4.96-5.06 (2H, m), 6.74 (1H, d, J = 3.3 Hz), 7.17 (1H , dd, J = 2.6 Hz, 8.1 Hz), 7.25 (1H, d, J = 8.8 Hz), 7.35 (1H, m), 7.47 (1H, t, J = 7.8 Hz), 7.58-7.66 (2H, m ), 7.85 (1H, s), 7.90 (1H, m), 8.05 (1H, m), 8.27 (3H, br s), 8.74 (1H, s), 10.04 (1H, br s). (iv) Production of N- (tert-butyl) -3- (2-chloro-4. {[[5- (2. {[[(methylsulfonyl) acetyl] amino]} ethyl) -5H hydrochloride -pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. phenoxy) enzamide A mixture of 3- (4. {[[5- (2-aminoethyl) -5H-pyrrolo [3], dihydrochloride] 2-d] pyrimidin-4-yl] amino.} -2-chlorophenoxy) -N- (tert-butyl) benzamide (166 mg), methylsulfonylacetic acid (62 mg), l-ethyl-3- (3-hydrochloride -dimethylaminopropyl) carbodiimide (86 mg), 1-hydroxybenzotriazole (69 mg), triethylamine (0.100 ml) and N, N-dimethylformamide (3 ml) was stirred at room temperature overnight. Water was added to the reaction mixture, and The mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100-> 15: 85). The object fractions were concentrated under reduced pressure. The residue was dissolved in ethyl acetate-ethanol and 1N hydrogen chloride solution / ethyl acetate (0.3 ml) was added. The solvent was evaporated under reduced pressure and the residue obtained was crystallized from ethanol-ethyl acetate to give the title compound (121 mg) as white crystals. aH-NMR (DMSO-d6) d: 1.36 (9H, s), 3.06 (3H, s), 3.50-3.61 (2H, m), 4.07 (2H, s), 4.67-4.77 (2H, m), 6.67 (1H, d, J = 3.1 Hz), 7.13-7.20 (1H, m), 7.25 (1H, d, J = 8.9 Hz), 7.37 (1H, m), 7.47 (1H, t, J = 8.0 Hz) , 7.60-7.69 (2H, m), 7.85 (1H, s), 7.93 (1H, d, J = 2.5 Hz), 7.96 (1H, d, J = 3.1 Hz), 8.74 (1H, s), 8.78- 8.87 (1H, m), 9.99 (1H, br s). Example C-23 Production of N- (tert-butyl) -3- [2-chloro-4- ((5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2- d] pyrimidin-4-yl} amino) phenoxy] -5- (trifluoromethyl) benzamide (i) Production of methyl 3-hydroxy-5- (trifluoromethyl) benzoate 3-Amino-5- (trifluoromethyl) benzoic acid (2.80 g) was dissolved in sulfuric acid concentrate (50 g) and water (50 ml) and the mixture was cooled to -10 ° C. Water (120 ml) was added., and an aqueous solution (20 ml) of sodium nitrite (0.942 g) was added dropwise. Water (10 ml) was added, and the mixture was stirred at -10 ° C for 10 min and at 0 ° C for 30 min. The mixture was further stirred with heating at reflux for 1 h. After allowing to cool, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was dissolved in methanol (30 ml). Concentrated hydrochloric acid (0.9 ml) was added and the mixture was stirred with heating under reflux overnight. The reaction mixture was concentrated under reduced pressure, aqueous sodium hydrogen carbonate solution was added to the residue, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and The residue obtained was subjected to silica gel column chromatography (eluent, ethyl acetate: hexane = 10: 90-> 30: 70). The object fractions were concentrated under reduced pressure to give the title compound (1.86 g) as a pale yellow powder. XH-NMR (CDC13) d: 3.95 (3H, s), 5.49 (1H, s), 7.29 (1H, m), 7.70 (1H, m), 7.87 (1H, m). (ii) Production of methyl 3- (4-amino-2-chlorophenoxy) -5- (trifluoromethyl) benzoate A mixture of 2-chloro-1-fluoro-4-nitrobenzene (1.48 g), 3-hydroxy-5- Methyl (trifluoromethyl) benzoate (1.86 g), potassium carbonate (1.75 g) and N, N-dimethylformamide (10 ral) was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure, water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, ethyl acetate: hexane = 5: 95- »15: 85). The object fractions were concentrated under reduced pressure. To the residue were added ethyl acetate (30 ml) and 5% activated carbon-platinum (90 mg) and the mixture was stirred under an atmosphere of hydrogen at room temperature for 4 h. The catalyst was filtered, and the filtrate was concentrated and the residue obtained was subjected to chromatography on silica gel column (eluent, ethyl acetate: hexane = 15: 85- »35: 65). The object fractions were concentrated under reduced pressure. Hexane was added to the residue, and the precipitated solid was collected by filtration to give the title compound (2.50 g) as a white powder. XH-NMR (CDC13) d: 3.76 (2H, br s), 3.92 (3H, s), 6.61 (1H, dd, J = 8.6, 2.7 Hz), 6.81 (1H, d, J = 2.7 Hz), 6.94 (1H, d, J = 8.6 Hz), 7.31 (1H, m), 7.64 (1H, m), 7.95 (1H, m). (iii) Production of 3-. { 4- [(5- { 2- [2- (benzyloxy) ethoxy] ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl) amino] -2-chlorophenoxy} -5- (trifluoromethyl) benzoate methyl A mixture of 2- [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethoxy] ethyl benzoate (346 mg), 3- (4-amino-2-chlorophenoxy) Methyl (trifluoromethyl) benzoate (346 mg) and isopropyl alcohol (5 ml) was stirred at 80 ° C for 5 h. 2- [2- (Chloro-5H-pyrrolo [3,2-d] pyriraidin-5-yl) ethoxy] ethyl benzoate (69 mg) was added and the mixture was then stirred at 80 ° C for 3 h . The reaction mixture was concentrated under reduced pressure, aqueous sodium hydrogen carbonate solution was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, ethyl acetate: hexane = 50: 50-> 100: 0). The object fractions are concentrated under reduced pressure to give the title compound (609 mg) as a white powder. XH-NMR (CDCl 3) d: 3.93 (3H, s), 3.95-4.00 (2H, m), 4.06-4.12 (2H, m), 4.47-4.53 (2H, m), 4.56-4.63 (2H, m) , 6.64 (1H, d, J = 3.3 Hz), 6.83 (1H, d, J = 8.8 Hz), 7.24 (1H, d, J = 3.3 Hz), 7.29-7.43 (4H, m), 7.45-7.52 ( 1H, m), 7.69 (1H, m), 7.77-7.83 (2H, m), 7.92 (1H, d, J = 2.5 Hz), 8.00 (1H, m), 8.52 (1H, s), 8.83 (1H , br s). (iv) Production of 3- [2-chloro-4- ((5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino acid) phenoxy] -5- (trifluoromethyl) benzoic A 3- {4 - [(5- (2- [2- (benzoyloxy) ethoxy] ethyl} -5H-pyrrolo [3,2-d] pyrimidin-4 methyl) -2-chlorophenoxy] -5- (trifluoromethyl) benzoate (609 mg) were added methanol (12 ml) and 1 N aqueous sodium hydroxide solution. (3 ml) and the mixture was stirred at room temperature overnight. Water and 1 N hydrochloric acid (3 ml) were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, ethanol-acetonitrile-diethyl ether was added to the obtained residue, and the precipitated solid was collected by filtration to give the title compound (416 mg) as a white powder. XH-NMR (DMSO-d6) d: 3.50 (4H, m), 3.85 (2H, t, J = 4. 4 Hz), 4.56-4.88 (1H, m), 4.68 (2H, t, J = 4.4 Hz), 6.54 (1H, d, J = 3.0 Hz), 7.38 (1H, d, J = 8.7 Hz), 7.52 (1H, m), 7.59-7.80 (3H, m), 7.90 (1H, m), 8.05 (1H, m), 8.40 (1H, s), 9.11 (1H, br s). (v) Production of N- (tert-butyl) -3- [2-chloro-4- ((5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4 -yl.}. amino) phenoxy] -5- (trifluoromethyl) benzamide A mixture of 3- [2-chloro-4- ((5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3, 2-d] pyrimidin-4-yl.}. Amino) phenoxy] -5- (trifluoromethyl) benzoic acid (322 mg), tert-butylamine (0.126 ml), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (138 mg), 1-hydroxybenzotriazole (153 mg) and N, N-dimethylformamide (5 ml) was stirred at room temperature overnight, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100 - > 20: 80.) The object fractions were concentrated under reduced pressure. crystallized from ethyl acetate-diethyl ether to give the title compound (247 mg) as white crystals. XH-NMR (CDC13) d: 1.46 (9H, s), 3.70-4.82 (4H, m), 4.02 (2H, t, J = 4.4 Hz), 4.57 (2H, t, J = 4.4 Hz), 6.00 ( 1 HOUR, br s), 6.61 (1H, d, J = 3.2 Hz), 7.06 (1H, d, J = 8.8 Hz), 7.21 (1H, d, J = 3.2 Hz), 7.29 (1H, m), 7.44 (1H , m), 7.57 (1H, m), 7.62 (1H, dd, J = 2.8 Hz, 8.8 Hz), 7.93 (1H, d, J = 2.8 Hz), 8.51 (1H, s), 8.87 (1H, br s).

Production of N- (tert-butyl) -3-. { 2-Chloro-4- [(5- (2- [(3-hydroxy-3-methylbutanoyl) amino] ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl) amino] phenoxy} -5- (trifluoromethyl) benzamide (i) Production of 3- {4- [(5- {2- [(tert-butoxycarbonyl) amino] ethyl} -5H-pyrrolo [3.2] -d] pyrimidin-1-yl) amino] -2-chlorophenoxy] -5- (trifluoromethyl) benzoate A mixture of tert-butyl [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] carbamate (1.48 g), 3- (4-amino-2-chlorophenoxy) Methyl (trifluoromethyl) benzoate (1.73 g) and isopropyl alcohol (20 ml) was stirred at 80 ° C for 5 h. [2- (4-Chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (0.30 g) was added and the mixture was then stirred at 80 ° C for 3 h . The reaction mixture was concentrated under reduced pressure, aqueous sodium hydrogen carbonate solution was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, ethyl acetate: hexane = 50: 50-> 100: 0). The object fractions were concentrated under reduced pressure. To the residue were added acetone and diisopropyl ether, and the precipitated solide was collected by filtration to give the title compound (2.06 g) as a white powder. XH-NMR (CDC13) d: 1.50 (9H, s), 3.45-3.55 (2H, m), 3. 93 (3H, s), 4.44-4.54 (2H, m), 5.10-5.18 (1H, m), 6.61 (1H, d, J = 3.2 Hz), 7.11 (1H, d, J = 8.9 Hz), 7.20 (1H, d, J = 3.2 Hz), 7.39 (1H, m), 7.77 (1H, m), 7.96 (1H, dd, J = 8.9, 2.5 Hz), 8.00 (1H, s), 8.07 (1H, d, J = 2.5 Hz), 8.53 (1H, s), 8.67 (1H, br s). (ii) Production of 3- (4- [(5- {2- [(tert-butoxycarbonyl) amino] ethyl} -5H-pyrrolo [3,2-d] pyrimidin-4-yl) amino acid ] -2-chlorophenoxy.}. -5- (trifluoromethyl) benzoic A 3- { 4 - [(5- { 2- [(tert-butoxycarbonyl) amino] ethyl.}. -5H-pyrrolo [3 , 2-d] pyrimidin-4-yl) amino] -2-chlorophenoxy] -5- (trifluoromethyl) benzoate (2.42 g) were added methanol (10 ml), tetrahydrofuran (10 ml) and aqueous solution 1 N sodium hydroxide (8 ml) and the mixture was stirred at room temperature overnight.to the reaction mixture was added water and 1 N hydrochloric acid (8 ml), and The mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was crystallized from methanol-diethyl ether to give the title compound (2.03 g) as white crystals. XH-NMR (DMSO-d6) d: 1.32 (9H, s), 3.20-3.36 (2H, m), 4.53 (2H, t, J = 6.4 Hz), 6.51 (1H, d, J = 3.0 Hz), 7.10-7.23 (1H, m), 7.39 (1H, d, J = 8.7 Hz), 7.54 (1H, m), 7.63 (2H, m), 7.80-7.90 (1H, m), 7.90 (1H, m), 8.02 (1H, m), 8.35 (1H, s ), 8.73 (1H, br s). (iii) Production of 3- (4. {[[5- (2-aminoethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino] -2-chlorophenoxy dihydrochloride] - N- (tert-butyl) -5- (trifluoromethyl) benzamide A mixture of 3- acid. { 4- [(5-. {2- [(tert-butoxycarbonyl) amino] ethyl] -5H-pyrrolo [3,2-d] pyrimidin-yl) amino] -2-chlorophenoxy} -5- (trifluoromethyl) benzoic acid (888 mg), tert-butylamine (0.189 ml), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (345 mg), 1-hydroxybenzotriazole (276 mg) and N, N dimethylformamide (10 ml) was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the The obtained residue was subjected to silica gel column chromatography (eluent, ethyl acetate: hexane = 70: 30 → 100: 0 → methanol: ethyl acetate = 10:90). The object fractions were concentrated under reduced pressure. To the residue were added ethanol (1 ral) and 4 N hydrogen chloride solution / ethyl acetate (5 ml) and the mixture was stirred at room temperature for 2 h. The reaction mixture was concentrated under reduced pressure, ethanol and diethyl ether were added, and the precipitated solid was collected by filtration to give the title compound (815 mg) as a white powder. 2 H-NMR (DMSO-d 6) d: 1.37 (9H, s), 3.23-3.38 (2H, m), 5.06 (2H, m), 6.76 (1H, d, J = 3.0 Hz), 7.37-7.44 (1H , m), 7.52 (1H, m), 7.59 (1H, ra), 7.66-7.75 (1H, m), 7.94-8.55 (7H, m), 8.76 (1H, s), 9.95-10.04 (1H, ). (iv) Production of N- (tert-butyl) -3- (2-chloro-4- [(5- (2- [(3-hydroxy-3-methylbutanoyl) amino] ethyl] -5H-pyrrolo [ 3,2-d] pyrimidin-4-yl) amino] phenoxy.]. -5- (trifluoromethyl) benzamide A mixture of 3- (4- {[5- (2-aminoethyl) -5H-pyrrolo dihydrochloride [3,2-d] pyrimidin-4-yl] amino.} -2-chlorophenoxy) -N- (tert-butyl) -5- (trifluoromethyl) benzamide (186 mg), 3-hydroxy-3-methylbutanoic acid (53 mg), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (86 mg), 1-hydroxybenzotriazole (69 mg), triethylamine (0.100 ml) and N, N-dimethylformamide (3 ml) was stirred at room temperature. room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue obtained was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100-10: 90). The object fractions were concentrated under reduced pressure. The residue was crystallized from ethyl acetate-diisopropyl ether to give the title compound (152 mg) as white crystals. XH-NMR (CDC13) d: 1.31 (6H, s), 1.48 (9H, s), 2.48 (2H, s), 3.54-3.66 (2H, m), 4.41-4.53 (2H, m), 6.01 (1H , br s), 6.57 (1H, d, J = 3.3 Hz), 7.07 (1H, d, J = 9.0 Hz), 7.18 (1H, d, J = 3.3 Hz), 7.25-7.35 (2H, m), 7.48 (1H, m), 7.62 (1H, m), 7.78 (1H, dd, J = 2.4 Hz, 9.0 Hz), 8.10 (1H, d, J = 2.4 Hz), 8.49 (1H, s), 8.72 ( 1H, br s). Example C-25 Production of N- (tert-butyl) -3- (2-chloro-4-. {[[5- (2- ([(rath-ylsulfonyl) acetyl] amino} ethyl) -5H-pyrrolo [3.2 -d] pyrimidin-4-yl] amino.}. phenoxy) -5- (trifluoromethyl) benzamide A mixture of 3- (4 -. {[[5- (2-aminoethyl) -5H-pyrrolo [3], dihydrochloride] 2-d] pyrimidin-4-yl] amino.} -2-chlorophenoxy) -N- (tert-butyl) -5- (trifluoromethyl) benzamide (186 mg), methylsulfonylacetic acid (62 mg), hydrochloride 1- ethyl-3- (3-dimethylaminopropyl) carbodiimide (86 mg), 1-hydroxybenzotriazole (69 mg), triethylamine (0.100 ml) and N, N-dimethylformamide (3 ml) was stirred at room temperature overnight. to the reaction mixture, and the mixture was extracted with ethyl acetate.The organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate.The solvent was evaporated under reduced pressure and the residue obtained was subjected to to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100- »15: 85) and column chromatography on silica gel (eluent, methanol: ethyl acetate = 0: 100- > 10: 90). The object fractions were concentrated under reduced pressure. The residue was crystallized from ethyl acetate-diisopropyl ether to give the title compound (146 mg) as white crystals. XH-NMR (CDC13) d: 1.48 (9H, s), 3.14 (3H, s), 3.60-3.74 (2H, m), 4.00 (2H, s), 4.40-4.54 (2H, m), 6.06 (1H , br s), 6.58 (1H, d, J = 3.0 Hz), 7.08 (1H, d, J = 8.8 Hz), 7.21 (1H, d, J = 3.0 Hz), 7.35 (1H, m), 7.46 (1H, m), 7.58 (1H, m), 7.78 (1H, dd, J = 2.3 Hz, 8.8 Hz), 7.87-7.96 (1H, m), 7.97 (1H, d, J = 2.3 Hz), 8.29 (1H, br s), 9.46 (1H, s). Example C-26 Production of N- (tert-butyl) -3- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2- d] pyrimidin-4-yl] ami no} phenoxy) benzamide (i) Production of 3- (2-chloro-4-. {[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimido-4-yl] amino] acid .}. phenoxy) benzoic A mixture of 2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethyl benzoate (1.51 g), 3- (4-amino-2-chlorophenoxy) Methyl benzoate (1.39 g) and isopropyl alcohol (20 ml) was stirred at 80 ° C overnight. Aqueous acid sodium carbonate solution was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue obtained was subjected to column chromatography on silica gel (eluent, acetate ethyl: hexane = 50: 50-100: 0). The object fractions were concentrated under reduced pressure. To the residue were added methanol (30 ml) and 1 N aqueous sodium hydroxide solution (13.5 ml) and the mixture was stirred at room temperature for 3 days. The reaction mixture was concentrated under reduced pressure, water and 1 N hydrochloric acid (13.5 ml) were added, and the mixture was extracted with ethyl acetate-tetrahydrofuran. The extract was washed with water and the solvent was evaporated under reduced pressure. The residue was crystallized from acetonitrile-diethyl ether to give the title compound (1.88 g) as white crystals. XH-NMR (DMSO-d6) d: 3.88 (2H, m), 4.50-4.60 (2H, m), 6.31 (1H, br s), 6.52 (1H, d, J = 3.0 Hz), 7.23-7.34 ( 3H, m), 7.51 (1H, t, J = 8.0 Hz), 7.59-7.71 (3H, m), 7.99 (1H, d, J = 2.7 Hz), 8.35 (1H, s), 9.90 (1H, br s). (ii) Production of N- (tert-butyl) -3- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. phenoxy) benzamide A mixture of 3- (2-chloro-4- ([5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino]. phenoxy) benzoic acid (850 mg), tert-butylamine (0.420 ml), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (466 mg), 1-hydroxybenzotriazole (368 mg) and N, N-dimethylformamide (10 mg). ml) was stirred at room temperature overnight.The reaction mixture was concentrated to reduced pressure, water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue obtained was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100-> 20:80) and silica gel column chromatography (eluent , methanol: ethyl acetate = 0: 100- »20: 80). The object fractions were concentrated under reduced pressure. The residue was crystallized from ethyl acetate-diisopropyl ether to give the title compound (630 mg) as white crystals. XH-NMR (CDC13) d: 1.45 (9H, s), 1.66 (1H, br s), 4.08-4.16 (2H, br), 4.35-4.42 (2H, m), 5.99 (1H, br s), 6.16 (1H, d, J = 3.3 Hz), 6.98-7.03 (2H, m), 7.04-7.12 (1H, m), 7.30-7.37 (3H, m), 7.41 (1H, dd, J = 2.6 Hz, 8.8 Hz), 7.80 (1H, d, J = 2.6 Hz), 8.23 (1H, s), 9.68 (1H, br s). Example C-27 Production of (4- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy ] cyclohexyl} tert-butyl carbamate A mixture of 2- [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethoxy] ethyl benzoate (300 mg), [ 4- (4-Amino-2-chlorophenoxy) cyclohexyl] tert-butyl carbamate (384 mg) and isopropyl alcohol (7.0 ml) was stirred at 80 ° C overnight.The reaction mixture was concentrated under reduced pressure, Water and saturated aqueous sodium hydrogen carbonate were added and the mixture was extracted with ethyl acetate.The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate.The solvent was evaporated under reduced pressure and the residue obtained was subjected to silica gel column chromatography (eluent, ethyl acetate: methanol = 100: 0- »80: 20) The subject fractions were concentrated under reduced pressure.The crude product was dissolved in methanol (5.0 ml) and tetrahydrofuran (1.0 ml), 1 N aqueous solution of sodium hydroxide (2.5 ml) was added and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100% IO: 90). The fractions object was concentrated under reduced pressure. The residue was crystallized from ethyl acetate / hexane to give the title compound (163 mg) as a white powder. Vi-NMR (DMSO-d6) d: 1.20-1.52 (4H, m), 1.38 (9H, s), 1.82-2.14 (4H, m), 3.25-3.32 (4H, m), 3.81 (2H, t, J = 4.9 Hz), 4.15-4.29 (1H, m), 4.60-4.72 (3H, m), 6.48 (1H, d, J = 3 Hz), 6.80-6.83 (1H, m), 7.17 (1H, d , J = 9 Hz), 7.46-7.49 (1H, m), 7.63 (1H, d, J = 3 Hz), 7.77 (1H, d, J = 3 Hz), 8.26 (1H, s), 8.68 (1H , br s). Example C-28 Production of (3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy ] phenyl.} tertbutyl carbamate When using 2- [2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethoxy] ethyl benzoate (165 mg), [3- ( 4-amino-2-chlorofenoxyl) phenyl] carbamic acid tert -butyl ester (200 mg), isopropyl alcohol (7.0 ml), methanol (5.0 ml), tetrahydrofuran (1.0 ml) and 1 N aqueous solution of sodium hydroxide (2.5 ml) and in the same manner as in Example C-27, the title compound (90 mg) was obtained as crystals.

XH-NMR (DMSO-d6) d: 1.45 (9H, s), 3.49 (4H, s), 3.83 (2H, t, J = 4.7 Hz), 4.63-4.72 (3H, m), 6.51 (2H, d , J = 3 Hz), 7.12-7.24 (4H, m), 7.63-7.69 (2H, m), 7.99 (1H, s), 8.34 (1H, s), 8.93 (1H, s), 9.43 (1H, s). Example C-29 hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] -5- (trifluoromethyl) phenyl] carbamic acid terbutyl When using 2- [2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethoxy] ethyl benzoate (206) mg), [3- (4-amino-2-chlorophenoxy) -5- (trifluoromethyl) phenyl] tert-butyl carbamate (300 mg), isopropyl alcohol (10 ml), methanol (2.0 ml), tetrahydrofuran (1.0 ml) ) and 1 N aqueous solution of sodium hydroxide (2.0 ral) and in the same manner as in Example C-27, the title compound (53 mg) was obtained as crystals. XH-NMR (CDC13) d: 1.53 (9H, s), 3.72-3.82 (5H, m), 4. 02? 2H, t, J = 4.9 Hz), 4.58 (2H, t, J = 4.9 Hz), 6.36 (1H, d, J = 2.1 Hz), 6.58 (2H, d, J = 4.7 Hz), 6.66 ( 1H, d, J = 3.2 Hz), 7.07 (1H, d, J = 8.9 Hz), 7.23-7.25 (2H, m), 7.62 (1H, dt, J = 8.9, 2.1 Hz), 7.87 (1H, s), 8.54 (1H, s ), 8.79 (1H, s). Example C-30 Production of N- [3- (2-chloro-4- ([5- (2- {[[2-methyl-2- (methylsulfonyl) propanoyl] amino} ethyl) -5H-pyrrolo [3.2 -d] pyrimidin-4-yl] amino.}. phenoxy) phenyl] -2, 2-dimethylpropanamide (i) Production of 5- (2-aminoethyl) -N- [4- (3-aminophenoxy) -3 trichlorohydrate -chlorophenyl] -5H-pyrrolo [3,2-d] pyrimidin-4-amine A solution of [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] carbamate of tert-butyl (267 mg) and tert-butyl [3- (4-amino-2-chlorophenoxy) phenyl] carbamate (430 mg) in l-methyl-2-pyrrolidone (15 ml) was stirred at 120 ° C for 5 h After cooling to room temperature, water was added to the reaction mixture and the mixture was extracted with ethyl acetate. ethyl. The organic layer was washed successively with water and saturated brine, and dried over magnesium sulfate. The residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 19: 1 → 3: 2- »ethyl acetate) to give a brown solid. To a solution of the solid obtained in tetrahydrofuran (20 ml) was added 2 N hydrochloric acid (10 ml) at room temperature, and the mixture was stirred at 60 ° C for 20 h. After concentrating under reduced pressure, ethanol was added and the mixture was then concentrated. Diisopropyl ether was added to the residue and the resulting crystals were collected by filtration. The crystals were washed with diisopropyl ether to give the title compound (342 mg) as pale yellow crystals. XH-NMR (DMSO-de) d: 3.26-3.34 (2H, m), 5.04-5.13 (2H, ra), 6.76-7.05 (4H, m), 7.28-7.69 (3H, m), 7.94 (1H, s), 8.11 (1H, s), 8.45 (3H, br s), 8.76 (1H, s), 10.39 (2H, br s). (ii) Production of N- [3- (2-chloro-4- ([5- (2 { [2-methyl-2- (methylsulfonyl) propanoyl] amino} ethyl) -5H-pyrrolo [ 3,2-d] pyrimidin-4-yl] amino.}. Phenoxy) phenyl] -2, 2-dimethylpropanamide A mixture of 5- (2-aminoethyl) -N- [4- (3-aminophenoxy) trichlorohydrate - 3-chlorophenyl] -5H-pyrrolo [3,2-d] pyrimidin-4-amine (114 mg), 2-methyl-2- (methylsulfonyl) propanoic acid (210 mg), l-ethyl-3- hydrochloride ( 3- dimethylaminopropyl) carbodiimide (380 mg), 1-hydroxybenzotriazole (41 mg), triethylamine (1.0 ml) and tetrahydrofuran (5.0 ml) was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100-> 10: 90). The object fractions were concentrated under reduced pressure. The obtained crude product was dissolved in tetrahydrofuran (5.0 ml), N-methyl-morpholine (1.0 ml) and 2, 2-dimethylpropanoyl chloride (0.25 ml) were added, and the mixture was stirred for 1 h. Under cooling with ice, saturated aqueous sodium hydrogen carbonate was added, and the mixture was extracted with dichloromethane. The extract was dried over magnesium sulfate and concentrated, and the residue was separated and purified by silica gel column chromatography. (eluent, ethyl acetate: methanol = 100: 0- »ethyl acetate: raetanol = 80:20), and crystallized from diethyl ether / ethyl acetate to give the title compound (82 mg) as crystals. XH-NMR (DMS0-d6) d: 1.19 (9H, s), 1.14 (6H, s), 2.96 (3H, s), 3.39-3.50 (2H, m), 4.55-4.59 (2H, m), 6.49 (1H, d, J = 3.2 Hz), 6.66-6.68 (1H, m), 7.17-7.74 (6H, m), 7.97 (1H, s), 8.22 (1H, br s), 8.34 (1H, s), 8.65 (1H, s), 9.26 (1H, Example C-31 Production of N- [2- (4- ([4- (3-aminophenoxy) -3-chlorophenyl] amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2- methyl-2- (methylsulfonyl) propanamide A mixture of 5- (2-aminoethyl) -N- [4- (3-aminophenoxy) -3-chlorophenyl] -5H-pyrrolo [3,2-d] pyrimidin-trichlorohydrate. -amine (860 mg), 2-methyl-2- (methylsulfonyl) propanoic acid (700 mg), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (1.10 g), 1-hydroxybenzotriazole (50 mg), triethylamine (3.0 ml) and tetrahydrofuran (30 ml) was stirred at room temperature overnight, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate.The organic layer was washed with saturated brine and dried on anhydrous magnesium sulfate The solvent was evaporated under reduced pressure and the residue obtained was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100- > 10:90). The object fractions were concentrated under reduced pressure. The obtained crude product was crystallized from diethyl ether / ethyl acetate to give the title compound (850 mg). XH-NMR (DMSO-d6) d: 1.41 (6H, s), 2.96 (3H, s), 3.39-3.51 (2H, m), 4.54-4.59 (2H, m), 5.32 (2H, m), 6.07 -6.11 (2H, m), 6.29 (1H, d, J = 8.8 Hz), 6.53 (1H, d, J = 3.0 Hz), 6.94-6.71 (1H, m), 7.11 (1H, d, J = 8.8 Hz), 7.56-7.60 (2H, m), 7.70 (1H, d, J = 3.0 Hz), 8.10 (1H, br s), 8.34 (1H, s), 8.91 (1H, s). Example C-32 Production of N- [3- (2-chloro-4. {[[5- (2 { [2-methyl-2- (methylsulfonyl) propanoyl] amino} ethyl) -5H-pyrrolo [3 , 2-d] pyrimidin-4-yl] amino.}. Phenoxy) phenyl] -2-methy1-2- (methylsulfonyl) propanamide When using 5- (2-aminoethyl) trichlorohydrate-N- [4- (3- aminophenoxy) -3-chlorophenyl] -5H-pyrrolo [3,2-d] pyrimidin-4-amine (80 mg), 2-methyl-2- (methylsulfonyl) propanoic acid (87 mg), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (210 mg), 1-hydroxybenzotriazole (71 mg), triethylamine (0.9 ml) and tetrahydrofuran (8.0 ml) and in the same manner as in Example C-31, the title compound (89 rag) was obtained in the form of crystals. XH-NMR (DMSO-d6) d: 1.41 (6H, s), 1.64 (6H, s), 2.96 (3H, s), 3.03 (3H, s), 3.41-3.52 (2H, m), 4.55-4.59 (2H, m), 6. 49 (1H, d, J = 3.2 Hz), 6.73-6.76 (1H, m), 7.17-7.76 (6H, m), 7.99 (1H, d.J = 3.2 Hz), 8.22 (1H, br s), 8.34 (1H, s), 8.66 (1H, s), 9.52 (1H, s). Example C-33 Production of N-. { 2- [4- ((- [3- (acetylamino) phenoxy] -3-chlorophenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl.} -2-methyl -2- (Methylsulfonyl) propanamide A mixture of N- [2- (4- { [4- (3-aminophenoxy) -3-chlorophenyl] amino.}. -5H-pyrrolo [3,2-d] pyrimidine -5-yl) ethyl] -2-methyl-2- (methylsulfonyl) propanamide (91 mg), triethylamine (0.2 ml), acetic anhydride (0.3 ml) and tetrahydrofuran (7.0 ml) it was stirred at room temperature for 1 h. Under cooling with ice, saturated aqueous sodium hydrogen carbonate was added, and the mixture was extracted with dichloromethane. The extract was dried over magnesium sulfate and concentrated, and the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: methanol = 100: 0-> 80: 20), and crystallized in diethyl ether / ethyl acetate to give the title compound (84 mg) as crystals. XH-NMR (DMSO-d6) d: 1.41 (6H, s), 2.00 (3H, s), 2.96 (3H, s), 3.39-3.50 (2H, m), 4.55-4.59 (2H, m), 6.49 (1H, d, J = 3.2 Hz), 6.63-6.68 (1H, m), 7.23-7.30 (4H, m), 7.59 (1H, s), 7.72-7.75 (1H, m), 7.96 (1H, s) ), 8.20 (1H, br s), 8.34 (1H, s), 8.65 (1H, s), 10.00 (1H, s). Example C-34 Production of 2- [2- (4- { [4- (3-aminophenoxy) -3-chlorophenyl] amino} -5H-pi-rolo [3,2-d] pyrimidin-5-yl) ethoxy] Ethanol dissolved. { 3- [2-chloro-4- ( { 5- [2- (2- hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] phenyl} tert-butyl carbamate (120 mg) in methanol (7.0 ml), 4N hydrogen chloride solution / ethyl acetate (8.0 ml) was added and the mixture was stirred for 5 h. 8 N aqueous solution of sodium hydroxide (8.0 ml) and water (10 ml) were added, and the mixture was extracted with dichloromethane. The extract was dried over magnesium sulfate and concentrated, and the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: methanol = 100: 0-> 80: 20), and crystallized in diethyl ether / ethyl acetate to give the title compound (59 mg) as crystals. XH-NMR (DMSO-d6) d: 3.49 (4H, s), 3.81-3.85 (2H, m), 4.62-4.65 (2H, t, J = 4.8Hz), 4.71 (1H, m), 5.32 (2H , m), 6.06-6.09 (2H, m), 6.27 (1H, d, J = 8.8 Hz), 6.51 (1H, d, J = 3.0 Hz), 6.94-6.70 (1H, m), 7.11 (1H, d, J = 8.8 Hz), 7.56-7.60 (1H, m), 7.70 (1H, d, J = 3.0 Hz), 7.95 (1H, s), 8.34 (1H, s), 8.93 (1H, s).

Production of N- (tert-butyl) -N '-. { 3- [2-Chloro-4- ((5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2- d] pyrimidin-4-yl} amino) phenoxy] phenyl}. urea (i) Production of 2- [2- (4. {[[4- (3-aminophenoxy) -3-chlorophenyl] amino] -5H-pyrrolo [3,2-d] pyrimidin benzoate dihydrochloride. -5-yl) ethoxy] ethyl A mixture of benzoate of 2- [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethoxy] ethyl (206 mg), [3- (Tert-Butyl 4-amino-2-chlorophenoxy) phenyl] carbamate (300 mg) and isopropyl alcohol (7.0 ml) was stirred at 80 ° C. for 12 h.The reaction mixture was concentrated under reduced pressure, water was added The aqueous layer was saturated aqueous sodium carbonate and the mixture was extracted with ethyl acetate.The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate.The solvent was evaporated under reduced pressure and the residue obtained was subjected to silica gel column (eluent, hexane: ethyl acetate = 80: 20-> 0: 100) .The subject fractions were concentrated in a The crude product was dissolved in methanol (8.0 ml), and by using 4 N hydrogen chloride solution / ethyl acetate (8.0 ml) and in the same manner as in Example C-34, the compound was obtained of the title (370 mg) in the form of crystals. XH-NMR (DMSO-d6) d: 3.76-3.80 (2H, m), 3.87-3.94 (2H, m), 4.22-4.35 (2H, m), 4.85-4.93 (2H, m), 6.62-6.77 ( 3H, m), 6.87-7.18 (3H, ra), 7.30-7.71 (8H, m), 7.90 (1H, s), 8.01 (1H, s), 8.65 (1H, s). (ii) Production of N- (tert-butyl) -N '- (3- [2-chloro-4- ((5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] ] pyrimidin-4-yl.}. amino) phenoxy] phenyl} urea Benzoate dihydrochloride of 2- [2- (4- ([4- (3-aminophenoxy) -3-chlorophenyl] amino] was suspended. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethoxy] ethyl (200 mg) in toluene (10 ml), triethylamine (0.9 ml) and 2-isocyanato-2-methylpropane (0.4 ml) were added and the mixture was stirred at 120 ° C for 6 h, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate.The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue obtained was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100-> g.; 15: 85). The object fractions were concentrated under reduced pressure. The residue was dissolved in raetanol (6.0 ml) and tetrahydrofuran (6.0 ml). Aqueous 1 N aqueous sodium hydroxide solution (3.0 ral) was added and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to gel column chromatography of silica (eluent, raetanol: ethyl acetate = 0: 100- »10: 90). The object fractions were concentrated under reduced pressure. The residue was crystallized from ethyl acetate-hexane to give the title compound (74 mg) as white crystals. XH-NMR (DMSO-d6) d: 1.26 (9H, s), 3.49 (4H, s), 3.83 (2H, t, J = 6.0 Hz), 4.64 (2H, t, J = 6.0 Hz), 4.71 (1H, m), . 93 (1H, s), 6.43-6.52 (2H, m), 6.96-7.21 (4H, m), 7.60-7.69 (2H, m), 7.98 (1H, d, J = 3.0 Hz), 8.34 (1H, s), 8.35 (1H, s), 8.92 (1H, s). Example C-36 Production of N- (3- [2-chloro-4- ((5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2- d] pyrimidin-4-yl} amino) phenoxy ] phenyl] -3,3-dimethylbutanamide A mixture of 2- [2- (4. {[[4- (3-aminophenoxy) -3-chlorophenyl] amino] -5H-pyrrolobenzoate dihydrochloride. [3,2-d] pyrimidin-5-yl) ethoxy] ethyl (270 mg), triethylamine (1.9 ml), 3,3-dimethylbutanoyl chloride (0.3 ral) and tetrahydrofuran (20 ml) was stirred at room temperature for 1 h. Under cooling with ice, saturated aqueous sodium hydrogen carbonate was added, and the mixture was extracted with dichloromethane. The extract was dried over magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography (eluent, ethyl acetate: methanol = 100: 0-> 80: 20). The object fractions were concentrated under reduced pressure. The residue was dissolved in methanol (6.0 ml) and tetrahydrofuran (6.0 ml). Aqueous 1 N aqueous sodium hydroxide solution (2.0 ml) was added and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100% IO: 90). The object fractions were concentrated under reduced pressure. The residue was crystallized from ethyl acetate-hexane to give the title compound (126 mg) as white crystals. 2 H-NMR (DMSO-de) d: 1.00 (9H, s), 2.15 (2H, s), 3.49 (4H, s), 3.84 (2H, t, J = 6.0 Hz), 4.66 (2H, t, J = 6.0 Hz), 4.71 (1H, m), 6.52 (1H, d, J = 3.0 Hz), 6.68 -6.70 (1H, ra), 7.16-7.37 (4H, m), 7.61-7.69 (2H, m), 7.99 (1H, d, J = 3.0 Hz), 8.34 (1H, s), 8.94 (1H, s) ), 9.85 (1H, s).

Example C-37 Production of N-. { 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] phenyl} -3-hydroxy-2, 2-dimethylpropanamide A mixture of 2- [2- (4. {[[4- (3-aminophenoxy) -3-chlorophenyl] amino] -5H-pyrrolobenzoate dihydrochloride. 3,2-d] pyrimidin-5-yl) ethoxy] ethyl (260 mg), 3-hydroxy-2,2-dimethylpropanoic acid (200 mg), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride ( 621 mg), 1-hydroxybenzotriazole (70 mg), triethylamine (2.0 ral) and tetrahydrofuran (15 ml) was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100-> 10: 90). The object fractions were concentrated under reduced pressure. The obtained crude product was dissolved in methanol (6.0 ml) and tetrahydrofuran (6.0 ml), 1N aqueous solution of sodium hydroxide (2.0 ml) was added, and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100-> 10: 90). The object fractions were concentrated under reduced pressure. The residue was crystallized from ethyl acetate-hexane to give the title compound (84 mg) as white crystals. XH-NMR (DMSO-d6) d: 1.30 (6H, s), 3.49 (4H, s), 3.56 (2H, br s), 3.84 (2H, t, J = 6.0 Hz), 4.64 (2H, t, J = 6.0 Hz), 4.71 (1H, s), 4.73 (1H, m), 6.50 (1H, d, J = 3.2 Hz), 6.64 (1H, d, J = 7.7 Hz), 7.15-7.38 (4H, m), 7.62-7.70 (2H, m), 7.99 (1H, d, J = 3.2 Hz), 8.34 (1H, s), 8.94 (1H, s), 9.90 (1H, s). Example C-38 Production of N-. { 3- [2-Chloro-4- ((5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2- d] pyrimidin-4-ylamino) phenoxy] phenyl}. Retylcyclopropanecarboxamide When using 2- [2- (4 - ([4- (3-arni-nphenoxy) -3-chlorophenyl] amino]} -5H-pyrrolo [3,2-d] pyrimidin-5-yl benzoate dihydrochloride ) ethoxy] ethyl (200 mg), 1-methylcyclopropanecarboxylic acid (179 mg), 1-ethyl-3- (3-dimethylareneopropyl) carbodiimide hydrochloride (600 mg), 1-hydroxybenzotriazole (70 mg), triethylamine (2.3 ml) , tetrahydrofuran (20 ml), 1 N aqueous solution of sodium hydroxide (2.0 ml), tetrahydrofuran (6.0 ml) and ethanol (6.0 ml) and in the same manner as in Example C-37, the title compound was obtained (69 mg) in the form of crystals XH-NMR (DMSO-d6) d: 0.59-0.62 (2H, m), 1.04-1.08 (2H, m), 1.37 (3H, s), 3.49 (4H, s) , 3.84 (2H, t, J = 6.0 Hz), 4.66 (2H, t, J = 6.0 Hz), 4.71 (1H, m), 6.52 (1H, d, J = 3.0 Hz), 6.60-6.70 (1H, ra), 7.15 (1H, d, J = 6.0 Hz), 7.23-7.41 (3H, ra), 7.60-7.64 (1H, m), 7.70 (1H, d, J = 3. 0 Hz), 7.98 (1H, d, J = 3.0 Hz), 8.36 (1H, s), 8.98 (1H, s), 9.22 (1H, s).

Example C-39 dimethylpropyl) amino] phenoxy} phenyl) amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl} ethoxy) ethanol 2- [2- (4- {[[4- (3-aminophenoxy) -3-chlorophenyl] amino] -5H-pyrrolo [3,2-d] pyrimidine- benzoate dihydrochloride was suspended. 5-yl) ethoxy] ethyl (220 mg) in dichloromethane (7.0 ml), and acetic acid (0.7 ml), molecular sieves 4A (300 mg) and pivalaldehyde (120 mg) were added, and the mixture was stirred for 30 min . Sodium triacetoxyborohydride (470 mg) was added and the mixture was stirred for 3 h. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100-> 15: 85). The object fractions were concentrated under reduced pressure. The residue was dissolved in methanol (6.0 ml) and tetrahydrofuran (6.0 ml). Aqueous 1 N aqueous solution was added Sodium hydroxide (2.0 ml) and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100-> 10: 90). The object fractions were concentrated under reduced pressure. The residue was crystallized from ethyl acetate-hexane to give the title compound (67 mg) as white crystals. XH-NMR (DMSO-d6) d: 0.93 (9H, s), 2.77 (2H, d, J = 6.0 Hz), 3.49 (4H, s), 3.83 (2H, t, J = 4.7 Hz), 4.63- 4.72 (3H, m), 5.63 (1H, t, J = 6.0 Hz), 6.02-6.05 (1H, m), 6.24 (1H, t, J = 3.0 Hz), 6.34-6.36 (1H, m), 6.51 (1H, d, J = 3.0 Hz), 7.00 (1H, t, J = 6.0 Hz), 7.08 (1H, d, J = 9.0 Hz), 7.56-7.60 (1H, m), 7.68 (1H, d, J = 3.0 Hz), 7.95 (1H, d, J = 3.0 Hz), 8.33 (1H, s), 8.91 (1H, s). Example C-40 Production of N-. { 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] phenyl} -4,4,4-trifluoro-2-methylbutanamide When using 2- [2- (4 - ([4- (3-aminophenoxy) -3-chlorophenyl] amino] -5H-pyrrolobenzoate dihydrochloride [3] , 2-d] pyrimidin-5-yl) ethoxy] ethyl (50 mg), 4, 4, -trifluoro-2-methylbutanoic acid (47 mg), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride ( 125 mg), 1-hydroxybenzotriazole (5 mg), triethylamine (0.7 ml), tetrahydrofuran (7.0 ml), 1 N aqueous solution of sodium hydroxide (1.5 ml), tetrahydrofuran (3.0 ml) and methanol (2.0 ml) and In the same manner as in Example C-37, the title compound (25 mg) was obtained in the form of crystals: rH-NMR (DMSO-d6) d: 1.18 (3H, d, J = 6.0 Hz), 2.26- 2.85 (3H, m), 3.49 (4H, s), 3.84 (2H, t, J = 6.0 Hz), 4.66 (2H, t, J = 6.0 Hz), 4. 71 (1H, m), 6.52 (1H, d, J = 3.0 Hz), 6.68-6.70 (1H, m), 7.14-7.38 (4H, m), 7.62-7.70 (2H, m), 7.99 (1H, d, J = 3.0 Hz), 8.34 (1H, s), 8.95 (1H, s), 10.14 (1H, s). Example C-41 Production of N-. { 3- [2-chloro-4- ((5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] phenyl}. -N'-cyclohexylurea When using 2- [2- (4. {[[4- (3-aminophenoxy) -3-chlorophenyl] amino] -5H-pyrrolo [3,2-d] benzoate dihydrochloride. pyrimidin-5-yl) ethoxy] ethyl (240 mg), toluene (15 ml), triethylamine (2.0 ml), cyclohexyl isocyanate (137 mg), 1 N aqueous solution of sodium hydroxide (3.0 ml), tetrahydrofuran (6.0 ml) and methanol (6.0 ml) and in the same manner as in Example C-35 (ii), the title compound (56 mg) was obtained as crystals XH-NMR (DMSO-d6) d: 1.09-1.82 (10H, ra), 3.34-3.51 (1H, m), 3.49 (4H, s), 3.84 (2H, t, J = 6.0 Hz), 4.64 (2H, t, J = 6.0 Hz), 4.71 (1H, ra), 6.00 (1H, d, J = 9.0 Hz), 6.46-6.52 (2H, m), 6.96-7.21 (4H, m), 7.61-7.69 (2H, m ), 7.98 (1H, d, J = 2.7 Hz), 8.34 (1H, s), 8.41 (1H, s), 8.93 (1H, s). Example C-42 Production of N-. { 3- [2-chloro-4- ((5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyriraidin-4-yl} amino) phenoxy] phenyl}. -3,3,3-trifluoro-2-hydroxy-2-methylpropanamide When using 2- [2- (4. {[[4- (3-aminophenoxy) -3-chlorophenyl] amino] benzoate dihydrochloride. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethoxy] ethyl (201 mg), 3,3,3-trifluoro-2-hydroxy-2-methylpropanoic acid (175 mg), hydrochloride of l- ethyl-3- (3-dimethylaminopropyl) carbodiimide (415 mg), 1-hydroxybenzotriazole (47 mg), triethylamine (1.8 ral), tetrahydrofuran (28 ml), 1 N aqueous solution of sodium hydroxide (4.0 ml), tetrahydrofuran ( 6.0 ral) and methanol (6.0 ml) and in the same manner as in Example C-37, the title compound (47 mg) was obtained as crystals XH-NMR (DMSO-d6) d: 1.01 (3H , s), 3.49 (4H, s), 3.84 (2H, t, J = 6.0 Hz), 4.65 (2H, t, J = 6.0 Hz), 4.71 (1H, m), 6.52 (1H, d, J = 3.0 Hz), 6.60-6.70 (1H, m) , 7.14 (1H, d, J = 6.0 Hz), 7.22-7.45 (3H, m), 7.60-7.65 (1H, m), 7.71 (1H, d, J = 3.0 Hz), 7.98 (1H, d, J = 3.0 Hz), 8.36 (1H, s), 8.98 (1H, s), 9.22 (1H, s).

Example C-43 Production of N-. { 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] phenyl} -1- (trifluoromethyl) cyclopropanecarboxamide When using 2- [2- (4 - ([4- (3-aminophenoxy) -3-chlorophenyl] amino] -5H-pyrrolo [3,2-d] benzoate dihydrochloride. pyrimidin-5-yl) ethoxy] ethyl (220 mg), 1- (trifluoromethyl) cyclopropanecarboxylic acid (300 mg), l-ethyl-3- (3-diraethylaminopropyl) carbodiimide hydrochloride (450 mg), 1-hydroxybenzotriazole (110 mg) rag), triethylamine (2.6 ml), tetrahydrofuran (15 ml), 1 N aqueous solution of sodium hydroxide (4.0 ml), tetrahydrofuran (6.0 ml) and methanol (6.0 ml) and in the same manner as in Example C- 37, the title compound (23 mg) was obtained as crystals: XH-NMR (DMSO-d6) d: 1.14-1.31 (2H, m), 1.42-1.45 (2H, ra), 3.49 (4H, s) ), 3.84 (2H, t, J = 6.0 Hz), 4.64 (2H, t, J = 6.0 Hz), 4.71 (1H, ra), 6.51 (1H, d, J = 3.0 Hz), 6.70-6.73 (1H , m), 7.15-7.41 (4H, m), 7.60-7.69 (2H, m), 7.99 (1H, d, J = 3.0 Hz), 8.34 (1H, s), 8.95 (1H, s), 9.84 (1H, s) Example C-44 Production of N-. { 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] phenyl} -N '- (tetrahydro-2H-pyran-4-yl) urea To a solution of 1,1' -carbonylbis (lH-imidazole) (401 mg) in toluene (10 ml) was added tetrahydro-2H-pyran-4 -amine (250 mg) and the mixture was stirred at room temperature for 1 h. Benzoate dihydrochloride of 2- [2- (4- ([4- (3-aminophenoxy) -3-chlorophenyl] amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethoxy was added. ] ethyl (220 mg) and triethylamine (2.0 ml), and the mixture was stirred at 70 ° C for 30 min.Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate.The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate The solvent was evaporated under reduced pressure and the residue obtained was dissolved in methanol (8.0 ml) and tetrahydrofuran (2.0 ml), 1 N aqueous solution of sodium hydroxide (3.0 ml) was added. ml) and the mixture was stirred at room temperature overnight.

Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100-> 10: 90). The object fractions were concentrated under reduced pressure. The solvent was evaporated under reduced pressure and the residue obtained was crystallized from ethyl acetate-hexane to give the title compound (12 mg) in white crystal fora. XH-NMR (DMSO-d6) d: 1.09-1.82 (4H, m), 3.20-3.63 (4H, m), 3.33-3.55 (1H, m), 3.49 (4H, s), 3.84 (2H, t, J = 6.0 Hz), 4.64 (2H, t, J = 6.0 Hz), 4.71 (1H, m), 6.00 (1H, d, J = 9.0 Hz), 6.45-6.52 (2H, m), 6.97-7.21 ( 4H, m), 7.59-7.71 (2H, m), 7.99 (1H, d, J = 2.7 Hz), 8.34 (1H, s), 8.41 (1H, s), 8.94 (1H, s). Example C-45 Production of N- (3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl}. ) phenoxy] phenyl}. cyclopropanecarboxamide When using 2- [2- (4. {[[4- (3-aminophenoxy) -3-chlorophenyl] amino] -5H-pyrrolo benzoate dihydrochloride [3,2 -d] pyrimidin-5-yl) ethoxy] ethyl (200 mg), cyclopropanecarboxylic acid (200 rag), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (470 mg), 1-hydroxybenzotriazole (42 mg) , triethylamine (2.0 ml), tetrahydrofuran (29 ml), 1 N aqueous solution of sodium hydroxide (3.0 ml), tetrahydrofuran (6.0 ml) and methanol (6.0 ml) and in the same manner as in Example C-37, the title compound (98 mg) was obtained in the form of crystals: XH-NMR (DMSO-de) d: 0.76-0.78 (2H, m), 1.04 (2H, d, J = 6.0 Hz), 1.71-1.75 ( 1H, m), 3.49 (4H, s), 3.84 (2H, t, J = 6.0 Hz), 4.66 (2H, t, J = 6.0 Hz), 4.71 (1H, m), 6.52 (1H, d, J = 3.0 Hz), 6.62-6.66 (1H, m), 7.17 (1H, d, J = 9.0 Hz), 7.23-7.31 (3H, m), 7.61-7.69 (2H, m), 7.99 (1H, d, J = 3.0 Hz), 8.34 (1H, s), 8.94 (1H, s), 10.25 (1H, s). Example C-46 Production of N-. { 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] phenyl} -3-hydroxy-3-methylbutanamide When using 2- [2- (4. {[[4- (3-aminophenoxy) -3-chlorophenyl] amino]} -5H-pyrrolobenzoate dihydrochloride [3,2 -d] pyrimidin-5-yl) ethoxy] ethyl (200 mg), 3-hydroxy-3-methylbutanoic acid (200 mg), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (470 mg), 1 -hydroxybenzotriazole (41 mg), triethylamine (1.8 ml), tetrahydrofuran (28 ml), 1 N aqueous sodium hydroxide solution (2.0 ml), tetrahydrofuran (6.0 ml) and methanol (6.0 ml) and in the same manner as in Example C-37, the title compound (53 mg) was obtained in the form of crystals. XH-NMR (DMSO-d6) d: 1.21 (6H, s), 2.38 (2H, s), 3.49 (4H, s), 3.84 (2H, t, J = 6.0 Hz), 4.64 (2H, t, J = 6.0 Hz), 4.71 (1H, s), 4.73 (1H, m), 6.51 (1H, d, J = 3.2 Hz), 6.63 (1H, d, J = 7.7 Hz), 7.15-7.37 (4H, m ), 7.61-7.69 (2H, m), 7.99 (1H, d, J = 3.2 Hz), 8.34 (1H, s), 8.94 (1H, s), 9.87 (1H, s).

Production of N- (2- { 4- [(3-chloro-4- { 3- [(3-hydroxy-2,2-dimethylpropanoyl) amino] phenoxyphenyl) amino] -5H-pyrrolo [3, 2-d] pyrimidin-5-yl.} Ethyl) -3-hydroxy-3-methylbutanamide When using 5- (2-aminoethyl) -N- [4- (3-aminophenoxy) -3-chlorophenyl] trichlorohydrate] - 5H-pyrrolo [3,2-d] pyrimidin-4-amino (150 mg), 3-hydroxy-3-methylbutanoic acid (42 mg), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (357 mg ), 1-hydroxybenzotriazole (18 mg) and triethylamine (0.9 ml) in tetrahydrofuran (4.0 ml) and in the same manner as in Example C-31, the reaction was carried out. When using the crude product obtained and 3-hydroxy-2,2-dimethylpropanoic acid (200 mg), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (460 mg), 1-hydroxybenzotriazole (150 mg), triethylamine (2.0 ml) in tetrahydrofuran (7.0 ml) and in the same manner as in Example C-31, the title compound (90 mg) was obtained as crystals. XH-NMR (CDC13) d: 1.25 (6H, s), 1.32 (6H, s), 2.48 (2H, s), 2.80 (2H, br s), 3.59 (2H, s), 3.57-3.65 (2H, m), 4.45-4.51 (2H, m), 6.62 (1H, d, J = 3.0 Hz), 7.05-7.44 (8H, ra), 7.73 (1H, dd, J = 8.7 Hz, 2.7 Hz), 8.03 ( 1H, d, J = 2.7 Hz), 8.30 (1H, s), 8.50 (1H, s).

Production of N-. { 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-yl]. Amino) phenoxy] phenyl} propanamide When using 2- [2- (4. {[[4- (3-aminophenoxy) -3-chlorophenyl] amino]} -5H-pyrrolo [3,2-d] pyrimidin-5-benzoate dihydrochloride il) ethoxy] ethyl (200 mg), propionic acid (0.5 ml), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (560 mg), 1-hydroxybenzotriazole (67 mg), triethylamine (2.1 ml), tetrahydrofuran (10 ml), 1 N aqueous solution of sodium hydroxide (2.0 ml), tetrahydrofuran (6.0 ml) and methanol (6.0 ml) and in the same manner as in Example C-37, the title compound was obtained ( 70 mg) in the form of crystals. XH-NMR (DMSO-d6) d: 1.04 (3H, t, J = 7.5 Hz), 2.28 (2H, dd, J = 7.5 Hz), 3.49 (4H, s), 3.84 (2H, t, J = 6.0 Hz), 4.64 (2H, t, J = 6.0 Hz), 4.73 (1H, m), 6.51 (1H, d, J = 3.2 Hz), 6.63 (1H, d, J = 7.7 Hz), 7.15-7.32 ( 4H, m), 7.61-7.69 (2H, m), 7.99 (1H, d, J = 3.2 Hz), 8.34 (1H, s), 8.94 (1H, s), 9. 92 (1H, s). Example C-49 Production of 4-. { 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] phenyl} tert-butyl piperidin-1-carboxylate (i) Production of tert-butyl 4- [3- (2-chloro-4-nitrophenoxy) phenyl] piperidine-1-carboxylate 2-chloro-1-fluoro-4 was dissolved -nitrobenzene (7.27 g) and 4- (3-hydroxyphenyl) piperidine-1-carboxylic acid terbutyl ester (11.5 g) in N, N-dimethylformamide (42 ml), potassium carbonate (8.28 g) was added and the mixture was stirred at room temperature for 16 h. The reaction mixture was diluted with ethyl acetate (300 ml) and washed with water (300 ml). The organic layer was dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The residue was subjected to silica gel column chromatography (hexane / ethyl acetate = 100 / 0-60 / 40) to give the title compound (17.6 g) as an oil. XH-NMR (CDC13) d: 1.47 (9H, s), 1.50-1.70 (2H, m), 1. 84 (2H, d, J = 13 Hz), 2.60-2.90 (3H, m), 4.23 (2H, m), 6.87 (1H, d, J = 9 Hz), 6.92 (2H, m), 7.12 (1H , d, J = 8 Hz), 7.37 (1H, m), 8.04 (1H, dd, J = 3 Hz, 9 Hz), 8.38 (1H, d, J = 3 Hz). (ii) Production of tert-butyl 4- [3- (4-amino-2-chlorophenoxy) phenyl] piperidine-1-carboxylate. 4- [3- (2-Chloro-4-nitrophenoxy) phenyl] piperidine was suspended. 1-tert-butyl carboxylate (1.9 g) in ethanol (43 ral) / water (4.81 ml), calcium chloride (270 mg) was added thereto and the mixture was dissolved with heating with stirring at 90 ° C for 10 min. . Reduced iron was added (1.63 g), and the mixture was stirred with heating at 90 ° C for 16 h. After cooling to room temperature, the reaction mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. The residual solid was diluted with ethyl acetate (150 ml) and washed with saturated brine (80 ml). The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (hexane / ethyl acetate = 80 / 20-> 60/40) to give the title compound (1.71 g) as an oil. ^ -RMN (CDC13) d: 1.48 (9H, s), 1.50-1.70 (2H, m), 1.80 (2H, d, J = 13 Hz), 2.58 (1H, m), 2.77 (2H, t, J = 13 Hz), 3.69 (2H, br s), 4.22 (2H, m), 6.57 (1H, dd, J = 3 Hz, 9 Hz), 6.60-6.90 (5H, m), 7.20 (1H, t, J = 8 Hz). (iii) Production of 4-. { 3- [2-chloro-4- ( { 5- [2- (2- hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] phenyl} piperidin-1-tert-butyl carboxylate A mixture of 2- [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethoxy] ethyl benzoate (150 mg), 4- [3- (4-amino-2-chlorophenoxy) phenyl] piperidine-1-carboxylic acid terbutyl ester (260 mg) and isopropyl alcohol (1.5 ml) was stirred with heating at 80 ° C for 16 h. The reaction mixture was diluted with ethyl acetate (80 ml), and washed with aqueous sodium bicarbonate (40 ml). The organic layer was separated, dried over anhydrous magnesium sulfate, and evaporated under reduced pressure. The residue was purified by silica gel column chromatography (hexane / ethyl acetate = 90 / 10-> g.; 0/100), and the object fractions were concentrated under reduced pressure. The obtained residue was dissolved in methanol (1.89 ml), thereto was added 1 N aqueous sodium hydroxide solution (0.433 ml) and the mixture was stirred at room temperature for 2 h. 1N Hydrochloric acid (0.433 ml) was added, and the mixture was diluted with ethyl acetate (30 ml), and washed with saturated brine (30 ral). The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the residue was subjected to silica gel column chromatography (ethyl acetate / methanol = 100 / 0-85 / 15) to give the title compound. Title (88 mg) in powder form. XH-NMR (CDC13) d: 1.47 (9H, s), 1.50-1.80 (2H, m), 1. 81 (2H, m), 2.61 (1H, m), 2.77 (2H, m), 3.72 (2H, ra), 3.79 (2H, m), 4.01 (2H, t, J = 5 Hz), 4.21 (2H , m), 4.55 (2H, t, J = 5 Hz), 6.59 (1H, d, J = 3 Hz), 6.79 (2H, ra), 6.90 (1H, d, J = 7.5 Hz), 7.00 (1H , d, J = 9 Hz), 7.18-7.30 (2H, m), 7.55 (1H, dd, J = 3 Hz, 9 Hz), 7.86 (1H, d, J = 3 Hz), 8.49 (1H, s ), 8.78 (1H, br s). Example C-50 Production of N- (2- {4- [(3-chloro-4-. {3- [4- (trifluoromethyl) -1,3-thiazol-2-yl] phenoxy} phenyl) amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl.} Ethyl) -2-methy1-2- (methylsulfonyl) propanamide When using 5- (2-aminoethyl) -N- (3-chloro) dihydrochloride -4- { 3- [4- (trifluoromethyl) -1,3-thiazol-2-yl] phenoxy] phenyl) -5H-pyrrolo [3,2-d] pyrimidin-4-amine (200 mg ), 2-phenyl-2- (methylsulfonyl) propanoic acid (83 rag), 1-hydroxybenzotriazole (75 mg), triethylamine (0.23 ml), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (105 mg) and N, N-dimethylformamide (5.0 ml) and in the same manner as in Example C-8 (iii), the title compound (171 mg) was obtained in the form of a pale yellow powder. XH-NMR (CDCl3) d: 1.70 (6H, s), 2.93 (3H, s), 3.6-3.75 (2H, m), 4.40-4.55 (2H, m), 6.63 (1H, d, J = 3.3 Hz ), 7.00-7.10 (1H, m), 7.09 (1H, d, J = 8.7 Hz), 7.21 (1H, d, J = 3.0 Hz), 7.25-7.45 (2H, m), 7.60-7.70 (2H, m), 7.75 (1H, s), 7.80-7.95 (1H, m), 8.04 (1H, d, J = 2.4 Hz), 8.36 (1H, s), 8.53 (1H, s). Example C-51 Production of N- (2- {4- [(3-chloro-4-. {3- [4- (trifluoromethyl) -1,3-thiazol-2-yl] phenoxy] phenyl) amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl.} Ethyl) -3-hydroxy-3-methylbutanamide When using 5- (2-aminoethyl) -N- (3-chloro-4- dihydrochloride {. 3- 3- [4- (trifluoromethyl) -l, 3-thiazol-2-yl] phenoxy] phenyl) -5H-pyrrolo [3,2-d] pyrimidine-4-araine (200 mg), acid 3-hydroxy-3-ethoxybutanoic acid (59 mg), 1-hydroxybenzotriazole (75 mg), triethylamine (0.23 ml), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (105 mg) and N, N-dimethylformamide (5.0 ml) and in the same way as in the Example C-8 (iii), the title compound (95.3 mg) was obtained in the form of a white powder. XH-NMR (CDCl3) d: 1.33 (6H, s), 2.48 (2H, s), 3.60-3.70 (2H, m), 4.40-4.50 (2H, m), 6.60 (1H, d, J = 3.0 Hz ), 6.85-6.95 (1H, m), 7.00-7.10 (2H, m), 7.18 (1H, d, J = 3.0 Hz), 7.40 (1H, t, J = 9.0 Hz), 7.60-7.80 (4H, m), 8.07 (1H, s), 8.52 (1H, s), 8.63 (1H, s). Example C-52 Production of N- (3- {2-chloro-4- [(6-cyano-5-butyl-5H-pyrrolo [3,2- d] pyrimidin-4-yl) amino] phenoxy} phenyl) Cyclopropanecarboxamide To a solution of diisopropylamine (545 rag) in tetrahydrofuran (15 ml) was added n-butyllithium (2.9 ml) at 0 ° C. After stirring for 30 min, the mixture was cooled to -78 ° C, and 4-chloro-5-methyl-5H-pyrrolo [3,2-d] pyrimidine (603 mg) was added thereto. The mixture was stirred for 1 h, p-toluenesulfonyl cyanide (1300 mg) was added, and the mixture was heated to -40 ° C for 1 h. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and brine saturated, and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, hexane: ethyl acetate = 80: 20-30: 70). After concentrating under reduced pressure, the resulting crystals were dissolved in isopropyl alcohol (7.0 ml). Thereto was added N- [3- (4-amino-2-chlorophenoxy) phenyl] cyclopropanecarboxamide (232 mg), and the mixture was stirred at 80 ° C for 3 h. After concentrating under reduced pressure, water and saturated aqueous sodium acid carbonate were added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, hexane: ethyl acetate = 80: 20-> 100). The object fractions were concentrated under reduced pressure. The residue was crystallized from ethyl acetate-hexane to give the title compound (103 mg) as a white powder. XH-NMR (DMSO-d6) d: 0.77 (4H, d, J = 6.1 Hz), 1.73-1.81 (1H, m), 4.31 (3H, s), 6.66-6.70 (1H, m), 7.21-7.40 (4H, m), 7.53 (1H, s), 7.62 (1H, d, J = 8.7 Hz), 7.90 (1H, s), 8.64 (1H, s), 9.87 (1H, br s), 10.25 (1H , s).

Example C-53 (dimethylamino) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide (i) Production of 3,5-dichloro-4- [3- (dimethylamino) phenoxy] aniline To a solution of 3- (dimethylamino) phenol (470 mg) and 1,3-dichloro- 2-Iodo-5-nitrobenzene (1.00 g) in N, N-dimethylformamide (15 ml) was added potassium carbonate (850 mg) and the mixture was stirred at room temperature for 18 h. Under ice-cooling, brine was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: methanol = 100: 0-> 95: 5) and the crude product obtained was dissolved in 15% of ethanol with water content (23 ml). Reduced iron (750 mg) and calcium chloride (120 mg) were added, and the mixture was stirred at 80 ° C. for 8 h. The solid was removed by filtration, and the filtrate was concentrated under reduced pressure. Water was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by column chromatography on silica gel (eluent, hexane: ethyl acetate = 4: 1-> 1: 1) to give the title compound (402 mg ) in the form of a brown oil. XH-NMR (DMS0-d6) d: 2.85 (6H, s), 5.58 (2H, s), 5.88 (1H, dd, J = 1.9 Hz, 8.0 Hz), 6.19 (1H, t, J = 2.2 Hz), 6.37 (1H, dd, J = 1.9 Hz, 8.0 Hz), 6.69 (2H, s), 7.04 ( 1H, t, J = 8.3 Hz). (ii) Production of N-. { 2- [4- ( {3,5-dichloro-4- [3- (dimethylamino) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide A mixture of [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (150 mg), 3.5- dichloro-4- [3- (dimethylamino) phenoxy] aniline (150 mg) and isopropyl alcohol (8.0 ml) was stirred at 80 ° C for 12 h. Under cooling with ice, aqueous sodium bicarbonate was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by column chromatography on silica gel (eluent, ethyl acetate: hexane = 60: 40-> 100: 0), the crude product obtained (150 mg) was dissolved in tetrahydrofuran (10 ml), chloride solution was added, 4 N hydrogen / ethyl acetate (5.0 ml), and the mixture was stirred at 70 ° C for 20 h. The solvent was evaporated under reduced pressure, ethanol and diisopropyl ether were added to the residue, and the precipitated powder was collected by filtration and dissolved in N, N-dimethylformamide (7.0 ml). Methylsulfonylacetic acid (70 mg), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (160 mg), 1-hydroxybenzotriazole (70 mg) and triethylamine (0.15 ml) were added to the mixture, and the mixture was stirred at room temperature for 16 h. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate -> ethyl acetate: methanol = 90:10), and crystallized from diisopropyl ether to give the co-hypothesis of the title (74 mg). XH-NMR (DMSO-d6) d: 2.89 (6H, s), 3.11 (3H, s), 3.44-3.49 (2H, m), 4.06 (2H, s), 4.55-4.59 (2H, m), 5.89 -7.11 (5H, m), 7.66-8.69 (5H, m), 8.77 (1H, s).

Example C-54 Production of N- (tert-butyl) -3-. { 2-Chloro-4- [(5-butyl-5H-pyrrolo [3,2-d] pyrimidin-4-yl) amino] phenoxy} benzamide (i) Production of 3-. { 2-Chloro-4- [(5-methyl-5H-pyrrolo [3,2-d] pyrimidin-4-yl) amino] phenoxy} Methyl benzoate A mixture of 4-chloro-5-methyl-5H-pyrrolo [3, 2-d] pyrimidine (1.01 g), methyl 3- (4-amino-2-chlorophenoxy) benzoate (1.39 g) and isopropyl alcohol (10 ml) was stirred at 80 ° C overnight. An aqueous solution of sodium acid carbonate was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, ethyl acetate: hexane = 60: 40- >); 100: 0). The object fractions were concentrated under reduced pressure. Ethyl acetate-diethyl ether was added to the residue, and the precipitated solid was collected by filtration to give the title compound (1.77 g) as a yellow powder. XH-NMR (CDC13) d: 3.90 (3H, s), 4.15 (3H, s), 6.56 (1H, d, J = 3.3 Hz), 6.83 (1H, br s), 7.06 (1H, d, J = 8.8 Hz), 7.16-7.22 (2H, m), 7.40 (1H, t, J = 8.0 Hz), 7.46 (1H, dd, J = 2.5 Hz, 8.8 Hz), 7.56-7.60 (1H, m), 7.74- 7.79 (1H, m), 7.81 (1H, d, J = 2.5 Hz), 8.51 (1H, s). (ii) Acid production 3-. { 2-Chloro-4- [(5-methyl-5H-pyrrolo [3,2-d] pyrimidin-4-yl) amino] phenoxy} benzoic A 3-. { 2-Chloro-4- [(5-methyl-5H-pyrrolo [3,2-d] pyrimidin-4-yl) amino] phenoxy} Methyl benzoate (1.68 g) were added methanol (20 ml), tetrahydrofuran (5 ml) and 1 N aqueous sodium hydroxide solution (8.2 ml), and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure, 1N hydrochloric acid (8.2 ml), ethyl acetate and diisopropyl ether were added. The precipitated solid was collected by filtration, washed with water and diisopropyl ether to give the title compound (1.62 g) as a white powder. XH-NMR (DMSO-d6) d: 4.16 (3H, s), 6.45 (1H, d, J = 3.0 Hz), 7.24-7.32 (3H, m), 7.51 (1H, t, J = 8.0 Hz), 7.60 (1H, d, J = 3.0 Hz), 7.64-7.73 (2H, m), 7.96 (1H, d, J = 2.4 Hz), 8.32 (1H, s), 8.62 (1H, br s). (iii) Production of N- (tert-butyl) -3-. { 2-Chloro-4- [(5-methyl-5H-pyrrolo [3,2-d] pyrimidin-4-yl) amino] phenoxy} benzamide A mixture of 3- acid. { 2-Chloro-4- [(5-methyl-5H-pyrrolo [3,2-d] pyrimidin-4-yl) amino] phenoxy} benzoic acid (197 mg), tert-butylamine (0.105 ml), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (115 mg), monohydrate 1- hydroxybenzotriazole (92 mg) and N, N-dimethylformamide (3 ml) was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100-> 20: 80). The object fractions were concentrated under reduced pressure. The residue was crystallized from ethyl acetate-diisopropyl ether to give the title compound (215 mg) as a white powder. XH-NMR (CDC13) d: 1.45 (9H, s), 4.15 (3H, s), 5.96 (1H, br s), 6.56 (1H, d, J = 3.0 Hz), 6.85 (1H, br s), 7.02 (1H, d, J = 8.5 Hz), 7.05-7.10 (1H, m), 7.18 (1H, d, J = 3.0 Hz), 7.31-7.44 (4H, m), 7.80 (1H, d, J = 2.5 Hz), 8.50 (1H, Example C-55 Production of N-. { 2- [4- ( { 3-Chloro-4- [3- (diethylamino) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide (i) Production of 3- (4-amino-2-chlorophenoxy) -N, N-diethylaniline When using 3- (diethylamino) phenol (920 mg), 3-chloro-4-fluoronitrobenzene ( 1.01 g), potassium carbonate (1.38 g), N, N-dimethylformamide (20 ml), platinum-activated charcoal 5% (300 mg), ethyl acetate (10 ml) and methanol (5.0 ml) and the same as in Example C-6 (iv) and (v), the title compound (954 mg) was obtained in the form of crystals. XH-NMR (DMSO-d6) d: 1.06-1.12 (6H, m), 3.25-3.34 (4H, m), 5.26 (2H, s), 5.94-6.57 (4H, m), 6.68 (1H, d, J = 2.0 Hz), 6.86 (1H, d, J = 8.0 Hz), 7.12 (1H, t, J = 8.3 Hz). (ii) Production of N-. { 2- [4- ( { 3-Chloro-4- [3- (diethylamino) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide When using 3- (4-amino-2-chlorophenoxy) -N, N-diethylaniline (150 mg), [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (150 mg), isopropyl alcohol (10 ml), tetrahydrofuran ( 15 ml), 4 N hydrogen chloride solution / ethyl acetate (5.0 ml), methylsulfonylacetic acid (190 mg), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (290 mg), 1-hydroxybenzotriazole ( 10 mg), triethylamine (4.0 ml) and N, N- dimethylformamide (15 ml) and in the same manner as in Example C-53 (ii), the title compound (117 mg) was obtained as crystals. XH-NMR (DMSO-d6) d: 1.05-1.10 (6H, m), 3.10 (3H, s), 3.27-3.34 (4H, m), 3.44-3.49 (2H, m), 4.05 (2H, s) , 4.53-4.57 (2H, m), 6.00-6.49 (4H, m), 7.07-7.91 (5H, m), 8.32 (1H, s), 8.62-8.68 (2H, m). Example C-56 Production of N-. { 2- [4- ( { 3-Chloro-4- [3- (diethylamino) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -3-hydroxy-3-methylbutanamide When using 3- (4-amino-2-chlorophenoxy) -N, N-diethylaniline (150 mg), [2- (4-chloro-5H-pyrrolo [3, 2-d] tert-butyl pyrimidin-5-yl) ethyl] carbamate (150 mg), isopropyl alcohol (10 ml), tetrahydrofuran (15 ml), 4 N hydrogen chloride solution / ethyl acetate (5.0 ml), 3- acid hydroxy-3-methylbutanoic (75 rag), l-ethyl-3- (3-diraethylaminopropyl) carbodiimide hydrochloride (191 mg), 1-hydroxybenzotriazole (5.0 mg), triethylamine (0.3 ml) and N, N- dimethylformamide (6 ml) and in the same manner as in Example C-53 (ii), the title compound (94 mg) was obtained as crystals. 2 H-NMR (DMSO-dg) d: 1.05-1.17 (12H, m), 2.20 (2H, s), 3.24-3.34 (4H, m), 3.37-3.44 (2H, ra), 4.48-4.53 (2H, m), 4.65 (1H, s), 6.01-6.48 (4H, m), 7.06-7.97 (5H, m), 8.22-8.26 (1H, m), 8.31 (1H, s), 8.80 (1H, s) . Example C-57 Production of N- [3- (2-chloro-4. {[[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino-phenoxy) -phenyl] -2, 2-dimethylpropanamide A mixture of N- [3- (4-amino-2-chlorophenoxy) phenyl] -2,2-dimethylpropanamide (70 mg) and benzoate of 2- (4-chloro-5H-pyrrolo [3, 2- d] pyriraidin-5-yl) ethyl (63 mg) was dissolved in isopropyl alcohol (3 ml), pyridine hydrochloride (5 mg) was added thereto, and the mixture was stirred at 80 ° C for 16 h. The reaction mixture was cooled to room temperature, 1 N aqueous sodium hydroxide solution (2 ml) was added, and the mixture was stirred at room temperature for 9 h. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 10: 90 → 0: 100 → ethyl acetate: methanol = 90:10), and crystallized from diisopropyl ether / ethyl acetate. ethyl to give the title compound (49 mg) as crystals. XH-NMR (DMSO-d6) d: 1.16 (9H, s), 3.86-3.89 (2H, ra), 4.52-4.55 (2H, m), 6.50-6.66 (2H, m), 7.18-7.97 (7H, m), 8.33 (1H, s), 9.22 (1H, s), 9.83 (1H, br s). Example C-58 Production of 2- [4- ( { 3-Chloro-4- [3- (diethylamino) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethanol Al use 3- (4-amino-2-chlorophenoxy) -N, N-diethylaniline (112 mg), 2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl benzoate ( 100 mg), isopropyl alcohol (5.0 ml), 1 N aqueous solution of sodium hydroxide (5.0 ml) and methanol (10 ml) and in the same manner as in Example C-57, the compound of the title (52 mg) in the form of crystals. XH-NMR (DMSO-d6) d: 1.05-1.09 (6H, m), 3.26-3.33 (4H, m), 3.85-3.88 (2H, m), 4.51-4.54 (2H, m), 5.99-6.41 ( 3H, m), 6.49 (1H, d, J = 3.0 Hz), 7.05-7.94 (5H, m), 8.32 (1H, s), 9.76 (1H, br s). Example C-59 Production of 3- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. Phenoxy) -N- (1 -methylcyclohexyl) benzamide A mixture of 3- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino} phenoxy ) benzoic acid (170 mg), 1-methylcyclohexaneamine hydrochloride (180 mg), l-ethyl-3- (3-dimethylareneopropyl) carbodiimide hydrochloride (115 mg), 1-hydroxybenzotriazole monohydrate (92 mg), triethylamine (0.170 ml) ) and N, N-dimethylformamide (5 ml) was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to column chromatography on silica gel (eluent, methanol: ethyl acetate = 0: 100-20: 80) and silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100-> 20: 80 ), and the subject fractions were concentrated under reduced pressure. The residue was crystallized from ethyl acetate-diisopropyl ether to give the title compound (92 mg) as a white powder. XH-NMR (CDC13) d: 1.20-1.70 (13H, m), 2.05-2.20 (2H, ra), 4.07-4.17 (2H, m), 4.35-4.42 (2H, m), 5.86 (1H, br s ), 6.14 (1H, d, J = 3.3 Hz), 6.68 (1H, br s), 6.97-7.12 (3H, m), 7. 30-7.45 (4H, m), 7.81 (1H, d, J = 2.4 Hz), 8.23 (1H, s), 9. 69 (1H, br s). Example C-60 Production of 3- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. Phenoxy) -N-cyclohexylbenzamide One 3- (2-chloro-4- {[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino} phenoxy) benzoic acid (170 mg) ), cyclohexanamine (119 mg), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (115 mg), 1-hydroxybenzotriazole monohydrate (92 mg) and N, N- dimethylformamide (5 ml) was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100-20: 80). The object fractions were concentrated under reduced pressure. The residue was crystallized from ethyl acetate-diisopropyl ether to give the title compound (178 mg) as a white powder. XH-NMR (CDC13) d: 1.10-1.82 (8H, ra), 1.95-2.07 (2H, m), 3.86-4.01 (1H, m), 4.01-4.18 (2H, m), 4.37-4.44 (2H, m), 6. 03 (1H, d, J = 8.1 Hz), 6.04-6.12 (1H, m), 6.22 (1H, d, J = 3.0 Hz), 6.98-7.11 (3H, m), 7.32-7.44 (4H, m) , 7.79 (1H, d, J = 2.7 Hz), 8.28 (1H, s), 9.57 (1H, br s). Example C-61 Production of N- (tert-butyl) -3- (4-. {[[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino] hydrochloride. 2-methylphenoxy) benzamide (i) Production of methyl 3- (2-methyl-4-nitrophenoxy) benzoate A raezcla of methyl 3-hydroxybenzoate (3.04 g), 2-fluoro-5-nitrotoluene (3.10 g), potassium carbonate (4.15 g) ) and N, N-dimethylformamide (20 ml) was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, ethyl acetate: hexane = 5: 95- »15: 85). The object fractions were concentrated under reduced pressure to give the title compound (5.66 g) as a pale yellow solid. XH-NMR (CDC13) d: 2.41 (3H, s), 3.91 (3H, s), 6.78 (1H, d, J = 8.9 Hz), 7.21-7.27 (1H, m), 7.49 (1H, t, J = 7.8 Hz), 7.65-7.68 (1H, m), 7.86-7.91 (1H, m), 8.01 (1H, dd, J = 2.8 Hz, 8.9 Hz), 8.17 (1H, d, J = 2.8 Hz). (ii) Production of 3- (2-methyl-4-nitrophenoxy) benzoic acid methyl 3- (2-methyl-4-nitrophenoxy) benzoate (5.66 g) was added isopropyl alcohol (100 ml) and 1 N aqueous solution of sodium hydroxide (22 ml) and the mixture was stirred at room temperature overnight. To the mixture of After the reaction, 1 N hydrochloric acid (25 ml) was added and the precipitated solid was collected by filtration, and washed with water to give the title compound (4.54 g) as a white powder. XH-NMR (CDC13) d: 2.41 (3H, s), 6.81 (1H, d, J = 8.9 Hz), 7.26-7.32 (1H, m), 7.52 (1H, t, J = 7.9 Hz), 7.70-7.74 (1H, m), 7.92-7.97 (1H, m), 8.02 (1H, dd, J = 2.9 Hz, 8.9 Hz), 8.17 (1H, d, J = 2.9 Hz). (iii) Production of N- (tert-butyl) -3- (2-methyl-4-nitrophenoxy) benzamide A mixture of 3- (2-methyl-4-nitrophenoxy) benzoic acid (820 mg), thionyl chloride ( 0.438 ml), N, N-dimethylformamide (one drop) and toluene (10 ml) was stirred at 80 ° C for 2 h. Thionyl chloride (0.656 ml) was added and the mixture was further stirred for 1 h. The reaction mixture was concentrated under reduced pressure, toluene was added, and the mixture was again concentrated under reduced pressure. A solution of the residue in tetrahydrofuran (5 ml) was added to a solution of tert-butylamine (439 mg) and triethylamine (0.627 ml) in tetrahydrofuran (10 ml) and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to column chromatography on silica gel (eluent, ethyl acetate: hexane = 10: 90- »30: 70). The object fractions were concentrated under reduced pressure. The residue was crystallized from ethyl acetate-hexane to give the title compound (948 mg) as a white powder. 2H-NMR (CDC13) d: 1.47 (9H, s), 2.40 (3H, s), 5.93 (1H, br s), 6.79 (1H, d, J = 8.9 Hz), 7.14 (1H, ddd, J = 1.2 Hz, 2.5 Hz, 7.8 Hz), 7.40-7.53 (3H, m), 8.00 (1H, dd, J = 2.8 Hz, 8.9 Hz), 8.15 (1H, d, J = 2.8 Hz). (iv) Production of 3- (4-amino-2-methylphenoxy) -N- (tert-butyl) benzamide To a solution of N- (tert-butyl) -3- (2-methyl-4-nitrophenoxy) benzamide ( 948 mg) in ethyl acetate (20 ml) was added 5% activated carbon-platinum (50 mg) and the mixture was stirred under an atmosphere of hydrogen at room temperature for 6 h. The catalyst was filtered, the filtrate was concentrated and the obtained residue was subjected to silica gel column chromatography (eluent, ethyl acetate: hexane = 25: 75-> 45: 55). The subject fractions were concentrated under reduced pressure to give the title compound (892 mg) as a reddish purple oil. XH-NMR (CDCl3) d: 1.45 (9H, s), 2.08 (3H, s), 3.56 (2H, br s), 5.89 (1H, br s), 6.51 (1H, dd, J = 2.5 Hz, 8.4 Hz), 6.58 (1H, d, J = 2.5 Hz), 6.77 (1H, d, J = 8.4 Hz), 6.87-6.94 (1H, m), 7.22-7.30 (3H, m). (v) Production of N- (tert-butyl) -3- (4-. {[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino hydrochloride} -2-methylphenoxy) benzamide A mixture of 2- (4-chloro-5H-pyrrolo [3,2-d] pyriraidin-5-yl) ethyl benzoate (121 mg), 3- (4-amino-2) -methylphenoxy) -N- (tert-butyl) benzamide (119 mg) and isopropyl alcohol (5 ml) was stirred at 80 ° C overnight. An aqueous solution of sodium acid carbonate was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue obtained was subjected to silica gel column chromatography (eluent, ethyl acetate: hexane = 60: 40-100: 0). The object fractions were concentrated under reduced pressure. The residue was crystallized from ethyl acetate-diisopropyl ether, and collected by filtration. Methanol (5 ml), tetrahydrofuran (1 ml) and 1 N aqueous sodium hydroxide solution (1 ml) were added to the obtained powder and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue obtained was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100- > 20:80). The object fractions were concentrated under reduced pressure. The residue was dissolved in ethyl acetate-ethanol and 1N hydrogen chloride solution / ethyl acetate (0.4 ml) was added. The solvent was evaporated under reduced pressure and the residue obtained was crystallized from ethanol-ethyl acetate to give the title compound (139 mg) as a white powder. XH-NMR (DMSO-de) d: 1.36 (9H, s), 2.20 (3H, s), 3.90 (2H, t, J = 4.4 Hz), 4.69 (2H, t, J = 4.4 Hz), 6.30- 6.55 (1H, m), 6.69 (1H, d, J = 3.0 Hz), 7.02-7.12 (2H, m), 7.28-7.32 (1H, m), 7.43 (1H, t, J = 8.0 Hz), 7.48 -7.59 (3H, m), 7.81 (1H, br s), 7.99 (1H, d, J = 3.0 Hz), 8.72 (1H, s), 10.77 (1H, br s). Example C-62 Production of N- (tert-butyl) -3- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.} phenoxy) -N-methylbenzamide (i) Production of methyl 3- (2-chloro-4-nitrophenoxy) benzoate When using methyl 3-hydroxybenzoate (8.20 g), 2- chloro-1-fluoro-4-nitrobenzene (9.46 g), potassium carbonate (11.2 g) and N, N-dimethylformamide (50 ml) and in the same manner as in Example C-61 (i), the compound of the title (16.0 g) in the form of a pale yellow solid. XH-NMR (CDC13) d: 3.92 (3H, s), 6.91 (1H, d, J = 9.1 Hz), 7.29 (1H, ddd, J = 0.8 Hz, 2.6 Hz, 8.0 Hz), 7.52 (1H, t, J = 8.0 Hz), 7.70-7.73 (1H, m), 7.91-7.97 (1H, m) , 8.07 (1H, dd, J = 2.8 Hz, 9.1 Hz), 8.39 (1H, d, J = 2.8 Hz). (ii) Production of 3- (2-chloro-4-nitrophenoxy) benzoic acid When using methyl 3- (2-chloro-4-nitrophenoxy) benzoate (7.08 g), isopropyl alcohol (150 ml), tetrahydrofuran (50 ml) and 1 N aqueous solution of sodium hydroxide (25.3 ml) and in the same manner as in Example C-61 (ii), the compound was obtained of the title (5.31 g) in the form of a white powder. XH-NMR (CDCl3) d: 6.94 (1H, d, J = 9.0 Hz), 7.31-7.37 (1H, m), 7.56 (1H, t, J = 8.0 Hz), 7.76-7.79 (1H, m), 7.97-8.03 (1H, m), 8.09 (1H, dd, J = 2.6 Hz, 9.0 Hz), 8.40 (1H, d, J = 2.6 Hz). (iii) Production of N- (tert-butyl) -3- (2-chloro-4-nitrophenoxy) -N-methylbenzamide When using 3- (2-chloro-4-nitrophenoxy) benzoic acid (881 rag), thionyl (1.09 ml), N, N-dimethylformamide (one drop), toluene (10 ml), tetrahydrofuran (5 ml), N-methyl-tert-butylamine (523 mg), triethylamine (0.627 ml) and tetrahydrofuran (10 ml) and in the same manner as in Example C-βl (iii), the title compound (1.14 g) was obtained as a colorless oil. XH-NMR (CDC13) d: 1.50 (9H, s), 2.87 (3H, s), 6.92 (1H, d, J = 9.1 Hz), 7.08-7.16 (2H, m), 7.30-7.35 (1H, m ), 7.45 (1H, t, J = 7.8 Hz), 8.06 (1H, dd, J = 2.6 Hz, 9.1 Hz), 8.38 (1H, d, J = 2.6 Hz). (iv) Production of 3- (4-amino-2-chlorophenoxy) -N- (tert-butyl) -N-methylbenzamide When using N- (tert-butyl) -3- (2-chloro-4-nitrophenoxy) - N-methylbenzamide (1.14 g), ethyl acetate (20 ml) and 5% activated carbon-platinum (50 mg) and in the same manner as in Example C-61 (iv), the title compound was obtained ( 868 mg) in the form of a yellow powder. XH-NMR (CDCl3) d: 1.48 (9H, s), 2.84 (3H, s), 3.69 (2H, br s), 6.55 (1H, dd, J = 2.8 Hz, 8.7 Hz), 6.76 (1H, d, J = 2.8 Hz), 6.86-6.93 (3H, m), 7.03-7.08 (1H, m ), 7.27 (1H, t, J = 7.8 Hz). (v) Production of N- (tert-butyl) -3- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. phenoxy) -N-methylbenzamide A mixture of 2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl benzoate (121 mg), 3- (4-amino) -2-chlorophenoxy) -N- (tert-butyl) -N-methylbenzamide (133 mg) and isopropyl alcohol (5 ml) was stirred at 80 ° C overnight.

An aqueous solution of sodium acid carbonate was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue obtained was subjected to silica gel column chromatography (eluent, ethyl acetate: hexane = 60: 40-> 100: 0). The object fractions were concentrated under reduced pressure. To the residue were added methanol (5 ml), tetrahydrofuran (1 ml) and 1 N aqueous sodium hydroxide solution (1 ml), and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100-> 20: 80). The object fractions were concentrated under reduced pressure. The residue was crystallized from ethyl acetate-diisopropyl ether to give the title compound (173 mg) as a white powder. XH-NMR (CDC13) d: 1.48 (9H, s), 2.86 (3H, s), 4.09 (2H, t, J = 4.5 Hz), 4.38 (2H, t, J = 4.5 Hz), 6.19 (1H, d, J = 3.3 Hz), 6.50-6.90 (1H, m), 6.95-7.03 (4H, m), 7.04-7.09 (1H, m), 7.26-7.39 (2H, m), 7.82 (1H, d, J = 2.5 Hz), 8.26 (1H, s), 9.73 (1H, br s).

Example C-63 Production of 3- (2-chloro-4. {[[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino] phenoxy) -N- hydrochloride (1-ethynylcyclohexyl) benzamide A mixture of 3- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3], 2-d] pyrimidin-4-yl] amino} phenoxy) benzoic acid (170 mg), 1-ethynylcyclohexaneamine (148 mg), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (115 mg), 1-hydroxybenzotriazole monohydrate (92 mg) and N, N-dimethylformamide (5 ml) was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100-> 20: 80). The object fractions were concentrated under reduced pressure. The residue was dissolved in ethyl acetate-ethanol, and 1N hydrogen chloride solution / ethyl acetate (0.4 ml) was added thereto. The solvent was evaporated under pressure reduced and the obtained residue was crystallized from ethanol-ethyl acetate to give the title compound (160 mg) as a white powder. XH-NMR (DMS0-d6) d: 1.20-1.37 (1H, m), 1.43-1.64 (5H, m), 1.71-1.88 (2H, m), 2.04-2.18 (2H, m), 3.16 (1H, s), 3.85-3.95 (2H, m), 4.64-4.74 (2H, m), 6.20-6.40 (1H, m), 6.70 (1H, d, J = 3.0 Hz), 7.17 (1H, dd, J = 2.3 Hz, 8.1 Hz), 7.27-7.35 (2H, m), 7.48 (1H, t, J = 8.0 Hz), 7.57-7.65 (2H, ra), 7.94 (1H, d, J = 2.5 Hz), 7.98 -8.03 (1H, m), 8.17 (1H, br s), 8.76 (1H, s), 10.76-10.86 (1H, m). Example C-64 Production of 3- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. Phenoxy) -N- (1 , 1-dimethylprop-2-yn-l-yl) benzamide When using 3- (2-chloro-4-. {[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-) 4-yl] amino.}. Phenoxy) benzoic acid (170 mg), 3-amino-3-methyl-l-butine (120 mg), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (115 mg) , 1-hydroxybenzotriazole monohydrate (92 mg) and N, N-dimethylformamide (5 ml) and in the same manner as in Example C-59, the title compound (155 mg) was obtained as a white powder.

XH-NMR (CDCl3) d: 1.75 (6H, s), 2.37 (1H, s), 4.13 (2H, t, J = 4.3 Hz), 4.39 (2H, t, J = 4.3 Hz), 6.15 (1H, d, J = 3.3 Hz), 6.25 (1H, br s), 6.45 (1H, br s), 6.98-7.03 (2H, m), 7.08-7.14 (1H, m), 7.31-7.45 (4H, m), 7.78 ( 1H, d, J = 2.5 Hz), 8.23 (1H, s), 9.62 (1H, br s). Example C-65 Production of 3- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2- d] pyrimidin-4-yl] amino.}. Phenoxy) -N- (1 -ethylcyclohexyl) benzamide When using 3- (2-chloro-4. {[[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino} phenoxy) benzoic acid (170 mg), 1-ethylcyclohexaneamine (153 mg), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (115 mg), 1-hydroxybenzotriazole monohydrate (92 mg) and N, N-dimethylformamide (5 mg). ml) and in the same manner as in Example C-59, the title compound (136 mg) was obtained as a white powder. XH-NMR (CDCl3) d: 0.84 (3H, t, J = 7.4 Hz), 1.20-1.70 (8H, m), 1.88 (2H, q, J = 7.4 Hz), 2.10-2.21 (2H, m), 4.12 (2H, t, J = 4.5 Hz), 4.38 (2H, t, J = 4.5 Hz), 5.70 (1H, br s), 6.15 (1H, d, J = 3.0 Hz), 6.50 (1H, br s) ), 6.99 (1H, d, J = 3.0 Hz), 7.02 (1H, d, J = 8.8 Hz), 7.04-7.11 (1H, m), 7. 30-7.44 (4H, m), 7.80 (1H, d, J = 2.5 Hz), 8.23 (1H, s), 9.64 (1H, br s). Example C-66 Production of 3- hydrochloride. { 2-Chloro-4- [(5-methyl-5H-pyrrolo [3,2-d] pyrimidin-4-yl) amino] phenoxy} -N- (1-methylcyclohexyl) benzamide When using 3- acid. { 2-Chloro-4- [(5-methyl-5H-pyrrolo [3,2-d] pyrimidin-4-yl) amino] phenoxy J-benzoic acid (197 mg), 1-methylcyclohexaneamine hydrochloride (150 mg), hydrochloride ethyl-3- (3-dimethylaminopropyl) carbodiimide (144 mg), 1-hydroxybenzotriazole monohydrate (115 mg), triethylamine (0.139 ml) and N, N-dimethylformamide (5 ml) and in the same manner as in Example C-63, the title compound (178 mg) was obtained as a white powder. XH-NMR (DMSO-de) d: 1.18-1.57 (8H, m), 1.31 (3H, s), 2.13-2.29 (2H, m), 4.29 (3H, s), 6.62-6.65 (1H, m) , 7.16 (1H, dd, J = 2.6 Hz, 8.1 Hz), 7.28 (1H, d, J = 8.8 Hz), 7.33 (1H, m), 7.48 (1H, t, J = 8.0 Hz), 7.55-7.68 (3H, m), 7.91-7.98 (2H, m), 8.71 (1H, s), 9.78-9.94 (1H, m).

Example C-67 Production of 3- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. Phenoxy) -N- (l -methylcyclopentyl) benzamide When using 3- (2-chloro-4. {[[5- (2-hydroxyethyl) -5H-pyrrolo [3, 2-d] pyrimidin-4-yl] amino} phenoxy) benzoic acid (212 mg), 1-methylcyclopentanoamine hydrochloride (136 mg), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (144 mg), 1-hydroxybenzotriazole (101 mg), triethylamine (0.139 ml) and N , N-dimethylformamide (5 ral) and in the same manner as in Ejeraplo C-59, the title compound (162 mg) was obtained in the form of a white powder. 2H-NMR (CDC13) d: 1.50 (3H, s), 1.65-1.82 (6H, m), 1.98-2.13 (2H, m), 4.12 (2H, t, J = 4.4 Hz), 4.39 (2H, t , J = 4.4 Hz), 6.06 (1H, br s), 6.17 (1H, d, J = 3.0 Hz), 6.52 (1H, br s), 7.00 (1H, d, J = 3.0 Hz), 7.01 (1H , d, J = 8.8 Hz), 7.05-7.12 (1H, m), 7.30-7.37 (3H, m), 7.41 (1H, dd, J = 2.6 Hz, 8.8 Hz), 7.80 (1H, d, J = 2.6 Hz), 8.24 (1H, s), 9.66 (1H, br s).

Example C-68 Production of N-. { 2- [4- ( { 3-Chloro-4- [3- (3-methylbutoxy) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (Methylsulfonyl) acetamide (i) Production of 3-chloro-4- [3- (3-methylbutoxy) phenoxy] aniline To a solution of 3- (2-chloro-4-nitrophenoxy) phenol (1.0 g) and 1-iodo-3-methylbutane (1.0 ral) in N, N-dimethylformamide (20 ml) was added cesium carbonate (1.6 g) and the mixture was stirred at room temperature for 2 h. Under ice-cooling, water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by column chromatography on silica gel (eluent, hexane: ethyl acetate = 1: 0-> 1: 1). The obtained crude product was dissolved in 15% ethanol containing water (25 ml), reduced iron (1.60 g) and calcium chloride (220 mg) were added, and the mixture was stirred at 80 ° C for 8 h. The solid was removed by filtration, and the filtrate was concentrated under reduced pressure. Water was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, hexane: ethyl acetate = 4: 1- »1: 1) to give the title compound (806 mg) in the form of a brown oil. XH-NMR (DMSO-d6) d: 0.89-0.92 (6H, m), 1.53-1.60 (2H, m), 1.70-1.79 (1H, m), 3.91-3.95 (2H, m), 5.33 (2H, s), 6.31-6.33 (2H, m), 6.53-6.60 (2H, m), 6.71-6.72 (1H, m), 6.88-6.91 (1H, m), 7.14-7.20 (1H, m). (ii) Production of N-. { 2- [4- ( { 3-chloro-4- [3- (3-methyl-butoxy) phenoxy] -phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide When using 3-chloro-4- [3- (3-methylbutoxy) phenoxy] aniline (250 mg), [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (250 mg), isopropyl alcohol (20 ml), ethyl acetate ethyl (10 ml), 4 N hydrogen chloride solution / ethyl acetate (15 ml), methylsulfonylacetic acid (72 mg), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (187 mg), 1- hydroxybenzotriazole (10 mg), triethylamine (1.5 ml) and tetrahydrofuran (10 ml) and in the same manner as in Example C-53 (ii), the title compound (277 mg) was obtained as crystals.

XH-NMR (DMSO-d6) d: 0.91-0.93 (6H, m), 1.56-1.78 (3H, m), 3.10 (3H, s), 3.42-3.49 (2H, m), 3.95-4.05 (4H, m), 4.52-4.60 (2H, m), 6.43-6.70 (4H, m), 7.16-7.94 (5H, m), 8.34 (1H, s), 8.64-8.68 (2H, m). Example C-69 Production of N- (2- { - [(3-chloro-4- { 3- [(3-methylbut-2-en-l-yl) oxy] phenoxy] phenyl) amino] -5H -pyrrolo [3,2-d] pyrimidin-5-yl.} ethyl) -2- (methylsulfonyl) acetamide (i) Production of 3-chloro-4-. { 3- [(3-methylbut-2-en-1-yl) oxy] phenoxy} Aniline To a solution of 3- (2-chloro-4-nitrophenoxy) phenol (1.0 g) and l-brorao-3-methylbut-2-ene (1.5 ml) in N, N-dimethylformamide (20 ml) was added carbonate of cesium (1.8 g) and the mixture was stirred at room temperature for 2 h. Under ice-cooling, water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by gel column chromatography of silica (eluent, hexane: ethyl acetate = 1: 0-> 1: 1). The obtained crude product was dissolved in 15% ethanol containing water (25 ml), reduced iron (1.60 g) and calcium chloride (220 mg) were added, and the mixture was stirred at 80 ° C for 8 h. The solid was removed by filtration, and the filtrate was concentrated under reduced pressure. Water was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by column chromatography on silica gel (eluent, hexane: ethyl acetate = 4: 1- >; 1: 1) to give the title compound (730 mg) as a brown oil. XH-NMR (DMSO-d6) d: 1.62-1.71 (6H, m), 4.42-4.47 (2H, m), 5.32-5.36 (1H, m), 6.32-6.35 (2H, ra), 6.56-6.59 ( 2H, m), 6.71-6.72 (1H, m), 6.87-6.90 (1H, m), 7.13-7.19 (1H, m). (ii) Production of N- (2- {4- [(3-chloro-4- {[3- [(3-methylbut-2-en-1-yl) oxy] phenoxy} phenyl) amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl.} ethyl) -2- (methylsulfonyl) acetamide When using 3-chloro-4-. { 3- [(3-methylbut-2-en-1-yl) oxy] phenoxy} aniline (150 rag), [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (150 mg), isopropyl alcohol (16 ml), acetate ethyl acetate (10 ml), 4 N hydrogen chloride solution / ethyl acetate (5 ml), methylsulfonylacetic acid (120 mg), l-ethyl-3- hydrochloride (3-dimethylaminopropyl) carbodiimide (470 mg), 1-hydroxybenzotriazole (10 mg), triethylamine (1.5 ml) and N, N-dimethylformamide (15 ml) and in the same manner as in Example C-53 (ii), the title compound (108 mg) was obtained in the form of crystals. XH-NMR (DMSO-d6) d: 1.75-1.79 (6H, m), 3.10 (3H, s), 3.40-3.52 (2H, m), 4.03 (2H, s), 4.47-4.60 (4H, m) , 5.40-5.51 (1H, m), 6.40-6.70 (4H, m), 7.15-7.95 (5H, m), 8.35 (1H, s), 8.62-8.70 (2H, m). Example C-70 Production of N- (2- {4- [(3-chloro-4. {[3- [(2,2-dimethylpropyl) amino] phenoxy} phenyl) amino] -5H-pyrrolo [3, 2-d] pyrimidin-5-yl.} Ethyl) -2- (methylsulfonyl) acetamide (i) Production of 3- (2-chloro-4-nitrophenoxy) -N- (2,2-dimethylpropyl) aniline Was suspended 3- (2-chloro-4-nitrophenoxy) aniline hydrochloride (1.98 g) in tetrahydrofuran (80 ml), and thereto were added triethylamine (0.87 ml), acetic acid (6.0 ml) and pivalaldehyde (2.10 g), and the mixture was stirred for 30 min. Sodium triacetoxyborohydride (470 mg) was added, and the mixture was stirred for 2 h. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was separated and purified by silica gel column chromatography (eluent, hexane: ethyl acetate = 95: 5-> 1: 1) to give the title compound ( 1.79 g) in the form of a brown oil. XH-NMR (CDC13) d: 0.99 (9H, s), 2.89 (2H, s), 6.31-6.54 (3H, m), 6.89-7.26 (3H, m), 8.01-8.09 (1H, m), 8.37 (1H, s). (ii) Production of 3-chloro-4-. { 3- [(2, 2-dimethylpropyl) amino] phenoxy} Aniline 3- (2-chloro-4-nitrophenoxy) -N- (2,2-dimethylpropyl) aniline (1.0 g) was dissolved in 15% ethanol containing water (30 ml), reduced iron (800 mg) was added. ) and calcium chloride (100 mg), and the mixture was stirred at 80 ° C for 8 h. The solid was removed by filtration, and the filtrate was concentrated under reduced pressure. Water was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, hexane: ethyl acetate = 4: 1- > 1: 1) to give the title compound (737 mg) as a brown oil. XH-NMR (DMSO-d6) d: 0.95 (9H, s), 2.78-2.82 (2H, m), 6.31-6.54 (3H, m), 6.89-7.26 (3H, m), 8.01-8.09 (1H, m), 8.37 (1H, s). (iii) Production of N- (2- { 4- [(3-chloro-4-. {3- [2, 2-dimethylpropyl) amino] phenoxy] phenyl) amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl.} Ethyl) -2- (methylsulfonyl) acetamide When using 3-chloro-4-. { 3- [(2, 2-dimethylpropyl) amino] phenoxy} aniline (73 mg), [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (71 mg), isopropyl alcohol (5 ml), acetate ethyl ether (10 μl), 4 N hydrogen chloride solution / ethyl acetate (10 ml), methylsulfonylacetic acid (61 mg), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (220 mg), 1 -hydroxybenzotriazole (5.0 mg), triethylamine (1.5 ml) and N, N-dimethylformamide (7.0 ml) and in the same manner as in Example C-53 (ii), the title compound (48 mg) was obtained in the form of crystals. XH-NMR (DMSO-d6) d: 0.93 (9H, s), 2.76-2.79 (2H, ra), 3. 10 (3H, s), 3.42-3.48 (2H, m), 4.05 (2H, s), 4.53-4.59 (2H, m), 5.61-6.50 (5H, m), 6.98-7.12 (2H, m), 7.61-7.91 (3H, m), 8.33 (1H, s), 8.64-8.68 (2H, m).

Example C-71 Production of 3- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. Phenoxy) -N- (1 -methyl-1-phenylethyl) benzamide When using 3- (2-chloro-4. {[[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino]. phenoxy) benzoic acid (170 mg), cumylaraine (108 mg), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (115 mg), 1-hydroxybenzotriazole (81 mg) and N, N-dimethylformamide (5 mg). ml) and in the same manner as in Example C-59, the title compound (139 mg) was obtained as a white powder. XH-NMR (CDC13) d: 1.79 (6H, s), 4.02 (2H, t, J = 4.5 Hz), 4.32 (2H, t, J = 4.5 Hz), 6.16 (1H, d, J = 3.0 Hz), 6.50 (1H, br s), 6.95-7.00 (2H, m), 7.07-7.13 (1H, m), 7.17-7.46 (9H, m), 7.77 (1H, d, J = 2.5 Hz), 8.22 (1H, s), 9.66 (1H, br s).

Production of 3- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. Phenoxy) -N- (2 -hydroxy-2-methylpropyl) benzamide (i) Production of 3- (2-chloro-4-nitrophenoxy) -N- (2-hydroxy-2-methylpropyl) benzamide 3- (2-chloro-4-nitrophenoxy) was dissolved ) benzoic (500 mg) in a mixed solvent of tetrahydrofuran (5 ml) / N, N-dimethylformamide (5 ml), and l-amino-2-methylpropan-2-ol (199 mg), 1-hydroxybenzotriazole was successively added (347 mg), triethylamine (0.7 ml) and l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (496 mg), and the mixture was stirred at room temperature for 2.5 h. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 33:67? 0: 100) to give the title compound (448 mg) as a white powder. XH-NMR (CDC13) d: 1.30 (6H, s), 3.48 (2H, d, J = 5.8 Hz), 6.60 (1H, br s), 6.92 (1H, d, J = 9.1 Hz), 7.19-7.25 (1H, ra), 7.47-7.58 (2H, m), 7.61-7.69 (1H, m), 8.07 (1H, dd, J = 2.8 Hz, 9.1 Hz), 8.39 (1H, d, J = 2.8 Hz). (ii) Production of 3- (4-amino-2-chlorophenoxy) -N- (2-hydroxy-2-methylpropyl) benzamide 3- (2-Chloro-4-nitrophenoxy) -N- (2-hydroxy-2-methylpropyl) benzamide (446 mg) was dissolved in a mixed solvent of ethanol (13.5 ml) / water (1.5 ml), iron was added reduced (347 mg) and calcium chloride (68 mg), and the mixture was stirred with heating under reflux for 15 h. The reaction mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. The residue was dissolved in ethyl acetate, and the solution was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 33: 67-0: 100) to give the title compound (349 mg) as a colorless oil. XH-NMR (CDC13) d: 1.27 (6H, s), 2.38 (1H, br s), 3.44 (2H, d, J = 6.0 Hz), 3.71 (2H, br s), 6.53-6.64 (1H, m ), 6.57 (1H, dd, J = 2.8 Hz, 8.7 Hz), 6.78 (1H, d, J = 2.8 Hz), 6.90 (1H, d, J = 8.7 Hz), 6.97-7.03 (1H, m), 7.29-7.37 (2H, m), 7.38-7.44 (1H, m). (iii) Production of 3- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. phenoxy) -N - (2-hydroxy-2-methylpropyl) benzamide A mixture of 2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl benzoate (84.3 mg) and 3- (4- araino-2-chlorophenoxy) -N- (2-hydroxy-2-methylpropyl) benzamide (110 mg) was dissolved in isopropyl alcohol (2 ml), an catalytic amount of pyridine hydrochloride, and the mixture was stirred at 70 ° C for 16 h. After cooling to room temperature, 1 N aqueous sodium hydroxide solution (1 ml) was added, and the mixture was stirred at room temperature for 9 h. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 10: 90-> 0: 100-> ethyl acetyl: methanol = 90:10), and crystallized from diisopropyl ether ethyl acetate to give the title compound (99.7 mg) as white crystals. XH-NMR (DMSO-de) d: 1.09 (6H, s), 3.23 (2H, d, J = 6. 0 Hz), 3.87 (2H, t, J = 4.5 Hz), 4.47-4.61 (3H, m), 6.30 (1H, br s), 6.51 (1H, d, J = 3.0 Hz), 7.05-7.13 (1H , m), 7.24 (1H, d, J = 8.9 Hz), 7.36-7.42 (1H, m), 7.46 (1H, t, J = 7.9 Hz), 7.56-7.64 (2H, m), 7.66 (1H, d, J = 3.0 Hz), 7.98 (1H, d, J = 2.6 Hz), 8.31 (1H, t, J = 6.0 Hz), 8.34 (1H, s), 9.87 (1H, br s).

Example C-73 Production of N- (tert-butyl) -5- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.} phenoxy) -2-fluorobenzamide When using 5- (4-amino-2-chlorophenoxy) -N- (tert-butyl) -2-fluorobenzamide (260 mg), 2- (4-chloro-5H-pyrrolo benzoate [ 3, 2-d] pyrimidin-5-yl) ethyl (150 mg), isopropyl alcohol (7.0 ml), 1 N aqueous solution of sodium hydroxide (4.0 ml) and methanol (10 ml) and in the same manner as in in Ejeraplo C-57, the title compound (285 mg) was obtained in the form of crystals. XH-NMR (DMSO-d6) d: 1.33 (9H, s), 3.85-3.89 (2H, m), 4.51-4.54 (2H, m), 6.50-7.29 (5H, m), 7.58-7.97 (4H, m), 8.33 (1H, s), 9.76 (1H, br s).

Production of N- (tert-butyl) -3- [2-chloro-4- (. {5- [2- (methylthio) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-hydrochloride] il.}. amino) phenoxy] benzamide (i) Production of 4-chloro-5- [2- (methylthio) ethyl] -5H-pyrrolo [3,2-d] pyrimidine A mixture of 4-chloro-5H-pyrrolo [3, 2-d] pyrimidine (768 mg), 2-chloroethylmethylsulfide (664 mg), cesium carbonate (1.95 g) and N, N-dimethylformamide (10 ml) was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. To a mixture of the obtained residue, cesium carbonate (3.91 g) and N, N-dimethylformamide (10 ml) was added dropwise a solution of 2-chloroethylmethylsulfide (553 mg) in N, N-dimethylformamide (3 ml) and The mixture was stirred at room temperature overnight. A solution of 2-chloroethylmethylsulfide (553 mg) in N, N-dimethylformamide (3 ml) was added dropwise and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, ethyl acetate: hexane = 40: 60-> 60: 40). The object fractions were concentrated under reduced pressure to give the title compound (880 mg) as a pale yellow solid. XH-NMR (CDC13) d: 2.04 (3H, s), 2.95 (2H, t, J = 6.9 Hz), 4.67 (2H, t, J = 6.9 Hz), 6.75 (1H, d, J = 3.2 Hz), 7.56 (1H, d, J = 3.2 Hz), 8.71 (1H, s). (ii) Production of N- (tert-butyl) -3- [2-chloro-4- (. {5- [2- (methylthio) ethyl] -5H-pyrrolo [3,2-d] pyrimidin hydrochloride] -4-yl.}. Amino) phenoxy] benzamide A mixture of 4-chloro-5- [2- (methylthio) ethyl] -5H-pyrrolo [3,2-d] pyrimidine (455 mg), 3- (4 -amino-2-chlorophenoxy) -N- (tert-butyl) benzamide (638 mg) and isopropyl alcohol (10 ml) was stirred at 80 ° C overnight. An aqueous solution of sodium acid carbonate was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, ethyl acetate: hexane = 50: 50-> 100: 0). The object fractions were concentrated under reduced pressure to give N- (tert-butyl) -3- [2-chloro-4- (. {5- [2- (methylthio) ethyl] -5H-pyrrolo [3,2- d] pyrimidin-4-yl.}. amino) phenoxy] benzamide (1.00 g) in the form of an amorphous powder. N- (tert-Butyl) -3- [2-chloro-4- (. {5- [2- (methylthio) ethyl] - 5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] benzamide (200 mg) was dissolved in ethyl acetate-ethanol, and 1N hydrogen chloride solution / ethyl acetate (0.5 ml) was added. The solvent was evaporated under reduced pressure and the obtained residue was crystallized from ethanol-ethyl acetate to give the title compound (138 mg) as a pale yellow powder. Vl-NMR (DMSO-d6) d: 1.36 (9H, s), 1.99 (3H, s), 2.88 (2H, t, J = 6.4 Hz), 4.92 (2H, t, J = 6.4 Hz), 6.69 ( 1H, d, J = 3.2 Hz), 7.16 (1H, dd, J = 3.0 Hz, 7.7 Hz), 7.24 (1H, d, J = 8.8 Hz), 7.36-7.39 (1H, m), 7.47 (1H, t, J = 8.0 Hz), 7.57-7.65 (2H, m), 7.84 (1H, br s), 7.92 (1H, d, J = 2.5 Hz), 8.06 (1H, d, J = 3.2 Hz), 8.73 (1H, s), 10.06 (1H, br s). Example C-75 Production of 3- (2-chloro-4-. {[[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino} phenoxy) -N- hydrochloride (1, l-dimethyl-2- (piperidin-1-yl) ethyl) benzamide When using 3- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3, 2 -d] pyrimidin-4-yl] amino.}. phenoxy) benzoic acid (170 mg), 2-methyl-1- (piperidin-1-yl) propan-2-amine (125 mg), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride 115 mg) 1-hydroxybenzotriazole mg; N, N-dimethylformamide (5 ml) and in the same manner as in Example C-63, the title compound (136 mg) was obtained as a white powder. Vl-NMR (DMSO-d6) d: 1.33-2.00 (6H, m), 1.51 (6H, s), 2.91-3.09 (2H, m), 3.27-3.62 (4H, m), 3.90 (2H, t, J = 4.5 Hz), 4.71 (2H, t, J = 4.5 Hz), 6.30-6.65 (1H, m), 6.71 (1H, d, J = 3.0 Hz), 7.15 (1H, dd, J = 2.3, 7.8 Hz), 7.30 (1H, d, J = 8.9 Hz), 7.45-7.53 (2H, m), 7.62 (1H, dd, J = 2.5 Hz, 8.9 Hz), 7.73 (1H, d, J = 7.7 Hz) , 7.96 (1H, d, J = 2.5 Hz), 8.02 (1H, d, J = 3.0 Hz), 8.17 (1H, br s), 8.76 (1H, s), 9.70 (1H, br s), 10.88 ( 1H, br s). Example C-76 Production of 5- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. Phenoxy) -N-cyclopropyl- 2-fluorobenzamide (i) Production of 5- [4- (. {5- [2- (Benzoyloxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) -2 methyl-chlorophenoxy] -2-fluorobenzoate When using methyl 5- (4-ammo-2-chlorophenoxy) -2-fluorobenzoate (1.50 g), 2- (4-chloro-5H-pyrrolo [3, 2-d] p? R? M benzoate ? d? n-5-? l) ethyl (1.53 g) and isopropyl alcohol (15 ml) and in the same manner as in Example C-2 (v), the title compound (2.12 g) was obtained in the form of crystals. XH-NMR (DMSO-d6) d: 3.80 (3H, s), 4.54-4.57 (2H, m), 4.94-4.97 (2H, m), 6.56 (1H, s), 7.21-7.79 (12H, m) , 8.32 (1H, s), 8.78 (1H, br s). (n) Production of 5- (2-chloro-4- { [5- (2-hydrox? et? l) -5H-pyrrolo [3,2-d] p? pm? dm- 4-? L] amino.}. Phenoxy?) -N-cyclopropy1-2-fluorobenzamide When using 5- [4- (. {5- [2- (benzoyloxy) ethyl] -5H-pyrrol [3, 2-d] p? R? M? Dm-4-? L.}. Ammo) -2-chlorophenoxy?] -2-fluorobenzoate methyl (200 mg), 1 N aqueous solution of sodium hydroxide (3.0 ml) and tetrahydrofuran (10 ml) and in the same manner as in Example C-2 (v), a compound was obtained. The obtained compound was reacted in the same manner as in Example C-9 (v) and cyclopropanamine (60 mg), l-et? -1-3- (3-dimethylareneopropyl) carbodiimide hydrochloride (200 mg) was used, 1-hydroxybenzotpazole (5.0 mg), tpetilamma (1.5 ml) and N, N-dimethylformamide (5.0 ml) to give the title compound (101 mg) in the form of crystals. VL-NMR (DMSO-de) d: 0.52-0.71 (4H, m), 2.77-2.83 (1H, m), 3.86-3.89 (2H, m), 4.52-4.55 (2H, m), 6.15-6.51 ( 2H, m), 7.01-7.97 (7H, m), 8.33 (1H, s), 8.37-1H, m) 9.84 (1H, br s). Example C-77 Production of 5- (4- { [5- (2-aminoethyl) -5H-pyrrolo [3, 2-d] pyrimidin-4-yl] amino.} -2-chlorophenoxy) -N-cyclopropy1-2 -fluorobenzamide A mixture of tert-butyl [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] carbamate (286 mg), 5- (4-amino-2- chlorophenoxy) -N-cyclopropyl-2-fluorobenzamide (310 mg) and isopropyl alcohol (5.0 ml) was stirred at 80 ° C for 12 h. Under cooling with ice, aqueous sodium bicarbonate was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The residue was separated and purified by column chromatography on silica gel (eluent, ethyl acetate: hexane = 60: 40-> 100: 0). The obtained crude product was dissolved in methanol (10 ml), 4N hydrogen chloride solution / ethyl acetate (5.0 ml) was added, and the mixture was stirred at 70 ° C for 20 h. Ethyl acetate and aqueous sodium hydrogen carbonate were added saturated, and the organic layer was dried over magnesium sulfate. The residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 10: 90 → 0: 100 → ethyl acetate: methanol = 90:10), and crystallized from diisopropyl ether / ethyl acetate. ethyl to give the title compound (356 mg) as crystals. ^ -RMN (DMSO-d6) d: 0.53-0.70 (4H, m), 2.77-2.85 (1H, m), 3.06 (2H, br s), 4.36 (2H, br s), 5.95 (2H, br s ), 6.48-8.01 (8H, m), 8.31 (1H, s), 8.37-8.38 (1H, m). Example C-78 Production of 3- (2-chloro-4. {[[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino] phenoxy) -N- ( 1, l-dimethyl-2- (morpholin-4-yl) ethyl) benzamide When using 3- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3, 2- d] pyriraidin-4-yl] amino.}. phenoxy) benzoic acid (170 mg), 2-methyl-1- (raorpholin-4-yl) propan-2-amine (127 mg), l-ethyl-3 hydrochloride - (3-dimethylaminopropyl) carbodiimide (115 mg), 1-hydroxybenzotriazole (81 mg) and N, N-dimethylformamide (5 ml) and in the same manner as in Example C-63, the title compound was obtained (128 mg) in the form of a white powder. XH-NMR (DMSO-d6) d: 1.52 (6H, s), 3.00-4.20 (12H, rn), 4.70 (2H, m), 6.20-6.70 (1H, m), 6.71 (1H, d, J = 3.0 Hz), 7.15 (1H, dd, J = 2.5 Hz, 7.8 Hz), 7.29 (1H, d, J = 8.8 Hz), 7.44-7.54 (2H, m), 7.62 (1H, dd, J = 2.5 Hz, 8.8 Hz), 7. 68-7.76 (1H, m), 7.95 (1H, d, J = 2.7 Hz), 8.01 (1H, d, J = 2.7 Hz), 8.15 (1H, br s), 8.75 (1H, s), 10.38 ( 1H, br s), 10.85 (1H, br s). Example C-79 Production of 5- (2-chloro-4- { [5- (2-methoxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. Phenoxy) -N-cyclopropyl- 2-fluorobenzamide When using 5- (4-amino-2-chlorophenoxy) -N-cyclopropyl-2-fluorobenzamide (100 mg), 4-chloro-5- (2-methoxyethyl) -5H-pyrrolo [3, 2-d pyrimidine (66 rag) and isopropyl alcohol (5.0 ml) and in the same manner as in Example C-22 (i), the title compound (131 mg) was obtained as crystals. XH-NMR (DMSO-d6) d: 0.52-0.71 (4H, m), 2.77-2.83 (1H, m), 3.31 (3H, s), 3.72-3.75 (2H, m), 4.64-4.67 (2H, m), 6.50-7.95 (8H, m), 8.34 (1H, s), 8.37-8.39 (1H, m), 9.97 (1H, br s).

Example C-80 Production of 5- [4- (. {5- [2- (acetylamino) ethyl] -5H-pyrrolo [3,2-d] p? R? M? D? N-4-? L.}. Amino ) -2-chlorophenoxy?] -N-cyclopropy1-2-fluorobenzamide When using 5- (4- { [5- (2-aramoet? L) -5H-pyrrolo [3, 2-d] p? pm? d? n-4-? l] amino.} -2-chlorophenoxy?) - Nc? clopropyl-2-fluorobenzamide (100 rag), acetic acid (40 mg), l-ethyl hydrochloride -3- (3-d? Met? Lam? Noprop?) Carbodnmide (120 mg), 1-hydroxybenzotriazole (5.0 mg), triethylamine (0.5 ml) and N, N-dimethylformamide (5.0 ral) and in the same way that in Example C-23 (v), the title compound (71 mg) was obtained as crystals. VH-NMR (DMSO-d6) d: 0.52-0.71 (4H, m), 1.79 (3H, s), 2.79-2.82 (1H, m), 3.33-3.39 (2H, m), 4.48-4.53 (2H, m), 6.49-6.50 (1H, m), 7.02-7.32 (4H, m), 7.63-8.43 (6H, m), 8.79 (1H, s).

Example C-81 Production of 5- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. Phenoxy) -2-fluoro- N- (1-methylcyclohexyl) benzamide Using 5- [4- (. {5- [2- (benzoyloxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) Methyl -2-chlorophenoxy] -2-fluorobenzoate (150 mg), 1 N aqueous solution of sodium hydroxide (3.0 ml) and tetrahydrofuran (10 ml) and in the same manner as in Example C-2 (v), a compound was obtained. The obtained compound was reacted in the same manner as in Example C-9 (v) and 1-methylcyclohexaneamine (110 mg), l-ethyl-3- (3-diraethylaminopropyl) carbodiimide hydrochloride (250 mg) was used, 1-hydroxybenzotriazole (5.0 mg), triethylamine (1.5 ml) and N, N-dimethylformamide (5.0 ml) to give the title compound (82 mg) as crystals. XH-NMR (DMSO-d6) d: 1.20-1.51 (13H, m), 2.14-2.18 (1H, m), 3.86-3.89 (2H, m), 4.52-4.56 (2H, m), 6.49-6.51 (1H, m), 7.17-7.68 (7H, m), 7.98 (1H, s), 8.34 (1H, br s), 9.85 (1H, br s).

Production of 5- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. Phenoxy) -2-fluorobenzamide use 5- [4- ( { 5- [2- (benzoyloxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) -2-chlorophenoxy] -2-fluorobenzoate of methyl (150 mg), 1 N aqueous solution of sodium hydroxide (3.0 ml) and tetrahydrofuran (10 ml) and in the same manner as in Example C-2 (v), a compound was obtained. The compound obtained was reacted in the same manner as in Example C-9 (v) and 30% solution of ammonia / methanol (5.0 ml), l-ethyl-3- (3-dimethylareneopropyl) carbodiimide hydrochloride was used. (300 mg), 1-hydroxybenzotriazole (30 mg), triethylamine (1.5 ml) and N, N-dimethylformamide (10 ml) to give the title compound (58 mg) as crystals. XH-NMR (DMSO-d6) d: 3.86-3.89 (2H, m), 4.52-4.56 (2H, m), 6.50-6.51 (1H, m), 7.22-8.04 (9H, m), 8.34 (1H, br s), 9.86 (1H, br s).

Example C-83 Production of 3- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. Phenoxy) -N- (1 -cyano-l-methylethyl) benzamide (i) Production of N- [3- (2-chloro-4-nitrophenoxy) benzoyl] -2-methylalaninate methyl A mixture of 3- (2-chloro-4-nitrophenoxy) benzoic acid (1.47 g), thionyl chloride (1.00 ml), N, N-dimethylformamide (one drop) and toluene (20 ml) was stirred at 80 ° C for 2 h. After concentrating under reduced pressure, toluene was added, and the mixture was re-concentrated under reduced pressure. A solution of the residue in tetrahydrofuran (5 ml) was added to a mixture of methyl 2-aminoisobutyrate hydrochloride (922 mg), triethylamine (1.67 ml) and tetrahydrofuran (10 ml) under ice-cooling, and the mixture was stirred under Cool with ice for 1 h and room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to column chromatography on silica gel (eluent, ethyl acetate: hexane = 20: 80-40: 60). The object fractions were concentrated under reduced pressure to give the title compound (1.72 g) as a white solid. XH-NMR (CDC13) d: 1.69 (6H, s), 3.79 (3H, s), 6.84 (1H, br s), 6.92 (1H, d, J = 9.2 Hz), 7.20-7.25 (1H, ra), 7.48-7.54 (2H, m), 7.61-7.66 (1H, m), 8.08 (1H, dd, J = 2.7 Hz, 9.2 Hz), 8.40 (1H, d, J = 2.7 Hz). (ii) Production of N- [3- (2-Chloro-4-nitrophenoxy) benzoyl] -2-methylalanine A N- [3- (2-Chloro-4-nitrophenoxy) benzoyl] -2-methylalaninate methyl (1.72 g) Isopropyl alcohol (20 ml), tetrahydrofuran (5 ml) and 1 N aqueous sodium hydroxide solution (6 ml) were added and the mixture was stirred at room temperature overnight. 1 N Hydrochloric acid (6.6 ml) was added to the reaction mixture, and the solvent was evaporated under reduced pressure. Water was added and the precipitated solid was collected by filtration, and washed with water to give the title compound (1.53 g) as a white powder. XH-NMR (DMSO-d6) d: 1.45 (6H, s), 7.08 (1H, d, J = 9.1 Hz), 7.39 (1H, dd, J = 2.5 Hz, 8.0 Hz), 7.61 (1H, t, J = 8.0 Hz), 7.68 (1H, m), 7.83 (1H, d, J = 8.0 Hz), 8.20 (1H, dd, J = 2.7 Hz, 9.1 Hz), 8.50 (1H, d, J = 2.7 Hz ), 8.55 (1H, br s). (iii) Production of 3- (2-chloro-4-nitrophenoxy) -N- (1-cyano-1-methylethyl) benzamide To a solution of N- [3- (2-chloro-4-nitrophenoxy) benzoyl] - 2-methylalanine (1.52 g) in N, N-dimethylformamide (20 ml) was added 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (920 mg) and 1-hydroxybenzotriazole (649 mg) under ice-cooling, and the mixture was stirred for 1 h under cooling with ice. 28% aqueous ammonia (1.4 ml) was added to the reaction mixture, and the mixture was stirred under ice-cooling for 1 h and at room temperature overnight. The reaction mixture was concentrated under reduced pressure, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with aqueous sodium hydroxide solution and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was crystallized from ethyl acetate. The powder obtained was subjected to column chromatography on silica gel (eluent, ethyl acetate). The object fractions were concentrated under reduced pressure to give N- (2-amino-1, 1-dimethyl-2-oxoethyl) -3- (2-chloro-4-nitrophenoxy) benzamide (0.95 g) as a white powder . To a solution of the obtained N- (2-amino-1, 1-dimethyl-2-oxoethyl) -3- (2-chloro-4-nitrophenoxy) benzamide (0.95 g) and triethylamine (1.12 ml) in tetrahydrofuran (30 g. ml) was added dropwise a solution of trifluoroacetic anhydride (0.556 ml) in tetrahydrofuran (5 ml) under cooling with ice, and the mixture was stirred at room temperature overnight. Triethylamine (0.697 ml) and trifluoroacetic anhydride (0.348 ml) were added back to the reaction mixture under ice cooling, and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvwas evaporated under reduced pressure and the residue obtained was subjected to silica gel column chromatography (elu ethyl acetate: hexane = 15: 85-> gt.; 50: 50). The subject fractions were concentrated under reduced pressure to give the title compound (419 mg) as a white amorphous powder. XH-NMR (CDC13) d: 1.82 (6H, s), 6.21 (1H, br s), 6.93 (1H, d, J = 9.1 Hz), 7.22-7.27 (1H, m), 7.48-7.55 (2H, m), 7.58-7.63 (1H, m), 8.08 (1H, dd, J = 2.6, 9.1 Hz), 8.39 (1H, d, J = 2.6 Hz). (iv) Production of 3- (4-amino-2-chlorophenoxy) -N- (1-cyano-1-methylethyl) benzamide To a solution of 3- (2-chloro-4-nitrophenoxy) -N- (1- cyano-1-methylethyl) benzamide (419 mg) in ethyl acetate (10 ml) was added 5% activated carbon-platinum (20 mg) under a hydrogen atmosphere and the mixture was stirred at room temperature. environment for 6 h. The catalyst was filtered, the filtrate was concentrated and the obtained residue was subjected to silica gel column chromatography (eluent, ethyl acetate: hexane = 30: 70-> 60: 40). The subject fractions were concentrated under reduced pressure to give the title compound (283 mg) as a yellowish green amorphous powder. XH-NMR (CDC13) d: 1.80 (6H, s), 3.72 (2H, br s), 6.15 (1H, br s), 6.58 (1H, dd, J = 2.7 Hz, 8.4 Hz), 6.78 (1H, d, J = 2.7 Hz), 6.90 (1H, d, J = 8.4 Hz), 7.00-7.10 (1H, m), 7.25-7.40 (3H, m). (v) Production of 3- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. phenoxy) -N - (1-cyano-l-methylethyl) benzamide When using 2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethyl benzoate (121 mg), 3- (4-amino) -2-chlorophenoxy) -N- (1-cyano-l-methylethyl) benzamide (132 mg), isopropyl alcohol (5 ml), methanol (5 ml), tetrahydrofuran (1 ml) and 1 N aqueous solution of sodium hydroxide (0.8 ml) and in the same manner as in Example C-62 (v), the title compound (68 mg) was obtained as a white powder. XH-NMR (CDCl3) d: 1.80 (6H, s), 4.13 (2H, t, J = 4.3 Hz), 4.38 (2H, t, J = 4.3 Hz), 6.24 (1H, d, J = 3.0 Hz) , 6.50 (1H, br s), 6.97 (1H, d, J = 9.1 Hz), 7.06 (1H, d, J = 3.0 Hz), 7.13-7.20 (1H, m), 7.28-7.44 (4H, m) , 7.76 (1H, d, J = 2. 7 Hz), 8.24 (1H, s), 9.58 (1H, br s). Example C-84 Production of N- (tert-butyl) -3- [2-chloro-4- (. {5- [2- (methylsulfonyl) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] benzamide To a solution of N- (tert-butyl) -3- [2-chloro-4- (. {5- [2- (methylthio) ethyl] -5H-pyrrolo [3.2] -d] pyrimidin-4-yl}. amino) phenoxy] benzamide (255 mg) in methanol (2 ml) was added a solution of monopersulphated compound OXONE® (615 mg) in water (1 ml) under ice-cooling. Methanol (18 ml) and water (9 ml) were added and the mixture was stirred at room temperature overnight. An aqueous solution of sodium acid carbonate was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed successively with 5% aqueous solution of sodium thiosulfate and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue obtained was subjected to silica gel column chromatography (eluent, ethyl acetate: hexane = 60: 40 → 100: 0-> methanol: ethyl acetate → 10: 90). . The object fractions were concentrated under reduced pressure. The residue is crystallized from ethyl acetate-diisopropyl ether to give the title compound (207 mg) as a white powder. XH-NMR (CDCl3) d: 1.46 (9H, s), 2.73 (3H, s), 3.67 (2H, t, J = 6.2 Hz), 4.87 (2H, t, J = 6.2 Hz), 5.95 (1H, br s), 6.74 (1H, d, J = 3.4 Hz), 7.00-7.12 (2H, m), 7.31-7.40 (4H, m), 7.48 (1H, dd, J = 2.7 Hz, 8.7 Hz), 7.86 (1H, d, J = 2.7 Hz), 7.97 (1H, br s), 8.56 (1H, s). Example C-85 Production of N- (tert-butyl) -5- (2-chloro-4- { [5- (2-methoxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.} phenoxy) -2-fluorobenzamide When using 5- (4-amino-2-chlorophenoxy) -N- (tert-butyl) -2-fluorobenzamide (60 mg), 4-chloro-5- (2-methoxyethyl) -5H pyrrolo [3, 2-d] pyrimidine (38 mg) and isopropyl alcohol (3.0 ml) and in the same manner as in Example C-22 (i), the title compound (84 mg) was obtained in the form of crystals. XH-NMR (DMSO-de) d: 1.32 (9H, s), 3.72-3.76 (2H, m), 3.80 (3H, s), 4.64-4.68 (2H, m), 6.51-7.99 (8H, m) , 8.36 (1H, s), 9.01 (1H, s), 9.97 (1H, br s).

Production of N-. { 2- [4- ( { 3-chloro-4- [3- (dimethylamino) phenoxy] phenyl} amino) -5H-? Irrolo [3,2-d] pyrimidin-5-yl] ethyl} -3-hydroxy-3-methylbutanamide (i) Production of 3- (4-amino-2-chlorophenoxy) -N, N-dimethylaniline When using 3- (dimethylamino) phenol (5.0 g), 3-chloro-4-fluoronitrobenzene (6.38 g), potassium carbonate (5.38 g), N, N-dimethylformamide (100 ral), platinum-activated carbon at 5% (0.73 g) and ethyl acetate (75 ml) and in the same manner as in the Example C-1 (i) and (ii), the title compound (8.95 g) was obtained. XH-NMR (DMSO-d6) d: 2.84 (6H, s), 5.27 (2H, s), 5.95-6.55 (4H, m), 6.69 (1H, d, J = 2.0 Hz), 6.86 (1H, d) , J = 8.0 Hz), 7.04 (1H, t, J = 8.3 Hz). (ii) Production of N-. { 2- [4- ( { 3-Chloro-4- [3- (dimethylamino) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -3-hydroxy-3-methylbutanamide When using 3- (4-amino-2-chlorophenoxy) -N, N-dimethylaniline (100 mg), [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (89 mg), isopropyl alcohol (5.0 ml), acetate ethyl ether (5.0 ml), 4 N hydrogen chloride solution / ethyl acetate (5.0 ml), 3-hydroxy-3-butyl butanoic acid (54 mg), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (136 mg), 1-hydroxybenzotriazole (5.0 mg), triethylamine (1.0 ml) and tetrahydrofuran (10 ml) and in the same manner as in Example C-53 (ii), the title compound (67 mg) was obtained in the form of crystals. XH-NMR (DMSO-d6) d: 1.13 (6H, s), 2.20 (2H, s), 2.89 (6H, s), 3.38-3.44 (2H, m), 4.49-4.53 (2H, m), 4.66 (1H, s), 6.09-7.15 (6H, m), 7.62-8.26 (4H, m), 8.31 (1H, s), 8.81 (1H, Example C-87 Production of N-. { 2- [4- ( { 3-Chloro-4- [3- (dimethylamino) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide When using 3- (4-amino-2-chlorophenoxy) -N, N- dimethylaniline (100 mg), [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (89 mg), isopropyl alcohol (5.0 ml), acetate ethyl ether (5.0 ml), 4 N hydrogen chloride solution / ethyl acetate (5.0 ml), methylsulfonylacetic acid (52 mg), 1-ethyl-3- (3-diraethylaminopropyl) carbodiimide hydrochloride (141 mg), 1 -hydroxybenzotriazole (5.0 mg), triethylamine (1.0 ml) and tetrahydrofuran (10 ml) and in the same manner as in Example C-53 (ii), the title compound (74 mg) was obtained as crystals. XH-NMR (DMSO-d6) d: 2.89 (6H, s), 3.09 (3H, s), 3.44-3.47 (2H, m), 4.04 (2H, s), 4.51-4.59 (2H, m), 6.08 -7.16 (6H, m), 7.60-7.91 (3H, ra), 8.32 (1H, s), 8.61-8.69 (2H, m). oxyethyl) -5H-pyrrolo [3, 2-d] pyrimidin-4-yl] amino} phenoxy) -2-fluoro-N- (2,2,2-trifluoroethyl) benzamide When using 5- [4- (. {5- [2- (benzoyloxy) ethyl] -5H-pyrrolo [3,2-d methyl pyrimidin-4-yl.} amino) -2-chlorophenoxy] -2-fluorobenzoate (100 mg), 1 N aqueous sodium hydroxide solution (2.0 ml) and tetrahydrofuran (5.0 ml) and in the same manner as in Example C-2 (v), a compound was obtained. The compound obtained was reacted in the same manner as in Example C-9 (v) and 2,2,2-trifluoroethanolamine (70 mg), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride ( 220 mg), 1-hydroxybenzotriazole (5.0 mg), triethylamine (0.5 ml) and N, N-dimethylformamide (5.0 ml) to give the title compound (52 mg) as crystals. Vl-NMR (DMSO-d6) d: 3.86-3.90 (2H, m), 3.99-4.10 (2H, m), 4.52-4.56 (2H, m), 6.15-6.52 (1H, m), 7.24-7.99 ( 7H, m), 8.34 (1H, s), 9.13-9.17 (1H, m), 9.87 (1H, br s). Example C-89 Production of N- (tert-butyl) -2- [3- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. phenoxy) phenyl] acetamide (i) Production of [3- (2-chloro-4-nitrophenoxy) phenyl] benzyl acetate When using (3-hydroxyphenyl) benzyl acetate (2.50 g), 3-chloro- 4-fluoronitrobenzene (1.83 g), potassium carbonate (1.90 g) and N, N-dimethylformamide (20 ml) and in the same manner as in Example C-1 (i), the compound of title (1.21 g) in the form of a brown oil. XH-NMR (DMSO-d6) d: 3.81 (2H, s), 5.12 (2H, s), 7.00-7.25 (4H, m), 7.31-7.37 (5H, m), 7.43-7.48 (1H, m) , 8.14-8.18 (1H, m), 8.46-8.47 (1H, m). (ii) Production of 2- [3- (4-amino-2-chlorophenoxy) phenyl] -N- (tert-butyl) acetamide A [3- (2-chloro-4-nitrophenoxy) phenyl] benzyl acetate (1.00 g) 1N aqueous solution of sodium hydroxide (5.3 ml) and tetrahydrofuran (4 ml) were added and the mixture was stirred at room temperature for 21 h. The reaction mixture was neutralized with 1N hydrochloric acid, and aqueous sodium bicarbonate and brine were added. The mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The obtained residue, 2-methylpropan-2-amine (1.1 ml), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (2.11 g), 1-hydroxybenzotriazole (30 mg), triethylamine (3.5 ml) and N , N-dimethylformamide (10 ml) were reacted in the same manner as in Example C-9 (v), and the compound obtained, 5% activated carbon-platinum (130 mg) and ethyl acetate (10 ml) were reacted in the same manner as in Example Cl (ii) to give the title compound (340 mg) as a pale yellow oil. XH-NMR (DMSO-d6) d: 1.21 (9H, s), 3.61 (2H, s), 5.27 (2H, s), 5.92-6.59 (4H, m), 6.65-6.69 (1H, m), 6.87 (1H, d, J = 8.0 Hz), 7.13 (1H, t, J = 8.3 Hz). (iii) Production of N- (tert-butyl) -2- [3- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidine- - il] amino.}. phenoxy) phenyl] acetamide When using 2- [3- (4-amino-2-chlorophenoxy) phenyl] -N- (tert-butyl) acetamide (330 mg), 2- (4-) benzoate chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl (270 mg), isopropyl alcohol (20 ml), 1 N aqueous solution of sodium hydroxide (2.0 ml) and methanol (6.0 ml) and in the same manner as in Example C-57, the title compound (115 mg) was obtained in the form of crystals. Vl-NMR (DMSO-d6) d: 1.22 (9H, s), 3.34-3.40 (2H, m), 3. 84-3.92 (2H, m), 4.51-4.57 (2H, m), 6.30 (1H, br s), 6.51-7.30 (6H, m), 7.56-7.96 (4H, m), 8.36 (1H, s) 9.91 (1H, br Production of N- [3- (2-chloro-4. {[[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. Phenoxy) benzyl] -2,2-dimethylpropanamide (i) Production of N- [3- (4-amino-2- chlorophenoxy) benzyl] -2, 2-dimethylpropanamide When using N- (3-hydroxybenzyl) -2,2-dimethylpropanamide (2.07 g), 3-chloro-4-fluoronitrobenzene (1.79 g), N, N-dimethylformamide (40 ml ), potassium carbonate (1.78 g), 15% ethanol with water content (23 ml), reduced iron (750 mg) and calcium chloride (120 mg) and in the same manner as in Example C-53 ( i), the title compound (1.73 g) was obtained in the form of a brown oil. XH-NMR (DMSO-d6) d: 1.09 (9H, s), 4.21-4.25 (2H, m), 5.26 (2H, s), 5.90-6.58 (4H, m), 6.64-6.68 (1H, m) , 6.85-6.98 (1H, m), 7.13 (1H, t, J = 8.3 Hz). (ii) Production of N- [3- (2-chloro-4. {[[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino] phenoxy ) benzyl] -2, 2-dimethylpropanamide When using N- [3- (4-amino-2-chlorophenoxy) benzyl] -2, 2-dimethylpropanamide (190 mg), 2- (4-chloro-5H-pyrrolobenzoate) [3, 2-d] pyrimidin-5-yl) ethyl (172 mg), isopropyl alcohol (5.0 ml), 1 N aqueous solution of sodium hydroxide (2.0 ral) and methanol (5.0 ml) and in the same manner as in Example C-57, the title compound (121 mg) was obtained as crystals. XH-NMR (DMSO-de) d: 1.07 (9H, s), 3.86-3.89 (2H, ra), 4.21-4.23 (2H, m), 4.51-4.55 (2H, m), 6.51-7.32 (6H, m), 7.56-8.06 (4H, m), 8.33 (1H, s), 9.82 (1H, br s).

Example C-91 Production of N- [3- (2-chloro-4. {[[5- (2. {[[(Methylsulfonyl) acetyl] amino} ethyl) -5H-pyrrolo [3,2-d] pyrimidine -4-yl] amino.}. Phenoxy) benzyl] -2,2-dimethylpropanamide When using N- [3- (4-amino-2-chlorophenoxy) benzyl] -2, 2-dimethylpropanaraide (350 mg), [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidine-5) ethyl) tert-butyl carbamate (312 mg), isopropyl alcohol (11 ml), tetrahydrofuran (17 ml), 4 N hydrogen chloride solution / ethyl acetate (7.0 ml), methylsulfonylacetic acid (220 mg) , 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (380 mg), 1-hydroxybenzotriazole (20 mg), triethylamine (4.0 ml) and N, N-dimethylformamide (15 ml) and in the same manner as in Example C-53 (ii), the title compound (263 mg) was obtained as crystals. XH-NMR (DMSO-d6) d: 1.08 (9H, s), 3.10 (3H, s), 3.45-3.49 (2H, m), 4.04 (2H, s), 4.22-4.24 (2H, m), 4.54 -4.59 (2H, m), 6.48-7.33 (6H, m), 7.62-8.08 (4H, ra), 8.34 (1H, s), 8.67 (1H, br s).

Example C-92 (cyclopropylmethoxy) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (Methylsulfonyl) acetamide (i) Production of 3- (2,6-dichloro-4-nitrophenoxy) phenyl benzoate To a solution of 3-hydroxyphenyl benzoate (675 mg) and 1,3-dichloro-2-iodo- 5-Nitrobenzene (1.0 g) in N, N-dimethylformamide (15 ml) was added potassium carbonate (1.25 g) and the mixture was stirred at room temperature for 18 h. Under cooling with ice, brine was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, hexane: ethyl acetate = 4: 1-> 1: 1) to give the title compound (269 mg ) in the form of a brown oil. XH-NMR (DMSO-d6) d: 6.90-6.97 (2H, m), 7.07-7.10 (1H, m), 7.44-7.77 (4H, m), 8.10-8.12 (2H, m), 8.55 (2H, s). (ii) Production of 3,5-dichloro-4- [3- (cyclopropylmethoxy) phenoxy] aniline To the benzoate of 3- (2,6-dichloro-4-nitrophenoxy) phenyl (269 mg) were added methanol (5 ml), tetrahydrofuran (1 ml) and 1 N aqueous solution of sodium hydroxide (0.6 ml) and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure. To a solution of the obtained residue and 1- (bromomethyl) cyclopropane (0.78 ml) in N, N-dimethylformamide (15 ml) was added potassium carbonate (430 mg) and the mixture was stirred at room temperature for 18 h. Under ice-cooling, brine was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by column chromatography on silica gel (eluent, hexane: ethyl acetate = 4: 1-> 1: 1). The obtained crude product was dissolved in 15% ethanol with water content (10 ml), reduced iron (250 mg) and calcium chloride (70 mg) were added, and the mixture was stirred at 80 ° C for 8 h. The solid was removed by filtration, and the filtrate was concentrated under reduced pressure. HE added water to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, hexane: ethyl acetate = 4: 1-0: 1) to give the title compound (112 mg) in shape of a brown oil. VYRMN (DMSO-d6) d: 0.30-0.57 (4H, m), 1.11-1.35 (1H, m), 3.79-3.81 (2H, m), 5.56 (2H, s), 5.90 (1H, dd, J = 2.0 Hz, 8.0 Hz), 6.22 (1H, t, J = 2.2 Hz), 6.36 (1H, dd, J = 2.0 Hz, 8.0 Hz), 6.71 (2H, s), 7.05 (1H, t, J = 8.3 Hz). (iii) Production of N-. { 2- [4- ( {3,5-dichloro-4- [3- (cyclopropylmethoxy) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide When using 3, 5-dichloro-4- [3- (cyclopropylmethoxy) phenoxy] aniline (110 mg), [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidine) -5-yl) ethyl] tert-butyl carbamate (101 mg), isopropyl alcohol (5.0 ml), methanol (10 ml), 4 N hydrogen chloride solution / ethyl acetate (3.0 ml), methylsulfonylacetic acid (90 ml) mg), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (120 mg), 1-hydroxybenzotriazole (5.0 mg), triethylamine (0.8 ml) and N, N-dimethylformamide (5 ml) and in the same manner that in Example C-53 (ii), the title compound (43 mg) was obtained in the form of crystals. 1 H-NMR (DMSO-d 6) d: 0.30-0.57 (4H, m), 1.11-1.35 (1H, m), 3.11 (3H, s), 3.40-3.50 (2H, ra), 3.79-3.81 (2H, m), 4.07 (2H, s), 4.54-4.59 (2H, m), 6.32-6.67 (4H, m), 7.19-7.67 2H, ra), 8.02 (2H, s), 8.41 (1H, s), 68 (1H, br s), 8.80 YH, s). Example C-93 Production of N- hydrochloride. { 2- [4- ( { 3-chloro-4- [3- (1, 1, 2, 2-tetrafluoroethoxy) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidine- 5-yl] ethyl} -3-hydroxy-3-methylbutanamide (i) Production of 2-chloro-4-nitro-l- [3- (1, 1, 2, 2-tetrafluoroethoxy) phenoxy] benzene A mixture of 3-chloro-4-fluoronitrobenzene (5 g) and 3- (1,1,2,2-tetrafluoroethoxy) phenol (6 g) was dissolved in N, N-dimethylformamide (28 ml), potassium carbonate was added (5.92 g), and the mixture was stirred at room temperature during h. Water (200 ml) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (200 ml). The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 90: 10-> 60: 40) to give the title compound (10 g) as a yellow oil. 1 H-NMR (CDC13) d: 5.91 (1H, tt, J = 3.0 Hz, 53.0 Hz), 6.90-7.10 (3H, m), 7.10-7.15 (1H, m), 7.44 (1H, t, J = 8.0 Hz), 8.10 (1H, dd, J = 3.0 Hz, 9.0 Hz), 8.39 (1H, d, J = 3.0 Hz). (ii) Production of 3-chloro-4- [3- (1,1,1,2,2-tetrafluoroethoxy) phenoxy] aniline A mixture of 2-chloro-4-nitro-l- [3- (1, 1, 2 , 2-tetrafluoroethoxy) phenoxy] benzene (10 g), reduced iron (10.2 g) and calcium chloride (1.7 g) in ethanol (270 ml) / water (30 ml) was stirred with heating at 90 ° C for 16 h . After cooling to room temperature, the mixture was filtered through celite. The filtrate was concentrated under reduced pressure, and the residue was partitioned between ethyl acetate (300 ml) / saturated brine (200 ml). The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 90: 10 → 60: 40) to give the title compound (7.91 g) as colorless crystals. 1 H-NMR (CDCl 3) d: 3.70 (2H, br s), 5.87 (1H, tt, J = 3.0 Hz, 53.0 Hz), 6.58 (1H, dd, J = 3.0 Hz, 8.0 Hz), 6.70-6.85 ( 3H, m), 6.85-7.00 (2H, ra), 7.26 (1H, t, J = 8.0 Hz). (iii) Production of. { 2- [4- ( { 3-chloro-4- [3- (1, 1, 2, 2-tetrafluoroethoxy) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidine- 5-yl] ethyl} tert-butyl carbamate [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (1.0 g) and 3-chloro-4- [ 3- (1,2,1,2-tetrafluoroethoxy) phenoxy] aniline (1.70 g) in isopropyl alcohol (10 ml), and the mixture was stirred at 80 ° C for 20 h. A saturated aqueous sodium hydrogen carbonate solution (50 ml) was added to the reaction mixture and the mixture was extracted with ethyl acetate (100 ml). The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 80: 20- »0: 100) to give the title compound (2.04 g) as an oil. Vl-NMR (CDC13) d: 1.49 (9H, s), 3.40-3.60 (2H, m), 4.40-4.60 (2H, m), 5.11 (1H, t, J = 6.0 Hz), 5.89 (1H, tt , J = 3.0 Hz, 53.0 Hz), 6.60 (1H, d, J = 3.0 Hz), 6.80-7.00 (3H, m), 7.09 (1H, d, J = 9.0 Hz), 7.19 (1H, d, J = 3.0 Hz), 7.31 (1H, t, J = 8.0 Hz), 7.89 (1H, dd, J = 3.0 Hz, 9.0 Hz), 8.03 (1H, d, J = 3.0 Hz), 8.52 (1H, s) , 8.64 (1H, br s). (iv) Production of 5- (2-aminoethyl) -N- dihydrochloride. { 3-chloro-4- [3- (1,1,2,2-tetrafluoroethoxy) phenoxy] phenyl} -5H-pyrrolo [3,2-d] pyrimidin-4-amine It dissolved. { 2- [4- ( { 3-chloro-4- [3- (1, 1, 2, 2-tetrafluoroethoxy) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidine- 5-yl] ethyl} tert-butyl carbamate (1.98 g) in tetrahydrofuran (47.2 ml), 2 N hydrochloric acid (23.6 ml) was added, and the mixture was stirred at 60 ° C for 15 h. The reaction mixture was concentrated under reduced pressure, the residue was dissolved in ethanol (50 ml), and the mixture was re-concentrated under reduced pressure. This operation was repeated twice. The residual solid was filtered with isopropyl alcohol and dried to give the title compound (1.65 g) as a pale yellow powder. Vl-NMR (DMSO-d6) d: 3.20-3.40 (2H, m), 5.00-5.10 (2H, m), 6.60-7.00 (4H, m), 7.35 (1H, d, J = 9.0 Hz), 7.51 (1H, t, J = 9.0 Hz), 7.60-7.70 (1H, m), 7.94 (1H, d, J = 2.4 Hz), 8.11 (1H, d, J = 3.0 Hz), 8.40 (3H, br s ), 8.75 (1H, s). (v) Production of N- hydrochloride. { 2- [- ( { 3-chloro-4- [3- (1, 1, 2, 2-tetrafluoroethoxy) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidine-5 -yl] ethyl} 3-hydroxy-3-methylbutanamide 5- (2-aminoethyl) -N- dihydrochloride was stirred. { 3-Chloro-4- [3- (1, 1,2,2-tetrafluoroethoxy) phenoxy] phenyl} -5H-pyrrolo [3,2-d] pyrimidin-4-amine (204 mg), 3-hydroxy-3-methylbutanoic acid (63.5 mg), N, N-dimethylformamide (6.9 ml), 1-hydroxybenzotriazole (72.5 mg) ), triethylamine (0.15 ml) and l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (103 mg) at room temperature for 16 h. The mixture was partitioned between ethyl acetate (80 ml) / water (50 ml), the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (ethyl acetate: methanol = 100: 0-> 85: 15) and silica gel column chromatography (ethyl acetate: methanol = 100: 0). - »85: 15). The residue was dissolved in ethyl acetate (5 ml), treated with 4 N hydrogen chloride solution / ethyl acetate (0.18 ml), and crystallized from diisopropyl ether / ethyl acetate to give the title compound (134 mg) in the form of white crystals. Vi-NMR (DMSO-d6) d: 1.11 (6H, s), 2.20 (2H, s), 3.44-3.56 (2H, m), 4.68 (2H, t, J = 6.0 Hz), 6.60-7.10 (5H , m), 7.35 (1H, d, J = 9.0 Hz), 7.51 (1H, t, J = 8.0 Hz), 7.73 (1H, dd, J = 3.0 Hz, 9.0 Hz), 7.98 (2H, dd, J = 3.0 Hz, 7.0 Hz), 8.43 (1H, m), 8.74 (1H, s). Example C-94 Production of N-. { 2- [4- ( { 3-chloro-4- [3- (1, 1, 2, 2-tetrafluoroethoxy) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2- d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide 5- (2-aminoethyl) -N- dihydrochloride was stirred. { 3-chloro-4- [3- (1, 1,2,2-tetrafluoroethoxy) phenoxy] phenyl} -5H-pyrrolo [3,2-d] pyrimidin-4-amine (204 mg), methylsulfonylacetic acid (74.2 mg), N, N-dimethylformamide (6.9 ml), 1-hydroxybenzotriazole (72.5 mg), triethylamine (0.15 ml) ) and l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (103 mg) at room temperature for 16 h. The mixture was partitioned with ethyl acetate (80 ml) / water (50 ral). The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (ethyl acetate: methanol = 100: 0 → 85: 15) and silica gel column chromatography (ethyl acetate: methanol = 100: 0-> 85: 15) to give the title compound (140 mg) in the form of pale yellow crystals. XH-NMR (DMS0-d6) d: 3.10 (3H, s), 3.40-3.50 (2H, m), 4.05 (2H, s), 4.56 (2H, t, J = 7.0 Hz), 6.50 (1H, d) , J = 3.0 Hz), 6.60-7.10 (4H, m), 7.29 (1H, d, J = 9.0 Hz), 7.47 (1H, t, J = 8.0 Hz), 7.63 (1H, d, J = 3.0 Hz ), 7.76 (1H, dd, J = 2.0 Hz, 9.0 Hz), 7.98 (1H, d, J = 3.0 Hz), 8.35 (1H, s), 8.68 (1H, m), 8.71 (1H, br s) .

Example C-95 Production of 2-. { 2- [4- ( { 3-chloro-4- [3- (1, 1, 2, 2-tetrafluoroethoxy) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidine- 5-yl] ethoxy} Ethanol 2- [2- (4-Chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethoxy] ethyl benzoate (150 mg) and 3-chloro-4- [3- (1) were stirred. , 1,2,2-tetrafluoroethoxy) phenoxy] aniline (217 mg) in isopropyl alcohol (3 ml) at 80 ° C for 16 h. a saturated aqueous solution of sodium hydrogen carbonate (40 ml) was added to the reaction mixture and the mixture was extracted with ethyl acetate (80 ml). The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 90: 10- »0: 100). The obtained oily residue was dissolved in methanol (1.89 ml), 1 N aqueous sodium hydroxide solution (0.433 ml) was added and the mixture was stirred at room temperature and stirred for 1 h. 1 N Hydrochloric acid (0.433 ml) was added to the mixture and the mixture was partitioned between ethyl acetate (50 ml) and saturated brine (20 ml). The organic layer was dried over sodium sulfate Anhydrous magnesium and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (ethyl acetate: methanol = 100: 0-> 90: 10) and silica gel column chromatography (ethyl acetate: methanol = 100: 0). - »90: 10) to give the title compound (136 mg) as white crystals. XH-NMR (DMSO-d6) d: 3.49 (4H, br s), 3.83 (2H, t, J = 4.5 Hz), 4.64 (2H, t, J = 4.5 Hz), 4.73 (1H, t, J = 4.5 Hz), 6.52 (1H, d, J = 3.0 Hz), 6.76 (1H, m), 6.79 (1H, tt, J = 3.0 Hz, 52.0 Hz), 6.91 (1H, dd, J = 2.0 Hz, 8.0 Hz), 7.02 (1H, d, J = 9.0 Hz), 7.27 (1H, d, J = 9.0 Hz), 7.47 (1H, t, J = 8.0 Hz), 7.60-7.70 (2H, m), 8.01 ( 1H, d, J = 2.0 Hz), 8.34 (1H, s), 8.99 (1H, br s). Example C-96 Production of N- [2- (4- { [3-chloro-4- (3-isobutoxy-phenoxy) -phenyl] -amino} -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2- (methylsulfonyl) acetamide (i) Production of 3-chloro-4- (3-isobutoxyphenoxy) aniline To a solution of 3- (2-chloro-4-nitrophenoxy) phenol (1.00 g) and l-iodo-2-methylpropane (1.5 ml) in N, N-dimethylformamide (15 ml) was added potassium carbonate (1.50 g). ) and the mixture was stirred at room temperature for 12 h. Under ice-cooling, brine was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by column chromatography on silica gel (eluent, hexane: ethyl acetate = 1: 0-> 1: 1). The obtained crude product was dissolved in 15% ethanol with water content (30 ml), reduced iron (750 mg) and calcium chloride (70 mg) were added, and the mixture was stirred at 80 ° C for 8 h. The solid was removed by filtration, and the filtrate was concentrated under reduced pressure. Water was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, hexane: ethyl acetate = 4: 1- »0: 1) to give the title compound (390 mg) in the form of a brown oil. VL-NMR (DMSO-d5) d: 0.94-0.96 (6H, m), 1.90-2.01 (1H, m), 3.67-3.69 (2H, m), 5.33 (2H, s), 6.32-7.34 (2H, m), 6.53-6.59 (2H, m), 6.71-6.72 (1H, m), 6.89-6.91 (1H, m), 7. 14-7.20 (1H, m). (ii) Production of N- [2- (4. {[[3-chloro-4- (3-isobutoxy-phenoxy) -phenyl] -amino} -5H-pyrrolo [3,2-d] pyrimidin-5-yl ) ethyl] -2- (methylsulfonyl) acetamide When using 3-chloro-4- (3-isobutoxyphenoxy) aniline (1.00 g), [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidine-5) ethyl) - tert-butyl carbamate (1.02 g), isopropyl alcohol (25 ml), methanol (35 ml), 4 N hydrogen chloride solution / ethyl acetate (10 ml), methylsulfonylacetic acid (870 mg ), l-ethyl-3- (3-dimethylaminopropyl) -carbodiimide hydrochloride (2.50 g), 1-hydroxybenzotriazole (100 mg), triethylamine (4.1 ml) and N, N-dimethylformamide (100 ml) and in the same manner that in Example C-53 (ii), the title compound (933 mg) was obtained in the form of crystals. XH-NMR (DMSO-d6) d: 0.95-0.97 (6H, m), 1.95-2.04 (1H, m), 3.09 (3H, s), 3.40-3.50 (2H, m), 3.72-3.74 (2H, m), 4.04 (2H, s), 4.54-4.59 (2H, m), 6.44-7.27 (6H, m), 7.61-7.75 (2H, m), 7.94 (1H, s), 8.33 (1H, s), 8.66 (2H, s). Example C-97 Production of N- hydrochloride. { 2- [4- ( { 3-Chloro-4- [3- (cyclopropylmethoxy) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (Methylsulfonyl) acetamide (i) Production of 2-chloro-l- [3- (cyclopropylmethoxy) phenoxy] -4-nitrobenzene To a solution of 3- (2-chloro-4-nitrophenoxy) phenol (2.92 g) in N, N-dimethylformamide (10.9 ml) were added cesium carbonate (5.39 g) and 1- (bromomethyl) cyclopropane (1.6 ml) and the mixture was stirred at room temperature for 16 h. The mixture was partitioned with ethyl acetate (150 ml) / water (80 ml). The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 100: 0- »70: 30) to give the title compound (3.17 g) as white crystals. XH-NMR (CDC13) d: 0.30-0.40 (2H, m), 0.60-0.70 (2H, m), 1.20-1.40 (1H, m), 3.79 (2H, d, J = 7.0 Hz), 6.60-6.70 (2H, m), 6.70-6.82 (1H, m), 6.92 (1H, d, J = 9.0 Hz), 7.29 (1H, m), 8.00-8.10 (1H, m), 8.36 (1H, d, J = 3.0 Hz). (ii) Production of 3-chloro-4- [3- (cyclopropylmethoxy) phenoxy] aniline. 2-Chloro-l- [3- (cyclopropylmethoxy) phenoxy] -4-nitrobenzene (3.1 g) was dissolved in ethanol. (97 ral) / water (11 ral), reduced iron (3.61 g) and calcium chloride (717 mg) were added, and the mixture was stirred at 90 ° C. for 16 h. The solid was removed by filtration through celite, and the filtrate was concentrated under reduced pressure. Ethyl acetate (150 ml) was added to the residue, and the mixture was washed with saturated brine (100 ml). The organic layer was dried over magnesium sulfate, concentrated under reduced pressure, and the residue was separated and purified by column chromatography on silica gel (eluent, hexane: ethyl acetate = 90: 10-> 60: 40 ) to give the title compound (2.50 g) in the form of an oil. XH-NMR (CDC13) d: 0.20-0.40 (2H, m), 0.50-0.70 (2H, m), 1.10-1.30 (1H, m), 3.66 (2H, br s), 3.74 (2H, d, J = 7.0 Hz), 6.40-6.50 (2H, m), 6.50-6.60 (2H, m), 6.76 (1H, d, J = 3.0 Hz), 6.85 (1H, d, J = 9.0 Hz), 7.10-7.20 (1H, m). (iii) Production of. { 2- [4- ( { 3-Chloro-4- [3- (cyclopropylmethoxy) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} tert-butyl carbamate [2- (2-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] carbamate [0.5 g] and 3-chloro-4- [3] were dissolved. - (cyclopropylmethoxy) phenoxy] aniline (732 mg) in isopropyl alcohol (5 ml), and the mixture was stirred at 80 ° C for 20 h. A saturated aqueous sodium hydrogen carbonate solution (60 ml) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (80 ml). The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 90: 10 → 0: 100) to give the title compound (742 mg) as a white powder. XH-NMR (CDC13) d: 0.30-0.40 (2H, m), 0.60-0.70 (2H, m), 1.10-1.30 (1H, m), 1.49 (9H, s), 3.40-3.60 (2H, m), 3.76 (2H, d, J = 7.0 Hz), 4.40-4.50 (2H, m), 5.21 (1H, t, J = 5.0 Hz), 6.50-6.70 (4H, m), 7.04 (1H, d, J = 9.0 Hz), 7.10-7.30 (2H, m) , 7.82 (1H, dd, J = 2.0 Hz, 9.0 Hz), 7.98 (1H, d, J = 3.0 Hz), 8.49 (1H, s), 8.59 (1H, br s). (iv) Production of 5- (2-aminoethyl) -N- dihydrochloride. { 3-Chloro-4- [3- (cyclopropylmethoxy) phenoxy] phenyl} -5H-pyrrolo [3, 2-d] pyrimidin-4-amine It was dissolved. { 2- [4- ( { 3-Chloro-4- [3- (cyclopropylmethoxy) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} tert-butyl carbamate (700 mg) in tetrahydrofuran (18 ml), 2N hydrochloric acid (9.0 ml) was added, and the mixture was stirred at 60 ° C for 15 h. The reaction mixture was concentrated under reduced pressure, the residue was dissolved in ethanol (50 ml), and the solution was re-concentrated under reduced pressure. This operation was repeated twice. The precipitated solid was taken up with isopropyl alcohol and dried to give the title compound (599 mg) as a pale yellow powder. XH-NMR (DMSO-d6) d: 0.20-0.40 (2H, m), 0.50-0.60 (2H, m), 1.10-1.40 (1H, m), 3.20-3.40 (2H, m), 3.80 (2H, d,J = 7.0 Hz), 5.00-5.10 (2H, m), 6.40-6.60 (2H, m), 6.60-6.80 (2H, m), 7.10-7.30 (2H, m), 7.50-7.70 (1H, m) , 7.88 (1H, m), 8.08 (1H, m), 8.37 (3H, br s), 8.73 (1H, s), 10.19 (1H, br s). (v) Production of N- hydrochloride. { 2- [4- ( { 3-Chloro-4- [3- (cyclopropylmethoxy) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide 5- (2-aminoethyl) -N- dihydrochloride was stirred. { 3-Chloro-4- [3- (cyclopropylmethoxy) phenoxy] phenyl} -5H-pyrrolo [3,2-d] pyrimidin-4-amine (187 mg), methylsulfonylacetic acid (74.2 rag), N, N-dimethylformamide (6.9 ml), 1-hydroxybenzotriazole (72.5 mg), triethylamine (0.15 ml) ) and l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (103 mg) at room temperature for 16 h. The mixture was partitioned with ethyl acetate (80 ml) / water (50 ml). The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (ethyl acetate: methanol = 100: 0-> 85: 15) and silica gel column chromatography (ethyl acetate methanol 100: 0- »85: 15). The obtained compound was dissolved in ethyl acetate (4 ml), treated with 4 N hydrogen chloride solution / ethyl acetate (0.18 ml), and crystallized from diisopropyl ether / ethyl acetate to give the title compound ( 167 mg) in the form of white crystals.

XH-NMR (DMSO-d6) d: 0.20-0.40 (2H, m), 0.50-0.60 (2H, m), 1.10-1.40 (1H, m), 3.05 (3H, s), 3.50-3.60 (2H, m), 3.80 (2H, d, J = 7.0 Hz), 4.07 (2H, s), 4.73 (1H, t, J = 7.0 Hz), 6.40-6.55 (2H, m), 6.60-6.75 (2H, m ), 7.20-7.30 (2H, m), 7.63 (1H, dd, J = 2.0 Hz, 9.0 Hz), 7.90 (1H, d, J = 2.0 Hz), 7.96 (1H, d, J = 3.0 Hz), 8.72 (1H, s), 17 (1H, m 10.05 (1H, br s) Example C-98 Production of N-. { 2- [4- ( { 3-Chloro-4- [3- (2, 2-dimethylpropoxy) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide (i) Production of 2-chloro-l- [3- (2, 2-dimethylpropoxy) phenoxy] -4-nitrobenzene To a solution of 3- (2-chloro-4-nitrophenoxy) phenol (1.0 g) in N, N-dimethylformamide (10 ml) were added potassium hydroxide (423 mg) and tris (dimethylamino) (2,2-dimethylpropoxy) phosphonium hexafluorophosphate (2.99 g) and the mixture was stirred at 180 °. C for 30 min. Under cooling with ice, water was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, hexane: ethyl acetate = 1: 0-> 1: 1) to give the title compound (180 mg) in the form of crystals. XH-NMR (CDC13) d: 1.03 (9H, s), 3.58 (2H, s), 6.63-6.65 (2H, m), 6.80-6.94 (2H, m), 7.30-7.34 (1H, m), 8.04 -8.08 (1H, m), 8.37-8.38 (1H, m). (ii) Production of 3-chloro-4- [3- (2, 2-dimethylpropoxy) phenoxy] aniline. 2-Chloro-l- [3- (2,2-dimethylpropoxy) phenoxy] -4-nitrobenzene (210 mg) in 15% ethanol with water content (7 ml), reduced iron (150 mg) and calcium chloride (20 mg) were added, and the mixture was stirred at 80 ° C for 8 h. The solid was removed by filtration, and the filtrate was concentrated under reduced pressure. Water was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, hexane: ethyl acetate = 4: 1-0: 1) to give the title compound (75 mg) in shape of a brown oil. XH-NMR (DMSO-d6) d: 0.98 (9H, s), 3.92 (2H, s), 5.34 (2H, s), 6.31-7.33 (2H, ra), 6.52-6.58 (2H, m), 6.70-6.72 (1H, m), 6.88-6.92 (1H, m), 7.13-7.20 (1H, m) . (iii) Production of N-. { 2- [4- ( { 3-Chloro-4- [3- (2, 2-dimethylpropoxy) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide When using 3-chloro-4- [3- (2, 2-dimethylpropoxy) phenoxy] -aniline (75 mg), [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (73 mg), isopropyl alcohol (10 ml), methanol (10 ml), 4 N hydrogen chloride solution / ethyl acetate (5 ml), methylsulfonylacetic acid (50 mg), l-ethyl-3- (3-dimethylaminopropyl) hydrochloride - carbodiimide (120 mg), 1-hydroxybenzotriazole (10 mg), triethylamine (0.7 ml) and N, N-dimethylformamide (10 ml) and in the same manner as in Example C-53 (ii), the compound of title (62 mg) in the form of crystals. XH-NMR (DMSO-d6) d: 0.98 (9H, s), 3.09 (3H, s), 3.45-3.49 (2H, m), 3.62 (2H, s), 4.05 (2H, s), 4.54-4.59 (2H, m), 6.44-7.28 (6H, m), 7.66-7.94 (3H, m), 8.39 (1H, s), 8.67 (1H, br s), 8.81 (1H, s).

Example C-99 Production of 2- (4- { [3-chloro-4- (3-isobutoxy-phenoxy) -phenyl] -amino} -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2- meti1-2- (methylsulfonyl) propanamide When using 3-chloro-4- (3-isobutoxy-phenoxy) aniline (180 mg), [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ) ethyl] tert-butyl carbamate (185 mg), isopropyl alcohol (5.0 ml), methanol (6.0 ml), 4 N hydrogen chloride solution / ethyl acetate (3.0 ml), 2-methyl-2- ( methylsulfonyl) propanoic acid (160 mg), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (320 mg), 1-hydroxybenzotriazole (20 mg), triethylamine (1.0 ml) and N, N-dimethylformamide (25 ml) and in the same manner as in Example C-53 (ii), the title compound (146 mg) was obtained as crystals. XH-NMR (DMSO-d6) d: 0.95-0.97 (6H, m), 1.41 (6H, s), 1.95-2.04 (1H, m), 2.95 (3H, s), 3.40-3.50 (2H, m) , 3.72-3.74 (2H, m), 4.54-4.59 (2H, m), 6.44-7.27 (6H, m), 7.56-7.97 (3H, m), 8.19-8.22 (1H, m), 8.33 (1H, s), 8.65 (1H, s).

Example C-100 Production of N-. { 2- [4- ( { 3-Chloro-4- [3- (cyclopropylmethoxy) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2-methyl-2- (methylsulfonyl) propanamide To a solution of 5- (2-aminoethyl) -N- dihydrochloride. { 3-Chloro-4- [3- (cyclopropylmethoxy) phenoxy] phenyl} -5H-pyrrolo [3,2-d] pyrimidine-4-araine (200 mg), 2-methyl-2- (methylsulfonyl) propanoic acid (170 mg) and 1-hydroxybenzotriazole (20 mg) in N, N-dimethylformamide (25 ml) triethylamine (0.87 ml) and l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (320 mg) were added under cooling with ice and the mixture was stirred at room temperature for 15 h. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: methanol = 100: 0-> 90: 10) and then recrystallized from ethyl acetate / diisopropyl ether for give the title compound (160 mg) as colorless crystals. XH-NMR (DMSO-d6) d: 0.29-0.58 (4H, m), 1.11-1.28 (1H, m), 1.41 (6H, s), 2.95 (3H, s), 3.44-3.50 (2H, m), 3.78- 3.80 (2H, ra), 4.55-4.59 (2H, m), 6.32-6.68 (4H, m), 7.16-7.96 (5H, m), 8.20 (1H, br s), 8.33 (1H, s), 8.65 (1H, br s). Example C-101 Production of N- [2- (4. {[[3-chloro-4- (3-isobutoxy-phenoxy) -phenyl] -amino} -5H-pyrrolo [3,2-d] pyrimidin-5-yl hydrochloride) ethyl] -2- (methylsulfonyl) acetamide N- [2- (4- {[[3-chloro-4- (3-isobutoxy-phenoxy) -phenyl] -amino} -5H-pyrrolo [3,2-d] was dissolved. ] pyrimidin-5-yl) ethyl] -2- (methylsulfonyl) acetamide (1.00 g) in ethyl acetate (10 ml), thereto was added 4N hydrogen chloride solution / ethyl acetate (5.0 ml), and the precipitated solid was collected by filtration. The solid was washed with diisopropyl ether to give the title compound (1.03 g) as colorless crystals. Vl-NMR (DMSO-d6) d: 0.95-0.98 (6H, m), 1.92-2.04 (1H, m), 3.05 (3H, s), 3.40-3.56 (2H, m), 3.72-3.75 (2H, ra), 4.07 (2H, s), 4.71-4.75 (2H, m), 6.47-7.32 (6H, m), 7.62-7.97 3H, m), 8.73 (1H, s), 8.83-8.88 (1H, m), 10.03 (1H, s).

Production of N-. { 2- [4- ( { 3-Chloro-4- [3- (cyclopropylmethoxy) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -3-hydroxy-3-methylbutanamide To a solution of 5- (2-aminoethyl) -N- dihydrochloride. { 3-Chloro-4- [3- (cyclopropylmethoxy) phenoxy] phenyl} -5H-pyrrolo [3,2-d] pyrimidin-4-amine (100 mg), 3-hydroxy-3-methylbutanoic acid (293 mg) and 1-hydroxybenzotriazole (10 mg) in tetrahydrofuran (15 ml) were added triethylamine (0.3 ml) and l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (216 mg) under ice-cooling, and the mixture was stirred at room temperature for 3 h. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by column chromatography on silica gel (eluent, ethyl acetate: methanol 100: 0- * 90: 10) and then recrystallized from ethyl acetate / diisopropyl ether to give the title compound (66 mg) in the form of colorless crystals. Vl-NMR (DMSO-d6) d: 0.29-0.58 (4H, m), 1.11-1.28 (1H, m), 1.16 (6H, s), 2.20 (2H, s), 3.35-3.41 (2H, m), 3.78- 3.80 (2H, m), 4.49-4.54 (2H, m), 4.66 (1H , s), 6.43-7.26 (6H, m), 7.63-8.00 (3H, m), 8.25 (1H, br s), 8.32 (1H, s), 8. 86 (1H, br s).

Production of N- (tert-butyl) -2- [3- (2-chloro-4-. {[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. phenoxy) phenoxy] acetamide (i) Production of 2- [3- (4-amino-2-chlorophenoxy) phenoxy] -N- (tert-butyl) acetamide To a solution of 3- (2-chloro- 4-Nitrophenoxy) phenol (1.0 g) in N, N-dimethylformamide (10 ml) were added ethyl bromoacetate (1.26 g) and potassium carbonate (1.20 g) and the mixture was stirred at room temperature for 18 h. Under ice-cooling, brine was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was dissolved in tetrahydrofuran (20 ml), aqueous solution was added thereto.

N sodium hydroxide (5.0 ml) and the mixture was stirred at room temperature for 12 h. The reaction mixture was neutralized with 1N hydrochloric acid, and aqueous sodium bicarbonate and brine were added. The mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. To a solution of the obtained residue, 2-methylpropan-2-amine (1.0 ml) and 1-hydroxybenzotriazole (10 mg) in tetrahydrofuran (15 ml) were added triethylamine (1.3 ml) and l-ethyl-3- (3) hydrochloride. dimethylaminopropyl) carbodiimide (1.50 g) under cooling with ice, and the mixture was stirred at room temperature for 3 h. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, hexane: ethyl acetate = 1: 0- »1: 1). The obtained crude product was dissolved in 15% ethanol with water content (23 ml), reduced iron (550 mg) and calcium chloride (70 mg) were added, and the mixture was stirred at 80 ° C for 8 h. The solid was removed by filtration, and the filtrate was concentrated under reduced pressure. Water was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over magnesium sulfate. After concentrating reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, hexane: ethyl acetate = 4: 1-> 0: 1) to give the title compound (375 mg) as a a brown oil XH-NMR (DMSO-d6) d: 1.29 (9H, s), 4.35 (2H, s), 5.35 (2H, s), 6.31-7.34 (2H, m), 6.52-6.58 (2H, ra), 6.70-6.72 (1H, m), 6.88-6.93 (1H, m), 7.13-7.20 (1H, m) . (ii) Production of N- (tert-butyl) -2- [3- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4 -yl] amino.}. phenoxy) phenoxy] acetamide When using 2- [3- (4-amino-2-chlorophenoxy) phenoxy] -N- (tert-butyl) acetamide (100 mg), benzoate 2- (4 -chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl (87 mg), isopropyl alcohol (5.0 ml), 1 N aqueous solution of sodium hydroxide (2.0 ml) and methanol (5.0 ml) and in the same manner as in Example C-57, the title compound (73 mg) was obtained as crystals. XH-NMR (DMSO-d6) d: 1.27 (9H, s), 3.86-3.89 (2H, m), 4.37 (2H, s), 4.51-4.55 (2H, ra), 6.48-7.66 (9H, m) , 7.95-8.97 (1H, m), 8.33 (1H, s), 9.87 (1H, br s). Ex Production of 2- [4- ( { 3-methyl-4- [3- (1, 1, 2, 2-tetrafluoroethoxy) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethanol (i) Production of 2-methyl-4-nitro-l- [3- (1,1,2,2-tetrafluoroethoxy) phenoxy] benzene A mixture of 2-fluoro-5-nitrotoluene ( 2.10 g) and 3- (1, 1,2, 2-tetrafluoroethoxy) phenol (3.01 g) was dissolved in N, N-dimethylformamide (13 ml), potassium carbonate was added (3.04 g), and the mixture was stirred at room temperature for 15 h. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 100: 0 → 80: 20) to give the title compound (4.05 g) as a yellow oil. Vl-NMR (CDC13) d: 2.39 (3H, s), 5.91 (1H, tt, J = 2.8 Hz, 53.0 Hz), 6.87 (1H, d, J = 9.0 Hz), 6.89-6.98 (2H, m) , 7.02-7.14 (1H, m), 7.41 (1H, t, J = 8.2 Hz), 8.04 (1H, dd, J = 2.6 Hz, 9.0 Hz), 8.18 (1H, d, J = 2.6 Hz). (ii) Production of 3-methyl-4- [3- (1, 1, 2, 2-tetrafluoroethoxy) phenoxy] aniline When using 2-methyl-4-nitro-l- [3- (1, 1, 2, 2-tetrafluoroethoxy) phenoxy] benzene (4.04 g), reduced iron (3.45 g), calcium chloride (691 mg) and ethanol (108 ml) / water (12 ml) and in the same manner as in Example C-72 (ii), the title compound was obtained (3.45 g) in the form of a brown oil. Vl-NMR (CDC13) d: 2.09 (3H, s), 3.59 (2H, br s), . 86 (1H, tt, J = 2.9 Hz, 53.0 Hz), 6.53 (1H, dd, J = 3.0 Hz, 8.7 Hz), 6.59 (1H, d, J = 3.0 Hz), 6.67 (1H, t, J = 2.2 Hz), 6.72-6.77 (1H, m), 6.80 (1H, d, J = 8.7 Hz), 6.81-6.86 (1H, m), 7.19-7.27 (1H, m). (ii) Production of 2- [4- ( { 3-methyl-4- [3- (1, 1, 2, 2-tetrafluoroethoxy) phenoxy] phenyl} amino) -5H-pyrrolo [3.2 -d] pyrimidin-5-yl] ethanol When using 2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethyl benzoate (102 mg), 3-methyl-4- [ 3- (1, 1, 2, 2-tetrafluoroethoxy) phenoxy] aniline (110 mg), isopropyl alcohol (3 ml) and 1 N aqueous sodium hydroxide solution (1.5 ml) and in the same manner as in Example C -72 (iii), the title compound (114 mg) was obtained as white crystals. XH-NMR (CDCI3) d: 2.23 (3H, s), 4.14 (2H, t, J = 4.5 Hz), 4.32-4.42 (2H, ra), 5.89 (1H, tt, J = 2.9 Hz, 53.0 Hz), 6.15 (1H, d, J = 3.4 Hz), 6.75-7.02 (5H, m), 7.20- 7.34 (1H, m), 7.40-7.52 (2H, m), 8.24 (1H, s), 9.30 (1H, s).

Example C-105 Production of 2- (methylsulfonyl) -N- hydrochloride. { 2- [4- ( { 3-methyl-4- [3- (1,1,2,2-tetrafluoroethoxy) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidine- 5-yl] ethyl} acetamide (i) Production of. { 2- [4- ( { 3-methyl-4- [3- (1, 1, 2, 2-tetrafluoroethoxy) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidine- 5-yl] ethyl} tert-butyl carbamate [2- [2- (chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (304 mg) and 3-methyl-4- [3] were dissolved. - (1,1,2,2-tetrafluoroethoxy) phenoxy] aniline (331 mg) in isopropyl alcohol (10 ml), and the mixture was stirred at 70 ° C for 20 h. A saturated aqueous solution of sodium acid carbonate was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 67: 33-> 10: 90) to give the title compound (540 mg) in the form of a colorless oil. XH-NMR (CDCl3) d: 1.46 (9H, s), 2.21 (3H, s), 3.43- 3.57 (2H, m), 4.40-4.54 (2H, m), 5.00 (1H, t, J = 5.5 Hz ), . 88 (1H, tt, J = 2.9 Hz, 53.0 Hz), 6.59 (1H, d, J = 3.0 Hz), 6.75-6.80 (1H, m), 6.82-6.93 (2H, m), 6.94-7.02 (1H , m), 7.16 (1H, d, J = 3.0 Hz), 7.27 (1H, t, J = 8.1 Hz), 7.64-7.74 (2H, m), 8.36 (1H, br s), 8.50 (1H, s). (ii) Production of 5- (2-aminoethyl) -N- dihydrochloride. { 3-methy1-4- [3- (1, 1,2,2-tetrafluoroethoxy) phenoxy] phenyl} -5H-pyrrolo [3,2-d] pyrimidin-4-amine It was dissolved. { 2- [4- ( { 3-methyl-4- [3- (1, 1, 2, 2-tetrafluoroethoxy) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidine- 5-yl] ethyl} tert-butyl carbamate (537 mg) in tetrahydrofuran (2 ml), 6N hydrochloric acid (0.8 ml) was added, and the mixture was stirred at 50 ° C for 15 h. The reaction mixture was concentrated under reduced pressure, the residue was dissolved in ethanol, and the mixture was concentrated again under reduced pressure. The precipitate was collected by filtration to give the title compound (460 mg) as a yellow powder. XH-NMR (DMSO-d6) d: 2.19 (3H, s), 3.22-3.48 (2H, m), 4.99 (2H, t, J = 6.1 Hz), 6.72 (1H, d, J = 3.2 Hz), 6.76 (1H, t, J = 2.3 Hz), 6.80 (1H, tt, J = 3.1 Hz, 52 Hz), 6.90-6.96 (1H, m), 7.00-7.07 (1H, m), 7.11 (1H, d) , J = 8.7 Hz), 7.47 (1H, dd, J = 2.5 Hz, 8.7 Hz), 7.49 (1H, t, J = 8.3 Hz), 7.54 (1H, d, J = 2.5 Hz), 8.03 (1H, d, J = 3.2 Hz), 8.29 (3H, br s), 8.68 (1H, s), 9.87 (1H, br s). (iii) Production of 2- (methylsulfonyl) -N- hydrochloride. { 2- [4- ( { 3-methyl-4- [3- (1, 1,2,2-tetrafluoroethoxy) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidine- 5-yl] ethyl} acetamide When using 5- (2-aminoethyl) -N- dihydrochloride. { 3-methyl-4- [3- (1, 1, 2, 2-tetrafluoroethoxy) phenoxy] phenyl} -5H-pyrrolo [3, 2-d] pyrimidin-4-amine (121 mg), methylsulfonylacetic acid (48.8 mg), tetrahydrofuran (0.6 ml) / N, N-dimethylformamide (0.6 ml), 1-hydroxybenzotriazole (47 mg) ), triethylamine (0.3 ml) and l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (64.3 mg) and in the same manner as in Example C-72 (i), 2- (methylsulfonyl) - N-. { 2- [4- ( { 3-methyl-4- [3- (1,1,2,2-tetrafluoroethoxy) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidine- 5-yl] ethyl} acetamide. The compound was dissolved in ethyl acetate, treated with 4 N hydrogen chloride solution / ethyl acetate, and crystallized from ethyl acetate / ethanol to give the title compound (104 mg) as yellow crystals. pale. XH-NMR (DMSO-d6) d: 2.19 (3H, s), 3.05 (3H, s), 3.49-3.60 (2H, m), 4.07 (2H, m), 4.70 (2H, t, J = 6.4 Hz ), 6.61-6.99 (1H, ra), 6.64 (1H, d, J = 3.2 Hz), 6.76 (1H, t, J = 2. 3 Hz), 6.91-6.96 (1H, m), 6.99-7.07 (1H, m), 7.12 (1H, d, J = 8.5 Hz), 7.44-7.61 (3H, m), 7.91 (1H, d, J = 3.2 Hz), 8.68 (1H, s), 8.78 (1H, t, J = 5.7 Hz), 9.85 (1H, s). Example C-106 Production of 3-hydroxy-3-methyl-N- hydrochloride. { 2- [4- ( { 3-methyl-4- [3- (1,1,2, 2, 2-tetrafluoroethoxy) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidine- 5-yl] ethyl} butanamide When using 5- (2-aminoethyl) -N- dihydrochloride. { 3-methyl-4- [3- (1, 1, 2, 2-tetrafluoroethoxy) phenoxy] phenyl} -5H-pyrrolo [3,2-d] pyrimidin-4-amine (120 mg), 3-hydroxy-3-methylbutanoic acid (40.5 mg), tetrahydrofuran (0.6 ml) / N, N-dimethylformamide (0.6 ml), 1-hydroxybenzotriazole (47.6 mg), triethylamine (0.3 ml) and l-ethyl-3- (3'-dimethylaminopropyl) carbodiimide hydrochloride (66.1 mg) and in the same manner as in Example C-72 (i), obtained 3-hydroxy-3 '-methyl-N-. { 2- [4- ( { 3-methy1-4- [3- (1, 1,2,2-tetrafluoroethoxy) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidine- 5-yl] ethyl} butanamide The compound was dissolved in ethyl acetate, treated with sodium chloride solution, 4 N hydrogen / ethyl acetate, and crystallized from diisopropyl ether / ethyl acetate to give the title compound (108 mg) as white crystals. XH-NMR (DMSO-d6) d: 1.11 (6H, s), 2.18 (3H, s), 2.20 (2H, s), 3.44-3.56 (2H, m), 4.65 (2H, t, J = 6.8 Hz ), 6.60-6.99 (1H, m), 6.65 (1H, d, J = 3.0 Hz), 6.75 (1H, t, J = 2.3 Hz), 6.91-6.96 (1H, m), 6.99-7.06 (1H, m), 7.11 (1H, d, J = 8.7 Hz), 7.49 (1H, t, J = 8.3 Hz), 7.54 (1H, dd, J = 2.5 Hz, 8.7 Hz), 7.60 (1H, d, J = 2.5 Hz), 7.95 (1H, d, J = 3.0 Hz), 8.37 (1H, t, J = 5.5 Hz), 8.68 (1H, s), 10.16 (1H, s). Example C-107 Production of N-. { 2- [4- ( { 3-Chloro-4- [4-chloro-3- (cyclopropylmethoxy) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (Methylsulfonyl) acetamide (i) Production of 3-chloro-4- [4-chloro-3- (cyclopropylmethoxy) phenoxy] aniline To a solution of 3-chloro-4-fluoronitrobenzene (5.00 g), 4-chlorobenzene-1,3-diol (4.11 g) in N, N-dimethylformamide (35 ml) was added potassium carbonate (5.50 g). g) and the mixture was stirred at room temperature for 5 h. Under ice-cooling, brine was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by column chromatography on silica gel (eluent, hexane: ethyl acetate = 1: 0-> 1: 1). The obtained crude product was dissolved in N, N-dimethylformamide (15 ml), 1- (bromomethyl) cyclopropane (1.3 ral) and potassium carbonate (1.50 g) were added and the mixture was stirred at room temperature for 12 h. Under ice-cooling, brine was added to the reaction mixture, and the mixture was extracted twice with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, hexane: ethyl acetate = 1: 0-> g.; 1: 1). The obtained crude product was dissolved in 15% ethanol with water content (30 ml), reduced iron (550 mg) and calcium chloride (70 mg) were added, and the mixture was stirred at 80 ° C for 8 h. The solid was removed by filtration, and the filtrate was concentrated under reduced pressure. Water was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over magnesium sulfate. After concentrating under reduced pressure, the The residue was separated and purified by silica gel column chromatography (eluent, hexane: ethyl acetate = 4: 1-> 0: 1) to give the title compound (868 mg) in fora of a brown oil. VL-NMR (CDC13) d: 0.35-0.68 (4H, m), 0.84-0.90 (1H, ra), 3.87 (2H, d, J = 6.7 Hz), 5.36 (2H, s), 6.33-7.34 (1H , m), 6.52-6.58 (2H, m), 6.69-6.71 (1H, m), 6.86-6.92 (1H, m), 7.13-7.21 (1H, m). (ii) Production of N-. { 2- [4- ( { 3-Chloro-4- [4-chloro-3- (cyclopropylmethoxy) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide When using 3-chloro-4- [4-chloro-3- (cyclopropylmethoxy) phenoxy] aniline (200 mg), [2- (4-chloro-5H-pyrrolo [3, 2-d] ] tert-butyl pyrimidin-5-yl) ethyl] carbamate (183 mg), isopropyl alcohol (9 ral), methanol (15 ml), 4 N hydrogen chloride solution / ethyl acetate (8.0 ml), methylsulfonylacetic acid (170 mg), 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (300 mg), 1-hydroxybenzotriazole (50 mg), triethylamine (1.1 ml) and N, N-dimethylformamide (10 ml) and from the In the same manner as in Example C-53 (ii), the title co-formula (61 mg) was obtained in the form of crystals. XH-NMR (CDCl3) d: 0.36-0.42 (2H, m), 0.62-0.68 (2H, m), 0.86-0.90 (1H, m), 3.13 (3H, s), 3.68-3.72 (2H, m) , 3.86 (2H, d, J = 6.7 Hz), 3.98 (2H, s), 4.45-4.52 (2H, m), 6.43- 7. 2! (6H, m), 7.50 (1H, br s), 7.68-7.72 (1H, m), 7.92 (1H, .18 (1H, br s), 8.49 (1H, s) Example C-108 Production of 2- [4- ( { 4- [3- (Cyclopropylmethoxy) phenoxy] -3-methylphenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethanol (i) ) Production of 3- (2-methyl-4-nitrophenoxy) phenol When using 2-fluoro-5-nitrotoluene (10.0 g), resorcinol (24.8 g), potassium carbonate (31.3 g) and N, N-dimethylformamide (120 ml) and in the same way as in the Example C-104 (i), the title compound (7.19 g) was obtained as a yellow oil. XH-NMR (CDC13) d: 2.39 (3H, s), 5.12 (1H, s), 6.52 (1H, t, J = 2.3 Hz), 6.55-6.61 (1H, m), 6.64-6.70 (1H, m ), 6.84 (1H, d, J = 9.0 Hz), 7.24 (1H, t, J = 8.1 Hz), 7.99 (1H, dd, J = 2.8 Hz, 9.0 Hz), 8.14 (1H, d, J = 2.8) Hz). (ii) Production of 1- [3- (cyclopropylmethoxy) phenoxy] -2-methyl-1,4-nitrobenzene When using 3- (2-methyl-4-nitrophenoxy) phenol (939 mg), 1- (bromomethyl) cyclopropane (0.55) ml), potassium carbonate (963 mg) and N, N-dimethylformamide (10 ml) and in the same manner as in Example C-104 (i), the title compound (1.02 g) was obtained as a pale yellow oil. XH-NMR (CDC13) d: 0.28-0.42 (2H, m), 0.58-0.71 (2H, m), 1.17-1.36 (1H, m), 2.39 (3H, s), 3.78 (2H, d, J = 7.2 Hz), 6. 53-6.63 (2H, ra), 6.71-6.78 (1H, m), 6.82 (1H, d, J = 8.8 Hz), 7.27 (1H, t, J = 8.1 Hz), 7.98 (1H, dd, J = 2.8 Hz, 8.8 Hz), 8.14 (1H, d, 2.8 Hz). (iii) Production of 4- [3- (cyclopropylmethoxy) phenoxy] -3-methylaniline When using 1- [3- (cyclopropylmethoxy) phenoxy] -2-methyl-4-nitrobenzene (1.01 g), reduced iron (964 mg) , calcium chloride (196 mg) and ethanol (36 ml) / water (4 ml) and in the same manner as in Example C-72 (ii), the title compound (809 mg) was obtained in the form of a oil blackish brown. 2 H-NMR (CDCl 3) d: 0.26-0.38 (2H, m), 0.55-0.68 (2H, m), 1.13-1.34 (1H, m), 2.09 (3H, s), 3.54 (2H, br s), 3.73 (2H, d, J = 6.9 Hz), 6.37-6.45 (2H, m), 6.47-6.54 (2H, m), 6.57 (1H, d, J = 2.5 Hz), 6.78 (1H, d, J = 8.5 Hz), 7.07-7.16 (1H, m). (iv) Production of 2- [4- ( { 4- [3- (cyclopropylmethoxy) phenoxy] -3-methylphenyl}. amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethanol When using benzoate 2- (4-chloro-5H-pyrrolo [3, 2- d] pyrimidin-5-yl) ethyl (99.7 mg), 4- [3- (cyclopropylmethoxy) phenoxy] -3-methylaniline (98.7 mg), isopropyl alcohol (3 ml) and 1 N aqueous solution of sodium hydroxide (1.5 ml) and in the same manner as in Example C-72 (iii), the title compound- (106 mg) was obtained as white crystals. XH-NMR (CDC13) d: 0.29-0.39 (2H, m), 0.58-0.70 (2H, m), 1.17-1.33 (1H, m), 2.24 (3H, s), 3.77 (2H, d, J = 7.0 Hz), 4. 08-4.17 (2H, m), 4.37 (2H, t, J = 4.4 Hz), 6.13 (1H, d, J = 3.0 Hz), 6.47-6.62 (3H, m), 6.94 (1H, d, J = 3.0 Hz), 6.97 (1H, d, J = 8.5 Hz), 7.17 (1H, t, J = 8.1 Hz), 7.37-7.48 (2H, m), 8.23 (1H, s), 9.28 (1H, s). Example C-109 Production of 2- (4- { [4- (3-Isobutoxyphenoxy) -3-methylphenyl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethanol (i) Production of 1- (3-isobutoxyphenoxy) -2-methyl-4-nitrobenzene When using 3- (2-methyl-4-nitrophenoxy) phenol (822 mg), isobutyl bromide (0.55 ml), potassium carbonate (834 mg) and N, N-dimethylformamide (10 ml) and in the same manner as in the Example C-104 (i), the title compound (884 mg) was obtained as a pale yellow oil. XH-NMR (CDCl 3) d: 1.02 (6H, d, J = 6.8 Hz), 1.97-2.18 (1H, m), 2.40 (3H, s), 3.70 (2H, d, J = 6.4 Hz), 6.52-6.64 (2H, m), 6.71-6.78 (1H, ra), 6.82 (1H, d, J = 9.1 Hz), 7.22- 7.33 (1H, m), 7.99 (1H, dd, J = 3.0 Hz, 9.1 Hz), 8.14 (1H, d, J = 3.0 Hz). (ii) Production of 4- (3-isobutoxyphenoxy) -3-Rethylaniline When using 1- (3-isobutoxy-phenoxy) -2-methyl-4-nitrobenzene (879 mg), reduced iron (823 mg), calcium chloride (162 mg) and ethanol (27 ml) / water (3 ml) and in the same manner as in Example C-72 (ii), the title compound (756 mg) was obtained as a brown oil. XH-NMR (CDCI3) d: 1.00 (6H, d, J = 6.6 Hz), 1.95-2.10 (1H, m), 2.11 (3H, s), 3.55 (2H, br s), 3.66 (2H, d, J = 6.3 Hz), 6.35-6.44 (2H, m), 6.49-6.52 (1H, m) , 6.52-6.55 (1H, m), 6.58 (1H, d, J = 3.0 Hz), 6.80 (1H, d, J = 8.5 Hz), 7.12 (1H, t, J = 8.1 Hz). (iii) Production of 2- (4- { [4- (3-isobutoxyphenoxy) -3-methylphenyl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethanol When using 2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl benzoate (110 rag), 4- (3-isobutoxy-phenoxy) -3-methylaniline (103 mg), isopropyl alcohol ( 3 ml) and 1 N aqueous solution of sodium hydroxide (1.5 ml) and the same so that in Example C-72 (iii), the title compound (116 mg) was obtained as white crystals. Vl-NMR (CDCI3) d: 1.02 (6H, d, J = 6.8 Hz), 1.97-2.16 (1H, m), 2.25 (3H, s), 3.70 (2H, d, J = 6.4 Hz), 4.12 ( 2H, t, J = 4.3 Hz), 4.35 (2H, t, J = 4.3 Hz), 6.10 (1H, d, J = 3.2 Hz), 6.45-6.54 (2H, m), 6.54-6.62 (1H, m ), 6.91 (1H, d, J = 3.2 Hz), 6.97 (1H, d, J = 8.5 Hz), 7.17 (1H, t, J = 8.3 Hz), 7.37-7.48 (2H, m), 8.21 (1H , s), 9.31 (1H, s).

Production of N-. { 2- [- ( { - [3- (Cyclopropylatoxy) phenoxy] -3-methylphenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide (i) Production of. { 2- [4- ( { - [3- (Cyclopropylmethoxy) phenoxy] -3-methylphenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} tert-butyl carbamate When using [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (402 mg), 4- [3- (cyclopropylmethoxy ) phenoxy] -3-methylaniline (395 mg) and isopropyl alcohol (15 ml) and in the same manner as in Example C-105 (i), the title compound (710 mg) was obtained in the form of a pale orange powder. Vl-NMR (CDCI3) d: 0.27-0.39 (2H, m), 0.54-0.69 (2H, m), 1.16-1.32 (1H, m), 1.46 (9H, s), 2.22 (3H, s), 3.41 -3.58 (2H, m), 3.76 (2H, d, J = 6.8 Hz), 4.39-4.53 (2H, m), 4.99 (1H, d, J = 9.5 Hz), 6.46-6.63 (4H, m), 6.95 ( 1H, d, J = 9.5 Hz), 7.09-7.20 (2H, m), 7.55-7.73 (2H, m), 8.28 (1H, br s), 8. 49 (1H, s). (ii) Production of 5- (2-aminoethyl) -N- dihydrochloride. { 4- [3- (Cyclopropylmethoxy) phenoxy] -3-methylphenyl} -5H-pyrrolo [3,2-d] pyrimidin-4-amine When using. { 2- [4- ( { 4- [3- (Cyclopropylmethoxy) phenoxy] -3-methylphenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} tert-butyl carbamate (707 mg), 6N hydrochloric acid (1 ml) and ethanol (3 ml) and in the same manner as in Example C-105 (ii), the title compound (578 mg) was obtained in the form of a yellow powder. XH-NMR (DMSO-d6) d: 0.25-0.36 (2H, m), 0.49-0.62 (2H, m), 1.12-1.27 (1H, m), 2.19 (3H, s), 3.20-3.33 (2H, m), 3.79 (2H, d, J = 6.9 Hz), 5.01 (2H, t, J = 6.1 Hz), 6.40-6.49 (2H, m), 6.62-6.69 (1H, m), 6.71 (1H, d , J = 3.0 Hz), 7.01 (1H, d, J = 8.5 Hz), 7.19-7.29 (1H, m), 7.40 (1H, dd, J = 2.5 Hz, 8.5 Hz), 7.49 (1H, d, J = 2.5 Hz), 8.04 (1H, d, J = 3.0 Hz), 8.33 (3H, br s), 8.67 (1H, s), 9.90 (1H, br s). (iii) Production of N-. { 2- [4- ( { 4- [3- (cyclopropylmethoxy) phenoxy] -3-methylphenyl.} Amino) -5H- pyrrolo [3, 2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide When using 5- (2-aminoethyl) -N- dihydrochloride. { 4- [3- (Cyclopropylmethoxy) phenoxy] -3-methylphenyl} -5H-pyrrolo [3,2-d] pyrimidin-4-amine (120 mg), methylsulfonylacetic acid (50.5 mg), tetrahydrofuran (0.6 ml) / N, N-dimethylformamide (0.6 ml), 1-hydroxybenzotriazole (51.5 mg) ), triethylamine (0.35 ml) and l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (116 mg) and in the same manner as in Example C-72 (i), the title compound was obtained (72.4 mg) in the form of a pale yellow powder. TH-NMR (CDC13) d: 0.28-0.39 (2H, m), 0.57-0.70 (2H, m), 1.17-1.34 (1H, m), 2.24 (3H, s), 3.08 (3H, s), 3.62 -3.75 (2H, m), 3.77 (2H, d, J = 7.0 Hz), 3.93 (2H, s), 4.38-4.53 (2H, m), 6.45-6.63 (4H, m), 6.95 (1H, d, J = 8.5 Hz), 7.11-7.23 (2H, m), 7.36-7.50 (2H, m), 7.57 (1H, d , J = 2.1 Hz), 7. 83 (1H, s), 8.47 (1H, s). Example C-III Production of N-. { 2- [4- ( { 4- [3- (cyclopropylmethoxy) phenoxy] -3-methylphenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -3-hydroxy-3- methylbutanamide When using 5- (2-aminoethyl) -N- dihydrochloride. { 4- [3- (Cyclopropylmethoxy) phenoxy] -3-methylphenyl} -5H-pyrrolo [3,2-d] pyrimidin-4-amino 121 mg, 3-hydroxy-3-methylbutanoic acid (46.2 mg), tetrahydrofuran (0.6 ml) / N, N-dimethylformamide (0.6 ml), 1- hydroxybenzotriazole (59.8 mg), triethylamine (0.35 ml) and l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (88.0 mg) and in the same manner as in Example C-72 (i), the compound was obtained of the title (60.0 mg) in the form of a white powder. XH-NMR (CDC13) d: 0.29-0.38 (2H, m), 0.58-0.68 (2H, m), 1.17-1.33 (1H, m), 1.30 (6H, s), 2.24 (3H, s), 2.44 (2H, s), 3.56-3.70 (2H, m), 3.77 (2H, d, J = 7.0 Hz), 4.41-4.53 (2H, m), 6.48-6.62 (4H, m), 6.86-6.93 (1H, m), 6.95 (1H, d, J = 8.7 Hz), 7.11-7.22 (2H, m), 7.54 (1H, dd , J = 2.5 Hz, 8.7 HZ: 7.62 (1H, d, J = 2.5 Hz), 8.32 (1H, s), 8.47 (1H, s). Example C-112 Production of N- [2- (- { [4- (3-Isobutoxyphenoxy) -3-methylphenyl] amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl hydrochloride] -2- (methylsulfonyl) acetamide (i) Production of [2- (4- { [4- (3-isobutoxy-phenoxy) -3-methylphenyl] amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate When using [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (307 mg), 4- (3-isobutoxyphenoxy) 3-methylaniline (304 mg) and isopropyl alcohol (12 ml) and in the same manner as in Example C-105 (i), the title compound (504 mg) was obtained as a white powder. XH-NMR (CDC13) d: 1.01 (6H, d, J = 6.8 Hz), 1.46 (9H, s), 1.97-2.14 (1H, m), 2.23 (3H, s), 3.41-3.58 (2H, m ), 3.68 (2H, d, J = 6.4 Hz), 4.39-4.54 (2H, m), 5.01 (1H, t, J = 5.5 Hz), 6.45-6.63 (4H, m), 6.96 (1H, d, J = 8.7 Hz), 7.09-7.21 (2H, m), 7.58-7.71 (2H, m), 8.32 (1H, br s), 8.49 (1H, s). (ii) Production of 5- (2-aminoethyl) -N- [4- (3-isobutoxy-phenoxy) -3-methylphenyl] -5H-pyrrolo [3,2-d] pyrimidin-4-amine dihydrochloride When using [2] - (4- {[[4- (3-isobutoxyphenoxy) -3-methylphenyl] amino} -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (499) mg), 6 N hydrochloric acid (1 ml) and ethanol (3 ml) and in the same manner as in Example C-105 (ii), the title compound (429 mg) was obtained as a yellow powder. XH-NMR (DMSO-d6) d: 0.96 (6H, d, J = 6.6 Hz), 1.91-2.08 (1H, m), 2.20 (3H, s), 3.21-3.85 (2H, m), 3.73 (2H , d J = 6. 4 Hz), 5.02 (2H, t, J = 6.1 Hz), 6.40-6.52 (2H, m), 6.64-6.70 (1H, m), 6.72 (1H, d, J = 3.2 Hz), 7.02 (1H, d, J = 8.7 Hz), 7.26 (1H, t, J = 8.2 Hz), 7.41 (1H, dd, J = 2.5 Hz, 8.7 Hz), 7.50 (1H, d, J = 2.5 Hz), 8.05 (1H , d, J = 3.2 Hz), 8.37 (3H, br s), 8.68 (1H, s), 9.94 (1H, br s). (iii) Production of N- [2- (4. {[[4- (3-isobutoxy-phenoxy) -3-methylphenyl] amino] -5H-pyrrolo [3,2-d] pyrimidin-5-hydrochloride il) ethyl] -2- (methylsulfonyl) acetamide When using 5- (2-aminoethyl) -N- [4- (3-isobutoxy-phenoxy) -3-methylphenyl] -5H-pyrrolo dihydrochloride [3, 2-d] pyrimidin-4-amine (119 mg), methylsulfonylacetic acid (50.3 mg), tetrahydrofuran (0.6 ml) / N, N-dimethylformamide (0.6 ml), 1-hydroxybenzotriazole (50.1 mg), triethylamine (0.35 ml) ) and l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (82.7 mg) and in the same manner as in Example C-72 (i), N- [2- (4-. {[[ 4- (3-isobutoxyphenoxy) -3-methylphenyl] amino.} - 5 H -pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2- (methylsulfonyl) acetamide. The compound was dissolved in ethyl acetate and treated with 4 N hydrogen chloride solution / ethyl acetate, and the precipitate was collected by filtration to give the title compound (104 mg) as white crystals. XH-NMR (DMSO-dg) d: 0.96 (6H, d, J = 6.6 Hz), 1.88-2.09 (1H, m), 2.20 (3H, s), 3.06 (3H, s), 3.54 (2H, q , J = 6.0 Hz), 3.73 (2H, d, J = 6.6 Hz), 4.06 (2H, s), 4.69 (2H, t, J = 6. 0 Hz), 6.39-6.52 (2H, m), 6.64 (1H, d, J = 3.2 Hz), 6.65-6.72 (1H, m), 7.02 (1H, d, J = 8.8 Hz), 7.26 (1H, t, J = 8.2 Hz), 7.45 (1H, dd, J = 2.5 Hz, 8.8 Hz), 7.52 (1H, d, J = 2.5 Hz), 7.90 (1H, d, J = 3.2 Hz), 8.67 (1H, s), 8.77 (1H, t, J = 6. 0 Hz), 9.82 (1H, s). Example C-113 Production of 3-hydroxy-N- [2- (- { [4- (3-isobutoxyphenoxy) -3-methylphenyl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -3-methylbutanamide When using 5- (2-aminoethyl) -N- [4- (3-isobutoxy-phenoxy) -3-methylphenyl] -5H-pyrrolo [3,2-d] pyrimidin-4-amine dihydrochloride ( 120 mg), 3-hydroxy-3-methylbutanoic acid (46.1 mg), tetrahydrofuran (0.6 ml) / N, N-dimethylformamide (0.6 ml), 1-hydroxybenzotriazole (50.2 mg), triethylamine (0.35 ml) and hydrochloride ethyl-3- (3-dimethylaminopropyl) carbodiimide (82.7 mg) and from the same manner as in Example C-72 (i), the title compound (91.0 mg) was obtained as white crystals. LH-NMR (CDC13) d: 1.01 (6H, d, J = 6.6 Hz), 1.30 (6H, s), 1.97-2.15 (1H, m), 2.25 (3H, s), 2.44 (2H, s), 3.57-3.67 (2H, m), 3.69 (2H, d, J = 6.6 Hz), 4.41-4.54 (2H, ra), 6.44-6.63 (4H, m), 6.84 (1H, t, J = 5.9 Hz), 6.95 (1H, d, J = 8.7 Hz), 7.11-7.21 (2H, ra), 7.55 ( 1H, dd, J = 2.5 Hz, 8.7 Hz), 7.63 (1H, d, J = 2.5 Hz), 8.31 (1H, s), 8.48 (1H, s). Example C-114 Production of 2- [4- ( { 3-methyl-4- [3- (2, 2, 2-trifluoroethoxy) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidine- 5-yl] ethanol (i) Production of 2-methyl-4-nitro-l- [3- (2,2,2-trifluoroethoxy) phenoxy] benzene When using 3- (2-methyl-4-nitrophenoxy) phenol ( 797 mg), 1. 1, 1-trifluoro-2-iodoethane (0.5 ml), potassium carbonate (903 mg) and N, N-dimethylformamide (10 ml) and in the same manner as in Example C-104 (i), the title compound was obtained (780 mg) in the form of a yellow oil. V-YRMN (CDC13) d: 2.39 (3H, s), 4.35 (2H, q, J = 8.0 Hz), 6.64 (1H, t, J = 2.4 Hz), 6.67-6.74 (1H, m), 6.74- 6.81 (1H, m), 6.84 (1H, d, J = 9.0 Hz), 7.34 (1H, t, J = 8.3 Hz), 8.02 (1H, dd, J = 2.8 Hz, 9.0 Hz), 8.16 (1H, d, J = 2.8 Hz). (ii) Production of 3-methyl-4- [3- (2, 2, 2-trifluoroethoxy) phenoxy] aniline When using 2-methyl-4-nitro-l- [3- (2, 2, 2-trifluoroethoxy) phenoxy] benzene (774 mg), reduced iron (685 mg), calcium chloride (138 mg) and ethanol (22.5 ml) / water (2.5 ml) and in the same manner as in Example C-72 (ii), the title compound (529 mg) was obtained in the form of a white powder. VL-NMR (CDC13) d: 2.08 (3H, s), 3.57 (2H, br s), 4.28 (2H, q, J = 8.0 Hz), 6.43 (1H, t, J = 2.5 Hz), 6.48-6.56 (3H, m), 6.58 (1H, d, J = 2.8 Hz), 6.78 (1H, d, J = 8.5 Hz), 7.17 (1H, t, J = 8.3 Hz). (iii) Production of 2- [4- ( {3-Retyl-4- [3- (2, 2, 2-trifluoroethoxy) phenoxy] phenyl}. amino) -5H-pyrrolo [3,2-d ] pyrimidin-5-yl] ethanol When using 2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethyl benzoate (101 mg), 3-methyl-4- [3- (2,2,2-trifluoroethoxy) phenoxy] aniline (100 mg), isopropyl alcohol (3 ml) and 1 N aqueous sodium hydroxide solution (1 ml) and in the same manner as in Example C-72 (iii ), the title compound (63.9 mg) was obtained in the form of a white powder. XH-NMR (CDCl 3) d: 2.23 (3H, s), 4.13 (2H, t, J = 4.4 Hz), 4.25-4.43 (4H, m), 6.13 (1H, d, J = 3.2 Hz), 6.54 (1H, t, J = 2.3 Hz), 6.56-6.68 (2H, m), 6.94 (1H, d, J = 3.2 Hz), 6.98 (1H, d, J = 8.5 Hz), 7.23 (1H, t, J = 8.3 Hz) , 7.39-7.49 (2H, m 23 (1H, s), 9.32 (1H, if Example C-115 Production of 2- [4- ( { 3-Methyl-4- [3- (3-methyl-butoxy) phenoxy] -phenyl} -amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethanol (i) Production of 2-methyl-l- [3- (3-ethoxybutoxy) phenoxy] -4-nitrobenzene When using 3- (2-methyl-4-nitrophenoxy) phenol (855 mg), 1-iodo-3 -methylbutane (0.8 ml), potassium carbonate (968 mg) and N, N-dimethylformamide (10 ml) and in the same manner as in the Example C-104 (i), the title compound (983 mg) was obtained as a yellow oil. VL-NMR (CDC13) d: 0.96 (6H, d, J = 6.6 Hz), 1.67 (2H, q, J = 6.6 Hz), 1.74-1.93 (1H, m), 2.40 (3H, s), 3.97 ( 2H, t, J = 6.6 Hz), 6.55-6.62 (2H, m), 6.71-6.79 (1H, m), 6.82 (1H, d, J = 9.0 Hz), 7.24-7.33 (1H, m), 8.00 (1H, dd, J = 2.6 Hz, 9. 0 Hz), 8.15 (1H, d, J = 2".6 Hz). (Ii) Production of 3-methyl-4- [3- (3-methylbutoxy) phenoxy] aniline When using 2-methyl-1- [ 3- (3-methylbutoxy) phenoxy] -4- nitrobenzene (978 mg), reduced iron (879 mg), calcium chloride (176 mg) and ethanol (27 ml) / water (3 ml) and from the same manner as in Example C-72 (ii), was obtained the title compound (835 mg) as a brown oil. XH-NMR (CDC13) d: 0.94 (6H, d, J = 6.7 Hz), 1.64 (2H, q, J = 6.7 Hz), 1.72-1.90 (1H, m), 2.10 (3H, s), 3.55 ( 2H, br s), 3.93 (2H, t, J = 6.7 Hz), 6.36-6.44 (2H, m), 6.48-6.55 (2H, m), 6.58 (1H, d, J = 2.8 Hz), 6.80 ( 1H, d, J = 8.3 Hz), 7.06-7.18 (1H, m). (iii) Production of 2- [4- ( { 3-methyl-4- [3- (3-methylbutoxy) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidine-5 -il] ethanol When using 2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethyl benzoate (105 mg), 3-methyl-4- [3- (3-methylbutoxy phenoxy] aniline (102 mg), isopropyl alcohol (3 ml) and 1 N aqueous solution of sodium hydroxide (1 ml) and in the same manner as in Example C-72 (iii), the title compound was obtained (91.5 mg) in the form of white crystals. XH-NMR (CDCl3) d: 0.96 (6H, d, J = 6.7 Hz), 1.66 (2H, q, J = 6.7 Hz), 1.75-1.92 (1H, m), 2.25 (3H, s), 3.96 ( 2H, t, J = 6.7 Hz), 4.12 (2H, t, J = 4.4 Hz), 4.31-4.41 (2H, m), 6.11 (1H, d, J = 3.2 Hz), 6.46-6.54 (2H, m ), 6.54-6.62 (1H, m), 6.92 (1H, d, J = 3.2 Hz), 6.97 (1H, d, J = 8.3 Hz), 7.12-7.22 (1H, m), 7.36-7.50 (2H, m), 8.22 (1H, s), 9.29 (1H, s).

Example C-116 Production of 2- (methylsulfonyl) -N- hydrochloride. { 2- [4- ( { 3-methyl-4- [3- (2,2,2-trifluoroethoxy) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidine-5- il] ethyl} acetamide (i) Production of. { 2- [4- ( { 3-methyl-4- [3- (2, 2, 2-trifluoroethoxy) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5- il] ethyl} tert-butyl carbamate When using [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (305 mg), 3-methyl-4- [ 3- (2,2,2-trifluoroethoxy) phenoxy] aniline (326 mg) and isopropyl alcohol (12 ml) and in the same manner as in Example C-105 (i), the title compound was obtained (489 mg ) in the form of a white powder. V -? - NMR (CDC13) d: 1.46 (9H, s), 2.21 (3H, s), 3.42- 3.58 (2H, m), 4.31 (2H, q, J = 8.1 Hz), 4.41-4.55 (2H , m), 5.03 (1H, t, J = 5.0 Hz), 6.53 (1H, t, J = 2.4 Hz), 6.56-6.67 (3H, m), 6.91-7.02 (1H, m), 7.16 (1H, d, J = 3.2 Hz), 7.21 (1H, t, J = 8.2 Hz), 7.56-7.77 (2H, m), 8.38 (1H, br s), 8.49 (1H, s). (ii) Production of 5- (2-aminoethyl) -N- dihydrochloride. { 3-methyl-4- [3- (2,2,2-trifluoroethoxy) phenoxy] phenyl} -5H-pyrrolo [3,2-d] pyrimidin-4-amine When using. { 2- [4- ( { 3-methyl-4- [3- (2, 2, 2-trifluoroethoxy) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidine-5- il] ethyl} tert-butyl carbamate (484 mg), 6 N hydrochloric acid (1 ml) and ethanol (3 ml) and in the same manner as in Example C-105 (ii), the title compound (423 mg) was obtained in the form of a yellow powder. Vi-NMR (DMSO-d6) d: 2.20 (3H, s), 3.21-3.33 (2H, m), 4.78 (2H, q, J = 8.9 Hz), 5.01 (2H, t, J = 6.1 Hz), 6.56 (1H, dd, J = 2.0 Hz, 8.0 Hz), 6.64 (1H, t, J = 2.0 Hz), 6.72 (1H, d, J = 3.2 Hz), 6.81 (1H, dd, J = 2.0 Hz, 8.0 Hz), 7.04 (1H, d, J = 8.7 Hz), 7.33 (1H, t, J = 8.0 Hz), 7.43 (1H, dd, J = 2.5 Hz, 8.7 Hz), 7.52 (1H, d, J = 2.5 Hz), 8.04 (1H, d, J = 3.2 Hz), 8.34 (3H, br s), 8.68 (1H, s), 9.92 (1H, br s). (iii) Production of 2- (methylsulfonyl) -N- hydrochloride. { 2- [4- ( { 3-methyl-4- [3- (2,2,2-trifluoroethoxy) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidine-5- il] ethyl} acetamide When using 5- (2-aminoethyl) -N- dihydrochloride. { 3-methyl-4- [3- (2,2, 2-trifluoroethoxy) phenoxy] phenyl} -5H-pyrrolo [3,2-d] pyrimidin-4-amine (152 mg), methylsulfonylacetic acid (64.5 mg), tetrahydrofuran (0.8 ml) / N, -dimethylformamide (0.8 ml), 1-hydroxybenzotriazole (70.6 mg), triethylamine (0.4 ml) and l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (93.8 mg) and in the same manner as in Example C-72 (i), 2- (methylsulfonyl) -N- was obtained. { 2- [4- ( { 3-methyl-4- [3- (2, 2,2-trifluoroethoxy) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} acetamide. The compound was dissolved in ethyl acetate and treated with 4 N hydrogen chloride solution / ethyl acetate, and the precipitate was collected by filtration to give the title compound (132 mg) as a pale yellow powder. . ^ -RMN (DMSO-d6) d: 2.20 (3H, s), 3.05 (3H, s), 3.49-3.60 (2H, m), 4.07 (2H, s), 4.69 (2H, t, J = 6.5 Hz ), 4.77 (2H, q, J = 8.9 Hz), 6.52-6.59 (1H, m), 6.61-6.68 (2H, m), 6.81 (1H, dd, J = 2.3 Hz, 8.1 Hz), 7.04 (1H , d, J = 8.7 Hz), 7.33 (1H, t, J = 8.1 Hz), 7.47 (1H, dd, J = 2.5 Hz, 8.7 Hz), 7.54 (1H, d, J = 2.5 Hz), 7.91 ( 1H, d, J = 3.0 Hz), 8.67 (1H, s), 8.79 (1H, t, J = 5.5 Hz), 9.85 (1H, s). Example C-117 Production of N- hydrochloride. { 2- [4- ( { 3-Methyl-4- [3- (3-methylbutoxy) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide (i) Production of. { 2- [4- ( { 3-Methyl-4- [3- (3-methylbutoxy) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidine-Sil] ethyl} tert-butyl carbamate When using [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (400 mg), 3-methyl-4- [ 3- (3-methylbutoxy) phenoxy] aniline (408 mg) and isopropyl alcohol (15 ml) and in the same manner as in Example C-105 (i), the title compound (692 mg) was obtained in the form of a white powder. Vl-NMR (CDC13) d: 0.95 (6H, d, J = 6.6 Hz), 1.46 (9H, s), 1.61-1.71 (2H, m), 1.74-1.91 (1H, m), 2.23 (3H, s) ), 3.42-3.58 (2H, m), 3.95 (2H, t, J = 6.6 Hz), 4.39-4.54 (2H, m), 5.01 (1H, t, J = 6.1 Hz), 6.45-6.62 (4H, m), 6.96 (1H, d, J = 8.9 Hz), 7.10-7.22 (2H, m), 7.57-7.74 (2H, m), 8.33 (1H, br s), 8.49 (1H, s). (ii) Production of 5- (2-aminoethyl) -N- dihydrochloride. { 3-methy1-4- [3- (3-methylbutoxy) phenoxy] phenyl} -5H-pyrrolo [3,2-d] pyrimidin-amine When using. { 2- [4- ( { 3-Methyl-4- [3- (3-methylbutoxy) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} tert-butyl carbamate (685 mg), 6 N hydrochloric acid (1 ml) and ethanol (3 ml) and in the same manner as in the Example C-105 (ii), the title compound (602 mg) was obtained in a yellow powder fora. Vl-NMR (DMSO-d6) d: 0.92 (6H, d, J = 6.6 Hz), 1.59 (2H, q, J = 6.6 Hz), 1.67-1.86 (1H, m), 2.20 (3H, s), 3.20-3.33 (2H, m), 3.97 (2H, t, J = 6.6 Hz), 5.01 (2H, t, J = 6.2 Hz), 6.40-6.52 (2H, m), 6.68 (1H, dd, J = 2.0 Hz, 8.3 Hz), 6.72 (1H, d, J = 3.0 Hz), 7.02 (1H, d, J = 8.7 Hz), 7.26 (1H, t, J = 8.3 Hz), 7.41 (1H, dd, J = 2.5 Hz, 8.7 Hz), 7.50 (1H, d, J = 2.0 Hz), 8.05 (1H, d, J = 3.0 Hz), 8.35 (3H, br s), 8.67 (1H, s), 9.91 (1H , br s). (iii) Production of N- hydrochloride. { 2- [4- ( { 3-Methyl-4- [3- (3-methylbutoxy) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide When using 5- (2-aminoethyl) -N- dihydrochloride. { 3-methy1-4- [3- (3-methylbutoxy) phenoxy] phenyl} -5H-pyrrolo [3,2-d] pyrimidin-4-amine (150 mg), methylsulfonylacetic acid (60.9 mg), tetrahydrofuran (0.8 ml) / N, N-dimethylformamide (0.8 ml), 1-hydroxybenzotriazole (68.1 mg), triethylamine (0.4 ml) and l-ethyl-3- (3-dimethylaminopropyl) -carbodiimide hydrochloride (92.2 mg) and in the same manner as in Example C-72 (i), N- was obtained. { 2- [4- ( { 3-Methyl-4- [3- (3-methylbutoxy) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide. The compound was dissolved in ethyl acetate and treated with 4 N hydrogen chloride solution / ethyl acetate, and the precipitate was collected by filtration to give the title compound (116 mg) in foil of a pale yellow powder. V-NMR (DMSO-d6) d: 0.92 (6H, d, J = 6.6 Hz), 1.59 (2H, q, J = 6.6 Hz), 1.67-1.84 (1H, m), 2.20 (3H, s), 3.05 (3H, s), 3.54 (2H, q, J = 6.0 Hz), 3.97 (2H, t, J = 6.6 Hz), 4. 06 (2H, s), 4.69 (2H, t, J = 6.0 Hz), 6.40-6.52 (2H, m), 6.64 (1H, d, J = 3.2 Hz), 6.66-6.72 (1H, m), 7.02 (1H, d, J = 8. 7 Hz), 7.26 (1H, t, J = 8.2 Hz), 7.45 (1H, dd, J = 2.5 Hz, 8.7 Hz), 7.52 (1H, d, J = 2.5 Hz), 7.90 (1H, d, J = 3.2 Hz), 8.67 (1H, s), 8.78 (1H, t, J = 6.0 Hz), 9.83 (1H, s). Example C-118 Production of N-. { 2- [4- ( { 4- [3- (2-Ratoxyethoxy) phenoxy] -3-methylphenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (Methylsulfonyl) acetamide (i) Production of 1- [3- (2-methoxyethoxy) phenoxy] -2-methy1-4-nitrobenzene When using 3- (2-methyl-4-nitrophenoxy) phenol (806 mg) , 1-bromo-2-methoxyethane (0.5 ml), potassium carbonate (910 mg) and N, N-dimethylformamide (10 ml) and in the same manner as in Example C-104 (i), the compound was obtained of the title (855 mg) in the form of a yellow oil. 1 H-RN (CDCl 3) d: 2.39 (3H, s), 3.45 (3H, s), 3.69-3.80 (2H, m), 4.06-4.15 (2H, m), 6.57-6.65 (2H, m), 6.75 -6.80 (1H, m), 6.82 (1H, d, J = 9.0 Hz), 7.24-7.33 (1H, m), 7.99 (1H, dd, J = 2.8 Hz, 9.0 Hz), 8.15 (1H, d, J = 2.8 Hz). (ii) Production of 4- [3- (2-methoxyethoxy) phenoxy] -3-methylaniline When using 1- [3- (2-methoxyethoxy) phenoxy] -2-methyl-4-nitrobenzene (850 mg), reduced iron (825 mg), calcium chloride (167 mg) and ethanol (27 ml) / water (3 ml) and from the same manner as in Example C-72 (ii), the title compound (707 mg) was obtained in the form of a brown oil. 1 H-NMR (CDCl 3) d: 2.09 (3H, s), 3.43 (3H, s), 3.56 (2H, br s), 3.67-3.76 (2H, m), 4.02-4.09 (2H, m), 6.35- 6.63 (5H, m), 6.79 (1H, d, J = 8.3 Hz), 7.13 (1H, t, J = 8.3 Hz). (iii) Production of. { 2- [4- ( { 4- [3- (2-methoxyethoxy) phenoxy] -3-methylphenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} tert-butyl carbamate When using [2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (358 mg), 4- [3- (2 -methoxyethoxy) phenoxy] -3-methylaniline (364 mg) and isopropyl alcohol (15 ml) and in the same manner as in Example C-105 (i), the title compound (563 mg) was obtained in the form of a white powder. XH-NMR (CDCI3) d: 1.46 (9H, s), 2.22 (3H, s), 3.44 (3H, s), 3.45-3.56 (2H, m), 3.69-3.77 (2H, m), 4.04-4.10 (2H, m), 4.40-4.52 (2H, m), 5.01 (1H, t, J = 5.7 Hz), 6.49-6.65 (4H, ra), 6.91-6.99 (1H, m), 7.12-7.23 (2H, m), 7.53-7.73 (2H, m), 8.31 (1H, br s), 8.49 ( 1H, s). (iv) Production of 5- (2-aminoethyl) -N- dihydrochloride. { 4- [3- (2-methoxyethoxy) phenoxy] -3-methylphenyl} -5H-pyrrolo [3,2-d] pyrimidin-4-amine When using. { 2- [4- ( { - [3- (2-methoxyethoxy) phenoxy] -3-methylphenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} tert-butyl carbamate (558 mg), 6 N hydrochloric acid (1 ml) and ethanol (4 ml) and in the same manner as in Example C-105 (ii), the title compound (471 mg) was obtained in the form of a yellow powder. Vi-NMR (DMSO-d5) d: 2.19 (3H, s), 3.21-3.38 (2H, m), 3.29 (3H, s), 3.58-3.69 (2H, m), 4.00-4.13 (2H, m) , 5.00 (2H, t, J = 6.0 Hz), 6.44-6.54 (2H, m), 6.65-6.71 (1H, m), 6.72 (1H, d, J = 3.2 Hz), 7.03 (1H, d, J = 8.7 Hz), 7.20-7.33 (1H, m), 7.41 (1H, dd, J = 2.5 Hz, 8.7 Hz), 7.50 (1H , d, J = 2.5 Hz), 8.04 (1H, d, J = 3.2 Hz), 8.32 (3H, br s), 8.68 (1H, s), 9.88 (1H, br s). (v) Production of N-. { 2- [4- ( { 4- [3- (2-methoxyethoxy) phenoxy] -3-methylphenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide When using 5- (2-aminoethyl) -N- dihydrochloride. { 4- [3- (2-methoxyethoxy) phenoxy] -3-methylphenyl} -5H-pyrrolo [3, 2- d) pyrimidin-4-amine (151 mg), methylsulfonylacetic acid (67.3 mg), tetrahydrofuran (0.8 ml) / N, N-dimethylformamide (0.8 ml), 1-hydroxybenzotriazole (94.2 mg), triethylamine (0.4 ml) and hydrochloride of l-ethyl-3- (3-dimethylaminopropyl) carbodiimide (122 mg) and in the same manner as in Example C-72 (i), the title compound (98.4 mg) was obtained as a colored powder pale yellow. XH-NMR (CDC13) d: 2.23 (3H, s), 3.08 (3H, s), 3.44 (3H, s), 3.63-3.78 (4H, m), 3.93 (2H, s), 4.04-4.13 (2H, m), 4.38-4.54 (2H, m), 6.51 (1H, t, J = 2.4 Hz ), 6.53-6.66 (3H, m), 6.94 (1H, d, J = 8.7 Hz), 7.13-7.23 (2H, m), 7.44 (1H, dd, J = 2.0 Hz, 8.7 Hz), 7.51 (1H, t, J = 5.7 Hz), 7.56 (1H, d, J = 2. 0 Hz), 7.83 (1H, s), 8.46 (1H, s).

Production of N- hydrochloride. { 2- [4- ( { 4- [3- (2,2-dimethylpropoxy) phenoxy] -3-methylphenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (Methylsulfonyl) acetamide (i) Production of 1- [3- (2,2-dimethylpropoxy) phenoxy] -2-methy1-4-nitrobenzene When using 3- (2-methyl-4-nitrophenoxy) phenol (803 mg) , 1- iodine-2, 2-dimethylpropane (0.75 ml), potassium carbonate (911 mg) and N, N-dimethylformamide (10 ml) and in the same manner as in Example C-104 (i), the composed of the title (826 mg) in the form of a yellow oil. VL-NMR (CDC13) d: 1.03 (9H, s), 2.40 (3H, s), 3.57 (2H, s), 6.55-6.62 (2H, m), 6.73-6.79 (1H, m), 6.82 (1H, d, J = 9.0 Hz), 7.28 (1H, t, J = 8.5 Hz), 8.00 (1H, dd, J = 2.5 Hz, 9. 0 Hz), 8.15 (1H, d, J = 2.5 Hz). (ii) Production of 4- [3- (2,2-dimethylpropoxy) phenoxy] -3-methylaniline When using 1- [3- (2, 2-dimethylpropoxy) phenoxy] -2-methyl-4-nitrobenzene (821 mg ), reduced iron (876 rag), calcium chloride (147 mg) and ethanol (27 ml) / water (3 ml) and in the same manner as in Example C-72 (ii), the title compound was obtained (745 mg) in the form of a brown oil. VL-NMR (CDCI3) d: 1.01 (9H, s), 2.11 (3H, s), 3.53 (2H, s), 3.54 (2H, br s), 6.35-6.41 (1H, m), 6.43 (1H, t, J = 2.4 Hz), 6.48-6.56 (2H, ra), 6.59 (1H, d, J = 2.8 Hz), 6.80 (1H, d, J = 8.0 Hz), 7.12 (1H, t, J = 8.0 Hz). (iii) Production of. { 2- [4- ( { 4- [3- (2, 2-dimethylpropoxy) phenoxy] -3-methylphenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl } tert-butyl carbamate When using [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (351 mg), 4- [3- (2 , 2-dimethylpropoxy) phenoxy] -3-methylaniline (357 mg) and alcohol isopropyl (15 ml) and in the same manner as in Example C-105 (i), the title compound (592 mg) was obtained as a white powder. Vi-NMR (CDC13) d: 1.02 (9H, s), 1.46 (9H, s), 2.24 (3H, s), 3.42-3.55 (2H, m), 3.56 (2H, s), 4.39-4.55 (2H , m),5. 02 (1H, t, J = 5.8 Hz), 6.44-6.65 (4H, m), 6.96 (1H, d, J = 8. 5 Hz), 7.09-7.22 (2H, m), 7.56-7.72 (2H, m), 8.32 (1H, br s), 8.49 (1H, s). (iv) Production of 5- (2-aminoethyl) -N- dihydrochloride. { 4- [3- (2, 2-dimethylpropoxy) phenoxy] -3-methylphenyl} -5H-pyrrolo [3,2-d] pyrimidin-4-amine When using. { 2- [4- ( { - [3- (2, 2-dimethylpropoxy) phenoxy] -3-methylphenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} tert-butyl carbamate (586 mg), 6 N hydrochloric acid (1 ml) and ethanol (4 ml) and in the same manner as in Example C-105 (ii), the title compound (369 mg) was obtained in the form of a yellow powder. Vl-NMR (DMS0-d6) d: 0.98 (9H, s), 2.20 (3H, s), 3.18-3.36 (2H, m), 3.62 (2H, s), 4.99 (2H, t, J = 6.2 Hz ), 6.40-6.55 (2H, m), 6.63-6.77 (2H, m), 7.02 (1H, d, J = 8.5 Hz), 7.26 (1H, t, J = 8.2 Hz), 7.41 (1H, dd, J = 2.3 Hz, 8.5 Hz), 7.50 (1H, d, J = 2.3 Hz), 8.03 (1H, d, J = 3.2 Hz), 8.29 (3H, br s), 8.67 (1H, s), 9.86 ( 1H, br s). (v) Production of N- hydrochloride. { 2- [4- ( { - [3- (2, 2-dimethylpropoxy) phenoxy] -3-methylphenyl.} Amino) -5H- pyrrolo [3, 2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide When using 5- (2-aminoethyl) -N- dihydrochloride. { 4- [3- (2, 2-dimethylpropoxy) phenoxy] -3-methylphenyl} -5H-pyrrolo [3,2-d] pyrimidin-4-amine (152 mg), methylsulfonylacetic acid (63.0 mg), tetrahydrofuran (0.8 ml) / N, N-dimethylformamide (0.8 ml), 1-hydroxybenzotriazole (86.5 mg), triethylamine (0.4 ml) and l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (125 mg) and in the same manner as in Example C-72 ( i), N- was obtained. { 2- [4- ( { 4- [3- (2, 2-dimethylpropoxy) phenoxy] -3-methylphenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl } -2- (methylsulfonyl) acetamide. The compound was dissolved in ethyl acetate and treated with 4 N hydrogen chloride solution / ethyl acetate, and the precipitate was collected by filtration to give the title compound (126 mg) as yellow crystals. Vl-NMR (DMSO-d6) d: 0.98 (9H, s), 2.20 (3H, s), 3.05 (3H, s), 3.54 (2H, q, J = 6.0 Hz), 3.61 (2H, s), 4.07 (2H, s), 4.70 (2H, t, J = 6.0 Hz), 6.40-6.53 (2H, m), 6.64 (1H, d, J = 3.0 Hz), 6.69 (1H, dd, J = 1.7 Hz , 8.0 Hz), 7.02 (1H, d, J = 8.5 Hz), 7.26 (1H, t, J = 8.0 Hz), 7.45 (1H, dd, J = 2.0 Hz, 8.5 Hz), 7.53 (1H, d, J = 2.0 Hz), 7.91 (1H, d, J = 3.0 Hz), 8.67 (1H, s), 8.80 (1H, t, J = 6.0 Hz), 9.86 (1H, s).

Example C-120 Production of 2-. { 4- [(3-chloro-4- { 3- [(2,2,2-trifluoroethyl) sulfonyl] phenoxy] phenyl) amino] -5H-pyrrolo [3,2-d] pyrimidine-5- il} ethanol (i) Production of 2-chloro-4-nitro-l-. { 3- [(2, 2, 2-trifluoroethyl) thio] phenoxy} benzene To a solution of 3-mercaptophenol (2.0 g) and triethylamine (2.70 ml) in N, N-dimethylformamide (20 ml) was added 2, 2, 2-trifluoro-1-iodoethane (1.72 ml) at room temperature. The reaction mixture was stirred at room temperature for 4 h, 3-chloro-4-fluoronitrobenzene (2.77 g) and potassium carbonate (2.18 g) were added. The reaction mixture was stirred at room temperature for 20 h, water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by column chromatography (eluent, hexane: ethyl acetate = 19: 1-> 3: 1) to give the title compound (4.27 g) as a a yellow oil Vl-NMR (CDC16) d: 3.48 (2H, q, J = 9.6 Hz), 6.91 (1H, d, J = 9.0 Hz), 6.98-7.02 (1H, m), 7.19-7.21 (1H, m), 7.34-7.44 (2H, m), 8.09 (1H, dd, J = 2.7 Hz, 9.0 Hz), 8.40 (1H, d, J = 2.7 Hz). (ii) Production of 2-chloro-4-nitro-l-. { 3- [(2, 2, 2-trifluoroethyl) sulfonyl] phenoxy Jbenzene To a solution of 2-chloro-4-nitro-1-. { 3- [(2, 2, 2-trifluoroethyl) thio] phenoxy Jbenzene (2.0 g) in ethyl acetate (20 ml) was added 70% 3-chloroperbenzoic acid (2.80 g) at 0 ° C. The reaction mixture was stirred at 0 ° C for 2 h and at room temperature for 4 days, aqueous solution of sodium thiosulfate was added to the reaction mixture, and the mixture was stirred for 1 h. The mixture was extracted with ethyl acetate, and the organic layer was washed successively with aqueous sodium bicarbonate and saturated brine, and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by column chromatography (eluent, hexane: ethyl acetate = 9: 1- >; 2: 3) to give the title compound (2.34 g) as colorless crystals. XH-NMR (CDC13) d: 3.94 (2H, q, J = 8.7 Hz), 7.01 (1H, d, J = 9.0 Hz), 7.38-7.43 (1H, m), 7.60-7.62 (1H, m), 7.66-7.71 (1H, ra), 7.81-7.85 (1H, m), 8.15 (1H, dd, J = 2.7 Hz, 9.0 Hz), 8.43 (1H, d, J = 2.7 Hz). (iii) Production of 3-chloro-4-. { 3- [(2, 2, 2- trifluoroethyl) sulfonyl] phenoxy} Aniline A mixture of 2-chloro-4-nitro-l-. { 3- [(2,2,2-trifluoroethyl) sulfonyl] phenoxy [benzene (2.34 g), reduced iron (1.54 g) and calcium chloride (0.31 g) in 15% ethanol with water content (70 ml) is heated at reflux for 10 h. The insoluble material was filtered, and the filtrate was concentrated under reduced pressure. Aqueous sodium bicarbonate was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by column chromatography (eluent, hexane: ethyl acetate = 3: 1-> 3: 7) to give the title compound (892 mg) as a solid yellow. XH-NMR (CDC13) d: 3.77 (2H, br s), 3.87 (2H, q, J = 9. 0 Hz), 6.60 (1H, dd, J = 2.7, 8.7 Hz), 6.79 (1H, d, J = 2.7 Hz), 6.85 (1H, d, J = 8.7 Hz), 7.20-7.25 (1H, m) , 7.35-7.37 (1H, m), 7.51 (1H, t, J = 8.1 Hz), 7.61 (1H, d, J = 8.1 Hz). (iv) Production of 2-. { 4- [(3-chloro-4-. {3- [2, 2, 2-trifluoroethyl] sulfonyl] phenoxy] phenyl) amino] -5H-pyrrolo [3,2-d] pyrimidin-5- il} ethanol A solution of 5- (2- {[tert-butyl (dimethyl) silyl] oxy} ethyl) -4-chloro-5H-pyrrolo [3,2-d] pyrimidine (100 mg) and 3- chlorine-4-. { 3- [(2, 2, 2-trifluoroethyl) sulfonyl] phenoxy} Aniline (117 mg) in alcohol Isopropyl (3.0 ml) was stirred at 80 ° C for 4 days. After concentrating under reduced pressure, methanol (5.0 ml) and 6 N hydrochloric acid (1.0 ral) were added to the residue. The mixture was stirred at room temperature for 4 h, and aqueous sodium bicarbonate was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by column chromatography (eluent, ethyl acetate -> ethyl acetate: methanol = 9: 1) to give the title compound (99 mg) as crystals pale yellow. H-NMR (CDC13) d: 3.90 (2H, q, J = 9.0 Hz), 4.16-4.25 (2H, m), 4.43-4.50 (2H, m), 4.91-5.02 (1H, m), 6.32 (1H , d, J = 3.0 Hz), 7.08 (1H, d, J = 3.0 Hz), 7.11 (1H, d, J = 8.7 Hz), 7.27-7.33 (1H, m), 7.42-7.47 (1H, m) , 7.52-7.58 (2H, m), 7.64-7.67 (1H, m), 7.83 (1H, d, J = 2.7 Hz), 8.35 (1H, s), 9.45 (1H, s). Example C-121 Production of 2- [4- ( { 3-chloro-4- [3- (methylsulfonyl) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethanol (i) Production of 2-chloro-l- [3- (methylthio) phenoxy] -4-nitrobenzene To a solution of 3-mercaptophenol (3.0 g) and triethylamine (3.64 ral) in N, N-dimethylformamide (30 ml) methyl iodide (1.48 ml) was added at 0 ° C. The reaction mixture was stirred at 0 ° C for 1 h and at room temperature for 30 min, 3-chloro-4-fluoronitrobenzene was added. (4.18 g) and potassium carbonate (3.29 g) to the reaction mixture. The reaction mixture was stirred at room temperature for 14 h, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by column chromatography (eluent, hexane: ethyl acetate = 19: 1-> 3: 1) to give the title compound (2.84 g) as a a yellow oil VL-NMR (CDC13) d: 2.49 (3H, s), 6.80-6.84 (1H, m), 6.91 (1H, d, J = 9.3 Hz), 6.96-6.97 (1H, m), 7.11-7.15 (1H , m), 7.32-7.37 (1H, m), 8.07 (1H, dd, J = 2.7 Hz, 9.3 Hz), 8.39 (1H, d, J = 2.7 Hz). (ii) Production of 2-chloro-l- [3- (methylsulfonyl) phenoxy] -4-nitrobenzene To a solution of 2-chloro-l- [3- (methylthio) phenoxy] -4-nitrobenzene (2.84 g) in Ethyl acetate (50 ml) was added 70% 3-chloroperbenzoic acid (5.21 g) at 0 ° C. The reaction mixture was stirred at 0 ° C for 1 h, aqueous sodium thiosulfate solution was added to the reaction mixture, and the mixture was stirred at room temperature for 1 h. The mixture was extracted with ethyl acetate, the organic layer was washed successively with aqueous sodium bicarbonate and saturated brine, and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by column chromatography (eluent, hexane: ethyl acetate = 4: 1- >; 2: 3) to give the title compound (2.79 g) as colorless crystals. XH-NMR (CDC13) d: 3.09 (3H, s), 7.02 (1H, d, J = 8.7 Hz), 7.32-7.36 (1H, m), 7.61-7.67 (2H, ra), 7.79-7.83 (1H , m), 8.13 (1H, dd, J = 2.4 Hz, 8.7 Hz), 8.42 (1H, d, J = 2.7 Hz). (iii) Production of 3-chloro-4- [3- (methylsulfonyl) phenoxy] aniline When using 2-chloro-l- [3- (methylsulfonyl) phenoxy] -4-nitrobenzene (2.90 g), reduced iron (2.50 g) ), calcium chloride (0.50 g) and 15% ethanol with water content (90 ml) and in the same manner as in Example C-120 (iii), the title compound (2.29 g) was obtained in the form of pale yellow crystals. VL-NMR (CDCI3) d: 3.03 (3H, s), 3.74 (2H, br s), 6.59 (1H, dd, J = 2.7 Hz, 8.4 Hz), 6.78 (1H, d, J = 2.7 Hz), 6.93 (1H, d, J = 8.4 Hz), 7.13-7.17 (1H, m), 7.36-7.38 (1H, m), 7.44-7.50 (1H, ra), 7.56-7.60 (1H, m). (iv) Production of 2- [4- ( { 3-chloro-4- [3- (methylsulfonyl) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl ] ethanol A solution of 2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl benzoate (100 mg) and 3-chloro-4- [3- (methylsulfonyl) phenoxy] Aniline (98.3 mg) in isopropyl alcohol (2.0 ml) was stirred at 80 ° C for 3 days. The reaction mixture was cooled to room temperature, 1 N aqueous solution of sodium hydroxide (1.0 ml) was added. The reaction mixture was stirred at room temperature for 2 h, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by column chromatography (eluent, ethyl acetate -> ethyl acetate: methanol = 9: 1) to give the title compound (116 mg) as crystals colorless Vl-NMR (CDC13) d: 3.06 (3H, s), 4.18 (2H, t, J = 4.7 Hz), 4.44 (2H, t, J = 4.7 Hz), 6.27 (1H, d, J = 3.0 Hz) , 7.05 (1H, d, J = 3.0 Hz), 7.11 (1H, d, J = 9.0 Hz), 7.22-7.28 (1H, m), 7.43-7.45 (1H, m), 7.50-7.55 (2H, m ), 7.61-7.64 (1H, ra), 7.83 (1H, d, J = 2.7 Hz), 8.31 (1H, s), 9.50 (1H, s).

Example C-122 Production of 2-. { 2- [4- ( { 3-Chloro-4- [3- (methylsulfonyl) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethoxy} ethanol When using 2- [2- (4-chloro-5H-pyrrolo [3, 2-d] pyrimidin-5-yl) ethoxy] ethyl benzoate (100 mg), 3-chloro-4- [3- (methylsulfonyl ) phenoxy] aniline (86.1 mg), isopropyl alcohol (2.0 ml) and 1 N aqueous solution of sodium hydroxide (1.0 ml) and in the same manner as in Example C-121 (iv), the title compound was obtained (117 mg) in the form of colorless crystals. XH-NMR (CDC13) d: 1.78-1.85 (1H, m), 3.05 (3H, s), 3.78-3.84 (4H, m), 4.03 (2H, t, J = 4.4 Hz), 4.59 (2H, t , J = 4.4 Hz), 6.64 (1H, d, J = 3.3 Hz), 7.09 (1H, d, J = 9.0 Hz), 7.22-7.27 (2H, m), 7.39-7.41 (1H, m), 7.48 -7.53 (1H, m), 7.61 (1H, s), 7.63 (1H, dd, J = 2.7 Hz, 9.0 Hz), 7.94 (1H, d, J = 2.7 Hz), 8.53 (1H, s), 8.85 (1H, s).

Example C-123 Production of 2- [4- ( { 3-chloro-4- [3- (isopropylsulfonyl) phenoxy] phenyl}. amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethanol ( i) Production of 2-chloro-l- [3- (isopropylthio) phenoxy] -4-nitrobenzene To a solution of 3-mercaptophenol (1.5 g) and sodium tert -butoxide (1.37 g) in N, N-dimethylformamide (25 ml) ) 2-Bromopropane (1.23 ml) was added at room temperature. The reaction mixture was stirred at room temperature for 16 h, sodium ter-butoxide (1.37 g) and 3-chloro-4-fluoronitrobenzene (1.88 g) were added to the reaction mixture, and the mixture was stirred for 4 h . 3-Chloro-4-fluoronitrobenzene (0.17 g) was also added to the reaction mixture and the mixture was stirred at room temperature for 2 h. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by column chromatography (eluent, hexane: ethyl acetate = 19: 1-> 4: 1) to give the compound of the title (3.36 g) in the form of a yellow oil. XH-NMR (CDCl3) d: 1.32 (6H, d, J = 6.9 Hz), 3.42 (1H, quintet, J = 6.9 Hz), 6.88-6.92 (2H, ra), 7.07-7.08 (1H, m), 7.21-7.27 (1H, m), 7.32-7.37 (1H, m), 8.06 (1H, dd, J = 2.7 Hz, 9.3 Hz), 8.38 (1H, d, J = 2.7 Hz). (ii) Production of 2-chloro-l- [3- (isopropylsulfonyl) phenoxy] -4-nitrobenzene When using 2-chloro-l- [3- (isopropylthio) phenoxy] -4-nitrobenzene (3.36 g), acid 3 -70% chloroperbenzoic acid (5.63 g) and ethyl acetate (50 ml) and in the same manner as in the Example C-121 (ii), the title compound (3.36 g) was obtained as pale yellow crystals. Vl-NMR (CDCI3) d: 1.32 (6H, d, J = 6.9 Hz), 3.22 (1H, quintet, J = 6.9 Hz), 6.99 (1H, d, J = 9.0 Hz), 7.33-7.37 (1H, m), 7.54-7.55 (1H, m), 7.61-7.66 (1H, m), 7.74-7.77 (1H, m), 8.13 (1H, dd, J = 2.7 Hz, 9.0 Hz), 8.41 (1H, d, J = 2. 7 Hz). (iii) Production of 3-chloro-4- [3- (isopropylsulfonyl) phenoxy] aniline When using 2-chloro-l- [3- (isopropylsulfonyl) phenoxy] -4-nitrobenzene (3.30 g), reduced iron (2.59 g) ), calcium chloride (0.52 g) and 15% ethanol with water content (100 ml) and in the same manner as in Example C-120 (iii), the title compound (3.00 g) was obtained in the form of a yellow oil.

Vl-NMR (CDCI3) d: 1.28 (6H, d, J = 6.9 Hz), 3.16 (1H, quintet, J = 6.9 Hz), 3.73 (2H, br s), 6.59 (1H, dd, J = 2.7 Hz, 8.7 Hz), 6.78 (1H, d, J = 2.7 Hz), 6.93 (1H, d, J = 8. 7 Hz), 7.14-7.19 (1H, m), 7.28-7.30 (1H, m), 7.44-7.54 (2H, m). (iv) Production of 2- [4- ( { 3-chloro-4- [3- (isopropylsulfonyl) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl ] ethanol When using 2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethyl benzoate (100 mg), 3-chloro-4- [3- (isopropylsulfonyl) phenoxy] aniline (140 mg), isopropyl alcohol (2.0 ml) and 1 N aqueous solution of sodium hydroxide (1.0 ml) and in the same manner as in Example C-121 (iv), the title compound (127 mg) was obtained in the form of pale yellow crystals. XH-NMR (CDCl3) d: 1.30 (6H, d, J = 6.9 Hz), 3.19 (1H, quintet, J = 6.9 Hz), 4.16 (2H, t, J = 4.5 Hz), 4.43 (2H, t, J = 4.5 Hz), 5.30-5.71 (1H, m), 6.26 (1H, d, J = 3.0 Hz), 7.05 (1H, d, J = 3.0 Hz), 7.10 (1H, d, J = 8.7 Hz) , 7.23-7.30 (1H, m), 7.35-7.37 (1H, m), 7.48-7.61 (3H, m), 7.84 (1H, d, J = 2.4 Hz), 8.31 (1H, s), 9.53 (1H , s).

Production of 2- hydrochloride. { 2- [4- ( { 3-Chloro-4- [3- (isopropylsulfonyl) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethoxy} ethanol When using 2- [2- (4-chloro-5H-pyrrolo [3, 2-d] pyrimidin-5-yl) ethoxy] ethyl benzoate (100 mg), 3-chloro-4- [3- (isopropylsulfonyl ) phenoxy] aniline (113 mg), isopropyl alcohol (2.0 ml) and 1 N aqueous solution of sodium hydroxide (1.0 ml) and in the same manner as in Example C-121 (iv), a colored oil was obtained pale yellow. To a solution of the oil obtained in ethanol (5.0 ml) was added 4N hydrogen chloride solution / ethyl acetate (0.50 ml) at room temperature. The mixture was concentrated under reduced pressure, and the resulting crystals were collected by filtration. The crystals were washed with ethyl acetate to give the title compound (130 mg) as pale yellow crystals. XH-NMR (DMSO-d6) d: 1.15 (6H, d, J = 6.9 Hz), 3.38-3.54 (5H, m), 3.82-3.89 (2H, ra), 4.75-4.83 (2H, m), 6.69 (1H, d, J = 3.0 Hz), 7.23-7.25 (1H, ra), 7.39-7.44 (2H, m), 7.61-7.75 (3H, ra), 7.99-8.03 (2H, m), 8.73 (1H , s), 9.84 (1H, br Example C-125 Production of 4- [(3-chloro-4-. {3- [3- (cyclopropylmethyl) sulfonyl] phenoxy] phenyl) amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl} ethanol (i) Production of 2-chloro-l-. { 3- [(cyclopropylmethyl) thio] phenoxy} -4-nitrobenzene To a solution of 3-mercaptophenol (1.5 g) and sodium tert -butoxide (1.26 g) in N, N-dimethylformamide (15 ml) was added 1- (bromomethyl) cyclopropane (1.27 ml) at room temperature. The reaction mixture was stirred at room temperature for 16 h, sodium tert -butoxide (1.27 g) and 3-chloro-4-fluoronitrobenzene (1.88 g) were added to the reaction mixture, and the mixture was stirred for 3 days . Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by column chromatography (eluent, hexane: ethyl acetate = 19: 1-4: 1) to give the title compound (2.93 g) as a yellow oil.

VL-NMR (CDCI3) d: 0.25-0.30 (2H, m), 0.58-0.64 (2H, m), 0.99-1.13 (1H, m), 2.89 (2H, d, J = 7.2 Hz), 6.84-6.89 (1H, m), 6.90 (1H, d, J = 9.0 Hz), 7.05 (1H, t, J = 2.1 Hz), 7. 20-7.24 (2H, m), 7.31-7.36 (1H, m), 8.06 (1H, dd, J = 2.7 Hz, 9.0 Hz), 8.39 (1H, d, J = 2.7 Hz). (ii) Production of 2-chloro-l-. { 3- [(cyclopropylmethyl) sulfonyl] phenoxy] } -4-nitrobenzene When using 2-chloro-l-. { 3- [(cyclopropylmethyl) thio] phenoxy} -4-nitrobenzene (2.93 g), 70% 3-chloroperbenzoic acid (4.73 g) and ethyl acetate (60 ml) and in the same manner as in Example C-121 (ii), the title compound was obtained (2.90 g) in the form of colorless crystals. XH-NMR (CDCl3) d: 0.14-0.20 (2H, m), 0.57-0.63 (2H, m), 0.95-1.09 (1H, m), 3.05 (2H, d, J = 7.2 Hz), 7.00 (1H , d, J = 9.0 Hz), 7.33-7.36 (1H, m), 7.59-7.66 (2H, m), 7.78-7.82 (1H, m), 8.13 (1H, dd, J = 2.7 Hz, 9.0 Hz), 8.41 (1H, d, J = 2. 7 Hz). (iii) Production of 3-chloro-4-. { 3- [(cyclopropylmethyl) sulfonyl] phenoxy] } Aniline When using 2-chloro-l-. { 3- [(cyclopropylmethyl) sulfonyl] phenoxy] } -4-nitrobenzene (2.84 g), reduced iron (2.57 g), calcium chloride (0.51 g) and 15% ethanol with water content (85 ml) and in the same manner as in Example C-120 (iii ), the title compound was obtained (2.60 g) in the form of a yellow oil. XH-NMR (CDCl3) d: 0.10-0.16 (2H, m), 0.52-0.58 (2H, m), 0.90-1.06 (1H, m), 2.99 (2H, d, J = 7.5 Hz), 3.74 (2H , br s), 6.59 (1H, dd, J = 2.7 Hz, 8.7 Hz), 6.78 (1H, d, J = 2.7 Hz), 6.93 (1H, d, J = 8.7 Hz), 7.15-7.19 (1H, m), 7.34-7.35 (1H, m), 7.44-7.49 (1H, m), 7.55-7.59 (1H, m). (iv) Production of 2-. { 4- [(3-chloro-4- { 3- [(cyclopropylmethyl) sulfonyl] phenoxy] phenyl) amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl} ethanol When using 2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethyl benzoate (100 mg), 3-chloro-4-. { 3- [(cyclopropylmethyl) sulfonyl] phenoxy] } aniline (123 mg), isopropyl alcohol (2.0 ml), l-methyl-2-pyrrolidone (2.0 ml) and 1 N aqueous sodium hydroxide solution (1.0 ml) and in the same manner as in Example C-121 ( iv), the title compound (126 mg) was obtained as colorless crystals. Vl-NMR (CDCI3) d: 0.11-0.19 (2H, m), 0.53-0.63 (2H, m), 0.94-1.05 (1H, m), 3.01 (2H, d, J = 7.2 Hz), 4.13-4.21 (2H, m), 4.39-4.47 (2H, ra), 5.11-5.31 (1H, m), 6.29 (1H, d, J = 3.3 Hz), 7.06 (1H, d, J = 3.3 Hz), 7.10 ( 1H, d, J = 8.7 Hz), 7.24-7.30 (1H, m), 7.40-7.42 (1H, m), 7.48-7.54 (2H, m), 7.60-7.63 (1H, m), 7.83 (1H, d, J = 2.4 Hz), 8.32 (1H, s), 9.48 (1H, s).

Example C-126 Production of 2- [4- ( { 3-chloro-4- [3- (isobutylsulfonyl) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethanol ( i) Production of 2-chloro-l- [3- (isobutylthio) phenoxy] -4-nitrobenzene To a solution of 3-mercaptophenol (1.5 g) and sodium terbutoxide (1.26 g) in N, N-dimethylformamide (15 ml) ) l-bromo-2-methylpropane (1.42 ml) was added at room temperature. The reaction mixture was stirred at room temperature for 2 days, sodium tert-butoxide (1.26 g) and 3-chloro-4-fluoronitrobenzene (2.08 g) were added to the reaction mixture and the mixture was stirred for 6 h. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by column chromatography (eluent, hexane: ethyl acetate = 19: 1- ^ 3: 1) to give the title compound (3.63 g) in fora of a yellow oil VL-NMR (CDC13) d: 1.04 (6H, d, J = 6.6 Hz), 1.83- 1. 96 (1H, m), 2.82 (2H, d, J = 6.3 Hz), 6.81-6.84 (1H, ra), 6.89 (1H, d, J = 9.0 Hz), 6.99-7.01 (1H, m), 7.15 -7.19 (1H, m), 7.29-7.34 (1H, m), 8.05 (1H, dd, J = 2.4 Hz, 9.0 Hz), 8.37 (1H, d, J = 2.4 Hz). (ü) Production of 2-chloro-l- [3- (isobutylsulfonyl) phenoxy] -4-nitrobenzene When using 2-chloro-l- [3- (isobutylthio) phenoxy] -4-nitrobenzene (3.63 g), acid 3 70% chloroperbenzoic acid (5.80 g) and ethyl acetate (50 ml) and in the same manner as in Example C-121 (ii), the title compound (3.88 g) was obtained as colorless crystals. XH-NMR (CDC13) d: 1.08 (6H, d, J = 6.6 Hz), 2.20-2.23 (1H, m), 3.00 (2H, d, J = 6.6 Hz), 7.00 (1H, d, J = 9.0 Hz), 7.31-7.35 (1H, m), 7.58 (1H, t, J = 2.1 Hz), 7.60-7.66 (1H, m), 7.76-7.80 (1H, m), 8.13 (1H, dd, J = 2.7 Hz, 9.0 Hz), 8.41 (1H, d, J = 2.7 Hz). (iii) Production of 3-chloro-4- [3- (isobutylsulfonyl) phenoxy] aniline When using 2-chloro-l- [3- (isobutylsulfonyl) phenoxy] -4-nitrobenzene (3.88 g), reduced iron (2.93 g) ), calcium chloride (0.58 g) and 15% ethanol with water content (120 ml) and in the same manner as in Example C-120 (iii), the title compound (3.40 g) was obtained in the form of a yellow oil. XH-NMR (CDCl 3) d: 1.04 (6H, d, J = 6.6 Hz), 2.13- 2. 28 (1H, m), 2.96 (2H, d, J = 6.6 Hz), 3.74 (2H, br s), 6.60 (1H, dd, J = 2.7 Hz, 8.7 Hz), 6.79 (1H, d, J = 2.7 Hz), 6.93 (1H, d, J = 8.7 Hz), 7.13-7.18 (1H, m), 7.34 (1H, t, J = 2.1 Hz), 7.47 (1H, t, J = 8.0 Hz), 7.54 -7.57 (1H, m). (iv) Production of 2- [4- ( { 3-chloro-4- [3- (isobutylsulfonyl) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl ] ethanol When using 2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethyl benzoate (100 mg), 3-chloro-4- [3- (isobutylsulfonyl) phenoxy] aniline (123 mg), isopropyl alcohol (5.0 ml) and 1 N aqueous solution of sodium hydroxide (2.0 ml) and in the same manner as in Example C-121 (iv), the title compound (112 mg) was obtained in the form of colorless crystals. XH-NMR (CDC13) d: 1.06 (6H, d, J = 6.9 Hz), 2.18-2.29 (1H, m), 2.98 (2H, d, J = 6.6 Hz), 4.12-4.21 (2H, ra), 4.39-4.48 (2H, m), 5.45-5.60 (1H, m), 6.25 (1H, d) , J = 3.0 Hz), 7.04 (1H, d, J = 3.0 Hz), 7.09 (1H, d, J = 8.7 Hz), 7.23-7.27 (1H, ra), 7.39-7.41 (1H, m), 7.48 -7.53 (2H, m), 7.57-7.61 (1H, m), 7.83 (1H, d, J = 2.4 Hz), 8.30 (1H, s), 9.50 (1H, s). Example C-127 Production of 2-. { 4- [(3-chloro-4- { 3- [(2,2-dimethylpropyl) sulfonyl] phenoxy] phenyl) amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl} ethanol (i) Production of 2-chloro-l-. { 3- [(2, 2-dimethylpropyl) thio] phenoxy} -4-nitrobenzene To a solution of 3-mercaptophenol (1.5 g) and sodium tert -butoxide (1.26 g) in N, N-dimethylformamide (15 ml) was added l-bromo-2,2-dimethylpropane (1.64 ml) at room temperature. ambient. After stirring at 70 ° C for 24 h, the mixture was cooled to room temperature, sodium tert -butoxide (1.26 g) and 3-chloro-4-fluoronitrobenzene (2.08 g) were added, and the mixture was stirred at room temperature for 3 days. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, hexane: ethyl acetate = 19: 1-> 7: 3) to give the title co-tax (2.80 g. ) in the form of a yellow oil. VL-NMR (CDC13) d: 1.05 (9H, s), 2.89 (2H, s), 6.80-6.84 (1H, ra), 6.88 (1H, d, J = 9.0 Hz), 7.02-7.04 (1H, m ), 7.18-7.22 (1H, m), 7.28-7.33 (1H, m), 8.05 (1H, dd, J = 3.0 Hz, 9.0 Hz), 8.37 (1H, d, J = 3.0 Hz). (ii) Production of 2-chloro-l-. { 3- [(2, 2- dimethylpropyl) sulfonyl] phenoxy} -4-nitrobenzene When using 2-chloro-l-. { 3- [(2, 2-dimethylpropyl) thio] phenoxy} -4-nitrobenzene (2.80 g), 70% 3-chloroperbenzoic acid (4.32 g) and ethyl acetate (56 ml) and in the same manner as in Example C-121 (ii), the title compound was obtained (3.04 g) in the form of pale yellow crystals. XH-NMR (CDC13) d: 1.20 (9H, s), 3.05 (2H, s), 7.00 (1H, d, J = 9.0 Hz), 7.30-7.34 (1H, m), 7.59-7.66 (2H, m ), 7.77-7.81 (1H, m), 8.13 (1H, dd, J = 2.7 Hz, 9.0 Hz), 8.42 (1H, d, J = 2.7 Hz). (iii) Production of 3-chloro-4-. { 3- [(2, 2-dimethylpropyl) sulfonyl] phenoxy} Aniline When using 2-chloro-l-. { 3- [(2, 2-dimethylpropyl) sulfonyl] phenoxy} -4-nitrobenzene (3.0 g), reduced iron (2.18 g), calcium chloride (0.43 g) and 15% ethanol with water content (90 ml) and in the same manner as in Example C-120 (iii ), the title compound (2.34 g) was obtained in the form of a pale yellow amorphous. XH-NMR (CDCI3) d: 1.17 (9H, s), 3.01 (2H, s), 3.73 (2H, br s), 6.59 (1H, dd, J = 2.7 Hz, 9.0 Hz), 6.78 (1H, d, J = 2.7 Hz), 6.92 (1H, d, J = 9.0 Hz), 7.08-7.14 ( 1H, m), 7.35-7.36 (1H, m), 7.42-7.47 (1H, m), 7.53-7.57 (1H, m). (iv) Production of 2-. { 4- [(3-chloro-4- { 3- [(2,2-dimethylpropyl) sulfonyl] phenoxy] phenyl) amino] -5H-pyrrolo [3,2- d] pyrimidin-5-yl} ethanol When using 2- (-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethyl benzoate (100 mg), 3-chloro-4-. { 3- [(2, 2-dimethylpropyl) sulfonyl] phenoxy} aniline (140 mg), isopropyl alcohol (3.0 ml) and 1 N aqueous sodium hydroxide solution (1.5 ml) and in the same manner as in Example C-121 (iv), the title compound (131 mg) was obtained as colorless crystals. VL-NMR (CDC13) d: 1.19 (9H, s), 3.04 (2H, s), 4.11-4.20 (2H, m), 4.35-5.46 (2H, ra), 5.81-5.96 (1H, m), 6.20 (1H, d, J = 3.3 Hz), 7.02 (1H, d, J = 3.3 Hz), 7.08 (1H, d, J = 8.7 Hz), 7.20-7.27 (1H, m), 7.41-7.43 (1H, m), 7.46-7.52 (2H, m), 7.56-7.63 (1H, m), 7.83 (1H, d, J = 2.7 Hz), 8.27 (1H, s), 9.55 (1H, s). Example C-128 Production of N- (2- {4- [(3-chloro-4. {[3- [(cyclopropylmethyl) sulfonyl] phenoxy} phenyl) amino] -5H-pyrrolo hydrochloride [3,2-] d] pyrimidin-5-yl.} ethyl) -2- (methylsulfonyl) acetamide (i) Production of (2- {4- [(3-chloro-4-. {3- [[(cyclopropylmethyl) sulfonyl]] ] phenoxy] phenyl) amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl.} ethyl) tert-butyl carbamate A solution of [2- (4-chloro-5H-pyrrolo [ 3, 2- d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (1.00 g) and 3-chloro-4-. { 3- [(cyclopropylmethyl) sulfonyl] phenoxy] } Aniline (1.14 g) in isopropyl alcohol (10 ml) was stirred at 80 ° C for 14 h. Aqueous sodium bicarbonate was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by column chromatography (eluent, hexane: ethyl acetate = 1: 1-> ethyl acetate → ethyl acetate: methanol = 9: 1) to give the title compound (1.86 g) in the form of pale yellow crystals. Vl-NMR (CDC13) d: 0.10-0.20 (2H, m), 0.54-0.61 (2H, m), 0.92-1.06 (1H, m), 1.50 (9H, s), 3.01 (2H, d, J = 6.9 Hz), 3.43-3.53 (2H, m), 4.43-4.52 (2H, m), 5.02-5.10 (1H, m), 6.61 (1H, d, J = 3.0 Hz), 7.09 (1H, d, J = 9.0 Hz), 7.19 (1H, d, J = 3.0 Hz), 7.21-7.28 (1H, m), 7.46-7.52 (2H, m), 7.60-7.63 (1H, m), 7.91 (1H, dd, J = 2.7 Hz, 9.0 Hz), 8.06 (1H, d, J = 2.7 Hz), 8.51 (1H, s), 8.62 (1H, br s). (ii) Production of 5- (2-aminoethyl) -N- (3-chloro-4-. {3- [3- (cyclopropylmethyl) sulfonyl] phenoxy] phenyl) -5H-pyrrolo dihydrochloride [3,2-] d] pyrimidin-4-amino A mixture of (2- {4- [(3-chloro-4- {[3- [(cyclopropylmethyl) sulfonyl] phenoxy} phenyl) amino] -5H- pyrrolo [3, 2-d] pyrimidin-5-yl} ethyl) tert-butyl carbamate (1.86 g), 6 N hydrochloric acid (5.0 ml) and ethanol (20 ml) was stirred at 60 ° C for 3 days. After concentrating under reduced pressure, ethanol was added to the residue. The mixture was concentrated under reduced pressure, and the resulting crystals were collected by filtration and washed with diisopropyl ether to give the title compound (1.66 g) as pale yellow crystals. XH-NMR (DMSO-d6) d: 0.09-0.14 (2H, m), 0.41-0.48 (2H, m), 0.76-0.88 (1H, m), 3.22-3.38 (4H, m), 4.94-5.05 ( 2H, m), 6.74 (1H, d, J = 2.7 Hz), 7.30-7.45 (3H, m), 7.61-7.74 (3H, m), 7.92-7.97 (1H, m), 8.00-8.08 (1H, m), 8.23-8.32 (3H, m), 8.72 (1H, s), 9.99 (1H, br s). (iii) Production of N- (2. {4 - [(3-chloro-4-. {3, 3- [(cyclopropylmethyl) sulfonyl] phenoxy] phenyl) amino] -5H-pyrrolo hydrochloride [3 , 2-d] pyrimidin-5-yl.} Ethyl) -2- (methylsulfonyl) acetamide A mixture of 5- (2-aminoethyl) -N- (3-chloro-4-. {3- 3- dihydrochloride] (cyclopropylmethyl) sulfonyl] phenoxy] phenyl) -5H-pyrrolo [3,2-d] pyrimidin-4-amine (100 mg), methylsulfonylacetic acid (48.4 mg), l-ethyl-3- (3-) hydrochloride dimethylaminopropyl) carbodiimide (101 mg), 1-hydroxybenzotriazole monohydrate (80 mg) and triethylamine (0.073 ml) in N, N-dimethylformamide (5.0 ml) was stirred at room temperature for 20 h. Water was added to the reaction mixture and the The mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate-> ethyl acetate: methanol = 85:15) to give a pale yellow amorphous. To a pale yellow amorphous solution obtained in ethanol (5.0 ml) was added 4N hydrogen chloride solution / ethyl acetate (0.5 ml) at room temperature. After stirring at room temperature for 1 h, the resulting crystals were collected by filtration and washed with ethyl acetate to give the title compound (81 mg) as colorless crystals. XH-NMR (DMSO-d6) d: 0.06-0.13 (2H, m), 0.40-0.47 (2H, m), 0.75-0.90 (1H, m), 3.06 (3H, s), 3.30 (2H, d, J = 6.9 Hz), 3.49-3.60 (2H, m), 4.06 (2H, s), 4.64-4.73 (2H, m), 6.66 (1H, d, J = 2.7 Hz), 7.30-7.44 (3H, m ), 7.65-7.74 (3H, m), 7.91-7.99 (2H, m), 8.68-8.79 (2H, m), 8.86 (1H, br s). Example C-129 Production of N- (2- {4- [(3-chloro-4-. {[3- [(cyclopropylmethyl) sulfonyl] phenoxy} phenyl) amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl.} ethyl) -2-methyl-2- (methylsulfonyl) propanamide A mixture of 5- (2-aminophenyl) -N- (3-chloro-4-. {3- [(cyclopropylmethyl) sulfonyl] phenoxy]} phenol) -5H-pyrrolo dihydrochloride. [3, 2-d] p? R? M? D? N-4-amma (120 mg), 2-met? L-2- (methylsulfonyl) propanoic acid (52 mg), l-et? L hydrochloride -3- (3-d? Met? Lammoprop? L) carbodpmide (90 mg), 1-hydroxybenzotriazole monohydrate (72 mg) and tpetilamma (0.088 ml) in N, N-dimethylformamide (5.0 ml) was stirred at room temperature for 2 days. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate -> ethyl acetate: methanol = 85:15) to give the title compound (120 mg) in the form of pale yellow crystals. XH-NMR (CDC13) d: 0.11-0.18 (2H, m), 0.54-0.61 (2H, m), 0.92-1.07 (1H, m), 1.70 (6H, s), 2.93 (3H, s), 3.01 (2H, d, J = 7.2 Hz), 3.64-3.74 (2H, m), 4.43-4.52 (2H, m), 6.64 (1H, d, J = 3.3 Hz), 6.99 (1H, d, J = 9.0 Hz), 7.21 (1H, d, J = 3.3 Hz), 7.22-7.32 (2H, m), 7.42-7.44 (1H, ra), 7.51 (1H, t, J = 8.1 Hz), 7.60-7.64 (1H , m), 7.89 (1H, dd, J = 2.7 Hz, 9.0 Hz), 8.07 (1H, d, J = 2.7 Hz), 8.37 (1H, s), 8.53 (1H, s).

Example C-130 Production of N- (2- {4- [(3-chloro-4. {[3- [(cyclopropylmethyl) sulfonyl] phenoxy} phenyl) amino] -5H-pyrrolo [3,2- methanesulfonate] d] pyrimidin-5-yl.} ethyl) -3-hydroxy-3-methylbutanamide A mixture of 5- (2-aminoethyl) -N- (3-chloro-4-. {3- [(cyclopropylmethyl) dihydrochloride] ) sulfonyl] phenoxy] phenyl) -5H-pyrrolo [3,2-d] pyrimidin-4-amine (120 mg), 3-hydroxy-3-methylbutanoic acid (49.7 mg), l-ethyl-3 hydrochloride - (3-dimethylaminopropyl) carbodiimide (121 mg), 1-hydroxybenzotriazole monohydrate (97 mg) and triethylamine (0.090 ml) in N, N-dimethylformamide (5.0 ml) was stirred at room temperature for 20 h. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate-ethyl acetate: methanol = 4: 1) to give a colorless amorphous form. To a solution of the pale yellow amorphous form obtained in ethyl acetate (5.0 ml) was added methanesulfonic acid (12.4 μl) at room temperature. After stirring at room temperature for 1 h, the resulting crystals were collected by filtration and washed with ethyl acetate to give the title compound (116 mg) as colorless crystals. Vi-NMR (DMSO-d6) d: 0.08-0.14 (2H, m), 0.41-0.47 (2H, m), 0.75-0.88 (1H, m), 1.12 (6H, s), 2.20 (2H, s) , 2.30 (3H, s), 3.29 (2H, d, J = 7.2 Hz), 3.43-3.56 (2H, m), 4.62 (2H, t, J = 7.5 Hz), 6.66 (1H, d, J = 3.0 Hz), 7.31-7.45 (3H, m), 7.64-7.76 (3H, m), 7.93-8.01 (2H, m), 8.34 (1H, t, J = 5.4 Hz), 8.72 (1H, s), 10.14 (1H, br s). Example C-131 Production of N- [2- (4- { [3-chloro-4- (3-cyanophenoxy) phenyl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2- (methylsulfonyl) acetamide When using 3- (4-amino-2-chlorophenoxy) benzonitrile (115 mg), [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (125 mg), isopropyl alcohol (2.0 ml), methanol (2 ml), sodium chloride solution 4 N hydrogen / ethyl acetate (3.0 ml), methylsulfonylacetic acid (170 rag), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (360 mg), 1-hydroxybenzotriazole (15 mg), triethylamine (0.86 ml) ) and N, N-dimethylformamide (15 ml) and in the same manner as in Example C-53 (ii), the title compound (169 mg) was obtained as colorless crystals. Vl-NMR (DMSO-d5) d: 3.10 (3H, s), 3.44-3.49 (2H, m), 4.05 (2H, s), 4.55-4.60 (2H, m), 6.51-6.52 (1H, m) , 7.24-8.01 (8H, m), 8.38 (1H, s), 8.66-8.69 (1H, m), 8.81 (1H, s). Example C-132 Pr -chloro-4- (3-cyanophenoxy) phenyl] amino} -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2-methy1-2- (methylsulfonyl) propanamide When using 3- (4-amino-2-chlorophenoxy) benzonitrile (115 mg), [ 2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (125 mg), isopropyl alcohol (2.0 ml), methanol (2 ml), 4 N hydrogen chloride / ethyl acetate (3.0 ml), 2-methyl-2- (methylsulfonyl) propanoic acid (210 mg), l-ethyl-3- hydrochloride [3-dimethylaminopropyl) carbodiimide 370 mg) 1-hydroxybenzotriazole (40 mg), triethylamine (1.0 ml) and N, N-dimethylformamide (20 ml) and in the same manner as in Example C-53 (ii), was obtained the title compound (173 mg) in pale yellow glass lined. XH-NMR (DMSO-d6) d: 1.41 (6H, s), 2.95 (3H, s), 3.42-3.49 (2H, m), 4.58-4.62 (2H, m), 6.50-6.51 (1H, m) , 7.24-8.00 (8H, m), 8.20 (1H, br s), 8.40 (1H, s), 8.88 (1H, Example C-133 Production of N- [2- (4- { [3-chloro-4- (3-cyanophenoxy) phenyl] amino} -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -3-hydroxy-3-methylbutanamide When using 3- (4-amino-2-chlorophenoxy) benzonitrile (115 mg), [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ) ethyl] tert-butyl carbamate (125 mg), isopropyl alcohol (2.0 ml), methanol (2 ml), 4 N hydrogen chloride solution / ethyl acetate (3.0 ml), 3-hydroxy-3-methylbutanoic acid (190 mg), l-ethyl-3- (3-) hydrochloride dimethylaminopropyl) carbodiimide (320 mg), 1-hydroxybenzotriazole (15 mg), triethylamine (0.5 ml) and N, N-dimethylformamide (20 ml) and in the same manner as in Example C-53 (ii), the compound of the title (115 mg) in the form of pale yellow crystals. Vl-NMR (DMSO-d6) d: 1.13 (6H, s), 2.20 (2H, s), 3.42-3.49 (2H, m), 4.50-4.55 (2H, m), 4.66 (1H, s), 6.50 -6.51 (1H, m), 7.24-8.06 (8H, m), 8.24 (1H, br s), 8.35 (1H, s), 8.92 (1H, s).

Production of 4-. { [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] methyl} piperidin-1-tert-butyl carboxylate A mixture of 2- [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethoxy] ethyl benzoate (156 mg), 4- [(4-amino-2-chlorophenoxy) methyl] piperidine-1-carboxylic acid terbutyl ester (200 mg) and isopropyl alcohol (15 ml) was stirred at 80 ° C overnight. After concentrating under reduced pressure, water and saturated aqueous sodium acid carbonate were added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, ethyl acetate: methanol = 100: 0-> 80: 20). The object fractions were concentrated under reduced pressure. The crude product was dissolved in methanol (5.0 ml), tetrahydrofuran (4.0 ml) and 1 N aqueous solution of sodium hydroxide (3.0 ml) were added and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100 → 10: 90). The object fractions were concentrated under reduced pressure. The residue was crystallized from ethyl acetate / hexane to give the title compound (74 mg) as crystals. XH-NMR (DMSO-d6) d: 1.13-1.27 (2H, m), 1.40 (9H, s), 1. 76-1.80 (2H, m), 1.86-2.03 (1H, m), 2.65-2.86 (2H, m), 3.47 (4H, s), 3.78-4.01 (6H, m), 4.60-4.68 (3H, m ), 6.47 (1H, d, J = 3.1 Hz), 7.12 (1H, d, J = 9.1 Hz), 7.50 (1H, dd, J = 9.1, 2.7 Hz), 7.63 (1H, d, J = 3.1 Hz ), 7.78 (1H, d, J = 2.7 Hz), 8.26 (1H, s), 8.68 (1H, br s).

Production of 4- [(2-chloro-4. {[[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino] phenoxy) ethyl] piperidin- tert-butyl l-carboxylate A mixture of 2- (4-chloro-5H-pyrrolo [3] benzoate, 2-d] pyrimidin-5-yl) ethyl (200 mg), 4- [(4-amino-2-chlorophenoxy) methyl] piperidine-1-carboxylic acid tert-butyl ester (293 mg) and isopropyl alcohol (5.0 ml ) was stirred at 80 ° C overnight. After concentrating under reduced pressure, water and saturated aqueous sodium acid carbonate were added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, ethyl acetate: methanol = 100: 0-80: 20). The object fractions were concentrated under reduced pressure. The crude product was dissolved in methanol (5.0 ml), tetrahydrofuran (4.0 ml) and 1 N aqueous sodium hydroxide solution (4.0 ml) were added. added to the mixture and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100-10: 90). The object fractions were concentrated under reduced pressure. The residue was crystallized from ethyl acetate / hexane to give the title compound (147 mg) as a white powder. Vi-NMR (DMSO-d6) d: 1.13-1.27 (2H, m), 1.40 (9H, s), 1.76-1.80 (2H, m), 1.86-2.03 (1H, m), 2.65-2.86 (2H, m), 3.83-4.01 (6H, m), 4.50 (2H, t, J = 4.1 Hz), 6.18-6.21 (1H, m), 6.46 (1H, d, J = 3.1 Hz), 7.13 (1H, d) , J = 9.1 Hz), 7.46 (1H, dd, J = 9.1, 2.7 Hz), 7.60 (1H, d, J = 3.1 Hz), 7.75 (1H, d, J = 2.7 Hz), 8.26 (1H, s ), 9.53 (1H, br s). Example E-l Production of 2- (2- { 4- [(3-chloro-4- { 3- [(2-methyl-lH-imidazol-1-yl) methyl] phenoxy] phenyl) amino] - 5H-pyrrolo [3,2-d] pyrimidin-5-yl.} Ethoxy) ethanol (i) Production of [3- (2-chloro-4-nitrophenoxy) phenyl] methanol To a solution of 3- (hydroxymethyl) phenol (6.21 g) and 3-chloro-4-fluoronitrobenzene (9.24 g) in N, N-dimethylformamide (50 ml) was added potassium carbonate (10.37 g) at room temperature and the mixture was stirred for 4 h. Under cooling with ice, brine was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure, and the residue was separated and purified by column chromatography on silica gel (eluent, ethyl acetate: hexane = 20: 80 → 40: 60) to give the title compound (5.55 g) as a pale yellow powder. XH-NMR (CDC13) d: 1.78 (1H, t, J = 5.7 Hz), 4.74 (2H, d, J = 5.7 Hz), 6.90 (1H, d, J = 9.0 Hz), 6.95-7.05 (1H, m), 7.12 (1H, s), 7.25-7.30 (1H, m), 7.43 (1H, t, J = 8.0 Hz), 8.05-8.10 (1H, m), 8.35-8.40 (1H, m). (ii) Production of 1- [3- (2-chloro-4-nitrophenoxy) benzyl] -2-methyl-1H-imidazole To a solution of [3- (2-chloro-4-nitrophenoxy) phenyl] methanol (1.12) g) in tetrahydrofuran (30 ml) triethylamine (0.67 ml) and methanesulfonyl chloride (0.33 ml) were added under cooling with ice, and the mixture was stirred at 0 ° C for 1 h. Aqueous sodium bicarbonate was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. 2-Methylimidazole (328 mg), potassium carbonate (829 mg) and N, N-dimethylformamide (10 ml) were added to the obtained residue, and the mixture was stirred at room temperature for 15 h. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate) to give the title compound (0.96 g) as a pale yellow oil. XH-NMR (CDC13) d: 2.35 (3H, s), 5.08 (2H, s), 6.75-6.9 (3H, m), 6.90-7.05 (3H, m), 7.41 (1H, t, J = 7.8 Hz ), 8.06 (1H, dd, J = 2.7 Hz, 9.0 Hz), 8.38 (1H, d, J = 2.7 Hz). (iii) Production of 3-chloro-4-. { 3- [(2-methyl-lH-iraidazol-1-yl) methyl] phenoxy} Aniline To a solution of 1- [3- (2-chloro-4-nitrophenoxy) benzyl] -2-methyl-1H-imidazole (0.96 g) in methanol (10 ml) was added 5% activated carbon-platinum (192%). mg) low an atmosphere of nitrogen. The reaction mixture was stirred under a hydrogen atmosphere at room temperature for 19 h, and the 5% activated carbon-platinum was filtered. The filtrate was concentrated under reduced pressure and the residue was separated and purified by column chromatography on silica gel (eluent, ethyl acetate: hexane = 60: 40-> 100: 0) to give the title compound (494 mg) in the form of a white powder. XH-NMR (CDC13) d: 2.32 (3H, s), 3.69 (2H, br s), 4.99 (2H, s), 6.56 (1H, dd, J = 2.7 Hz, 9.0 Hz), 6.60-6.70 (2H, m), 6.70-6.85 (3H, m ), 6.87 (1H, d, J = 9.0 Hz), 6.93 (1H, d, J = 1.2 Hz), 7.22 (1H, t, J = 7.6 Hz). (iv) Production of 2- (2-. {4- [(3-chloro-4-. {3- [2-methyl-1H-imidazol-1-yl] methyl] phenoxy] phenyl) amino] -5H-pyrrolo [3, 2-d] pyrimidin-5-yl.} ethoxy) ethanol A mixture of 2- [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin benzoate] -5-yl) ethoxy] ethyl (207 mg), 3-chloro-4-. { 3- [(2-methyl-lH-imidazol-1-yl) methyl] phenoxy} aniline (154 mg), l-methyl-2-pyrrolidone (5.0 ml) and pyridine hydrochloride (139 mg) was stirred at 120 ° C for 22 h. Aqueous sodium bicarbonate was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by column chromatography on silica gel (eluent, acetate ethyl: methanol = 100: 0- »95: 5). To the obtained compound were added 1 N aqueous sodium hydroxide solution (2.3 ml) and tetrahydrofuran (4 ml) and the mixture was stirred at room temperature for 21 h. The reaction mixture was neutralized with 1N hydrochloric acid and aqueous sodium bicarbonate and brine were added. The mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: methanol = 100: 0-> 95: 5) to give the title compound (119 mg) as a colored powder pale yellow. Vl-NMR (CDC13) d: 2.21 (3H, s), 3.70-3.85 (4H, m), 4.02 (2H, t, J = 4.2 Hz), 4.57 (2H, t, J = 4.2 Hz), 5.01 ( 2H, s), 5.99 (1H, s), 6.63 (1H, d, J = 3.3 Hz), 6.75-6.85 (1H, m), 6.83 (1H, d, J = 8.1 Hz), 6.92 (1H, d , J = 9.0 Hz), 6.95-7.05 (1H, m), 7.21 (1H, d, J = 3.0 Hz), 7.25-7.30 (1H, m), 7.32 (1H, t, J = 8.0 Hz), 7.65 (1H, dd, J = 2.4 Hz, 9.0 Hz), 8.02 (1H, d, J = 2.4 Hz), 8.54 (1H, s), 8.98 (1H, s). Example E-2 O-ethylimex production of (1E) -1-. { 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] phenyl} ethanone (i) Production of O-ethyl oxime of (1E) -1- [3- (4-amino-2-chlorophenoxy) phenyl] ethanone To a solution of 1- [3- (4-amino-2-chlorophenoxy) phenyl ] ethanone (1.31 g) in ethanol (50 ml) were added O-ethylhydroxylamine hydrochloride (2.44 g) and sodium acetate (2.05 g) and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure, water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, ethyl acetate: hexane = 20: 80- »40: 60). The object fractions were concentrated under reduced pressure to give the title compound (1.54 g) as an orange oil. XH-NMR (CDC13) d: 1.31 (3H, t, J = 7.0 Hz), 2.19 (3H, s), 3.66 (2H, br s), 4.22 (2H, q, J = 7.0 Hz), 6.56 (1H , dd, J = 2.8 Hz, 8.7 Hz), 6.77-6.83 (2H, m), 6.89 (1H, d, J = 8.7 Hz), 7.21-7.28 (2H, m), 7.29-7.35 (1H, m) . (ii) Production of O-ethyl oxime of (1E) -1-. { 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3, 2- d] pyrimidin-4-yl} amino) phenoxy] phenyl} ethanone A mixture of 2- [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethoxy] ethyl benzoate (173 mg), 0-ethyl oxime (1E) -1- [3- (4-amino-2-chlorophenoxy) phenyl] ethanone (153 mg) and isopropyl alcohol (3 ral) was stirred at 80 ° C overnight. An aqueous solution of sodium acid carbonate was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, ethyl acetate: hexane = 50: 50-> 100: 0). The object fractions were concentrated under reduced pressure. To the residue were added methanol (5 ml), tetrahydrofuran (1 ml) and 1 N aqueous sodium hydroxide solution (1 ml), and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100-> 10: 90). The object fractions were concentrated under reduced pressure. The residue was crystallized from ethyl acetate-diisopropyl ether to give the title compound (134 mg) as a white powder. 2 H-NMR (CDCl 3) d: 1.32 (3H, t, J = 7.1 Hz), 1.88-2.04 (1H, m), 2.21 (3H, s), 3.70-3.82 (4H, m), 3.99-4.05 (2H , m), 4.24 (2H, q, J = 7.1 Hz), 4.53-4.59 (2H, m), 6.61 (1H, d, J = 3.0 Hz), 6.86-6.92 (1H, m), 7.01 (1H, d, J = 8.9 Hz), 7.20 (1H, d, J = 3.0 Hz), 7.27-7.40 (3H, m), 7.56 (1H, dd, J = 2.7 Hz, 8.9 Hz), 7.87 (1H, d, J = 2.7 Hz), 8.51 (1H, s), 8.75 (1H, br s). Example E-3 Production of 2- [2- (4- { [4- (3-tert-Butylphenoxy) -3-chlorophenyl] amino} -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethoxy ] ethanol When using 2- [2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethoxy] ethyl benzoate (173 mg), 4- (3-tert-butylphenoxy) - 3-chloroaniline (138 mg), isopropyl alcohol (3 ml), methanol (5 ml), tetrahydrofuran (1 ml) and 1 N aqueous sodium hydroxide solution (1 ml) and in the same manner as in Example E- 2 (ii), the title compound (189 mg) was obtained as a white powder. V-YRMN (CDCl 3) d: 1.32 (9H, s), 1.95-2.30 (1H, m), 3. 70-3.82 (4H, m), 3.99-4.05 (2H, m), 4.52-4.59 (2H, ra), 6.60 (1H, d, J = 3.0 Hz), 6.68-6.74 (1H, ra), 6.99 ( 1H, d, J = 8.9 Hz), 7.08-7.15 (2H, m), 7.14-7.28 (2H, m), 7.54 (1H, dd, J = 2.5 Hz, 8.9 Hz), 7.86 (1H, d, J = 2.5 Hz), 8.49 (1H, s), 8.73 (1H, br s).

Production of oxime hydrochloride of (1E) -1-. { 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] phenyl} ethanone (i) 2- [2- (4. {[[4- (3-Acetylphenoxy) -3-chlorophenyl] amino] -5H-pyrrolo [3,2-d] pyrimidin-benzoate production -yl) ethoxy] ethyl A mixture of benzoate of 2- [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethoxy] ethyl (1.04 g), 1- [3- (4-amino-2-chlorophenoxy) phenyl] ethanone (785 mg) and isopropyl alcohol (10 ml) was stirred at 80 ° C overnight. An aqueous solution of sodium acid carbonate was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent is evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, ethyl acetate: hexane = 50: 50-> 100: 0). The object fractions were concentrated under reduced pressure to give the title compound (1.59 g) as a yellow solid. VL-NMR (CDC13) d: 2.59 (3H, s), 3.93-3.99 (2H, m), 4. 05-4.12 (2H, m), 4.46-4.52 (2H, m), 4.55-4.62 (2H, m), 6.63 (1H, d, J = 3.2 Hz), 6.82 (1H, d, J = 8.8 Hz), 7.07-7.12 (1H, m), 7.22 (1H, d, J = 3.2 Hz), 7.29-7.54 (6H, m), 7.63-7.69 (1H, m), 7.75-7.82 (2H, m), 7.89 (1H, d, J = 2.7 Hz), 8.50 (1H, s), 8.77 (1H, br s). (ii) Production of oxime hydrochloride of (1E) -1-. { 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] phenyl} ethanone To a solution of 2- [2- (4. {[[4- (3-acetylphenoxy) -3-chlorophenyl] amino]} -5H-pyrrolo [3,2-d] pyrimidin-5-benzoate. il) ethoxy] ethyl (171 mg) in ethanol (5 ml) were added hydroxylamine hydrochloride (104 mg) and sodium acetate (123 mg) and the mixture was stirred at room temperature for 4 h. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure, and raetanol (5 ml), tetrahydrofuran (1 ml) and 1 N aqueous solution of sodium hydroxide (0.6 ml) were added to the obtained residue.

The mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100-> 10: 90). The object fractions were concentrated under reduced pressure. The residue was dissolved in ethyl acetate-ethanol, and 1N hydrogen chloride solution / ethyl acetate (0.3 ml) was added. The solvent was evaporated under reduced pressure and the residue obtained was crystallized from ethanol-ethyl acetate to give the title compound (75 mg) as a white powder. Vl-NMR (DMSO-d6) d: 2.14 (3H, s), 3.40-3.54 (4H, m), 3. 81-3.89 (2H, m), 4.76-4.85 (2H, ra), 6.69 (1H, d, J = 3.0 Hz), 7.00-7.06 (1H, m), 7.22 (1H, m), 7.27 (1H, d, J = 8.7 Hz), 7.37-7.48 (2H, m), 7.62 (1H, dd, J = 2.5 Hz, 8.7 Hz), 7.96 (1H, d, J = 2.5 Hz), 8.01 (1H, m) , 8.73 (1H, s), 9.80-9. 90 (1H, m), 11. 31 (1H, s). Example E-5 Production of 2- [2- (4. {[[3-chloro-4- (3-phenoxyphenoxy) phenol] ammo] -5H-pyrrolo [3,2-d] hydrochloride ] p? pm? dm-5-yl) ethoxy] ethanol (i) Production of 2-chloro-4-n? tro-l- (3-phenoxyphenoxy) benzene 2-chloro-l-fluoro-4-n was dissolved Trobencene (0.943 g) and 3-phenoxyphenol (1 g) in N, N-dimethylformamide (5.4 ml), and potassium carbonate (1.07 g) was added. The mixture was stirred at room temperature for 16 h. The reaction mixture was diluted with ethyl acetate (80 ml), and washed with water (70 ml). The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (hexane / ethyl acetate = 100/0? 70/30) to give the title compound (1.75 g) as an oil. ^ -RMN (CDC13) d: 6.73 (1H, t, J = 2 Hz), 6.78 (1H, m), 6.89 (1H, ra), 6.95 (2H, d, J = 9 Hz), 7.05 (2H, m), 7.16 (1H, m), 7.37 (3H, m), 8.07 (1H, dd, J = 3 Hz, 9 Hz), 8.37 (1H, d, J = 3 Hz). (11) Production of 3-chloro-4- (3-phenoxyphenoxy) aniline 2-Chloro-4-n-tro-l- (3-phenoxyphenoxy) benzene (1.7 g) in ethanol (49 ml) / water was suspended ( 5.45 ml), calcium chloride (306 mg) was added and the mixture was dissolved with heating with stirring at 90 ° C for 10 min. HE added reduced iron (1.85 g) and the mixture was stirred with heating at 90 ° C for 16 h. After cooling to room temperature, the reaction mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. The residual solid was diluted with ethyl acetate (200 ml), and washed with saturated brine (100 ml). The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by chromatography on silica gel (hexane / ethyl acetate = 80/20? 60/40) to give the title compound (1.58 g) as an oil. Vl-NMR (CDC13) d: 3.67 (2H, br s), 6.50-6.70 (4H, m), 6.76 (1H, d, J = 3 Hz), 6.92 (1H, d, J = 9 Hz), 7.01 (2H, m), 7.10 (1H, m), 7.20 (1H, m), 7.33 (2H, m). (ii) Production of 2- [2- (4. {[[3-chloro-4- (3-phenoxyphenoxy) phenyl] amino]} -5H-pyrrolo [3,2-d] pyrimidin-5 hydrochloride. -yl) ethoxy] ethanol A mixture of 2- [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethoxy] ethyl benzoate (150 mg), 3-chloro-4 - (3-phenoxyphenoxy) aniline (201 mg) and l-methyl-2-pyrrolidone (0.863 ml) was stirred with heating at 140 ° C for 3 h. The reaction mixture was diluted with ethyl acetate (80 ml), and washed with aqueous sodium bicarbonate (30 ml). The organic layer was dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 90: 10- »0: 100) and the subject fractions were concentrated under reduced pressure. The obtained residue was dissolved in methanol (1.89 ral), 1N aqueous solution of sodium hydroxide (0.433 ml) was added, and the mixture was stirred at room temperature for 2 h. 1N Hydrochloric acid (0.433 ml) was added, and the mixture was diluted with ethyl acetate (80 ml), and washed with saturated brine (30 ml). The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (ethyl acetate: methanol = 100: 0-85: 15). The fraction with the title compound was concentrated under reduced pressure, and the residue was dissolved in ethyl acetate (4 ml). 4 N Hydrochloric acid (0.125 ml) was added to the mixture, and the mixture was crystallized from isopropyl ether / ethyl acetate to give the title compound (129 mg). XH-NMR (DMSO-d6) d: 3.46 (4H, d, J = 2 Hz), 3.84 (2H, br s), 4.85 (2H, br s), 6.60 (1H, s), 7.07 (2H, d , J = 8 Hz), 7.18 (2H, t, J = 8 Hz), 7.29 (1H, d, J = 8 Hz), 7.30-7.50 (3H, m), 7.64 (1H, d, J = 9 Hz ), 7.96 (1H, d, J = 1 Hz), 8.04 (1H, d, J = 3 Hz), 8.74 (1H, s), 10.02 (1H, br s).

Example E-6 Production of N- [2- (4. {[[3-chloro-4- (3-phenoxyphenoxy) phenyl] amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl hydrochloride) ethyl] -3-hydroxy-3-methylbutanamide (i) Production of [2- (4- { [3-chloro-4- (3-phenoxyphenoxy) phenyl] amino.}. -5H-pyrrolo [3, 2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate A solution of [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] carbamate ter -butyl (0.5 g) and 3-chloro-4- (3-phenoxyphenoxy) aniline (786 mg) in isopropyl alcohol (5 ml) was stirred at 80 ° C for 12 h. Aqueous sodium bicarbonate (30 ml) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (80 ml). The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by column chromatography on silica gel (eluent, hexane: ethyl acetate = 7: 3- »ethyl acetate) to give the title compound (713 mg). in the form of colorless crystals. VL-NMR (CDC13) d: 1.48 (9H, s), 3.48 (2H, ra), 4.46 (2H, m), 5.12 (1H, t, J = 5 Hz), 6.59 (1H, d, J = 3 Hz), 6.69 (3H, m), 7.00-7.40 (8H, m), 7.85 (1H, dd, J = 3 Hz, 9 Hz), 7.98 (1H, d, J = 3 Hz), 8.50 (1H, s), 8.58 (1H, br s). (ii) Production of 5- (2-aminoethyl) -N- [3-chloro-4- (3-phenoxyphenoxy) phenyl] -5H-pyrrolo [3,2-d] pyrimidin-4-amine dihydrochloride A mixture of [2- (4- { [3-Chloro-4- (3-phenoxyphenoxy) phenyl] amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] carbamate of ter- Butyl (683 mg), 2 N hydrochloric acid (8.46 ml) and tetrahydrofuran (16.9 ml) were stirred at 60 ° C for 20 h. The solvent was evaporated under reduced pressure, ethanol was added, and the mixture was then concentrated. The precipitated powder was collected by filtration. The powder was washed with isopropyl ether to give the title compound (622 mg) as a pale yellow powder. XH-NMR (DMSO-d6) d: 3.30 (2H, m), 5.08 (2H, m), 6.60 (1H, t, J = 2 Hz), 6.73 (3H, m), 7.06 (2H, m), 7.18 (1H, m), 7. 29 (1H, d, J = 9 Hz), 7.41 (3H, m), 7.64 (1H, dd, J = 3 Hz, 9 Hz), 7.90 (1H, d, J = 3 Hz), 8.10 (1H, d, J = 3 Hz), 8.42 (3H, br s), 8.73 (1H, s). (iii) Production of N- [2- (4. {[[3-chloro-4- (3-phenoxyphenoxy) phenyl] amino]} -5H-pyrrolo [3,2-d] pyrimidin-5 hydrochloride -yl) ethyl] -3-hydroxy-3-methylbutanamide A mixture of 5- (2-aminoethyl) -N- [3-chloro-4- (3-phenoxyphenoxy) phenyl] -5H-pyrrolo dihydrochloride [3,2 -d] pyrimidin- 4-amine (195 mg), 3-hydroxy-3-methylbutanoic acid (0.058 ml), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (103 mg), 1-hydroxybenzotriazole (72.5 mg), triethylamine ( 0.15 ml) and N, N-dimethylformamide (6.9 ml) was stirred at room temperature for 16 h. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate -> ethyl acetate: methanol = 85:15). The fraction with the title compound was concentrated under reduced pressure, and the residue was dissolved in ethyl acetate (4 ml). 4 N Hydrochloric acid (0.169 mL) was added, and the mixture was crystallized from ethyl acetate to give the title compound (176 mg). XH-NMR (DMSO-d6) d: 1.10 (6H, s), 2.19 (2H, s), 3.48 (2H, q, J = 6 Hz), 4.66 (2H, t, J = 6 Hz), 6.60 ( 1H, t, J = 3 Hz), 6.67 (1H, d, J = 3 Hz), 6.72 (2H, dt, J = 3 Hz, 9 Hz), 7.06 (2H, d, J = 8 Hz), 7.17 (1H, t, J = 7 Hz), 7.29 (1H, d, J = 9 Hz), 7.40 (3H, m), 7.67 (1H, dd, J = 3 Hz, 9 Hz), 7.92 (1H, d , J = 3 Hz), 7.98 (1H, d, J = 3 Hz), 8.40 (1H, m), 8.71 (1H, s).

Production of 2-. { 2- [4- ( { 3-Chloro-4- [3- (1,1-difluoro-2,2-dimethylpropyl) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethoxy} ethanol (i) Production of 1- [3- (2-chloro-4-nitrophenoxy) phenyl] -2, 2-dimethylpropan-l-one A mixture of 2-chloro-l-fluoro-4-nitrobenzene (2.63 g) , 1- (3-hydroxyphenyl) -2,2-dimethylpropan-l-one (2.55 g), potassium carbonate (2.97 g) and N, N-dimethylformamide (20 ml) was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure, water was added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue obtained was subjected to chromatography on silica gel coluran (eluent, ethyl acetate: hexane = 2: 98- »15: 85). The object fractions were concentrated under reduced pressure to give the title compound (5.17 g) as a pale yellowish green chlorine oil. XH-NMR (CDC13) d: 1.35 (9H, s), 6.92 (1H, d, J = 9.1 Hz), 7.18 (1H, ddd, J = 1.1 Hz, 2.6 Hz, 8.1 Hz), 7.37 (1H, m), 7.45-7.52 (1H, ra), 7.56-7.60 (1H, m), 8.08 (1H, dd, J = 2.7 Hz, 9.1 Hz), 8.40 (1H, d, J = 2.7 Hz). (ii) Production of 2-chloro-l- [3- (1,1-difluoro-2,2-dimethylpropyl) phenoxy] -4-nitrobenzene A solution of 1- [3- (2-chloro-4-nitrophenoxy) phenyl] -2, 2-dimethylpropan-l-one (3.34 g) and diethylaminosulfur trifluoride (6.85 g) in dichloromethane (100 ml) was stirred with heating under reflux overnight. Ice and aqueous sodium carbonate solution were added to the reaction mixture, and the mixture was extracted with dichloromethane. The dichloromethane layer was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, ethyl acetate: hexane = 2: 98- >; 15: 85). The object fractions were concentrated under reduced pressure to give the title compound (3.63 g) as a colorless oil. XH-NMR (CDC13) d: 1.05 (9H, s), 6.87 (1H, d, J = 9.1 Hz), 7.11-7.18 (2H, m), 7.31-7.37 (1H, m), 7.44-7.52 (1H , m), 8.07 (1H, dd, J = 2.7 Hz, 9.1 Hz), 8.40 (1H, d, J = 2.7 Hz). (iii) Production of 3-chloro-4- [3- (1,1-difluoro-2,2-dimethylpropyl) phenoxy] aniline A mixture of 2-chloro-l- [3- (1,1-difluoro-2) , 2-dimethylpropyl) phenoxy] -4-nitrobenzene (712 mg), iron reduced (372 mg), calcium chloride (123 mg) and 10% ethanol with water content (20 ml) was stirred with heating under reflux for 7 h. Separately, a mixture of 2-chloro-l- [3- (1,1-difluoro-2,2-dimethylpropyl) phenoxy] -4-nitrobenzene (3.00 g), reduced iron (1.57 g), calcium (520 mg) and 10% ethanol with water content (100 ml) with heating at reflux overnight. They were combined and the solid was removed by filtration. The filtrate was concentrated and water was added to the obtained residue, and the mixture was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, ethyl acetate: hexane = 15: 85-30: 70). The object fractions were concentrated under reduced pressure to give the title compound (2.40 g) as a pale brown solid. XH-NMR (CDC13) d: 1.02 (9H, s), 3.68 (2H, br s), 6.57 (1H, dd, J = 2.7 Hz, 8.8 Hz), 6.79 (1H, d, J = 2.7 Hz), 6.87-6.95 (3H, m), 7.05-7.11 (1H, m), 7.28-7.33 (1H, m). (iv) Production of 2-. { 2- [4- ( { 3-Chloro-4- [3- (1,1-difluoro-2,2-dimethylpropyl) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethoxy} ethanol When using 2- [2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethoxy] ethyl benzoate (173 mg), 3-chloro-4- [3- (1 , 1- difluoro-2, 2-dimethylpropyl) phenoxy] aniline (163 mg), isopropyl alcohol (3 ml), methanol (5 ml), tetrahydrofuran (1 ml) and 1 N aqueous sodium hydroxide solution (1 ml) and the same as in Ejeraplo E-2 (ii), the title compound (198 mg) was obtained in the form of a white powder. Vl-NMR (CDC13) d: 1.04 (9H, s), 2.05 (1H, br s), 3.70-3.84 (4H, m), 4.02 (2H, t, J = 4.3 Hz), 4.56 (2H, t, J = 4.3 Hz), 6.61 (1H, d, J = 3.2 Hz), 6.94-7.08 (3H, m), 7.13 (1H, d, J = 7.7 Hz), 7.20 (1H, d, J = 3.2 Hz) , 7.32 (1H, t, J = 8.0 Hz), 7.58 (1H, dd, J = 2.6 Hz, 8.9 Hz), 7.89 (1H, d, J = 2.6 Hz), 8.51 (1H, s), 8.78 (1H , br s). Example E-8 Production of 2- [4- ( { 3-chloro-4- [3- (1,1-difluoro-2,2-dimethylpropyl) phenoxy] phenyl} amino) -5H-pyrrolo [3, 2- d] pyrimidin-5-yl] ethanol A mixture of 2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl benzoate (151 mg), 3-chloro-4- [ 3- (1,1-difluoro-2,2-dimethylpropyl) phenoxy] aniline (163 rag) and isopropyl alcohol (3 ml) was stirred at 80 ° C for 9 h. An aqueous solution of sodium hydrogen carbonate was added to the reaction mixture, and the mixture was extracted with ethyl acetate. ethyl. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, ethyl acetate: hexane = 60: 40-> 100: 0). The object fractions were concentrated under reduced pressure. To the residue were added methanol (5 ml), tetrahydrofuran (1 ml) and 1 N aqueous solution of sodium hydroxide (1 ml) and the mixture was stirred at room temperature for 4 h. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100-> 10: 90). The object fractions were concentrated under reduced pressure. The residue was crystallized from ethyl acetate-diisopropyl ether to give the title compound (191 mg) as a white powder. XH-NMR (CDC13) d: 1.05 (9H, s), 4.11-4.18 (2H, m), 4.33-4.40 (2H, m), 6.09 (1H, d, J = 3.3 Hz), 6.50 (1H, br s), 6.95 (1H, d, J = 3.3 Hz), 6.97-7.08 (3H, m), 7.14 (1H, d, J = 7. 7 Hz), 7.34 (1H, t, J = 8.0 Hz), 7.47 (1H, dd, J = 2.5 Hz, 8. 8 Hz), 7.82 (1H, d, J = 2.5 Hz), 8.21 (1H, s), 9.56 (1H, br Production of N- (2- {4- [(3-chloro-4-. {3- [(1 E) -N-ethoxyacetoimidoyl] phenoxy] phenyl) amino] -5H-pyrrolo hydrochloride [3, 2-d] pyrimidin-5-yl} ethyl) -3-hydroxy-3-methylbutanamide (i) Production of [2- (4- { [4- (3-acetylphenoxy) -3-chlorophenyl] amino.}. -5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethyl] tert-butyl carbamate A mixture of tert-butyl [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] carbamate ( 890 mg), l- [3- (4-amino-2-chlorophenoxy) phenyl] ethanone (785 rag) and isopropyl alcohol (10 ml) was stirred at 80 ° C overnight. An aqueous solution of sodium acid carbonate was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue obtained was subjected to silica gel column chromatography (eluent, ethyl acetate: hexane = 50: 50-> gt).; 100: 0). The object fractions were concentrated under reduced pressure and the residue was crystallized from acetone-diethyl ether to give the title compound (1.14 g) in the form of a pale yellow powder. VL-NMR (CDCI3) d: 1.50 (9H, s), 2.59 (3H, m), 3.44-3.55 (2H, m), 4.44-4.53 (2H, m), 5.08 (1H, t, J = 5.6 Hz ), 6.61 (1H, d, J = 3.3 Hz), 7.05 (1H, d, J = 8.9 Hz), 7.15-7.21 (2H, m), 7.41 (1H, t, J = 8.0 Hz), 7.56 (1H , m), 7.66 (1H, d, J = 7.7 Hz), 7.89 (1H, dd, J = 2.7 Hz, 8.9 Hz), 8.03 (1H, d, J = 2.7 Hz), 8.52 (1H, s), 8.60 (1H, br s). (ii) Production of N- [2- (4. {[[4- (3-acetylphenoxy) -3-chlorophenyl] amino]} -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -3-hydroxy-3-methylbutanamide A [2- (4-. {[[4- (3-acetylphenoxy) -3-chlorophenyl] amino]} -5H-pyrrolo [3,2-d] pyrimidine- 5-yl) ethyl] tert-butyl carbamate (1.10 g) were added ethanol (2 ml) and 4 N hydrogen chloride solution / ethyl acetate (5 ml) and the mixture was stirred at room temperature overnight. The reaction mixture was concentrated under reduced pressure. To a solution of the residue obtained in N, N-dimethylformamide (20 ml) were added 3-hydroxy-3-methylbutanoic acid (374 mg), l-ethyl-3- (3-dimethylareneopropyl) carbodiimide hydrochloride (607 mg), 1-hydroxybenzotriazole monohydrate (485 mg) and triethylamine (0.882 ml) and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue obtained was subjected to silica gel column chromatography (eluent, ethyl acetate: hexane = 50: 50 → 100: 0 → methanol: ethyl acetate = 20:80) and silica gel column chromatography (eluent) , methanol: ethyl acetate = 0: 100- »10: 90). The subject fractions were concentrated under reduced pressure to give the title compound (596 mg) as a white amorphous powder. XH-NMR (CDC13) d: 1.32 (6H, s), 2.48 (2H, s), 2.59 (3H, s), 3.58-3.68 (2H, m), 4.44-4.54 (2H, m), 6.59 (1H , d, J = 3.3 Hz), 7.05 (1H, d, J = 8.8 Hz), 7.09-7.22 (3H, m), 7.42 (1H, t, J = 7.8 Hz), 7.57 (1H, m), 7.64-7.69 (1H, m), 7.74 (1H, dd, J = 2.6 Hz, 8.8 Hz), 8.07 (1H, d, J = 2.6 Hz), 8.50 (1H, s), 8.66 (1H, br s). (iii) Production of N- (2- {4 - [(3-chloro-4-. {3- [(1 E) -N-ethoxyacetoimidoyl] phenoxy] phenyl) amino] -5H- hydrochloride pyrrolo [3,2-d] pyrimidin-5-yl.} ethyl) -3-hydroxy-3-methylbutanamide To a solution of N- [2- (4- { [4- (3-acetylphenoxy) - 3-chlorophenyl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -3-hydroxy-3-methylbutanamide (157 mg) in ethanol (5 ml) were added O-hydrochloride ethylhydroxylamine (88 mg) and sodium acetate (74 mg) and the mixture was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue obtained was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate 0: 100-> 15: 85). The object fractions were concentrated under reduced pressure. The residue was dissolved in ethyl acetate-ethanol, and 1N hydrogen chloride solution / ethyl acetate (0.3 ml) was added. The solvent was evaporated under reduced pressure and the obtained residue was crystallized from ethyl acetate-diethyl ether to give the title compound (91 mg) as a white powder. XH-NMR (DMSO-d6) d: 1.11 (6H, s), 1.25 (3H, t, J = 7.1 Hz), 2.18 (3H, s), 2.20 (2H, s), 3.43-3.55 (2H, m ), 4.17 (2H, q, J = 7.1 Hz), 4.66 (2H, t, J = 6.7 Hz), 6.67 (1H, d, J = 3.2 Hz), 6.95-7.02 (1H, m), 7.22 (1H, d, J = 8.9 Hz), 7.33 (1H, m), 7.40-7.49 (2H, m), 7.67 (1H, dd, J = 2.5 Hz, 8.9 Hz), 7.94 (1H, d, J = 2.5 Hz), 7.98 (1H, d, J = 3.2 Hz), 8.40 (1H, t, J = 5.6 Hz), 8.72 (1H, s), 10.28 (1H, br s). Example E-10 Production of N- (2- {4- [(3-chloro-4-. {3- [(1 E) -N-isobutoxy-acetoimidoyl] phenoxy] phenyl) amino] -5H-pyrrolo hydrochloride [3, 2-d] pyrimidin-5-yl} ethyl) -3-hydroxy-3-methylbutanamide When using N- [2- (4- { [4- (3-acetylphenoxy) -3-chlorophenyl] amino.}. -5H-pyrrolo [3,2-d ] pyrimidin-5-yl) ethyl] -3-hydroxy-3-methylbutanamide (157 mg), ethanol (5 ml), O-isobutylhydroxylamine hydrochloride (113 mg), sodium acetate (74 mg) and sodium chloride solution. 1 N hydrogen / ethyl acetate (0.3 ml) and in the same manner as in Example E-9 (iii), the title compound (87 mg) was obtained as a white powder. Vl-NMR (DMSO-d6) d: 0.92 (6H, d, J = 6.9 Hz), 1.11 (6H, s), 1.90-2.05 (1H, m), 2.20 (5H, s), 3.44-3.54 (2H , m), 3.91 (2H, d, J = 6.6 Hz), 4.66 (2H, t, J = 6.7 Hz), 6.67 (1H, d, J = 3.0 Hz), 6.94-7.02 (1H, m), 7.22 (1H, d, J = 8.9 Hz), 7.32 (1H, m), 7.40-7.48 (2H, m), 7.67 (1H, dd, J = 2.5 Hz, 8.9 Hz), 7.94 (1H, d, J = 2.5 Hz), 7.99 (1H, d, J = 3.0 Hz), 8.40 (1H, t, J = 5.5 Hz), 8.72 (1H, s), 10.29 (1H, br s). Example E-ll Production of N- hydrochloride. { 2- [4- ( { 3-chloro-4- [3- (1, l-difluoro-2,2-dimethylpropyl) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -3-hydroxy-3-methylbutanamide (i) Production of. { 2- [4- ( { 3-Chloro-4- [3- (1,1-difluoro-2,2-dimethylpropyl) phenoxy] phenyl} amino) -5H-pyrrolo [3, 2-d] pyrimidin-5-yl] ethyl} tert-butyl carbamate When using [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (594 mg), 3-chloro-4- [ 3- (1,1-difluoro-2, 2-dimethylpropyl) phenoxy] aniline (652 mg) and isopropyl alcohol (10 ml) and in the same manner as in Example E-9 (i), the compound of title (1.15 g) in the form of a pale yellow amorphous powder. 2H-NMR (CDC13) d: 1.04 (9H, s), 1.49 (9H, s), 3.42-3.54 (2H, m), 4.41-4.52 (2H, m), 5.20 (1H, t, J = 5.4 Hz ), 6.58 (1H, d, J = 3.3 Hz), 6.96-7.08 (3H, m), 7.12 (1H, d, J = 7.7 Hz), 7.17 (1H, d, J = 3.3 Hz), 7.32 (1H , t, J = 8.0 Hz), 7.84 (1H, dd, J = 2.5 Hz, 8.8 Hz), 8.01 (1H, d, J = 2.5 Hz), 8.50 (1H, s), 8.61 (1H, br s) . (ii) Production of 5- (2-aminoethyl) -N- dihydrochloride. { 3-Chloro-4- [3- (1, 1-difluoro-2, 2-dimethylpropyl) phenoxy] phenyl} -5H-pyrrolo [3,2-d] pyrimidin-4-amine A. { 2- [4- ( { 3-Chloro-4- [3- (1,1-difluoro-2,2-dimethylpropyl) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin- -yl] ethyl} tert-butyl carbamate (1.15 g) methanol (10 ml) was added and hydrochloric acid (2 ml) was concentrated, and the mixture was stirred at room temperature overnight and at 60 ° C for 3 h. The reaction mixture was concentrated under reduced pressure, isopropyl alcohol and methanol were added, and the mixture was concentrated again under reduced pressure. Isopropyl alcohol and diisopropyl ether were added to the residue, and the crystals were collected by filtration to give the title compound (1.09 g) as a white powder. Vl-NMR (DMSO-d6) d: 0.99 (9H, s), 3.24-3.36 (2H, m), 5.01 (2H, t, J = 6.1 Hz), 6.73 (1H, d, J = 3.1 Hz), 6.93 (1H, m), 7.11 (1H, dd, J = 2.4 Hz, 8.0 Hz), 7.19 (1H, d, J = 8.1 Hz), 7.27 (1H, d, J = 8.9 Hz), 7.51 (1H, t, J = 8.0 Hz), 7.62 (1H, dd, J = 2.4 Hz, 8.9 Hz), 7.90 (1H, d, J = 2.4 Hz), 8.05 (1H, d, J = 3.1 Hz), 8.23-8.33 (3H, m), 8.71 (1H, s), 10.06 (1H, br s). (iii) Production of N- hydrochloride. { 2- [4- ( { 3-Chloro-4- [3- (1,1-difluoro-2,2-dimethylpropyl) phenoxy] phenyl} amino) -5H-pyrrolo [3, 2-d] pyrimidin-5-yl] ethyl} -3-hydroxy-3-methylbutanamide A mixture of 5- (2-aminoethyl) -N- dihydrochloride. { 3-Chloro-4- [3- (1, 1-difluoro-2, 2-dimethylpropyl) phenoxy] phenyl} -5H-pyrrolo [3,2-d] pyrimidin-4-amine (168 mg), 3-hydroxy-3-methylbutanoic acid (53 mg), l-ethyl-3- (3-) hydrochloride dimethylaminopropyl) carbodiimide (86 mg), 1-hydroxybenzotriazole monohydrate (69 mg), triethylamine (0.100 ml) and N, N-dimethylformamide (3 ml) was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue obtained was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100- »20: 80). The object fractions were concentrated under reduced pressure. The residue was dissolved in ethyl acetate-ethanol, and 1N hydrogen chloride solution / ethyl acetate (0.3 ml) was added. The solvent was evaporated under reduced pressure and the obtained residue was crystallized from ethyl acetate to give the title compound (134 mg) as a white powder. XH-NMR (DMSO-d6) d: 0.99 (9H, s), 1.11 (6H, s), 2.20 (2H, s), 3.44-3.54 (2H, m), 4.66 (2H, t, J = 7.0 Hz ), 6.67 (1H, d, J = 3.2 Hz), 6.92 (1H, m), 7.13 (1H, dd, J = 2.3 Hz, 8.1 Hz), 7.20 (1H, d, J = 7.7 Hz), 7.29 ( 1H, d, J = 8.9 Hz), 7.52 (1H, t, J = 8.0 Hz), 7.70 (1H, dd, J = 2.5 Hz, 8.9 Hz), 7.96 (1H, d, J = 2.5 Hz), 7.99 (1H, d, J = 3.2 Hz), 8.41 (1H, t, J = 5.1 Hz), 8.73 (1H, s), 10.28 (1H, br s).

Example E-12 Production of N-. { 2- [4- ( { 3-chloro-4- [3- (1,1-difluoro-2,2-dimethylpropyl) phenoxy] phenyl} amino) -5H-pyrrolo [3, 2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide A mixture of 5- (2-aminoethyl) -N- dihydrochloride. { 3-Chloro-4- [3- (1, 1-difluoro-2, 2-dimethylpropyl) phenoxy] phenyl} -5H-pyrrolo [3,2-d] pyrimidin-4-amine (168 mg), methylsulfonylacetic acid (62 mg), l-ethyl-3- (3-diraethylareneopropyl) carbodiimide hydrochloride (86 mg), monohydrate of 1 -hydroxybenzotriazole (69 mg), triethylamine (0.100 ml) and N, N-dimethylformamide (3 ml) was stirred at room temperature overnight. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, methanol: ethyl acetate = 0: 100-> 20: 80). The object fractions were concentrated under reduced pressure. The residue was crystallized from ethyl acetate-diisopropyl ether to give the title compound (153 mg) as a white powder.

VYRMN (CDCI3) d: 1.04 (9H, s), 3.14 (3H, s), 3.65- 3.75 (2H, m), 3.98 (2H, s), 4.44-4.53 (2H, m), 6.59 (1H, d) , J = 3.0 Hz), 6.98-7.04 (2H, m), 7.07 (1H, m), 7.15 (1H, d, J = 7. 7 Hz), 7.21 (1H, d, J = 3.0 Hz), 7.34 (1H, d, J = 8.0 Hz), 7.62 (1H, t, J = 5.5 Hz), 7.72 (1H, dd, J = 2.5 Hz 8.9 Hz), 7. 94 (1H, d, J = 2.5 Hz), 8.18 (1H, br s), 8.50 (1H, s). Example E-13 Production of 1-. { 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] phenyl} -2, 2-dimethylpropan-l-one (i) Production of 1- [3- (-amino-2-chlorophenoxy) phenyl] -2,2-diraethylpropan-l-one A mixture of 1- [3- (2 -chloro-4-nitrophenoxy) phenyl] -2, 2-dimethylpropan-l-one (1.03 g), reduced iron (575 mg), calcium chloride (190 mg) and 10% ethanol with water content (30 ml ) was stirred with heating at reflux overnight. The reaction mixture was filtered to remove the solid, and the filtrate was concentrated. Water was added to the residue, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under pressure reduced and the residue obtained was subjected to silica gel column chromatography (eluent, ethyl acetate: hexane = 20: 80-> 40: 60). The object fractions were concentrated under reduced pressure to give the title compound (708 mg) as a brown oil. Vl-NMR (CDC13) d: 1.31 (9H, s), 3.69 (2H, br s), 6.58 (1H, dd, J = 2.7 Hz, 8.5 Hz), 6.79 (1H, d, J = 2.7 Hz), 6.91 (1H, d, J = 8.5 Hz), 6.94-7.00 (1H, m), 7.16 (1H, m), 7.26-7.35 (2H, m). (ii) Production of 1-. { 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] phenyl} -2, 2-dimethylpropan-l-one When using 2- [2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethoxy] ethyl benzoate (734 mg), 1- [3- (4-amino-2-chlorophenoxy) phenyl] -2,2-dimethylpropan-l-one (645 mg), isopropyl alcohol (10 ml), methanol (25 ml), tetrahydrofuran (5 ml) and aqueous solution 1 N sodium hydroxide (5 ml) and in the same manner as in Example E-2 (ii), the title compound (858 mg) was obtained as a white powder. V-NMR (CDCl 3) d: 1.33 (9H, s), 3.70-3.82 (4H, m), 4. 02 (2H, t, J = 4.4 Hz), 4.55 (2H, t, J = 4.4 Hz), 6.58 (1H, d, J = 3.3 Hz), 7.00-7.06 (2H, m), 7.19 (1H, d , J = 3.3 Hz), 7.22 (1H, m), 7.28-7.39 (2H, m), 7.57 (1H, dd, J = 2.6 Hz, 8.8 Hz), 7.89 (1H, d, J = 2.6 Hz), 8.48 (1H, s), 8.81 (1H, br s).

Production of O-methyloxime hydrochloride (1Z) -l-. { 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] phenyl} -2, 2-dimethylpropan-l-one When using 1-. { 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3, 2-d] pyrimidin-4-yl} amino) phenoxy] phenyl} -2, 2-dimethylpropan-l-one (204 mg), ethanol (5 ml), O-methylhydroxylamine hydrochloride (100 mg), sodium acetate (98 mg) and 1 N hydrogen chloride solution / ethyl acetate (0.4 ml) and in the same manner as in Example E-9 (iii), the title compound (201 mg) was obtained as a white powder. Vl-NMR (DMSO-d6) d: 1.10 (9H, s), 3.41-3.51 (4H, m), 3.65 (3H, s), 3.84 (2H, t, J = 4.4 Hz), 4.78-4.85 (2H , m), 6.62 (1H, m), 6.69 (1H, d, J = 3.0 Hz), 6.82 (1H, d, J = 7.7 Hz), 6.94 (1H, dd, J = 2.5 Hz, 8.0 Hz), 7.22 (1H, d, J = 8.9 Hz), 7.42 (1H, t, J = 8.0 Hz), 7.61 (1H, dd, J = 2.5 Hz, 8.9 Hz), 7.95 (1H, d, J = 2.5 Hz) , 8.02 (1H, d, J = 3.0 Hz), 8.73 (1H, s), 9.92 (1H, br s).

Example E-15 Production of 2- [4- ( { 3-chloro-4- [3- (1,1-difluoroethyl) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5- il] ethanol (i) Production of 1- [3- (2-chloro-4-nitrophenoxy) phenyl] ethanone When using 2-chloro-l-fluoro-4-nitrobenzene (3.51 g), 3 '-hydroxyacetophenone (2.72 g) ), potassium carbonate (4.15 g) and N, N-dimethylformamide (20 ml) and in the same manner as in Example E-7 (i), the title compound (5.60 g) was obtained as a solid White. XH-NMR (CDC13) d: 2.62 (3H, s), 6.92 (1H, d, J = 9.1 Hz), 7.28-7.33 (1H, m), 7.56 (1H, t, J = 8.0 Hz), 7.65 ( 1H, m), 7.82-7.88 (1H, m), 8.09 (1H, dd, J = 2.6 Hz, 9.1 Hz), 8.41 (1H, d, J = 2.6 Hz). (ii) Production of 2-chloro-l- [3- (1, 1-difluoroethyl) phenoxy] -4-nitrobenzene A solution of l- [3- (2-chloro-4-nitrophenoxy) phenyl] ethanone (2.92 g) ), diethylaminosulfur trifluoride (8.06 g) in 1,2-dimethoxyethane (10 ral) was stirred at 50 ° C for 5 days. The reaction mixture was poured on ice, and 8 N aqueous sodium hydroxide solution (20 ml) was added thereto. Ethyl acetate was added, and the organic layer was separated, washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure and the obtained residue was subjected to silica gel column chromatography (eluent, ethyl acetate: hexane = 0: 100-> 20: 80). The object fractions were concentrated under reduced pressure to give the title compound (2.75 g) as an orange solid. XH-NMR (CDC13) d: 1.93 (3H, t, J = 18.1 Hz), 6.92 (1H, d, J = 9.1 Hz), 7.11-7.17 (1H, ra), 7.25 (1H, m), 7.38-7.44 (1H, m), 7.51 (1H, t, J = 7.8 Hz), 8.08 ( 1H, dd, J = 2.7 Hz, 9.1 Hz), 8.40 (1H, d, J = 2.7 Hz). (iii) Production of 3-chloro-4- [3- (1,1-difluoroethyl) phenoxy] aniline When using 2-chloro-l- [3- (1,1-difluoroethyl) phenoxy] -4-nitrobenzene (2.51) g), reduced iron (1.99 g), calcium chloride (493 mg) and 10% ethanol with water content (100 ml) and in the same manner as in Example E-13 (i), the compound was obtained of the title (1.81 g) in the form of a yellow oil. 1 H-NMR (CDCl 3) d: 1.89 (3 H, t, J = 18.1 Hz), 3.69 (2 H, br s), 6.58 (1 H, dd, J = 2.7 Hz, 8.6 Hz), 6.79 (1 H, d, J = 2.7 Hz), 6.86-6.92 (1H, m), 6.91 (1H, d, J = 8.6 Hz), 7.04 (1H, m), 7.13-7.18 (1H, m), 7.32 (1H, t, J = 8.0 Hz). (iv) Production of 2- [4- ( { 3-chloro-4- [3- (1,1-difluoroethyl) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidine -5-yl] ethanol When using 2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethyl benzoate (151 mg), 3-chloro-4- [3- (1 , 1-difluoroethyl) phenoxy] aniline (142 mg), isopropyl alcohol (3 ml), methanol (5 ml), tetrahydrofuran (1 ml) and 1 N aqueous sodium hydroxide solution (1 ml) and in the same manner as in Example E-8, the title compound (149 mg) was obtained as a white powder. Vl-NMR (CDC13) d: 1.92 (3H, t, J = 18.1 Hz), 4.10-4.18 (2H, m), 4.32-4.39 (2H, m), 6.06 (1H, d, J = 3.2 Hz), 6.72 (1H, br s), 6.93 (1H, d, J = 3.2 Hz), 6.97-7.02 (1H, m), 7.05 (1H, d, J = 8.8 Hz), 7.13 (1H, m), 7.20 ( 1H, d, J = 8.0 Hz), 7.36 (1H, t, J = 7.8 Hz), 7.47 (1H, dd, J = 2.5 Hz, 8.8 Hz), 7.81 (1H, d, J = 2.5 Hz), 8.18 (1H, s), 9.61 (1H, br s). Example E-16 Production of 2- [4- ( { 3-chloro-4- [3- (1,1-difluoro-3, 3-dimethylbutyl) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2- d] pyrimidin-5-yl] ethanol (i) Production of 1- [3- (2-chloro-4-nitrophenoxy) phenyl] -3,3-dimethylbutan-1-one Using 2-chloro-l-fluoro-4-nitrobenzene (1.76 g), 1- (3-hydroxyphenyl) -3,3-dimethylbutan-1-one (1.92 g), potassium carbonate (2.07 g) and N, N-dimethylformamide (10 ml) and in the same manner as in Example E- 7 (i), the title compound (3.24 g) was obtained as a yellow oil. XH-NMR (CDC13) d: 1.07 (9H, s), 2.85 (2H, s), 6.90 (1H, d, J = 9.1 Hz), 7.25-7.30 (1H, m), 7.54 (1H, t, J = 8.0 Hz), 7.63 (1H, m), 7.80-7.86 (1H, m), 8.08 (1H, dd, J = 2.7 Hz, 9.1 Hz), 8.41 (1H, d, J = 2.7 Hz). (ii) Production of 2-chloro-l- [3- (1,1-difluoro-3, 3-dimethylbutyl) phenoxy] -4-nitrobenzene When using 1- [3- (2-chloro-4-nitrophenoxy) phenyl ] -3, 3-diraethylbutan-1-one (1.90 g), diethylaminosulfur trifluoride (5.0 ml) and 1,2-dimethoxyethane (10 ml) and in the same manner as in Example E-15 (ii), the title compound (52 mg) was obtained as a yellow oil. H-NMR (CDCl 3) d: 1.02 (9H, s), 2.07 (2H, t, J = 19.1 Hz), 6.88 (1H, d, J = 9.3 Hz), 7.09-7.15 (1H, m), 7.21 ( 1H, m), 7.38 (1H, d, J = 7.7 Hz), 7.49 (1H, t, J = 7.8 Hz), 8.08 (1H, dd, J = 2.7 Hz, 9.3 Hz), 8.40 (1H, d, J = 2.7 Hz). (iii) Production of 3-chloro-4- [3- (1,1-difluoro-3, 3-dimethylbutyl) phenoxy] aniline When using 2-chloro-l- [3- (1,1-difluoro-3, 3- dimethylbutyl) phenoxy] -4-nitrobenzene (130 mg), reduced iron (99 mg), calcium chloride (25 mg) and 10% ethanol with water content (10 ml) and in the same manner as in Example E -13 (i), the title compound (100 mg) was obtained as a yellow oil. Vi-NMR (CDC13) d: 0.99 (9H, s), 2.04 (2H, t, J = 18.9 Hz), 3.69 (2H, br s), 6.58 (1H, dd, J = 2.7 Hz, 8.6 Hz), 6.79 (1H, d, J = 2.7 Hz), 6.85-6.90 (1H, ra), 6.90 (1H, d, J = 8.6 Hz), 7.00 (1H, m), 7.12 (1H, d, J = 7.7 Hz ), 7.30 (1H, t, J = 8.1 Hz). (iv) Production of 2- [4- ( { 3-chloro-4- [3- (1,1-difluoro-3, 3-dimethylbutyl) phenoxy] phenyl} amino) -5H-pyrrolo [3 , 2-d] pyrimidin-5-yl] ethanol When using 2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethyl benzoate (121 mg), 3-chloro-4 - [3- (1, 1-difluoro-3, 3-dimethylbutyl) phenoxy] aniline (100 mg), isopropyl alcohol (5 ml), methanol (5 ml), tetrahydrofuran (1 ml) and 1 N aqueous hydroxide solution of sodium (1 ml) and in the same manner as in Example E-8, the title compound (67 mg) was obtained as a white powder. Vl-NMR (CDCl 3) d: 1.01 (9H, s), 2.07 (2H, t, J = 19.0 Hz), 4.11-4.18 (2H, m), 4.33-4.40 (2H, m), 6.09 (1H, d) , J = 3.3 Hz), 6.49 (1H, br s), 6.94 (1H, d, J = 3.3 Hz), 6.95-7.01 (1H, m), 7.04 (1H, d, J = 8.7 Hz), 7.10 ( 1H, m), 7.17 (1H, d, J = 7.7 Hz), 7.35 (1H, t, J = 8.0 Hz), 7.47 (1H, dd, J = 2.6 Hz, 8.7 Hz), 7.81 (1H, d, J = 2.6 Hz), 8.20 (1H, s), 9.55 (1H, br s). Example E-17 Production of 2- [4- ( { 3-chloro-4- [3- (1,1-difluoro-2-phenylethyl) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethanol (i) Production of 1- [3- (2-chloro-4-nitrophenoxy) phenyl] -2-phenylethanone When using 2-chloro-l-fluoro-4-nitrobenzene (702 mg), 1- (3-hydroxyphenyl) -2-phenylethanone (849 mg), potassium carbonate (829 mg) and N, N-dimethylformamide (10 ml) and in the same manner as in Example E-7 (i), obtained the title compound (725 mg) as a pale yellow oil. XH-NMR (CDC13) d: 4.26 (2H, s), 6.86 (1H, d, J = 9.1 Hz), 7.20-7.36 (6H, m), 7.53 (1H, t, J = 8.0 Hz), 7.65 ( 1H, m), 7.86-7.92 (1H, m), 8.05 (1H, dd, J = 2.6 Hz, 9.1 Hz), 8.39 (1H, d, J = 2.6 Hz). (ii) Production of 2-chloro-l- [3- (1,1-difluoro-2-phenylethyl) phenoxy] -4-nitrobenzene When using 1- [3- (2-chloro-4-nitrophenoxy) phenyl] - 2- phenylethanone (478 rag), diethylaminosulfur trifluoride (2.0 ml) and 1,2-dimethoxyethane (5 ml) and in the same manner as in Example E-15 (ii), the title compound (372 mg) was obtained in shape of a yellow oil. XH-NMR (CDC13) d: 3.41 (2H, t, J = 15.4 Hz), 6.59 (1H, d, J = 9.1 Hz), 6.91 (1H, m), 7.01-7.13 (3H, m), 7.20-7.29 (4H, m), 7.44 (1H, t, J = 8.0 Hz), 7.99 ( 1H, dd, J = 2.5 Hz, 9.1 Hz), 8.35 (1H, d, J = 2.5 Hz). (iii) Production of 3-chloro-4- [3- (1,1-difluoro-2-phenylethyl) phenoxy] aniline When using 2-chloro-l- [3- (1,1-difluoro-2-phenylethyl) phenoxy] -4-nitrobenzene (372 mg), reduced iron (186 mg), calcium chloride (62 mg) and 10% ethanol with water content (10 ml) and in the same manner as in Example E-13 (i), the title compound (200 mg) was obtained as a yellow oil. XH-NMR (CDCl3) d: 3.36 (2H, t, J = 15.9 Hz), 3.67 (2H, br s), 6.54 (1H, dd, J = 2.7 Hz, 8.8 Hz), 6.77 (1H, d, J = 2.7 Hz), 6.78-6.84 (2H, m), 6.85-6.91 (1H, m), 6.98 (1H, d, J = 8.0 Hz), 7.05-7.12 (2H, m), 7.20-7.30 (4H, m). (iv) Production of 2- [4- ( { 3-chloro-4- [3- (1,1-difluoro-2-phenylethyl) phenoxy] phenyl} amino) -5H-pyrrolo [3.2 -d] pyrimidin-5-yl] ethanol When using benzoate of 2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethyl (169 mg), 3-chloro-4- [ 3- (1, 1-difluoro- 2-phenylethyl) phenoxy] aniline (200 mg), isopropyl alcohol (3 ml), methanol (5 ml), tetrahydrofuran (1 ml) and 1 N aqueous solution of sodium hydroxide (1 ml) and in the same manner as in Example E-8, the title compound (171 mg) was obtained in the form of a white powder. VL-NMR (CDC13) d: 3.39 (2H, t, J = 15.8 Hz), 4.10-4.19 (2H, m), 4.32-4.40 (2H, m), 6.09 (1H, d, J = 3.3 Hz), 6.53 (1H, br s), 6.90-7.14 (7H, m), 7.20-7.38 (4H, m), 7.45 (1H, dd, J = 2.5 Hz, 8.8 Hz), 7.80 (1H, d, J = 2.5 Hz), 8.21 (1H, s), 9.57 (1H, br s). Ex Production of 1- [3- (4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.} -2-methylphenoxy) phenyl] cyclopropanecarboxamide (i) Production of l- (3-methoxyphenyl) cyclopropanecarbonitrile. 60% sodium hydride (2.72 g) was suspended in N, N-dimethylformamide (80 ml) and the mixture was cooled to 0 ° C. A solution of (3-methoxyphenyl) acetonitrile (4.00 g) in N, N-dimethylformamide (20 ml) was added dropwise to the mixture and the mixture was stirred at 0 ° C for 1 h. 1,2-Dibromoethane (3.5 ml) was added dropwise to the reaction mixture, and the mixture was stirred at room temperature for 17 h. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was extracted with diethyl ether. The organic layer was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 100: 0-> 80: 20) to give the title compound (2.76 g) as a yellow oil. XH-NMR (CDC13) d: 1.36-1.44 (2H, m), 1.67-1.75 (2H, m), 3.81 (3H, s), 6.77-6.89 (3H, ra), 7.21-7.29 (1H, m) . (ii) Production of l- (3-methoxyphenyl) cyclopropanecarboxamide and l- (3-methoxyphenyl) cyclopropanecarboxylic acid l- (3-methoxyphenyl) cyclopropanecarbonitrile (2.75 g) was dissolved in a mixed solvent of ethanol (100 ml) / water ( 50 ml), potassium hydroxide (8.94 g) was added, and the mixture was stirred with heating at reflux for 5 h. The reaction mixture was concentrated under reduced pressure, the residue was adjusted to pH 1-2 with 6N hydrochloric acid, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 50: 50-> 0: 100) to give l- (3-ethoxyphenyl) cyclopropanecarboxamide (762 mg) and l-1 acid. (3-methoxyphenyl) cyclopropanecarboxylic acid (1.78 g), each in the form of pale orange crystals. 1- (3-methoxyphenyl) cyclopropanecarboxamide XH-NMR (DMSO-d6) d: 0.91-0.98 (2H, ra), 1.26-1.34 (2H, ra), 3.75 (3H, s), 6.11 (1H, br s) , 6.79-6.96 (3H, m), 7.02 (1H, br s), 7.25 (1H, t, J = 8.0 Hz). 1- (3-methoxyphenyl) -cyclopropanecarboxylic acid XH-NMR (DMSO-d6) d: 1.02-1.20 (2H, m), 1.33-1.50 (2H, m), 3.73 (3H, s), 6.71-7.00 (3H, m), 7.20 (1H, t, J = 7.8 Hz), 12.27 (1H, br s). (iii) Production of l- (3-hydroxyphenyl) cyclopropanecarboxamide 1- (3-methoxyphenyl) cyclopropanecarboxamide was dissolved (756 mg) in benzotrifluoride (20 ml), thereto was added 1N boron tribromide solution / dichloromethane (10 ml) at 0 ° C, and the mixture was stirred at room temperature for 2 days. The reaction mixture was cooled with ice, saturated aqueous sodium hydrogen carbonate solution was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue is separated and purified by silica gel column chromatography (hexane: ethyl acetate = 67: 33-0: 100) to give the title compound (350 mg) as a white powder. XH-NMR (DMS0-d6) d: 0.85-0.95 (2H, m), 1.22-1.32 (2H, m), 6.04 (1H, br s), 6.59-6.71 (1H, m), 6.71-6.82 (2H , m), 7.02 (1H, br s), 7.12 (1H, t, J = 7.8 Hz), 9.40 (1H, s). (iv) Production of 1- [3- (2-methyl-4-nitrophenoxy) phenyl] cyclopropanecarboxamide A mixture of l- (3-hydroxyphenyl) cyclopropanecarboxamide (345 mg) and 2-fluoro-5-nitrotoluene (347 mg) is dissolved in N, N-dimethylformamide (5 ml), potassium carbonate (588 mg) was added, and the mixture was stirred at room temperature for, 19 h. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 67: 33- »10: 90) to give the title compound (561 mg) as a white powder. XH-NMR (CDC13) d: 1.11 (2H, q, J = 3.9 Hz), 1.58-1.70 (2H, m), 2.41 (3H, s), 5.35 (1H, br s), 5.56 (1H, br s) ), 6.80 (1H, d, J = 9.0 Hz), 6.93-7.00 (1H, m), 7.13 (1H, t, J = 2.1 Hz), 7.27-7.33 (1H, m), 7.41 (1H, t, J = 7.8 Hz), 8.02 (1H, dd, J = 2.0 Hz, 9.0 Hz), 8.18 (1H, d, J = 2.0 Hz). (v) Production of 1- [3- (4-amino-2-methylphenoxy) phenyl] cyclopropanecarboxamide 1- [3- (2-Methyl-4-nitrophenoxy) phenyl] cyclopropanecarboxamide (556 mg) was suspended in a mixed solvent of Ethanol (18 ml) / water (2 ml), reduced iron (615 mg) and calcium chloride (105 mg) were added, and the mixture was stirred under heating at reflux for 4 h. The reaction mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. The residue was dissolved in ethyl acetate, and the solution was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 50: 50 → 0: 100) to give the title compound (433 mg) as a brown oil. XH-NMR (CDC13) d: 1.03-1.11 (2H, m), 1.54-1.63 (2H, m), 2.09 (3H, s), 3.59 (2H, br s), 5.38 (2H, br s), 6.49 -6.56 (1H, m), 6.60 (1H, d, J = 2.8 Hz), 6.72-6.82 (2H, ra), 6.89-6.94 (1H, m), 7.01-7.07 (1H, m), 7.23 (1H , t, J = 8.4 Hz). (vi) Production of 1- [3- (4-. {[[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.} -2-methylphenoxy) phenyl] cyclopropanecarboxamide A mixture of benzoate of 2- (4-chloro-5H-pyrrolo [3,2-d] pyriraidin-5-yl) ethyl (113 mg) and 1- [3- (4-amino- 2-methylphenoxy) phenyl] cyclopropancarboxamide (108 mg) was dissolved in isopropyl alcohol (3 ml), and the mixture was stirred at 70 ° C for 21 h. The reaction mixture was cooled to room temperature, 1N aqueous solution of sodium hydroxide (1 ml) was added and the mixture was stirred at room temperature for 1 h. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 20: 80-> 0: 100-> ethyl acetate: methanol = 90:10) and crystallized from ethyl acetate to give the title compound (110 mg) as crystals whites. XH-NMR (DMSO-d6) d :, 0.90-0.98 (2H, ra), 1.25-1.33 (2H, m), 2.16 (3H, s), 3.87 (2H, t, J = 4.5 Hz), 4.52 ( 2H, t, J = 4.5 Hz), 6.25 (2H, br s), 6.48 (1H, d, J = 3.0 Hz), 6.74-6.82 (1H, m), 6.82-6.87 (1H, m), 6.96- 7.09 (3H, m), 7.30 (1H, t, J = 7.9 Hz), 7.47-7.56 (2H, m), 7.62 (1H, d, J = 3.0 Hz), 8.27 (1H, s), 9.61 (1H , br s).

Example E-19 Production of l- [3- (4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.} -2-methylphenoxy) phenyl] cyclopropanecarbonitrile (i) Production of l- (3-hydroxyphenyl) cyclopropanecarbonitrile When using 1- (3-methoxyphenyl) cyclopropanecarbonitrile (1.28 g), toluene (75 ml) and boron tribromide solution 1 N / dichloromethane (25 ml) and from the same manner as in Example E-18 (iii), the title compound (1.11 g) was obtained as a colorless oil. XH-NMR (CDC13) d: 1.37-1.46 (2H, m), 1.69-1.77 (2H, m), 5.16 (1H, s), 6.70-6.81 (2H, m), 6.83 (1H, t, J = 2.1 Hz), 7. 21 (1H, t, J = 7.8 Hz). (ii) Production of 1- [3- (2-methyl-4-nitrophenoxy) phenyl] cyclopropanecarbonitrile When using 2-fluoro-5-nitrotoluene (409 mg), l- (3-hydroxyphenyl) cyclopropanecarbonitrile (450 rag), carbonate of potassium (731 mg) and N, N-dimethylformamide (8 ml) and in the same manner as in Example E-18 (iv), the compound of the title (776 mg) in the form of a white powder. 2 H-NMR (CDCl 3) d: 1.38-1.47 (2H, m), 1.72-1.82 (2H, m), 2.40 (3H, s), 6.78 (1H, d, J = 9.0 Hz), 6.88-6.95 (1H , ra), 7. 01 (1H, t, J = 2.1 Hz), 7.10-7.17 (1H, m), 7.38 (1H, t, J = 8.0 Hz), 8.01 (1H, dd, J = 2.8 Hz, 9.0 Hz), 8.12- 8.22 (1H, m). (iii) Production of 1- [3- (4-amino-2-methylphenoxy) phenyl] cyclopropanecarbonitrile When using 1- [3- (2-methyl-4-nitrophenoxy) phenyl] cyclopropanecarbonitrile (771 mg), reduced iron (847) mg), calcium chloride (151 mg) and ethanol (27 ml) / water (3 ml) and in the same manner as in Example E-18 (v), the title compound (665 mg) was obtained in the form of a yellow oil. XH-NMR (CDCI3) d: 1.36-1.39 (2H, m), 1.67-1.71 (2H, m), 2.09 (3H, s), 3.57 (2H, br s), 6.52 (1H, dd, J = 2.7 Hz, 8.7 Hz), 6.59 (1H, d, J = 2.7 Hz), 6.67-6.70 (1H, m), 6.75-6.79 (2H, m), 6.93-6.96 (1H, m), 7.21 (1H, t , J = 8.1 Hz). (iv) Production of 1- [3- (4-. {[[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.} -2-methylphenoxyphenyl] cyclopropanecarbonitrile When using 2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethyl benzoate (127 mg), 1- [3- (4-amino-2-methylphenoxy) phenyl] cyclopropancarbonitrile (130 mg), isopropyl alcohol (3 ml) and 1 N aqueous solution of sodium hydroxide (1 ml) and in the same manner as in Example E-18 (vi), the title compound (115 mg) was obtained in the form of a white powder. Vl-NMR (CDCI3) d: 1.38-1.45 (2H, m), 1.69-1.76 (2H, m), 2.24 (3H, s), 4.08-4.18 (2H, m), 4.31-4.43 (2H, m) , 6.12 (1H, d, J = 3.3 Hz), 6.35 (1H, br s), 6.80 (1H, dd, J = 1.9 Hz, 8. 0 Hz), 6.88-7.03 (4H, m), 7.25 (1H, t, J = 8.0 Hz), 7.38- 7.51 (2H, m), 8.22 (1H, s), 9.31 (1H, m). Example E-20 Production of O-ethylime hydrochloride (1Z) -1-. { 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] phenyl} -2, 2-dimethylpropan-l-one When using 1-. { 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] phenyl} -2, 2-dimethylpropan-l-one (255 mg), ethanol (5 ml), O-ethylhydroxylamine hydrochloride (146 mg), sodium acetate (123 mg) and 1 N hydrogen chloride solution / ethyl acetate (0.5 ml) and from the same manner as in Example E-9 (iii), the title compound (144 mg) was obtained as a white powder. XH-NMR (DMSO-d6) d: 1.07 (3H, t, J = 7.0 Hz), 1.10 (9H, s), 3.40-3.50 (4H, m), 3.84 (2H, t, J = 4.5 Hz), 3.92 (2H, q, J = 7.0 Hz), 4.82 (2H, t, J = 4.5 Hz), 6.61 (1H, m), 6.69 (1H, d, J = 3.0 Hz), 6.82 (1H, d, J = 7.4 Hz), 6.93-6.99 (1H, m), 7.19 (1H, d, J = 8.8 Hz), 7.42 (1H, t, J = 7.8 Hz), 7.61 (1H, dd, J = 2.5 Hz, 8.8 Hz ), 7.95 (1H, d, J = 2.5 Hz), 8.01 (1H, d, J = 3.0 Hz), 8.71 (1H, s), 9.92 (1H, br s). Example E-21 Production of 1-. { 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] phenyl} -2, 2-dimethylpropan-l-ol To a solution of 1-. { 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl Jaraino) phenoxy] phenyl} -2,2-dimethylpropan-l-one (255 mg) in methanol (5 ml) was added sodium borohydride (38 mg) and the mixture was stirred at room temperature for 4 h. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the residue obtained was crystallized from ethyl acetate-diisopropyl ether to give the title compound (206 mg) as a white powder.

XH-NMR (CDCl3) d: 0.92 (9H, s), 2.02 (1H, br s), 2.12 (1H, br s), 3.69-3.80 (4H, m), 4.01 (2H, t, J = 4.4 Hz ), 4.36 (1H, s), 4.55 (2H, t, J = 4.4 Hz), 6.59 (1H, d, J = 3.0 Hz), 6.82-6.88 (1H, m), 6.92 (1H, ra), 6.96 -7.04 (2H, m), 7.19 (1H, d, J = 3.0 Hz), 7.24 (1H, t, J = 7.8 Hz), 7.54 (1H, dd, J = 2.5 Hz, 8.8 Hz), 7.85 (1H , d, J = 2.5 Hz), 8.47 (1H, s), 8.73 (1H, br s). Example E-22 Production of 1- [3- (2-chloro-4. {[[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. Phenoxy) phenyl] -3,3-dimethylbutan-1-one (i) Production of 1- [3- (4-amino-2-chlorophenoxy) phenyl] -3,3-dimethylbutan-1-one To a solution of 1- [3- (2-Chloro-4-nitrophenoxy) phenyl] -3,3-dimethylbutan-1-one (1.04 g) in ethyl acetate (20 ml) was added 5% activated carbon-platinum (50 mg) and the mixture stirred under a hydrogen atmosphere at room temperature for 3 h. The catalyst was filtered, and the filtrate was concentrated. The residue obtained was subjected to silica gel column chromatography (eluent, acetate ethyl acetate: hexane = 15: 85- »35: 65) and the object fractions were concentrated under reduced pressure to give the title compound (964 mg) as a brown oil. XH-NMR (CDC13) d: 1.04 (9H, s), 2.80 (2H, s), 3.69 (2H, br s), 6.57 (1H, dd, J = 2.7 Hz, 8.7 Hz), 6.78 (1H, d , J = 2.7 Hz), 6.90 (1H, d, J = 8.7 Hz), 7.05 (1H, ddd, J = 0.9 Hz, 2.6 Hz, 8.1 Hz), 7.34 (1H, t, J = 8.0 Hz), 7.41 (1H, m), 7.55-7.59 (1H, m). (ii) Production of 1- [3- (2-chloro-4. {[[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino] phenoxy ) phenyl] -3,3-dimethylbutan-1-one When using 2- (4-chloro-5H-pyrrolo [3,2-d] pyriraidin-5-yl) ethyl benzoate (754 mg), 1- [3 - (4-amino-2-chlorophenoxy) phenyl] -3,3-dimethylbutan-l-one (795 mg), isopropyl alcohol (5 ml), methanol (10 ml), tetrahydrofuran (2 ml) and 1 N aqueous solution of sodium hydroxide (2.5 ml) and in the same manner as in Example E-8, the compound of title (878 mg) in the form of a white powder. 2 H-NMR (CDCl 3) d: 1.06 (9H, s), 2.84 (2H, s), 4.13 (2H, t, J = 4.4 Hz), 4.37 (2H, t, J = 4.4 Hz), 6.09 (1H, d, J = 3.2 Hz), 6.58 (1H, br s), 6.95 (1H, d, J = 3.2 Hz), 7.04 (1H, d, J = 8.8 Hz), 7.13-7.18 (1H, m), 7.39 (1H, t, J = 8.0 Hz), 7.46 (1H, dd, J = 2.6 Hz, 8.8 Hz), 7.50 (1H, m), 7.62 (1H, d, J = 7.7 Hz), 7.81 (1H, d , J = 2.6 Hz), 8.19 (1H, s), 9.59 (1H, br s).

Example E-23 Production of 1- [3- (2-chloro-4. {[[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino] phenoxy) phenyl] -3, 3-dimethylbutan-1-ol When using 1- [3- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4- il] amino.}. phenoxy) phenyl] -3,3-dimethylbutan-1-one (239 mg), methanol (5 ml) and sodium borohydride (38 mg) and in the same manner as in Example E-21 , the title compound (234 mg) was obtained in the form of a white powder. VL-NMR (CDC13) d: 1.00 (9H, s), 1.61 (1H, dd, J = 3. 4 Hz, 14.5 Hz), 1.74 (1H, dd, J = 8.3 Hz, 14.5 Hz), 1.91 (1H, br s), 4.13 (2H, t, J = 4.5 Hz), 4.36 (2H, t, J = 4.5 Hz), 4.82 (1H, dd, J = 3.4 Hz, 8.3 Hz), 6.09 (1H, d, J = 3.0 Hz), 6.52 (1H, br s), 6.85 (1H, dd, J = 2.5 Hz, 8.0 Hz), 6.95 (1H, d, J = 3.0 Hz), 7.00-7.08 (3H, m), 7.28 (1H, t, J = 7.8 Hz), 7.45 (1H, dd, J = 2.6 Hz, 8.8 Hz ), 7.80 (1H, d, J = 2.6 Hz), 8.19 (1H, s), 9.56 (1H, br s).

Example E-24 Production of 1- [3- (2-chloro-4. {[[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. Phenoxy) phenyl] -2-phenylethanone (i) Production of 1- [3- (4-amino-2-chlorophenoxy) phenyl] -2-phenylethanone When using 1- [3- (2-chloro-4-nitrophenoxy) phenyl] -2- phenyletanone (240 mg), ethyl acetate (10 ml) and platinum-activated carbon 5% (12 mg) and in the same manner as in Example E-22 (i), the title compound was obtained (192 mg ) in the form of a colorless oil. XH-NMR (CDC13) d: 3.70 (2H, br s), 4.21 (2H, s), 6.57 (1H, dd, J = 2.7 Hz, 8.8 Hz), 6.78 (1H, d, J = 2.7 Hz), 6.89 (1H, d, J = 8.8 Hz), 7.06-7.11 (1H, m), 7.19-7.40 (6H, m), 7.46 (1H, m), 7.64-7.69 (1H, m). (ii) Production of 1- [3- (2-chloro-4. {[[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-yl] amino] phenoxy) phenyl] -2-phenylethanone When using 2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethyl benzoate (166 mg), 1- [3- (4-amino-2 -chlorophenoxy) phenyl] -2-phenylethanone (186 mg), alcohol isopropyl ether (3 ml), methanol (5 ml), tetrahydrofuran (1 ml) and 1 N aqueous sodium hydroxide solution (1 ml) and in the same manner as in Example E-8, the title compound was obtained ( 123 mg) in the form of a pale brown powder. Vl-NMR (CDC13) d: 4.14 (2H, t, J = 4.5 Hz), 4.25 (2H, s), 4.38 (2H, t, J = 4.5 Hz), 6.15 (1H, d, J = 3.2 Hz) , 6.19 (1H, br s), 6.97 (1H, d, J = 3.2 Hz), 7.05 (1H, d, J = 8.7 Hz), 7.17-7.37 (6H, m), 7.42 (1H, t, J = 8.0 Hz), 7.49 (1H, dd, J = 2.7 Hz, 8.7 Hz), 7.54 (1H, m), 7.72 (1H, d, J = 7.7 Hz), 7.82 (1H, d, J = 2.7 Hz), 8.24 (1H, s), 9.55 (1H, br s). Example E-25 Production of 1- [3- (2-chloro-4. {[[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. Phenoxy) phenyl] -2-phenylethanol When using 1- [3- (2-chloro-4. {[[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino]. phenoxy) phenyl] -2-phenylethanone (60 mg), methanol (2 ml) and sodium borohydride (10 mg) and in the same manner as in Example E-21, the title compound (24 mg) was obtained in the form of a powder.

White. VL-NMR (CDCI3) d: 2.08 (1H, br s), 2.98 (1H, dd, J = 8.2 Hz, 13.7 Hz), 3.05 (1H, dd, J = 4.9 Hz, 13.7 Hz), 4.14 (2H, t, J = 4.6 Hz), 4.38 (2H, t, J = 4.6 Hz), 4.89 (1H, dd, J = 4.9 Hz, 8.2 Hz), 6.07 (1H, br s), 6.15 (1H, d, J = 3.3 Hz), 6.87-6.93 (1H, m), 6.96-7.02 (3H, m), 7.08 (1H, d, J = 7. 7 Hz), 7.17-7.35 (6H, m), 7.45 (1H, dd, J = 2.5 Hz, 8.8 Hz), 7.79 (1H, d, J = 2.5 Hz), 8.24 (1H, s), 9.48 (1H, br s). Example E-26 Production of 2-. { 4- [(3-methyl-4- { 3- [(1 E) -3-Rethylbut-1-en-l-yl] phenoxy] phenyl) amino] -5H-pyrrolo [3,2-d] ] pyrimidin-5-yl} ethanol (i) Production of 3- (2-methyl-4-nitrophenoxy) benzaldehyde When using 2-fluoro-5-nitrotoluene (3.00 g), 3-hydroxybenzaldehyde (2.59 g), potassium carbonate (4.58 g) and N, N-dimethylformamide (30 ml) and in the same manner as in Example E-18 (iv), the title compound (4.14 g) was obtained as a pale yellow solid. Vi-NMR (CDCl 3) d: 2.40 (3H, s), 6.85 (1H, d, J = 9 Hz), 7.28-7.36 (1H, m), 7.46-7.54 (1H, m), 7.60 (1H, t, J = 7.8 Hz), 7.68-7.76 (1H, m), 8.04 (1H, dd, J = 2.8 Hz, 9.0 Hz), 8.19 (1H, d, J = 2.8 Hz ), 10.00 (1H, s). (ii) Production of 2-methyl-l-. { 3- [3-methylbut-l-en-l-yl] phenoxy} -4-Nitrobenzene Isobutyltriphenylphosphonium bromide (1.86 g) was suspended in tetrahydrofuran (20 ml) and the suspension was cooled to 0 ° C. Dropwise 1.6 M solution of n-butyllithium / hexane (3.5 ml) was added, and the mixture was stirred at 0 ° C for 1 h. A solution of 3- (2-methyl-4-nitrophenoxy) benzaldehyde (1.00 g) in tetrahydrofuran (10 ml) was added dropwise to the reaction mixture, and the mixture was stirred at room temperature for 2 h. A saturated aqueous solution of ammonium chloride was added to the reaction mixture, and the mixture was extracted with diethyl ether. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 100: 0-90: 10) to give the title compound (1.09 g, E / Z = about 1/5) in shape of a yellow oil. XH-NMR (CDC13) d: 1.03 (5H, d, J = 6.5 Hz), 1.09 (1H, d, J = 6.5 Hz), 2.41 (3H, s), 2.40-2.51 (0.17H, m), 2.77 -2.92 (0.83H, m), 5.51 (0.83H, dd, J = 10.3 Hz, 11.6 Hz), 6.15-6.38 (1.17H, m), 6.72-6.96 (2.83H, m), 7.03 (0.17H, t, J = 7.7 Hz), 7. 11 (0.83H, d, J = 7.7 Hz), 7.20 (0.17H, d, J = 7.7 Hz), 7.28-7.41 (1H, m), 7.94-8.06 (1H, m), 8.11-8.21 (1H, ra). (iii) Production of 3-methyl-4-. { 3- [3-methylbut-l-en-1-yl] phenoxy} Aniline When using 2-methyl-l-. { 3- [3-methylbut-l-en-l-yl] phenoxy} - 4-nitrobenzene (1.08 g), reduced iron (1.01 g), calcium chloride (205 mg) and ethanol (36 ml) / water (4 ml) and in the same manner as in Example E-18 (v) , the title compound (821 mg, E / Z = about 1/5) was obtained as a yellow oil. XH-NMR (CDC13) d: 1.00 (5H, d, J = 6.6 Hz), 1.07 (1H, d, J = 6.6 Hz), 2.12 (3H, s), 2.36-2.52 (0.17H, ra), 2.74 -2.96 (0.83H, ra), 3.55 (2H, br s), 5.43 (0.83H, dd, J = 10.2 Hz, 11.6 Hz), 6.08-6.33 (1.17H, m), 6.47-6.92 (5.83H, m), 6.95-7.01 (0.17H, m), 7.16 (0.17H, t, J = 8.0 Hz), 7.19 (0.83H, t, J = 8.0 Hz). (iv) Production of 3-RETHYL-4-. { 3- [(1E) -3-methylbut-1-en-1-yl] phenoxy Janiline 3-methyl-4 was dissolved. { 3- [3-methylbut-l-en-l-yl] phenoxy} aniline (815 mg) in tetrahydrofuran (15 ml), diphenyl disulfide (133 mg) and 2,2'-azobis (butyronitrile) (103 mg) were added, and the mixture was stirred with heating under reflux for 3 days. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 90: 10 → 50: 50) to give the title compound (181 mg) as an orange oil. Vi-NMR (CDC13) d: 1.06 (6H, d, J = 6.9 Hz), 2.11 (3H, s), 2.35-2.53 (1H, m), 3.55 (2H, br s), 6.13 (1H, dd, J = 6.3 Hz, 16.0 Hz), 6.25 (1H, d, J = 16.0 Hz), 6.51 (1H, dd, J = 3.0 Hz, 8.4 Hz), 6.59 (1H, d, J = 3.0 Hz), 6.65 ( 1H, dd, J = 2.6 Hz, 8.0 Hz), 6.78 (1H, d, J = 8.4 Hz), 6.81-6.86 (1H, ra), 6.97 (1H, d, J = 8.0 Hz), 7.15 (1H, t, J = 8.0 Hz). (v) Production of 2-. { 4- [(3-methyl-4- { 3- [(1 E) -3-methylbut-1-en-l-yl] phenoxy] phenyl) amino] -5H-pyrrolo [3,2-d ] pyrimidin-5-yl} ethanol When using 2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethyl benzoate (69.6 mg), 3-methyl-4-. { 3- [(1E) -3-Rethylbutyl-1-en-l-yl] phenoxy} aniline (65.0 mg), isopropyl alcohol (2 ml) and 1 N aqueous solution of sodium hydroxide (1 ml) and in the same manner as in Example E-18 (vi), the title compound was obtained (47.7 mg ) in the form of a white powder. Vl-NMR (CDCI3) d: 1.09 (6H, d, J = 6.8 Hz), 2.26 (3H, s), 2.36-2.56 (1H, m), 4.13 (2H, t, J = 4.5 Hz), 4.31- 4.42 (2H, m), 6.12 (1H, d, J = 3.2 Hz), 6.19 (1H, dd, J = 6.6 Hz, 16.2 Hz), 6.30 (1H, d, J = 16.2 Hz), 6.72-6.81 ( 1H, m), 6.90- 6. 99 (3H, m), 7.04 (1H, d, J = 8.0 Hz), 7.21 (1H, t, J = 8.0 Hz), 7.37-7.48 (2H, m), 8.23 (1H, s), 9.28 (1H , s).

Production of N- (2- {4- [(3-methyl-4-. {3- [(1 E) -3-methylbut-1-en-1-yl] phenoxy] phenyl} hydrochloride. amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl.} ethyl) -2- (methylsulfonyl) acetamide (i) Production of (2- {4- [(3-methyl-4) - { 3- [(1E) -3-methylbut-1-en-l-yl] phenoxy] phenyl) amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl}. ethyl) tert-butyl carbamate A mixture of tert-butyl [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] carbamate (120 mg) and 3-methyl- 4-. { 3- [(1 E) -3-methylbut-l-en-l-yl] phenoxy} Aniline (109 mg) was dissolved in isopropyl alcohol (5 ml), and stirred at 70 ° C for 22 h. A saturated aqueous solution of sodium acid carbonate was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate). ethyl = 67: 33 → 10: 90) to give the title compound (186 mg) as a white powder. Vl-NMR (CDCl 3) d: 1.08 (6H, d, J = 6.6 Hz), 1.46 (9H, s), 2.24 (3H, s), 2.35-2.55 (1H, m), 3.42-3.58 (2H, ), 4.40-4.52 (2H, m), 4.95-5.08 (1H, m), 6.18 (1H, dd, J = 6.6 Hz, 16.2 Hz), 6.29 (1H, d, J = 16.2 Hz), 6.58 (1H, d, J = 3.0 Hz ), 6.73-6.81 (1H, m), 6.90-6.98 (2H, m), 7.03 (1H, d, J = 8.0 Hz), 7.16 (1H, d, J = 3.0 Hz), 7.20 (1H, t, J = 8.0 Hz), 7.58-7.70 (2H, ra), 8.32 (1H, br s), 8.49 (1H, s). (ii) Production of 5- (2-aminoethyl) -N- (3-methyl-4 -. {3, 3- [(1 E) -3-methylbut-1-en-1-yl] phenoxy dihydrochloride. phenyl) -5H-pyrrolo [3,2-d] pyrimidin-4-amino It was dissolved (2- {4- [(3-methyl-4-. {3- [(1E) -3-methylbut- 1-en-l-yl] phenoxy] phenyl) amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl.} Ethyl) tert-butyl carbamate (180 mg) in ethanol (1 ml), 6N hydrochloric acid (0.3 ml) was added thereto, and the mixture was stirred at 50 ° C for 12 h. The reaction mixture was concentrated under reduced pressure, the residue was dissolved in ethanol, and the mixture was re-concentrated under reduced pressure. The precipitate was collected by filtration to give the title compound (158 mg) as a pale yellow powder. Vl-NMR (DMSO-dg) d: 1.05 (6H, d, J = 6.8 Hz), 2.22 (3H, s), 2.37-2.54 (1H, m), 3.18-3.32 (2H, m), 5.00 (2H , t, J = 6.1 Hz), 6.22-6.41 (2H, m), 6.67-6.79 (2H, m), 6.92-7.04 (2H, m), 7.16 (1H, d, J = 7.9 Hz), 7.31 (1H, t, J = 7.9 Hz), 7.39 (1H, dd, J = 2.0 Hz, 8.6 Hz), 7.49 (1H, d , J = 2.0 Hz), 8.03 (1H, d, J = 3.2 Hz), 8.31 (3H br s), 8.67 (1H, s), 9.87 (1H, br s). (iii) Production of N- (2- {4 - [(3-butyl-4-. {3- [(1 E) -3-methylbut-1-en-1-yl] phenoxy] hydrochloride. phenyl) amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl}. ethyl) -2- (methylsulfonyl) acetamide A mixture of 5- (2-aminoethyl) -N- (3-dihydrochloride -methyl-4 - { 3- [(1E) -3-methylbut-1-en-l-yl] phenoxy] phenyl) -5H-pyrrolo [3,2-d] pyrimidin-4-amine ( 74.8 mg) and methylsulfonylacetic acid (31.1 mg) was dissolved in tetrahydrofuran (0.4 ml) / N, N-dimethylformamide (0.4 ml), successively adding 1-hydroxybenzotriazole (32.5 mg), triethylamine (0.2 ml) and hydrochloride of l- ethyl-3- (3-dimethylaminopropyl) carbodiimide (45.0 mg), and the mixture was stirred at room temperature for 24 h. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 20: 80 → 0: 100 → ethyl acetate: methanol = 90:10) to give N- (2-. 4- [(3-methyl-4- { 3- [(1 E) -3-methylbut-l-en-l-yl] phenoxy] phenyl) amino] -5H-pyrrolo [3,2-d] ] pyrimidin-5-yl.} ethyl) -2- (methylsulfonyl) acetamide. The compound dissolved in ethyl acetate and treated with 4N hydrogen chloride solution / ethyl acetate, and the precipitate was collected by filtration to give the title compound (32.5 mg) as a yellow powder. XH-NMR (DMSO-d6) d: 1.05 (6H, d, J = 6.8 Hz), 2.22 (3H, s), 2.36-2.55 (1H, m), 3.06 (3H, s), 3.47-3.62 (2H , m), 4.06 (2H, s), 4.69 (2H, t, J = 6.4 Hz), 6.20-6.42 (2H, m), 6.64 (1H, d, J = 3.0 Hz), 6.69-6.78 (1H, m), 6.93-7.03 (2H, m), 7.16 (1H, d, J = 8.0 Hz), 7.31 (1H, t, J = 8.0 Hz), 7.44 (1H, dd, J = 2.5 Hz, 8.6 Hz) , 7.53 (1H, d, J = 2.5 Hz), 7.90 (1H, d, J = 3.0 Hz), 8.67 (1H, s), 8.79 (1H, t, J = 5.6 Hz), 9.85 (1H, s) .

Production of N- (2- {4- [(4. {{{{3- [{3- [(E) -2-cyclopropylvinyl] phenoxy} -3-methylphenyl) amino] -5H-pyrrolo [3] hydrochloride 2-d] pyrimidin-5-yl.} Ethyl) -2- (methylsulfonyl) acetamide (i) Production of 1-. { 3- [2-cyclopropylvinyl] phenoxy} -2-methy1-4-nitrobenzene When using (cyclopropylmethyl) triphenylphosphonium bromide (1.86 g), tetrahydrofuran (30 ml), 1.6 M solution of n-butyllithium / hexane (3.5 ml) and 3- (2-methyl-4-nitrophenoxy) benzaldehyde (1.00 g) and in the same manner as in Example E-26 ( ii), the title compound (1.15 g, E / Z = about 1/2) was obtained as a yellow oil. VL-NMR (CDC13) d: 0.43-0.56 (2H, m), 0.76-0.89 (2H, m), 1.50-1.63 (0.33H, m), 1.75-1.91 (0.67H, m), 2.40 (1H, s), 2. 41 (2H, s), 5.10 (0.67H, dd, J = 10 Hz, 11.5 Hz), 5.72 (0.33H, dd, J = 8.9 Hz, 15.7 Hz), 6.30 (0.67H, d, J = 11.5 Hz), 6.43 (0.33H, d, J = 15.7 Hz), 6.76 (0.33H, d, J = 9.0 Hz), 6.80 (0.67H, d, J = 9.0 Hz), 6.79-6.84 (0.33H, m), 6.84-6.90 (0.67H, m), 6.96 (0.33H, t, J = 1.9 Hz), 7.09 (0.67H, t, J = 1.9 Hz), 7.13 (0.33H, d, J = 8.0 Hz), 7.27 (0.67H, d, J = 8.0 Hz), 7.30 (0.33H, t, J = 8.0 Hz ), 7.36 (0.67H, t, J = 8.0 Hz), 7.93-8.02 (1H, m), 8.09 (1H, m). (ii) Production of l-. { 3 - [(E) -2-cyclopropylvinyl] phenoxy} -2-methyl-4-nitrobenzene When using 1-. { 3- [2-cyclopropylvinyl] phenoxy} -2-methyl-4-nitrobenzene (1.14 g), tetrahydrofuran (25 ml), diphenyl disulfide (172 mg) and 2.2 '-azobis (butyronitrile) (134 mg) and in the same manner as in Example E-26 (iv), the title compound (734 mg) was obtained in the form of an orange oil. XH-NMR (CDCl3) d: 0.47-0.55 (2H, m), 0.79-0.89 (2H, m), 1.50-1.63 (1H, m), 2.41 (3H, s), 5.73 (1H, dd, J = 9.0 Hz, . 7 Hz), 6.44 (1H, d, J = 15.7 Hz), 6.77 (1H, d, J = 9.0 Hz), 6.80-6.85 (1H, m), 6.97 (1H, t, J = 2.0 Hz), 7.14 (1H, d, J = 7.7 Hz), 7.30 (1H, t, J = 7.7 Hz), 7.98 (1H, dd, J = 2.2 Hz, 9.0 Hz), 8.15 (1H, d, J = 2.2 Hz). (iii) Production of 4-. { 3 - [(E) -2-cyclopropylvinyl] phenoxy} -3-methylaniline When using 1-. { 3- [(E) -2-cyclopropylvinyl] phenoxy} -2-methyl-4-nitrobenzene (729 mg), reduced iron (712 mg), calcium chloride (156 mg) and ethanol (18 ml) / water (2 ml) and in the same manner as in Example E- 18 (v), the title compound (352 mg) was obtained as a brown oil. XH-NMR (CDC13) d: 0.44-0.53 (2H, m), 0.75-0.85 (2H, m), 1.44-1.63 (1H, m), 2.10 (3H, s), 3.54 (2H, br s), 5.67 (1H, dd, J = 9.0 Hz, 15.7 Hz), 6.39 (1H, d, J = 15.7 Hz), 6.51 (1H, dd, J = 2.7 Hz, 8.7 Hz), 6.59 (1H, d, J = 2.7 Hz), 6.61-6.67 (1H, m), 6.75-6.82 (2H, m), 6.92 (1H, d, J = 7.8 Hz), 7.14 (1H, t, J = 7.8 Hz). (iv) Production of (2- {4- [(4- {3- [(E) -2-cyclopropylvinyl] phenoxy} -3-methylphenyl) amino] -5H-pyrrolo [3.2 -d] pyrimidin-5-yl.} ethyl) tert-butyl carbamate When [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] carbamate is used Butyl (352 mg), 4-. { 3 - [(E) -2-cyclopropylvinyl] phenoxy} 3-methylaniline (347 mg) and isopropyl alcohol (15 ral) and in the same manner as in Example E-27 (i), the title compound (540 mg) was obtained in the form of a white solid. Vl-NMR (CDCI3) d: 0.47-0.55 (2H, m), 0.75-0.87 (2H, m), 1.46 (9H, s), 1.50-1.61 (1H, m), 2.23 (3H, s), 3.43 -3.56 (2H, m), 4.39-4.54 (2H, ra), 4.98 (1H, t, J = 5.9 Hz), 5.71 (1H, dd, J = 9.0 Hz, 15.7 Hz), 6.41 (1H, d, J = 15.7 Hz), 6.59 (1H, d, J = 3.2 Hz), 6.75 (1H, dd, J = 1.6 Hz, 8.2 Hz), 6.87-7.01 (3H, m), 7.12-7.23 (2H, m) , 7.57-7.71 (2H, m), 8.31 (1H, br s), 8.50 (1H, s). (v) Production of 5- (2-aminoethyl) -N- (4-. {3 - [(E) -2-cyclopropylvinyl] phenoxy] -3-methylphenyl) -5H-pyrrolo dihydrochloride [3, 2-d] pyrimidin-4-amine When using (2- {4- [(4- {3- [(E) -2-cyclopropylvinyl] phenoxy} -3-methylphenyl) amino] -5H Pyrrolo [3,2-d] pyrimidin-5-yl.} ethyl) tert-butyl carbamate (536 rag), 6 N hydrochloric acid (1 ml) and ethanol (4 ml) and in the same manner as in Example E-27 (ii), the title compound (399 mg) was obtained as a yellow solid. XH-NMR (DMSO-de) d: 0.47-0.55 (2H, m), 0.74-0.84 (2H, m), 1.49-1.64 (1H, m), 2.21 (3H, s), 3.21-3.34 (2H. m), 5.02 (2H, t, J = 6.2 Hz), 5.85 (1H, dd, J = 9.4 Hz, 15.7 Hz), 6. 44 (1H, d, J = 15.7 Hz), 6.66-6.74 (2H, m), 6.90-6.99 (2H, m), 7.09 (1H, d, J = 7.8 Hz), 7.27 (1H, t, J = 7.8 Hz), 7.38 (1H, dd, J = 2.6 Hz, 8.7 Hz), 7.48 (1H, d, J = 2.5 Hz), 8.04 (1H, d, J = 3.3 Hz), 8.37 (3H, br s), 8.66 (1H, s), 9.93 (1H, br s). (vi) Production of N- (2- {4- [(4. {[3- ({E} -2-cyclopropylvinyl] phenoxy} -3-methylphenyl) amino] -5H-pyrrolohydrochloride [3,2-d] pyrimidin-5-yl.} Ethyl) -2- (methylsulfonyl) acetamide When using 5- (2-aminoethyl) -N- (4-. {3- [3- E] dihydrochloride] -2-cyclopropylvinyl] phenoxy] -3-methylphenyl) -5H-pyrrolo [3,2-d] pyriraidin-4-amine (149 mg), methylsulfonylacetic acid (85.1 mg), tetrahydrofuran (0.8 ml) / N, N-dimethylformamide (0.8 ml), 1-hydroxybenzotriazole (118 mg), triethylamine (0.4 ml), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (178 mg) and 4 N hydrogen chloride solution / acetate ethyl acetate and the mixture so that in Example E-27 (iii), the title compound (123 mg) was obtained as yellow crystals. XH-NMR (DMS0-d6) d: 0.47-0.56 (2H, m), 0.74-0.86 (2H, m), 1.47-1.66 (1H, m), 2.22 (3H, s), 3.06 (3H, ra) , 3.49-3.63 (2H, m), 4.06 (2H, s), 4.69 (2H, t, J = 6.2 Hz), 5.86 (1H, dd, J = 9.2 Hz, 15.8 Hz), 6.44 (1H, d, J = 15.8 Hz), 6.64 (1H, d, J = 3.0 Hz), 6.70 (1H, dd, J = 1.8 Hz, 8.0 Hz), 6.90-7.00 (2H, m), 7.10 (1H, d, J = 8.0 Hz), 7.28 (1H, t, J = 8.0 Hz), 7.43 (1H, dd, J = 2.5 Hz, 8.6 Hz), 7.52 (1H, d, J = 2.5 Hz), 7.90 (1H, d, J = 3.0 Hz), 8.66 (1H, s), 8.79 (1H, t, J = 5.7 Hz), 9.85 (1H, br s).

Example E-29 Production of N- hydrochloride. { 2- [4- ( { 4- [3- (1-cyanocyclopropyl) phenoxy] -3-methylphenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide (i) Production of. { 2- [4- ( { 4- [3- (1-cyanocyclopropyl) phenoxy] -3-methylphenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} tert-butyl carbamate When using [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (350 mg), 1- [3- (4 amino-2-methylphenoxy) phenyl] cyclopropanecarbonitrile (351 rag) and isopropyl alcohol (10 ml) and from the same manner as in Example E-27 (i), the title compound (590 mg) was obtained in the form of a white powder. XH-NMR (CDC13) d: 1.35-1.43 (2H, m), 1.47 (9H, s), 1.66-1.75 (2H, m), 2.21 (3H, s), 3.43-3.57 (2H, ra), 4.41 -4.53 (2H, m), 5.01 (1H, t, J = 5.8 Hz), 6.59 (1H, d, J = 3.2 Hz), 6. 76-6.83 (1H, m), 6.86-6.95 (2H, m), 6.98-7.05 (1H, m), 7.16 (1H, d, J = 3.2 Hz), 7.24 (1H, t, J = 7.9 Hz), 7.58-7.76 (2H, m), 8.35 (1H, br s), 8.50 (1H, s). (ii) Production of dihydrochloride of 1- [3- (4- { [5- (2- aminoethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino} -2-methylphenoxy) phenyl] cyclopropanecarbonitrile When using. { 2- [4- ( { 4- [3- (1-cyanocyclopropyl) phenoxy] -3-methylphenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} tert-butyl carbamate (586 mg), 6 N hydrochloric acid (1 ml) and ethanol (6 ml) and in the same manner as in Example E-27 (ii), the title compound (478 mg) was obtained in the form of white crystals. XH-NMR (DMSO-d6) d: 1.47-1.58 (2H, ra), 1.71-1.82 (2H, m), 2.21 (3H, s), 3.19-3.49 (2H, m), 4.98 (2H, t, J = 6.1 Hz), 6.71 (1H, d, J = 3.0 Hz), 6.80 (1H, dd, J = 2.3 Hz, 7.7 Hz), 6.98 (1H, t, J = 2.3 Hz), 7.01 (1H, d , J = 8.7 Hz), 7.04-7.09 (1H, m), 7.39 (1H, t, J = 7.7 Hz), 7.42 (1H, dd, J = 2.3 Hz, 8.7 Hz), 7.51 (1H, d, J = 2.3 Hz), 8.01 (1H, d, J = 3.0 Hz), 8.26 (3H, br s), 8.66 (1H, s), 9.81 (1H, br s). (iii) Production of N- hydrochloride. { 2- [4- ( { 4- [3- (1-cyanocyclopropyl) phenoxy] -3-methylphenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide When using 1- [3- (4. {[[5- (2-aminoethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino dihydrochloride]. -2-methylphenoxy) phenyl] cyclopropanecarbonitrile (150 mg), methylsulfonylacetic acid (65.2 mg), tetrahydrofuran (0.8 ml) / N, N-dimethylformamide (0.8 ml), 1-hydroxybenzotriazole (82.1 mg), triethylamine (0.4 ml), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (117 mg) and solution of 4 N hydrogen chloride / ethyl acetate and in the same manner as in Example E-27 (iii), the title compound (133 mg) was obtained as a pale yellow powder. Vl-NMR (DMSO-d6) d: 1.49-1.57 (2H, m 1.73-1.81 (2H, m), 2.21 (3H, s), 3.05 (3H, s), 3.49-3.60 (2H, m), 4.06 (2H, s), 4.70 (2H, t, J = 6.2 Hz), 6.63 ( 1H, d, J = 3.0 Hz), 6.79 (1H, dd, J = 2.5 Hz, 8.0 Hz), 6.98 (1H, t, J = 2.5 Hz), 7.01 (1H, d, J = 8.0 Hz), 7.03 -7.09 (1H, m), 7.38 (1H, t, J = 8.0 Hz), 7.46 (1H, dd, J = 2.6 Hz, 8.7 Hz), 7.54 (1H, d, J = 2.6 Hz), 7.90 (1H , d, J = 3.0 Hz), 8.66 (1H, s),! 1 (1H, t, J = 5.5 Hz), 9.87 (1H, s).

Production of N- hydrochloride. { 2- [4- ( { 3-Chloro-4- [3- (1-cyanocyclopropyl) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide (i) Production of 1- [3- (2-chloro-4-nitrophenoxy) phenyl] cyclopropanecarbonitrile When using 3-chloro-4-fluoronitrobenzene (362 rag), 1- (3-hydroxyphenyl) Cyclopropancarbonitrile (350 mg), carbonate of potassium (493 mg) and N, N-dimethylformamide (7 ml) and in the same manner as in Example E-18 (iv), the title compound (650 mg) was obtained as a white powder. VL-NMR (CDC13) d: 1.39-1.48 (2H, m), 1.74-1.84 (2H, m), 6.90 (1H, d, J = 9 Hz), 6.95-7.01 (1H, m), 7.04 (1H , t, J = 2.0 Hz), 7.20 (1H, d, J = 8.0 Hz), 7.42 (1H, t, J = 8.0 Hz), 8.08 (1H, dd, J = 2.6 Hz, 9.0 Hz), 8.40 ( 1H, d, J = 2.6 Hz). (ii) Production of 1- [3- (4-amino-2-chlorophenoxy) phenyl] cyclopropanecarbonitrile When using 1- [3- (2-chloro-4-nitrophenoxy) phenyl] cyclopropanecarbonitrile (643 mg), reduced iron (570) mg), calcium chloride (113 mg) and ethanol (18 ml) / water (2 ml) and in the same manner as in Example E-18 (v), the title compound (508 mg) was obtained in of a yellow oil. XH-NMR (CDCl3) d: 1.34-1.41 (2H, ra), 1.66-1.74 (2H, m), 3.68 (2H, br s), 6.57 (1H, dd, J = 2.8 Hz, 8.5 Hz), 6.68 - 6.74 (1H, m), 6.78 (1H, d, J = 2.8 Hz), 6.80 (1H, t, J = 2.1 Hz), 6.88 (1H, d, J = 8.5 Hz), 6.95-7.01 (1H, m), 7.23 (1H, t, J = 8.0 Hz). (iii) Production of. { 2- [4- ( { 3-Chloro-4- [3- (1-cyanocyclopropyl) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} tert-butyl carbamate When using [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (350 mg), 1- [3- (4 -amino-2- chlorophenoxy) phenyl] cyclopropanecarbonitrile (349 mg) and isopropyl alcohol (8 ml) and in the same manner as in Example E-27 (i), the title compound (632 mg) was obtained as a white powder. V -? - NMR (CDC13) d: 1.36-1.45 (2H, m), 1.50 (9H, s), 1. 66-1.77 (2H, m), 3.43-3.57 (2H, m), 4.40-4.55 (2H, m), 5.07 (1H, t, J = 5.5 Hz), 6.60 (1H, d, J = 3.0 Hz) , 6.84 (1H, dd, J = 2.2 Hz, 8.0 Hz), 6.91 (1H, t, J = 2.2 Hz), 7.03 (1H, d, J = 9.1 Hz), 7.05-7.11 (1H, m), 7.18 (1H, d, J = 3.0 Hz), 7.28 (1H, t, J = 8.0 Hz), 7.87 (1H, dd, J = 2.7 Hz, 9.1 Hz), 8.02 (1H, d, J = 2.7 Hz), 8.51 (1H, s), 8.58 (1H, s). (iv) Production of 1- [3- (4. {[[5- (2-aminoethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino dihydrochloride] -2- chlorophenoxy) phenyl] cyclopropanecarbonitrile It was dissolved. { 2- [4- ( { 3-Chloro-4- [3- (1-cyanocyclopropyl) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyriraidin-5-yl] ethyl} tert-butyl carbamate (627 mg) in a mixed solvent of ethanol (7 ml) / tetrahydrofuran (1 ml), 6N hydrochloric acid (1 ml) was added, and the mixture was stirred at 50 ° C for 14 h. The reaction mixture was concentrated under reduced pressure, the residue was dissolved in concentrated hydrochloric acid (2 ml), and the mixture was stirred at room temperature for 10 min. Ethanol was added to the reaction mixture and the resulting precipitate was collected by filtration to give the title compound (433 mg) in the form of a yellow powder. Vl-NMR (DMSO-d6) d: 1.48-1.60 (2H, m), 1.72-1.84 (2H, m), 3.21-3.37 (2H, m), 5.01 (2H, t, J = 6.4 Hz), 6.74 (1H, d, J = 3.0 Hz), 6.85 (1H, dd, J = 8.0 Hz, 2.2 Hz), 7.03 (1H, t, J = 2.2 Hz), 7.08-7.15 (1H, m), 7.23 (1H , d, J = 8.9 Hz), 7.42 (1H, t, J = 8.0 Hz), 7.61 (1H, dd, J = 2.5 Hz, 8.9 Hz), 7.90 (1H, d, J = 2.5 Hz), 8.05 ( 1H, d, J = 3.0 Hz), 8.29 (3H, br s), 8.71 (1H, s), 10.05 (1H, br s). (v) Production of N- hydrochloride. { 2- [4- ( { 3-Chloro-4- [3- (1-cyanocyclopropyl) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide When using 1- [3- (4. {[[5- (2-aminoethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino dihydrochloride]. -2-chlorophenoxy) phenyl] cyclopropanecarbonitrile (149 mg), methylsulfonylacetic acid (60.0 mg), tetrahydrofuran (0.8 ml) / N, N-dimethylformamide (0.8 ml), 1-hydroxybenzotriazole (77.4 mg), triethylamine (0.4 ml), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (110 mg) and 4 N hydrogen chloride solution / ethyl acetate and in the same manner as in Example E-27 (iii), the title compound (131 mg) was obtained as a white powder. XH-NMR (DMSO-d6) d: 1.50-1.60 (2H, m), 1.74-1.83 (2H, m), 3.06 (3H, s), 3.54 (2H, q, J = 6.0 Hz), 4.06 (2H , s), 4.70 (2H, t, J = 6.0 Hz), 6.66 (1H, d, J = 3.0 Hz), 6.85 (1H, dd, J = 2.2 Hz, 8.0 Hz), 7.02 (1H, t, J = 2.2 Hz), 7.08-7.14 (1H, ra), 7.24 (1H, d, J = 9.0 Hz), 7.41 (1H, t, J = 8.0 Hz), 7.64 (1H, dd, J = 2.5 Hz, 9.0 Hz), 7.92 (1H, d , J = 2.5 Hz), 7. 93 (1H, d, J = 3.0 Hz; 71 (1H, 77 (1H, t, J = 5 Hz), 9.91 (1H, br s) Example E-31 Production of N- (tert-butyl) -1- [3- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. phenoxy) phenyl] cyclopropanecarboxamide (i) Production of N- (tert-butyl) -1- (3-methoxyphenyl) cyclopropanecarboxamide l- (3-methoxyphenyl) cyclopropanecarboxylic acid (400 mg) was dissolved in tetrahydrofuran (6 ml ), a catalytic amount of N, N-dimethylformamide and thionyl chloride (0.4 ml) were added, and the mixture was stirred at room temperature for 6 h. The reaction mixture was concentrated under reduced pressure, and the residue was dissolved in tetrahydrofuran (4 ml). The solution was added dropwise to a mixture cooled to 0 ° C of tert-butylamine (0.25 ml), triethylamine (1 ml) and tetrahydrofuran (3 ral), and the mixture was stirred at room temperature for 2 h. HE added water to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 95: 5-6: 33: 33) to give the title compound (477 mg) as a pale yellow oil . 1 H-NMR (CDC13) d: 0.97 (2H, q, J = 3.7 Hz), 1.22 (9H, s), 1.52 (2H, q, J = 3.7 Hz), 3.82 (3H, s), 5.22 (1H, br s), 6.81-6.87 (1H, m ), 6.90-6.94 (1H, m), 6.95-7.01 (1H, m), 7.27 (1H, t, J = 7.9 Hz). (ii) Production of N- (tert-butyl) -1- (3-hydroxyphenyl) cyclopropanecarboxamide When using N- (tert-butyl) -1- (3-methoxyphenyl) cyclopropanecarboxamide (470 mg), benzotrifluoride (10 ml) and 1N boron tribromide solution / dichloromethane (4 ml) and in the same manner as in Example E-18 (iii), the title compound (245 mg) was obtained as a white powder . XH-NMR (CDCI3) d: 0.95-1.04 (2H, m), 1.22 (9H, s), 1.50-1.58 (2H, m), 5.36 (1H, br s), 6.13 (1H, br s), 6.76 -6.88 (2H, m), 6.90-6.98 (1H, m), 7.19-7.29 (1H, ra). (iii) Production of N- (tert-butyl) -1- [3- (2-chloro-4-nitrophenoxy) phenyl] cyclopropanecarboxamide When using N- (tert-butyl) -1- (3-hydroxyphenyl) cyclopropanecarboxamide (242 mg), 3-chloro-4-fluoronitrobenzene (237 mg), potassium carbonate (223 mg) and N, N-dimethylformamide (5 mg). ml) and in the same manner as in Example E-18 (iv), the title compound (397 mg) was obtained as white crystals. XH-NMR (CDC13) d: 0.96-1.01 (2H, m), 1.23 (9H, s), 1.52-1.59 (2H, m), 5.08 (1H, br s), 6.88 (1H, d, J = 9.1 Hz), 6.98-7.04 (1H, m), 7.08-7.13 (1H, m), 7.27-7.32 (1H, m), 7.43 (1H, t, J = 8.0 Hz), 8.07 (1H, dd, J = 2.8 Hz, 9.1 Hz), 8.40 (1H, d, J = 2.8 Hz). (iv) Production of 1- [3- (4-amino-2-chlorophenoxy) phenyl] -N- (tert-butyl) cyclopropanecarboxamide N- (tert-butyl) -1- [3- (2-chloro- 4-nitrophenoxy) phenyl] cyclopropanecarboxamide (392 mg) in a mixed solvent of methanol (7.5 ml) / ethyl acetate (7.5 ml), 5% activated carbon-platinum (44.4 mg) was added and the mixture was stirred under a hydrogen atmosphere at room temperature for 1.5 h. The reaction mixture was filtered through celite, and the filtrate was concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (hexane: ethyl acetate = 95: 5-50:50) to give the title compound (324 mg) as a colorless oil. Vl-NMR (CDCI3) d: 0.91-0.98 (2H, m), 1.21 (9H, s), 1. 45-1.52 (2H, m), 3.70 (2H, s), 5.17 (1H, br s), 6.59 (1H, dd, J = 2.7 Hz, 8.6 Hz), 6.79 (1H, d, J = 2.7 Hz) , 6.81-6.87 (2H, m), 6.91 (1H, d, J = 8.6 Hz), 6.99-7.06 (1H, m), 7.21-7.31 (1H, m). (v) Production of N- (tert-butyl) -1- [3- (2-chloro-4- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4 -yl] amino.}. phenoxy) phenyl] cyclopropanecarboxamide When using 2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethyl benzoate (120 mg), 1- [3- (4-amino-2-chlorophenoxy) phenyl] -N- (tert-butyl) cyclopropanecarboxamide (160 mg), isopropyl alcohol (4 ml) and 1 N aqueous solution of sodium hydroxide (1.5 ml) and in the same manner as in Example E-18 (vi), the title compound (155 mg) was obtained as a white powder. Vl-NMR (CDC13) d: 0.96 (2H, q, J = 3.7 Hz), 1.21 (9H, s), 1.49 (2H, q, J = 3.7 Hz), 4.14-4.22 (2H, m), 4.37- 4.46 (2H, m), 5.19 (1H, s), 6.06 (1H, br s), 6.19 (1H, d, J = 3.2 Hz), 6.89-6.98 (2H, m), 7.02 (1H, d, J = 3.2 Hz), 7.04-7.11 (2H, m), 7.31 (1H, t, J = 7.8 Hz), 7.52 (1H, dd, J = 2.5 Hz, 8.7 Hz), 7.81 (1H, d, J = 2.5 Hz), 8.29 (1H, s), 9.58 (1H, s).

Example G-1 Production of N- [1- (3-fluorobenzyl) -lH-indazol-5-yl] -5H-pyrrolo [3,2-d] pyrimidin-4-amine hydrochloride A solution of 4-chloro-5H-pyrrolo [ 3, 2-d] pyrimidine (153 mg) and 1- (3-fluorobenzyl) -lH-indazol-5-amine (362 mg) in N, N-dimethylformamide (2 ml) was stirred at 120 ° C for 2.5 h . The reaction mixture was cooled to room temperature, ethyl acetate (30 ml) was added and the mixture was stirred at room temperature for 30 min. The resulting crystals were collected by filtration, washed with ethyl acetate and dried under reduced pressure to give the title compound (361 mg) as crystals. VL-NMR (DMSO-de) d: 5.70 (2H, s), 6.57 (1H, d, J = 2 Hz), 7.00-7.20 (3H, m), 7.36 (1H, m), 7.70-7.90 (3H , m), 8.17 (1H, s), 8.41 (1H, m), 8.59 (1H, s), 10.97 (1H, br s), 12.58 (1H, br s).

Example G-2 Production of 2- [2- (4- { [1- (3-Fluorobenzyl) -1H-indazol-5-yl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl ) ethoxy] ethanol A mixture of 2- [2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethoxy] ethyl benzoate (150 mg), 1- (3-fluorobenzyl) -lH-indazol-5-amine (156 mg) and l-methyl-2-pyrrolidone (0.863 ml) was stirred with heating at 140 ° C for 2 h. The reaction mixture was diluted with ethyl acetate (80 ml), and the organic layer was washed with aqueous sodium bicarbonate (30 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 70: 30-> 0: 100), and the object fractions were concentrated under reduced pressure. The residue obtained was dissolved in methanol (1.89 ml), 1N aqueous solution of sodium hydroxide (0.433 ml) was added, and the mixture was stirred at room temperature for 2 h. 1 N Hydrochloric acid (0.433 ml) was added to the mixture, and the mixture was diluted with ethyl acetate (80 ml), and the organic layer was washed with Saturated brine (30 ml), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (ethyl acetate: methanol = 100: 0- »90: 10) and crystallized from isopropyl ether to give the title compound (153 mg) as crystals. XH-NMR (DMSO-d6) d: 3.50 (4H, br s), 3.84 (2H, t, J = 4 Hz), 4.64 (2H, t, J = 4 Hz), 4.69 (1H, m), 5.69 (2H, s), 6.47 (1H, d, J = 3 Hz), 7.00-7.20 (3H, m), 7.36 (1H, m), 7.53 (1H, d, J = 9 Hz), 7.60-7.70 ( 2H, m), 8.05 (1H, s), 8.09 (1H, s), 8.23 (1H, s), 8.76 (1H, br s). Example G-3 Production of N- [2- (4- { [1- (3-Fluorobenzyl) -1H-indazol-5-yl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl ) ethyl] -2- (methylsulfonyl) acetamide (i) Production of [2- (4- { [1- (3-fluorobenzyl) -1H-indazol-5-yl] amino.}. -5H-pyrrolo [ 3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate A solution of [2- (4-chloro-5H-pyrrolo [3,2-d] pyriraidin-5-yl) ethyl] carbamate of tert-butyl (0.5 g) and l- (3- fluorobenzyl) -lH-indazol-5-amine (608 mg) in isopropyl alcohol (5 ml) was stirred at 80 ° C for 12 h. Aqueous sodium bicarbonate (30 ml) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (80 ml). The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, hexane: ethyl acetate = 7: 3-> ethyl acetate) to give the title compound (820 mg ) in the form of colorless crystals. Vl-NMR (CDC13) d: 1.44 (9H, s), 3.50 (2H, m), 4.46 (2H, m), 5.07 (1H, m), 5.58 (2H, s), 6.57 (1H, d, J = 3 Hz), 6.80-7.00 (3H, m), 7.14 (1H, d, J = 3 Hz), 7.20-7.40 (2H, m), 7.74 (1H, dd, J = 2 Hz, 9 Hz), 7.99 (1H, s), 8.05 (1H, d, J = 1 Hz), 8.45 (1H, s), 8.53 (1H, br s). (ii) Production of 5- (2-aminoethyl) -N- [1- (3-fluorobenzyl) -lH-indazol-5-yl] -5H-pyrrolo [3,2-d] pyrimidin-4-amine trichlorohydrate A mixture of [2- (4- { [1- (3-Fluorobenzyl) -1H-indazol-5-yl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (780 mg), 2 N hydrochloric acid (11.1 ml) and tetrahydrofuran (22.2 ml) was stirred at 60 ° C for 20 h. The solvent was evaporated under reduced pressure, ethanol was added to the mixture, and the mixture was then concentrated. He Precipitated powder was collected by filtration and washed with isopropyl ether to give the title compound (668 mg) as a pale yellow powder. XH-NMR (DMSO-dg) d: 3.32 (2H, m), 5.08 (2H, m), 5.74 (2H, s), 6.72 (1H, d, J = 3 Hz), 7.00-7.20 (3H, m ), 7.38 (1H, m), 7.52 (1H, dd, J = 2 Hz, 9 Hz), 7.80 (1H, d, J = 9 Hz), 7.91 (1H, d, J = 2 Hz), 8.07 (1H, m), 8.20 (1H, s), 8.45 (3H, br s), 8.60 (1H, s). (iii) Production of N- [2- (4-. {[1- (3-fluorobenzyl) -lH-indazol-5-yl] amino.}. -5H-pyrrolo [3,2-d] pyrimidine- 5-yl) ethyl] -2- (methylsulfonyl) acetamide A mixture of 5- (2-aminoethyl) -N- [1- (3-fluorobenzyl) -1H-indazol-5-yl] -5H-pyrrolo trichlorohydrate [ 3,2-d] pyrimidine-4-araine (183 mg), methylsulfonylacetic acid (74.2 rag), l-ethyl-3- (3-dimethylareneopropyl) carbodiimide hydrochloride (103 mg), 1-hydroxybenzotriazole (72.5 mg), triethylamine (0.15 ml) and N, N-dimethylformamide (6.9 ml) was stirred at room temperature for 16 h. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate-ethyl acetate: methanol = 90:10) and crystallized in isopropyl ether to give the title compound (134 mg) as crystals. XH-NMR (DMSO-dg) d: 3.07 (3H, s), 3.48 (2H, q, J = 6 Hz), 4.04 (2H, s), 4.56 (2H, t, J = 6 Hz), 5.69 (2H, s), 6.45 (1H, d, J = 3 Hz), 7.00-7.20 (3H, m), 7.30-7.40 (1H, m), 7.57 (2H, m), 7.68 (1H, d, J = 9 Hz), 7.95 (1H, m), 8.10 (1H, s), 8. 21 (1H, s), 8.58 (1H, br s), 8.65 (1H, t, J = 6 Hz). Example G-4 Production of N- [1- (3-fluorobenzyl) -lH-indol-5-yl] -5H-pyrrolo [3,2-d] pyrimidin-4-amine hydrochloride A solution of 4-chloro-5H-pyrrolo [ 3, 2-d] pyrimidine (153 mg) and 1- (3-fluorobenzyl) -lH-indol-5-amine (360 mg) in N, N-dimethylformamide (2 ml) was stirred at 120 ° C for 2 h. The reaction mixture was cooled to room temperature, thereto was added ethyl acetate (30 ml), and the mixture was stirred at room temperature for 30 min. The resulting crystals were collected by filtration, washed with ethyl acetate and dried under reduced pressure to give the title compound (377 mg) as crystals.

Vl-NMR (DMSO-dg) d: 5.46 (2H, s), 6.53 (2H, d, J = 3 Hz), 7.05 (3H, m), 7.36 (1H, m), 7.49 (2H, m), 7.56 (1H, d, J = 3 Hz), 7.79 (1H, br s), 8.16 (1H, br s), 8.51 (1H, s), 10.61 (1H, br s), 12.45 (1H, br s) . Example G-5 Production of N- [2- (4- { [1- (3-Fluorobenzyl) -1H-indazol-5-yl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl ) ethyl] -3-hydroxy-3-methylbutanamide A mixture of 5- (2-aminoethyl) -N- [1- (3-fluorobenzyl) -lH-indazol-5-yl] -5H-pyrrolo trichlorohydrate [3, 2-d] pyrimidin-4-amine (183 mg), 3-hydroxy-3-methylbutanoic acid (0.058 ml), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (103 mg), 1-hydroxybenzotriazole ( 72.5 mg), triethylamine (0.15 ml) and N, N-dimethylformamide (6.9 ml) was stirred at room temperature for 4 h. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by column chromatography on silica gel (eluent, ethyl acetate-> ethyl acetate: methanol = 85:15) and crystallized from isopropyl ether to give the title compound (100 mg) as crystals. Vl-NMR (DMSO-d6) d: 1.12 (6H, s), 2.20 (2H, s), 3.44 (2H, q, J = 7 Hz), 4.52 (2H, t, J = 7 Hz), 4.69 ( 1H, s), 5.69 (2H, s), 6.44 (1H, d, J = 3 Hz), 7.00-7.20 (3H, m), 7.30-7.40 (1H, m), 7.50-7.70 (3H, m) , 8.00 (1H, d, J = 2 Hz), 8.09 (1H, s), 8.20 (1H, s), 8.23 (1H, t, J = 7 Hz), 8.76 (1H, br s). Example G-6 Production of 2- [2- (4- { [1- (3-Fluorobenzyl) -1H-indol-5-yl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl ) ethoxy] ethanol A mixture of 2- [2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethoxy] ethyl benzoate (150 mg), 1- (3-fluorobenzyl) -lH-indole-5-araine (155 mg) and l-methyl-2-pyrrolidone (0.863 ml) was stirred with heating at 140 ° C for 2 h. The reaction mixture was diluted with ethyl acetate (80 ml) and washed with aqueous sodium bicarbonate (30 ml). The organic layer was separated, dried over sodium sulfate anhydrous magnesium, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 70: 30-> 0: 100: ethyl acetate: methanol = 95: 5), and the object fractions were concentrated under reduced pressure. The residue obtained was dissolved in methanol (1.89 ml), 1N aqueous solution of sodium hydroxide (0.433 ml) was added, and the mixture was stirred at room temperature for 2 h. 1 N Hydrochloric acid (0.433 ml) was added to the mixture, and the mixture was diluted with ethyl acetate (80 ml). The organic layer was washed with saturated brine (30 ml), dried over magnesium sulfate and concentrated under reduced pressure. The residue was subjected to silica gel column chromatography (ethyl acetate: methanol = 100: 0- »90: 10) and crystallized from isopropyl ether / ethyl acetate to give the title compound (107 mg) as of crystals. XH-NMR (DMSO-dg) d: 3.49 (4H, br s), 3.83 (2H, t, J = 4 Hz), 4.61 (2H, t, J = 4 Hz), 4.67 (1H, t, J = 4 Hz), 5.45 (2H, s), 6.44 (1H, dd, J = 1.5 Hz, 3 Hz), 6.47 (1H, d, J = 3 Hz), 6.90-7.10 (3H, m), 7.25 (1H , d, J = 9 Hz), 7.3-7.5 (2H, m), 7.51 (1H, d, J = 3 Hz), 7.59 (1H, d, J = 3 Hz), 7.81 (1H, s), 8.17 (1H, s), 8.58 (1H, br s).

Production of N- [2- (4- { [1- (3-Fluorobenzyl) -1H-indol-5-yl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl. ) ethyl] -3-hydroxy-3-methylbutanamide (i) Production of [2- (4- { [1- (3-Fluorobenzyl) -1H-indol-5-yl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate A solution of [2- (4-chloro-5H-pyrrolo [3,2-d] pyriraidin-5-yl) ethyl] carbamate of tert-butyl (0.5 g) and l- (3-fluorobenzyl) -lH-indol-5-amine (606 mg) in isopropyl alcohol (5 ml) was stirred at 80 ° C for 12 h. Aqueous sodium bicarbonate (30 ml) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (80 ml). The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, hexane: ethyl acetate = 7: 3- ^ ethyl acetate-> ethyl acetate: ethanol = 95: 5) to give the title compound (840 mg) as colorless crystals.

VL-NMR (CDCI3) d: 1.42 (9H, s), 3.45 (2H, ra), 4.38 (2H, t, J = 7 Hz), 5.17 (1H, m), 5.29 (2H, s), 6.51 ( 1H, dd, J = 1 Hz, 3 Hz), 6.53 (1H, d, J = 3 Hz), 6.78 (1H, d, J = 9 Hz), 6.80-7.00 (2H, m), 7.10 (2H, t, J = 3 Hz), 7.18-7.30 (2H, m), 7.47 (1H, d, J = 9 Hz), 7.89 (1H, br s), 8.20 (1H, br s), 8.43 (1H, s ). (ii) Production of 5- (2-aminoethyl) -N- [1- (3-fluorobenzyl) -lH-indol-5-yl] -5H-pyrrolo [3,2-d] pyrimidin-4-amine dihydrochloride A mixture of [2- (4- { [1- (3-fluorobenzyl) -lH-indol-5-yl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (830 mg), 2N hydrochloric acid (11.8 ml) and tetrahydrofuran (23.6 ml) was stirred at 60 ° C for 20 h. The solvent was evaporated under reduced pressure, ethanol was added to the mixture, and the mixture was then concentrated. The precipitated powder was collected by filtration and washed with isopropyl ether to give the title compound (828 mg) as a pale yellow powder. Vl-NMR (DMSO-d6) d: 3.27 (2H, m), 5.07 (2H, m), 5.43 (2H, s), 6.50-6.70 (2H, m), 6.80-7.30 (4H, m), 7.37 (1H, m), 7.68 (1H, m), 7.86 (1H, s), 8.04 (1H, d, J = 3 Hz), 8.44 (1H, s), 8.50 (3H, br s), 8.55 (1H , s), 10.01 (1H, br s). (iii) Production of N- [2- (4-. {[1- (3-fluorobenzyl) -1H-indol-5-yl] amino.}. -5H-pyrrolo [3,2-d] pyrimidine- 5-yl) ethyl] -3-hydroxy-3-butylbutanamide A mixture of 5- (2-aminoethyl) -N- [1- (3-fluorobenzyl) -lH-indol-5-yl] -5H-pyrrolo [3,2-d] pyrimidin-4-amine dihydrochloride (183 mg), 3-hydroxy-3-methylbutanoic acid (0.058 ml), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (103 mg), 1-hydroxybenzotriazole (72.5 mg), triethylamine (0.15 ml) and N , N-dimethylformamide (6.9 ml) was stirred at room temperature for 16 h. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate -> ethyl acetate: methanol = 85:15) and crystallized from isopropyl ether to give the compound of the title (43 mg) in the form of crystals. XH-NMR (DMSO-d6) d: 1.12 (6H, s), 2.20 (2H, s), 3.44 (2H, q, J = 7 Hz), 4.50 (2H, t, J = 7 Hz), 4.70 ( 1H, br s), 5.46 (2H, s), 6.41 (1H, d, J = 3 Hz), 6.47 (1H, d, J = 3 Hz), 6.9-7.2 (3H, m), 7.20-7.50 ( 3H, m), 7.52 (2H, t, J = 3 Hz), 7.76 (1H, s), 8.15 (1H, s), 8.19 (1H, t, J = 6 Hz), 8.57 (1H, br s) .

Example G-8 Production of 3-hydroxy-3-methyl-N- [2- (4. {[[1- (pyridin-2-ylmethyl) -lH-indol-5-yl] amino.}. -5H-pyrrolo [3 , 2-d] pyrimidin-5-yl) ethyl] butanamide (i) Production of 5-nitro-l- (pyridin-2-ylmethyl) -1H-indole To a solution of 5-nitroindole (1.62 g) and 2- (chloromethyl) pyridine hydrochloride (1.80 g) in N, N-dimethylformamide (20 ml) was added potassium carbonate (3.46 g) under cooling with ice, and the mixture was stirred at room temperature for 16 h. Under cooling with ice, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate / diisopropyl ether to give the title compound (2.05 g) as yellow crystals. VL-NMR (CDC13) d: 5.49 (2H, s), 6.75-6.80 (2H, m), 7.15-7.25 (1H, m), 7.32 (1H, d, J = 9.0 Hz), 7.36 (1H, d) , J = 3. 3 Hz), 7.58 (1H, dt, J = 2.1 Hz, 7.8 Hz), 8.07 (1H, dd, J = 2.1 Hz, 9.0 Hz), 8.55-8.65 (2H, m). (ii) Production of 1- (pyridin-2-ylmethyl) -lH-indol-5-amine To a solution of 5-nitro-l- (pyridin-2-ylmethyl) -1H-indole (507 mg) in ethyl acetate ethyl (10 ml) / methanol (2 ml) was added 5% activated carbon-platinum (84.5 mg) under a nitrogen atmosphere. The reaction mixture was stirred under an atmosphere of hydrogen at room temperature for 6 h. The activated carbon with platinum was filtered, and the filtrate was concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: hexane = 70: 30-> 100: 0) and then recrystallized from ethyl acetate / hexane to give the title compound (357 mg) as a whitish peach-colored powder. XH-NMR (CDC13) d: 3.48 (2H, br s), 5.38 (2H, s), 6.39 (1H, d, J = 3.0 Hz), 6.55-6.70 (2H, ra), 6.94 (1H, s) , 7.03 (1H, d, J = 8.7 Hz), 7.10-7.20 (2H, m), 7.49 (1H, t, J = 7.8 Hz), 8.57 (1H, d, J = 4.2 Hz). (iii) Production of [2- (4-. {[1- (pyridin-2-ylmethyl) -lH-indol-5-yl] amino.}. -5H-pyrrolo [3,2-d] pyrimidine- 5-yl) ethyl] tert-butyl carbamate A mixture of tert-butyl [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] carbamate (297 mg), 1- (pyridin-2-ylmethyl) -lH-indol-5-amine (246 mg) and isopropyl alcohol (5.0 ml) was stirred at 80 ° C for 16 h. Under cooling with ice, aqueous sodium bicarbonate was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: methanol = 100: 0-> 90: 10) to give the title compound (498 mg) as a colored powder pale purple. Vi-NMR (CDC13) d: 1.43 (9H, s), 3.45-3.55 (2H, m), 4. 35-4.45 (2H, m), 4.9-5.0 (1H, m), 5.45 (2H, s), 6.53 (1H, d, J = 3.0 Hz), 6.55 (1H, d, J = 3.0 Hz), 6.71 (1H, d, J = 8. 1 Hz), 7.10-7.30 (4H, m), 7.40-7.50 (1H, m), 7.52 (1H, dt, J = 1.8, 7.8 Hz), 7.90 (1H, s), 8.17 (1H, br s) , 8.44 (1H, s), 8.58 (1H, d, J = 4.2 Hz). (iv) Production of 5- (2-aminoethyl) -N- [1- (pyridin-2-ylmethyl) -lH-indol-5-yl] -5H-pyrrolo [3,2-d] pyrimidin-tetrachlorohydrate -amine A mixture of [2- (4-. {[1- (pyridin-2-yl-ethyl) -1H-indol-5-yl] amino.}. -5H-pyrrolo [3,2-d] pyrimidine- 5-yl) ethyl] tert-butyl carbamate (439 mg) and 10% hydrochloric acid (w / w) / methanol (5 ml) was stirred at 65 ° C for 18 h. The reaction mixture was concentrated under reduced pressure, and the precipitate was collected by filtration and washed with ether diethyl ester to give the title compound (422 mg) as pale green crystals. VL-NMR (DMSO-dg) d: 3.2-3.4 (2H, m), 4.90-5.10 (2H, m), 5.63 (2H, s), 6.57 (1H, d, J = 3.3 Hz), 6.69 (1H , d, J = 3.3 Hz), 7.08 (1H, d, J = 7.2 Hz), 7.20 (1H, d, J = 8.7 Hz), 7.35-7.45 (1H, m), 7.52 (1H, d, J = 8.7 Hz), 7.61 (1H, d, J = 3.3 Hz), 7.67 (1H, s), 7.85-7.95 (1H, m), 8.01 (1H, d, J = 2.7 Hz), 8.25-8.4 (3H, m), 8.56 (1H, s), 8.61 (1H, d, J = 5.1 Hz), 9.97 (1H, s). (v) Production of 3-hydroxy-3-methyl-N- [2- (4-. {[1- (pyridin-2-ylmethyl) -1H-indol-5-yl] amino.}. -5H- pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] butanamide To a solution of 5- (2-arainoethyl) -N- [1- (pyridin-2-ylmethyl) -lH-indole-5-tetrahydrochloride il] -5H-pyrrolo [3, 2-d] pyrimidine-4-araine (200 mg), 3-hydroxy-3-methylbutanoic acid (67 mg) and 1-hydroxybenzotriazole (85 mg) in N, N-dimethylformamide ( 5.0 ml) were added triethylamine (0.52 ml) and l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (120 mg) under ice-cooling, and the mixture was stirred at room temperature for 16 h. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by gel column chromatography of silica (eluent, ethyl acetate: methanol = 100: 0- »70: 30) and then recrystallized from ethyl acetate / diisopropyl ether to give the title compound (85.3 mg) as colorless crystals. Vl-NMR (DMSO-dg) d: 1.26 (6H, s), 2.37 (2H, s), 3. 55-3.7 (2H, m), 4.35-4.45 (2H, m), 5.45 (2H, s), 6.55 (2H, dd, J = 3.3 Hz, 7.8 Hz), 6.73 (1H, d, J = 7.8 Hz ), 6.75-6.85 (1H, m), 7.1-7.25 (3H, m), 7.39 (1H, dd, J = 1.8 Hz, 8.7 Hz), 7. 53 (1H, dt, J = 1.8 Hz, 7.8 Hz), 7.87 (1H, d, J = 1.5 Hz), 8.22 (1H, s), 8.43 (1H, s), 8.58 (1H, d, J = 4.8 Hz). Example G-9 Production of 3-hydroxy-3-methyl-N-. { 2- [4- ( { 1- [3- (trifluoromethoxy) benzyl] -lH-indol-5-yl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl } butanamide (i) Production of 5-nitro-l- [3- (trifluoromethoxy) benzyl] -1H-indole When using 5-nitroindole (538 mg), 1- (bromomethyl) -3- (trifluoromethoxy) benzene (0.96 g) , potassium carbonate (551 mg) and N, N-dimethylformamide (8.0 ml) and in the same way as in Example G-8 (i), the title compound (0.95 g) was obtained as a pale yellow powder. Vl-NMR (CDCI3) d: 5.39 (2H, s), 6.76 (1H, d, J = 3.3 Hz), 6.90-7.00 (2H, m), 7.15 (1H, d, J = 8.1 Hz), 7.20- 7.30 (2H, m), 7.35 (1H, t, J = 8.1 Hz), 8.09 (1H, dd, J = 2.1 Hz, 9.0 Hz), 8.62 (1H, d, J = 2.4 Hz). (ii) Production of 1- [3- (trifluoromethoxy) benzyl] -1H-indol-5-amine When using 5-nitro-l- [3- (trifluoromethoxy) benzyl] -1H-indole (504 mg), platinum- 5% activated carbon (84 mg) and ethyl acetate (15 ml) and in the same manner as in the Example G-8 (ii), the title compound (466 mg) was obtained as a pale yellow powder. XH-NMR (CDCl3) d: 3.50 (2H, br s), 5.26 (2H, s), 6.37 (1H, d, J = 3.0 Hz), 6.62 (1H, dd, J = 2.4 Hz, 8.7 Hz), 6.90-7.10 (5H, m), 7.08 (1H, d, J = 8.7 Hz), 7.25-7.35 (1H, m). (iii) Production of. { 2- [4- ( { 1- [3- (trifluoromethoxy) benzyl] -lH-indol-5-yl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl } tert-butyl carbamate When using [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (405 mg), l- [3- (trifluoromethoxy ) benzyl] -lH-indole-5-amine (459 mg) and isopropyl alcohol (8.0 ml) and in the same manner as in Example G-8 (iii), the title compound (692 mg) was obtained in the form of a white amorphous XH-NMR (CDCl3) d: 1.42 (9H, s), 3.45-3.55 (2H, m), 4. 35-4.45 (2H, m), 4.93 (1H, br s), 5.33 (2H, s), 6.52 (1H, d, J = 3.3 Hz), 6.55 (1H, d, J = 3.0 Hz), 6.95- 7.05 (2H, m), 7.10-7.25 (4H, m), 7.30 (1H, t, J = 8.2 Hz), 7.45-7.55 (1H, m), 7.90 (1H, s), 8.18 (1H, br s ), 8.44 (1H, s). (iv) Production of 5- (2-aminoethyl) -N- dihydrochloride. { 1- [3- (trifluoromethoxy) benzyl] -1H-indol-5-yl} - 5H-pyrrolo [3,2-d] pyrimidin-4-amine When using. { 2- [4- ( { 1- [3- (trifluoromethoxy) benzyl] -1H-indol-5-yl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl } tert-butyl carbamate (675 mg), 10% hydrochloric acid (w / w) / methanol (8.0 ml) and methanol (6.0 ml) and in the same manner as in Example G-8 (iv), was obtained the title compound (568 mg) in the form of an orange powder. Vl-NMR (DMSO-dg) d: 3.20-3.35 (2H, m), 4.90-5.10 (2H, m), 5.54 (2H, s), 6.55 (1H, d, J = 3.3 Hz), 6.68 (1H, d, J = 3.0 Hz), 7.15-7.30 (4H, m), 7.46 (1H, t, J = 7.8 Hz), 7.53 (1H, d, J = 8.7 Hz), 7.63 (1H, d, J = 3.3 Hz) , 7.67 (1H, s), 8. 01 (1H, d, J = 3.0 Hz), 8.25-8.45 (3H, m), 8.55 (1H, s), 9. 93 (1H, s). (v) Production of 3-hydroxy-3-methyl-N-. { 2- [4- ( { 1- [3- (trifluoromethoxy) benzyl] -lH-indol-5-yl} amino) -5H-pyrrolo [3,2-d] pyriraidin-5-yl] ethyl } butanamide When using 5- (2-aminoethyl) -N- dihydrochloride. { 1- [3- (trifluoromethoxy) benzyl] -lH-indol-5-yl} -5H-pyrrolo [3,2-d] pyrimidin-4-amine (200 mg), 3-hydroxy-3-methylbutanoic acid (62 mg), 1-hydroxybenzotriazole (76 mg), triethylamine (0.48 ml), hydrochloride l-ethyl-3- (3-dimethylaminopropyl) carbodiimide (106 mg) and N, N-dimethylformamide (5.0 ml) and in the same manner as in the Example G-8 (v), the title compound (143 mg) was obtained as colorless crystals. VL-NMR (CDC13) d: 1.26 (6H, s), 2.38 (2H, s), 3.55-3.70 (2H, m), 4.35-4.50 (2H, m), 5.32 (2H, s), 6.54 (2H , t, J = 3.6 Hz), 6.80-6.90 (1H, m), 6.95-7.05 (2H, ra), 7.10-7.20 (3H, m), 7.20-7.45 (3H, m), 7.88 (1H, s), 8.25 (1H, s), 8.43 1H, Example G-10 Production of N- (tert-butyl) -3 - [(5- {[5- (2-hydroxyethyl) -5H-pyrrolo [3,2- d] pyrimidin-4-yl] amino.}. -indol-1-yl) methyl] benzamide (i) Production of methyl 3- [(5-nitro-lH-indol-l-yl) methyl] benzoate When using 5-nitroindol (0.87 g), methyl 3- (bromomethyl) benzoate (1.35 g), potassium carbonate (0.89 g) and N, N-dimethylformamide (10 ml) and in the same manner as in Example G-8 (i), the title compound (0.83 g) was obtained as pale yellow crystals. XH-NMR (CDC13) d: 3.89 (3H, s), 5.41 (2H, s), 6.75 (1H, d, J = 3.3 Hz), 7.20-7.35 (3H, m), 7.39 (1H, t, J = 7.8 Hz), 7.88 (1H, s), 7.97 (1H, d, J = 7.8 Hz), 8.07 (1H, dd, J = 2.4 Hz, 9.1 Hz), 8.60 (1H, d, J = 1.8 Hz) . (ü) Production of 3- [(5-nitro-lH-indol-l-yl) methyl] benzoic acid To a suspension of methyl 3- [(5-nitro-lH-indol-l-yl) methyl] benzoate (0.75 g) in methanol (12 ml) was added 1N aqueous solution of sodium hydroxide (12 ml) and the mixture was stirred at room temperature for 1.5 h. Tetrahydrofuran (12 ml) was added to the mixture and the mixture was stirred at room temperature for 5 h. Under cooling with ice, 1N hydrochloric acid (12 ml) was added to the reaction mixture, and the mixture was concentrated under reduced pressure. The precipitate was collected by filtration, and washed with ethanol and diisopropyl ether to give the title compound (621 mg) as a yellow powder. XH-NMR (DMSO-d6) d: 5.55 (2H, s), 6.80 (1H, d, J = 2.4 Hz), 7.15-7.35 (2H, m), 7.67 (1H, d, J = 9.0 Hz), 7.70-7.85 (3H, m), 7.99 (1H, d, J = 7.8 Hz), 8.57 (1H, s). (iii) Production of N- (tert-butyl) -3- [(5-nitro-lH-indol-1-yl) methyl] benzamide To a suspension of 3- [(5-nitro-lH-indol-l methyl) benzoic acid (600 mg) and tert-butylamine (222 mg) in N, N-dimethylformamide (5.0 ml) were added triethylamine (0.45 ml) and diethyl cyanophosphate (0.49 ml) under ice-cooling, and the The mixture was stirred at room temperature for 21 h. Tert-butylamine (0.32 ml) was added to the mixture, and the mixture was stirred at room temperature for 20 h. Aqueous sodium bicarbonate was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: hexane = 35: 65-70: 30) to give the title compound (266 mg) in Form of a pale yellow powder. XH-NMR (CDC13) d: 1.45 (9H, s), 5.39 (2H, s), 5.87 (1H, br,), 6.70-6.75 (1H, ra), 7.10 (1H, d, J = 7.8 Hz) , 7.25-7.30 (2H, m), 7.33 (1H, t, J = 7.8 Hz), 7.55 (1H, d, J = 7.8 Hz), 7.67 (1H, s), 8.06 (1H, dd, J = 2.1 Hz, 9.0 Hz), 8.60 (1H, d, J = 2.1 Hz). (iv) Production of 3- [(5-araino-lH-indol-l-yl) methyl] -N- (tert-butyl) benzamide When using N- (tert-butyl) -3- [(5-nitro- lH-indol-l- il) methyl] benzamide (263 mg), 5% activated carbon-platinum (44 mg) and ethyl acetate (10 ml) and in the same manner as in Example G-8 (ii), the title compound (241 mg) was obtained as a pale yellow amorphous. XH-NMR (CDC13) d: 1.45 (9H, s), 3.50 (2H, br s), . 28 (2H, s), 5.84 (1H, br s), 6.37 (1H, d, J = 3.0 Hz), 6.62 (1H, dd, J = 2.4 Hz, 8.7 Hz), 6.94 (1H, d, J = 2.1 Hz), 7.00- 7.15 (3H, m), 7.25-7.35 (1H, m), 7.54 (1H, d, J = 7.5 Hz), 7. 60 (1H, s). (v) Production of N- (tert-butyl) -3- [(5- {[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino} .1H-indol-1-yl) methyl] benzamide A mixture of 2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl benzoate (105 mg), 3- [ (5-amino-lH-indol-1-yl) methyl] -N- (tert-butyl) benzamide (123 mg) and isopropyl alcohol (5.0 ml) was stirred at 80 ° C for 16 h. Under cooling with ice, aqueous sodium bicarbonate was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was concentrated under reduced pressure. The residue was separated and purified by column chromatography on silica gel (eluent, ethyl acetate: methanol = 100: 0-> 95: 5). To the obtained compound were added 1 N aqueous solution of sodium hydroxide (1.5 ml) and tetrahydrofuran (3.0 ml) and the mixture was stirred at room temperature for 18 h. The reaction mixture was neutralized with acid 1N hydrochloric acid, and aqueous sodium bicarbonate and brine were added. The mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate / methanol to give the title compound (90 mg) as pale yellow crystals. XH-NMR (CDC13) d: 1.46 (9H, s), 4.00-4.10 (2H, m), 4. 25-4.35 (2H, m), 5.33 (2H, s), 5.90 (1H, br s), 6.14 (1H, d, J = 3.0 Hz), 6.52 (1H, d, J = 2.7 Hz), 6.87 ( 1H, d, J = 3.0 Hz), 7.10-7.35 (5H, m), 7.54 (1H, d, J = 7.5 Hz), 7.63 (1H, s), 7.76 (1H, s), 8.19 (1H, s ), 9.15 (1H, s). Example G-ll Production of 2-methyl-2- (methylsulfonyl) -N-. { 2- [4- ( { 1- [3- (trifluoromethoxy) benzyl] -1H-indol-5-yl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl } propanamide When using 5- (2-aminoethyl) -N- dihydrochloride. { 1- [3- (trifluoromethoxy) benzyl] -lH-indol-5-yl} -5H-pyrrolo [3,2-d] pyrimidin-4-amine (200 mg), 2-methyl-2- (methylsulfonyl) propanoic acid (87 mg), 1-hydroxybenzotriazole (76 mg), triethylamine (0.48 ml) , l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (106 mg) and N, N- dimethylformamide (5.0 ml) and in the same manner as in Example G-8 (v), the title compound (100 mg) was obtained as colorless crystals. XH-NMR (CDC13) d: 1.61 (6H, s), 2.84 (3H, s), 3.65-3.75 (2H, m), 4.35-4.45 (2H, m), 5.34 (2H, s), 6.55 (1H , d, J = 3.0 Hz), 6.60 (1H, d, J = 3.0 Hz), 7.00-7.45 (9H, m), 7.86 (1H, s), 7.91 (1H, br s), 8.46 (1H, s ). Example G-12 Production of 2-. { 4- [(1- { [1- (2, 2-dimethylpropanoyl) piperidin-4-yl] methyl} - lH-indol-5-yl) amino] -5H-pyrrolo [3,2-d ] pyrimidin-5-yl} ethanol (i) Production of tert-butyl 4- [(5-nitro-lH-indol-l-yl) methyl] piperidine-1-carboxylate To a solution of 4- (hydroxymethyl) piperidine-1-carboxylate ter- Butyl (1.29 g) and triethylamine (1.17 ml) in tetrahydrofuran (30 ml) were added dropwise methanesulfonyl chloride (0.56 ml) under ice-cooling, and the mixture was stirred at room temperature for 1 h. Aqueous sodium bicarbonate was added to the reaction mixture under ice cooling, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give a yellow oil. To a solution of 5-nitroindole (811 mg) in N, N-dimethylformamide (5.0 ml) was added sodium hydride (60% in oil (220 mg)) under ice-cooling, and the mixture was stirred at 0 ° C. for 10 min. Under cooling with ice, a solution of the yellow oil obtained previously in N, N-dimethylformamide (5.0 ml) was added dropwise to the reaction mixture and the mixture was stirred at room temperature for 1 h, and at 60 ° C for 18 h. Under cooling with ice, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: hexane = 30: 70-> 50:50) to give the title compound (1.79 g) as a yellow amorphous form. XH-NMR (CDC13) d: 1.15-1.30 (2H, m), 1.45 (9H, s), 1. 50-1.60 (2H, ra), 1.90-2.05 (1H, m), 2.55-2.70 (2H, m), 4.00-4.20 (4H, m), 6.69 (1H, d, J = 3.0 Hz), 7.20 ( 1H, d, J = 3.0 Hz), 7.34 (1H, d, J = 9.0 Hz), 8.12 (1H, dd, J = 2.1 Hz, 9.0 Hz), 8.60 (1H, d, J = 2.1 Hz). (ii) Production of 4- [(5-amino-lH-indole-l- il) methyl] piperidin-1-carboxylate of tert-butyl When using 4- [(5-nitro-lH-indol-l-yl) methyl] piperidin-1-carboxylate of tert-butyl (0.90 g), platinum-carbon activated at 5% (0.15 g) and ethyl acetate (10 ml) and in the same manner as in Example G-8 (ii), the title compound (0.83 g) was obtained as a pale red amorphous. XH-NMR (CDC13) d: 1.10-1.25 (2H, m), 1.44 (9H, s), 1.50-1.60 (2H, m), 1.90-2.05 (1H, m), 2.55-2.70 (2H, m), 3.91 (2H, d, J = 7.2 Hz), 4.00-4.20 (2H, m), 6.28 (1H, d, J = 3.0 Hz), 6.67 (1H, dd, J = 2.1 Hz, 8.7 Hz), 6.92 (1H, d, J = 2.1 Hz), 6.96 (1H, d, J = 3.3 Hz), 7.12 (1H, d, J = 8.7 Hz). (iii) Production of 4-. { [5- (. {5- [2- (Benzoyloxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) -1H-indol-1-yl] methyl} piperidin-1-tert-butyl carboxylate A mixture of 2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl benzoate (686 mg), 4- [(5-amino -lH-indol-1-yl) methyl] piperidine-1-carboxylic acid tert-butyl ester (824 mg) and isopropyl alcohol (20 ml) was stirred at 80 ° C for 12 h. Under cooling with ice, aqueous sodium bicarbonate was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: methanol = 100: 0- »95: 5) to give the title compound (1.04 g) in the form of a powder yellow . XH-NMR (CDCI3) d: 1.15-1.30 (2H, m), 1.45 (9H, s), 1.50-1.60 (2H, m), 1.95-2.10 (1H, m), 2.55-2.70 (2H, m) , 3.98 (2H, d, J = 7.5 Hz), 4.05-4.20 (2H, m), 4.55-4.70 (4H, m), 6.43 (1H, d, J = 3.3 Hz), 6.63 (1H, d, J = 3.3 Hz), 7.04 (1H, d, J = 3.3 Hz), 7.25-7.35 (3H, m), 7.35-7.45 (3H, m), 7.50-7.65 (2H, m), 7.90-8.00 (2H, m), 8.48 (1H, s). (iv) Production of 2- (4. {[[1- (piperidin-4-ylmethyl) -lH-indol-5-yl] amino] -5H-pyrrolobenzoate dihydrochloride [3, 2-d] ] pyrimidin-5-yl) ethyl To a solution of 4-. { [5- (. {5- [2- (Benzoyloxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) -lH-indol-1-yl] methyl} piperidin-1-tert-butyl carboxylate (820 mg) in methanol (10 ml) was added 10% hydrochloric acid (w / w) / methanol (10 ml) and the mixture was stirred at room temperature for 17 h. The reaction mixture was concentrated under reduced pressure, ethanol was added, and the mixture was concentrated again. This operation was repeated twice. Diisopropyl ether was added, and the mixture was concentrated. The obtained powder was collected by filtration, and washed with diisopropyl ether to give the title compound (621 mg) as a pale yellow powder. XH-NMR (DMSO-dg) d: 1.35-1.55 (2H, m), 1.60-1.70 (2H, m), 2.05-2.20 (1H, m), 2.70-2.90 (2H, m), 3.20-3.30 (2H, m), 4.14 (2H, d, J = 6.9 Hz), 4.60-4.70 (2H , m), 5.10-5.20 (2H, m), 6.45 (1H, d, J = 3.0 Hz), 6.65 (1H, d, J = 2.7 Hz), 7.15 (1H, d, J = 9.6 Hz), 7.40-7.50 (3H, m) , 7.55 (1H, d, J = 8.7 Hz), 7.66 (1H, t, J = 7.5 Hz), 7.81 (2H, d, J = 8.1 Hz), 8.07 (1H, d, J = 3.0 Hz), 8.53 (1H, s), 8.55-8.70 (1H, br m), 8.90-9.00 (1H, br m), 9.90 (1H, br s). (v) Production of 2-. { 4- [(1- { [1- (2, 2-dimethylpropanoyl) piperidin-4-yl] methyl} - lH-indol-5-yl) amino] -5H-pyrrolo [3,2-d ] pyrimidin-5-yl} ethanol To a suspension of 2- (4. {[[1- (piperidin-4-ylmethyl) -lH-indol-5-yl] amino]} -5H-pyrrolo [3, 2-d] benzoate dihydrochloride. ] pyrimidin-5-yl) ethyl (200 mg) in tetrahydrofuran (5.0 ml) were added dropwise triethylamine (0.23 ml) and 2,2-dimethylpropanoyl chloride (0.045 ml) under ice-cooling. The mixture was stirred at 0 ° C for 30 min and at room temperature for 30 min. Under cooling with ice, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: methanol = 100: 0-95: 5). To the obtained compound were added 1 N aqueous solution of sodium hydroxide (1.5 ml) and tetrahydrofuran (4.0 ml) and the mixture was stirred at room temperature for 15 h. The reaction mixture was neutralized with 1 N hydrochloric acid and added aqueous sodium bicarbonate and salrauera. The mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate / methanol / diisopropyl ether to give the title compound (104 mg) as pale-colored crystals. XH-NMR (CDC13) d: 1.10-1.30 (2H, m), 1.27 (9H, s), 1.55-1.70 (2H, m), 2.05-2.20 (1H, m), 2.60-2.75 (2H, m) , 3.98 (2H, d, J = 7.2 Hz), 4.05-4.15 (2H, ra), 4.30-4.50 (4H, m), 6.10 (1H, d, J = 3.0 Hz), 6.46 (1H, d, J = 3.0 Hz), 6.85 (1H, d, J = 3.0 Hz), 7.04 (1H, d, J = 3.0 Hz), 7.25-7.35 (1H, m), 7.35-7.45 (1H, m), 7.75 (1H , s), 8.18 (1H, s), 9.27 (1H, br Example G-13 Production of N- (tert-butyl) -4- [(5- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.} -1H -indol-1-yl) methyl] piperidin-l-carboxamide To a suspension of 2- benzoate dihydrochloride (4- { [1- (piperidin-4-ylmethyl) -1H-indol-5-yl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl (200 mg ) in tetrahydrofuran (5.0 ml) were added dropwise triethylamine (0.23 ml) and 2-isocyanat-2-methylpropane (0.045 ml) under cooling with ice. The reaction mixture was stirred at room temperature for 1.5 h, water was added to the reaction mixture under cooling with ice, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and concentrated under reduced pressure. The residue was separated and purified by column chromatography on silica gel (eluent, ethyl acetate: methanol = 100: 0- »95: 5). To the obtained compound were added 1 N aqueous solution of sodium hydroxide (1.6 ml) and tetrahydrofuran. (4.0 ml) and the mixture was stirred at room temperature for 15 h. The reaction mixture was neutralized with 1N hydrochloric acid and aqueous sodium bicarbonate and brine were added. The mixture was extracted with ethyl acetate and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was recrystallized from ethyl acetate / methanol / diisopropyl ether to give the title compound (112 mg) as pale-colored crystals. XH-NMR (CDC13) d: 1.15-1.30 (2H, m), 1.34 (9H, s), 1.50-1.65 (2H, m), 1.95-2.10 (1H, m), 2.55-2.70 (2H, m) , 3.85-3.95 (2H, m), 3.99 (2H, d, J = 7.2 Hz), 4.05-4.15 (2H, m), 4.29 (1H, s), 4.30-4.40 (2H, m), 6.19 (1H, d, J = 3.0 Hz), 6.45-6.50 (1H, m), 6.90-6.95 (1H, m), 7.05 -7.10 (1H, ra), 7.25-7.45 (2H, m), 7.75 (1H, s), 8.23 (1H, s), 9.20 (1H, br Example G-14 Production of N- (tert-butyl) -3- [(5- {[[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino} -lH -indazol-l-yl) methyl] benzamide (i) Production of methyl 3- [(5-nitro-lH-indazol-l-yl) methyl] benzoate To a solution of 5-nitroindazole (816 mg) and 3- Methyl (bromomethyl) benzoate (2.29 g) in N, N-dimethylformamide (10 ml) was added potassium carbonate (2.07 g) under ice-cooling, and the mixture was stirred at room temperature for 2 h. Under cooling with ice, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: hexane = 20: 80-> 50:50) to give the title compound (805 mg) as pale yellow crystals. XH-NMR (CDC13) d: 3.90 (3H, s), 5.68 (2H, s), 7.30-7.45 (3H, ra), 7.90-8.00 (2H, ra), 8.23 (1H, dd, J = 1.8 Hz , 9.0 Hz), 8.20-8.25 (1H, ra), 8.74 (1H, d, J = 1.8 Hz). (ii) Production of 3- [(5-nitro-lH-indazol-1-yl) methyl] benzoic acid When using methyl 3- [(5-nitro-lH-indazol-l-yl) methyl] benzoate (0.79 g), 1 N aqueous solution of sodium hydroxide (12 ml), methanol (15 ml) and tetrahydrofuran (15 ml) and in the same manner as in Example G-10 (ii), the title compound (732 mg) was obtained as a yellow powder pale. XH-NMR (DMSO-dg) d: 5.86 (2H, s), 7.40-7.55 (2H, m), 7. 75-7.90 (2H, m), 8.00 (1H, d, J = 9.3 Hz), 8.25 (1H, dd, J = 2. 1 Hz, 9.3 Hz), 8.48 (1H, s), 8.86 (1H, d, J = 2.1 Hz), 13.07 (1H, br s). (iii) Production of N- (tert-butyl) -3- [(5-nitro-lH-indazol-1-yl) methyl] benzamide To a suspension of 3- [(5-nitro-lH-indazol-l)] -yl) methyl] benzoic acid (595 mg) in tetrahydrofuran (10 ml) were added N, N-dimethylformamide (one drop) and thionyl chloride (0.144 ml) and the mixture was stirred at room temperature for 3.5 h. To a solution of tert-butylamine (0.73 g) and triethylamine (0.25 g) in N, N-dimethylformamide (4.0 ml) was added the aforesaid reaction mixture under cooling with ice, and the mixture was stirred at room temperature for 4.5 h. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: hexane = 30: 70-> 50:50) to give the title compound (0.56 g). ) in the form of a pale yellow amorphous shape. XH-NMR (CDC13) d: 1.45 (9H, s), 5.66 (2H, s), 5.8.8 (1H, br s), 7.20-7.30 (1H, m), 7.35 (1H, t, J = 7.5 Hz), 7.40 (1H, d, J = 9.0 Hz), 7.56 (1H, d, J = 7.5 Hz), 7.73 (1H, s), 8.23 (1H, dd, J = 2.1 Hz, 9.0 Hz), 8.25 (1H, s), 8.74 (1H, d, J = 2.1 Hz). (iv) Production of 3- [(5-amino-lH-inda zol-l, l) -Retyl] -N- (tert-butyl) benzamide When using N- (tert-butyl) -3- [(5-nitro) -lH-inda zol-l -yl) methyl] benzamide (0.55 g), 5% activated carbon-platinum (92 mg) and ethyl acetate (20 ml) and in the same manner as in Ejeraplo G-8 ( ii), the title compound (0.47 g) was obtained in the form of a white powder. VL-NMR (CDCI3) d: 1.44 (9H, s), 3.61 (2H, br s), 5.55 (2H, s), 5.86 (1H, br s), 6.81 (1H, d, J = 9.0 Hz), 6.95- 7. 00 (1H, m), 7.14 (1H, d, J = 8.7 Hz), 7.20 (1H, d, J = 7.5 Hz), 7.30 (1H, t, J = 7.5 Hz), 7.56 (1H, d, J = 8.1 Hz), 7.63 (1H, s), 7.83 (1H, s). (v) Production of N- (tert-butyl) -3- [(5- {[5- (2-hydroxyethyl) -5H-pyrrolo [3,2- d] pyrimidin-4-yl] amino}. .-lH-indazol-l-yl) methyl] benzamide When using 2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethyl benzoate (151 mg), 3- [( 5-amino-lH-indazol-1-yl) methyl] -N- (tert-butyl) benzamide (177 mg), isopropyl alcohol (8.0 ml), 1 N aqueous solution of sodium hydroxide (2.0 ml) and tetrahydrofuran ( 4.0 ml) and in the same manner as in Example G-10 (v), the title compound (169 mg) was obtained as colorless crystals. XH-NMR (CDC13) d: 1.45 (9H, s), 4.05-4.15 (2H, m), 4.30-4.40 (2H, m), 5.59 (2H, s), 5.92 (1H, br s), 6.18 ( 1H, d, J = 3.0 Hz), 6.93 (1H, d, J = 3.6 Hz), 7.25-7.35 (4H, m), 7. 40-7.50 (1H, m), 7.56 (1H, d, J = 7.2 Hz), 7.65 (1H, s), 7. 88 (1H, s), 7.98 (1H, s), 8.22 (1H, s), 9.33 (1H, br s). Example G-15 Production of N- (tert-butyl) -3- (5- { [5- (2-hydroxyethyl) -5H-pyrrolo [3, 2-d] pyrimidin-4-yl] amino.}. -lH- indol-1-yl) benzamide (i) Production of ethyl 3- (5-nitro-lH-indol-l-yl) benzoate A mixed solution of 5-nitroindole (1.62 g), ethyl 3-iodobenzoate (3.04 g), N, N-dimethylenediamine (0.97 g), potassium carbonate (1.66 g), copper iodide (I) (0.19 g) and toluene (10 ml) was stirred at 120 ° C for 24 h. Under cooling with ice, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: hexane = 20: 80 → 40: 60) to give the title compound (0.95 g) as a pale yellow powder. XH-NMR (CDC13) d: 1.43 (3H, t, J = 7.0 Hz), 4.44 (2H, q, J = 7.0 Hz), 6.89 (1H, d, J = 3.3 Hz), 7.50-7.55 (2H, m), 7.60-7.75 (2H, m), 8.10-8.20 (3H, m), 8.66 (1H, d, J = 2.4 Hz). (ii) Production of 3- (5-nitro-lH-indol-l-yl) benzoic acid When using ethyl 3- (5-nitro-lH-indol-l-yl) benzoate (0.95 g), 1 N aqueous solution of sodium hydroxide (15 ml), ethanol (15 ml) and tetrahydrofuran (15 ml) and in the same manner as in Example G-10 (ii), the compound of title (0.71 g) in the form of a yellow powder.

XH-NMR (DMSO-d6) d: 6.95-7.05 (1H, m), 7.60-7.75 (2H, m), 7.83 (1H, d, J = 7.2 Hz), 7.90-8.10 (4H, m), 8.68 (1H, s). (iii) Production of N- (tert-butyl) -3- (5-nitro-lH-indol-1-yl) benzamide When using 3- (5-nitro-lH-indol-l-yl) benzoic acid (565 mg), thionyl chloride (0.144 ml), tetrahydrofuran (10 ml), tert-butylamine (0.73 g), triethylamine (0.25 g) and N, N-dimethylformamide (4.0 ml) and in the same manner as in the Example G-14 (iii), the title compound (0.32 g) was obtained as a yellow powder. XH-NMR (CDC13) d: 1.50 (9H, s), 5.99 (1H, br s), 6.89 (1H, d, J = 3.3 Hz), 7.50-7.65 (4H, m), 7.65-7.75 (1H, m), 7.93 (1H, s), 8.13 (1H, dd, J = 2.1 Hz, 9.0 Hz), 8.66 (1H, d, J = 2.4 Hz). (iv) Production of 3- (5-araino-lH-indol-l-yl) -N- (tert-butyl) benzamide When using N- (tert-butyl) -3- (5-nitro-lH-indol- 1-yl) benzamide (0.32 g), 5% activated carbon platinum (0.05 g) and ethyl acetate (20 ml) and in the same manner as in the Example G-8 (ii), the title compound (253 rag) was obtained in the form of a pale pink amorphous. Vl-NMR (CDCI3) d: 1.49 (9H, s), 3.58 (2H, br s), . 94 (1H, br s), 6.51 (1H, d, J = 3.0 Hz), 6.68 (1H, dd, J = 2.1 Hz, 8.7 Hz), 6.96 (1H, d, J = 2.1 Hz), 7.20-7.30 (1H, m), 7. 37 (1H, d, J = 8.7 Hz), 7.50-7.65 (3H, m), 7.84 (1H, s). (v) Production of N- (tert-butyl) -3- (5- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2- d] pyrimidin-4-yl] amino.}. -lH-indol-1-yl) benzamide When using 2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethyl benzoate (164 mg), 3- (5-amino- lH-indol-1-yl) -N- (tert-butyl) benzamide (200 mg), isopropyl alcohol (8.0 ml), 1 N aqueous solution of sodium hydroxide (2.5 ml) and tetrahydrofuran (5.0 ml) and the In the same manner as in Example G-10 (v), the title compound (154 mg) was obtained in the form of pale yellow crystals. Vl-NMR (CDC13) d: 1.51 (9H, s), 4.10-4.15 (2H, m), 4. 35-4.45 (2H, m), 6.03 (1H, br s), 6.17 (1H, d, J = 3.3 Hz), 6. 67 (1H, d, J = 3.3 Hz), 6.91 (1H, d, J = 3.3 Hz), 7.30-7.40 (2H, m), 7.50-7.70 (4H, m), 7.80-7.85 (1H, m) 7.89 (1H, s), 8. 23 (1H, s), 9.24 (1H, br s). Example G-16 Production of 3-hydroxy-3-methyl-N- [2- (4- { [1- (1,3-thiazol-4-ylmethyl) -lH-indol-5-yl] amino.}. -5H -pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] butanamide (i) Production of 5-nitro-l- (1,3-thiazol-4-ylmethyl) - lH-indole When using 5-nitroindole (1.62 g), 4- (chloromethyl) -1,3-thiazole hydrochloride (1.87 g), potassium carbonate (4.15 g) and N, N-dimethylformamide (20 ml) and in the same manner as in Example G-8 (i), the title compound (1.98 g) was obtained in the form of a yellow powder. XH-NMR (CDC13) d: 5.54 (2H, s), 6.74 (1H, d, J = 3.3 Hz), 6.95-7.00 (1H, m), 7.30-7.45 (2H, m), 8.10 (1H, dd , J = 2.1 Hz, 9.0 Hz), 8.60 (1H, d, J = 2.1 Hz), 8.81 (1H, d, J = 2.1 Hz). (ii) Production of 1- (1,3-thiazol-4-ylmethyl) -1H-indole-5-araine To a solution of 5-nitro-l- (1,3-thiazol-4-ylmethyl) -lH- indole (519 mg) in ethyl acetate (20 ml) / methanol (4 ml) was added 5% activated carbon-platinum (87 mg) under a nitrogen atmosphere. The reaction mixture was stirred at room temperature for 3 days under a hydrogen atmosphere. Under a nitrogen atmosphere, 10% palladium / carbon (87 mg) was added, and the mixture was stirred at room temperature for 9 h under an atmosphere of hydrogen. The catalyst was filtered, and the filtrate was concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: hexane = 60: 40-> 100: 0) to give the title compound (424 mg) as a red oil.

VL-NMR (CDCI3) d: 3.50 (2H, br s), 5.44 (2H, s), 6.37 (1H, d, J = 3.3 Hz), 6.64 (1H, dd, J = 2.1 Hz, 8.4 Hz), 6.75-6.80 (1H, m), 6.94 (1H, d, J = 2.1 Hz), 7.10-7.15 (2H, m), 8.77 (1H, d, J = 1.8 Hz). (iii) Production of [2- (4-. {[1- (1, 3-thiazol-4-ylmethyl) -lH-indol-5-yl] amino.}. -5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethyl] tert-butyl carbamate When using [2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (446 mg), 1- (1,3-thiazol-4-ylmethyl) -lH-indol-5-amine (414 mg) and isopropyl alcohol (10 ml) and in the same manner as in Example G-8 (iii) , the title compound (697 mg) was obtained in the form of a pale red amorphous. XH-NMR (CDCl3) d: 1.43 (9H, s), 3.45-3.55 (2H, m), 4.35-4.45 (2H, m), 4.92 (1H, br s), 5.51 (2H, s), 6.51 ( 1H, d, J = 3.0 Hz), 6.56 (1H, d, J = 3.0 Hz), 6.81 (1H, s), 7.13 (1H, d, J = 3.3 Hz), 7.20 (1H, d, J = 3.0 Hz), 7.28 (1H, d, J = 8.7 Hz), 7.48 (1H, d, J = 7.2 Hz), 7.88 (1H, s), 8.18 (1H, br s), 8.44 (1H, s), 8.79 (1H, d, J = 2.1 Hz). (iv) Production of 5- (2-aminoethyl) -N- [1- (1,3-thiazol-4-ylmethyl) -lH-indol-5-yl] -5H-pyrrolo dihydrochloride [3,2-d] ] pyrimidin-4-amine When using [2- (4-. {[1- (1, 3-thiazol-4-ylmethyl) -lH-indol-5-yl] amino.}. -5H-pyrrolo [3 , 2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (675 mg), 10% hydrochloric acid (w / w) / methanol (10 ral) and methanol (8.0 ml) and from the same manner as in Example G-8 (iv), the title compound (610 mg) was obtained as a pale green powder. Vl-NMR (DMSO-d6) d: 3.25-3.35 (2H, m), 4.90-5.10 (2H, m), 5.57 (2H, s), 6.50 (1H, d, J = 3.3 Hz), 6.69 (1H , d, J = 3.0 Hz), 7.20 (1H, dd, J = 1.8 Hz, 8.4 Hz), 7.50-7.65 (4H, m), 8.01 (1H, d, J = 3.0 Hz), 8.25-8.45 (3H, m) , 8.55 (1H, s), 9. 05 (1H, d, J = 1.8 Hz), 9.97 (1H, s). (v) Production of 3-hydroxy-3-methyl-N- [2- (4. {[1- (1,3-thiazol-4-ylmethyl) -lH-indol-5-yl] amino]. .5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] butanamide When using 5- (2-aminoethyl) -N- [1- (1,3-thiazol-4-ylmethyl) dihydrochloride - lH-indol-5-yl] -5H-pyrrolo [3,2-d] pyrimidin-4-amine (200 mg), 3-hydroxy-3-methylbutanoic acid (71 mg), 1-hydroxybenzotriazole (88 mg), triethylamine (0.56 ml), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (123 mg) and N, N-dimethylformamide (5.0 ml) and in the same manner as in Example G-8 (v), the title compound (118 mg) was obtained as colorless crystals. V ^ -NMR (CDC13) d: 1.27 (6H, s), 2.38 (2H, s), 3.55-3.70 (2H, m), 4.35-4.50 (2H, m), 5.50 (2H, s), 6.50- 6.60 (2H, m), 6.65-6.75 (1H, m), 6.82 (1H, s), 7.13 (1H, d, J = 3.3 Hz), 7.15-7.45 (4H, m), 7.83 (1H, s) , 8.25 (1H, s), 8.42 (1H, s), 8.78 (1H, d, J = 1.5 Hz).

Example G-17 Production of N- (tert-butyl) -3- [(7-chloro-5-. {[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] araino}-lH-indol-1-yl) methyl] benzamide (i) Production of 7-chloro-5-nitroindoline A mixed solution of 5-nitroindoline (3.28 g), N-chlorosuccimide (2.94 g) and acetonitrile (100 ml ) was heated to reflux for 19 h. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: hexane = 30: 70-> 50:50) to give the title co-tax (2.09 g) as a yellow powder . XH-NMR (CDC13) d: 3.23 (2H, t, J = 8.7 Hz), 3.84 (2H, t, J = 8.7 Hz), 4.68 (1H, br s), 7.85-7.90 (1H, m), 8.05 -8.10 (1H, m). (ii) Production of 7-chloro-5-nitro-lH-indole To a solution of 7-chloro-5-nitroindoline (2.09 g) in ethyl acetate (100 ml) was added manganese oxide (9.13 g), and the mixture was stirred at 60 ° C for 15 h. The manganese oxide was filtered, and the filtrate was concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate) and washed with hexane to give the title compound (1.92 g) as a pale brown powder. Vi-NMR (CDC13) d: 6.79-6.82 (1H, m), 7.40-7.45 (1H, m), 8.15 (1H, d, J = 1.8 Hz), 8.53 (1H, d, J = 1.8 Hz), 8.65-8.85 (1H, m). (iii) Production of methyl 3- [(7-chloro-5-nitro-lH-indol-l-yl) methyl] benzoate When using 7-chloro-5-nitro-lH-indole (950 mg), 3- Methyl (bromomethyl) benzoate (1.22 g), potassium carbonate (0.80 g) and N, N-dimethylformamide (15 ml) and in the same manner as in Example G-8 (i), the title compound was obtained (1.43 g) in the form of pale yellow crystals. VL-NMR (CDCI3) d: 3.89 (3H, s), 5.84 (2H, s), 6.80 (1H, d, J = 3.3 Hz), 7.13 (1H, dd, J = 0.9 Hz, 7.8 Hz), 7.25-7.30 (1H, m), 7.38 (1H, t, J = 7.8 Hz), 7.79 (1H , s), 7.95 (1H, d, J = 8.1 Hz), 8.07 (1H, d, J = 2.1 Hz), 8.50 (1H, d, J = 2. 1 Hz). (iv) Production of 3- [(7-chloro-5-nitro-lH-indol-1-yl) methyl] benzoic acid When using 3- [(7-chloro-5-nitro-lH-indol-l- il) methyl] benzoate (1.30 g), 1 N aqueous sodium hydroxide solution (20 ml), methanol (20 ml) and tetrahydrofuran (30 ml) and in the same manner as in Example G-10 (ii) ), the title compound (1.20 g) was obtained in the form of a pale-colored powder. Vl-NMR (DMSO-d6) d: 5.92 (2H, s), 6.99 (1H, d, J = 3.0 Hz), 7.26 (1H, d, J = 7.5 Hz), 7.44 (1H, t, J = 7.5 Hz), 7.56 (1H, s), 7.82 (1H, d, J = 7.5 Hz), 7.88 (1H, d, J = 3.0 Hz), 7.98 (1H, d, J = 1.8 Hz), 8.62 (1H, d, J = 1.8 Hz), 12.90-13.10 (1H, br). (v) Production of N- (tert-butyl) -3- [(7-chloro-5-nitro-lH-indol-1-yl) methyl] benzamide When using 3- [(7-chloro-5-nitro]] -lH-indol-1-yl) methyl] benzoic acid (595 mg), thionyl chloride (0.13 ml), tetrahydrofuran (10 ml), tert-butylamine (0.66 g), triethylamine (0.23 g) and N, N-dimethylformamide (4.0 ml) and in the same manner as in Example G-14 (iii), the title compound (460 mg) was obtained as pale yellow crystals. VL-NMR (CDC13) d: 1.45 (9H, s), 5.83 (2H, s), 5.86 (1H, br s), 6.79 (1H, t, J = 3.3 Hz), 7.02 (1H, d, J = 7.8 Hz), 7.20-7.30 (1H, m), 7.33 (1H, t, J = 7.8 Hz ), 7.53 (1H, d, J = 7.8 Hz), 7.58 (1H, s), 8.07 (1H, d, J = 2.4 Hz), 8.49 (1H, d, J = 2.4 Hz). (vi) Production of 3- [(5-araino-7-chloro-lH-indole-l- il) methyl] -N- (tert-butyl) benzamide N- (tert-butyl) -3 - [(7-chloro-5-nitro-lH-indol-1-yl) methyl] benzamide (212 mg) was suspended in ethanol (10 ml) / water (1 ml), calcium chloride (30.5 mg) was added, and the mixture was dissolved at 90 ° C. Reduced iron (184 mg) was added to the mixture, and the mixture was stirred at 90 ° C for 4 h. The reaction mixture was allowed to return to room temperature, and the insoluble material was filtered. The filtrate was concentrated under reduced pressure, ethyl acetate was added, and the mixture was washed with brine. The mixture was dried over anhydrous magnesium sulfate and concentrated under reduced pressure to give the title compound (203 mg) as a yellow amorphous form. VL-NMR (CDC13) d: 1.44 (9H, s), 3.45-3.60 (2H, br), 5.69 (2H, s), 5.84 (1H, br s), 6.37 (1H, d, J = 3.3 Hz) , 6.61 (1H, d, J = 2.0 Hz), 6.82 (1H, d, J = 2.0 Hz), 6.95-7.05 (1H, m), 7.02 (1H, d, J = 3.3 Hz), 7.29 (1H, t, J = 7.8 Hz), 7.50-7.55 (1H, m), 7.53 (1H, d, J = 7.8 Hz). (vii) Production of N- (tert-butyl) -3- [(7-chloro-5-. {[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl) ] amino.}. - lH-indol-1-yl) methyl] benzamide When using 2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethyl benzoate (151 mg), 3- [(5-amino-7-chloro-lH-indol-1-yl) methyl] -N- (tert-butyl) benzamide (196 mg), isopropyl alcohol (8.0 ml), aqueous 1 N hydroxide solution Sodium (2.0 ml) and tetrahydrofuran (4.0 ml) and from the mixture so that in Example G-10 (v), the title compound (157 mg) was obtained as colorless crystals. XH-NMR (CDC13) d: 1.45 (9H, s), 4.05-4.15 (2H, m), 4.30-4.40 (2H, m), 5.75 (2H, s), 5.89 (1H, s), 6.17 (1H , d, J = 3.0 Hz), 6.53 (1H, d, J = 3.0 Hz), 6.92 (1H, d, J = 3.0 Hz), 7.05 (1H, d, J = 7.2 Hz), 7.09 (1H, d , J = 3.0 Hz), 7.25-7.35 (2H, m), 7.50-7.55 (2H, m), 7.65-7.70 (1H, m), 8.22 (1H, s), 9.22 (1H, s). Example G-18 Production of N- (tert-butyl) -6- [(5- {[[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino]} -lH -indol-1-yl) methyl] pyridine-2-carboxamide (i) Production of ethyl 6- (hydroxymethyl) pyridine-2-carboxylate To a solution of diethyl pyridine-2,6-dicarboxylate (4.46 g) in ethanol (50 ml). ml) was added sodium borohydride (454 mg) and the mixture was stirred at room temperature for 3 h. The reaction mixture was concentrated under reduced pressure, brine was added, and the mixture was extracted with ethyl acetate. The aqueous layer was poured off, and the mixture was extracted with ethyl acetate. The combined organic layers were dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: hexane = 50: 50-> 100: 0) to give the title compound (2.42 g) as colorless crystals. XH-NMR (CDC13) d: 1.44 (3H, t, J = 7.2 Hz), 3.53 (1H, t, J = 5.4 Hz), 4.46 (2H, q, J = 7.2 Hz), 4.86 (2H, d, J = 5.4 Hz), 7.49 (1H, d, J = 7.8 Hz), 7.84 (1H, t, J = 7.8 Hz), 8.02 (1H, d, J = 7.8 Hz). (ii) Production of ethyl 6- [(5-nitro-lH-indol-l-yl) methyl] pyridine-2-carboxylate To a solution of ethyl 6- (hydroxymethyl) pyridine-2-carboxylate (1.00 g) and triethylamine (0.84 ral) in tetrahydrofuran (20 ml) was added dropwise methanesulfonyl chloride (0.43 ml) under ice-cooling, and the mixture was stirred at room temperature for 1.5 h. Under cooling with ice, aqueous sodium bicarbonate and brine were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. To the obtained compound were added 5-nitroindole (757 mg), potassium carbonate (0.97 g) and N, N-dimethylformamide (10 ml) and the mixture was stirred at room temperature. environment for 24 h at 60 ° C for 20 h, and at 80 ° C for 1 h. Under cooling with ice, water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The aqueous layer was poured off, and the mixture was extracted with ethyl acetate. The combined organic layers were dried over anhydrous magnesium sulfate, concentrated under reduced pressure, and the residue was recrystallized from ethyl acetate to give the title compound (1.31 g) as a pale-colored powder. XH-NMR (CDC13) d: 1.47 (3H, t, J = 7.2 Hz), 4.51 (2H, q, J = 7.2 Hz), 5.62 (2H, s), 6.76 (1H, d, J = 7.8 Hz) , 6.79 (1H, d, J = 3.0 Hz), 7.30 (1H, d, J = 9.0 Hz), 7.36 (1H, d, J = 3.0 Hz), 7.70 (1H, t, J = 7.8 Hz), 8.02 (1H, d, J = 7.8 Hz), 8.08 (1H, dd, J = 2.1 Hz, 9.0 Hz), 8.63 (1H, d, J = 2.1 Hz). (iii) Production of 6- [(5-nitro-lH-indol-l-yl) methyl] pyridine-2-carboxylic acid When using 6- [(5-nitro-lH-indol-l-yl) methyl] pyridine Ethyl 2-carboxylate (1.20 g), 1 N aqueous solution of sodium hydroxide (20 ml), ethanol (20 ml) and tetrahydrofuran (40 ml) and in the same manner as in Example G-10 (ii) , the title co-formula (1.01 g) was obtained in the form of a pale yellow powder. Vl-NMR (DMSO-dg) d: 5.68 (2H, s), 6.80-6.85 (1H, m), 6.89 (1H, d, J = 7.2 Hz), 7.67 (1H, d, J = 8.1 Hz), 7.70-7.90 (3H, m), 7.99 (1H, d, J = 9.0 Hz), 8.60 (1H, s). (iv) Production of N- (tert-butyl) -6- [(5-nitro-lH-indol-1-yl) methyl] pyridine-2-carboxamide When using 6- [(5-nitro-lH-indole -l-yl) methyl] pyridine-2-carboxylic acid (0.95 g), thionyl chloride (0.23 ml), tetrahydrofuran (20 ml), tert-butylamine (1.17 g), triethylamine (0.40 g) and N, N-dimethylformamide (8.0 ml) and in the same manner as in Example G-14 (iii), the title compound (636 mg) was obtained in the form of a pale yellow amorphous. XH-NMR (CDC13) d: 1.41 (9H, s), 5.51 (2H, s), 6.78 (1H, d, J = 3.3 Hz), 6.98 (1H, d, J = 7.8 Hz), 7.30-7.40 (2H, m), 7.66 (1H, br s), 7.76 (1H, t, J = 7.8 Hz ), 8.05-8.15 (2H, ra), 8.63 (1H, d, J = 2.1 Hz). (v) Production of 6- [(5-amino-lH-indol-l-yl) methyl] -N- (tert-butyl) pyridine-2-carboxamide To a solution of N- (tert-butyl) -6- [(5-Nitro-lH-indol-1-yl) methyl] pyridine-2-carboxamide (211 mg) in ethyl acetate (8.0 ml) was added 5% activated carbon-platinum (35 mg) under an atmosphere of nitrogen. The reaction mixture was stirred under an atmosphere of hydrogen at room temperature for 5 h. Under a nitrogen atmosphere, 10% palladium / carbon (69 mg) was added to the reaction mixture, and the mixture was further stirred under a hydrogen atmosphere at room temperature for 2.5 h. The catalyst was filtered, and the filtrate was concentrated under reduced pressure. The residue is separated and purified by silica gel column chromatography (eluent, ethyl acetate: hexane = 50: 50-80: 20) to give the title compound (160 mg) in a pale pink amorphous fora. VL-NMR (CDC13) d: 1.48 (9H, s), 3.52 (2H, br s), . 39 (2H, s), 6.41 (1H, d, J = 3.0 Hz), 6.64 (1H, dd, J = 2.4 Hz, 8.7 Hz), 6.82 (1H, d, J = 8.1 Hz), 6.97 (1H, d, J = 2.4 Hz), 7.00-7.10 (1H, m), 7.11 (1H, d, J = 3.0 Hz), 7.68 (1H, t, J = 7.5 Hz), 7.89 (1H, br s), 8.03 (1H, d, J = 7.5 Hz). (vi) Production of N- (tert-butyl) -6- [(-5- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino}-lH-indol-1-yl) methyl] pyridine-2-carboxamide When using 2- (4-chloro-5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethyl benzoate (136 mg) 6- [(5-amino-lH-indol-l-yl) -ethyl] -N- (tert-butyl) pyridine-2-carboxamide (160 mg), isopropyl alcohol (8.0 ml), 1 N aqueous hydroxide solution of sodium (2.0 ml) and tetrahydrofuran (4.0 ral) and in the same manner as in Example G-10 (v), the title compound (137 mg) was obtained as colorless crystals. Vi-NMR (CDCl 3) d: 1.50 (9H, s), 4.05-4.15 (2H, m), 4.30-4.40 (2H, m), 5.46 (2H, s), 6.16 (1H, d, J = 3.0 Hz ), 6.57 (1H, d, J = 3.0 Hz), 6.85-6.90 (2H, m), 7.19 (1H, d, J = 3.0 Hz), 7.20-7.30 (1H, m), 7.35 (1H, d, J = 9.0 Hz), 7.69 (1H, t, J = 7.5 Hz), 7.81 (1H, s), 7.92 (1H, s), 8.04 (1H, d, J = 7.5 Hz), 8.20 (1H, s), 9.15 (1H, br s) Example G-19 Production of N- (tert-butyl) -3- (. {5- [(5- {2- [3-hydroxy-3-methylbutanoyl) amino] ethyl} -5H-pyrrolo [3, 2-d] pyrimidin-4-yl) amino] -1H-indol-1-yl.} Methyl) benzamide (i) Production of (2- {4- [(1-. {3- ([ tert-butylamino) carbonyl] benzyl] -lH-indol-5-yl) amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl} ethyl) tert-butyl carbamate When using [ 2- (4-chloro-5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] tert-butyl carbamate (297 mg), 3- [(5-amino-lH-indol-1-yl ) methyl] -N- (tert-butyl) benzamide (354 mg) and isopropyl alcohol (8.0 ml) and in the same manner as in Example G-8 (iii), the title compound (478 mg) was obtained in form of colorless crystals. XH-NMR (CDC13) d: 1.43 (9H, s), 1.46 (9H, s), 3.45- 3.55 (2H, m), 4.35-4.50 (2H, m), 4.93 (1H, br s), 5.33 ( 2H, s), 5.88 (1H, s), 6.49 (1H, d, J = 3.0 Hz), 6.55 (1H, d, J = 2.4 Hz), 7.10-7.30 (4H, m), 7.30 (1H, t , J = 7.8 Hz), 7.40-7.50 (1H, m), 7.54 (1H, d, J = 8.1 Hz), 7.64 (1H, s), 7.86 (1H, s), 8.16 (1H, br s), 8.43 (1H, s). (ii) Production of 3- [(5. {[5- (2-aminoethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino] -lH-indole dihydrochloride 1-yl) methyl] -N- (tert-butyl) benzamide When using (2- {4- [[1- {3- [(tert-butylamino) carbonyl] benzyl} -1H-indole -5-yl) amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl.} Ethyl) tert-butyl carbamate (449 mg) and 10% hydrochloric acid (w / w) / methanol (5.0 ml) and in the same manner as in Example G-8 (iv), the title compound (400 mg) was obtained as a pale orange powder. XH-NMR (DMSO-dg) d: 1.36 (9H, s), 3.25-3.35 (2H, ra), 4.90-5.05 (2H, m), 5.51 (2H, s), 6.56 (1H, d, J = 3.0 Hz), 6.69 (1H, d, J = 3.3 Hz), 7.20 (1H, d, J = 9.0 Hz), 7.29 (1H, d, J = 7.2 Hz), 7.37 (1H, t, J = 7.8 Hz), 7.51 (1H, d, J = 9.0 Hz), 7.62 (1H, d, J = 3.0 Hz), 7.65-7.70 (2H, m), 7.68 (1H, s), 7.99 (1H, d, J = 3.0 Hz), 8.15-8.30 (3H, m), 8.58 (1H, s), 9.89 (1H, s). (iii) Production of N- (tert-butyl) -3- (. {5- [(5- {2- [(3-hydroxy-3-methylbutanoyl) amino] ethyl} -5H-pyrrolo [3, 2-d] pyrimidin-4-yl) amino] -lH-indol-1-yl.} Methyl) benzamide When using 3- [(5- {[5- (2-aminoethyl) dihydrochloride] - 5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.} - lH-indol-1-yl) methyl] -N- (tert-butyl) benzamide (150 mg), 3-hydroxy acid -3-methylbutanoic acid (48 mg), 1-hydroxybenzotriazole (59 mg), triethylamine (0.38 ml), l-ethyl-3- (3-) hydrochloride dimethylaminopropyl) carbodiimide (83 mg) and N, N-dimethylformamide (4.0 ml) and in the same manner as in Example G-8 (v), the title compound (80 mg) was obtained in the form of aracarine-colored crystals. pale. XH-NMR (CDC13) d: 1.25 (6H, s), 1.46 (9H, s), 2.44 (2H, s), 3.55-3.65 (2H, m), 4.45-4.55 (2H, m), 5.30 (2H, s), 5.99 (1H, s), 6.51 (1H, d, J = 3.0 Hz), 6.57 (1H, d, J = 3.3 Hz), 7.10-7.35 (6H, ra), 7.55 (1H, d, J = 8.1 Hz), 7.64 (1H, s), 7.75-7.80 (1H, m), 8.05 -8.10 (1H, m), 8.28 (1H, s), 9.55-9.65 (1H, br). Example G-20 Production of N- (tert-butyl) -3- [(5- { [5- (2- { [2-methyl-2- (methylsulfonyl) propanoyl] amino.} Ethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.} - lH-indol-1-yl) methyl] benzamide When using 3- [(5- {[5- (2-aminoethyl) dihydrochloride] - 5H-pyrrolo [3,2-d] pyriraidin-4-yl] amino.} - 1 H -indol-1-yl) methyl] -N- (tert-butyl) benzamide (150 mg), 2-methyl acid -2- (methylsulfonyl) propanoic (68 mg), 1-hydroxybenzotriazole (59 mg), triethylamine (0.38 ml), l-ethyl-3- (3-dimethylaminopropyl) carbodiimide hydrochloride (83 mg) and N, N- dimethylformamide (4.0 ml) and in the same manner as in Example G-8 (v), the title compound (91 mg) was obtained as colorless crystals. XH-NMR (CDC13) d: 1.46 (6H, s), 1.60 (9H, s), 2.84 (3H, s), 3.60-3.75 (2H, m), 4.30-4.45 (2H, m), 5.34 (2H , s), 5.90 (1H, s), 6.51 (1H, d, J = 2.7 Hz), 6.55-6.60 (1H, m), 7.00-7.10 (1H, m), 7.10-7.40 (6H, m), 7.53 (1H, d, J = 7.5 Hz), 7.65 (1H, s), 7.81 (1H, s), 7.89 (1H, s), 8.44 (1H, s). Example H-l Production of N- (3. {2-chloro-4- [(6-chloro-5-methyl-5H-pyrrolo [3,2-d] pyrimidin-4-yl) amino] phenoxy] phenyl) Cyclopropanecarboxamide (i) Production of 4.6-dichloro-5-methyl-5H-pyrrolo [3,2-d] pyrimidine To a solution of diisopropylamine (540 mg) in tetrahydrofuran (12 ml) was added n-butyllithium (2.7 ml ) at 0 ° C. After stirring for 30 min, the mixture was cooled to -78 ° C, and 4-chloro-5-methyl-5H-pyrrolo [3,2-d] pyrimidine (500 mg) was added. The reaction mixture was stirred for 1 h, p-toluenesulfonyl chloride (690 mg) was added, and the mixture was It allowed to reach -40 ° C for 1 h. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by column chromatography on silica gel (eluent, hexane: ethyl acetate = 80: 20- »30: 70). After concentrating under reduced pressure, the resulting crystals were collected by filtration, and washed with diisopropyl ether to give the title compound (191 mg) as crystals. VL-NMR (CDC13) d: 4.13 (3H, s), 6.72 (1H, s), 8.68 (1H, s). (ii) Production of N- (3. {2-chloro-4- [(6-chloro-5-methyl-5H-pyrrolo [3,2-d] pyrimidin-4-yl) amino] phenoxy] phenyl) cyclopropanecarboxamide A mixture of 4.6-dichloro-5-methyl-5H-pyrrolo [3,2-d] pyrimidine (98 mg), N- [3- (4-amino-2-chlorophenoxy) phenyl] cyclopropanecarboxamide (167 mg) and isopropyl alcohol (7.0 ml) was stirred at 80 ° C for 3 h. The reaction mixture was concentrated under reduced pressure, water and saturated aqueous sodium acid carbonate were added and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine and dried over anhydrous magnesium sulfate. The solvent was evaporated under reduced pressure and the The residue obtained was subjected to silica gel column chromatography (eluent, hexane: ethyl acetate = 80: 20- »0: 100). The object fractions were concentrated under reduced pressure. The residue was crystallized from ethyl acetate-hexane to give the title compound (146 mg) as a white powder. VL-NMR (CDC13) d: 0.78-0.84 (2H, m), 0.99-1.05 (2H, m), 1.47-1.54 (1H, m), 4.07 (3H, s), 6.60 (1H, s), 6.75 -6.77 (2H, m), 7.01-7.04 (2H, m), 7.20-7.26 (3H, m), 7.62 (1H, s), 8.10 (1H, br s), 8.47 (1H, s). Example H-2 production of 6-chloro-N-. { 3-Chloro-4- [3- (trifluoromethyl) phenoxy] phenyl} -5-methyl-5H-pyrrolo [3,2-d] pyrimidin-4-amine When using 4.6-dichloro-5-methyl-5H-pyrrolo [3,2-d] pyrimidine (70 mg), 3-chloro- 4- [3- (trifluoromethyl) phenoxy] aniline (109 mg) and isopropyl alcohol (7.0 ml) and in the same manner as in Example Hl (ii), the title compound (61 mg) was obtained as crystals . Vl-NMR (DMSO-d6) d: 4.07 (3H, s), 6.73 (1H, s), 7. 21-7.33 (3H, m), 7.46-7.67 (3H, m), 7.93 (1H, br s), 8.40 (1H, br s), 8.97 (1H, br s). Example H-3 Production of 6-chloro-5-methyl-N-. { 3-methyl-4- [(6-methylpyridin-3-yl) oxy] phenyl} -5H-pyrrolo [3,2-d] pyrimidin-4-amine When using 4.6-dichloro-5-methyl-5H-pyrrolo [3,2-d] pyrimidine (150 mg), 3-methyl-4- [( 6-methylpyridin-3-yl) oxy] aniline (160 mg) and isopropyl alcohol (8.0 ml) and in the same manner as in Example Hl (ii), the title compound (116 mg) was obtained as crystals . Vl-NMR (DMSO-d6) d: 2.17 (3H, s), 2.43 (3H, s), 4.04 (3H, s), 6.65 (1H, s), 6.94 (1H, d, J = 8.3 Hz), 7.16-7.25 (2H, m), 7.44-7.51 (2H, m), 7.16 (1H, d, J = 2.7 Hz), 8.28 (1H, s), 8.57 (1H, s). Example H-4 Production of 6-chloro-N- [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] -5-methyl-5H-pyrrolo [3,2-d] pyrimidin-4-amine When using 4.6-dichloro- 5-methyl-5H-pyrrolo [3,2-d] pyrimidine (150 rag), 3-chloro-4- (pyridin-2-yl-ethoxy) aniline (210 mg) and isopropyl alcohol (10 ml) and in the same manner that in Example Hl (ii), the title compound was obtained (170 mg) in the form of crystals. XH-NMR (DMSO-dg) d: 4.03 (3H, s), 5.27 (2H, s), 6.64 (1H, s), 7.20-7.91 (6H, m), 8.25 (1H, s), 8.54 (1H , br s), 8.58-8.62 (1H, m). Example H-5 Production of N- [3- (2-chloro-4- { [6-chloro-5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-yl] amino.}. Phenoxy ) phenyl] cyclopropanecarboxamide (i) Production of 5- (2. {[[tert-butyl (dimethyl) silyl] oxy} ethyl) -4-chloro-5H-pyrrolo [3,2-d] pyrimidine 4- chloro-5H-pyrrolo [3,2-d] pyrimidine (2.00 g), (2-bromoethoxy) (tert-butyl) diraethylsilane (4.00 g) and cesium carbonate (6.40 g) were dissolved in N, N-dimethylformamide ( 10 ral) and the mixture was stirred at room temperature for 4 h. Under cooling with ice, brine was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: hexane = 20: 80-> 40: 60) to give the title compound (3.02 g) as a brown solid . XH-NMR (DMSO-dg) d: -0.24 (6H, s), 0.69 (9H, s), 3. 90-3.93 (2H, m), 4.61-4.64 (2H, m), 6.76 (1H, s), 8.00 (1H, s), 8.61 (1H, s). (ii) Production of N- [3- (2-chloro-4- { [6-chloro-5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino phenoxy) phenyl] cyclopropanecarboxamide When using diisopropylamine (2.20 g), 1.6 M n-butyllithium (14 ml), tetrahydrofuran (50 ml), 5- (2- {[tert-butyl (dimethyl) silyl) ] oxy] ethyl) -4-chloro-5H-pyrrolo [3,2-d] pyrimidine (500 mg), p-toluenesulfonyl chloride (6.10 g), N- [3- (4-amino-2- chlorophenoxy) phenyl] cyclopropancarboxamide (190 mg) and isopropyl alcohol (10 ml) and in the same manner as in Example Hl (i) and (ii), a co-tax was obtained. The obtained compound was dissolved in methanol (10 ml), 4N hydrogen chloride solution / ethyl acetate (3.0 ml) was added, and the mixture was stirred at 80 ° C for 18 h. Low After cooling with ice, aqueous sodium bicarbonate was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: methanol = 100: 0- »95: 5) to give the title compound (73 mg) as crystals. XH-NMR (DMSO-dg) d: 0.75-0.77 (4H, m), 1.69-1.75 (1H, m), 3.88-3.91 (2H, m), 4.53-4.55 (2H, m), 6.62-6.68 ( 1H, m), 6.72 (1H, s), 7.20-7.96 (6H, m), 8.37 (1H, s), 9.87-9.97 (1H, m), 10.24 (1H, s). Example H-6 Production of 6-chloro-N-. { 3-Chloro-4- [(3-fluorobenzyl) oxy] phenyl} -5-methyl-5H-pyrrolo [3,2-d] pyrimidin-amine When using 4.6-dichloro-5-methyl-5H-pyrrolo [3,2-d] pyrimidine (150 mg), 3-chloro-4 - [(3-fluorobenzyl) oxy] aniline (167 mg) and isopropyl alcohol (10 ml) and in the same manner as in Example H-1 (ii), the title compound (61 mg) was obtained as crystals.

Vl-NMR (DMSO-dg) d: 4.03 (3H, s), 5.24 (2H, s), 6.64 1H, s), 7.14-7.50 (6H, m), 7.71-7.72 (1H, m), 8.26 ( 1H, s), .52 (1H, s). Example H-7 Production of 3- (2-chloro-4- { [6-chloro-5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino} phenoxy) benzoic When using diisopropylamine (2.00 g), n-butyllithium 1.6 M (13 ml), tetrahydrofuran (50 ml), 5- (2- {[tert-butyl (dimethyl) silyl] oxy} ethyl) -4-chloro-5H-pyrrolo [3,2-d] pyrimidine (450 mg), p-toluenesulfonyl chloride (6.01 g), methyl 3- (4-amino-2-chlorophenoxy) benzoate (190 mg), isopropyl alcohol (10 ml), methanol (10 ml) and 4 N hydrogen chloride solution / ethyl acetate (3.0 ml) and in the same manner as in Example Hl (i), (ii) and Example H-5 (ii), a compound was obtained. To the obtained compound were added 1 N aqueous solution of sodium hydroxide (0.8 ml) and tetrahydrofuran (4.0 ml) and the mixture was stirred at room temperature for 2 days. The reaction mixture was neutralized with 1 N hydrochloric acid and bicarbonate was added thereto. of aqueous sodium and brine. The mixture was extracted with ethyl acetate, and the organic layer was dried over anhydrous magnesium sulfate and concentrated under reduced pressure. The residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate: methanol = 100: 0-> 95: 5) to give the title compound (127 mg) as crystals. XH-NMR (DMSO-dg) d: 3.83-3.91 (2H, m), 4.54-4.57 (2H, m), 6.49 (1H, br s), 6.73 (1H, s), 7.24-7.68 (6H, m ), 7.98 (1H, s), 9.97 (1H, s), 13.14 (1H, br s). Example H-8 Production of N- (tert-butyl) -3-. { 2-Chloro-4- [(6-chloro-5-methyl-5H-pyrrolo [3,2-d] pyrimidin-4-yl) amino] phenoxy} benzamide When using 4.6-dichloro-5-methyl-5H-pyrrolo [3,2-d] pyrimidine (110 mg), 3- (4-amino-2-chlorophenoxy) -N- (tert-butyl) benzamide (197 mg ) and isopropyl alcohol (10 ral) and in the same manner as in Example Hl (ii), the title compound (86 mg) was obtained as crystals. XH-NMR (DMSO-dg) d: 1.36 (9H, s), 4.06 (3H, s), 6.69 1H, s), 7.06-7.64 (6H, m), 7.81 (1H, s), 7.89 (1H, br s), .34 (1H, s), 8.81 (1H, s). Example H-9 Production of N- (tert-butyl) -3- (2-chloro-4- { [6-chloro-5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl) ] amino.}. phenoxy) benzamide When using diisopropylamine (2.80 g), 1.6 M n-butyllithium (16 ml), tetrahydrofuran (50 ral), 5- (2- {[tert-butyl (dimethyl) silyl) ] oxy] ethyl) -4-chloro-5H-pyrrolo [3,2-d] pyrimidine (800 mg), p-toluenesulfonyl chloride (7.10 g), 3- (4-amino-2-chlorophenoxy) - N- (tert-butyl) benzamide (811 mg) and isopropyl alcohol (16 ml) and in the same manner as in the H1 (i) and (ii), a compound was obtained. The obtained compound was dissolved in methanol (10 ml), 4 N hydrogen chloride solution / ethyl acetate (10 ml) was added, and the mixture was stirred at 80 ° C for 18 h. Under cooling with ice, aqueous sodium bicarbonate was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The residue was separated and purified by column chromatography on silica gel (eluent, ethyl acetate: methanol = 100: 0-95: 5) to give the title compound (576 mg) as crystals. Vl-NMR (DMSO-dg) d: 1.36 (9H, s), 3.88-3.91 (2H, m), 4.53-4.57 (2H, m), 6.72 (1H, s), 7.06-7.61 (6H, m) , 7.81 (1H, s), 7.96-7.97 (1H, m), 8.37 (1H, s), 9.52-10.53 (1H, m). Example H-10 Production of N- (tert-butyl) -3- (2-chloro-4- { [5- (2-hydroxyethyl) -6- (trifluoromethyl) -5H-pyrrolo [3,2-d] pyrimidin-4 -yl] amino.}. phenoxy) benzamide (i) Production of 5- (2- {[[tert-butyl (dimethyl) silyl] oxy} ethyl) -4-chloro-6- (trifluoromethyl) -5H pyrrolo [3,2-d] pyrimidine To a solution of diisopropylamine (300 mg) in tetrahydrofuran (20 ml) was added 1.6 M n-butyllithium (2.0 ml) at 0 ° C. After stirring for 30 min, the mixture was cooled to -78 ° C, and 5- (2- {[[tert-butyl (dimethyl) silyl] oxy} ethyl) -4-chloro-5H-pyrrolo was added. [3,2-d] pyrimidine (520 mg). The reaction mixture was stirred for 1 h, S-trifluoromethanesulfonate. (trifluoromethyl) dibenzothiophenium (2.00 g), and the mixture was allowed to reach -40 ° C for 1 h. Water was added to the reaction mixture and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, and dried over magnesium sulfate. After concentrating under reduced pressure, the residue was separated and purified by silica gel column chromatography (eluent, hexane: ethyl acetate = 80: 20-> 30: 70). After concentrating under reduced pressure, the resulting crystals were collected by filtration and washed with diisopropyl ether to give the title compound (29 mg) as crystals. VL-NMR (CDC13) d: 0.02 (6H, s), 0.74 (9H, s), 3.92-3.96 (2H, m), 4.74-4.78 (2H, m), 7.17 (1H, s), 8.79 (1H , s). (ii) Production of N- (tert-butyl) -3- (2-chloro-4- { [5- (2-hydroxyethyl) -6- (trifluoromethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. phenoxy) enamide When using 5- (2- {[[tert-butyl (dimethyl) silyl] oxy} ethyl) -4-chloro-6- (trifluoromethyl) -5H -pyrrolo [3, 2-d] pyrimidine (25 rag), 3- (4-amino-2-chlorophenoxy) -N- (tert-butyl) benzamide (26 mg) and isopropyl alcohol (1.5 ml) and the same so that in Example H-2 (ii), a compound was obtained. The obtained co-formula was dissolved in methanol (2.0 ml), 4N hydrogen chloride solution / ethyl acetate (1.0 ml) was added, and the mixture was stirred at 80 ° C for 18 h. Baking soda was added aqueous sodium to the reaction mixture under cooling with ice, and the mixture was extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous magnesium sulfate. The residue was separated and purified by silica gel column chromatography (eluent, ethyl acetate-methanol = 100: 0- »95: 5) to give the title compound (9.2 mg) as crystals. XH-NMR (CDC13) d: 1.36 (9H, s), 3.92-3.96 (2H, ra), 4.61-4.64 (2H, m), 7.06-7.45 (5H, m), 7.55-7.61 (2H, m) , 7.82 (1H, s), 7.97 (1H, s), 8.44 (1H, s), 9.50-10.55 (1H, m). Formulation example 1 (amount per tablet) (1) Compound obtained in Example Al 10.0 mg (2) Lactose 60.0 mg (3) Corn starch 35.0 mg (4) Gelatin 3.0 mg (5) Magnesium stearate 2.0 mg A mixture of 10.0 mg of the compound obtained in Example Al, 60.0 mg of lactose and 35.0 mg of corn starch is granulated through a 1-mesh sieve using 0.03 ml of a 10% by weight aqueous solution of gelatin (3.0 mg of gelatin), after which the granules are dried at 40 ° C and refiltered. The obtained granules are mixed with 2.0 mg of magnesium stearate and compressed. The cores of the obtained tablets are covered with a coverage of sugar comprising a suspension of sucrose, titanium dioxide, talc and gum arabic and polishing with beeswax to obtain sugar-coated tablets. Formulation Example 2 (dose per tablet) (1) Compound obtained in Example Al 10.0 mg (2) Lactose 70.0 mg (3) Corn starch 50.0 mg (4) Soluble starch 7.0 mg (5) Magnesium stearate 3.0 mg granulate 10.0 mg of the compound obtained in Example Al and 3.0 mg of magnesium stearate using 0.07 ml of an aqueous solution of soluble starch (7.0 mg of soluble starch), after which these granules are dried and mixed with 70.0 mg of lactose and 50.0 mg. mg of corn starch. This mixture is compressed to obtain tablets. EXPERIMENTAL EXAMPLE Cloning of human HER2 gene and preparation of recombinant baculoviruses The human HER2 gene was cloned by RT-PCR using total RNA prepared from MCF7 cells as a template. The primer used for RT-PCR was prepared from a nucleotide sequence information (access to Genbank No. M11730) of the HER2 gene by addition of a nucleotide sequence encoding the DYKDDDD peptide and a restriction enzyme recognition sequence. in a sequence of Nucleotides (2176-3918 of Genbank Accession No. M11730) encoding the region of the intracellular domain of HER2, so that the protein contains an N-terminal DYKDDDD peptide tag. The nucleotide sequence of the primer is indicated below. HER2-U: 5 '-AATTAAGTCGACATGGACTACAAAGACGATGACGACAAGCGACGGCAGCAGAAGATCCGGA AGTAC-3' (SEQ ID NO: 1) and HER2-L: 5 '-AATTAAGCATGCTCACACTGGCACGTCCAGACCCAGGTACTC-3' (SEQ ID NO: 2) The RT reaction was performed with a SuperScript First Synthesis system -Strand for RT-PCR (Invitrogen) and the PCR reaction was performed with a KOD-plus kit (TOYOBO). The obtained PCR product was subjected to agarose gel electrophoresis (1%), the DNA fragment was amplified by PCR, the gel was recovered and then digested with restriction enzymes Sal I and Sph I. The DNA treated with the enzymes of restriction was subjected to agarose gel electrophoresis (1%), and the DNA fragment obtained was recovered and ligated to plasmid pFASTBACl (Invitrogen) digested with the restriction enzymes Sal I and Sph I to give the expression plasmid pFB- HER2. The nucleotide sequence of the insert fragment was confirmed and found to be identical to the nucleotide sequence (2176-3918 of Genbank access M11730) of intracellular domain HER2. In addition, by the BAC-TO-BAC baculovirus expression system (Invitrogen), BAC-HER2 recombinant baculovirus was prepared. Experimental example IB Preparation of intracellular domain protein HER2 Cells SF-21 were seeded as 1 > 106 cells / ml in Sf-900H SFM medium (1 L, Invitrogen) containing 10% fetal bovine serum (traces), 50 mg / l gentamicin (Invitrogen) and 0.1% Pluronic F-68 (Invitrogen), and culture was carried out with agitation in a Erlenmeyer flask of 2 L volume at 27 ° C, 100 rpm. After culturing for 24 BAC-HER2 recombinant baculovirus (13.4 ml) was added, and the mixture was then cultured for 3 days. The culture medium was centrifuged at 2,000 rpm for 5 min to give cells infected by virus. The infected cells were washed with a physiological solution with phosphate pH regulator (Invitrogen), centrifuged under the same conditions, and the cells were stored at -80 ° C. The cryopreserved cells were thawed on ice, suspended in pH A regulator (50 mM pH regulator Tris (30 ml, pH 7.4) containing 20% glycerol, 0.15 M NaCl) supplemented with complete protease inhibitor (Boehringer) , and were decomposed three times with a Polytron (Kinematica) homogenizer at 20,000 rpm for 30 s. The means of rupture was clarified by centrifugation at 40,000 rpm for 30 min., and filtered with a 0.45 μm filter. The filtrate was passed through a column packed with M2 Anti-FLAG affinity gel (4 ml, Sigma) with a flow rate of about 0.5 ml / min. The column was washed with pH A regulator, and eluted with pH A regulator containing 100 μg / ml of FLAG peptide. Eluate was concentrated with Vivaspin 20 (Vivascience) with a molecular weight cut-off of 30K. The concentrate was purified by gel filtration with Hi Load Superdex 200pg 16/60 (Amersham Bioscience) equilibrated with pH regulator A. Fractions containing an HER2 intracellular domain were pooled, glycerol was added to the final concentration of 50% and cryocon-served at -80 ° C. Experimental example 1C Determination of inhibitory activity of HER2 kinase A test compound dissolved in dimethisulfoxide (DMSO) was diluted with a pH regulator for kinase reaction (50 mM Tris-HCl (pH 7.5), 5 mM MgCl2, 5 mM MnCl2, 2 mM dithiothreitol, 0.01% T een-20). To this compound solution (10 μL) was added a pH regulator for kinase reaction (20 μL) containing 5 μg / ml of intracellular domain HER2 obtained in Experimental Example IB and 12.5 μg / ml of poly-peptide substrate. Glu: Tir (4: 1) (Sigma). To the obtained mixture was added 20 μL of ATP solution (1.25 μM of ATP, 0.05 μCi [? -32P] ATP), the mixture was allowed to react at 25 ° C for 10 min. and the reaction was adjusted to pH with 50 μl of 20% TCA solution. The reaction solution was allowed to stand at 4 ° C for 20 min. , and the more soluble acid fraction was transferred to a GF / C filter (PerkmElmer) with a cell harvester (PerkinElmer) and washed with 250 mM phosphoric acid solution. After washing, the plate was dried at 45 ° C for 60 min., And 35 μL of MicroScmti 0 (PerkmElmer) was added. The radioactivity was measured with TopCount (PerkmElmer). The inhibitory rate of HER2 cmasa (%) of the test compound was calculated according to the following formula: Inhibitory rate (%) = (1- (test compound count - blank) - (control - blank)) xl00 The count of the solution that reacted without addition of the compound was used as "control", and the count of the solution without the compound and the intracellular domain HER2 was used as "blank". The results of the inhibitory rate of the compounds are shown in Table 1. From the above, it was shown that the compounds of the present invention strongly inhibited the activity of HER2 c asa.

Table 1 Example No. Inhibition rate [compound No. at 1.0 μM at 98 A-15 99 Bl 99 C-26 98 C-45 97 C-89 100 E-22 99 G-5 93 G-14 100 Experimental example 2 Inhibitory action on breast cancer cell proliferation BT-474 in vi tro A suspension of human breast cancer cells BT-474 (100 μl (6, 000 cells)) was seeded for its attachment in a 96-well microplate and cultured in an incubator (37 ° C, 5% carbon dioxide). The next day, 100 μl of a solution of each test compound previously diluted serially in halves was added to give the indicated dose, and the cells were cultured for 5 days. After extracting the culture medium containing the test compound, the cells were washed and fixed with 50% trichloroacetic acid, after which at 0.4% (w / v) of SRB solution (dissolved in 1% acetic acid) a dye was added to the cellular protein (Skehan et al., Journal of the National Cancer Institute, Vol. 82, p. 1107-1112, 1990). After washing with a 1% solution of acetic acid, 100 μl of Tris solution (10 mM) was added to extract the pigment and the absorbance was measured at a wavelength of 550 nm to quantify the number of cells as a content of proteins If the protein content of the control group, which did not receive the test compound solution, was taken as 100%, the ratio of residual protein content for each treatment group was determined, and the concentration of compound required to obtain 50% was calculated. of suppression of the residual cells content with respect to the control (IC50 value). The results are shown in Table 2. Table 2 Example No. (Compound No.) IC50 (nM) A-l < 100 C-45 < 100 C-97 < 100 C-116 < 100 G-5 < 100 Industrial Applicability According to the present invention, pyrrolo [3,2-d] pyrimidine and pyrazolo [4, 3-d] pyrimidine compounds, one of their production methods and their use, are provided. These fused pyrimidine compounds have superior inhibitory action of tyrosine kinase, are very safe, and are sufficiently satisfactory as pharmaceuticals. This application is based on patent applications No. 2005-349858 and 2006-060648 filed in Japan, the contents of which are hereby incorporated by reference in their entirety. It is noted that in relation to this date, the best method known to the applicant to carry out the aforementioned invention, is that which is clear from the present description of the invention.

Claims

CLAIMS Having described the invention as above, property is claimed as contained in the following claims: 1. A compound represented by the formula: characterized in that Rla is a hydrogen atom, R 2a is a C?-6 alkyl group substituted with a group represented by C? alkyl - optionally halogenated with -NR6a-C0- (CH2) n ~ S02- wherein n is a integer from 1 to 4, R6a is a hydrogen atom or an alkyl group of C? _, and - (CH2) n- is optionally substituted by C? _ alkyl, R, 3a is a hydrogen atom or a group alkyl of Ci- R > 4a is a halogen atom or an alkyl group of R, 5a is a halogen atom or an alkyl group of Ci-g, and Xa is a hydrogen atom or a halogen atom, or a salt thereof, with the proviso that N- [2- (4- { [3-chloro-4- (3 -chlorophenoxy) phenyl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2- (ethethylsulfonyl) acetamide.
2. The compound according to claim 1, characterized in that Xa is a hydrogen atom.
3. The compound according to claim 2, characterized in that Rla is a hydrogen atom, R2a is an alkyl group of Ci-g substituted with a group represented by -NR6aa-CO-CR7aR8a-S02-alkyl of C? _4 wherein R6aa is a hydrogen atom or a methyl group, R7a and R8a are the same or different and each is a hydrogen atom or a methyl group, R3a is a hydrogen atom, R4a is a chlorine atom or a methyl group , and R5a is a fluorine atom, a chlorine atom or a methyl group.
4. The compound according to claim 3, characterized in that R7a and R8a are methyl groups. 5. - A compound, characterized in that select from the following: N- [2- (4- { [3-chloro-4- (3-chlorophenoxy) phenyl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl. ) ethyl] -2-methy1-2- (methylsulfonyl) propanamide, N- [2- (4- { [3-chloro-4- (3-chlorophenoxy) phenyl] amino.}. -5H-pyrrolo [3 , 2-d] pyrimidin-5-yl) ethyl] -2- (ethylsulfonyl) acetaraide, N- [2- (4- { [3-chloro-4- (3-chlorophenoxy) phenyl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -N , 2-dimethyl-2- (methylsulfonyl) propanamide, N- [2- (4- { [3-chloro-4- (3-methylphenoxy) phenyl] amino.}. -5H-pyrrolo [3,2- d] pyrimidin-5-yl) ethyl] -2- (methylsulfonyl) acetamide, N- [2- (4- { [3-chloro-4- (3-fluorophenoxy) phenyl] amino.}. -5H- pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2- (methylsulfonyl) acetamide, and N- [2- (4- { [4- (3-chlorophenoxy) -3-methylphenyl] amino .5. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2-methy1-2- (methylsulfonyl) propanamide, or one of its salts, or one of its hydrates. 6. A compound represented by the formula: characterized because WD is C (R lb v N, the ring Ab is an optionally substituted pyridine ring, Xlb is -NR3b-Ylb-, -0-, -S-, -SO-, -S02- or -CHR3b- in wherein R3b is a hydrogen atom or an optionally substituted aliphatic hydrocarbon group, or R3b is optionally bonded to the carbon atom in the pyridine ring for the Ab ring to form an optionally substituted ring structure, and Ylb is a bond, or an alkylene of C? _ u -0- (C? _4 alkylene) -, each of which is optionally substituted, and Rlb is a hydrogen atom, a halogen atom, or an optionally substituted group attached through an atom carbon, a nitrogen atom or an oxygen atom, R2b is a hydrogen atom, or an optionally substituted group attached through a carbon atom or a sulfur atom, or Rlb and R2b, or R2b and R3b are joined optionally to form an optionally substituted ring structure, or one of its salts. omitted in accordance with claim 6, characterized in that it is represented by the formula: wherein ring A is a pyridine ring also optionally substituted, ring Bb is an aryl group of Cg_? optionally substituted, and the other symbols are as defined in claim 6. 8. The compound according to claim 7, characterized in that Rlb is a hydrogen atom, a halogen atom, a cyano group or an optionally halogenated C? _6 alkyl group, R2b is a C? _6 alkyl group substituted with substituents selected from the group consisting of (i) -NR6ba-CO- (CH2) ni-S02-alkyl of C? _ Wherein R is a hydrogen atom or a methyl group, nor is an integer from 1 to 4, and - (CH2) ni- is optionally substituted with C? - alkyl, (ii) -NR6bb-CO- (CH2) n2-OH wherein R6bb is a hydrogen atom or a methyl group, n2 is an integer from 1 to 4, and - (CH2) n2 - is optionally substituted with C? - alkyl, (iii) -0- (CH2) n3-OH wherein n3 is an integer from 1 to 4, and - (CH2) n3_ is optionally substituted with C? _ alkyl, and (iv) hydroxy, R3b is an atom of hydrogen, the Ab ring is a pyridine ring optionally substituted with substituents selected from the group consisting of halogen and methyl, and the ring Bb is a phenyl group optionally substituted with substituents selected from the group consisting of optionally halogenated C? -6 alkyl , optionally halogenated C? _6 alkoxy, C? -6-carbamoyl alkyl and halogen. 9. The compound according to claim 7, characterized in that the ring Ab 'is a pyridine ring optionally substituted with halogen, and the ring Bb is a phenyl group optionally substituted at the 3-position by substituents selected from the group consisting of alkyl of optionally halogenated C? -6, optionally halogenated C? _, alkoxy, alkyl of Ci-g-carbamoyl and halogen. 10. A compound, characterized in that it is selected from the following: 2-. { 2- [4- ( { 5-chloro-6- [3- (trifluoromethyl) phenoxy] pyridin-3-yl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethoxy} Ethanol, N-. { 2- [4- ( { 5-Chloro-6- [3- (trifluoromethyl) phenoxy] pyridin-3-yl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide, N-. { 2- [4- ( { 5-Chloro-6- [3- (trifluoromethyl) phenoxy] pyridin-3-yl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -3-hydroxy-3-methylbutanamide, N-. { 2- [4- ( { 5-Chloro-6- [3- (trifluoromethoxy) phenoxy] pyridin-3-yl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (Rethylsulfonyl) acetamide, and N- (tert-butyl) -3- [(3-chloro-5- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidine -4-yl] amino.}. Pyridin-2-yl) oxy] benzamide, or one of its salts. 11. A compound represented by the formula: characterized in that Rlc is a hydrogen atom, or an optionally substituted group attached through a hydrogen atom carbon, a nitrogen atom or an oxygen atom, R2c is an optionally substituted group attached through a carbon atom or a sulfur atom, or Rlc and R2c, or R2c and R3c are optionally attached to form a ring structure optionally substituted, R3c is a hydrogen atom or an optionally substituted aliphatic hydrocarbon group, or R3c is optionally attached to the carbon atom in the adjacent Benzene ring to form an optionally substituted ring structure, the Ac ring is an optionally substituted benzene ring, R5c is (i) an optionally substituted amino group, (ii) an optionally substituted carbamoyl group, (ii) an optionally substituted ureido group, (iv) an optionally substituted sulfamoyl group, (v) an optionally substituted heterocyclic group, (vi) an optionally substituted C 2-6 alkoxy group, (vii) an optionally substituted aminomethyl group, (viii) an optionally substituted carbamoylmethyl group, (ix) an alkylsulfonyl group optionally substituted, or (x) a cyano group, and the ring Bc is an aryl group of C6_? 4 or a cycloalkyl group of C5-8, each of which is also optionally substituted in addition to R5c, or a salt thereof, with the proviso that N- (tert-butyl) -4- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3.2] hydrochloride is excluded. -d] pyrimidin-4-yl.}. amino) phenoxy] benzamide, 4- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3.2 -d] pyrimidin-4-yl.}. amino) phenoxy] -N- (2,2-dimethylpropyl) benzamide, 3- (2-chloro-4- { [5- (2-hydroxyethyl) -5H- pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. phenoxy) benzonitrile, 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H- pyrrolo [3,2-d] pyrimidin-4-yl.}. amino) phenoxy] benzonitrile, 3- [2-chloro-4- (6,7-dihydro-9H-pyrimido [4 ', 5': 4.5] hydrochloride] pyrrolo [2.1-c] [1.4] oxazin-4-ylamino) phenoxy] benzonitrile, and (2E) -N- [(2E) -3- (4- { [3-chloro-4- (3-cyanophenoxy) ) phenyl] amino.}. -5-methy1-5H-pyrrole [3, 2-d] pyrimidin-6-yl) prop-2-en-1-yl] -4- (dimethylamino) but-2-enamide. 12. The compound according to claim 11, characterized in that Rlc is an hydrogen 13. A compound, characterized in that it is selected from the following: 2-. { 2- [4- ( { 3-chloro-4- [3- (1, 3-thiazol-5-yl) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidine- 5-yl] ethoxy} ethanol, N- (tert-butyl) -3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidine-4- il.}. amino) phenoxy] benzamide, 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4- il.}. amino) phenoxy] -N- (2-hydroxy-1,1-dimethylethyl) benzaraide, N- (tert-butyl) -3- (2-chloro-4- { [5- (2- hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. phenoxy) benzamide, N- (3. {2-chloro-4- [(6-cyano-5-methyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl) amino] phenoxy] phenyl) cyclopropanecarboxamide, N- (tert-butyl) -5- (2-chloro-4-. {[[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}. Phenoxy) -2-fluorobenzamide, N-. { 2- [4- ( { 3-Chloro-4- [3- (dimethylamino) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -3-hydroxy-3-methylbutanamide, N-. { 2- [4- ( { 3-Chloro-4- [3- (dimethylamino) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide, N- (tert-butyl) -2- [3- (2-chloro-4- { [5- (2-hydroxyethyl) - 5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino} phenoxy) phenyl] acetamide, N-. { 2- [4- ( { 3-Chloro-4- [3- (cyclopropylmethoxy) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (Rethylsulfonyl) acetamide, N-. { 2- [4- ( { 3-Chloro-4- [3- (2,2-dimethylpropoxy) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethyl} -2- (methylsulfonyl) acetamide, 2- (methylsulfonyl) -N-. { 2- [4- ( { 3-methyl-4- [3- (2,2,2-trifluoroethoxy) phenoxy] phenyl}. Amino) -5H-pyrrolo [3,2-d] pyrimidine-5- il] ethyl} acetamide, 2- [4- ( { 3-chloro-4- [3- (isopropylsulfonyl) phenoxy] phenyl} amino) -5H-pyrrolo [3,2-d] pyrimidin-5-yl] ethanol, and N- [2- (4- { [3-chloro-4- (3-cyanophenoxy) phenyl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] - 2- (Methylsulfonyl) acetamide, or one of its salts. 14. A compound represented by the formula: characterized because Rld is a hydrogen atom, or an optionally substituted group attached through a carbon atom, a nitrogen atom or an oxygen atom, R2d is an optionally substituted group attached through a carbon atom or a sulfur atom , or Rld and R2d, or R2d and R3d optionally join to form an optionally substituted ring structure, R3d is a hydrogen atom or an optionally substituted aliphatic hydrocarbon group, or R3d is optionally attached to the carbon atom in the adjacent Benzene ring to form an optionally substituted ring structure, the Ad ring is an optionally substituted benzene ring, Zd is an optionally substituted C? _3 alkylene, the Bd ring is an optionally substituted heterocyclic group, or a salt thereof, provided that to be excluded 5- [(4- {[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} -5H-pyrrolo [3,2-d] pyrimidin-5-yl) methyl ] -2-ethyl furoate, 5- [(4 - { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino} -5H-pyrrolo [3,2-d] pyrimidin-5-yl) methyl] -2-furancarboxylic acid, 2- [2- (4 { [3-chloro-4- (pyridin-2-ylmethoxy) phenyl) ] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5- il) ethoxy] ethanol, and N- [2- (4. {[[3-chloro-4- (pyridin-2-ylmethoxy) phenyl] amino]} -5H-pyrrolo [3,2-d] pyrimidine -5-yl) ethyl] -2- (methylsulfonyl) acetamide. 15. The compound according to claim 14, represented by the formula: characterized in that R4d is an acyl group or an optionally substituted ureido group, the Bd 'ring is a piperidyl group also optionally substituted in addition to R4d, and the other symbols are in accordance with claim 14. 16. A compound, characterized in that it is selected from the following: 4-. { [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] methyl} tert-butyl piperidine-1-carboxylate, and 4- [(2-chloro-4. {[[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino] .}. phenoxy) methyl] piperidine-1-carboxylate of tert-butyl, or one of its salts. 17. A compound represented by the formula: characterized in that Rle is a hydrogen atom, or an optionally substituted group attached through a carbon atom, a nitrogen atom or an oxygen atom, R2e is an optionally substituted group attached through a carbon atom or atom of sulfur, or Rle and R2e, or R2e and R3e are optionally attached to form an optionally substituted ring structure, R3e is a hydrogen atom or an optionally substituted aliphatic hydrocarbon group, or R3e is optionally attached to the carbon atom in the ring Adjacent benzene to form an optionally substituted ring structure, ring Ae is an optionally substituted benzene ring, R5e is a linear alkyl group substituted with group optionally substituted heterocyclic, (ii) a linear alkyl group substituted by optionally substituted imino, (iii) a linear alkyl group substituted by optionally substituted aryl, which is also optionally halogenated or hydroxylated, (iv) an optionally substituted branched alkyl group, (v) ) an optionally substituted alkenyl group, (vi) an optionally substituted aryl substituted hydroxy group, (vii) a hydroxy group substituted with C? -6 alkyl, (viii) a hydroxy group substituted with halogenated C2-g alkyl, ( ix) a halogenated C2-g alkyl group, (x) an optionally substituted cycloalkyl group, or (xi) a Ci-g-carbonyl alkyl group optionally substituted with optionally substituted aryl, and the Be ring is an aryl group of Cg_ 4 also optionally substituted in addition to R5e, or one of its salts, with the proviso that 2- (2-. {4- [(3-chloro-4-. {4-4- 3- dihydrochloride]] is excluded. ( 1 HOUR- imidazol-1-yl) propyl] phenoxy} phenyl) amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl} ethoxy) ethanol, 2- (2-. {4- [(3-chloro-4-. {4- [4- (1H-1,2,3-triazol-1-yl) butyl] phenoxy] phenyl ) amino] -5H-pyrrolo [3,2-d] pyrimidin-5-yl.} ethoxy) ethanol, and l-. { 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] phenyl} Ethanone 18. A compound, characterized in that it is selected from the following: 2- [4- ( { 3-chloro-4- [3- (1,1-difluoroethyl) phenoxy] phenyl} amino) -5H- pyrrolo [3,2-d] pyrimidin-5-yl] ethanol, O-ethyl oxime of (1Z) -1-. { 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] phenyl} -2, 2-dimethylpropan-l-one, l-. { 3- [2-chloro-4- (. {5- [2- (2-hydroxyethoxy) ethyl] -5H-pyrrolo [3,2-d] pyrimidin-4-yl} amino) phenoxy] phenyl} -2, 2-dimethylpropan-1-ol, l- [3- (2-chloro-4. {[[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] ] amino.}. phenoxy) phenyl] -3,3-dimethylbutan-1-one, N- (2- { 4- [(3-methyl-4- { 3- [(1 E) -3-methylbut-l-en-1-yl] phenoxy] phenyl) amino] -5H -pyrrolo [3,2-d] pyriraidin-5-yl.} ethyl) -2- (methylsulfonyl) acetamide, and N-. { 2- [4- ( { 3-chloro-4- [3- (l-cyanocyclopropyl) phenoxy] phenyl} amino) -5H-pyrrolo [3,2- d] pyrimidin-5-yl] ethyl} -2- (Methylsulfonyl) acetamide, or one of its salts. 19.- A compound represented by the formula characterized in that g is C (Rlg) or N, ring A9 is an optionally substituted benzene ring, ring B9 is a heterocycle with optionally substituted nitrogen content, Xlg is -NR3g-Ylg-, -O-, -S-, -SO-, -S02- or -CHR3g- wherein R3g is a hydrogen atom or an optionally substituted aliphatic hydrocarbon group, or R3g is optionally attached to the carbon atom in the Benzene ring for the Ag ring to form a ring structure optionally substituted, and Ylg is a bond, or an alkylene of C? _ u -0- (alkylene of C? _) -, each of which is optionally substituted, and Rlg is a hydrogen atom, a halogen atom , or an optionally substituted group attached through a carbon atom, a nitrogen atom or an atom of oxygen, R2g is a hydrogen atom, or an optionally substituted group attached through a carbon atom or a sulfur atom, or Rlg and R2g, or R2g and R3g are optionally attached to form an optionally substituted ring structure, or one of its salts. 20. The compound according to claim 19, which is a compound represented by the formula: characterized in that R4g is an optionally substituted hydrocarbon group, ring Bg 'is a heterocycle with 5- or 6-membered nitrogen content also optionally substituted in addition to R4g, and the other symbols are in accordance with claim 19. 21.- The co-pay according to claim 20, characterized in that Rlg is a hydrogen atom, a halogen atom, a cyano group or an optionally halogenated C? _ alkyl group, R2g is a hydrogen atom or an optionally substituted C? -6 alkyl group, R3g is a hydrogen atom or an alkyl group of R g is (i) an optionally substituted aryl Cg-14-C 8 alkyl group, (ii) an optionally substituted heterocyclyl C-8 alkyl group, (iii) an alkyl group of C 8, or iv) an optionally substituted C6-? 4 aryl group. 22. The compound according to claim 20, characterized in that Rlg is a hydrogen atom, a halogen atom, a cyano group or an optionally halogenated C? -6 alkyl group, R2g is (i) a hydrogen atom , (ii) an alkyl group of C? _6, or (iii) a C? -6 alkyl group substituted with substituents selected from the group consisting of (a) -0- (CH2) n-OH, (b) - NR5g-CO- (CH2) n-OH, (c) -NR5g-CO- (CH2) n-S02-optionally halogenated C? -4 alkyl, (d) hydroxy, and (e) amino wherein n is a integer from 1 to 4, R5g is a hydrogen atom or an alkyl group of C? _, and - (CH2) n- is optionally substituted by C? _ alkyl, R3g is a hydrogen atom or an alkyl group of It is the formula R 4g is i) an aryl C6-? 4-C? _8 alkyl optionally substituted with substituents selected from the group consisting of halogen, Ci-g-carbamoyl alkyl and Ci-g haloalkoxy, (ii) a heterocyclic group - optionally substituted Ci-β alkyl, or (iii) an optionally substituted Cg_i 4 aryl group. 23. A compound, characterized in that it is selected from the following: N- [2- (4- { [1- (3-fluorobenzyl) -lH-indazol-5-yl] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -2- (methylsulfonyl) acetamide, N- [2- (4. {[[1- (3-fluorobenzyl) -lH-indol-5-yl] ] amino.}. -5H-pyrrolo [3,2-d] pyrimidin-5-yl) ethyl] -3-hydroxy-3-methylbutanamide, N- (tert-butyl) -3- [(5- { [5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] amino.}.-LH-indole -1-yl) methyl] benzamide, N- (tert-butyl) -3- [(5- {[5- (2-hydroxyethyl) -5H-pyrrolo [3,2-d] pyrimidin-4-yl] ] amino.}. - lH-indazol-1-yl) methyl] benzamide, and N- (tert-butyl) -6- [(5 { [5- (2-hydroxyethyl) -5H-pyrrolo [3 , 2-d] pyrimidin-4-yl] amino.} - lH-indol-1-yl) methyl] pyridine-2-carboxamide, or one of its salts. 24.- A compound represented by the formula: characterized in that Rlh is a halogen atom or a halogenated C? _6 alkyl group, R2h is a hydrogen atom, or an optionally substituted group attached through a carbon atom or a sulfur atom, or Rlh and R2h, or R2h and R3h are united to form a optionally substituted ring structure, R3h is a hydrogen atom or an optionally substituted aliphatic hydrocarbon group, or R3h is optionally bonded to the carbon atom in the adjacent Benzene ring to form an optionally substituted ring structure, Zh is a bond or an alkylene of C1-3 optionally substituted, ring A is an optionally substituted benzene ring, and ring Bh is (i) an optionally substituted C6-14 aryl group, (ii) an optionally substituted heterocyclic group, or (iii) a group optionally substituted C5_8 cycloalkyl, or a salt thereof. 25. The compound according to claim 24, represented by the formula: characterized in that R5h is (i) an optionally substituted amino group, (ii) an optionally substituted carbamoyl group, (iii) an optionally substituted ureido group, (iv) an optionally substituted sulfamoyl group, (v) an optionally substituted heterocyclic group, (vi) a group optionally substituted hydrocarbon, (vii) a halogen atom, or (viii) an optionally substituted carboxyl group, and the Bh 'ring is (i) an aryl group of Cg-? 4, (ii) a heterocyclic group, or (iii) a group C5_8 cycloalkyl, each of which is also optionally substituted in addition to R5h, and the other symbols are in accordance with claim 24. 26. A compound, characterized in that it is selected from the following: N- (3- { 2-Chloro-4- [(6-chloro-5-methyl-5H-pyrrolo [3,2-d] pyrimidin-4-yl) amino] phenoxy] phenyl) cyclopropanecarboxamide, 6-chloro-N-. { 3-Chloro-4- [3- (trifluoromethyl) phenoxy] phenyl} -5-methyl-5H-pyrrolo [3,2-d] pyrimidin-4-amine, N- [3- (2-chloro-4- { [6-chloro-5- (2-hydroxyethyl) -5H -pyrrolo [3, 2-d] pyrimidin-4- il] amino} phenoxy) phenyl] cyclopropanecarboxamide, and N- (tert-butyl) -3- (2-chloro-4 { [6-chloro-5- (2-hydroxyethyl) -5H-pyrrolo [3, 2-d] pyrimidin-4-yl] amino.}. phenoxy) enzamide, or one of its salts. 27. A prodrug, characterized in that it is of the compound according to any of claims 1 to 26. 28.- A pharmaceutical agent, characterized in that it comprises any of claims 1 to 26 or one of its salts or one of its prodrugs. 29. - The pharmaceutical agent according to claim 28, characterized in that it is a tyrosine kinase inhibitor. 30. The pharmaceutical agent according to claim 28, characterized in that it is an agent for the prevention or treatment of cancer. 31. The pharmaceutical agent according to claim 30, characterized in that the cancer is breast cancer, ovarian cancer, colorectal cancer, gastric cancer, esophageal cancer, prostate cancer, lung cancer, pancreatic cancer or cancer. kidney. 32. Use of the compound according to any of claims 1 to 26 or one of its salts or one of its prodrugs, for the production of an agent for the prevention or treatment of cancer.