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WO2025230262A1 - Novel heteroaryl derivatives and use thereof in inhibiting aak1 - Google Patents

Novel heteroaryl derivatives and use thereof in inhibiting aak1

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Publication number
WO2025230262A1
WO2025230262A1 PCT/KR2025/005735 KR2025005735W WO2025230262A1 WO 2025230262 A1 WO2025230262 A1 WO 2025230262A1 KR 2025005735 W KR2025005735 W KR 2025005735W WO 2025230262 A1 WO2025230262 A1 WO 2025230262A1
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WO
WIPO (PCT)
Prior art keywords
pyridin
amine
oxy
pyrrolo
difluoromethyl
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
PCT/KR2025/005735
Other languages
French (fr)
Korean (ko)
Inventor
김보람
이형근
김인우
조성진
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Cimplrx Co Ltd
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Cimplrx Co Ltd
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Publication of WO2025230262A1 publication Critical patent/WO2025230262A1/en
Pending legal-status Critical Current
Anticipated expiration legal-status Critical

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
    • C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
    • C07D471/04—Ortho-condensed systems
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
    • A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
    • A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
    • A61K31/444—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
    • A61P25/16—Anti-Parkinson drugs
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/18—Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/24—Antidepressants
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond

Definitions

  • Adaptor-associated kinase 1 is a 104 kDa serine/threonine kinase belonging to the Numb-associated kinase (NAK) family, also known as AP2-associated protein kinase 1. It is encoded by the AAK1 gene in humans and is involved in clathrin-mediated endocytosis.
  • AAK1 is a key endocytic kinase known to be expressed in the plasma membrane and cytoplasm and to have two physiological substrates.
  • AAK1 has been proposed as a drug target for the treatment of various neurological and psychiatric disorders, including schizophrenia, cognitive deficits in schizophrenia, Parkinson's disease, bipolar disorder, Alzheimer's disease, and neuropathic pain. Recently, AAK1 has been identified as a cellular factor essential for viral replication, making it a potential host target for the development of broad-spectrum antiviral agents.
  • WO 2017/059085 A1 discloses a biaryl kinase inhibitor for the treatment of pain, Alzheimer's disease, Parkinson's disease, and schizophrenia.
  • AAK1 as a drug target for treating neuropathic pain has stimulated the search for AAK1 inhibitors.
  • the number of companies developing drugs in this area is limited, necessitating further research on this target.
  • the problem to be solved by the present invention is to provide a novel heteroaryl derivative having a structure that exhibits excellent inhibitory activity against AAK1.
  • the problem to be solved by the present invention is to provide a pharmaceutical composition for preventing or treating a disease related to AAK1 inhibition, which comprises a heteroaryl derivative having the novel structure.
  • the problem to be solved by the present invention is to provide a method for preventing or treating a disease related to AAK1 inhibition, which comprises administering a therapeutically effective amount of a heteroaryl derivative having the novel structure to a subject in need thereof.
  • the problem to be solved by the present invention is to provide a use of the novel heteroaryl derivative as an effective ingredient in the manufacture of a pharmaceutical for preventing or treating a disease related to AAK1 inhibition.
  • a heteroaryl derivative compound represented by the following chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof is provided.
  • A is CH or N
  • B 1 , B 3 , B 4 and B 5 are C, CH, N or NH,
  • B 2 is C, CH, N, NH or O
  • the B ring is a 5-membered aromatic heterocycle containing 1 to 4 heteroatoms selected from N and O,
  • Y is NH, NR 6 or O
  • R 2 is H or halogen
  • R 4 is H, C 1-4 alkyl, halogen or C 1-4 haloalkyl
  • R 5 is a C 1-9 straight or branched chain alkyl, optionally including a C 3-5 cycloalkyl; or is connected to R 6 to form a 5- to 7-membered non-aromatic heterocycle, comprising N connected to R 5 and R 6 , and further comprising N or O,
  • R 5 is substituted or unsubstituted with singular or plural R 5a ,
  • R 5a is C 1-4 alkyl, amino or hydroxy
  • R 6 is connected to R 5 to form a 5- to 7-membered non-aromatic heterocycle containing N connected to R 5 and R 6 , and further containing N or O,
  • R b1 is C 1-4 alkyl or is connected to R b2 to form a C ring containing 0 to 2 N and fused with the B ring,
  • R b2 is connected to R b1 to form a C ring containing 0 to 2 N and fused with the B ring,
  • R b4 is C 1-4 alkyl or halogen
  • the fused ring of the above B ring and C ring is a fused ring of two rings containing 1 to 4 N, which is substituted or unsubstituted with R f ,
  • R f is halogen, C 1-4 haloalkyl or C 1-4 alkoxy.
  • a pharmaceutical composition for preventing or treating a disease related to AAK1 inhibition comprising a heteroaryl derivative compound represented by the above chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.
  • a method for preventing or treating a disease associated with AAK1 inhibition comprising administering a therapeutically effective amount of a heteroaryl derivative compound represented by the above chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof to a subject in need thereof.
  • a heteroaryl derivative compound represented by the above chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof as an effective ingredient in the manufacture of a medicament for preventing or treating a disease associated with AAK1 inhibition.
  • a pharmaceutical composition comprising a heteroaryl derivative compound represented by the above chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable additive is provided.
  • heteroaryl derivative compound of the present invention exhibits excellent inhibitory activity against AAK1, and thus it was revealed that it can be used for the prevention and treatment of diseases related to AAK1 inhibition.
  • heteroaryl derivative compound of the present invention can be usefully used in the fields of medicine and pharmacy for the prevention and treatment of acute and chronic pain and neuropathic pain, which are diseases related to AAK1 inhibition.
  • AAK1 refers to Adapter-associated kinase 1 (AAK1), a 104 kDa serine/threonine kinase belonging to the Numb-associated kinase (NAK) family, also referred to as AP2-associated protein kinase 1, which is encoded by the AAK1 gene in humans and is an enzyme involved in clathrin-mediated endocytosis.
  • AAK1 Adapter-associated kinase 1
  • NAK Numb-associated kinase
  • A is CH or N
  • B 1 , B 3 , B 4 and B 5 are C, CH, N or NH,
  • the B ring is a 5-membered aromatic heterocycle containing 1 to 4 heteroatoms selected from N and O,
  • Y is NH, NR 6 or O
  • R 2 is H or halogen
  • R 4 is H, C 1-4 alkyl, halogen or C 1-4 haloalkyl
  • R 5 is a C 1-9 straight or branched chain alkyl, optionally including a C 3-5 cycloalkyl; or is connected to R 6 to form a 5- to 7-membered non-aromatic heterocycle, comprising N connected to R 5 and R 6 , and further comprising N or O,
  • R 5 is substituted or unsubstituted with singular or plural R 5a ,
  • R 5a is C 1-4 alkyl, amino or hydroxy
  • R 6 is connected to R 5 to form a 5- to 7-membered non-aromatic heterocycle containing N connected to R 5 and R 6 , and further containing N or O,
  • R b1 is C 1-4 alkyl or is connected to R b2 to form a C ring containing 0 to 2 N and fused with the B ring,
  • R b2 is connected to R b1 to form a C ring containing 0 to 2 N and fused with the B ring,
  • R b4 is C 1-4 alkyl or halogen
  • the fused ring of the above B ring and C ring is a fused ring of two rings containing 1 to 4 N, which is substituted or unsubstituted with R f ,
  • R f is halogen, C 1-4 haloalkyl or C 1-4 alkoxy.
  • the B ring can be pyrrolyl, pyrazolyl, imidazolyl, isoxazolyl, or triazolyl.
  • R 2 can be H, fluoro or chloro.
  • R 4 can be H, methyl, fluoro, chloro, difluoromethyl or trifluoromethyl.
  • R 5 can be ethyl, 2-methyl-propyl-, 4-methyl-pentyl-, 2,4-dimethylpentyl-, cyclopropyl-methyl-, or cyclobutyl-methyl-.
  • the non-aromatic heterocycle formed by linking R 5 and R 6 may be piperazinyl or morpholino.
  • R 5a can be methyl, amino or hydroxy.
  • R b1 can be methyl
  • the fused ring of the B ring and the C ring may be any one selected from the group consisting of the following chemical formulas:
  • R b4 can be methyl or fluoro.
  • R f can be fluoro, chloro, trifluoromethyl or methoxy.
  • heteroaryl derivative compounds according to the present invention are as follows:
  • alkyl refers to a straight or branched chain saturated hydrocarbon, preferably C 1-10 alkyl.
  • the alkyl includes, but is not limited to, methyl, ethyl, n -propyl, iso -propyl, n -butyl, iso -butyl, tert -butyl, n -pentyl, iso -pentyl, n -hexyl, 3-methylhexyl, 2,2-dimethylpentyl, 2,3-dimethylpentyl, n -heptyl, n -octyl, n -nonyl, and n -decyl.
  • hydroxy or "hydroxy” is defined as -OH, and the term “alkoxy”, unless otherwise defined, means alkyloxy, a radical in which the hydrogen atoms of the hydroxy group are replaced by 1 to 10 alkyl groups.
  • heteroatom as used herein means N, O or S.
  • aryl refers to an aromatic hydrocarbon, including a polycyclic aromatic ring system in which a carbocyclic aromatic ring or a heteroaryl ring is fused with one or more other rings. Preferably, it is C 5-12 aryl, and more preferably, C 5-10 aryl. Examples of aryl include, but are not limited to, phenyl, naphthyl, tetrahydronaphthyl, and the like.
  • heteroaryl or "aromatic heterocycle” as used herein means a 3 to 12 membered, more preferably 5 to 10 membered aromatic hydrocarbon containing one or more heteroatoms selected from N, O and S as a reducing group, and forming a single or fused ring which may be fused with benzo or C 3-8 cycloalkyl.
  • the heteroaryl includes, but is not limited to, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrazinyl, pyrimidyl, pyridazinyl, triazinyl, oxadiazolyl, isoxadiazolyl, tetrazolyl, indolyl, indazolyl, isoxazolyl, oxazolyl, thiazolyl, isothiazolyl, furanyl, benzofuranyl, thiophenyl, benzothiophenyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, quinolinyl, isoquinolinyl, and the like.
  • heterocycle or “heterocycloalkyl” as used herein refers to a non-aromatic alkyl ring, which is a non-aromatic carbocyclic ring containing one or more heteroatoms, such as N, O or S, within the ring.
  • the ring may be 5, 6, 7 or 8-membered and/or may be fused to another ring, such as a cycloalkyl or aromatic ring.
  • Examples of such compounds include pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl, isooxazolidinyl, thiazolidinyl, isothiazolidinyl, dioxolanyl, oxathiolanyl, dithiolanyl, piperidinyl, tetrahydropyranyl, thianyl, piperazinyl, morpholino, and dioxanyl.
  • the compound represented by the above chemical formula 1 according to the present invention can be prepared and used in the form of a prodrug, a hydrate, a solvate, and a pharmaceutically acceptable salt to promote absorption in the body or increase solubility, and therefore the above prodrug, hydrate, solvate, and pharmaceutically acceptable salt also fall within the scope of the present invention.
  • the compound represented by the above chemical formula 1 has a chiral carbon, and thus its stereoisomers exist, and such stereoisomers are also included within the scope of the present invention.
  • prodrug refers to a substance that is transformed into the parent drug in vivo. Prodrugs are often used because, in some cases, they are easier to administer than the parent drug. For example, they may be bioactive by oral administration, whereas the parent drug may not be. Prodrugs may also have improved solubility in pharmaceutical compositions compared to the parent drug. For example, prodrugs may be biohydrolyzable esters of compounds according to the present invention and pharmaceutically acceptable salts thereof. Another example of a prodrug may be a short peptide (polyamino acid) attached to an acid group that is metabolized to reveal the active site of the peptide.
  • hydrate as used herein means a compound of the present invention or a salt thereof containing a stoichiometric or non-stoichiometric amount of water bound by non-covalent intermolecular forces.
  • solvate refers to a compound of the present invention or a salt thereof that contains a stoichiometric or non-stoichiometric amount of a solvent bound by non-covalent intermolecular forces.
  • Preferred solvents include those that are volatile, non-toxic, and/or suitable for human administration.
  • isomers refers to a compound of the present invention or a salt thereof that has the same chemical formula or molecular formula but is structurally or sterically different.
  • Such isomers include structural isomers such as tautomers, and stereoisomers such as R or S isomers having an asymmetric carbon center, geometric isomers (trans, cis), and diastereomers. All of these isomers and mixtures thereof are also included in the scope of the present invention.
  • the compound of formula 1 has optical isomers, stereoisomers, regioisomers, or rotamers, these are also included in the compound of formula 1, and can be obtained as a single product according to synthetic and separation methods known in the art.
  • optical isomers optical isomers resolved from this compound are also included in the compound of formula 1.
  • Optical isomers can be prepared by methods known per se.
  • pharmaceutically acceptable salt means a salt form of a compound that does not cause serious irritation to an organism to which the compound is administered and does not impair the biological activity and physical properties of the compound.
  • the pharmaceutical salt includes acid addition salts formed by acids that form non-toxic acid addition salts containing pharmaceutically acceptable anions, for example, inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrobromic acid, and hydroiodic acid; organic carboxylic acids such as tartaric acid, formic acid, citric acid, acetic acid, trichloroacetic acid, trifluoroacetic acid, gluconic acid, benzoic acid, lactic acid, fumaric acid, maleic acid, and salicylic acid; and sulfonic acids such as methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid.
  • inorganic acids such as hydrochloric acid,
  • carboxylic acid salts include metal salts or alkaline earth metal salts formed by lithium, sodium, potassium, calcium, magnesium, etc.; amino acid salts such as lysine, arginine, guanidine, etc.; organic salts such as dicyclohexylamine, N-methyl-D-glucamine, tris(hydroxymethyl)methylamine, diethanolamine, choline, and triethylamine, etc.
  • the compound of formula 1 according to the present invention can be converted into its salt by a conventional method.
  • the present invention also provides a method for preparing a compound of the above chemical formula 1.
  • the synthetic methods of Examples 1 to 136 are exemplified as a method for preparing a compound of the chemical formula 1 of the present invention, and the synthetic methods of Examples 1 to 136 do not limit the method for preparing a compound of the chemical formula 1 according to the present invention.
  • the synthetic methods of Examples 1 to 136 are merely examples, and it is obvious that they can be easily modified by those skilled in the art depending on specific substituents.
  • the present invention also provides a pharmaceutical composition for preventing or treating a disease related to AAK1 inhibition, comprising a heteroaryl derivative compound represented by the above chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.
  • the present invention also provides a method for preventing or treating a disease associated with AAK1 inhibition, comprising administering a therapeutically effective amount of a heteroaryl derivative compound represented by the above chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof to a subject in need thereof.
  • the present invention also provides the use of a heteroaryl derivative compound represented by the above chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof as an effective ingredient in the manufacture of a medicine for preventing or treating a disease associated with AAK1 inhibition.
  • the AAK1 inhibitory activity (IC 50 ) of the heteroaryl derivative compound of the present invention As a result of measuring the AAK1 inhibitory activity (IC 50 ) of the heteroaryl derivative compound of the present invention, it was confirmed that it exhibited excellent inhibitory activity against AAK1, and it was revealed that it can be used for the prevention and treatment of diseases related to AAK1 inhibition.
  • the disease associated with AAK1 inhibition may be selected from the group consisting of acute pain, chronic pain, inflammatory pain, neuropathic pain, Parkinson's disease, Alzheimer's disease, schizophrenia, bipolar disorder, muscular dystrophy, and viral infection diseases.
  • the heteroaryl derivative compound of the present invention can be used as a broad-spectrum antiviral agent.
  • the present invention also provides a pharmaceutical composition
  • a pharmaceutical composition comprising a heteroaryl derivative compound represented by the above chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable additive.
  • the above additives may include pharmaceutically acceptable carriers such as excipients, disintegrants, sweeteners, lubricants or flavoring agents that are commonly used, and may be formulated into oral preparations such as tablets, capsules, powders, granules and suspensions, emulsions or syrups according to a conventional method; or parenteral preparations such as external solutions, external suspensions, external emulsions, gels (ointments, etc.), inhalants, sprays and injections.
  • pharmaceutically acceptable carriers such as excipients, disintegrants, sweeteners, lubricants or flavoring agents that are commonly used
  • oral preparations such as tablets, capsules, powders, granules and suspensions, emulsions or syrups according to a conventional method
  • parenteral preparations such as external solutions, external suspensions, external emulsions, gels (ointments, etc.), inhalants, sprays and injections.
  • the above preparations may be formulated into various forms, for
  • the subject to which the pharmaceutical composition of the present invention is administered may be, for example, a human, a monkey, a cow, a horse, a sheep, a pig, a chicken, a turkey, a cat, a dog, a mouse, a rat, a rabbit, or a guinea pig, and may be, for example, a mammal, for example, a human, but is not limited thereto.
  • the pharmaceutical composition of the present invention can be administered orally or parenterally, and in case of parenteral administration, it can be administered by routes such as skin, transdermally, ocularly, intraperitoneally, rectal, or intravenously, intramuscularly, subcutaneously, intrauterinely, intracerebroventricularly, or topical administration.
  • Topical ocular administration includes, for example, direct intraocular administration, or administration around the eye, behind the eye, subretinal, central retinal, extrafoveal, subconjunctival, intravitreous, intracameral, or suprachoroidal.
  • the pharmaceutical composition can be administered through an insertion device.
  • the dosage of the active ingredient contained in the pharmaceutical composition of the present invention varies depending on the patient's condition and weight, the degree of the disease, the form of the active ingredient, the route and period of administration, and can be appropriately adjusted depending on the patient.
  • the active ingredient may be administered at a dosage of 0.0001 to 1000 mg/kg per day, preferably 0.001 to 100 mg/kg, and the administration may be administered once a day or divided into several times.
  • the pharmaceutical composition of the present invention may contain the active ingredient at a weight percentage of 0.001 to 90% based on the total weight of the composition.
  • Example 1 ( S )-1-((6-(5-fluoro-1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Part B (S)-1-((6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine
  • Example 2 was prepared according to a similar procedure as described for Example 1.
  • Part B (S)-1-((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine
  • This compound was prepared using ( S )-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) to obtain an ivory powder (34.3 mg, 30.3%).
  • Example 3 was prepared according to a similar procedure as described for Example 1.
  • Part B (S)-1-((6-(1H-pyrrolo[3,2-c]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine
  • This compound was prepared using ( S )-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[3,2- c ]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) and a powder (24.3 mg, 21.5%) was obtained.
  • Example 4 was prepared according to a similar procedure as described for Example 1.
  • Part B (S)-1-((6-(1H-pyrrolo[2,3-c]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine
  • This compound was prepared using ( S )-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- c ]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) to obtain a pale- powder (30.90 mg, 27.3%).
  • Part B (S)-1-((6-(7-fluoroimidazo[1,2-a]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine
  • This compound was prepared using ( S )-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (24.0 mg, 0.08 mmol) (Example 1, Part A) and 7-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2- a ]pyridine (136.9 mg, 0.52 mmol) and an ivory powder (11.4 mg, 39.8%) was obtained.
  • Example 6 was prepared according to a similar procedure as described for Example 1.
  • Part B (S)-1-((6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine
  • This compound was prepared using ( S )-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A) and tert -butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole-1-carboxylate (153.6 mg, 0.52 mmol) to obtain a pale-ivory powder (24.1 mg, 25.2%).
  • Example 7 ( S )-1-((6-(1 H -pyrrol-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((6-(1 H -pyrrol-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 7 was prepared according to a similar procedure as described for Example 1.
  • Part B (S)-1-((6-(1H-pyrrol-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine
  • Example 8 ( S )-1-((6-(2 H -1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((6-(2 H -1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 8 was prepared according to a procedure similar to that described for Example 1.
  • This compound was prepared using ( S )-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A) and 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole (116.0 mg, 0.52 mmol) to obtain a pale-ivory powder (15.6 mg, 14.8%).
  • Example 10 ( S )-1-((6-(1 H -Pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 11 ( S )-1-((6-(6-fluoro-1 H -Pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((6-(6-fluoro-1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 11 was prepared according to a similar procedure as described for Example 10 using ( S )-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A), 6-fluoro-1 H -pyrrolo[3,2- b ]pyridine (47.4 mg, 0.35 mmol) to obtain an ivory powder (25.7 mg, 21.5%).
  • Example 12 ( S )-1-((6-(6-chloro-1 H -Pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((6-(6-chloro-1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 12 was prepared according to a similar procedure as described for Example 10 using ( S )-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A), 6-chloro-1 H -pyrrolo[3,2- b ]pyridine (53.1 mg, 0.35 mmol) to obtain a pale-brown powder (24.3 mg, 19.4%).
  • Example 13 ( S )-1-((2-(difluoromethyl)-6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((2-(difluoromethyl)-6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Part B (S)-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine
  • This compound was prepared according to a similar procedure as described for Part B of Example 1 using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and tert -butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole-1-carboxylate (130.8 mg, 0.44 mmol) to obtain an ivory powder (30.7 mg, 31.9%).
  • Example 14 ( S )-1-((2-(difluoromethyl)-6-(isoxazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((2-(difluoromethyl)-6-(isoxazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 14 was prepared according to a similar procedure as described for Example 13.
  • This compound was prepared using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoxazole (86.7 mg, 0.44 mmol) to obtain an ivory powder (20.8 mg, 21.5%).
  • Example 15 ( S )-1-((2-(difluoromethyl)-6-(1 H -imidazol-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((2-(difluoromethyl)-6-(1 H -imidazol-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 15 was prepared according to a similar procedure as described for Example 10 using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and 1 H -imidazole (20.1 mg, 0.30 mmol) to obtain an ivory powder (13.5 mg, 14.0%).
  • Example 16 ( S )-1-((2-(difluoromethyl)-6-(3-fluoro-1 H -pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((2-(difluoromethyl)-6-(3-fluoro-1 H -pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 16 was prepared according to a procedure similar to that described for Example 13.
  • This compound was prepared using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and 3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole (94.3 mg, 0.44 mmol) to obtain a pale-brown powder (15.4 mg, 15.9%).
  • Example 17 ( S )-1-((2-(difluoromethyl)-6-(1 H -imidazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((2-(difluoromethyl)-6-(1 H -imidazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 17 was prepared according to a procedure similar to that described for Example 13.
  • This compound was prepared using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and tert -butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -imidazole-1-carboxylate, and a pale-yellow powder (20.3 mg, 21.1%) was obtained.
  • Example 18 ( S )-1-((2-(difluoromethyl)-6-(1 H -pyrrol-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((2-(difluoromethyl)-6-(1 H -pyrrol-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 18 was prepared according to a procedure similar to that described for Example 13.
  • This compound was prepared using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrole-1-carboxylate (130.4 mg, 0.44 mmol) to obtain a pale-brown powder (15.2 mg, 15.8%).
  • Example 19 ( S )-1-((2-(difluoromethyl)-6-(1 H -pyrazol-5-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((2-(difluoromethyl)-6-(1 H -pyrazol-5-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 19 was prepared according to a procedure similar to that described for Example 13.
  • This compound was prepared using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole-1-carboxylate (130.8 mg, 0.44 mmol) and an ivory powder (25.3 mg, 26.3%) was obtained.
  • Example 20 ( S )-1-((2-(difluoromethyl)-6-(2 H -1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((2-(difluoromethyl)-6-(2 H -1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 20 was prepared according to a procedure similar to that described for Example 8.
  • Part B (S)-1-((2-(difluoromethyl)-6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine
  • This compound was prepared using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and 2-(tetrahydro-2 H -pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2 H -1,2,3-triazole (124.1 mg, 0.44 mmol) and an ivory powder (30.2 mg, 31.3%) was obtained.
  • Example 21 ( S )-1-((2-(difluoromethyl)-6-(5-fluoro-1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((2-(difluoromethyl)-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 21 was prepared according to a procedure similar to that described for Example 13.
  • This compound was prepared using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (161.1 mg, 0.44 mmol) to obtain a pale-yellow powder (28.6 mg, 24.5%).
  • Example 22 ( S )-1-(2-(difluoromethyl)-4-(5-fluoro-1 H -Pyrrolo[2,3- b ]pyridin-3-yl)phenoxy)-2,4-dimethylpentan-2-amine [( S )-1-(2-(difluoromethyl)-4-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)phenoxy)-2,4-dimethylpentan-2-amine]
  • Example 22 was prepared according to a procedure similar to that described for Example 13.
  • Part B (S)-1-(4-bromo-2-(difluoromethyl)phenoxy)-2,4-dimethylpentan-2-amine
  • This compound was prepared using ( S )-1-(4-bromo-2-(difluoromethyl)phenoxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 22, Part B) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (161.5 mg, 0.45 mmol) and an ivory powder (30.2 mg, 25.9%) was obtained.
  • Example 23 ( S )-1-((2-(difluoromethyl)-6-(5-(trifluoromethyl)-1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((2-(difluoromethyl)-6-(5-(trifluoromethyl)-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 23 was prepared according to a procedure similar to that described for Example 13.
  • This compound was prepared using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (183.3 mg, 0.44 mmol) to obtain a pale-yellow powder (35.4 mg, 26.9%).
  • Example 24 ( S )-1-((2-(difluoromethyl)-6-(4-fluoro-1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((2-(difluoromethyl)-6-(4-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 24 was prepared according to a procedure similar to that described for Example 13.
  • This compound was prepared using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and tert -butyl 4-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (161.1 mg, 0.44 mmol) to obtain a pale-brown powder (20.4 mg, 17.5%).
  • Example 25 (( S )-1-((2-(difluoromethyl)-6-(1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(( S )-1-((2-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 25 was prepared according to a procedure similar to that described for Example 13.
  • This compound was prepared using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 14, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (153.1 mg, 0.44 mmol) and an ivory powder (30.9 mg, 27.8%) was obtained.
  • Example 26 ( S )-1-((6-(5-chloro-1 H -Pyrazolo[3,4- b ]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((6-(5-chloro-1 H -pyrazolo[3,4- b ]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 26 was prepared according to a procedure similar to that described for Example 8.
  • Part B (S)-1-((6-(5-chloro-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine
  • Example 27 ( S )-1-((2-(difluoromethyl)-6-(4-methoxy-1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((2-(difluoromethyl)-6-(4-methoxy-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 27 was prepared according to a procedure similar to that described for Example 13.
  • This compound was prepared using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and tert -butyl 4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (166.4 mg, 0.44 mmol) to obtain a pale-yellow powder (34.9 mg, 29.1%).
  • Example 28 ( S )-1-((2-(difluoromethyl)-6-(6-fluoro-1 H -Pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((2-(difluoromethyl)-6-(6-fluoro-1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 28 was prepared according to a similar procedure as described for Example 10 using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and 6-fluoro-1 H -pyrrolo[3,2- b ]pyridine (440.3 mg, 0.30 mmol) to obtain an ivory powder (20.4 mg, 17.5%).
  • Example 29 was prepared according to a similar procedure as described for Example 10 using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and 1 H -pyrrolo[3,2- b ]pyridine (35.0 mg, 0.30 mmol) to obtain an ivory powder (24.7 mg, 22.2%).
  • Example 30 ( S )-1-((4-(difluoromethyl)-6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((4-(difluoromethyl)-6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 30 was prepared according to a procedure similar to that described for Example 13.
  • Part A 2-bromo-4-(difluoromethyl)-5-fluoropyridine
  • Part B (S)-1-((6-bromo-4-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine
  • This compound was prepared using ( S )-1-((6-bromo-4-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 30, Part B) and tert -butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole-1-carboxylate (130.8 mg, 0.44 mmol) to obtain a pale-brown powder (28.3 mg, 29.4%).
  • Example 31 ( S )-1-((4-(difluoromethyl)-6-(2 H -1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((4-(difluoromethyl)-6-(2 H -1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 31 was prepared according to a procedure similar to that described for Example 8.
  • Part B (S)-1-((4-(difluoromethyl)-6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine
  • This compound was prepared using ( S )-1-((6-bromo-4-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 30, Part B) and 2-(tetrahydro-2 H -pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2 H -1,2,3-triazole (124.1 mg, 0.44 mmol) and an ivory powder (17.8 mg, 18.4%) was obtained.
  • Example 32 (( S )-1-((4-(difluoromethyl)-6-(1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(( S )-1-((4-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 32 was prepared according to a procedure similar to that described for Example 13.
  • This compound was prepared using ( S )-1-((6-bromo-4-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 30, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (153.1 mg, 0.44 mmol) to obtain a pale-brown powder (34.2 mg, 30.8%).
  • Example 33 ( S )-1-((5-(difluoromethyl)-6-(1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((5-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 33 was prepared according to a procedure similar to that described for Example 13.
  • Part A 2-bromo-3-(difluoromethyl)-5-fluoropyridine
  • Part B (S)-1-((6-bromo-5-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine
  • This compound was prepared using ( S )-1-((6-bromo-5-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 33, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (153.1 mg, 0.44 mmol) to obtain a pale-brown powder (26.5 mg, 23.8%).
  • Example 34 ( S )-1-((6-(1 H -pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((6-(1 H -pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 34 was prepared according to a procedure similar to that described for Example 13.
  • Part B (S)-1-((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine
  • This compound was prepared using ( S )-1-((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.28 mmol) (Example 34, Part B) and tert -butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole-1-carboxylate (124.2 mg, 0.42 mmol) to obtain a pale-brown powder (26.5 mg, 27.4%).
  • Example 35 ( S )-1-((6-(5-fluoro-1 H -Pyrrolo[2,3- b ]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 35 was prepared according to a procedure similar to that described for Example 13.
  • This compound was prepared using ( S )-1-((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.28 mmol) (Example 34, Part B) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (152.9 mg, 0.42 mmol) and an ivory powder (30.2 mg, 26.1%) was obtained.
  • Example 36 ( S )-1-((5-(5-fluoro-1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((5-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 36 was prepared according to a procedure similar to that described for Example 13.
  • Part B (S)-1-((5-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine
  • This compound was prepared using ( S )-1-((5-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 36, Part B) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (189.1 mg, 0.52 mmol) and an ivory powder (20.7 mg, 17.3%) was obtained.
  • Example 37 ( S )-1-((3-(1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((3-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 37 was prepared according to a procedure similar to that described for Example 13.
  • Part B (S)-1-((3-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine
  • This compound was prepared using ( S )-1-((3-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 37, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) and an ivory powder (21.5 mg, 19.0%) was obtained.
  • Example 38 ( S )-1-((4-(1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((4-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 38 was prepared according to a procedure similar to that described for Example 13.
  • Part B (S)-1-((4-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine
  • This compound was prepared using ( S )-1-((4-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 38, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) and an ivory powder (28.6 mg, 25.3%) was obtained.
  • Example 39 ( S )-1-((6-(1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 39 was prepared according to a procedure similar to that described for Example 13.
  • Part B (S)-1-((6-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine
  • This compound was prepared using ( S )-1-((6-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 39, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) and an ivory powder (20.7 mg, 18.3%) was obtained.
  • Example 40 ( S )-1-((4-(1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((4-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 40 was prepared according to a procedure similar to that described for Example 13.
  • Part B (S)-1-((4-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine
  • This compound was prepared using ( S )-1-((4-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 40, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) and an ivory powder (25.9 mg, 22.9%) was obtained.
  • Example 41 ( S )-1-((5-(1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((5-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 41 was prepared according to a procedure similar to that described for Example 13.
  • Part B (S)-1-((5-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine
  • This compound was prepared using ( S )-1-((5-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 41, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) and an ivory powder (19.7 mg, 17.4%) was obtained.
  • Example 42 ( S )-1-((3-(1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((3-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 42 was prepared according to a procedure similar to that described for Example 13.
  • Part B (S)-1-((3-bromopyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine
  • This compound was prepared using ( S )-1-((3-bromopyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 42, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) and an ivory powder (18.6 mg, 16.4%) was obtained.
  • Example 43 ( S )-1-((2-(1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((2-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 43 was prepared according to a procedure similar to that described for Example 13.
  • Part B (S)-1-((2-bromopyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine
  • This compound was prepared using ( S )-1-((2-bromopyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 43, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) and an ivory powder (19.8 mg, 17.5%) was obtained.
  • Example 44 ( S )-1-((2-(1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((2-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 44 was prepared according to a procedure similar to that described for Example 13.
  • Part B (S)-1-((2-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine
  • This compound was prepared using ( S )-1-((2-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 44, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) and an ivory powder (21.6 mg, 19.1%) was obtained.
  • Example 45 1-((2-(difluoromethyl)-6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((2-(difluoromethyl)-6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]
  • Example 45 was prepared according to a procedure similar to that described for Example 13.
  • Part B 1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine
  • This compound was prepared using 1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine (100.0 mg, 0.34 mmol) (Example 45, Part B) and tert -butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole-1-carboxylate (149.5 mg, 0.51 mmol) to obtain an ivory powder (62.2 mg, 65.0%).
  • Example 46 1-((2-(difluoromethyl)-6-(1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((2-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]
  • Example 46 was prepared according to a procedure similar to that described for Example 13.
  • This compound was prepared using 1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine (100.0 mg, 0.34 mmol) (Example 45, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (174.9 mg, 0.51 mmol) and an ivory powder (25.8 mg, 26.9%) was obtained.
  • Example 47 1-((2-(difluoromethyl)-6-(5-fluoro-1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((2-(difluoromethyl)-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]
  • Example 47 was prepared according to a procedure similar to that described for Example 13.
  • This compound was prepared using 1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine (100.0 mg, 0.34 mmol) (Example 45, Part B) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (184.0 mg, 0.51 mmol) to obtain a pale-yellow powder (49.1 mg, 41.3%).
  • Example 48 1-((2-(difluoromethyl)-6-(1 H -Pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((2-(difluoromethyl)-6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]
  • Example 48 was prepared according to a similar procedure as described for Example 10 using 1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine (100.0 mg, 0.34 mmol) (Example 45, Part B) and 1 H -pyrrolo[3,2- b ]pyridine (40.0 mg, 0.34 mmol) to obtain an off-white powder (16.9 mg, 15.0%).
  • Example 49 1-((6-(1 H -pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((6-(1 H -pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]
  • Example 49 was prepared according to a procedure similar to that described for Example 13.
  • Example 50 1-((6-(1 H -Pyrrolo[2,3- b ]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]
  • Example 50 was prepared according to a procedure similar to that described for Example 13.
  • This compound was prepared using 1-((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine (100.0 mg, 0.32 mmol) (Example 49, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (164.9 mg, 0.48 mmol) to obtain a pale-yellow powder (24.1 mg, 21.5%).
  • Example 51 2-((6-(5-chloro-1 H -Pyrazolo[3,4- b ]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-ol [2-((6-(5-chloro-1 H -pyrazolo[3,4- b ]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-ol]
  • Example 51 was prepared according to a procedure similar to that described for Example 13.
  • Part B 2-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-ol
  • Example 51 was prepared according to a procedure similar to that described for Example 8.
  • Part B 2-((6-(5-chloro-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-ol
  • This compound was prepared using 2-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-ol (100.0 mg, 0.37 mmol) (Example 51, Part B) and 5-chloro-1-(tetrahydro-2 H -pyran-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazolo[3,4- b ]pyridine (203.4 mg, 0.56 mmol) to obtain a yellow powder (20.8 mg, 16.3%).
  • Example 52 2-((6-(5-chloro-1 H -Pyrazolo[3,4- b ]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-amine [2-((6-(5-chloro-1 H -pyrazolo[3,4- b ]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-amine]
  • Example 52 was prepared according to a procedure similar to that described for Example 13.
  • Part B 2-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-amine
  • Example 52 was prepared according to a procedure similar to that described for Example 8.
  • Part B 2-((6-(5-chloro-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-amine
  • This compound was prepared using 2-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-amine (100.0 mg, 0.37 mmol) (Example 52, Part B) and 5-chloro-1-(tetrahydro-2 H -pyran-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazolo[3,4- b ]pyridine (204.2 mg, 0.56 mmol) and a yellow powder (33.6 mg, 26.4%) was obtained.
  • Example 53 was prepared according to a similar procedure as described for Example 10 using ( S )-1-((4-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 38, Part B) and 1 H -pyrrolo[3,2- b ]pyridine (41.1 mg, 0.35 mmol) to obtain a pale-brown powder (22.5 mg, 19.9%).
  • Example 54 ( S )-1-((5-(1 H -Pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((5-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 54 was prepared according to a similar procedure as described for Example 10 using ( S )-1-((5-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 41, Part B) and 1 H -pyrrolo[3,2- b ]pyridine (41.1 mg, 0.35 mmol) to obtain a pale-brown powder (19.7 mg, 17.4%).
  • Example 55 ( S )-1-((5-(1 H -Pyrrolo[3,2- b ]pyridin-1-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine [( S )-1-((5-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine]
  • Example 55 was prepared according to a similar procedure as described for Example 10 using ( S ) -1-((5-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 36, Part B) and 1 H -pyrrolo[3,2- b ]pyridine (41.1 mg, 0.35 mmol) to obtain a pale-brown powder (19.0 mg, 16.8%).
  • Example 56 ( S )-1-(4-(1 H -Pyrrolo[3,2- b ]pyridin-1-yl)phenoxy)-2,4-dimethylpentan-2-amine [( S )-1-(4-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)phenoxy)-2,4-dimethylpentan-2-amine]
  • Example 56 was prepared according to a similar procedure as described for Example 10 using ( S )-1-(4-bromo-2-(difluoromethyl)phenoxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 22, Part B) and 1 H -pyrrolo[3,2- b ]pyridine (41.2 mg, 0.35 mmol) to obtain an ivory powder (20.5 mg, 18.1%).
  • Example 57 ( S )-1-((2-(difluoromethyl)-6-(5-fluoro-1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [( S )-1-((2-(difluoromethyl)-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]
  • Example 57 was prepared according to a procedure similar to that described for Example 13.
  • Part B tert -Butyl (S)-(1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate
  • Example 58 ( S )-1-((2-(difluoromethyl)-6-(1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [( S )-1-((2-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]
  • Example 58 was prepared according to a procedure similar to that described for Example 57.
  • This compound was prepared using tert -butyl ( S )-(1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 57, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (121.9 mg, 0.35 mmol) to obtain an ivory powder (20.8 mg, 24.4%).
  • Example 59 ( S )-1-((2-(difluoromethyl)-6-(4-methoxy-1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [( S )-1-((2-(difluoromethyl)-6-(4-methoxy-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]
  • Example 59 was prepared according to a procedure similar to that described for Example 57.
  • This compound was prepared using tert -butyl ( S )-(1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 57, Part B) and tert -butyl 4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (132.6 mg, 0.35 mmol) to obtain an ivory powder (19.5 mg, 21.1%).
  • Example 60 ( S )-1-((2-(difluoromethyl)-6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [( S )-1-((2-(difluoromethyl)-6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]
  • Example 60 was prepared according to a procedure similar to that described for Example 57.
  • This compound was prepared using tert -butyl ( S )-(1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 57, Part B) and tert -butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole-1-carboxylate (104.2 mg, 0.35 mmol) and an ivory powder (16.7 mg, 22.7%) was obtained.
  • Example 61 1-((4-(difluoromethyl)-6-(1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((4-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]
  • Example 61 was prepared according to a procedure similar to that described for Example 57.
  • Part B tert -Butyl (1-((6-bromo-4-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-yl)carbamate
  • This compound was prepared using tert -butyl (1-((6-bromo-4-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.25 mmol) (Example 61, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (130.6 mg, 0.38 mmol) to obtain a pale-yellow powder (29.5 mg, 35.0%).
  • Example 62 1-((4-(difluoromethyl)-6-(5-fluoro-1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((4-(difluoromethyl)-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]
  • Example 62 was prepared according to a procedure similar to that described for Example 57.
  • Part C 1-((4-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine
  • This compound was prepared using tert -butyl ( S )-(1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.25 mmol) (Example 61, Part B) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (137.4 mg, 0.38 mmol) to obtain a pale-yellow powder (52.8 mg, 59.5%).
  • Example 63 1-((5-(difluoromethyl)-6-(1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((5-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]
  • Example 63 was prepared according to a procedure similar to that described for Example 57.
  • This compound was prepared using tert -butyl (1-((6-bromo-5-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.25 mmol) (Example 63, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (130.6 mg, 0.38 mmol) to obtain an off-white powder (23.3 mg, 27.7%).
  • Example 64 1-((5-(difluoromethyl)-6-(1 H -Pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((5-(difluoromethyl)-6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]
  • Example 64 was prepared as an intermediate according to a procedure similar to that described for Example 10 using tert -butyl (1-((6-bromo-5-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.25 mmol) (Example 63, Part B) and 1 H -pyrrolo[3,2- b ]pyridine (29.8 mg, 0.25 mmol). After purification, hydrochloric acid (1.0 M EtOAc solution, 10 mL) was added and stirred at room temperature for deprotection of the tert -butoxy carbonyl group. The progress of the reaction was monitored by HPLC.
  • Example 65 1-(((2-(difluoromethyl)-6-(1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((2-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]
  • Example 65 was prepared according to a procedure similar to that described for Example 57.
  • Part B tert-butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate
  • This compound was prepared using tert -butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 65, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (131.3 mg, 0.38 mmol) to obtain an ivory powder (17.2 mg, 20.4%).
  • Example 66 1-(((2-(difluoromethyl)-6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((2-(difluoromethyl)-6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]
  • Example 66 was prepared according to a procedure similar to that described for Example 57.
  • This compound was prepared using tert -butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 65, Part B) and tert -butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole-1-carboxylate (112.2 mg, 294.2 mmol) to obtain an off-white powder (24.2 mg, 33.9%).
  • Example 67 1-(((2-(difluoromethyl)-6-(2 H -1,2,3-triazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((2-(difluoromethyl)-6-(2 H -1,2,3-triazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]
  • Example 67 was prepared according to a procedure similar to that described for Example 8.
  • Part B 1-(((2-(difluoromethyl)-6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine
  • This compound was prepared using tert -butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 65, Part B) and 2-(tetrahydro-2 H -pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2 H -1,2,3-triazole (106.4 mg, 0.38 mmol) to obtain an off-white powder (17.1 mg, 23.9%).
  • Example 68 1-(((2-(difluoromethyl)-6-(5-fluoro-1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((2-(difluoromethyl)-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]
  • Example 68 was prepared according to a procedure similar to that described for Example 57.
  • This compound was prepared using tert -butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 65, Part B) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (138.1 mg, 0.38 mmol) to obtain a pale-yellow powder (34.1 mg, 38.5%).
  • Example 69 1-(((2-(difluoromethyl)-6-(1 H -Pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((2-(difluoromethyl)-6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]
  • Example 69 was prepared according to a similar procedure as described for Example 64 using tert -butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 65, part B) and 1 H -pyrrolo[3,2- b ]pyridine (30.0 mg, 0.25 mmol) to obtain an off-white powder (15.4 mg, 18.3%).
  • Example 70 1-(((6-(1 H -pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((6-(1 H -pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]
  • Example 70 was prepared according to a procedure similar to that described for Example 57.
  • Part B tert-butyl (1-(((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate
  • This compound was prepared using tert -butyl (1-(((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.24 mmol) (Example 70, Part B) and tert -butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole-1-carboxylate (107.3 mg, 0.36 mmol) to obtain a pale-brown powder (38.2 mg, 52.6%).
  • Example 71 1-((5-(difluoromethyl)-6-(1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((5-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]
  • Example 71 was prepared according to a procedure similar to that described for Example 57.
  • Part B tert-butyl (1-(((6-bromo-5-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate
  • This compound was prepared using tert -butyl (1-(((6-bromo-5-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 71, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (131.3 mg, 0.38 mmol) to obtain an off-white powder (33.9 mg, 40.3%).
  • Example 72 1-(((5-(difluoromethyl)-6-(5-fluoro-1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((5-(difluoromethyl)-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]
  • Example 72 was prepared according to a procedure similar to that described for Example 57.
  • This compound was prepared using tert -butyl (1-(((6-bromo-5-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 71, Part B) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (138.1 mg, 0.38 mmol) to obtain an off-white powder (35.7 mg, 40.3%).
  • Example 73 1-(((2-(difluoromethyl)-6-(1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine [1-(((2-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine]
  • Example 73 was prepared according to a procedure similar to that described for Example 57.
  • Part B tert-butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutyl)carbamate
  • This compound was prepared using tert -butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutyl)carbamate (100.0 mg, 0.25 mmol) (Example 73, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (126.7 mg, 0.37 mmol) to obtain a pale-brown powder (34.6 mg, 40.9%).
  • Example 74 1-(((2-(difluoromethyl)-6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine [1-(((2-(difluoromethyl)-6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine]
  • Example 74 was prepared according to a procedure similar to that described for Example 57.
  • This compound was prepared using tert -butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutyl)carbamate (100.0 mg, 0.25 mmol) (Example 73, Part B) and tert -butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole-1-carboxylate (108.3 mg, 0.37 mmol) and an ivory powder (30.7 mg, 42.4%) was obtained.
  • Example 75 1-(((2-(difluoromethyl)-6-(2 H -1,2,3-triazol-4-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine [1-(((2-(difluoromethyl)-6-(2 H -1,2,3-triazol-4-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine]
  • Example 75 was prepared according to a procedure similar to that described for Example 8.
  • Part B 1-(((2-(difluoromethyl)-6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine
  • This compound was prepared using (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutyl)carbamate (100.0 mg, 0.25 mmol) (Example 73, Part B) and 2-(tetrahydro-2 H -pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2 H -1,2,3-triazole (102.8 mg, 0.37 mmol) to obtain a pale-yellow powder (36.6 mg, 50.4%).
  • Example 76 1-(((2-(difluoromethyl)-6-(1 H -Pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine [1-(((2-(difluoromethyl)-6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine]
  • Example 76 was prepared according to a similar procedure as that described for Example 64 using tert -butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutyl)carbamate (100.0 mg, 0.25 mmol) (Example 73, Part B) and 1 H -pyrrolo[3,2- b ]pyridine (29.0 mg, 0.25 mmol) to obtain an off-white powder (18.7 mg, 22.1%).
  • Example 77 1-(((6-(1 H -pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine [1-(((6-(1 H -pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine]
  • Example 77 was prepared according to a procedure similar to that described for Example 57.
  • Part B tert-butyl (1-(((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutyl)carbamate
  • This compound was prepared using tert -butyl (1-(((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutyl)carbamate (100.0 mg, 0.24 mmol) (Example 77, Part B) and tert -butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole-1-carboxylate (103.7 mg, 0.35 mmol) to obtain a pale-brown powder (42.6 mg, 58.0%).
  • Example 78 1-(((6-(2 H -1,2,3-triazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine [1-(((6-(2 H -1,2,3-triazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine]
  • Example 78 was prepared according to a procedure similar to that described for Example 8.
  • Part B 1-(((6-(2H-1,2,3-triazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine
  • This compound was prepared using tert -butyl (1-(((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutyl)carbamate (100.0 mg, 0.24 mmol) (Example 77, Part B) and 2-(tetrahydro-2 H -pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2 H -1,2,3-triazole (98.4 mg, 0.35 mmol) to obtain a pale-yellow powder (58.4 mg, 79.2%).
  • Example 79 1-((2-(difluoromethyl)-6-(1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-ol [1-((2-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-ol]
  • Example 79 was prepared according to a procedure similar to that described for Example 13.
  • Part B 1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-ol
  • This compound was prepared using 1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-ol (100.0 mg, 0.34 mmol) (Example 79, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (174.3 mg, 0.51 mmol) to obtain a pale-yellow powder (43.3 mg, 38.4%).
  • Example 80 1-((2-(difluoromethyl)-6-(1 H -Pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-ol [1-((2-(difluoromethyl)-6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-ol]
  • Example 80 was prepared according to a similar procedure as described for Example 10 using 1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-ol (100.0 mg, 0.34 mmol) (Example 79, Part B), 1 H -pyrrolo[3,2- b ]pyridine (39.9 mg, 0.34 mmol) to obtain an ivory powder (31.2 mg, 27.7%).
  • Example 81 ( S )-1-(4-(1 H -Pyrrolo[2,3- b ]pyridin-3-yl)phenoxy)-2,4-dimethylpentan-2-amine [( S )-1-(4-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)phenoxy)-2,4-dimethylpentan-2-amine]
  • Example 81 was prepared according to a procedure similar to that described for Example 13.
  • This compound was prepared using ( S )-1-(4-iodophenoxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 81, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (154.9 mg, 0.45 mmol) to obtain a dark-ivory powder (41.3 mg, 42.5%).
  • Example 82 ( S )-1-((6-(5-fluoro-1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [( S )-1-((6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]
  • Diisopropyl azodicarboxylate (6.2 mL, 31.67 mmol) was added dropwise to a solution of 6-iodopyridin-3-ol (3.5 g, 15.84 mmol), tert -butyl ( S )-(1-hydroxy-4-methylpentan-2-yl)carbamate (8.6 g, 39.59 mmol), and triphenyl phosphine (8.3 g, 31.67 mmol) in tetrahydrofuran (100 mL). The reaction mixture was stirred at room temperature for 2 h. The progress of the reaction was monitored by TLC and HPLC. After the reaction was completed, water and EtOAc were added.
  • Example 82 was prepared according to a procedure similar to that described for Example 57.
  • This compound was prepared using tert -butyl ( S )-(1-((6-iodopyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 82, Part A) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (129.2 mg, 0.36 mmol) to obtain a pale-yellow powder (15.6 mg, 19.9%).
  • Example 83 ( S )-1-((6-(4-methoxy-1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [( S )-1-((6-(4-methoxy-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]
  • Example 83 was prepared according to a procedure similar to that described for Example 57.
  • This compound was prepared using tert -butyl ( S )-(1-((6-iodopyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 82, Part A) and tert -butyl 4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (133.5 mg, 0.36 mmol) to obtain an ivory powder (17.8 mg, 21.9%).
  • Example 84 ( S )-1-((6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [( S )-1-((6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]
  • Example 84 was prepared according to a procedure similar to that described for Example 57.
  • This compound was prepared using tert -butyl (S)-(1-((6-iodopyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 82, Part A) and tert -butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (133.5 mg, 0.36 mmol) to obtain an ivory powder (23.3 mg, 37.6%).
  • Example 85 ( S )-1-((6-(1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [( S )-1-((6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]
  • Example 85 was prepared according to a procedure similar to that described for Example 57.
  • This compound was prepared using tert -butyl ( S )-(1-((6-iodopyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 82, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (122.8 mg, 0.36 mmol) to obtain an ivory powder (16.7 mg, 22.6%).
  • Example 86 ( S )-1-((6-(4-fluoro-1 H -Pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [( S )-1-((6-(4-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

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Abstract

The present invention provides: a novel heteroaryl derivative compound, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof; and a pharmaceutical composition for preventing or treating AAK1 inhibition-related diseases, the composition comprising same as an active ingredient. The heteroaryl derivative compound according to the present invention exhibits excellent inhibitory activity against AAK1, and thus can be effectively used for preventing and treating AAK1 inhibition-related diseases such as acute pain and neuropathic pain.

Description

신규한 헤테로아릴 유도체 및 이의 AAK1 억제 용도Novel heteroaryl derivatives and their use for inhibiting AAK1

본 출원은 2024년 4월 29일 출원된 한국특허출원 제10-2024-0057110호에 기초한 우선권을 주장하며, 해당 출원의 명세서 및 도면에 개시된 모든 내용은 본 출원에 원용된다. This application claims priority to Korean Patent Application No. 10-2024-0057110, filed April 29, 2024, the entire disclosure of which is incorporated herein by reference.

본 발명은 신규한 헤테로아릴 유도체에 관한 것으로, 더욱 상세하게는 신규한 헤테로아릴 유도체 및 이의 AAK1 억제 용도에 관한 것이다.The present invention relates to novel heteroaryl derivatives, and more particularly, to novel heteroaryl derivatives and their use for inhibiting AAK1.

어댑터-연관 키나아제 1(Adaptor-associated kinase 1, AAK1)은 Numb 관련 키나아제(Numb-associated kinase, NAK) 계열에 속하는 104 kDa 세린/트레오닌 키나아제로서, AP2-연관 단백질 키나아제 1으로도 지칭되며, 인간에서 AAK1 유전자에 의해 암호화되고 클라트린(clatherin) 매개 세포내 이입에 관여하는 효소이다. AAK1은 세포막과 세포질 내에서 발현되며, 두 가지 생리적 기질을 갖는 것으로 알려진 핵심적인 세포내이입 키나아제이다. Adaptor-associated kinase 1 (AAK1) is a 104 kDa serine/threonine kinase belonging to the Numb-associated kinase (NAK) family, also known as AP2-associated protein kinase 1. It is encoded by the AAK1 gene in humans and is involved in clathrin-mediated endocytosis. AAK1 is a key endocytic kinase known to be expressed in the plasma membrane and cytoplasm and to have two physiological substrates.

AAK1은 정신분열증, 정신분열증의 인지 결함, 파킨슨병, 양극성 장애, 알츠하이머병 및 신경병증성 통증과 같은 다양한 신경 및 정신 질환의 치료를 위한 약물 표적으로 제안되고 있다. 최근에는 AAK1이 바이러스 복제에 필수적인 세포 인자인 것으로 밝혀져 광범위한 항바이러스제 개발을 위한 숙주 표적으로 여겨지고 있다. AAK1 has been proposed as a drug target for the treatment of various neurological and psychiatric disorders, including schizophrenia, cognitive deficits in schizophrenia, Parkinson's disease, bipolar disorder, Alzheimer's disease, and neuropathic pain. Recently, AAK1 has been identified as a cellular factor essential for viral replication, making it a potential host target for the development of broad-spectrum antiviral agents.

이에 따라, AAK1을 표적으로 하는 다양한 질환 치료제가 개발되고 있으며, 대표적으로 WO 2017/059085 A1에서는 통증, 알츠하이머병, 파킨슨병 및 정신분열증의 치료를 위한 바이아릴 키나아제 억제제를 개시하고 있다.Accordingly, various disease treatments targeting AAK1 are being developed, and WO 2017/059085 A1, for example, discloses a biaryl kinase inhibitor for the treatment of pain, Alzheimer's disease, Parkinson's disease, and schizophrenia.

이와 같이, 신경병증성 통증 치료를 위한 약물 표적으로 AAK1이 유망하다는 점은 AAK1 억제제에 대한 탐색을 자극하였다. 그러나, 이 분야에서 약물을 개발하고 있는 회사는 제한적이어서, 이 표적에 대한 연구가 더욱더 필요하다.Thus, the promising potential of AAK1 as a drug target for treating neuropathic pain has stimulated the search for AAK1 inhibitors. However, the number of companies developing drugs in this area is limited, necessitating further research on this target.

본 발명이 해결하고자 하는 과제는 AAK1에 대하여 우수한 억제 활성을 나타내는 신규한 구조의 헤테로아릴 유도체를 제공하는 것이다.The problem to be solved by the present invention is to provide a novel heteroaryl derivative having a structure that exhibits excellent inhibitory activity against AAK1.

또한, 본 발명의 해결 과제는 상기 신규한 구조의 헤테로아릴 유도체를 포함하는 AAK1 억제 관련 질환의 예방 또는 치료용 약학 조성물을 제공하는 것이다.In addition, the problem to be solved by the present invention is to provide a pharmaceutical composition for preventing or treating a disease related to AAK1 inhibition, which comprises a heteroaryl derivative having the novel structure.

또한, 본 발명의 해결 과제는 상기 신규한 구조의 헤테로아릴 유도체의 치료적 유효량을 이를 필요로 하는 개체에게 투여하는 것을 포함하는, AAK1 억제 관련 질환의 예방 또는 치료 방법을 제공하는 것이다.In addition, the problem to be solved by the present invention is to provide a method for preventing or treating a disease related to AAK1 inhibition, which comprises administering a therapeutically effective amount of a heteroaryl derivative having the novel structure to a subject in need thereof.

또한, 본 발명의 해결 과제는 AAK1 억제 관련 질환의 예방 또는 치료용 의약 제조에 있어서, 상기 신규한 구조의 헤테로아릴 유도체의 유효성분으로서의 용도를 제공하는 것이다.In addition, the problem to be solved by the present invention is to provide a use of the novel heteroaryl derivative as an effective ingredient in the manufacture of a pharmaceutical for preventing or treating a disease related to AAK1 inhibition.

본 발명이 해결하고자 하는 과제는 이상에서 언급한 해결 과제로 제한되지 않으며, 언급되지 않은 또 다른 기술적 과제들은 아래의 기재로부터 본 발명이 속하는 기술 분야에서 통상의 지식을 가진 자에게 명확하게 이해될 수 있을 것이다.The problems to be solved by the present invention are not limited to the problems mentioned above, and other technical problems not mentioned can be clearly understood by a person having ordinary skill in the technical field to which the present invention belongs from the description below.

상기 해결 과제를 달성하기 위하여, 본 발명의 일 측면에 따라, 하기 화학식 1로 표시되는 헤테로아릴 유도체 화합물, 이의 수화물, 이의 용매화물 또는 이의 약학적으로 허용가능한 염이 제공된다.In order to achieve the above-mentioned problem, according to one aspect of the present invention, a heteroaryl derivative compound represented by the following chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof is provided.

<화학식 1><Chemical Formula 1>

상기 식에서, In the above formula,

A는 CH 또는 N이고,A is CH or N,

B1, B3, B4 및 B5는 C, CH, N 또는 NH이고,B 1 , B 3 , B 4 and B 5 are C, CH, N or NH,

B2는 C, CH, N, NH 또는 O이고,B 2 is C, CH, N, NH or O,

B 고리는 N 및 O 중에서 선택되는 1 내지 4개의 헤테로원자를 포함하는 5원의 방향족 헤테로사이클이고,The B ring is a 5-membered aromatic heterocycle containing 1 to 4 heteroatoms selected from N and O,

Y는 NH, NR6 또는 O이고,Y is NH, NR 6 or O,

R2는 H 또는 할로겐이고,R 2 is H or halogen,

R4는 H, C1-4 알킬, 할로겐 또는 C1-4 할로알킬이고,R 4 is H, C 1-4 alkyl, halogen or C 1-4 haloalkyl,

R5는 C1-9 직쇄 또는 분지쇄 알킬로서 C3-5 사이클로알킬을 포함하거나 포함하지 않고; 또는 R6와 연결되어, R5 및 R6에 연결된 N을 포함하고, N 또는 O를 추가로 포함하는, 5원 내지 7원의 비방향족 헤테로사이클을 형성하고,R 5 is a C 1-9 straight or branched chain alkyl, optionally including a C 3-5 cycloalkyl; or is connected to R 6 to form a 5- to 7-membered non-aromatic heterocycle, comprising N connected to R 5 and R 6 , and further comprising N or O,

상기 R5는 단수 또는 복수의 R5a로 치환되거나 치환되지 않고,wherein R 5 is substituted or unsubstituted with singular or plural R 5a ,

상기 R5a는 C1-4 알킬, 아미노 또는 하이드록시이고,wherein R 5a is C 1-4 alkyl, amino or hydroxy,

R6는 R5와 연결되어, R5 및 R6에 연결된 N을 포함하고, N 또는 O를 추가로 포함하는, 5원 내지 7원의 비방향족 헤테로사이클을 형성하고,R 6 is connected to R 5 to form a 5- to 7-membered non-aromatic heterocycle containing N connected to R 5 and R 6 , and further containing N or O,

상기 B1은 Rb1으로 치환되거나 치환되지 않고,The above B 1 is substituted or not substituted with R b1 ,

상기 Rb1은 C1-4 알킬이거나; Rb2와 연결되어 0개 내지 2개의 N을 포함하고 B 고리와 융합된 C 고리를 형성하고,wherein R b1 is C 1-4 alkyl or is connected to R b2 to form a C ring containing 0 to 2 N and fused with the B ring,

상기 B2는 Rb2로 치환되거나 치환되지 않고,The above B 2 is substituted or not substituted with R b2 ,

상기 Rb2는 Rb1과 연결되어 0개 내지 2개의 N을 포함하고 B 고리와 융합된 C 고리를 형성하고,The above R b2 is connected to R b1 to form a C ring containing 0 to 2 N and fused with the B ring,

상기 B4는 Rb4로 치환되거나 치환되지 않고,The above B 4 is substituted or not substituted with R b4 ,

상기 Rb4는 C1-4 알킬 또는 할로겐이고,wherein R b4 is C 1-4 alkyl or halogen,

상기 B 고리와 C 고리의 융합 고리는 1 내지 4개의 N을 포함하는 2개환의 융합 고리로서, Rf로 치환되거나 치환되지 않고,The fused ring of the above B ring and C ring is a fused ring of two rings containing 1 to 4 N, which is substituted or unsubstituted with R f ,

상기 Rf는 할로겐, C1-4 할로알킬 또는 C1-4 알콕시이다.wherein R f is halogen, C 1-4 haloalkyl or C 1-4 alkoxy.

본 발명의 다른 측면에 따라, 상기 화학식 1로 표시되는 헤테로아릴 유도체 화합물, 이의 수화물, 이의 용매화물 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는, AAK1 억제 관련 질환의 예방 또는 치료용 약학 조성물이 제공된다.According to another aspect of the present invention, a pharmaceutical composition for preventing or treating a disease related to AAK1 inhibition is provided, comprising a heteroaryl derivative compound represented by the above chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.

본 발명의 또 다른 측면에 따라, 상기 화학식 1로 표시되는 헤테로아릴 유도체 화합물, 이의 수화물, 이의 용매화물 또는 이의 약학적으로 허용가능한 염의 치료적 유효량을 이를 필요로 하는 개체에게 투여하는 것을 포함하는, AAK1 억제 관련 질환의 예방 또는 치료 방법이 제공된다.According to another aspect of the present invention, a method for preventing or treating a disease associated with AAK1 inhibition is provided, comprising administering a therapeutically effective amount of a heteroaryl derivative compound represented by the above chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof to a subject in need thereof.

본 발명의 또 다른 측면에 따라, AAK1 억제 관련 질환의 예방 또는 치료용 의약 제조에 있어서, 상기 화학식 1로 표시되는 헤테로아릴 유도체 화합물, 이의 수화물, 이의 용매화물 또는 이의 약학적으로 허용가능한 염의 유효성분으로서의 용도가 제공된다.According to another aspect of the present invention, there is provided a use of a heteroaryl derivative compound represented by the above chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof as an effective ingredient in the manufacture of a medicament for preventing or treating a disease associated with AAK1 inhibition.

본 발명의 또 다른 측면에 따라, 상기 화학식 1로 표시되는 헤테로아릴 유도체 화합물, 이의 수화물, 이의 용매화물 또는 이의 약학적으로 허용가능한 염과, 약제학적으로 허용가능한 첨가제를 포함하는 약학 조성물이 제공된다.According to another aspect of the present invention, a pharmaceutical composition comprising a heteroaryl derivative compound represented by the above chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable additive is provided.

본 발명의 헤테로아릴 유도체 화합물은 AAK1에 대하여 우수한 억제 활성을 나타내는 것이 확인되어, AAK1 억제 관련 질환의 예방 및 치료 용도로 사용될 수 있음이 밝혀졌다.It was confirmed that the heteroaryl derivative compound of the present invention exhibits excellent inhibitory activity against AAK1, and thus it was revealed that it can be used for the prevention and treatment of diseases related to AAK1 inhibition.

따라서, 본 발명의 헤테로아릴 유도체 화합물은 의약 및 약학 분야에서 AAK1 억제 관련 질환인 급만성 통증 및 신경병증성 통증 등의 예방 및 치료에 유용하게 사용될 수 있다.Therefore, the heteroaryl derivative compound of the present invention can be usefully used in the fields of medicine and pharmacy for the prevention and treatment of acute and chronic pain and neuropathic pain, which are diseases related to AAK1 inhibition.

본 발명의 효과는 상기한 효과로 한정되는 것은 아니며, 본 발명의 설명 또는 특허청구범위에 기재된 발명의 구성으로부터 추론 가능한 모든 효과를 포함하는 것으로 이해되어야 한다.The effects of the present invention are not limited to the effects described above, and should be understood to include all effects that can be inferred from the composition of the invention described in the description or claims of the present invention.

본 명세서에서, AAK1은 어댑터-연관 키나아제 1(Adaptor-associated kinase 1, AAK1)를 의미하며, Numb 관련 키나아제(Numb-associated kinase, NAK) 계열에 속하는 104 kDa 세린/트레오닌 키나아제로서, AP2-연관 단백질 키나아제 1으로도 지칭되며, 인간에서 AAK1 유전자에 의해 암호화되고 클라트린(clatherin) 매개 세포내 이입에 관여하는 효소이다.In this specification, AAK1 refers to Adapter-associated kinase 1 (AAK1), a 104 kDa serine/threonine kinase belonging to the Numb-associated kinase (NAK) family, also referred to as AP2-associated protein kinase 1, which is encoded by the AAK1 gene in humans and is an enzyme involved in clathrin-mediated endocytosis.

본 발명은 하기 화학식 1로 표시되는 헤테로아릴 유도체 화합물, 이의 수화물, 이의 용매화물 또는 이의 약학적으로 허용가능한 염을 제공한다.The present invention provides a heteroaryl derivative compound represented by the following chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof.

<화학식 1><Chemical Formula 1>

상기 식에서, In the above formula,

A는 CH 또는 N이고,A is CH or N,

B1, B3, B4 및 B5는 C, CH, N 또는 NH이고,B 1 , B 3 , B 4 and B 5 are C, CH, N or NH,

B2는 C, CH, N, NH 또는 O이고,B 2 is C, CH, N, NH or O,

B 고리는 N 및 O 중에서 선택되는 1 내지 4개의 헤테로원자를 포함하는 5원의 방향족 헤테로사이클이고,The B ring is a 5-membered aromatic heterocycle containing 1 to 4 heteroatoms selected from N and O,

Y는 NH, NR6 또는 O이고,Y is NH, NR 6 or O,

R2는 H 또는 할로겐이고,R 2 is H or halogen,

R4는 H, C1-4 알킬, 할로겐 또는 C1-4 할로알킬이고,R 4 is H, C 1-4 alkyl, halogen or C 1-4 haloalkyl,

R5는 C1-9 직쇄 또는 분지쇄 알킬로서 C3-5 사이클로알킬을 포함하거나 포함하지 않고; 또는 R6와 연결되어, R5 및 R6에 연결된 N을 포함하고, N 또는 O를 추가로 포함하는, 5원 내지 7원의 비방향족 헤테로사이클을 형성하고,R 5 is a C 1-9 straight or branched chain alkyl, optionally including a C 3-5 cycloalkyl; or is connected to R 6 to form a 5- to 7-membered non-aromatic heterocycle, comprising N connected to R 5 and R 6 , and further comprising N or O,

상기 R5는 단수 또는 복수의 R5a로 치환되거나 치환되지 않고,wherein R 5 is substituted or unsubstituted with singular or plural R 5a ,

상기 R5a는 C1-4 알킬, 아미노 또는 하이드록시이고,wherein R 5a is C 1-4 alkyl, amino or hydroxy,

R6는 R5와 연결되어, R5 및 R6에 연결된 N을 포함하고, N 또는 O를 추가로 포함하는, 5원 내지 7원의 비방향족 헤테로사이클을 형성하고,R 6 is connected to R 5 to form a 5- to 7-membered non-aromatic heterocycle containing N connected to R 5 and R 6 , and further containing N or O,

상기 B1은 Rb1으로 치환되거나 치환되지 않고,The above B 1 is substituted or not substituted with R b1 ,

상기 Rb1은 C1-4 알킬이거나; Rb2와 연결되어 0개 내지 2개의 N을 포함하고 B 고리와 융합된 C 고리를 형성하고,wherein R b1 is C 1-4 alkyl or is connected to R b2 to form a C ring containing 0 to 2 N and fused with the B ring,

상기 B2는 Rb2로 치환되거나 치환되지 않고,The above B 2 is substituted or not substituted with R b2 ,

상기 Rb2는 Rb1과 연결되어 0개 내지 2개의 N을 포함하고 B 고리와 융합된 C 고리를 형성하고,The above R b2 is connected to R b1 to form a C ring containing 0 to 2 N and fused with the B ring,

상기 B4는 Rb4로 치환되거나 치환되지 않고,The above B 4 is substituted or not substituted with R b4 ,

상기 Rb4는 C1-4 알킬 또는 할로겐이고,wherein R b4 is C 1-4 alkyl or halogen,

상기 B 고리와 C 고리의 융합 고리는 1 내지 4개의 N을 포함하는 2개환의 융합 고리로서, Rf로 치환되거나 치환되지 않고,The fused ring of the above B ring and C ring is a fused ring of two rings containing 1 to 4 N, which is substituted or unsubstituted with R f ,

상기 Rf는 할로겐, C1-4 할로알킬 또는 C1-4 알콕시이다.wherein R f is halogen, C 1-4 haloalkyl or C 1-4 alkoxy.

일 구현예에서, 상기 B 고리는 피롤릴, 피라졸릴, 이미다졸릴, 이속사졸릴 또는 트리아졸릴일 수 있다.In one embodiment, the B ring can be pyrrolyl, pyrazolyl, imidazolyl, isoxazolyl, or triazolyl.

일 구현예에서, 상기 R2는 H, 플루오로 또는 클로로일 수 있다.In one embodiment, R 2 can be H, fluoro or chloro.

일 구현예에서, 상기 R4는 H, 메틸, 플루오로, 클로로, 다이플루오로메틸 또는 트리플루오로메틸일 수 있다.In one embodiment, R 4 can be H, methyl, fluoro, chloro, difluoromethyl or trifluoromethyl.

일 구현예에서, 상기 R5는 에틸, 2-메틸-프로필-, 4-메틸-펜틸-, 2,4-다이메틸펜틸-, 사이클로프로필-메틸- 또는 사이클로부틸-메틸-일 수 있다.In one embodiment, R 5 can be ethyl, 2-methyl-propyl-, 4-methyl-pentyl-, 2,4-dimethylpentyl-, cyclopropyl-methyl-, or cyclobutyl-methyl-.

일 구현예에서, 상기 R5 및 R6가 연결되어 형성하는 비방향족 헤테로사이클은 피페라지닐 또는 모폴리노일 수 있다.In one embodiment, the non-aromatic heterocycle formed by linking R 5 and R 6 may be piperazinyl or morpholino.

일 구현예에서, 상기 R5a는 메틸, 아미노 또는 하이드록시일 수 있다.In one embodiment, R 5a can be methyl, amino or hydroxy.

일 구현예에서, 상기 Rb1은 메틸일 수 있다.In one embodiment, R b1 can be methyl.

일 구현예에서, 상기 B 고리와 C 고리의 융합 고리는 하기 화학식으로 구성되는 군으로부터 선택되는 어느 하나일 수 있다:In one embodiment, the fused ring of the B ring and the C ring may be any one selected from the group consisting of the following chemical formulas:

일 구현예에서, 상기 Rb4는 메틸 또는 플루오로일 수 있다.In one embodiment, R b4 can be methyl or fluoro.

일 구현예에서, 상기 Rf는 플루오로, 클로로, 트리플루오로메틸 또는 메톡시일 수 있다.In one embodiment, R f can be fluoro, chloro, trifluoromethyl or methoxy.

본 발명에 따른 헤테로아릴 유도체 화합물의 구체적인 예는 다음과 같다:Specific examples of heteroaryl derivative compounds according to the present invention are as follows:

[1] (S)-1-((6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[1] ( S )-1-((6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[2] (S)-1-((6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[2] (S)-1-((6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[3] (S)-1-((6-(1H-피롤로[3,2-c]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[3] ( S )-1-((6-(1 H -pyrrolo[3,2- c ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[4] (S)-1-((6-(1H-피롤로[2,3-c]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[4] ( S )-1-((6-(1 H -pyrrolo[2,3- c ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[5] (S)-1-((6-(7-플루오로이미다조[1,2-a]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[5] ( S )-1-((6-(7-fluoroimidazo[1,2- a ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[6] (S)-1-((6-(1H-피라졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[6] ( S )-1-((6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[7] (S)-1-((6-(1H-피롤-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[7] ( S )-1-((6-(1 H -pyrrol-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[8] (S)-1-((6-(2H-1,2,3-트리아졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[8] ( S )-1-((6-(2 H -1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[9] (S)-1-((6-(3,5-다이메틸-1H-피라졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[9] ( S )-1-(( 6 -( 3 , 5 -dimethyl-1 H -pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[10] (S)-1-((6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[10] ( S )-1-((6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[11] (S)-1-((6-(6-플루오로-1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[11] ( S )-1-((6-(6-fluoro-1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[12] (S)-1-((6-(6-클로로-1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[12] ( S )-1-((6-(6-chloro-1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[13] (S)-1-((2-(다이플루오로메틸)-6-(1H-피라졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[13] ( S )-1-((2-(difluoromethyl)-6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[14] (S)-1-((2-(다이플루오로메틸)-6-(이속사졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[14] ( S )-1-((2-(difluoromethyl)-6-(isoxazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[15] (S)-1-((2-(다이플루오로메틸)-6-(1H-이미다졸-1-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[15] ( S )-1-((2-(difluoromethyl)-6-(1 H -imidazol-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[16] (S)-1-((2-(다이플루오로메틸)-6-(3-플루오로-1H-피라졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[16] ( S )-1-((2-(difluoromethyl)-6-(3-fluoro-1 H -pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[17] (S)-1-((2-(다이플루오로메틸)-6-(1H-이미다졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[17] ( S )-1-((2-(difluoromethyl)-6-(1 H -imidazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[18] (S)-1-((2-(다이플루오로메틸)-6-(1H-피롤-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[18] ( S )-1-((2-(difluoromethyl)-6-(1 H -pyrrol-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[19] (S)-1-((2-(다이플루오로메틸)-6-(1H-피라졸-5-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[19] ( S )-1-((2-(difluoromethyl)-6-(1 H -pyrazol-5-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[20] (S)-1-((2-(다이플루오로메틸)-6-(2H-1,2,3-트리아졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[20] ( S )-1-((2-(difluoromethyl)-6-(2 H -1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[21] (S)-1-((2-(다이플루오로메틸)-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[21] ( S )-1-((2-(difluoromethyl)-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[22] (S)-1-(2-(다이플루오로메틸)-4-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)펜옥시)-2,4-다이메틸펜탄-2-아민,[22] ( S )-1-(2-(difluoromethyl)-4-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)phenoxy)-2,4-dimethylpentan-2-amine,

[23] (S)-1-((2-(다이플루오로메틸)-6-(5-(트리플루오로메틸)-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[23] ( S )-1-((2-(difluoromethyl)-6-(5-(trifluoromethyl)-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[24] (S)-1-((2-(다이플루오로메틸)-6-(4-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[24] ( S )-1-((2-(difluoromethyl)-6-(4-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[25] ((S)-1-((2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[25] (( S )-1-((2-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[26] (S)-1-((6-(5-클로로-1H-피라졸로[3,4-b]피리딘-3-일)-2-(다이플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[26] ( S )-1-((6-(5-chloro-1 H -pyrazolo[3,4- b ]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[27] (S)-1-((2-(다이플루오로메틸)-6-(4-메톡시-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[27] ( S )-1-((2-(difluoromethyl)-6-(4-methoxy-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[28] (S)-1-((2-(다이플루오로메틸)-6-(6-플루오로-1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[28] ( S )-1-((2-(difluoromethyl)-6-(6-fluoro-1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[29] (S)-1-((2-(다이플루오로메틸)-6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[29] (S)-1-((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[30] (S)-1-((4-(다이플루오로메틸)-6-(1H-피라졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[30] ( S )-1-((4-(difluoromethyl)-6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[31] (S)-1-((4-(다이플루오로메틸)-6-(2H-1,2,3-트리아졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[31] ( S )-1-((4-(difluoromethyl)-6-(2 H -1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[32] ((S)-1-((4-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[32] (( S )-1-((4-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[33] (S)-1-((5-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[33] ( S )-1-((5-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[34] (S)-1-((6-(1H-피라졸-4-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[34] ( S )-1-((6-(1 H -pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[35] (S)-1-((6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[35] ( S )-1-((6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[36] (S)-1-((5-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민,[36] ( S )-1-((5-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine,

[37] (S)-1-((3-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민,[37] ( S )-1-((3-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine,

[38] (S)-1-((4-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민,[38] ( S )-1-((4-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine,

[39] (S)-1-((6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민,[39] ( S )-1-((6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine,

[40] (S)-1-((4-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[40] ( S )-1-((4-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[41] (S)-1-((5-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[41] ( S )-1-((5-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[42] (S)-1-((3-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-4-일)옥시)-2,4-다이메틸펜탄-2-아민,[42] ( S )-1-((3-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine,

[43] (S)-1-((2-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-4-일)옥시)-2,4-다이메틸펜탄-2-아민,[43] ( S )-1-((2-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine,

[44] (S)-1-((2-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[44] ( S )-1-((2-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[45] 1-((2-(다이플루오로메틸)-6-(1H-피라졸-4-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민,[45] 1-((2-(difluoromethyl)-6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine,

[46] 1-((2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민,[46] 1-((2-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine,

[47] 1-((2-(다이플루오로메틸)-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민,[47] 1-((2-(difluoromethyl)-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine,

[48] 1-((2-(다이플루오로메틸)-6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민,[48] 1-((2-(difluoromethyl)-6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine,

[49] 1-((6-(1H-피라졸-4-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)-2-메틸프로판-2-아민,[49] 1-((6-(1 H -pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine,

[50] 1-((6-(1H-피롤로[2,3-b]피리딘-3-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)-2-메틸프로판-2-아민,[50] 1-((6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine,

[51] 2-((6-(5-클로로-1H-피라졸로[3,4-b]피리딘-3-일)-2-(다이플루오로메틸)피리딘-3-일)옥시)에탄-1-올,[51] 2-((6-(5-chloro-1 H -pyrazolo[3,4- b ]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-ol,

[52] 2-((6-(5-클로로-1H-피라졸로[3,4-b]피리딘-3-일)-2-(다이플루오로메틸)피리딘-3-일)옥시)에탄-1-아민,[52] 2-((6-(5-chloro-1 H -pyrazolo[3,4- b ]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-amine,

[53] (S)-1-((4-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민,[53] ( S )-1-((4-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine,

[54] (S)-1-((5-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[54] ( S )-1-((5-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine,

[55] (S)-1-((5-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민,[55] ( S )-1-((5-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine,

[56] (S)-1-(4-(1H-피롤로[3,2-b]피리딘-1-일)펜옥시)-2,4-다이메틸펜탄-2-아민,[56] ( S )-1-(4-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)phenoxy)-2,4-dimethylpentan-2-amine,

[57] (S)-1-((2-(다이플루오로메틸)-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[57] ( S )-1-((2-(difluoromethyl)-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[58] (S)-1-((2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[58] ( S )-1-((2-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[59] (S)-1-((2-(다이플루오로메틸)-6-(4-메톡시-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[59] ( S )-1-((2-(difluoromethyl)-6-(4-methoxy-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[60] (S)-1-((2-(다이플루오로메틸)-6-(1H-피라졸-4-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[60] ( S )-1-((2-(difluoromethyl)-6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[61] 1-((4-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민,[61] 1-((4-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine,

[62] 1-((4-(다이플루오로메틸)-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민,[62] 1-((4-(difluoromethyl)-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine,

[63] 1-((5-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민,[63] 1-((5-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine,

[64] 1-((5-(다이플루오로메틸)-6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민,[64] 1-((5-(difluoromethyl)-6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine,

[65] 1-(((2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[65] 1-(((2-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[66] 1-(((2-(다이플루오로메틸)-6-(1H-피라졸-4-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[66] 1-(((2-(difluoromethyl)-6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[67] 1-(((2-(다이플루오로메틸)-6-(2H-1,2,3-트리아졸-4-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[67] 1-(((2-(difluoromethyl)-6-(2 H -1,2,3-triazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[68] 1-(((2-(다이플루오로메틸)-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[68] 1-(((2-(difluoromethyl)-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[69] 1-(((2-(다이플루오로메틸)-6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[69] 1-(((2-(difluoromethyl)-6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[70] 1-(((6-(1H-피라졸-4-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[70] 1-(((6-(1 H -pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[71] 1-((5-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민,[71] 1-((5-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine,

[72] 1-(((5-(다이플루오로메틸)-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[72] 1-(((5-(difluoromethyl)-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[73] 1-(((2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로부탄-1-아민,[73] 1-(((2-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine,

[74] 1-(((2-(다이플루오로메틸)-6-(1H-피라졸-4-일)피리딘-3-일)옥시)메틸)사이클로부탄-1-아민,[74] 1-(((2-(difluoromethyl)-6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine,

[75] 1-(((2-(다이플루오로메틸)-6-(2H-1,2,3-트리아졸-4-일)피리딘-3-일)옥시)메틸)사이클로부탄-1-아민,[75] 1-(((2-(difluoromethyl)-6-(2 H -1,2,3-triazol-4-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine,

[76] 1-(((2-(다이플루오로메틸)-6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)메틸)사이클로부탄-1-아민,[76] 1-(((2-(difluoromethyl)-6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine,

[77] 1-(((6-(1H-피라졸-4-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)메틸)사이클로부탄-1-아민,[77] 1-(((6-(1 H -pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine,

[78] 1-(((6-(2H-1,2,3-트리아졸-4-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)메틸)사이클로부탄-1-아민,[78] 1-(((6-(2 H -1,2,3-triazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine,

[79] 1-((2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2-메틸프로판-2-올,[79] 1-((2-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-ol,

[80] 1-((2-(다이플루오로메틸)-6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)-2-메틸프로판-2-올,[80] 1-((2-(difluoromethyl)-6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-ol,

[81] (S)-1-(4-(1H-피롤로[2,3-b]피리딘-3-일)펜옥시)-2,4-다이메틸펜탄-2-아민,[81] ( S )-1-(4-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)phenoxy)-2,4-dimethylpentan-2-amine,

[82] (S)-1-((6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[82] ( S )-1-((6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[83] (S)-1-((6-(4-메톡시-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[83] ( S )-1-((6-(4-methoxy-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[84] (S)-1-((6-(1H-피라졸-4-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[84] ( S )-1-((6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[85] (S)-1-((6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[85] ( S )-1-((6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[86] (S)-1-((6-(4-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[86] ( S )-1-((6-(4-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[87] (S)-1-((6-(6-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[87] ( S )-1-((6-(6-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[88] (S)-1-((6-(6-플루오로-1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[88] ( S )-1-((6-(6-fluoro-1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[89] (S)-1-((6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[89] ( S )-1-((6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[90] (S)-1-((6-(1H-피롤로[2,3-c]피리딘-1-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[90] ( S )-1-((6-(1 H -pyrrolo[2,3- c ]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[91] (S)-1-((6-(1H-피롤로[2,3-b]피리딘-1-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[91] ( S )-1-((6-(1 H -pyrrolo[2,3- b ]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[92] (S)-1-((6-(1H-피롤로[3,2-c]피리딘-1-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[92] ( S )-1-((6-(1 H -pyrrolo[3,2- c ]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine,

[93] (S)-1-(4-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)펜옥시)-4-메틸펜탄-2-아민,[93] ( S )-1-(4-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)phenoxy)-4-methylpentan-2-amine,

[94] (S)-1-(4-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)-2-(트리플루오로메틸)펜옥시)-4-메틸펜탄-2-아민,[94] ( S )-1-(4-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)-2-(trifluoromethyl)phenoxy)-4-methylpentan-2-amine,

[95] 1-(((6-(2H-1,2,3-트리아졸-4-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[95] 1-(((6-(2 H -1,2,3-triazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[96] 1-(((6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[96] 1-(((6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[97] 1-(((6-(1H-피라졸-4-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[97] 1-(((6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[98] 1-(((6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[98] 1-(((6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[99] 1-(((2-플루오로-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[99] 1-(((2-fluoro-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[100] 1-(((2-플루오로-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[100] 1-(((2-fluoro-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[101] 1-(((2-플루오로-6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[101] 1-(((2-fluoro-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[102] 1-(((4-플루오로-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[102] 1-(((4-fluoro-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[103] 1-(((4-플루오로-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[103] 1-(((4-fluoro-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[104] 1-(((5-플루오로-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[104] 1-(((5-fluoro-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[105] 1-(((5-플루오로-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[105] 1-(((5-fluoro-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine,

[106] 1-(((6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로부탄-1-아민,[106] 1-(((6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine,

[107] 1-(2-(다이플루오로메틸)-4-(1H-피롤로[2,3-b]피리딘-3-일)펜옥시)-2-메틸프로판-2-아민,[107] 1-(2-(difluoromethyl)-4-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine,

[108] N 1-(2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)-2-메틸프로판-1,2-다이아민,[108] N 1 -(2-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)-2-methylpropane-1,2-diamine,

[109] N 1-(2-(다이플루오로메틸)-6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)-2-메틸프로판-1,2-다이아민,[109] N 1 -(2-(difluoromethyl)-6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)-2-methylpropane-1,2-diamine,

[110] N 1-(6-(1H-피롤로[2,3-b]피리딘-3-일)-2-(트리플루오로메틸)피리딘-3-일)-2-메틸프로판-1,2-다이아민,[110] N 1 -(6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)-2-methylpropane-1,2-diamine,

[111] N 1-(2-(다이플루오로메틸)-4-(1H-피롤로[2,3-b]피리딘-3-일)페닐)-2-메틸프로판-1,2-다이아민,[111] N 1 -(2-(difluoromethyl)-4-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)phenyl)-2-methylpropane-1,2-diamine,

[112] N-((1-아미노사이클로프로필)메틸)-2-(다이플루오로메틸)-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-아민,[112] N -((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-amine,

[113] N-((1-아미노사이클로프로필)메틸)-2-(다이플루오로메틸)-6-(1H-피라졸-4-일)피리딘-3-아민,[113] N -((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1 H -pyrazol-4-yl)pyridin-3-amine,

[114] N-((1-아미노사이클로프로필)메틸)-2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-아민,[114] N -((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-amine,

[115] N-((1-아미노사이클로프로필)메틸)-2-(다이플루오로메틸)-6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-아민,[115] N -((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-amine,

[116] N-((1-아미노사이클로프로필)메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-아민,[116] N -((1-aminocyclopropyl)methyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-amine,

[117] N-((1-아미노사이클로프로필)메틸)-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-아민,[117] N -((1-aminocyclopropyl)methyl)-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-amine,

[118] N-((1-아미노사이클로프로필)메틸)-4-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-아민,[118] N -((1-aminocyclopropyl)methyl)-4-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-amine,

[119] N-((1-아미노사이클로프로필)메틸)-5-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-아민,[119] N -((1-aminocyclopropyl)methyl)-5-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-amine,

[120] 1-((2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)아미노)-2-메틸프로판-2-올,[120] 1-((2-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)amino)-2-methylpropan-2-ol,

[121] 1-((2-(다이플루오로메틸)-6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)아미노)-2-메틸프로판-2-올,[121] 1-((2-(difluoromethyl)-6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)amino)-2-methylpropan-2-ol,

[122] 1-(2-클로로-4-(1H-피롤로[2,3-b]피리딘-3-일)펜옥시)-2-메틸프로판-2-아민,[122] 1-(2-chloro-4-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine,

[123] 1-(2-플루오로-4-(1H-피롤로[2,3-b]피리딘-3-일)펜옥시)-2-메틸프로판-2-아민,[123] 1-(2-fluoro-4-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine,

[124] 1-(2,5-다이클로로-4-(1H-피롤로[2,3-b]피리딘-3-일)펜옥시)-2-메틸프로판-2-아민,[124] 1-(2,5-dichloro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine,

[125] 2-메틸-1-(2-메틸-4-(1H-피롤로[2,3-b]피리딘-3-일)펜옥시)프로판-2-아민,[125] 2-methyl-1-(2-methyl-4-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)phenoxy)propan-2-amine,

[126] 1-(2,6-다이플루오로-4-(1H-피롤로[2,3-b]피리딘-3-일)펜옥시)-2-메틸프로판-2-아민,[126] 1-(2,6-difluoro-4-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine,

[127] 1-(2,5-다이플루오로-4-(1H-피롤로[2,3-b]피리딘-3-일)펜옥시)-2-메틸프로판-2-아민,[127] 1-(2,5-difluoro-4-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine,

[128] 5-플루오로-3-(4-(피페라진-1-일)페닐)-1H-피롤로[2,3-b]피리딘,[128] 5-Fluoro-3-(4-(piperazin-1-yl)phenyl)-1 H -pyrrolo[2,3- b ]pyridine,

[129] 5-플루오로-3-(4-(4-메틸피페라진-1-일)페닐)-1H-피롤로[2,3-b]피리딘,[129] 5-Fluoro-3-(4-(4-methylpiperazin-1-yl)phenyl)-1 H -pyrrolo[2,3- b ]pyridine,

[130] 4-(4-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)페닐)모폴린,[130] 4-(4-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)phenyl)morpholine,

[131] 5-플루오로-3-(5-(피페라진-1-일)피리딘-2-일)-1H-피롤로[2,3-b]피리딘,[131] 5-Fluoro-3-(5-(piperazin-1-yl)pyridin-2-yl)-1 H -pyrrolo[2,3- b ]pyridine,

[132] 5-플루오로-3-(5-(4-메틸피페라진-1-일)피리딘-2-일)-1H-피롤로[2,3-b]피리딘,[132] 5-Fluoro-3-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)-1 H -pyrrolo[2,3- b ]pyridine,

[133] 4-(6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)모폴린,[133] 4-(6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)morpholine,

[134] 4-(2-(다이플루오로메틸)-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)모폴린,[134] 4-(2-(difluoromethyl)-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)morpholine,

[135] 4-(2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)-2,2-다이메틸모폴린, 및[135] 4-(2-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)-2,2-dimethylmorpholine, and

[136] 3-(6-(다이플루오로메틸)-5-(3,3-다이메틸피페라진-1-일)피리딘-2-일)-1H-피롤로[2,3-b]피리딘.[136] 3-(6-(difluoromethyl)-5-(3,3-dimethylpiperazin-1-yl)pyridin-2-yl)-1 H -pyrrolo[2,3- b ]pyridine.

본 명세서를 통하여 화학식 1의 화합물을 정의함에 있어서는 달리 언급하지 않는 한 다음의 정의가 적용된다.In defining the compound of formula 1 throughout this specification, the following definitions apply unless otherwise stated.

본 명세서에 사용된 용어 "알킬"은 직쇄형 또는 분지쇄형 포화 탄화수소로서, C1-10　알킬이 바람직하다. 예를 들어, 상기 알킬은 메틸, 에틸, n-프로필, iso-프로필, n-부틸, iso-부틸, tert-부틸, n-펜틸, iso-펜틸, n-헥실, 3-메틸헥실, 2,2-디메틸펜틸, 2,3-디메틸펜틸, n-헵틸, n-옥틸, n-노닐 및 n-데실 등을 포함하지만, 이에 한정되는 것은 아니다.The term "alkyl" as used herein refers to a straight or branched chain saturated hydrocarbon, preferably C 1-10 alkyl. For example, the alkyl includes, but is not limited to, methyl, ethyl, n -propyl, iso -propyl, n -butyl, iso -butyl, tert -butyl, n -pentyl, iso -pentyl, n -hexyl, 3-methylhexyl, 2,2-dimethylpentyl, 2,3-dimethylpentyl, n -heptyl, n -octyl, n -nonyl, and n -decyl.

본 명세서에 사용된 용어 "사이클로알킬"은 부분적 또는 전체적으로 포화된 단일 또는 융합 고리형 탄화수소이며, C3-10의 모노사이클릭, 바이사이클릭 또는 트리사이클릭 작용기를 의미한다. 사이클로알킬 중 모노사이클릭 작용기의 예는 사이클로프로필, 사이클로부틸, 사이클로펜틸, 사이클로헥실, 사이클로헥시닐 등을 포함한다. 사이클로알킬 중 바이사이클릭 작용기는 바이사이클로알킬 및 스파이로 작용기를 포함한다.The term "cycloalkyl" as used herein means a partially or fully saturated single or fused ring hydrocarbon, and a C 3-10 monocyclic, bicyclic, or tricyclic functional group. Examples of monocyclic functional groups in cycloalkyl include cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, cyclohexynyl, and the like. Bicyclic functional groups in cycloalkyl include bicycloalkyl and spiro functional groups.

본 명세서에 사용된 용어 "히드록시" 또는 "하이드록시"는 -OH로서 정의되고, 용어 "알콕시"는 달리 정의하지 않는 한, 하이드록시 기의 수소 원자가 1 내지 10개의 알킬로 치환된 라디칼인 알킬옥시를 의미한다.As used herein, the term "hydroxy" or "hydroxy" is defined as -OH, and the term "alkoxy", unless otherwise defined, means alkyloxy, a radical in which the hydrogen atoms of the hydroxy group are replaced by 1 to 10 alkyl groups.

본 명세서에 사용된 용어 "할로겐" 또는 "할로"는 불소/플루오르(F), 염소(Cl), 브롬(Br) 또는 요오드(I)를 의미한다.The term “halogen” or “halo” as used herein means fluorine (F), chlorine (Cl), bromine (Br), or iodine (I).

본 명세서에 사용된 용어 "할로알킬" 및 "할로알콕시"는 1 이상의 할로겐 원자로 치환된 알킬 또는 알콕시를 의미한다.The terms “haloalkyl” and “haloalkoxy” as used herein mean alkyl or alkoxy substituted with one or more halogen atoms.

본 명세서에 사용된 용어 "헤테로 원자"는 N, O 또는 S를 의미한다.The term “heteroatom” as used herein means N, O or S.

본 명세서에 사용된 용어 "아릴"은 방향족 탄화수소를 의미하며, 카보사이클 방향족 고리 또는 헤테로아릴 고리가 1 이상의 다른 고리와 융합된, 폴리사이클 방향족 고리계를 포함한다. 바람직하게는 C5-12　아릴, 더 바람직하게는 C5-10　아릴이다. 예를 들어, 상기 아릴은 페닐, 나프틸, 테트라하이드로나프틸 등을 포함하지만, 이에 한정되는 것은 아니다.The term "aryl" as used herein refers to an aromatic hydrocarbon, including a polycyclic aromatic ring system in which a carbocyclic aromatic ring or a heteroaryl ring is fused with one or more other rings. Preferably, it is C 5-12 aryl, and more preferably, C 5-10 aryl. Examples of aryl include, but are not limited to, phenyl, naphthyl, tetrahydronaphthyl, and the like.

본 명세서에 사용된 용어 "헤테로아릴" 또는 "방향족 헤테로사이클"은 N, O 및 S 중에서 선택된 하나 이상의 헤테로 원자를 환원자로서 포함하고, 벤조 또는 C3-8　사이클로알킬과 융합될 수 있는 단일 또는 융합고리환을 이루는 3 내지 12원, 더 바람직하게는 5 내지 10원 방향족 탄화수소를 의미한다. 예를 들어, 상기 헤테로아릴은 피롤릴, 이미다졸릴, 피라졸릴, 트리아졸릴, 피리딜, 피라지닐, 피리미딜, 피리다지닐, 트리아지닐, 옥사디아졸릴, 이속사디아졸릴, 테트라졸릴, 인돌릴, 인다졸릴, 이속사졸릴, 옥사졸릴, 티아졸릴, 아이소티아졸릴, 퓨라닐, 벤조퓨라닐, 티오페닐, 벤조티오페닐, 벤조티아졸릴, 벤조옥사졸릴, 벤즈이미다졸릴, 퀴놀리닐, 이소퀴놀리닐 등을 포함하지만, 이에 한정되는 것은 아니다.The term "heteroaryl" or "aromatic heterocycle" as used herein means a 3 to 12 membered, more preferably 5 to 10 membered aromatic hydrocarbon containing one or more heteroatoms selected from N, O and S as a reducing group, and forming a single or fused ring which may be fused with benzo or C 3-8 cycloalkyl. For example, the heteroaryl includes, but is not limited to, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, pyridyl, pyrazinyl, pyrimidyl, pyridazinyl, triazinyl, oxadiazolyl, isoxadiazolyl, tetrazolyl, indolyl, indazolyl, isoxazolyl, oxazolyl, thiazolyl, isothiazolyl, furanyl, benzofuranyl, thiophenyl, benzothiophenyl, benzothiazolyl, benzoxazolyl, benzimidazolyl, quinolinyl, isoquinolinyl, and the like.

본 명세서에 사용된 용어 “헤테로사이클” 또는 “헤테로사이클로알킬”은 비-방향족 알킬 고리로서, 그 고리 내에 N, O 또는 S와 같은 1 이상의 헤테로원자를 포함하는 비-방향족 카보사이클 고리이다. 상기 고리는 5, 6, 7 또는 8-원이고/이거나 사이클로알킬 또는 방향족 고리와 같은 다른 고리에 융합될 수 있다. 그러한 화합물의 예로는 피롤리디닐, 테트라하이드로퓨라닐, 테트라하이드로티오페닐, 이미다졸리디닐, 피라졸리디닐, 옥사졸리디닐, 이소옥사졸리디닐, 티아졸리디닐, 이소티아졸리디닐, 디옥솔라닐, 옥사티올라닐, 디티올라닐, 피페리디닐, 테트라하이드로피라닐, 티아닐, 피페라지닐, 모폴리노, 및 디옥사닐 등이 있다.The term “heterocycle” or “heterocycloalkyl” as used herein refers to a non-aromatic alkyl ring, which is a non-aromatic carbocyclic ring containing one or more heteroatoms, such as N, O or S, within the ring. The ring may be 5, 6, 7 or 8-membered and/or may be fused to another ring, such as a cycloalkyl or aromatic ring. Examples of such compounds include pyrrolidinyl, tetrahydrofuranyl, tetrahydrothiophenyl, imidazolidinyl, pyrazolidinyl, oxazolidinyl, isooxazolidinyl, thiazolidinyl, isothiazolidinyl, dioxolanyl, oxathiolanyl, dithiolanyl, piperidinyl, tetrahydropyranyl, thianyl, piperazinyl, morpholino, and dioxanyl.

본 발명에 따른 상기 화학식 1로 표시되는 화합물은 생체내 흡수를 증진시키거나 용해도를 증가시키기 위하여 프로드럭, 수화물, 용매화물 및 약제학적으로 허용되는 염의 형태로 만들어 사용할 수 있으므로, 상기의 프로드럭, 수화물, 용매화물 및 약제학적으로 허용되는 염 역시 본 발명의 범위에 속한다. 또한, 상기 화학식 1로 표시되는 화합물은 키랄 탄소를 갖고 있어서, 그의 입체이성질체가 존재하며, 이러한 입체이성질체 역시 본 발명의 범주 내에 포함된다.The compound represented by the above chemical formula 1 according to the present invention can be prepared and used in the form of a prodrug, a hydrate, a solvate, and a pharmaceutically acceptable salt to promote absorption in the body or increase solubility, and therefore the above prodrug, hydrate, solvate, and pharmaceutically acceptable salt also fall within the scope of the present invention. In addition, the compound represented by the above chemical formula 1 has a chiral carbon, and thus its stereoisomers exist, and such stereoisomers are also included within the scope of the present invention.

본 명세서에 사용된 용어 "프로드럭(prodrug)"은 생체내에서 모 약제(parent drug)로 변형되는 물질을 의미한다. 프로드럭은, 몇몇 경우에 있어서, 모 약제보다 투여하기 쉽기 때문에 종종 사용된다. 예를 들어, 이들은 구강 투여에 의해 생활성을 얻을 수 있음에 반하여, 모 약제는 그렇지 못할 수 있다. 프로드럭은 또한 모 약제보다 제약 조성물에서 향상된 용해도를 가질 수도 있다. 예를 들어, 프로드럭은, 본 발명에 따른 화합물의 생체 내 가수분해 가능한 에스테르 및 이의 제약상 허용되는 염일 수 있다. 프로드럭의 또 다른 예는 펩티드가 활성 부위를 드러내도록 물질 대사에 의해 변환되는 산기에 결합되어 있는 짧은 펩티드(폴리아미노산)일 수 있다.The term "prodrug," as used herein, refers to a substance that is transformed into the parent drug in vivo. Prodrugs are often used because, in some cases, they are easier to administer than the parent drug. For example, they may be bioactive by oral administration, whereas the parent drug may not be. Prodrugs may also have improved solubility in pharmaceutical compositions compared to the parent drug. For example, prodrugs may be biohydrolyzable esters of compounds according to the present invention and pharmaceutically acceptable salts thereof. Another example of a prodrug may be a short peptide (polyamino acid) attached to an acid group that is metabolized to reveal the active site of the peptide.

본 명세서에 사용된 용어 "수화물(hydrate)"은 비공유적 분자간력(non-covalent intermolecular force)에 의해 결합된 화학양론적(stoichiometric) 또는 비화학양론적(non-stoichiometric) 량의 물을 포함하고 있는 본 발명의 화합물 또는 그것의 염을 의미한다.The term "hydrate" as used herein means a compound of the present invention or a salt thereof containing a stoichiometric or non-stoichiometric amount of water bound by non-covalent intermolecular forces.

본 명세서에 사용된 용어 "용매화물(solvate)"은 비공유적 분자간력에 의해 결합된 화학양론적 또는 비화학양론적 양의 용매를 포함하고 있는 본 발명의 화합물 또는 그것의 염을 의미한다. 그에 관한 바람직한 용매들로는 휘발성, 비독성, 및/또는 인간에게 투여되기에 적합한 용매들이 있다.The term "solvate" as used herein refers to a compound of the present invention or a salt thereof that contains a stoichiometric or non-stoichiometric amount of a solvent bound by non-covalent intermolecular forces. Preferred solvents include those that are volatile, non-toxic, and/or suitable for human administration.

본 명세서에 사용된 용어 "이성질체(isomer)"는 동일한 화학식 또는 분자식을 가지지만 구조적 또는 입체적으로 다른 본 발명의 화합물 또는 그것의 염을 의미한다. 이러한 이성질체에는 호변 이성질체(tautomer) 등의 구조 이성질체와, 비대칭 탄소 중심을 가지는 R 또는 S 이성질체, 기하 이성질체(트랜스, 시스), 부분입체이성질체(diastereomer) 등의 입체 이성질체가 모두 포함된다. 이들 모든 이성질체 및 그것의 혼합물들 역시 본 발명의 범위에 포함된다. 특히, 화학식 1의 화합물이 광학 이성질체, 입체 이성질체, 위치 이성질체(regioisomer), 또는 회전체(rotamer)를 갖는 경우, 이들도 화학식 1의 화합물에 포함되며, 그 자체로 공지된 합성 및 분리 방법에 따라 단일 생성물로서 수득될 수 있다. 예를 들어, 화학식 1의 화합물이 광학 이성질체를 포함하는 경우, 이 화합물로부터 분할되는 광학 이성질체도 화학식 1의 화합물에 포함된다. 광학 이성질체는 그 자체로 공지된 방법에 따라 제조할 수 있다.The term "isomer" as used herein refers to a compound of the present invention or a salt thereof that has the same chemical formula or molecular formula but is structurally or sterically different. Such isomers include structural isomers such as tautomers, and stereoisomers such as R or S isomers having an asymmetric carbon center, geometric isomers (trans, cis), and diastereomers. All of these isomers and mixtures thereof are also included in the scope of the present invention. In particular, when the compound of formula 1 has optical isomers, stereoisomers, regioisomers, or rotamers, these are also included in the compound of formula 1, and can be obtained as a single product according to synthetic and separation methods known in the art. For example, when the compound of formula 1 includes optical isomers, optical isomers resolved from this compound are also included in the compound of formula 1. Optical isomers can be prepared by methods known per se.

본 명세서에 사용된 용어 "약학적으로 허용가능한 염"은, 화합물이 투여되는 유기체에 심각한 자극을 유발하지 않고 화합물의 생물학적 활성과 물성들을 손상시키지 않는 화합물의 염의 형태를 의미한다. 상기 약학적 염은, 약제학적으로 허용되는 음이온을 함유하는 무독성 산부가염을 형성하는 산, 예를 들어, 염산, 황산, 질산, 인산, 브롬화수소산, 요드화수소산 등과 같은 무기산, 타르타르산, 포름산, 시트르산, 아세트산, 트리클로로아세트산, 트리플로로아세트산, 글루콘산, 벤조산, 락트산, 푸마르산, 말레인산, 살리신산 등과 같은 유기 카본산, 메탄설폰산, 에탄술폰산, 벤젠설폰산, p-톨루엔설폰산 등과 같은 설폰산 등에 의해 형성된 산부가염이 포함된다. 예를 들어, 약제학적으로 허용되는 카르복실산 염에는, 리튬, 나트륨, 칼륨, 칼슘, 마그네슘 등에 의해 형성된 금속염 또는 알칼리 토금속 염, 라이신, 아르기닌, 구아니딘 등의 아미노산 염, 디사이클로헥실아민, N-메틸-D-글루카민, 트리스(히드록시메틸)메틸아민, 디에탄올아민, 콜린 및 트리에틸아민 등과 같은 유기염 등이 포함된다. 본 발명에 따른 화학식 1의 화합물은 통상적인 방법에 의해 그것의 염으로 전환시킬 수 있다.The term "pharmaceutically acceptable salt" as used herein means a salt form of a compound that does not cause serious irritation to an organism to which the compound is administered and does not impair the biological activity and physical properties of the compound. The pharmaceutical salt includes acid addition salts formed by acids that form non-toxic acid addition salts containing pharmaceutically acceptable anions, for example, inorganic acids such as hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, hydrobromic acid, and hydroiodic acid; organic carboxylic acids such as tartaric acid, formic acid, citric acid, acetic acid, trichloroacetic acid, trifluoroacetic acid, gluconic acid, benzoic acid, lactic acid, fumaric acid, maleic acid, and salicylic acid; and sulfonic acids such as methanesulfonic acid, ethanesulfonic acid, benzenesulfonic acid, and p-toluenesulfonic acid. For example, pharmaceutically acceptable carboxylic acid salts include metal salts or alkaline earth metal salts formed by lithium, sodium, potassium, calcium, magnesium, etc.; amino acid salts such as lysine, arginine, guanidine, etc.; organic salts such as dicyclohexylamine, N-methyl-D-glucamine, tris(hydroxymethyl)methylamine, diethanolamine, choline, and triethylamine, etc. The compound of formula 1 according to the present invention can be converted into its salt by a conventional method.

본 발명은 또한, 상기 화학식 1의 화합물의 제조방법을 제공한다. 본 발명의 화학식 1의 화합물의 제조방법으로 실시예 1 내지 136의 합성 방법을 예시하였으며, 실시예 1 내지 136의 합성 방법이 본 발명에 따른 화학식 1의 화합물을 제조하는 방법을 한정하는 것은 아니다. 실시예 1 내지 136의 합성 방법은 예시일 뿐이며, 특정 치환체에 따라 통상의 기술자에 의해 용이하게 변형될 수 있음은 자명하다.The present invention also provides a method for preparing a compound of the above chemical formula 1. The synthetic methods of Examples 1 to 136 are exemplified as a method for preparing a compound of the chemical formula 1 of the present invention, and the synthetic methods of Examples 1 to 136 do not limit the method for preparing a compound of the chemical formula 1 according to the present invention. The synthetic methods of Examples 1 to 136 are merely examples, and it is obvious that they can be easily modified by those skilled in the art depending on specific substituents.

본 발명은 또한, 상기 화학식 1로 표시되는 헤테로아릴 유도체 화합물, 이의 수화물, 이의 용매화물 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는, AAK1 억제 관련 질환의 예방 또는 치료용 약학 조성물을 제공한다.The present invention also provides a pharmaceutical composition for preventing or treating a disease related to AAK1 inhibition, comprising a heteroaryl derivative compound represented by the above chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient.

본 발명은 또한, 상기 화학식 1로 표시되는 헤테로아릴 유도체 화합물, 이의 수화물, 이의 용매화물 또는 이의 약학적으로 허용가능한 염의 치료적 유효량을 이를 필요로 하는 개체에게 투여하는 것을 포함하는, AAK1 억제 관련 질환의 예방 또는 치료 방법을 제공한다.The present invention also provides a method for preventing or treating a disease associated with AAK1 inhibition, comprising administering a therapeutically effective amount of a heteroaryl derivative compound represented by the above chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof to a subject in need thereof.

본 발명은 또한, AAK1 억제 관련 질환의 예방 또는 치료용 의약 제조에 있어서, 상기 화학식 1로 표시되는 헤테로아릴 유도체 화합물, 이의 수화물, 이의 용매화물 또는 이의 약학적으로 허용가능한 염의 유효성분으로서의 용도를 제공한다.The present invention also provides the use of a heteroaryl derivative compound represented by the above chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof as an effective ingredient in the manufacture of a medicine for preventing or treating a disease associated with AAK1 inhibition.

본 발명의 헤테로아릴 유도체 화합물에 대하여 AAK1 억제 활성(IC50)을 측정한 결과, AAK1에 대하여 우수한 억제 활성을 나타내는 것이 확인되어, AAK1 억제 관련 질환의 예방 및 치료 용도로 사용될 수 있음이 밝혀졌다.As a result of measuring the AAK1 inhibitory activity (IC 50 ) of the heteroaryl derivative compound of the present invention, it was confirmed that it exhibited excellent inhibitory activity against AAK1, and it was revealed that it can be used for the prevention and treatment of diseases related to AAK1 inhibition.

일 구현예에서, 상기 AAK1 억제 관련 질환은 급성 통증, 만성 통증, 염증성 통증, 신경병증성 통증, 파킨슨병, 알츠하이머병, 조현병, 조울증, 근이영양증 및 바이러스 감염 질환으로 이루어진 군으로부터 선택되는 것일 수 있다. 이에 따라, 본 발명의 헤테로아릴 유도체 화합물은 광범위 항바이러스제(broad-spectrum antiviral agent)로 사용될 수 있다.In one embodiment, the disease associated with AAK1 inhibition may be selected from the group consisting of acute pain, chronic pain, inflammatory pain, neuropathic pain, Parkinson's disease, Alzheimer's disease, schizophrenia, bipolar disorder, muscular dystrophy, and viral infection diseases. Accordingly, the heteroaryl derivative compound of the present invention can be used as a broad-spectrum antiviral agent.

본 발명은 또한, 상기 화학식 1로 표시되는 헤테로아릴 유도체 화합물, 이의 수화물, 이의 용매화물 또는 이의 약학적으로 허용가능한 염과, 약제학적으로 허용가능한 첨가제를 포함하는 약학 조성물을 제공한다.The present invention also provides a pharmaceutical composition comprising a heteroaryl derivative compound represented by the above chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable additive.

상기 첨가제는 통상적으로 사용되는 부형제, 붕해제, 감미제, 활택제 또는 향미제 등의 약학적으로 허용가능한 담체를 포함할 수 있으며, 통상의 방법에 따라 정제, 캅셀제, 산제, 과립제 및 현탁제, 유제 또는 시럽제와 같은 경구용 제제; 또는 외용 액제, 외용 현탁제, 외용 에멀젼, 겔제(연고제 등), 흡입제, 분무제, 주사제 등의 비경구 투여용 제제로 제제화될 수 있다. 상기 제제는 다양한 형태, 예를 들어 단회 투여형 또는 수회 투여형 투여 형태로 제제화될 수 있다.The above additives may include pharmaceutically acceptable carriers such as excipients, disintegrants, sweeteners, lubricants or flavoring agents that are commonly used, and may be formulated into oral preparations such as tablets, capsules, powders, granules and suspensions, emulsions or syrups according to a conventional method; or parenteral preparations such as external solutions, external suspensions, external emulsions, gels (ointments, etc.), inhalants, sprays and injections. The above preparations may be formulated into various forms, for example, single-dose or multiple-dose dosage forms.

본 발명의 약학 조성물이 투여되는 개체는 예를 들어, 인간, 원숭이, 소, 말, 양, 돼지, 닭, 칠면조, 고양이, 개, 마우스, 랫트, 토끼 또는 기니피그일 수 있고, 예를 들어, 포유류, 예를 들어, 인간일 수 있으나, 이에 한정되는 것은 아니다.The subject to which the pharmaceutical composition of the present invention is administered may be, for example, a human, a monkey, a cow, a horse, a sheep, a pig, a chicken, a turkey, a cat, a dog, a mouse, a rat, a rabbit, or a guinea pig, and may be, for example, a mammal, for example, a human, but is not limited thereto.

또한, 본 발명의 약학 조성물은 경구 또는 비경구로 투여할 수 있고, 비경구 투여인 경우에는 피부, 경피, 안구, 복강, 직장 또는 정맥, 근육, 피하, 자궁 내 경막, 뇌혈관 내(intracerebroventricular) 주사, 또는 국소적 투여 등의 경로로 투여할 수 있다. 안구 국소 투여는 예를 들어, 직접적으로 안구 내 투약되거나, 안구 주위, 안구 뒤, 망막 하(subretinal), 망막 중심(central retinal), 중심와(fovea) 외부, 결막하(subconjunctival), 유리체내(intravitreous), 전방내(intracameral), 또는 맥락막위(suprachoroidal) 등에 투여하는 것을 포함한다. 상기 약학 조성물은 삽입 장치를 통하여 투약될 수 있다.In addition, the pharmaceutical composition of the present invention can be administered orally or parenterally, and in case of parenteral administration, it can be administered by routes such as skin, transdermally, ocularly, intraperitoneally, rectal, or intravenously, intramuscularly, subcutaneously, intrauterinely, intracerebroventricularly, or topical administration. Topical ocular administration includes, for example, direct intraocular administration, or administration around the eye, behind the eye, subretinal, central retinal, extrafoveal, subconjunctival, intravitreous, intracameral, or suprachoroidal. The pharmaceutical composition can be administered through an insertion device.

본 발명의 약학 조성물에 함유되는 유효성분의 투여량은 환자의 상태 및 체중, 질병의 정도, 유효성분 형태, 투여 경로 및 기간에 따라 다르며, 환자에 따라 적절하게 조절될 수 있다. 예를 들면, 상기 유효성분은 1일 0.0001 내지 1000 mg/kg으로, 바람직하게는 0.001 내지 100 mg/kg의 용량으로 투여할 수 있으며, 상기 투여는 하루에 한번 또는 수회 나누어 투여할 수도 있다. 또한, 본 발명의 약학 조성물은 조성물 총 중량에 대하여 상기 유효성분을 0.001 내지 90 % 중량백분율로 포함할 수 있다.The dosage of the active ingredient contained in the pharmaceutical composition of the present invention varies depending on the patient's condition and weight, the degree of the disease, the form of the active ingredient, the route and period of administration, and can be appropriately adjusted depending on the patient. For example, the active ingredient may be administered at a dosage of 0.0001 to 1000 mg/kg per day, preferably 0.001 to 100 mg/kg, and the administration may be administered once a day or divided into several times. In addition, the pharmaceutical composition of the present invention may contain the active ingredient at a weight percentage of 0.001 to 90% based on the total weight of the composition.

이하, 본 발명을 실시예 및 실험예를 통하여 더욱 상세히 설명한다. 그러나, 하기 실시예 및 실험예는 본 발명을 예시하기 위한 것으로, 본 발명의 범위가 이에 제한되는 것은 아니다.Hereinafter, the present invention will be described in more detail through examples and experimental examples. However, the following examples and experimental examples are intended to illustrate the present invention and are not intended to limit the scope of the present invention.

<공통 반응식 I><Common Reaction Formula I>

하기 실시예에서는 브루커 500MHz NMR 분광기(Bruker 500 MHz NMR spectrometer)로 양성자 NMR 스펙트럼을 기록하였다. 화학적 이동은 δ 값으로 기록되었다. 액체 크로마토그래피-질량 분석법(Liquid chromatography-mass spectrometry, LC-MS)은 ACQUITY QDa 검출기와 결합된 Waters ACQUITY UPLC H-Class에서 실행하였다.In the following examples, proton NMR spectra were recorded on a Bruker 500 MHz NMR spectrometer. Chemical shifts were reported as δ values. Liquid chromatography-mass spectrometry (LC-MS) was performed on a Waters ACQUITY UPLC H-Class coupled to an ACQUITY QDa detector.

실시예 1: (Example 1: ( SS )-1-((6-(5-플루오로-1)-1-((6-(5-fluoro-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((6-(5-fluoro-1)-1-((6-(5-fluoro-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

A 파트:Part A: (S)-1-((6-브로모피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

(S)-2-아미노-2,4-다이메틸펜탄-1-올 (1.6 g, 6.25 mmol)의 테트라하이드로퓨란 (20 mL) 용액에 칼륨 tert-부톡사이드 (2.5g, 8.52 mmol)를 실온에서 첨가했다. 3분 후, 2-브로모-5-플루오로피리딘 (1.0 g, 5.68 mmol)의 일부를 첨가하고 반응 혼합물을 실온에서 교반하였다. 반응 진행은 TLC 및 HPLC로 모니터링하였다. 반응이 완료된 후 물을 첨가하여 종결시키고 EtOAc로 희석하였다. 분리된 유기층을 물과 염수로 세척하고 황산마그네슘으로 건조시킨 후 농축하였다. 잔류물을 MPLC (실리카겔, CH2Cl2 : MeOH = 10 : 1, v/v)로 정제하여 연한-황색 액체(0.90g, 55.1%)를 얻었다. LC-MS (ESI+) m/z 287.3 [(M+H)+, calcd. C12H19BrN2O m/z 286.0].To a solution of ( S )-2-amino-2,4-dimethylpentan-1-ol (1.6 g, 6.25 mmol) in tetrahydrofuran (20 mL) was added potassium tert -butoxide (2.5 g, 8.52 mmol) at room temperature. After 3 min, a portion of 2-bromo-5-fluoropyridine (1.0 g, 5.68 mmol) was added, and the reaction mixture was stirred at room temperature. The reaction progress was monitored by TLC and HPLC. After the reaction was completed, water was added to quench the reaction and diluted with EtOAc. The separated organic layer was washed with water and brine, dried over magnesium sulfate, and concentrated. The residue was purified by MPLC (silica gel, CH 2 Cl 2 : MeOH = 10 : 1, v/v ) to give a pale-yellow liquid (0.90 g, 55.1%). LC-MS (ESI+) m/z 287.3 [(M+H) + , calcd. C 12 H 19 BrN 2 O m/z 286.0].

B 파트:Part B: (S)-1-((6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

(S)-1-((6-브로모피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.35 mmol) (실시예 1, A 파트), tert-부틸 5-플루오로-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (189.1 mg, 0.52 mmol), 테트라키스(트리페닐포스핀)팔라듐(0) (40.2 mg, 0.03 mmol) 및 탄산칼륨 (192.4 mg, 1.39 mmol)의 1,4-디옥산 (8 mL) 및 물 (2 mL) 용액을 130°C의 마이크로파에서 1시간 동안 조사하였다. TLC와 HPLC로 반응의 진행을 모니터링하였다. 반응이 완료된 후 EtOAc와 물로 희석하였다. 분리된 유기층을 물과 염수로 세척하고 황산마그네슘으로 건조시킨 후 농축하였다. 잔류물을 PLC (실리카겔, CH2Cl2 : MeOH = 9 : 1, v/v로 용출)로 정제하였다. 필요한 스팟을 수집하고 5% 메탄올의 디클로로메탄 (20mL)에 녹인 후 여과하고 감압농축하여 아이보리색 분말 (34.3mg, 28.7%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.56 (s, 1H), 8.30-8.39 (m, 5H), 4.36-4.44 (m, 2H), 1.83-1.93 (m, 2H), 1.71-1.75 (m, 1H), 1.54 (s, 3H), 1.07 (d, 3H), 1.04 (d, 3H). LC-MS (ESI+) m/z 343.2 [(M+H)+, calcd. C19H23FN4O m/z 342.1].A solution of ( S )-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A), tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (189.1 mg, 0.52 mmol), tetrakis(triphenylphosphine)palladium(0) (40.2 mg, 0.03 mmol) and potassium carbonate (192.4 mg, 1.39 mmol) in 1,4-dioxane (8 mL) and water (2 mL) was irradiated in a microwave at 130 °C for 1 h. The progress of the reaction was monitored by TLC and HPLC. After the reaction was completed, the mixture was diluted with EtOAc and water. The separated organic layer was washed with water and brine, dried over magnesium sulfate, and concentrated. The residue was purified by PLC (silica gel, eluted with CH 2 Cl 2 : MeOH = 9 : 1, v/v ). The required spot was collected, dissolved in 5% methanol dichloromethane (20 mL), filtered, and concentrated under reduced pressure to obtain an ivory-colored powder (34.3 mg, 28.7%). 1H NMR (500 MHz, MeOD) δ 8.56 (s, 1H), 8.30-8.39 (m, 5H), 4.36-4.44 (m, 2H), 1.83-1.93 (m, 2H), 1.71-1.75 (m, 1H), 1.54 (s, 3H), 1.07 (d, 3H), 1.04 (d, 3H). LC-MS (ESI+) m/z 343.2 [(M+H) + , calcd. C 19 H 23 FN 4 O m/z 342.1].

실시예 2: (S)-1-((6-(1Example 2: (S)-1-((6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(S)-1-((6-(1]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 2를 실시예 1에 대하여 설명한 것과 유사한 절차에 따라 제조하였다.Example 2 was prepared according to a similar procedure as described for Example 1.

B 파트: Part B: (S)-1-((6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((6-브로모피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.35 mmol) (실시예 1, A 파트)을 사용하고 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (179.7 mg, 0.52 mmol)를 사용하여 제조하였고, 아이보리색 분말 (34.3 mg, 30.3%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.61-8.62 (m, 1H), 8.34 (d, 1H), 8.22-8.23 (m, 1H), 7.87 (s, 1H), 7.74 (d, 1H), 7.46-7.48 (m, 1H), 7.17-7.20 (m, 1H), 3.89-4.00 (m, 2H), 1.81-1.87 (m, 1H), 1.62-1.66 (m, 1H), 1.53-1.57 (m, 1H), 1.32 (s, 3H), 1.01 (d, 3H), 0.99 (d, 3H). LC-MS (ESI+) m/z 325.3 [(M+H)+, calcd. C19H24N4O m/z 324.1].This compound was prepared using ( S )-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) to obtain an ivory powder (34.3 mg, 30.3%). 1H NMR (500 MHz, MeOD) δ 8.61-8.62 (m, 1H), 8.34 (d, 1H), 8.22-8.23 (m, 1H), 7.87 (s, 1H), 7.74 (d, 1H), 7.46-7.48 (m, 1H), 7.17-7.20 (m, 1H), 3.89-4.00 (m, 2H), 1.81-1.87 (m, 1H), 1.62-1.66 (m, 1H), 1.53-1.57 (m, 1H), 1.32 (s, 3H), 1.01 (d, 3H), 0.99 (d, 3H). LC-MS (ESI+) m/z 325.3 [(M+H) + , calcd. C 19 H 24 N 4 O m/z 324.1].

실시예 3: (Example 3: ( SS )-1-((6-(1)-1-((6-(1 HH -피롤로[3,2--Pyrrolo[3,2- cc ]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((6-(1)-1-((6-(1 HH -pyrrolo[3,2--pyrrolo[3,2- cc ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 3을 실시예 1에 대하여 설명한 것과 유사한 절차에 따라 제조하였다.Example 3 was prepared according to a similar procedure as described for Example 1.

B 파트: Part B: (S)-1-((6-(1H-피롤로[3,2-c]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((6-(1H-pyrrolo[3,2-c]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((6-브로모피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.35 mmol) (실시예 1, A 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[3,2-c]피리딘-1-카복실레이트 (179.7 mg, 0.52 mmol)를 사용하여 제조하였고, 분말 (24.3 mg, 21.5%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.74 (s, 1H), 8.63 (d, 1H), 8.47-8.51 (m, 2H), 8.22 (d, 1H), 8.04-8.09 (m, 2H), 4.29-4.38 (m, 2H), 1.83-1.91 (m, 2H), 1.70-1.74 (m, 1H), 1.52 (s, 3H), 1.06 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+) m/z 325.4 [(M+H)+, calcd. C19H24N4O m/z 324.1].This compound was prepared using ( S )-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[3,2- c ]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) and a powder (24.3 mg, 21.5%) was obtained. 1H NMR (500 MHz, MeOD) δ 9.74 (s, 1H), 8.63 (d, 1H), 8.47-8.51 (m, 2H), 8.22 (d, 1H), 8.04-8.09 (m, 2H), 4.29-4.38 (m, 2H), 1.83-1.91 (m, 2H), 1.70-1.74 (m, 1H), 1.52 (s, 3H), 1.06 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+) m/z 325.4 [(M+H) + , calcd. C 19 H 24 N 4 O m/z 324.1].

실시예 4: (Example 4: ( SS )-1-((6-(1)-1-((6-(1 HH -피롤로[2,3--Pyrrolo[2,3- cc ]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((6-(1)-1-((6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- cc ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 4를 실시예 1에 대하여 설명한 것과 유사한 절차에 따라 제조하였다.Example 4 was prepared according to a similar procedure as described for Example 1.

B 파트: Part B: (S)-1-((6-(1H-피롤로[2,3-c]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((6-(1H-pyrrolo[2,3-c]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((6-브로모피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.35 mmol) (실시예 1, A 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-c]피리딘-1-카복실레이트 (179.7 mg, 0.52 mmol)를 사용하여 제조하였고, 연한- 분말 (30.90 mg, 27.3%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.89 (s, 1H), 8.55 (d, 1H), 8.13-8.17 (m, 2H), 8.04 (d, 1H), 7.63 (d, 1H), 7.41 (s, 1H), 4.17-4.27 (m, 2H), 1.78-1.85 (m, 2H), 1.65-1.68 (m, 1H), 1.47 (s, 3H), 1.02 (d, 3H), 0.98 (d, 3H). LC-MS (ESI+) m/z 325.4 [(M+H)+, calcd. C19H24N4O m/z 324.1].This compound was prepared using ( S )-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- c ]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) to obtain a pale- powder (30.90 mg, 27.3%). 1H NMR (500 MHz, MeOD) δ 8.89 (s, 1H), 8.55 (d, 1H), 8.13-8.17 (m, 2H), 8.04 (d, 1H), 7.63 (d, 1H), 7.41 (s, 1H), 4.17-4.27 (m, 2H), 1.78-1.85 (m, 2H), 1.65-1.68 (m, 1H), 1.47 (s, 3H), 1.02 (d, 3H), 0.98 (d, 3H). LC-MS (ESI+) m/z 325.4 [(M+H) + , calcd. C 19 H 24 N 4 O m/z 324.1].

실시예 5: (Example 5: ( SS )-1-((6-(7-플루오로이미다조[1,2-)-1-((6-(7-fluoroimidazo[1,2- aa ]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((6-(7-fluoroimidazo[1,2-)-1-((6-(7-fluoroimidazo[1,2- aa ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 5를 실시예 1에 대하여 설명한 것과 유사한 절차에 따라 제조하였다.Example 5 was prepared according to a similar procedure as described for Example 1.

B 파트: Part B: (S)-1-((6-(7-플루오로이미다조[1,2-a]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((6-(7-fluoroimidazo[1,2-a]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((6-브로모피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (24.0 mg, 0.08 mmol) (실시예 1, A 파트) 및 7-플루오로-5-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)이미다조[1,2-a]피리딘 (136.9 mg, 0.52 mmol)를 사용하여 제조하였고, 아이보리색 분말 (11.4 mg, 39.8%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.85-9.88 (m, 1H), 8.38 (d, 1H), 8.03 (s, 1H), 7.81 (d, 1H), 7.46-7.49 (m, 1H), 7.27-7.29 (m, 1H), 6.94-6.98 (m, 1H), 3.87-3.92 (m, 2H), 1.80-1.85 (m, 1H), 1.48-1.59 (m, 2H), 1.25 (s, 3H), 1.00 (d, 3H), 0.98 (d, 3H). LC-MS (ESI+) m/z 343.4 [(M+H)+, calcd. C19H23FN4O m/z 342.1].This compound was prepared using ( S )-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (24.0 mg, 0.08 mmol) (Example 1, Part A) and 7-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)imidazo[1,2- a ]pyridine (136.9 mg, 0.52 mmol) and an ivory powder (11.4 mg, 39.8%) was obtained. 1H NMR (500 MHz, MeOD) δ 9.85-9.88 (m, 1H), 8.38 (d, 1H), 8.03 (s, 1H), 7.81 (d, 1H), 7.46-7.49 (m, 1H), 7.27-7.29 (m, 1H), 6.94-6.98 (m, 1H), 3.87-3.92 (m, 2H), 1.80-1.85 (m, 1H), 1.48-1.59 (m, 2H), 1.25 (s, 3H), 1.00 (d, 3H), 0.98 (d, 3H). LC-MS (ESI+) m/z 343.4 [(M+H) + , calcd. C 19 H 23 FN 4 O m/z 342.1].

실시예 6: (Example 6: ( SS )-1-((6-(1)-1-((6-(1 HH -피라졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((6-(1)-1-((6-(1 HH -pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 6을 실시예 1에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 6 was prepared according to a similar procedure as described for Example 1.

B 파트: Part B: (S)-1-((6-(1H-피라졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((6-브로모피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.35 mmol) (실시예 1, A 파트) 및 tert-부틸 4-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피라졸-1-카복실레이트 (153.6 mg, 0.52 mmol)를 사용하여 제조하였고, 연한-아이보리색 분말 (24.1 mg, 25.2%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.43-8.48 (m, 3H), 8.28 (d, 2H), 4.23-4.40 (m, 2H), 1.80-1.89 (m, 2H), 1.70-1.73 (m, 1H), 1.51 (s, 3H), 1.06 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+) m/z 275.3 [(M+H)+, calcd. C15H22N4O m/z 274.1].This compound was prepared using ( S )-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A) and tert -butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole-1-carboxylate (153.6 mg, 0.52 mmol) to obtain a pale-ivory powder (24.1 mg, 25.2%). 1H NMR (500 MHz, MeOD) δ 8.43-8.48 (m, 3H), 8.28 (d, 2H), 4.23-4.40 (m, 2H), 1.80-1.89 (m, 2H), 1.70-1.73 (m, 1H), 1.51 (s, 3H), 1.06 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+) m/z 275.3 [(M+H) + , calcd. C 15 H 22 N 4 O m/z 274.1].

실시예 7: (Example 7: ( SS )-1-((6-(1)-1-((6-(1 HH -피롤-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(-pyrrol-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((6-(1)-1-((6-(1 HH -pyrrol-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]-pyrrol-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 7을 실시예 1에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 7 was prepared according to a similar procedure as described for Example 1.

B 파트: Part B: (S)-1-((6-(1H-피롤-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((6-(1H-pyrrol-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((6-브로모피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.35 mmol) (실시예 1, A 파트) 및 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤 (100.8 mg, 0.52 mmol)을 사용하여 제조하였고, 연한-적색 액체 (15.8 mg, 16.6%)를 얻었다. 1H NMR (500 MHz, MeOD) δ 10.00 (d, 1H), 7.53 (d, 1H), 7.36-7.38 (m, 1H), 7.27 (s, 1H), 6.77 (d, 1H), 6.56 (d, 1H), 3.80-3.86 (m, 2H), 1.78-1.82 (m, 1H), 1.46-1.57 (m, 2H), 1.23 (s, 3H), 0.99 (d, 3H), 0.97 (d, 3H)LC-MS (ESI+) m/z 274.5 [(M+H)+, calcd. C16H23N3O m/z 273.1].This compound was prepared using ( S )-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A) and 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrole (100.8 mg, 0.52 mmol) to obtain a pale-red liquid (15.8 mg, 16.6%). 1H NMR (500 MHz, MeOD) δ 10.00 (d, 1H), 7.53 (d, 1H), 7.36-7.38 (m, 1H), 7.27 (s, 1H), 6.77 (d, 1H), 6.56 (d, 1H), 3.80-3.86 (m, 2H), 1.78-1.82 (m, 1H), 1.46-1.57 (m, 2H), 1.23 (s, 3H), 0.99 (d, 3H), 0.97 (d, 3H) LC-MS (ESI+) m/z 274.5 [(M+H) + , calcd. C 16 H 23 N 3 O m/z 273.1].

실시예 8: (Example 8: ( SS )-1-((6-(2)-1-((6-(2 HH -1,2,3-트리아졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((6-(2)-1-((6-(2 HH -1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 8을 실시예 1에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 8 was prepared according to a procedure similar to that described for Example 1.

B 파트: Part B: (S)-1-((6-(2H-1,2,3-트리아졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((6-브로모피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.35 mmol) (실시예 1, A 파트) 및 2-(테트라하이드로-2H-피란-2-일)-4-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-2H-1,2,3-트리아졸 (145.8 mg, 0.52 mmol)을 사용하여 중간체로 제조하였다. 정제 후 염산 (1.25 M 메탄올 용액, 10 mL)을 첨가하고, 테트라하이드로-2H-피라닐기의 탈보호를 위해 80°C에서 교반하였다. 반응이 완료된 후, 생성물을 감압 하에 농축하였다. 잔류물을 EtOAc 및 10% NaOH 용액(aq.)으로 추출하였다. 분리된 유기층을 물과 염수로 세척하고 황산마그네슘으로 건조시킨 후 농축하였다. 잔류물을 테트라하이드로퓨란과 n-헥산으로 재결정화하여 연한-아이보리색 분말을 얻었다. (42.2 mg, 44.0%). 1H NMR (500 MHz, MeOD) δ 8.58-8.60 (m, 2H), 8.39-8.40 (m, 1H), 8.21-8.23 (m, 1H), 4.35-4.41 (m, 2H), 1.82-1.90 (m, 2H), 1.73-1.75 (m, 1H), 1.52 (s, 3H), 1.06 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+) m/z 276.3 [(M+H)+, calcd. C14H21N5O m/z 275.1].This compound was prepared as an intermediate using ( S )-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A) and 2-(tetrahydro-2 H -pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2 H - 1,2,3-triazole (145.8 mg, 0.52 mmol). After purification, hydrochloric acid (1.25 M methanol solution, 10 mL) was added and stirred at 80 °C for deprotection of the tetrahydro-2 H -pyranyl group. After completion of the reaction, the product was concentrated under reduced pressure. The residue was extracted with EtOAc and 10% NaOH solution (aq.). The separated organic layer was washed with water and brine, dried over magnesium sulfate, and concentrated. The residue was recrystallized from tetrahydrofuran and n -hexane to give a pale-ivory powder (42.2 mg, 44.0%). 1 H NMR (500 MHz, MeOD) δ 8.58-8.60 (m, 2H), 8.39-8.40 (m, 1H), 8.21-8.23 (m, 1H), 4.35-4.41 (m, 2H), 1.82-1.90 (m, 2H), 1.73-1.75 (m, 1H), 1.52 (s, 3H), 1.06 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+) m/z 276.3 [(M+H) + , calcd. C 14 H 21 N 5 O m/z 275.1].

실시예 9: (Example 9: ( SS )-1-(()-1-(( 66 -(-( 33 ,, 55 -다이메틸-1-Dimethyl-1 HH -피라졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-(()-1-(( 66 -(-( 33 ,, 55 -dimethyl-1-dimethyl-1 HH -pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 9를 실시예 1에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 9 was prepared according to a similar procedure as described for Example 1.

B 파트: Part B: (S)-1-((6-(3,5-다이메틸-1H-피라졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((6-(3,5-dimethyl-1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((6-브로모피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.35 mmol) (실시예 1, A 파트) 및 3,5-다이메틸-4-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피라졸 (116.0 mg, 0.52 mmol)을 사용하여 제조하였고, 연한-아이보리색 분말 (15.6 mg, 14.8%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.29 (d, 1H), 7.45-7.47 (m, 1H), 7.34 (d, 1H), 3.84-3.91 (m, 2H), 2.26 (s, 6H), 1.77-1.81 (m, 1H), 1.54-1.58 (m, 1H), 1.47-1.51 (m, 1H), 1.24 (s, 3H), 0.98 (d, 3H), 0.96 (d, 3H). LC-MS (ESI+) m/z 303.5 [(M+H)+, calcd. C17H26N4O m/z 302.2].This compound was prepared using ( S )-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A) and 3,5-dimethyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole (116.0 mg, 0.52 mmol) to obtain a pale-ivory powder (15.6 mg, 14.8%). 1H NMR (500 MHz, MeOD) δ 8.29 (d, 1H), 7.45-7.47 (m, 1H), 7.34 (d, 1H), 3.84-3.91 (m, 2H), 2.26 (s, 6H), 1.77-1.81 (m, 1H), 1.54-1.58 (m, 1H), 1.47-1.51 (m, 1H), 1.24 (s, 3H), 0.98 (d, 3H), 0.96 (d, 3H). LC-MS (ESI+) m/z 303.5 [(M+H) + , calcd. C 17 H 26 N 4 O m/z 302.2].

실시예 10: (Example 10: ( SS )-1-((6-(1)-1-((6-(1 HH -피롤로[3,2--Pyrrolo[3,2- bb ]피리딘-1-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((6-(1)-1-((6-(1 HH -pyrrolo[3,2--pyrrolo[3,2- bb ]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

제3인산칼륨 (147.8 mg, 0.70 mmol)을 (S)-1-((6-브로모피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.35 mmol) (실시예 1, A 파트), 1H-피롤로[3,2-b]피리딘 (41.1 mg, 0.35 mmol), 구리(II) 아세테이트(6.3 mg, 0.03 mmol), (2Z)-2-하이드록시이미노-1,2-다이페닐에탄올 (7.9 mg, 0.03 mmol)의 디메틸설폭시드 (2 mL) 용액에 첨가하였다. 반응 혼합물을 140°C의 마이크로파에서 1시간 동안 조사하였다. TLC와 HPLC로 반응의 진행을 모니터링하였다. 반응이 완료된 후, EtOAc와 물로 희석하였다. 분리된 유기층을 물과 염수로 세척하고, 황산마그네슘으로 건조시킨 후 농축하였다. 잔류물을 PLC (실리카겔, CH2Cl2 : MeOH = 10 : 1, v/v로 용출)로 정제하였다. 필요한 스팟을 수집하고, 5% 메탄올의 디클로로메탄 (20mL)에 녹인 후 여과하고 감압농축하여 (S)-1-((6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민을 아이보리색 분말 (30.8 mg, 27.2%)로 얻었다. 1H NMR (500 MHz, MeOD) δ 9.39 (d, 1H), 8.65-8.69 (m, 2H), 8.45 (d, 1H), 7.79-7.86 (m, 3H), 7.12 (d, 1H), 4.20-4.30 (m, 2H), 1.83-1.85 (m, 2H), 1.72-1.73 (m, 1H), 1.51 (s, 3H), 1.06 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+) m/z 325.3 [(M+H)+, calcd. C19H24N4O m/z 324.1].Potassium triphosphate (147.8 mg, 0.70 mmol) was added to a solution of ( S )-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A), 1 H -pyrrolo[3,2- b ]pyridine (41.1 mg, 0.35 mmol), copper(II) acetate (6.3 mg, 0.03 mmol), and (2 Z )-2-hydroxyimino-1,2-diphenylethanol (7.9 mg, 0.03 mmol) in dimethylsulfoxide (2 mL). The reaction mixture was irradiated in a microwave at 140 °C for 1 h. The progress of the reaction was monitored by TLC and HPLC. After the reaction was complete, the mixture was diluted with EtOAc and water. The separated organic layer was washed with water and brine, dried over magnesium sulfate, and concentrated. The residue was purified by PLC (silica gel, eluted with CH 2 Cl 2 : MeOH = 10 : 1, v/v ). The required spot was collected, dissolved in 5% methanol in dichloromethane (20 mL), filtered, and concentrated under reduced pressure to obtain ( S )-1-((6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine as an ivory powder (30.8 mg, 27.2%). 1H NMR (500 MHz, MeOD) δ 9.39 (d, 1H), 8.65-8.69 (m, 2H), 8.45 (d, 1H), 7.79-7.86 (m, 3H), 7.12 (d, 1H), 4.20-4.30 (m, 2H), 1.83-1.85 (m, 2H), 1.72-1.73 (m, 1H), 1.51 (s, 3H), 1.06 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+) m/z 325.3 [(M+H) + , calcd. C 19 H 24 N 4 O m/z 324.1].

실시예 11: (Example 11: ( SS )-1-((6-(6-플루오로-1)-1-((6-(6-fluoro-1 HH -피롤로[3,2--Pyrrolo[3,2- bb ]피리딘-1-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((6-(6-fluoro-1)-1-((6-(6-fluoro-1 HH -pyrrolo[3,2--pyrrolo[3,2- bb ]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 11은 (S)-1-((6-브로모피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.35 mmol) (실시예 1, A 파트), 6-플루오로-1H-피롤로[3,2-b]피리딘 (47.4 mg, 0.35 mmol)을 사용하여 실시예 10에 대하여 설명한 것과 유사한 절차에 따라 제조하였고, 아이보리색 분말 (25.7 mg, 21.5%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.39 (d, 1H), 8.65-8.69 (m, 1H), 8.43 (d, 1H), 7.76-7.84 (m, 3H), 7.12 (d, 1H), 4.20-4.30 (m, 2H), 1.83-1.85 (m, 2H), 1.71-1.73 (m, 1H), 1.52 (s, 3H), 1.06 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+) m/z 343.5 [(M+H)+, calcd. C19H23FN4O m/z 342.1].Example 11 was prepared according to a similar procedure as described for Example 10 using ( S )-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A), 6-fluoro-1 H -pyrrolo[3,2- b ]pyridine (47.4 mg, 0.35 mmol) to obtain an ivory powder (25.7 mg, 21.5%). 1H NMR (500 MHz, MeOD) δ 9.39 (d, 1H), 8.65-8.69 (m, 1H), 8.43 (d, 1H), 7.76-7.84 (m, 3H), 7.12 (d, 1H), 4.20-4.30 (m, 2H), 1.83-1.85 (m, 2H), 1.71-1.73 (m, 1H), 1.52 (s, 3H), 1.06 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+) m/z 343.5 [(M+H) + , calcd. C 19 H 23 FN 4 O m/z 342.1].

실시예 12: (Example 12: ( SS )-1-((6-(6-클로로-1)-1-((6-(6-chloro-1 HH -피롤로[3,2--Pyrrolo[3,2- bb ]피리딘-1-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((6-(6-chloro-1)-1-((6-(6-chloro-1 HH -pyrrolo[3,2--pyrrolo[3,2- bb ]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 12는 (S)-1-((6-브로모피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.35 mmol) (실시예 1, A 파트), 6-클로로-1H-피롤로[3,2-b]피리딘 (53.1 mg, 0.35 mmol)을 사용하여 실시예 10에 대하여 설명한 것과 유사한 절차에 따라 제조하였고, 연한-갈색 분말 (24.3 mg, 19.4%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.19 (s, 1H), 8.70 (s, 1H), 8.49 (d, 1H), 8.44 (d, 1H), 7.78-7.81 (m, 2H), 7.01 (d, 1H), 4.19-4.30 (m, 2H), 1.83-1.90 (m, 2H), 1.69-1.73 (m, 1H), 1.52 (s, 3H), 1.08 (d, 3H), 1.04 (d, 3H). LC-MS (ESI+) m/z 359.6 [(M+H)+, calcd. C19H23ClN4O m/z 358.1].Example 12 was prepared according to a similar procedure as described for Example 10 using ( S )-1-((6-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 1, Part A), 6-chloro-1 H -pyrrolo[3,2- b ]pyridine (53.1 mg, 0.35 mmol) to obtain a pale-brown powder (24.3 mg, 19.4%). 1H NMR (500 MHz, MeOD) δ 9.19 (s, 1H), 8.70 (s, 1H), 8.49 (d, 1H), 8.44 (d, 1H), 7.78-7.81 (m, 2H), 7.01 (d, 1H), 4.19-4.30 (m, 2H), 1.83-1.90 (m, 2H), 1.69-1.73 (m, 1H), 1.52 (s, 3H), 1.08 (d, 3H), 1.04 (d, 3H). LC-MS (ESI+) m/z 359.6 [(M+H) + , calcd. C 19 H 23 ClN 4 O m/z 358.1].

실시예 13: (Example 13: ( SS )-1-((2-(다이플루오로메틸)-6-(1)-1-((2-(difluoromethyl)-6-(1 HH -피라졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((2-(difluoromethyl)-6-(1)-1-((2-(difluoromethyl)-6-(1 HH -pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

A 파트: Part A: 6-브로모-2-(다이플루오로메틸)-3-플루오로피리딘6-bromo-2-(difluoromethyl)-3-fluoropyridine

바닥이 둥근 500 mL 플라스크에 6-브로모-3-플루오로피콜린알데히드(5.0 g, 24.51 mmol)와 CH2Cl2 (100 mL)를 첨가하여 용액을 만들었다. 20°C로 냉각한 후 디에틸아미노황 삼불화물(7.1 mL, 49.02 mmol)를 한 방울씩 첨가하였다. 혼합물을 실온으로 서서히 가온한 후 실온에서 1시간 동안 교반하였다. TLC와 HPLC로 반응의 진행을 모니터링하였다. 반응이 완료된 후, -10°C에서 포화 NaHCO3 용액 (aq.)으로 천천히 종결시켰다. 물 (100 mL)을 첨가하고 분리된 유기층을 물과 염수로 세척하고, 황산마그네슘으로 건조시킨 후 농축하였다. 잔류물을 MPLC (실리카겔, 0 내지 20%의 n-헥산 중 EtOAc로 용출)로 정제하여 6-브로모-2-(다이플루오로메틸)-3-플루오로피리딘 (4.4 g, 80.2%)을 아이보리색 분말로 얻었다. LC-MS (ESI+) m/z 226.3 [(M+H)+, calcd. C6H3BrF3N m/z 224.9].A solution was prepared by adding 6-bromo-3-fluoropicolinaldehyde (5.0 g, 24.51 mmol) and CH 2 Cl 2 (100 mL) to a 500 mL round-bottomed flask. After cooling to 20°C, diethylaminosulfur trifluoride (7.1 mL, 49.02 mmol) was added dropwise. The mixture was slowly warmed to room temperature and stirred at room temperature for 1 h. The progress of the reaction was monitored by TLC and HPLC. After completion of the reaction, the mixture was slowly quenched with saturated NaHCO 3 solution (aq.) at -10°C. Water (100 mL) was added, and the separated organic layer was washed with water and brine, dried over magnesium sulfate, and concentrated. The residue was purified by MPLC (silica gel, eluted with 0–20% EtOAc in n -hexane) to give 6-bromo-2-(difluoromethyl)-3-fluoropyridine (4.4 g, 80.2%) as an ivory powder. LC-MS (ESI+) m/z 226.3 [(M+H) + , calcd. C 6 H 3 BrF 3 N m/z 224.9].

B 파트: Part B: (S)-1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-2-아미노-2,4-다이메틸펜탄-1-올 (0.639 g, 4.87 mmol) 및 6-브로모-2-(다이플루오로메틸)-3-플루오로피리딘 (1.0 g, 4.42 mmol) (실시예 13, A 파트)을 사용하여 실시예 1의 A 파트에 대하여 설명한 것과 유사한 절차에 따라 제조하였고, 연한-황색 액체 (1.2 g, 85.1%)를 얻었다. LC-MS (ESI+) m/z 337.5 [(M+H)+, calcd. m/z C13H19BrF2N2O 336.0].This compound was prepared according to a similar procedure as that described for Part A of Example 1 using ( S )-2-amino-2,4-dimethylpentan-1-ol (0.639 g, 4.87 mmol) and 6-bromo-2-(difluoromethyl)-3-fluoropyridine (1.0 g, 4.42 mmol) (Example 13, Part A) to obtain a pale-yellow liquid (1.2 g, 85.1%). LC-MS (ESI+) m/z 337.5 [(M+H) + , calcd. m/z C 13 H 19 BrF 2 N 2 O 336.0].

C 파트: Part C: (S)-1-((2-(다이플루오로메틸)-6-(1H-피라졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (S)-1-((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.30 mmol) (실시예 13, B 파트) 및 tert-부틸 4-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피라졸-1-카복실레이트 (130.8 mg, 0.44 mmol)을 사용하여 실시예 1의 B 파트에 대하여 설명한 것과 유사한 절차에 따라 제조하였고, 아이보리색 분말 (30.7 mg, 31.9%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.54 (d, 2H), 7.91 (d, 1H), 7.73 (d, 1H), 7.00-7.21 (m, 1H), 4.18-4.26 (m, 2H), 1.82-1.86 (m, 2H), 1.65-1.70 (m, 1H), 1.49 (s, 3H), 1.03 (d, 3H), 0.97 (d, 3H). LC-MS (ESI+) m/z 325.3 [(M+H)+, calcd. C16H22F2N4O m/z 324.1].This compound was prepared according to a similar procedure as described for Part B of Example 1 using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and tert -butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole-1-carboxylate (130.8 mg, 0.44 mmol) to obtain an ivory powder (30.7 mg, 31.9%). 1H NMR (500 MHz, MeOD) δ 8.54 (d, 2H), 7.91 (d, 1H), 7.73 (d, 1H), 7.00-7.21 (m, 1H), 4.18-4.26 (m, 2H), 1.82-1.86 (m, 2H), 1.65-1.70 (m, 1H), 1.49 (s, 3H), 1.03 (d, 3H), 0.97 (d, 3H). LC-MS (ESI+) m/z 325.3 [(M+H) + , calcd. C 16 H 22 F 2 N 4 O m/z 324.1].

실시예 14: (Example 14: ( SS )-1-((2-(다이플루오로메틸)-6-(이속사졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [()-1-((2-(difluoromethyl)-6-(isoxazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((2-(difluoromethyl)-6-(isoxazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine])-1-((2-(difluoromethyl)-6-(isoxazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 14를 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 14 was prepared according to a similar procedure as described for Example 13.

C 파트: Part C: (S)-1-((2-(다이플루오로메틸)-6-(이속사졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((2-(difluoromethyl)-6-(isoxazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.30 mmol) (실시예 13, B 파트), 4-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)이속사졸 (86.7 mg, 0.44 mmol)를 사용하여 제조하였고, 아이보리색 분말 (20.8 mg, 21.5%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.47 (d, 2H), 7.88 (d, 1H), 7.71 (d, 1H), 7.00-7.18 (m, 1H), 4.16-4.23 (m, 2H), 1.79-1.72 (m, 2H), 1.67-1.69 (m, 1H), 1.46 (s, 3H), 1.02 (d, 3H), 0.99 (d, 3H). LC-MS (ESI+) m/z 326.3 [(M+H)+, calcd. C16H21F2N3O2 m/z 325.1].This compound was prepared using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)isoxazole (86.7 mg, 0.44 mmol) to obtain an ivory powder (20.8 mg, 21.5%). 1H NMR (500 MHz, MeOD) δ 8.47 (d, 2H), 7.88 (d, 1H), 7.71 (d, 1H), 7.00-7.18 (m, 1H), 4.16-4.23 (m, 2H), 1.79-1.72 (m, 2H), 1.67-1.69 (m, 1H), 1.46 (s, 3H), 1.02 (d, 3H), 0.99 (d, 3H). LC-MS (ESI+) m/z 326.3 [(M+H) + , calcd. C 16 H 21 F 2 N 3 O 2 m/z 325.1].

실시예 15: (Example 15: ( SS )-1-((2-(다이플루오로메틸)-6-(1)-1-((2-(difluoromethyl)-6-(1 HH -이미다졸-1-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(-imidazol-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((2-(difluoromethyl)-6-(1)-1-((2-(difluoromethyl)-6-(1 HH -imidazol-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]-imidazol-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 15는 (S)-1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.30 mmol) (실시예 13, B 파트) 및 1H-이미다졸 (20.1 mg, 0.30 mmol)을 사용하여 실시예 10에 대하여 설명한 것과 유사한 절차에 따라 제조하였고, 아이보리색 분말 (13.5 mg, 14.0%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.04 (s, 1H), 8.05 (s, 1H), 7.89-7.86 (m, 2H), 7.41 (s, 1H), 7.02-7.24 (m, 1H), 4.20-4.28 (m, 2H), 1.79-1.83 (m, 2H), 1.64-1.68 (m, 1H), 1.46 (s, 3H), 1.00 (d, 3H), 0.95 (d, 3H). LC-MS (ESI+) m/z 325.3 [(M+H)+, calcd. C16H22F2N4O m/z 324.1].Example 15 was prepared according to a similar procedure as described for Example 10 using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and 1 H -imidazole (20.1 mg, 0.30 mmol) to obtain an ivory powder (13.5 mg, 14.0%). 1H NMR (500 MHz, MeOD) δ 9.04 (s, 1H), 8.05 (s, 1H), 7.89-7.86 (m, 2H), 7.41 (s, 1H), 7.02-7.24 (m, 1H), 4.20-4.28 (m, 2H), 1.79-1.83 (m, 2H), 1.64-1.68 (m, 1H), 1.46 (s, 3H), 1.00 (d, 3H), 0.95 (d, 3H). LC-MS (ESI+) m/z 325.3 [(M+H) + , calcd. C 16 H 22 F 2 N 4 O m/z 324.1].

실시예 16: (Example 16: ( SS )-1-((2-(다이플루오로메틸)-6-(3-플루오로-1)-1-((2-(difluoromethyl)-6-(3-fluoro-1 HH -피라졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((2-(difluoromethyl)-6-(3-fluoro-1)-1-((2-(difluoromethyl)-6-(3-fluoro-1 HH -pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 16을 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 16 was prepared according to a procedure similar to that described for Example 13.

C 파트: Part C: (S)-1-((2-(다이플루오로메틸)-6-(3-플루오로-1H-피라졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((2-(difluoromethyl)-6-(3-fluoro-1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.30 mmol) (실시예 13, B 파트), 3-플루오로-4-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피라졸 (94.3 mg, 0.44 mmol)을 사용하여 제조하였고, 연한-갈색 분말 (15.4 mg, 15.9%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.04 (d, 1H), 7.59 (d, 1H), 6.82-7.04 (m, 1H), 3.93-4.00 (m, 2H), 2.15-2.18 (m, 1H), 2.00-2.02 (m, 1H), 1.79-1.81 (m, 1H), 1.31 (s, 3H), 0.98 (d, 3H), 0.96 (d, 3H). LC-MS (ESI+) m/z 343.0 [(M+H)+, calcd. C16H21F3N4O m/z 342.1].This compound was prepared using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and 3-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole (94.3 mg, 0.44 mmol) to obtain a pale-brown powder (15.4 mg, 15.9%). 1H NMR (500 MHz, MeOD) δ 8.04 (d, 1H), 7.59 (d, 1H), 6.82-7.04 (m, 1H), 3.93-4.00 (m, 2H), 2.15-2.18 (m, 1H), 2.00-2.02 (m, 1H), 1.79-1.81 (m, 1H), 1.31 (s, 3H), 0.98 (d, 3H), 0.96 (d, 3H). LC-MS (ESI+) m/z 343.0 [(M+H) + , calcd. C 16 H 21 F 3 N 4 O m/z 342.1].

실시예 17: (Example 17: ( SS )-1-((2-(다이플루오로메틸)-6-(1)-1-((2-(difluoromethyl)-6-(1 HH -이미다졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(-imidazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((2-(difluoromethyl)-6-(1)-1-((2-(difluoromethyl)-6-(1 HH -imidazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]-imidazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 17을 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 17 was prepared according to a procedure similar to that described for Example 13.

C 파트: Part C: (S)-1-((2-(다이플루오로메틸)-6-(1H-이미다졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((2-(difluoromethyl)-6-(1H-imidazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.30 mmol) (실시예 13, B 파트) 및 tert-부틸 4-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-이미다졸-1-카복실레이트를 사용하여 제조하였고, 연한-황색 분말 (20.3 mg, 21.1%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.13 (s, 1H), 8.04 (s, 1H), 7.81 (d, 1H), 7.03-7.22 (m, 2H), 4.23-4.32 (m, 2H), 1.85-1.87 (m, 2H), 1.69-1.72 (m, 1H), 1.51 (s, 3H), 1.04 (d, 3H), 1.00 (d, 3H). LC-MS (ESI+) m/z 325.3 [(M+H)+, calcd. C16H22F2N4O m/z 324.1].This compound was prepared using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and tert -butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -imidazole-1-carboxylate, and a pale-yellow powder (20.3 mg, 21.1%) was obtained. 1H NMR (500 MHz, MeOD) δ 8.13 (s, 1H), 8.04 (s, 1H), 7.81 (d, 1H), 7.03-7.22 (m, 2H), 4.23-4.32 (m, 2H), 1.85-1.87 (m, 2H), 1.69-1.72 (m, 1H), 1.51 (s, 3H), 1.04 (d, 3H), 1.00 (d, 3H). LC-MS (ESI+) m/z 325.3 [(M+H) + , calcd. C 16 H 22 F 2 N 4 O m/z 324.1].

실시예 18: (Example 18: ( SS )-1-((2-(다이플루오로메틸)-6-(1)-1-((2-(difluoromethyl)-6-(1 HH -피롤-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(-pyrrol-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((2-(difluoromethyl)-6-(1)-1-((2-(difluoromethyl)-6-(1 HH -pyrrol-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]-pyrrol-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 18을 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 18 was prepared according to a procedure similar to that described for Example 13.

C 파트: Part C: (S)-1-((2-(다이플루오로메틸)-6-(1H-피롤-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((2-(difluoromethyl)-6-(1H-pyrrol-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.30 mmol) (실시예 13, B 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤-1-카복실레이트 (130.4 mg, 0.44 mmol)를 사용하여 제조하였고, 연한-갈색 분말 (15.2 mg, 15.8%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 7.62 (d, 1H), 7.47 (d, 1H), 7.31 (s, 1H), 6.77-6.99 (m, 1H), 6.74-6.75 (m, 1H), 6.58 (d, 1H), 3.86-3.93 (m, 2H), 1.78-1.87 (m, 1H), 1.58-1.61 (m, 1H), 1.48-1.52 (m, 1H), 1.29 (s, 3H), 0.98 (d, 3H), 0.95 (d, 3H). LC-MS (ESI+) m/z 324.6 [(M+H)+, calcd. C17H23F2N3O m/z 323.1].This compound was prepared using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrole-1-carboxylate (130.4 mg, 0.44 mmol) to obtain a pale-brown powder (15.2 mg, 15.8%). 1H NMR (500 MHz, MeOD) δ 7.62 (d, 1H), 7.47 (d, 1H), 7.31 (s, 1H), 6.77-6.99 (m, 1H), 6.74-6.75 (m, 1H), 6.58 (d, 1H), 3.86-3.93 (m, 2H), 1.78-1.87 (m, 1H), 1.58-1.61 (m, 1H), 1.48-1.52 (m, 1H), 1.29 (s, 3H), 0.98 (d, 3H), 0.95 (d, 3H). LC-MS (ESI+) m/z 324.6 [(M+H) + , calcd. C 17 H 23 F 2 N 3 O m/z 323.1].

실시예 19: (Example 19: ( SS )-1-((2-(다이플루오로메틸)-6-(1)-1-((2-(difluoromethyl)-6-(1 HH -피라졸-5-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(-pyrazol-5-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((2-(difluoromethyl)-6-(1)-1-((2-(difluoromethyl)-6-(1 HH -pyrazol-5-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]-pyrazol-5-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 19를 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 19 was prepared according to a procedure similar to that described for Example 13.

C 파트:Part C: (S)-1-((2-(다이플루오로메틸)-6-(1H-피라졸-5-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((2-(difluoromethyl)-6-(1H-pyrazol-5-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.30 mmol) (실시예 13, B 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피라졸-1-카복실레이트 (130.8 mg, 0.44 mmol)를 사용하여 제조하였고, 아이보리색 분말 (25.3 mg, 26.3%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.15 (d, 1H), 8.04 (s, 1H), 7.81 (d, 1H), 7.04-7.25 (m, 2H), 4.23-4.32 (m, 2H), 1.85-1.87 (m, 2H), 1.69-1.72 (m, 1H), 1.51 (s, 3H), 1.04 (d, 3H), 1.00 (d, 3H). LC-MS (ESI+) m/z 325.1 [(M+H)+, calcd. C16H22F2N4O m/z 324.1].This compound was prepared using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole-1-carboxylate (130.8 mg, 0.44 mmol) and an ivory powder (25.3 mg, 26.3%) was obtained. 1H NMR (500 MHz, MeOD) δ 8.15 (d, 1H), 8.04 (s, 1H), 7.81 (d, 1H), 7.04-7.25 (m, 2H), 4.23-4.32 (m, 2H), 1.85-1.87 (m, 2H), 1.69-1.72 (m, 1H), 1.51 (s, 3H), 1.04 (d, 3H), 1.00 (d, 3H). LC-MS (ESI+) m/z 325.1 [(M+H) + , calcd. C 16 H 22 F 2 N 4 O m/z 324.1].

실시예 20: (Example 20: ( SS )-1-((2-(다이플루오로메틸)-6-(2)-1-((2-(difluoromethyl)-6-(2 HH -1,2,3-트리아졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((2-(difluoromethyl)-6-(2)-1-((2-(difluoromethyl)-6-(2 HH -1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 20을 실시예 8에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 20 was prepared according to a procedure similar to that described for Example 8.

B 파트:Part B: (S)-1-((2-(다이플루오로메틸)-6-(2H-1,2,3-트리아졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (S)-1-((2-(difluoromethyl)-6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.30 mmol) (실시예 13, B 파트) 및 2-(테트라하이드로-2H-피란-2-일)-4-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-2H-1,2,3-트리아졸 (124.1 mg, 0.44 mmol)을 사용하여 제조하였고, 아이보리색 분말 (30.2 mg, 31.3%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.44-8.48 (m, 1H), 8.17 (d, 1H), 7.80 (d, 1H), 7.03-7.25 (m, 1H), 4.23-4.31 (m, 2H), 1.8-1.88 (m, 2H), 1.69-1.72 (m, 1H), 1.51 (s, 3H), 1.05 (d, 3H), 0.99 (d, 3H). LC-MS (ESI+) m/z 000.0 [(M+H)+, calcd. C15H21F2N5O m/z 325.1].This compound was prepared using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and 2-(tetrahydro-2 H -pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2 H -1,2,3-triazole (124.1 mg, 0.44 mmol) and an ivory powder (30.2 mg, 31.3%) was obtained. 1H NMR (500 MHz, MeOD) δ 8.44-8.48 (m, 1H), 8.17 (d, 1H), 7.80 (d, 1H), 7.03-7.25 (m, 1H), 4.23-4.31 (m, 2H), 1.8-1.88 (m, 2H), 1.69-1.72 (m, 1H), 1.51 (s, 3H), 1.05 (d, 3H), 0.99 (d, 3H). LC-MS (ESI+) m/z 000.0 [(M+H)+, calcd. C 15 H 21 F 2 N 5 O m/z 325.1].

실시예 21: (Example 21: ( SS )-1-((2-(다이플루오로메틸)-6-(5-플루오로-1)-1-((2-(difluoromethyl)-6-(5-fluoro-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((2-(difluoromethyl)-6-(5-fluoro-1)-1-((2-(difluoromethyl)-6-(5-fluoro-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 21을 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 21 was prepared according to a procedure similar to that described for Example 13.

C 파트:Part C: (S)-1-((2-(다이플루오로메틸)-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.30 mmol) (실시예 13, B 파트) 및 tert-부틸 5-플루오로-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (161.1 mg, 0.44 mmol)를 사용하여 제조하였고, 연한-황색 분말 (28.6 mg, 24.5%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.06-9.08 (m, 1H), 8.43 (s, 1H), 8.28 (s, 1H), 8.02 (m, 1H), 7.72 (d, 1H), 7.11-7.33 (m, 1H), 4.19-4.28 (m, 2H), 1.83-1.88 (m, 2H), 1.67-1.72 (m, 1H), 1.51 (s, 3H), 1.06 (d, 3H), 1.00 (d, 3H). LC-MS (ESI+) m/z 392.4 [(M+H)+, calcd. C20H23F3N4O m/z 392.1].This compound was prepared using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (161.1 mg, 0.44 mmol) to obtain a pale-yellow powder (28.6 mg, 24.5%). 1H NMR (500 MHz, MeOD) δ 9.06-9.08 (m, 1H), 8.43 (s, 1H), 8.28 (s, 1H), 8.02 (m, 1H), 7.72 (d, 1H), 7.11-7.33 (m, 1H), 4.19-4.28 (m, 2H), 1.83-1.88 (m, 2H), 1.67-1.72 (m, 1H), 1.51 (s, 3H), 1.06 (d, 3H), 1.00 (d, 3H). LC-MS (ESI+) m/z 392.4 [(M+H) + , calcd. C 20 H 23 F 3 N 4 O m/z 392.1].

실시예 22: (Example 22: ( SS )-1-(2-(다이플루오로메틸)-4-(5-플루오로-1)-1-(2-(difluoromethyl)-4-(5-fluoro-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)펜옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-3-yl)phenoxy)-2,4-dimethylpentan-2-amine [( SS )-1-(2-(difluoromethyl)-4-(5-fluoro-1)-1-(2-(difluoromethyl)-4-(5-fluoro-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)phenoxy)-2,4-dimethylpentan-2-amine]]pyridin-3-yl)phenoxy)-2,4-dimethylpentan-2-amine]

실시예 22를 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 22 was prepared according to a procedure similar to that described for Example 13.

B 파트: Part B: (S)-1-(4-브로모-2-(다이플루오로메틸)펜옥시)-2,4-다이메틸펜탄-2-아민(S)-1-(4-bromo-2-(difluoromethyl)phenoxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-2-아미노-4-메틸펜탄-2-올 (320.7 mg, 2.44 mmol) 및 4-브로모-2-(다이플루오로메틸)-1-플루오로벤젠 (500.0 mg, 2.22 mmol)을 사용하여 제조하였고, 연한-황색 액체 (580.3 mg, 77.6%)를 얻었다. LC-MS (ESI+) m/z 336.6 [(M+H)+, calcd. C14H20BrF2NO m/z 335.0].This compound was prepared using ( S )-2-amino-4-methylpentan-2-ol (320.7 mg, 2.44 mmol) and 4-bromo-2-(difluoromethyl)-1-fluorobenzene (500.0 mg, 2.22 mmol) and a pale-yellow liquid (580.3 mg, 77.6%) was obtained. LC-MS (ESI+) m/z 336.6 [(M+H) + , calcd. C 14 H 20 BrF 2 NO m/z 335.0].

C 파트: Part C: (S)-1-(2-(다이플루오로메틸)-4-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)펜옥시)-2,4-다이메틸펜탄-2-아민(S)-1-(2-(difluoromethyl)-4-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-(4-브로모-2-(다이플루오로메틸)펜옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.30 mmol) (실시예 22, B 파트) 및 tert-부틸 5-플루오로-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (161.5 mg, 0.45 mmol)를 사용하여 제조하였고, 아이보리색 분말 (30.2 mg, 25.9%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.04-9.07 (m, 1H), 8.44 (s, 1H), 8.28 (s, 1H), 8.03 (m, 1H), 7.74 (d, 1H), 7.12-7.33 (m, 2H), 4.19-4.28 (m, 2H), 1.83-1.88 (m, 2H), 1.67-1.72 (m, 1H), 1.51 (s, 3H), 1.06 (d, 3H), 1.00 (d, 3H). LC-MS (ESI+) m/z 392.6 [(M+H)+, calcd. C21H24F3N3O m/z 391.1].This compound was prepared using ( S )-1-(4-bromo-2-(difluoromethyl)phenoxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 22, Part B) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (161.5 mg, 0.45 mmol) and an ivory powder (30.2 mg, 25.9%) was obtained. 1H NMR (500 MHz, MeOD) δ 9.04-9.07 (m, 1H), 8.44 (s, 1H), 8.28 (s, 1H), 8.03 (m, 1H), 7.74 (d, 1H), 7.12-7.33 (m, 2H), 4.19-4.28 (m, 2H), 1.83-1.88 (m, 2H), 1.67-1.72 (m, 1H), 1.51 (s, 3H), 1.06 (d, 3H), 1.00 (d, 3H). LC-MS (ESI+) m/z 392.6 [(M+H) + , calcd. C 21 H 24 F 3 N 3 O m/z 391.1].

실시예 23: (Example 23: ( SS )-1-((2-(다이플루오로메틸)-6-(5-(트리플루오로메틸)-1)-1-((2-(difluoromethyl)-6-(5-(trifluoromethyl)-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((2-(difluoromethyl)-6-(5-(trifluoromethyl)-1)-1-((2-(difluoromethyl)-6-(5-(trifluoromethyl)-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 23을 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 23 was prepared according to a procedure similar to that described for Example 13.

C 파트: Part C: (S)-1-((2-(다이플루오로메틸)-6-(5-(트리플루오로메틸)-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((2-(difluoromethyl)-6-(5-(trifluoromethyl)-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.30 mmol) (실시예 13, B 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-5-(트리플루오로메틸)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (183.3 mg, 0.44 mmol)를 사용하여 제조하였고, 연한-황색 분말 (35.4 mg, 26.9%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.21 (s, 1H), 9.08-9.10 (m, 1H), 8.28-8.29 (m, 1H), 8.19 (s, 1H), 7.85-7.87 (m, 1H), 7.10-7.31 (m, 1H), 4.26-4.34 (m, 2H), 1.86-1.90 (m, 2H), 1.71-1.73 (m, 1H), 1.54 (s, 3H), 1.07 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+) m/z 443.3 [(M+H)+, calcd. C21H23F5N4O m/z 442.1].This compound was prepared using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-5-(trifluoromethyl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (183.3 mg, 0.44 mmol) to obtain a pale-yellow powder (35.4 mg, 26.9%). 1H NMR (500 MHz, MeOD) δ 9.21 (s, 1H), 9.08-9.10 (m, 1H), 8.28-8.29 (m, 1H), 8.19 (s, 1H), 7.85-7.87 (m, 1H), 7.10-7.31 (m, 1H), 4.26-4.34 (m, 2H), 1.86-1.90 (m, 2H), 1.71-1.73 (m, 1H), 1.54 (s, 3H), 1.07 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+) m/z 443.3 [(M+H) + , calcd. C 21 H 23 F 5 N 4 O m/z 442.1].

실시예 24: (Example 24: ( SS )-1-((2-(다이플루오로메틸)-6-(4-플루오로-1)-1-((2-(difluoromethyl)-6-(4-fluoro-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((2-(difluoromethyl)-6-(4-fluoro-1)-1-((2-(difluoromethyl)-6-(4-fluoro-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 24를 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 24 was prepared according to a procedure similar to that described for Example 13.

C 파트: Part C: (S)-1-((2-(다이플루오로메틸)-6-(4-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((2-(difluoromethyl)-6-(4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.30 mmol) (실시예 13, B 파트) 및 tert-부틸 4-플루오로-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (161.1 mg, 0.44 mmol)를 사용하여 제조하였고, 연한-갈색 분말 (20.4 mg, 17.5%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.23-8.25 (d, 1H), 7.92-7.95 (m, 2H), 7.66 (d, 1H), 7.92-7.13 (m, 2H), 4.04-4.12 (m, 2H), 1.82-1.91 (m, 1H), 1.71-1.75 (m, 1H), 1.59-1.63 (m, 1H), 1.39 (s, 3H), 1.03 (d, 3H), 1.10 (d, 3H). LC-MS (ESI+) m/z 393.1 [(M+H)+, calcd. C20H23F3N4O m/z 392.1].This compound was prepared using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and tert -butyl 4-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (161.1 mg, 0.44 mmol) to obtain a pale-brown powder (20.4 mg, 17.5%). 1H NMR (500 MHz, MeOD) δ 8.23-8.25 (d, 1H), 7.92-7.95 (m, 2H), 7.66 (d, 1H), 7.92-7.13 (m, 2H), 4.04-4.12 (m, 2H), 1.82-1.91 (m, 1H), 1.71-1.75 (m, 1H), 1.59-1.63 (m, 1H), 1.39 (s, 3H), 1.03 (d, 3H), 1.10 (d, 3H). LC-MS (ESI+) m/z 393.1 [(M+H) + , calcd. C 20 H 23 F 3 N 4 O m/z 392.1].

실시예 25: ((Example 25: (( SS )-1-((2-(다이플루오로메틸)-6-(1)-1-((2-(difluoromethyl)-6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [((]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(( SS )-1-((2-(difluoromethyl)-6-(1)-1-((2-(difluoromethyl)-6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 25를 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 25 was prepared according to a procedure similar to that described for Example 13.

C 파트: Part C: ((S)-1-((2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민((S)-1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.30 mmol) (실시예 14, B 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (153.1 mg, 0.44 mmol)를 사용하여 제조하였고, 아이보리색 분말 (30.9 mg, 27.8%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.87 (d, 1H), 8.22 (d, 1H), 7.96 (s, 1H), 7.88 (m, 1H), 7.56 (d, 1H), 7.18-7.20 (m, 1H), 6.91-7.13 (m, 1H), 3.89-3.95 (m, 2H), 1.78-1.82 (m, 1H), 1.49-1.61 (m, 2H), 1.26 (s, 3H), 0.98 (d, 3H), 0.98 (d, 3H). LC-MS (ESI+) m/z 375.2 [(M+H)+, calcd. C20H24F2N4O m/z 374.1].This compound was prepared using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 14, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (153.1 mg, 0.44 mmol) and an ivory powder (30.9 mg, 27.8%) was obtained. 1H NMR (500 MHz, MeOD) δ 8.87 (d, 1H), 8.22 (d, 1H), 7.96 (s, 1H), 7.88 (m, 1H), 7.56 (d, 1H), 7.18-7.20 (m, 1H), 6.91-7.13 (m, 1H), 3.89-3.95 (m, 2H), 1.78-1.82 (m, 1H), 1.49-1.61 (m, 2H), 1.26 (s, 3H), 0.98 (d, 3H), 0.98 (d, 3H). LC-MS (ESI+) m/z 375.2 [(M+H) + , calcd. C 20 H 24 F 2 N 4 O m/z 374.1].

실시예 26: (Example 26: ( SS )-1-((6-(5-클로로-1)-1-((6-(5-chloro-1 HH -피라졸로[3,4--Pyrazolo[3,4- bb ]피리딘-3-일)-2-(다이플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((6-(5-chloro-1)-1-((6-(5-chloro-1 HH -pyrazolo[3,4--pyrazolo[3,4- bb ]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 26을 실시예 8에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 26 was prepared according to a procedure similar to that described for Example 8.

B 파트: Part B: (S)-1-((6-(5-클로로-1H-피라졸로[3,4-b]피리딘-3-일)-2-(다이플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((6-(5-chloro-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.30 mmol) (실시예 13, B 파트) 및 5-클로로-1-(테트라하이드로-2H-피란-2-일)-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피라졸로[3,4-b]피리딘 (161.7 mg, 0.44 mmol)을 사용하여 제조하였고, 연한-황색 분말 (40.2 mg, 33.0%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.95 (d, 1H), 8.50 (d, 1H), 8.32 (d, 1H), 7.77 (d, 1H), 7.13-7.36 (m, 1H), 4.17-4.31 (m, 2H), 1.82-1.88 (m, 2H), 1.69-1.71 (m, 1H), 1.52 (s, 3H), 1.06 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+) m/z 410.2 [(M+H)+, calcd. C19H22ClF2N5O m/z 409.1].This compound was prepared using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and 5-chloro-1-(tetrahydro-2 H -pyran-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazolo[3,4- b ]pyridine (161.7 mg, 0.44 mmol) to obtain a pale-yellow powder (40.2 mg, 33.0%). 1H NMR (500 MHz, MeOD) δ 8.95 (d, 1H), 8.50 (d, 1H), 8.32 (d, 1H), 7.77 (d, 1H), 7.13-7.36 (m, 1H), 4.17-4.31 (m, 2H), 1.82-1.88 (m, 2H), 1.69-1.71 (m, 1H), 1.52 (s, 3H), 1.06 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+) m/z 410.2 [(M+H) + , calcd. C 19 H 22 ClF 2 N 5 O m/z 409.1].

실시예 27: (Example 27: ( SS )-1-((2-(다이플루오로메틸)-6-(4-메톡시-1)-1-((2-(difluoromethyl)-6-(4-methoxy-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((2-(difluoromethyl)-6-(4-methoxy-1)-1-((2-(difluoromethyl)-6-(4-methoxy-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 27을 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 27 was prepared according to a procedure similar to that described for Example 13.

C 파트: Part C: (S)-1-((2-(다이플루오로메틸)-6-(4-메톡시-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((2-(difluoromethyl)-6-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.30 mmol) (실시예 13, B 파트) 및 tert-부틸 4-메톡시-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (166.4 mg, 0.44 mmol)를 사용하여 제조하였고, 연한-황색 분말 (34.9 mg, 29.1%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.23 (m, 1H), 8.12 (d, 1H), 7.80 (d, 1H), 7.48-7.51 (m, 2H), 7.13-7.36 (m, 1H), 4.17-4.31 (m, 2H), 3.91 (s, 3H), 1.82-1.88 (m, 2H), 1.69-1.71 (m, 1H), 1.52 (s, 3H), 1.06 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+) m/z 405.6 [(M+H)+, calcd. C21H26F2N4O2 m/z 404.2].This compound was prepared using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and tert -butyl 4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (166.4 mg, 0.44 mmol) to obtain a pale-yellow powder (34.9 mg, 29.1%). 1H NMR (500 MHz, MeOD) δ 8.23 (m, 1H), 8.12 (d, 1H), 7.80 (d, 1H), 7.48-7.51 (m, 2H), 7.13-7.36 (m, 1H), 4.17-4.31 (m, 2H), 3.91 (s, 3H), 1.82-1.88 (m, 2H), 1.69-1.71 (m, 1H), 1.52 (s, 3H), 1.06 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+) m/z 405.6 [(M+H) + , calcd. C 21 H 26 F 2 N 4 O 2 m/z 404.2].

실시예 28: (Example 28: ( SS )-1-((2-(다이플루오로메틸)-6-(6-플루오로-1)-1-((2-(difluoromethyl)-6-(6-fluoro-1 HH -피롤로[3,2--Pyrrolo[3,2- bb ]피리딘-1-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((2-(difluoromethyl)-6-(6-fluoro-1)-1-((2-(difluoromethyl)-6-(6-fluoro-1 HH -pyrrolo[3,2--pyrrolo[3,2- bb ]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 28은 (S)-1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.30 mmol) (실시예 13, B 파트) 및 6-플루오로-1H-피롤로[3,2-b]피리딘 (440.3 mg, 0.30 mmol)을 사용하여 실시예 10에 대하여 설명한 것과 유사한 절차에 따라 제조하였고, 아이보리색 분말 (20.4 mg, 17.5%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.66-8.69 (m, 1H), 8.32 (s, 1H), 8.16 (d, 1H), 7.82 (s, 2H), 7.04-7.26 (m, 1H), 6.80 (d, 1H), 4.06-4.16 (m, 2H), 1.70-1.81 (m, 2H), 1.57-1.61 (m, 1H), 1.39 (s, 3H), 0.99 (d, 3H), 0.95 (d, 3H). LC-MS (ESI+) m/z 393.4 [(M+H)+, calcd. C20H23F3N4O m/z 392.1].Example 28 was prepared according to a similar procedure as described for Example 10 using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and 6-fluoro-1 H -pyrrolo[3,2- b ]pyridine (440.3 mg, 0.30 mmol) to obtain an ivory powder (20.4 mg, 17.5%). 1H NMR (500 MHz, MeOD) δ 8.66-8.69 (m, 1H), 8.32 (s, 1H), 8.16 (d, 1H), 7.82 (s, 2H), 7.04-7.26 (m, 1H), 6.80 (d, 1H), 4.06-4.16 (m, 2H), 1.70-1.81 (m, 2H), 1.57-1.61 (m, 1H), 1.39 (s, 3H), 0.99 (d, 3H), 0.95 (d, 3H). LC-MS (ESI+) m/z 393.4 [(M+H) + , calcd. C 20 H 23 F 3 N 4 O m/z 392.1].

실시예 29: (S)-1-((2-(다이플루오로메틸)-6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(S)-1-((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]Example 29: (S)-1-((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(S)-1-((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 29는 (S)-1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.30 mmol) (실시예 13, B 파트) 및 1H-피롤로[3,2-b]피리딘 (35.0 mg, 0.30 mmol)을 사용하여 실시예 10에 대하여 설명한 것과 유사한 절차에 따라 제조하였고, 아이보리색 분말 (24.7 mg, 22.2%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.91 (d, 1H), 8.42 (d, 1H), 8.22 (d, 1H), 7.90-7.92 (m, 2H), 7.32-7.35 (m, 1H), 6.88-7.23 (m, 2H), 4.22-4.32 (m, 2H), 1.85-1.88 (m, 2H), 1.68-1.73 (m, 1H), 1.53 (s, 3H), 1.07 (d, 3H), 1.03 (d, 3H). LC-MS (ESI+) m/z 375.1 [(M+H)+, calcd. C20H24F2N4O m/z 374.1].Example 29 was prepared according to a similar procedure as described for Example 10 using ( S )-1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 13, Part B) and 1 H -pyrrolo[3,2- b ]pyridine (35.0 mg, 0.30 mmol) to obtain an ivory powder (24.7 mg, 22.2%). 1H NMR (500 MHz, MeOD) δ 8.91 (d, 1H), 8.42 (d, 1H), 8.22 (d, 1H), 7.90-7.92 (m, 2H), 7.32-7.35 (m, 1H), 6.88-7.23 (m, 2H), 4.22-4.32 (m, 2H), 1.85-1.88 (m, 2H), 1.68-1.73 (m, 1H), 1.53 (s, 3H), 1.07 (d, 3H), 1.03 (d, 3H). LC-MS (ESI+) m/z 375.1 [(M+H) + , calcd. C 20 H 24 F 2 N 4 O m/z 374.1].

실시예 30: (Example 30: ( SS )-1-((4-(다이플루오로메틸)-6-(1)-1-((4-(difluoromethyl)-6-(1 HH -피라졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((4-(difluoromethyl)-6-(1)-1-((4-(difluoromethyl)-6-(1 HH -pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 30을 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 30 was prepared according to a procedure similar to that described for Example 13.

A 파트: Part A: 2-브로모-4-(다이플루오로메틸)-5-플루오로피리딘2-bromo-4-(difluoromethyl)-5-fluoropyridine

이 화합물은 2-브로모-5-플루오로이소니코틴알데히드 (2.0 g, 9.80 mmol) 및 디에틸아미노황 삼불화물 (2.8 mL, 19.6 mmol)을 사용하여 제조하였고, 연한-황색 액체 (1.6 g, 75.3%)를 얻었다. LC-MS (ESI+) m/z 226.6 [(M+H)+, calcd. C6H3BrF3N m/z 224.9].This compound was prepared using 2-bromo-5-fluoroisonicotinaldehyde (2.0 g, 9.80 mmol) and diethylaminosulfur trifluoride (2.8 mL, 19.6 mmol) to obtain a pale-yellow liquid (1.6 g, 75.3%). LC-MS (ESI+) m/z 226.6 [(M+H) + , calcd. C 6 H 3 BrF 3 N m/z 224.9].

B 파트: Part B: (S)-1-((6-브로모-4-(다이플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((6-bromo-4-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-2-아미노-2,4-다이메틸펜탄-1-올 (319.3 mg, 2.43 mmol) 및 2-브로모-4-(다이플루오로메틸)-5-플루오로피리딘 (500.0 mg, 2.21 mmol) (실시예 30, A 파트)을 사용하여 제조하였고, 연한-황색 액체 (488.6 mg, 76.9%)를 얻었다. LC-MS (ESI+) m/z 337.2 [(M+H)+, calcd. C13H19BrF2N2O m/z 336.0].This compound was prepared using ( S )-2-amino-2,4-dimethylpentan-1-ol (319.3 mg, 2.43 mmol) and 2-bromo-4-(difluoromethyl)-5-fluoropyridine (500.0 mg, 2.21 mmol) (Example 30, Part A) to obtain a pale-yellow liquid (488.6 mg, 76.9%). LC-MS (ESI+) m/z 337.2 [(M+H) + , calcd. C 13 H 19 BrF 2 N 2 O m/z 336.0].

C 파트Part C : (S)-1-((4-(다이플루오로메틸)-6-(1H-피라졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민: (S)-1-((4-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((6-브로모-4-(다이플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.30 mmol) (실시예 30, B 파트) 및 tert-부틸 4-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피라졸-1-카복실레이트 (130.8 mg, 0.44 mmol)를 사용하여 제조하였고, 연한-갈색 분말 (28.3 mg, 29.4%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.57 (s, 1H), 8.46 (s, 2H), 8.27 (s, 1H), 7.22-7.44 (m, 1H), 4.36-4.45 (m, 2H), 1.82-1.86 (m, 2H), 1.65-1.70 (m, 1H), 1.50 (s, 3H), 1.04 (d, 3H), 0.98 (d, 3H). LC-MS (ESI+) m/z 325.2 [(M+H)+, calcd. C16H22F2N4O m/z 324.1].This compound was prepared using ( S )-1-((6-bromo-4-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 30, Part B) and tert -butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole-1-carboxylate (130.8 mg, 0.44 mmol) to obtain a pale-brown powder (28.3 mg, 29.4%). 1H NMR (500 MHz, MeOD) δ 8.57 (s, 1H), 8.46 (s, 2H), 8.27 (s, 1H), 7.22-7.44 (m, 1H), 4.36-4.45 (m, 2H), 1.82-1.86 (m, 2H), 1.65-1.70 (m, 1H), 1.50 (s, 3H), 1.04 (d, 3H), 0.98 (d, 3H). LC-MS (ESI+) m/z 325.2 [(M+H) + , calcd. C 16 H 22 F 2 N 4 O m/z 324.1].

실시예 31: (Example 31: ( SS )-1-((4-(다이플루오로메틸)-6-(2)-1-((4-(difluoromethyl)-6-(2 HH -1,2,3-트리아졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((4-(difluoromethyl)-6-(2)-1-((4-(difluoromethyl)-6-(2 HH -1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 31을 실시예 8에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 31 was prepared according to a procedure similar to that described for Example 8.

B 파트: Part B: (S)-1-((4-(다이플루오로메틸)-6-(2H-1,2,3-트리아졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (S)-1-((4-(difluoromethyl)-6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((6-브로모-4-(다이플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.30 mmol) (실시예 30, B 파트) 및 2-(테트라하이드로-2H-피란-2-일)-4-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-2H-1,2,3-트리아졸 (124.1 mg, 0.44 mmol)을 사용하여 제조하였고, 아이보리색 분말 (17.8 mg, 18.4%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.72 (s, 1H), 8.64 (s, 1H), 8.42 (s, 1H), 7.28-7.49 (m, 1H), 4.44-4.52 (m, 2H), 1.87-1.92 (m, 2H), 1.72-1.75 (m, 1H), 1.55 (s, 3H), 1.08 (d, 3H), 1.04 (d, 3H). LC-MS (ESI+) m/z 326.5 [(M+H)+, calcd. C15H21F2N5O m/z 325.1].This compound was prepared using ( S )-1-((6-bromo-4-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 30, Part B) and 2-(tetrahydro-2 H -pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2 H -1,2,3-triazole (124.1 mg, 0.44 mmol) and an ivory powder (17.8 mg, 18.4%) was obtained. 1H NMR (500 MHz, MeOD) δ 8.72 (s, 1H), 8.64 (s, 1H), 8.42 (s, 1H), 7.28-7.49 (m, 1H), 4.44-4.52 (m, 2H), 1.87-1.92 (m, 2H), 1.72-1.75 (m, 1H), 1.55 (s, 3H), 1.08 (d, 3H), 1.04 (d, 3H). LC-MS (ESI+) m/z 326.5 [(M+H) + , calcd. C 15 H 21 F 2 N 5 O m/z 325.1].

실시예 32: ((Example 32: (( SS )-1-((4-(다이플루오로메틸)-6-(1)-1-((4-(difluoromethyl)-6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [((]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [(( SS )-1-((4-(difluoromethyl)-6-(1)-1-((4-(difluoromethyl)-6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 32를 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 32 was prepared according to a procedure similar to that described for Example 13.

C 파트: Part C: ((S)-1-((4-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민((S)-1-((4-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((6-브로모-4-(다이플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.30 mmol) (실시예 30, B 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (153.1 mg, 0.44 mmol)를 사용하여 제조하였고, 연한-갈색 분말 (34.2 mg, 30.8%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.87 (d, 1H), 8.22 (d, 1H), 7.96 (s, 1H), 7.88 (m, 1H), 7.56 (d, 1H), 7.18-7.20 (m, 1H), 6.91-7.13 (m, 1H), 4.44-4.52 (m, 2H), 1.87-1.92 (m, 2H), 1.72-1.75 (m, 1H), 1.55 (s, 3H), 1.08 (d, 3H), 1.04 (d, 3H). LC-MS (ESI+) m/z 375.4 [(M+H)+, calcd. C20H24F2N4O m/z 374.1].This compound was prepared using ( S )-1-((6-bromo-4-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 30, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (153.1 mg, 0.44 mmol) to obtain a pale-brown powder (34.2 mg, 30.8%). 1H NMR (500 MHz, MeOD) δ 8.87 (d, 1H), 8.22 (d, 1H), 7.96 (s, 1H), 7.88 (m, 1H), 7.56 (d, 1H), 7.18-7.20 (m, 1H), 6.91-7.13 (m, 1H), 4.44-4.52 (m, 2H), 1.87-1.92 (m, 2H), 1.72-1.75 (m, 1H), 1.55 (s, 3H), 1.08 (d, 3H), 1.04 (d, 3H). LC-MS (ESI+) m/z 375.4 [(M+H) + , calcd. C 20 H 24 F 2 N 4 O m/z 374.1].

실시예 33: (Example 33: ( SS )-1-((5-(다이플루오로메틸)-6-(1)-1-((5-(difluoromethyl)-6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((5-(difluoromethyl)-6-(1)-1-((5-(difluoromethyl)-6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 33을 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 33 was prepared according to a procedure similar to that described for Example 13.

A 파트: Part A: 2-브로모-3-(다이플루오로메틸)-5-플루오로피리딘2-bromo-3-(difluoromethyl)-5-fluoropyridine

이 화합물은 2-브로모-5-플루오로니코틴알데히드 (3.0 g, 14.71 mmol) 및 디에틸아미노황 삼불화물 (4.2 mL, 29.41 mmol)을 사용하여 제조하였고, 연한-황색 액체 (2.5 g, 77.0%)를 얻었다. LC-MS (ESI+) m/z 287.3 [(M+H)+, calcd. C6H3BrF3N m/z 224.9].This compound was prepared using 2-bromo-5-fluoronicotinaldehyde (3.0 g, 14.71 mmol) and diethylaminosulfur trifluoride (4.2 mL, 29.41 mmol) to obtain a pale-yellow liquid (2.5 g, 77.0%). LC-MS (ESI+) m/z 287.3 [(M+H) + , calcd. C 6 H 3 BrF 3 N m/z 224.9].

B 파트: Part B: (S)-1-((6-브로모-5-(다이플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((6-bromo-5-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-2-아미노-2,4-다이메틸펜탄-1-올 (0.6 g, 4.87 mmol) 및 2-브로모-3-(다이플루오로메틸)-5-플루오로피리딘 (1.0 g, 4.42 mmol) (실시예 33, A 파트)을 사용하여 제조하였고, 연한-황색 액체 (0.26 g, 17.4%)를 얻었다. LC-MS (ESI+) m/z 337.4 [(M+H)+, calcd. C13H19BrF2N2O m/z 336.0].This compound was prepared using ( S )-2-amino-2,4-dimethylpentan-1-ol (0.6 g, 4.87 mmol) and 2-bromo-3-(difluoromethyl)-5-fluoropyridine (1.0 g, 4.42 mmol) (Example 33, Part A) to obtain a pale-yellow liquid (0.26 g, 17.4%). LC-MS (ESI+) m/z 337.4 [(M+H) + , calcd. C 13 H 19 BrF 2 N 2 O m/z 336.0].

C 파트: Part C: (S)-1-((5-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((5-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((6-브로모-5-(다이플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.30 mmol) (실시예 33, B 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (153.1 mg, 0.44 mmol)를 사용하여 제조하였고, 연한-갈색 분말 (26.5 mg, 23.8%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.56-8.59 (m, 1H), 8.25-8.28 (m, 1H), 7.66-7.81 (m, 2H), 7.17-7.21 (m, 1H), 5.39-5.9 (m, 2H), 4.42-4.44 (m, 2H), 1.82-1.88 (m, 1H), 1.56-1.68 (m, 2H), 1.34 (s, 3H), 1.01 (d, 3H), 1.00 (d, 3H). LC-MS (ESI+) m/z 375.3 [(M+H)+, calcd. C20H24F2N4O m/z 374.1].This compound was prepared using ( S )-1-((6-bromo-5-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 33, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (153.1 mg, 0.44 mmol) to obtain a pale-brown powder (26.5 mg, 23.8%). 1H NMR (500 MHz, MeOD) δ 8.56-8.59 (m, 1H), 8.25-8.28 (m, 1H), 7.66-7.81 (m, 2H), 7.17-7.21 (m, 1H), 5.39-5.9 (m, 2H), 4.42-4.44 (m, 2H), 1.82-1.88 (m, 1H), 1.56-1.68 (m, 2H), 1.34 (s, 3H), 1.01 (d, 3H), 1.00 (d, 3H). LC-MS (ESI+) m/z 375.3 [(M+H) + , calcd. C 20 H 24 F 2 N 4 O m/z 374.1].

실시예 34: (Example 34: ( SS )-1-((6-(1)-1-((6-(1 HH -피라졸-4-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((6-(1)-1-((6-(1 HH -pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 34를 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 34 was prepared according to a procedure similar to that described for Example 13.

B 파트:Part B: (S)-1-((6-브로모-2-(트리플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-2-아미노-2,4-다이메틸펜탄-1-올 (295.8 mg, 2.25 mmol) 및 6-브로모-3-플루오로-2-(트리플루오로메틸)피리딘 (500.0 mg, 2.05 mmol)을 사용하여 제조하였고, 회백색 분말 (642.5 mg, 88.2%)을 얻었다. LC-MS (ESI+) m/z 355.7 [(M+H)+, calcd. C13H18BrF3N2O m/z 354.0].This compound was prepared using ( S )-2-amino-2,4-dimethylpentan-1-ol (295.8 mg, 2.25 mmol) and 6-bromo-3-fluoro-2-(trifluoromethyl)pyridine (500.0 mg, 2.05 mmol) and an off-white powder (642.5 mg, 88.2%) was obtained. LC-MS (ESI+) m/z 355.7 [(M+H) + , calcd. C 13 H 18 BrF 3 N 2 O m/z 354.0].

C 파트:Part C: (S)-1-((6-(1H-피라졸-4-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((6-(1H-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((6-브로모-2-(트리플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.28 mmol) (실시예 34, B 파트) 및 tert-부틸 4-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피라졸-1-카복실레이트 (124.2 mg, 0.42 mmol)를 사용하여 제조하였고, 연한-갈색 분말 (26.5 mg, 27.4%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.09 (br, 2H), 7.82 (d, 1H), 7.62 (d, 1H), 3.92-3.97 (m, 2H), 1.78-1.81 (m, 1H), 1.43-1.60 (m, 2H), 1.28 (s, 3H), 0.98 (d, 3H), 0.96 (d, 3H). LC-MS (ESI+) m/z 343.6 [(M+H)+, calcd. C16H21F3N4O m/z 342.1].This compound was prepared using ( S )-1-((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.28 mmol) (Example 34, Part B) and tert -butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole-1-carboxylate (124.2 mg, 0.42 mmol) to obtain a pale-brown powder (26.5 mg, 27.4%). 1H NMR (500 MHz, MeOD) δ 8.09 (br, 2H), 7.82 (d, 1H), 7.62 (d, 1H), 3.92-3.97 (m, 2H), 1.78-1.81 (m, 1H), 1.43-1.60 (m, 2H), 1.28 (s, 3H), 0.98 (d, 3H), 0.96 (d, 3H). LC-MS (ESI+) m/z 343.6 [(M+H) + , calcd. C 16 H 21 F 3 N 4 O m/z 342.1].

실시예 35: (Example 35: ( SS )-1-((6-(5-플루오로-1)-1-((6-(5-fluoro-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((6-(5-fluoro-1)-1-((6-(5-fluoro-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 35를 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 35 was prepared according to a procedure similar to that described for Example 13.

C 파트: Part C: (S)-1-((6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((6-(5-Fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((6-브로모-2-(트리플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.28 mmol) (실시예 34, B 파트) 및 tert-부틸 5-플루오로-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (152.9 mg, 0.42 mmol)를 사용하여 제조하였고, 아이보리색 분말 (30.2 mg, 26.1%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.59-8.61 (m, 1H), 8.16 (s, 1H), 8.09 (s, 1H), 7.98 (d, 1H), 7.65 (d, 1H), 3.93-3.98 (m, 2H), 1.81-1.85 (m, 1H), 1.57-1.61 (m, 1H), 1.50-1.57 (m, 1H), 1.27 (s, 3H), 1.00 (d, 3H), 0.98 (d, 3H). LC-MS (ESI+) m/z 411.4 [(M+H)+, calcd. C20H22F4N4O m/z 410.1].This compound was prepared using ( S )-1-((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.28 mmol) (Example 34, Part B) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (152.9 mg, 0.42 mmol) and an ivory powder (30.2 mg, 26.1%) was obtained. 1H NMR (500 MHz, MeOD) δ 8.59-8.61 (m, 1H), 8.16 (s, 1H), 8.09 (s, 1H), 7.98 (d, 1H), 7.65 (d, 1H), 3.93-3.98 (m, 2H), 1.81-1.85 (m, 1H), 1.57-1.61 (m, 1H), 1.50-1.57 (m, 1H), 1.27 (s, 3H), 1.00 (d, 3H), 0.98 (d, 3H). LC-MS (ESI+) m/z 411.4 [(M+H) + , calcd. C 20 H 22 F 4 N 4 O m/z 410.1].

실시예 36: (Example 36: ( SS )-1-((5-(5-플루오로-1)-1-((5-(5-fluoro-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((5-(5-fluoro-1)-1-((5-(5-fluoro-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 36을 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 36 was prepared according to a procedure similar to that described for Example 13.

B 파트: Part B: (S)-1-((5-브로모피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((5-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-2-아미노-2,4-다이메틸펜탄-1-올 (246.0 mg, 1.88 mmol) 및 5-브로모-2-플루오로피리딘 (300.0 mg, 1.70 mmol)을 사용하여 제조하였고, 연한-황색 액체 (280.4 mg, 57.2%)를 얻었다. LC-MS (ESI+) m/z 287.3 [(M+H)+, calcd. C12H19BrN2O m/z 286.0].This compound was prepared using ( S )-2-amino-2,4-dimethylpentan-1-ol (246.0 mg, 1.88 mmol) and 5-bromo-2-fluoropyridine (300.0 mg, 1.70 mmol) and a pale-yellow liquid (280.4 mg, 57.2%) was obtained. LC-MS (ESI+) m/z 287.3 [(M+H) + , calcd. C 12 H 19 BrN 2 O m/z 286.0].

C 파트:Part C: (S)-1-((5-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((5-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((5-브로모피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.35 mmol) (실시예 36, B 파트) 및 tert-부틸 5-플루오로-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (189.1 mg, 0.52 mmol)를 사용하여 제조하였고, 아이보리색 분말 (20.7 mg, 17.3%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.51 (s, 1H), 8.34-8.40 (m, 2H), 8.14-8.15 (m, 1H), 7.93-7.94 (m, 1H), 7.13-7.14 (m, 1H) 4.42-4.50 (m, 2H), 1.80-1.89 (m, 2H), 1.67-1.71 (m, 1H), 1.49 (s, 3H), 1.02 (d, 3H), 1.06 (d, 3H). LC-MS (ESI+) m/z 343.4 [(M+H)+, calcd. C19H23FN4O m/z 342.1].This compound was prepared using ( S )-1-((5-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 36, Part B) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (189.1 mg, 0.52 mmol) and an ivory powder (20.7 mg, 17.3%) was obtained. 1H NMR (500 MHz, MeOD) δ 8.51 (s, 1H), 8.34-8.40 (m, 2H), 8.14-8.15 (m, 1H), 7.93-7.94 (m, 1H), 7.13-7.14 (m, 1H) 4.42-4.50 (m, 2H), 1.80-1.89 (m, 2H), 1.67-1.71 (m, 1H), 1.49 (s, 3H), 1.02 (d, 3H), 1.06 (d, 3H). LC-MS (ESI+) m/z 343.4 [(M+H) + , calcd. C 19 H 23 FN 4 O m/z 342.1].

실시예 37: (Example 37: ( SS )-1-((3-(1)-1-((3-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((3-(1)-1-((3-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 37을 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 37 was prepared according to a procedure similar to that described for Example 13.

B 파트: Part B: (S)-1-((3-브로모피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((3-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-2-아미노-2,4-다이메틸펜탄-1-올 (246.0 mg, 1.88 mmol) 및 3-브로모-2-플루오로피리딘 (300.0 mg, 1.70 mmol)을 사용하여 제조하였고, 연한-황색 액체 (267.8 mg, 54.7%)를 얻었다. LC-MS (ESI+) m/z 287.2 [(M+H)+, calcd. C12H19BrN2O m/z 286.0].This compound was prepared using ( S )-2-amino-2,4-dimethylpentan-1-ol (246.0 mg, 1.88 mmol) and 3-bromo-2-fluoropyridine (300.0 mg, 1.70 mmol) and a pale-yellow liquid (267.8 mg, 54.7%) was obtained. LC-MS (ESI+) m/z 287.2 [(M+H) + , calcd. C 12 H 19 BrN 2 O m/z 286.0].

C 파트: Part C: (S)-1-((3-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((3-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((3-브로모피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.35 mmol) (실시예 37, B 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (179.7 mg, 0.52 mmol)를 사용하여 제조하였고, 아이보리색 분말 (21.5 mg, 19.0%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.25 (d, 1H), 8.10-8.15 (m, 2H), 7.97-7.98 (m, 1H), 7.77 (s, 1H), 7.13-7.19 (m, 2H), 4.46-4.61 (m, 2H), 1.76-1.78 (m, 1H), 1.66-1.70 (m, 1H), 1.51-1.55 (m, 1H), 1.38 (s, 3H), 0.92 (d, 3H), 0.87 (d, 3H). LC-MS (ESI+) m/z 325.4 [(M+H)+, calcd. C19H24N4O m/z 324.1].This compound was prepared using ( S )-1-((3-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 37, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) and an ivory powder (21.5 mg, 19.0%) was obtained. 1H NMR (500 MHz, MeOD) δ 8.25 (d, 1H), 8.10-8.15 (m, 2H), 7.97-7.98 (m, 1H), 7.77 (s, 1H), 7.13-7.19 (m, 2H), 4.46-4.61 (m, 2H), 1.76-1.78 (m, 1H), 1.66-1.70 (m, 1H), 1.51-1.55 (m, 1H), 1.38 (s, 3H), 0.92 (d, 3H), 0.87 (d, 3H). LC-MS (ESI+) m/z 325.4 [(M+H) + , calcd. C 19 H 24 N 4 O m/z 324.1].

실시예 38: (Example 38: ( SS )-1-((4-(1)-1-((4-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((4-(1)-1-((4-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 38을 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 38 was prepared according to a procedure similar to that described for Example 13.

B 파트Part B : (S)-1-((4-브로모피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민: (S)-1-((4-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-2-아미노-2,4-다이메틸펜탄-1-올 (246.0 mg, 1.88 mmol) 및 4-브로모-2-플루오로피리딘 (300.0 mg, 1.70 mmol)을 사용하여 제조하였고, 연한-황색 액체 (360.2 mg, 73.5%)를 얻었다. LC-MS (ESI+) m/z 287.1 [(M+H)+, calcd. C12H19BrN2O m/z 286.0].This compound was prepared using ( S )-2-amino-2,4-dimethylpentan-1-ol (246.0 mg, 1.88 mmol) and 4-bromo-2-fluoropyridine (300.0 mg, 1.70 mmol) and a pale-yellow liquid (360.2 mg, 73.5%) was obtained. LC-MS (ESI+) m/z 287.1 [(M+H) + , calcd. C 12 H 19 BrN 2 O m/z 286.0].

C 파트:Part C: (S)-1-((4-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((4-브로모피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.35 mmol) (실시예 38, B 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (179.7 mg, 0.52 mmol)를 사용하여 제조하였고, 아이보리색 분말 (28.6 mg, 25.3%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.42 (d, 1H), 8.30 (d, 1H), 8.17 (d, 1H), 7.97 (s, 1H), 7.41 (d, 1H), 7.25-7.27 (m, 2H), 4.37-4.46 (m, 2H), 1.81-1.90 (m, 2H), 1.67-1.71 (m, 1H), 1.49 (s, 3H), 1.06 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+) m/z 000.0 [(M+H)+, calcd. C19H24N4O m/z 324.1].This compound was prepared using ( S )-1-((4-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 38, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) and an ivory powder (28.6 mg, 25.3%) was obtained. 1H NMR (500 MHz, MeOD) δ 8.42 (d, 1H), 8.30 (d, 1H), 8.17 (d, 1H), 7.97 (s, 1H), 7.41 (d, 1H), 7.25-7.27 (m, 2H), 4.37-4.46 (m, 2H), 1.81-1.90 (m, 2H), 1.67-1.71 (m, 1H), 1.49 (s, 3H), 1.06 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+) m/z 000.0 [(M+H) + , calcd. C 19 H 24 N 4 O m/z 324.1].

실시예 39: (Example 39: ( SS )-1-((6-(1)-1-((6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((6-(1)-1-((6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 39를 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 39 was prepared according to a procedure similar to that described for Example 13.

B 파트: Part B: (S)-1-((6-브로모피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((6-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-2-아미노-2,4-다이메틸펜탄-1-올 (246.0 mg, 1.88 mmol) 및 2-브로모-6-플루오로피리딘 (300.0 mg, 1.70 mmol)을 사용하여 제조하였고, 연한-황색 액체 (282.3 mg, 57.6%)를 얻었다. LC-MS (ESI+) m/z 287.1 [(M+H)+, calcd. C12H19BrN2O m/z 286.0].This compound was prepared using ( S )-2-amino-2,4-dimethylpentan-1-ol (246.0 mg, 1.88 mmol) and 2-bromo-6-fluoropyridine (300.0 mg, 1.70 mmol) and a pale-yellow liquid (282.3 mg, 57.6%) was obtained. LC-MS (ESI+) m/z 287.1 [(M+H) + , calcd. C 12 H 19 BrN 2 O m/z 286.0].

C 파트: Part C: (S)-1-((6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((6-브로모피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.35 mmol) (실시예 39, B 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (179.7 mg, 0.52 mmol)를 사용하여 제조하였고, 아이보리색 분말 (20.7 mg, 18.3%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.86 (d, 1H), 8.30 (d, 1H), 8.09 (s, 1H), 7.76 (t, 1H), 7.50 (d, 1H), 7.24-7.27 (m, 1H), 6.77 (d, 1H), 4.54-4.63 (m, 2H), 1.85-1.96 (m, 2H), 1.73-1.77 (m, 1H), 1.56 (s, 3H), 1.11 (d, 3H), 1.08 (d, 3H). LC-MS (ESI+) m/z 000.0 [(M+H)+, calcd. C19H24N4O m/z 324.1].This compound was prepared using ( S )-1-((6-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 39, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) and an ivory powder (20.7 mg, 18.3%) was obtained. 1H NMR (500 MHz, MeOD) δ 8.86 (d, 1H), 8.30 (d, 1H), 8.09 (s, 1H), 7.76 (t, 1H), 7.50 (d, 1H), 7.24-7.27 (m, 1H), 6.77 (d, 1H), 4.54-4.63 (m, 2H), 1.85-1.96 (m, 2H), 1.73-1.77 (m, 1H), 1.56 (s, 3H), 1.11 (d, 3H), 1.08 (d, 3H). LC-MS (ESI+) m/z 000.0 [(M+H) + , calcd. C 19 H 24 N 4 O m/z 324.1].

실시예 40: (Example 40: ( SS )-1-((4-(1)-1-((4-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((4-(1)-1-((4-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 40을 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 40 was prepared according to a procedure similar to that described for Example 13.

B 파트: Part B: (S)-1-((4-브로모피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((4-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-2-아미노-2,4-다이메틸펜탄-1-올 (246.0 mg, 1.88 mmol) 및 4-브로모-3-플루오로피리딘 (300.0 mg, 1.70 mmol)를 사용하여 제조하였고, 연한-황색 액체 (246.4 mg, 50.3%)를 얻었다. LC-MS (ESI+) m/z 287.1 [(M+H)+, calcd. C12H19BrN2O m/z 286.0].This compound was prepared using ( S )-2-amino-2,4-dimethylpentan-1-ol (246.0 mg, 1.88 mmol) and 4-bromo-3-fluoropyridine (300.0 mg, 1.70 mmol) and a pale-yellow liquid (246.4 mg, 50.3%) was obtained. LC-MS (ESI+) m/z 287.1 [(M+H) + , calcd. C 12 H 19 BrN 2 O m/z 286.0].

C 파트: Part C: (S)-1-((4-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((4-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((4-브로모피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.35 mmol) (실시예 40, B 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (179.7 mg, 0.52 mmol)를 사용하여 제조하였고, 아이보리색 분말 (25.9 mg, 22.9%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.90 (d, 2H), 8.61 (d, 1H), 8.58 (d, 1H), 8.52 (s, 1H), 8.34 (d, 1H), 7.68-7.70 (m, 1H), 4.46-4.53 (m, 2H), 1.73-1.81 (m, 2H), 1.46-1.66 (m, 1H), 1.46 (s, 3H), 0.96 (d, 3H), 0.88 (d, 3H). LC-MS (ESI+) m/z 325.4 [(M+H)+, calcd. C19H24N4O m/z 324.1].This compound was prepared using ( S )-1-((4-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 40, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) and an ivory powder (25.9 mg, 22.9%) was obtained. 1H NMR (500 MHz, MeOD) δ 8.90 (d, 2H), 8.61 (d, 1H), 8.58 (d, 1H), 8.52 (s, 1H), 8.34 (d, 1H), 7.68-7.70 (m, 1H), 4.46-4.53 (m, 2H), 1.73-1.81 (m, 2H), 1.46-1.66 (m, 1H), 1.46 (s, 3H), 0.96 (d, 3H), 0.88 (d, 3H). LC-MS (ESI+) m/z 325.4 [(M+H) + , calcd. C 19 H 24 N 4 O m/z 324.1].

실시예 41: (Example 41: ( SS )-1-((5-(1)-1-((5-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((5-(1)-1-((5-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 41을 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 41 was prepared according to a procedure similar to that described for Example 13.

B 파트: Part B: (S)-1-((5-브로모피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((5-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-2-아미노-2,4-다이메틸펜탄-1-올 (246.0 mg, 1.88 mmol) 및 3-브로모-5-플루오로피리딘 (300.0 mg, 1.70 mmol)을 사용하여 제조하였고, 연한-황색 액체 (324.1 mg, 66.2%)를 얻었다. LC-MS (ESI+) m/z 287.3 [(M+H)+, calcd. C12H19BrN2O m/z 286.0].This compound was prepared using ( S )-2-amino-2,4-dimethylpentan-1-ol (246.0 mg, 1.88 mmol) and 3-bromo-5-fluoropyridine (300.0 mg, 1.70 mmol) and a pale-yellow liquid (324.1 mg, 66.2%) was obtained. LC-MS (ESI+) m/z 287.3 [(M+H) + , calcd. C 12 H 19 BrN 2 O m/z 286.0].

C 파트: Part C: (S)-1-((5-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((5-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((5-브로모피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.35 mmol) (실시예 41, B 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (179.7 mg, 0.52 mmol)를 사용하여 제조하였고, 아이보리색 분말 (19.7 mg, 17.4%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.05 (d, 1H), 8.95 (s, 1H), 8.65 (d, 2H), 8.54 (d, 1H), 8.43 (s, 1H), 7.69 (t, 1H), 4.45-4.52 (m, 2H), 1.83-1.92 (m, 2H), 1.71-1.75 (m, 1H), 1.53 (s, 3H), 1.05 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+) m/z 000.0 [(M+H)+, calcd. C19H24N4O m/z 324.1].This compound was prepared using ( S )-1-((5-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 41, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) and an ivory powder (19.7 mg, 17.4%) was obtained. 1H NMR (500 MHz, MeOD) δ 9.05 (d, 1H), 8.95 (s, 1H), 8.65 (d, 2H), 8.54 (d, 1H), 8.43 (s, 1H), 7.69 (t, 1H), 4.45-4.52 (m, 2H), 1.83-1.92 (m, 2H), 1.71-1.75 (m, 1H), 1.53 (s, 3H), 1.05 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+) m/z 000.0 [(M+H) + , calcd. C 19 H 24 N 4 O m/z 324.1].

실시예 42: (Example 42: ( SS )-1-((3-(1)-1-((3-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-4-일)옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-3-yl)pyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((3-(1)-1-((3-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-3-yl)pyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 42를 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 42 was prepared according to a procedure similar to that described for Example 13.

B 파트: Part B: (S)-1-((3-브로모피리딘-4-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((3-bromopyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-2-아미노-2,4-다이메틸펜탄-1-올 (246.0 mg, 1.88 mmol) 및 3-브로모-4-플루오로피리딘 (300.0 mg, 1.70 mmol)을 사용하여 제조하였고, 연한-황색 액체 (283.3 mg, 57.6%)를 얻었다. LC-MS (ESI+) m/z 287.3 [(M+H)+, calcd. C12H19BrN2O m/z 286.0].This compound was prepared using ( S )-2-amino-2,4-dimethylpentan-1-ol (246.0 mg, 1.88 mmol) and 3-bromo-4-fluoropyridine (300.0 mg, 1.70 mmol) and a pale-yellow liquid (283.3 mg, 57.6%) was obtained. LC-MS (ESI+) m/z 287.3 [(M+H) + , calcd. C 12 H 19 BrN 2 O m/z 286.0].

C 파트: Part C: (S)-1-((3-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-4-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((3-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((3-브로모피리딘-4-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.35 mmol) (실시예 42, B 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (179.7 mg, 0.52 mmol)를 사용하여 제조하였고, 아이보리색 분말 (18.6 mg, 16.4%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.92 (s, 1H), 8.83 (d, 1H), 8.70 (d, 1H), 8.54 (d, 1H), 8.15 (s, 1H), 7.92 (d, 1H), 7.60-7.63 (m, 1H), 4.57-4.63 (m, 2H), 1.75-1.78 (m, 1H), 1.52-1.65 (m, 2H), 1.37 (s, 3H), 0.92 (d, 3H), 0.90 (d, 3H). LC-MS (ESI+) m/z 000.0 [(M+H)+, calcd. C19H24N4O m/z 324.1].This compound was prepared using ( S )-1-((3-bromopyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 42, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) and an ivory powder (18.6 mg, 16.4%) was obtained. 1H NMR (500 MHz, MeOD) δ 8.92 (s, 1H), 8.83 (d, 1H), 8.70 (d, 1H), 8.54 (d, 1H), 8.15 (s, 1H), 7.92 (d, 1H), 7.60-7.63 (m, 1H), 4.57-4.63 (m, 2H), 1.75-1.78 (m, 1H), 1.52-1.65 (m, 2H), 1.37 (s, 3H), 0.92 (d, 3H), 0.90 (d, 3H). LC-MS (ESI+) m/z 000.0 [(M+H) + , calcd. C 19 H 24 N 4 O m/z 324.1].

실시예 43: (Example 43: ( SS )-1-((2-(1)-1-((2-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-4-일)옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-3-yl)pyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((2-(1)-1-((2-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-3-yl)pyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 43을 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 43 was prepared according to a procedure similar to that described for Example 13.

B 파트: Part B: (S)-1-((2-브로모피리딘-4-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((2-bromopyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-2-아미노-2,4-다이메틸펜탄-1-올 (246.0 mg, 1.88 mmol) 및 2-브로모-4-플루오로피리딘 (300.0 mg, 1.70 mmol)를 사용하여 제조하였고, 연한-황색 액체 (292.1 mg, 59.6%)를 얻었다. LC-MS (ESI+) m/z 287.3 [(M+H)+, calcd. C12H19BrN2O m/z 286.0].This compound was prepared using ( S )-2-amino-2,4-dimethylpentan-1-ol (246.0 mg, 1.88 mmol) and 2-bromo-4-fluoropyridine (300.0 mg, 1.70 mmol) and a pale-yellow liquid (292.1 mg, 59.6%) was obtained. LC-MS (ESI+) m/z 287.3 [(M+H) + , calcd. C 12 H 19 BrN 2 O m/z 286.0].

C 파트: Part C: (S)-1-((2-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-4-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((2-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((2-브로모피리딘-4-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.35 mmol) (실시예 43, B 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (179.7 mg, 0.52 mmol)를 사용하여 제조하였고, 아이보리색 분말 (19.8 mg, 17.5%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.85 (d, 1H), 8.64 (d, 1H), 8.53 (d, 1H), 8.47 (s, 1H), 7.89 (s, 1H), 7.49-7.61 (m, 2H), 4.52-4.60 (m, 2H), 1.82-1.89 (m, 2H), 1.71-1.74 (m, 1H), 1.53 (s, 3H), 1.05 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+) m/z 325.3 [(M+H)+, calcd. C19H24N4O m/z 324.1].This compound was prepared using ( S )-1-((2-bromopyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 43, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) and an ivory powder (19.8 mg, 17.5%) was obtained. 1H NMR (500 MHz, MeOD) δ 8.85 (d, 1H), 8.64 (d, 1H), 8.53 (d, 1H), 8.47 (s, 1H), 7.89 (s, 1H), 7.49-7.61 (m, 2H), 4.52-4.60 (m, 2H), 1.82-1.89 (m, 2H), 1.71-1.74 (m, 1H), 1.53 (s, 3H), 1.05 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+) m/z 325.3 [(M+H) + , calcd. C 19 H 24 N 4 O m/z 324.1].

실시예 44: (Example 44: ( SS )-1-((2-(1)-1-((2-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((2-(1)-1-((2-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 44를 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 44 was prepared according to a procedure similar to that described for Example 13.

B 파트: Part B: (S)-1-((2-브로모피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((2-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-2-아미노-2,4-다이메틸펜탄-1-올 (246.0 mg, 1.88 mmol) 및 2-브로모-3-플루오로피리딘 (300.0 mg, 1.70 mmol)을 사용하여 제조하였고, 연한-황색 액체 (197.5 g, 40.3%)를 얻었다. LC-MS (ESI+) m/z 287.1 [(M+H)+, calcd. C12H19BrN2O m/z 286.0].This compound was prepared using ( S )-2-amino-2,4-dimethylpentan-1-ol (246.0 mg, 1.88 mmol) and 2-bromo-3-fluoropyridine (300.0 mg, 1.70 mmol) to obtain a pale-yellow liquid (197.5 g, 40.3%). LC-MS (ESI+) m/z 287.1 [(M+H) + , calcd. C 12 H 19 BrN 2 O m/z 286.0].

C 파트: Part C: (S)-1-((2-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민(S)-1-((2-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-((2-브로모피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.35 mmol) (실시예 44, B 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (179.7 mg, 0.52 mmol)를 사용하여 제조하였고, 아이보리색 분말 (21.6 mg, 19.1%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.79 (d, 1H), 8.48-8.53 (m, 2H), 8.41 (d, 1H), 8.33 (t, 1H), 7.86-7.89 (m, 1H), 7.57-7.60 (m, 1H), 4.37-4.43 (m, 2H), 1.65-1.77 (m, 2H), 1.55-1.59 (m, 1H), 1.40 (s, 3H), 0.92 (d, 3H), 0.85 (d, 3H). LC-MS (ESI+) m/z 325.3[(M+H)+, calcd. C19H24N4O m/z 324.1].This compound was prepared using ( S )-1-((2-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 44, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (179.7 mg, 0.52 mmol) and an ivory powder (21.6 mg, 19.1%) was obtained. 1H NMR (500 MHz, MeOD) δ 8.79 (d, 1H), 8.48-8.53 (m, 2H), 8.41 (d, 1H), 8.33 (t, 1H), 7.86-7.89 (m, 1H), 7.57-7.60 (m, 1H), 4.37-4.43 (m, 2H), 1.65-1.77 (m, 2H), 1.55-1.59 (m, 1H), 1.40 (s, 3H), 0.92 (d, 3H), 0.85 (d, 3H). LC-MS (ESI+) m/z 325.3[(M+H) + , calcd. C 19 H 24 N 4 O m/z 324.1].

실시예 45: 1-((2-(다이플루오로메틸)-6-(1Example 45: 1-((2-(difluoromethyl)-6-(1 HH -피라졸-4-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민 [1-((2-(difluoromethyl)-6-(1-pyrazol-4-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((2-(difluoromethyl)-6-(1 HH -pyrazol-4-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]-pyrazol-4-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]

실시예 45를 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 45 was prepared according to a procedure similar to that described for Example 13.

B 파트: Part B: 1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-2-메틸프로판-2-아민1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine

이 화합물은 2-아미노-2-메틸프로판-1-올 (0.4 g, 4.87 mmol) 및 6-브로모-2-(다이플루오로메틸)-3-플루오로피리딘 (1.0 g, 4.42 mmol) (실시예 13, A 파트)을 사용하여 제조하였고, 투명한 액체 (0.8 g, 61.2%)를 얻었다. LC-MS (ESI+) m/z 295.4 [(M+H)+, calcd. C10H13BrF2N2O m/z 294.0].This compound was prepared using 2-amino-2-methylpropan-1-ol (0.4 g, 4.87 mmol) and 6-bromo-2-(difluoromethyl)-3-fluoropyridine (1.0 g, 4.42 mmol) (Example 13, Part A) and a clear liquid (0.8 g, 61.2%) was obtained. LC-MS (ESI+) m/z 295.4 [(M+H) + , calcd. C 10 H 13 BrF 2 N 2 O m/z 294.0].

C 파트: Part C: 1-((2-(다이플루오로메틸)-6-(1H-피라졸-4-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민1-((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine

이 화합물은 1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-2-메틸프로판-2-아민 (100.0 mg, 0.34 mmol) (실시예 45, B 파트) 및 tert-부틸 4-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피라졸-1-카복실레이트 (149.5 mg, 0.51 mmol)를 사용하여 제조하였고, 아이보리색 분말 (62.2 mg, 65.0%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.53 (s, 2H), 7.93 (d, 1H), 7.74 (d, 1H), 7.03-7.24 (m, 1H), 4.20 (s, 2H), 1.52 (s, 6H). LC-MS (ESI+) m/z 283.4 [(M+H)+, calcd. C13H16F2N4O m/z 282.1].This compound was prepared using 1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine (100.0 mg, 0.34 mmol) (Example 45, Part B) and tert -butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole-1-carboxylate (149.5 mg, 0.51 mmol) to obtain an ivory powder (62.2 mg, 65.0%). 1H NMR (500 MHz, MeOD) δ 8.53 (s, 2H), 7.93 (d, 1H), 7.74 (d, 1H), 7.03-7.24 (m, 1H), 4.20 (s, 2H), 1.52 (s, 6H). LC-MS (ESI+) m/z 283.4 [(M+H)+, calcd. C 13 H 16 F 2 N 4 O m/z 282.1].

실시예 46: 1-((2-(다이플루오로메틸)-6-(1Example 46: 1-((2-(difluoromethyl)-6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민 [1-((2-(difluoromethyl)-6-(1]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((2-(difluoromethyl)-6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]

실시예 46을 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 46 was prepared according to a procedure similar to that described for Example 13.

C 파트: Part C: 1-((2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine

이 화합물은 1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-2-메틸프로판-2-아민 (100.0 mg, 0.34 mmol) (실시예 45, B 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (174.9 mg, 0.51 mmol)를 사용하여 제조하였고, 아이보리색 분말 (25.8 mg, 26.9%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.87 (d, 1H), 8.20 (d, 1H), 7.96 (s, 1H), 7.88 (d, 1H), 7.57 (d, 1H), 6.94-7.19 (m, 2H), 3.96 (s, 2H), 1.33 (s, 6H). LC-MS (ESI+) m/z 332.4 [(M+H)+, calcd. C17H18F2N4O m/z 332.1].This compound was prepared using 1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine (100.0 mg, 0.34 mmol) (Example 45, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (174.9 mg, 0.51 mmol) and an ivory powder (25.8 mg, 26.9%) was obtained. 1H NMR (500 MHz, MeOD) δ 8.87 (d, 1H), 8.20 (d, 1H), 7.96 (s, 1H), 7.88 (d, 1H), 7.57 (d, 1H), 6.94-7.19 (m, 2H), 3.96 (s, 2H), 1.33 (s, 6H). LC-MS (ESI+) m/z 332.4 [(M+H) + , calcd. C17H18F2N4O m/z 332.1].

실시예 47: 1-((2-(다이플루오로메틸)-6-(5-플루오로-1Example 47: 1-((2-(difluoromethyl)-6-(5-fluoro-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민 [1-((2-(difluoromethyl)-6-(5-fluoro-1]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((2-(difluoromethyl)-6-(5-fluoro-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]

실시예 47을 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 47 was prepared according to a procedure similar to that described for Example 13.

C 파트: Part C: 1-((2-(다이플루오로메틸)-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민1-((2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine

이 화합물은 1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-2-메틸프로판-2-아민 (100.0 mg, 0.34 mmol) (실시예 45, B 파트) 및 tert-부틸 5-플루오로-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (184.0 mg, 0.51 mmol)를 사용하여 제조하였고, 연한-황색 분말 (49.1 mg, 41.3%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.16-9.18 (m, 1H), 8.49-8.50 (m, 1H), 8.33 (s, 1H), 8.03 (d, 1H), 7.73 (d, 1H), 7.13-7.34 (m, 1H), 4.19 (s, 2H), 1.51 (s, 6H). LC-MS (ESI+) m/z 351.5 [(M+H)+, calcd. C17H17F3N4O m/z 350.1].This compound was prepared using 1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine (100.0 mg, 0.34 mmol) (Example 45, Part B) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (184.0 mg, 0.51 mmol) to obtain a pale-yellow powder (49.1 mg, 41.3%). 1H NMR (500 MHz, MeOD) δ 9.16-9.18 (m, 1H), 8.49-8.50 (m, 1H), 8.33 (s, 1H), 8.03 (d, 1H), 7.73 (d, 1H), 7.13-7.34 (m, 1H), 4.19 (s, 2H), 1.51 (s, 6H). LC-MS (ESI+) m/z 351.5 [(M+H) + , calcd. C 17 H 17 F 3 N 4 O m/z 350.1].

실시예 48: 1-((2-(다이플루오로메틸)-6-(1Example 48: 1-((2-(difluoromethyl)-6-(1 HH -피롤로[3,2--Pyrrolo[3,2- bb ]피리딘-1-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민 [1-((2-(difluoromethyl)-6-(1]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((2-(difluoromethyl)-6-(1 HH -pyrrolo[3,2--pyrrolo[3,2- bb ]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]

실시예 48은 1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-2-메틸프로판-2-아민 (100.0 mg, 0.34 mmol) (실시예 45, B 파트) 및 1H-피롤로[3,2-b]피리딘 (40.0 mg, 0.34 mmol)을 사용하여 실시예 10에 대하여 설명한 것과 유사한 절차에 따라 제조하였고, 회백색 분말 (16.9 mg, 15.0%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.52 (d, 1H), 8.69-8.73 (m, 2H), 7.99-8.06 (m, 2H), 7.82-7.85 (m, 1H), 7.18-7.39 (m, 1H), 7.13 (d, 1H), 4.26 (s, 2H), 1.15 (m, 6H). LC-MS (ESI+) m/z 333.4 [(M+H)+, calcd. C17H18F2N4O m/z 332.1].Example 48 was prepared according to a similar procedure as described for Example 10 using 1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine (100.0 mg, 0.34 mmol) (Example 45, Part B) and 1 H -pyrrolo[3,2- b ]pyridine (40.0 mg, 0.34 mmol) to obtain an off-white powder (16.9 mg, 15.0%). 1H NMR (500 MHz, MeOD) δ 9.52 (d, 1H), 8.69-8.73 (m, 2H), 7.99-8.06 (m, 2H), 7.82-7.85 (m, 1H), 7.18-7.39 (m, 1H), 7.13 (d, 1H), 4.26 (s, 2H), 1.15 (m, 6H). LC-MS (ESI+) m/z 333.4 [(M+H) + , calcd. C 17 H 18 F 2 N 4 O m/z 332.1].

실시예 49: 1-((6-(1Example 49: 1-((6-(1 HH -피라졸-4-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)-2-메틸프로판-2-아민 [1-((6-(1-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((6-(1 HH -pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]

실시예 49를 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 49 was prepared according to a procedure similar to that described for Example 13.

B 파트: Part B: tert-부틸 (1-((6-브로모-2-(트리플루오로메틸)피리딘-3-일)옥시)-2-메틸프로판-2-일)카바메이트tert-Butyl (1-((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-yl)carbamate

이 화합물은 2-아미노-2-메틸프로판-1-올 (0.4 g, 4.51 mmol) 및 6-브로모-3-플루오로-2-(트리플루오로메틸)피리딘 (1.0 g, 4.10 mmol)을 사용하여 제조하였고, 투명한 액체 (0.7 g, 54.7%)를 얻었다. LC-MS (ESI+) m/z 313.3 [(M+H)+, calcd. C10H12BrF3N2O m/z 312.0].This compound was prepared using 2-amino-2-methylpropan-1-ol (0.4 g, 4.51 mmol) and 6-bromo-3-fluoro-2-(trifluoromethyl)pyridine (1.0 g, 4.10 mmol) and a clear liquid (0.7 g, 54.7%) was obtained. LC-MS (ESI+) m/z 313.3 [(M+H) + , calcd. C 10 H 12 BrF 3 N 2 O m/z 312.0].

C 파트: Part C: 1-((6-(1H-피라졸-4-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)-2-메틸프로판-2-아민1-((6-(1H-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine

이 화합물은 1-((6-브로모-2-(트리플루오로메틸)피리딘-3-일)옥시)-2-메틸프로판-2-아민 (100.0 mg, 0.32 mmol) (실시예 49, B 파트) 및 tert-부틸 4-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피라졸-1-카복실레이트 (140.9 mg, 0.48 mmol)를 사용하여 제조하였고, 아이보리색 분말 (24.8 mg, 25.8%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.41 (s, 2H), 7.96 (d, 1H), 7.78 (d, 1H), 4.17 (s, 2H), 1.47 (s, 6H). LC-MS (ESI+) m/z 301.1 [(M+H)+, calcd. C13H15F3N4O m/z 300.1].This compound was prepared using 1-((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine (100.0 mg, 0.32 mmol) (Example 49, Part B) and tert -butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole-1-carboxylate (140.9 mg, 0.48 mmol) and an ivory powder (24.8 mg, 25.8%) was obtained. 1 H NMR (500 MHz, MeOD) δ 8.41 (s, 2H), 7.96 (d, 1H), 7.78 (d, 1H), 4.17 (s, 2H), 1.47 (s, 6H). LC-MS (ESI+) m/z 301.1 [(M+H) + , calcd. C 13 H 15 F 3 N 4 O m/z 300.1].

실시예 50: 1-((6-(1Example 50: 1-((6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)-2-메틸프로판-2-아민 [1-((6-(1]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]

실시예 50을 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 50 was prepared according to a procedure similar to that described for Example 13.

C 파트: Part C: 1-((6-(1H-피롤로[2,3-b]피리딘-3-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)-2-메틸프로판-2-아민1-((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine

이 화합물은 1-((6-브로모-2-(트리플루오로메틸)피리딘-3-일)옥시)-2-메틸프로판-2-아민 (100.0 mg, 0.32 mmol) (실시예 49, B 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (164.9 mg, 0.48 mmol)를 사용하여 제조하였고, 연한-황색 분말 (24.1 mg, 21.5%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.58 (d, 1H), 8.52 (d, 1H), 8.42 (s, 1H), 8.23 (d, 1H), 7.89 (d, 1H), 7.70-7.73 (m, 1H), 4.25 (s, 2H), 1.53 (s, 6H). LC-MS (ESI+) m/z 000.0 [(M+H)+, calcd. C17H17F3N4O m/z 350.1].This compound was prepared using 1-((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine (100.0 mg, 0.32 mmol) (Example 49, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (164.9 mg, 0.48 mmol) to obtain a pale-yellow powder (24.1 mg, 21.5%). 1H NMR (500 MHz, MeOD) δ 9.58 (d, 1H), 8.52 (d, 1H), 8.42 (s, 1H), 8.23 (d, 1H), 7.89 (d, 1H), 7.70-7.73 (m, 1H), 4.25 (s, 2H), 1.53 (s, 6H). LC-MS (ESI+) m/z 000.0 [(M+H) + , calcd. C 17 H 17 F 3 N 4 O m/z 350.1].

실시예 51: 2-((6-(5-클로로-1Example 51: 2-((6-(5-chloro-1 HH -피라졸로[3,4--Pyrazolo[3,4- bb ]피리딘-3-일)-2-(다이플루오로메틸)피리딘-3-일)옥시)에탄-1-올 [2-((6-(5-chloro-1]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-ol [2-((6-(5-chloro-1 HH -pyrazolo[3,4--pyrazolo[3,4- bb ]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-ol]]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-ol]

실시예 51을 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다.Example 51 was prepared according to a procedure similar to that described for Example 13.

B 파트: Part B: 2-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)에탄-1-올2-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-ol

이 화합물은 에탄-1,2-다이올 (151.0 mg, 2.43 mmol) 및 6-브로모-2-(다이플루오로메틸)-3-플루오로피리딘 (500.0 mg, 2.21 mmol) (실시예 13, A 파트)을 사용하여 제조하였고, 투명한 액체 (280.4 mg, 40.6%)를 얻었다. LC-MS (ESI+) m/z 267.0 [(M+H)+, calcd. C8H8BrF2NO2 m/z 266.9].This compound was prepared using ethane-1,2-diol (151.0 mg, 2.43 mmol) and 6-bromo-2-(difluoromethyl)-3-fluoropyridine (500.0 mg, 2.21 mmol) (Example 13, Part A) and a clear liquid (280.4 mg, 40.6%) was obtained. LC-MS (ESI+) m/z 267.0 [(M+H) + , calcd. C 8 H 8 BrF 2 NO 2 m/z 266.9].

실시예 51을 실시예 8에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 51 was prepared according to a procedure similar to that described for Example 8.

B 파트: Part B: 2-((6-(5-클로로-1H-피라졸로[3,4-b]피리딘-3-일)-2-(다이플루오로메틸)피리딘-3-일)옥시)에탄-1-올2-((6-(5-chloro-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-ol

이 화합물은 2-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)에탄-1-올 (100.0 mg, 0.37 mmol) (실시예 51, B 파트) 및 5-클로로-1-(테트라하이드로-2H-피란-2-일)-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피라졸로[3,4-b]피리딘 (203.4 mg, 0.56 mmol)을 사용하여 제조하였고, 황색 분말 (20.8 mg, 16.3%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.01 (d, 1H), 8.52 (d, 1H), 8.29 (d, 1H), 7.72 (d, 1H), 7.09-7.31 (m, 1H), 4.25-4.27 (m, 2H), 3.95-3.97 (m, 2H). LC-MS (ESI+) m/z 341.5 [(M+H)+, calcd. C14H11ClF2N4O2 m/z 340.0].This compound was prepared using 2-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-ol (100.0 mg, 0.37 mmol) (Example 51, Part B) and 5-chloro-1-(tetrahydro-2 H -pyran-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazolo[3,4- b ]pyridine (203.4 mg, 0.56 mmol) to obtain a yellow powder (20.8 mg, 16.3%). 1H NMR (500 MHz, MeOD) δ 9.01 (d, 1H), 8.52 (d, 1H), 8.29 (d, 1H), 7.72 (d, 1H), 7.09-7.31 (m, 1H), 4.25-4.27 (m, 2H), 3.95-3.97 (m, 2H). LC-MS (ESI+) m/z 341.5 [(M+H) + , calcd. C 14 H 11 ClF 2 N 4 O 2 m/z 340.0].

실시예 52: 2-((6-(5-클로로-1Example 52: 2-((6-(5-chloro-1 HH -피라졸로[3,4--Pyrazolo[3,4- bb ]피리딘-3-일)-2-(다이플루오로메틸)피리딘-3-일)옥시)에탄-1-아민 [2-((6-(5-chloro-1]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-amine [2-((6-(5-chloro-1 HH -pyrazolo[3,4--pyrazolo[3,4- bb ]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-amine]]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-amine]

실시예 52를 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 52 was prepared according to a procedure similar to that described for Example 13.

B 파트: Part B: 2-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)에탄-1-아민2-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-amine

이 화합물은 2-아미노에탄-1-올 (148.6 mg, 2.43 mmol) 및 6-브로모-2-(다이플루오로메틸)-3-플루오로피리딘 (500.0 mg, 2.21 mmol) (실시예 13, A 파트)을 사용하여 제조하였고, 투명한 액체 (325.4 mg, 55.0%)를 얻었다. LC-MS (ESI+) m/z 266.3 [(M+H)+, calcd. C8H9BrF2N2O m/z 265.9].This compound was prepared using 2-aminoethanol-1-ol (148.6 mg, 2.43 mmol) and 6-bromo-2-(difluoromethyl)-3-fluoropyridine (500.0 mg, 2.21 mmol) (Example 13, Part A) and a clear liquid (325.4 mg, 55.0%) was obtained. LC-MS (ESI+) m/z 266.3 [(M+H) + , calcd. C 8 H 9 BrF 2 N 2 O m/z 265.9].

실시예 52를 실시예 8에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 52 was prepared according to a procedure similar to that described for Example 8.

B 파트Part B : 2-((6-(5-클로로-1H-피라졸로[3,4-b]피리딘-3-일)-2-(다이플루오로메틸)피리딘-3-일)옥시)에탄-1-아민: 2-((6-(5-chloro-1H-pyrazolo[3,4-b]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-amine

이 화합물은 2-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)에탄-1-아민 (100.0 mg, 0.37 mmol) (실시예 52, B 파트) 및 5-클로로-1-(테트라하이드로-2H-피란-2-일)-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피라졸로[3,4-b]피리딘 (204.2 mg, 0.56 mmol)를 사용하여 제조하였고, 황색 분말 (33.6 mg, 26.4%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.97 (d, 1H), 8.51 (d, 1H), 8.32 (d, 1H), 7.76 (d, 1H), 7.14-7.35 (m, 1H), 4.43-4.45 (m, 2H), 3.47-3.49 (m, 2H). LC-MS (ESI+) m/z 340.3 [(M+H)+, calcd. C14H12ClF2N5O m/z 339.0].This compound was prepared using 2-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-amine (100.0 mg, 0.37 mmol) (Example 52, Part B) and 5-chloro-1-(tetrahydro-2 H -pyran-2-yl)-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazolo[3,4- b ]pyridine (204.2 mg, 0.56 mmol) and a yellow powder (33.6 mg, 26.4%) was obtained. 1H NMR (500 MHz, MeOD) δ 8.97 (d, 1H), 8.51 (d, 1H), 8.32 (d, 1H), 7.76 (d, 1H), 7.14-7.35 (m, 1H), 4.43-4.45 (m, 2H), 3.47-3.49 (m, 2H). LC-MS (ESI+) m/z 340.3 [(M+H) + , calcd. C 14 H 12 ClF 2 N 5 O m/z 339.0].

실시예 53: (Example 53: ( SS )-1-((4-(1)-1-((4-(1 HH -피롤로[3,2--Pyrrolo[3,2- bb ]피리딘-1-일)피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-1-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((4-(1)-1-((4-(1 HH -pyrrolo[3,2--pyrrolo[3,2- bb ]pyridin-1-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-1-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 53은 (S)-1-((4-브로모피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.35 mmol) (실시예 38, B 파트) 및 1H-피롤로[3,2-b]피리딘 (41.1 mg, 0.35 mmol)을 사용하여 실시예 10에 대하여 설명한 것과 유사한 절차에 따라 제조하였고, 연한-갈색 분말 (22.5 mg, 19.9%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.90 (d, 1H), 8.75 (d, 1H), 8.51 (d, 1H), 8.42 (d, 1H), 7.83-7.85 (m, 1H), 7.43 (d, 1H), 7.31 (s, 1H), 7.19 (d, 1H), 4.47-4.55 (m, 2H), 1.80-1.89 (m, 2H), 1.67-1.71 (m, 1H), 1.49 (s, 3H), 1.05 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+) m/z 325.5 [(M+H)+, calcd. C19H24N4O m/z 324.1].Example 53 was prepared according to a similar procedure as described for Example 10 using ( S )-1-((4-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 38, Part B) and 1 H -pyrrolo[3,2- b ]pyridine (41.1 mg, 0.35 mmol) to obtain a pale-brown powder (22.5 mg, 19.9%). 1H NMR (500 MHz, MeOD) δ 8.90 (d, 1H), 8.75 (d, 1H), 8.51 (d, 1H), 8.42 (d, 1H), 7.83-7.85 (m, 1H), 7.43 (d, 1H), 7.31 (s, 1H), 7.19 (d, 1H), 4.47-4.55 (m, 2H), 1.80-1.89 (m, 2H), 1.67-1.71 (m, 1H), 1.49 (s, 3H), 1.05 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+) m/z 325.5 [(M+H) + , calcd. C 19 H 24 N 4 O m/z 324.1].

실시예 54: (Example 54: ( SS )-1-((5-(1)-1-((5-(1 HH -피롤로[3,2--Pyrrolo[3,2- bb ]피리딘-1-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((5-(1)-1-((5-(1 HH -pyrrolo[3,2--pyrrolo[3,2- bb ]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 54는 (S)-1-((5-브로모피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.35 mmol) (실시예 41, B 파트) 및 1H-피롤로[3,2-b]피리딘 (41.1 mg, 0.35 mmol)을 사용하여 실시예 10에 대하여 설명한 것과 유사한 절차에 따라 제조하였고, 연한-갈색 분말 (19.7 mg, 17.4%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.74-8.77 (m, 2H), 8.61 (br, 2H), 8.47 (d, 1H), 7.93 (s, 1H), 7.81-7.83 (m, 1H), 7.19 (d, 1H), 4.26-4.35 (m, 2H), 1.82-1.89 (m, 2H), 1.69-1.73 (m, 1H), 1.51 (s, 3H), 1.07 (d, 3H), 1.03 (d, 3H). LC-MS (ESI+) m/z 325.4 [(M+H)+, calcd. C19H24N4O m/z 324.1].Example 54 was prepared according to a similar procedure as described for Example 10 using ( S )-1-((5-bromopyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 41, Part B) and 1 H -pyrrolo[3,2- b ]pyridine (41.1 mg, 0.35 mmol) to obtain a pale-brown powder (19.7 mg, 17.4%). 1H NMR (500 MHz, MeOD) δ 8.74-8.77 (m, 2H), 8.61 (br, 2H), 8.47 (d, 1H), 7.93 (s, 1H), 7.81-7.83 (m, 1H), 7.19 (d, 1H), 4.26-4.35 (m, 2H), 1.82-1.89 (m, 2H), 1.69-1.73 (m, 1H), 1.51 (s, 3H), 1.07 (d, 3H), 1.03 (d, 3H). LC-MS (ESI+) m/z 325.4 [(M+H) + , calcd. C 19 H 24 N 4 O m/z 324.1].

실시예 55: (Example 55: ( SS )-1-((5-(1)-1-((5-(1 HH -피롤로[3,2--Pyrrolo[3,2- bb ]피리딘-1-일)피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-1-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine [( SS )-1-((5-(1)-1-((5-(1 HH -pyrrolo[3,2--pyrrolo[3,2- bb ]pyridin-1-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine]]pyridin-1-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine]

실시예 55는 (S)-1-((5-브로모피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.35 mmol) (실시예 36, B 파트) 및 1H-피롤로[3,2-b]피리딘 (41.1 mg, 0.35 mmol)을 사용하여 실시예 10에 대하여 설명한 것과 유사한 절차에 따라 제조하였고, 연한-갈색 분말 (19.0 mg, 16.8%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.68 (d, 1H), 8.47-8.53 (m, 2H), 8.29 (d, 1H), 8.04-8.07 (m, 1H), 7.71-7.74 (m, 1H), 7.21 (d, 1H), 7.10 (d, 1H), 4.45-4.53 (m, 2H), 1.80-1.88 (m, 2H), 1.65-1.71 (m, 1H), 1.49 (s, 3H), 1.06 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+) m/z 325.1 [(M+H)+, calcd. C19H24N4O m/z 324.1].Example 55 was prepared according to a similar procedure as described for Example 10 using ( S ) -1-((5-bromopyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 36, Part B) and 1 H -pyrrolo[3,2- b ]pyridine (41.1 mg, 0.35 mmol) to obtain a pale-brown powder (19.0 mg, 16.8%). 1H NMR (500 MHz, MeOD) δ 8.68 (d, 1H), 8.47-8.53 (m, 2H), 8.29 (d, 1H), 8.04-8.07 (m, 1H), 7.71-7.74 (m, 1H), 7.21 (d, 1H), 7.10 (d, 1H), 4.45-4.53 (m, 2H), 1.80-1.88 (m, 2H), 1.65-1.71 (m, 1H), 1.49 (s, 3H), 1.06 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+) m/z 325.1 [(M+H) + , calcd. C 19 H 24 N 4 O m/z 324.1].

실시예 56: (Example 56: ( SS )-1-(4-(1)-1-(4-(1 HH -피롤로[3,2--Pyrrolo[3,2- bb ]피리딘-1-일)펜옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-1-yl)phenoxy)-2,4-dimethylpentan-2-amine [( SS )-1-(4-(1)-1-(4-(1 HH -pyrrolo[3,2--pyrrolo[3,2- bb ]pyridin-1-yl)phenoxy)-2,4-dimethylpentan-2-amine]]pyridin-1-yl)phenoxy)-2,4-dimethylpentan-2-amine]

실시예 56은 (S)-1-(4-브로모-2-(다이플루오로메틸)펜옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.35 mmol) (실시예 22, B 파트) 및 1H-피롤로[3,2-b]피리딘 (41.2 mg, 0.35 mmol)을 사용하여 실시예 10에 대하여 설명한 것과 유사한 절차에 따라 제조하였고, 아이보리색 분말 (20.5 mg, 18.1%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.65 (d, 1H), 8.58 (d, 1H), 8.32 (d, 1H), 7.74-7.77 (m, 1H), 7.63 (d, 2H), 7.33 (d, 2H), 7.10 (d, 1H), 4.13-4.24 (m, 2H), 1.85-1.91 (m, 2H), 1.69-1.73 (m, 1H), 1.52 (s, 3H), 1.07 (d, 3H), 1.03 (d, 3H). LC-MS (ESI+) m/z 324.2 [(M+H)+, calcd. C20H25N3O m/z 323.1].Example 56 was prepared according to a similar procedure as described for Example 10 using ( S )-1-(4-bromo-2-(difluoromethyl)phenoxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.35 mmol) (Example 22, Part B) and 1 H -pyrrolo[3,2- b ]pyridine (41.2 mg, 0.35 mmol) to obtain an ivory powder (20.5 mg, 18.1%). 1H NMR (500 MHz, MeOD) δ 8.65 (d, 1H), 8.58 (d, 1H), 8.32 (d, 1H), 7.74-7.77 (m, 1H), 7.63 (d, 2H), 7.33 (d, 2H), 7.10 (d, 1H), 4.13-4.24 (m, 2H), 1.85-1.91 (m, 2H), 1.69-1.73 (m, 1H), 1.52 (s, 3H), 1.07 (d, 3H), 1.03 (d, 3H). LC-MS (ESI+) m/z 324.2 [(M+H) + , calcd. C 20 H 25 N 3 O m/z 323.1].

실시예 57: (Example 57: ( SS )-1-((2-(다이플루오로메틸)-6-(5-플루오로-1)-1-((2-(difluoromethyl)-6-(5-fluoro-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민 [(]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [( SS )-1-((2-(difluoromethyl)-6-(5-fluoro-1)-1-((2-(difluoromethyl)-6-(5-fluoro-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

실시예 57을 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 57 was prepared according to a procedure similar to that described for Example 13.

B 파트: Part B: terttert -부틸 (S)-(1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-4-메틸펜탄-2-일)카바메이트-Butyl (S)-(1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate

이 화합물은 tert-부틸 (S)-(1-하이드록시-4-메틸펜탄-2-일)카바메이트 (1.1 g, 4.87 mmol) 및 6-브로모-2-(다이플루오로메틸)-3-플루오로피리딘 (1.0 g, 4.42 mmol) (실시예 13, A 파트)을 사용하여 제조하였고, 회백색 분말 (1.1 g, 61.1%)을 얻었다. LC-MS (ESI+) m/z 423.3 [(M+H)+, calcd. C17H25BrF2N2O3 m/z 422.1].This compound was prepared using tert -butyl ( S )-(1-hydroxy-4-methylpentan-2-yl)carbamate (1.1 g, 4.87 mmol) and 6-bromo-2-(difluoromethyl)-3-fluoropyridine (1.0 g, 4.42 mmol) (Example 13, Part A) and an off-white powder (1.1 g, 61.1%) was obtained. LC-MS (ESI+) m/z 423.3 [(M+H) + , calcd. C 17 H 25 BrF 2 N 2 O 3 m/z 422.1].

C 파트: Part C: (S)-1-((2-(다이플루오로메틸)-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민(S)-1-((2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine

이 화합물은 tert-부틸 (S)-(1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-4-메틸펜탄-2-일)카바메이트 (100.0 mg, 0.24 mmol) 및 tert-부틸 5-플루오로-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (128.3 mg, 0.35 mmol) (실시예 57, B 파트)를 사용하여 중간체로 제조하였다. 정제 후 염산 (1.0 M EtOAc 용액, 10 mL)을 첨가하고, tert-부톡시 카르보닐기의 탈보호를 위해 실온에서 교반하였다. 반응 진행은 HPLC로 모니터링하였다. 반응이 완료된 후, 생성물을 EtOAc 및 10% NaOH 용액 (aq.)으로 추출하였다. 분리된 유기층을 물과 염수로 세척하고 황산마그네슘으로 건조시킨 후 농축하였다. 잔류물을 n-헥산으로 세척하여 연한-황색 분말 (28.7 mg, 32.1%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.42-8.24 (m, 2H), 8.13 (s, 1H), 7.72 (s, 1H), 7.64 (d, 1H), 7.49-7.52 (m, 1H), 4.24-4.14 (m, 1H), 4.13-4.07 (m, 1H), 3.52-3.43 (m, 1H), 1.81-1.84 (m, 1H), 1.52-1.63 (m, 2H), 1.05 (t, 6H). LC-MS (ESI+) m/z 379.3 [(M+H)+, calcd. C19H21F3N4O m/z 378.1].This compound was prepared as an intermediate using tert -butyl ( S )-(1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (128.3 mg, 0.35 mmol) (Example 57, Part B). After purification, hydrochloric acid (1.0 M EtOAc solution, 10 mL) was added and stirred at room temperature for deprotection of the tert -butoxy carbonyl group. The reaction progress was monitored by HPLC. After the reaction was completed, the product was extracted with EtOAc and 10% NaOH solution (aq.). The separated organic layer was washed with water and brine, dried over magnesium sulfate, and concentrated. The residue was washed with n -hexane to obtain a pale-yellow powder (28.7 mg, 32.1%). 1H NMR (500 MHz, MeOD) δ 8.42-8.24 (m, 2H), 8.13 (s, 1H), 7.72 (s, 1H), 7.64 (d, 1H), 7.49-7.52 (m, 1H), 4.24-4.14 (m, 1H), 4.13-4.07 (m, 1H), 3.52-3.43 (m, 1H), 1.81-1.84 (m, 1H), 1.52-1.63 (m, 2H), 1.05 (t, 6H). LC-MS (ESI+) m/z 379.3 [(M+H) + , calcd. C 19 H 21 F 3 N 4 O m/z 378.1].

실시예 58: (Example 58: ( SS )-1-((2-(다이플루오로메틸)-6-(1)-1-((2-(difluoromethyl)-6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민 [(]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [( SS )-1-((2-(difluoromethyl)-6-(1)-1-((2-(difluoromethyl)-6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

실시예 58을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 58 was prepared according to a procedure similar to that described for Example 57.

C 파트Part C : (S)-1-((2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민: (S)-1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine

이 화합물은 tert-부틸 (S)-(1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-4-메틸펜탄-2-일)카바메이트 (100.0 mg, 0.24 mmol) (실시예 57, B 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (121.9 mg, 0.35 mmol)를 사용하여 제조하였고, 아이보리색 분말 (20.8 mg, 24.4%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.88-8.90 (m, 1H), 8.22 (d, 1H), 7.97 (s, 1H), 7.89 (d, 1H), 7.59 (d, 1H), 7.15-7.22 (m, 1H), 6.94-7.15 (m, 1H), 4.12-4.15 (m, 1H), 3.91-3.94 (m, 1H), 1.80-1.83 (m, 1H), 1.40-1.47 (m, 2H), 1.28-1.31 (m, 1H), 0.97-1.00 (m, 6H). LC-MS (ESI+) m/z 361.3 [(M+H)+, calcd. C19H22F2N4O m/z 360.1].This compound was prepared using tert -butyl ( S )-(1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 57, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (121.9 mg, 0.35 mmol) to obtain an ivory powder (20.8 mg, 24.4%). 1H NMR (500 MHz, MeOD) δ 8.88-8.90 (m, 1H), 8.22 (d, 1H), 7.97 (s, 1H), 7.89 (d, 1H), 7.59 (d, 1H), 7.15-7.22 (m, 1H), 6.94-7.15 (m, 1H), 4.12-4.15 (m, 1H), 3.91-3.94 (m, 1H), 1.80-1.83 (m, 1H), 1.40-1.47 (m, 2H), 1.28-1.31 (m, 1H), 0.97-1.00 (m, 6H). LC-MS (ESI+) m/z 361.3 [(M+H) + , calcd. C 19 H 22 F 2 N 4 O m/z 360.1].

실시예 59: (Example 59: ( SS )-1-((2-(다이플루오로메틸)-6-(4-메톡시-1)-1-((2-(difluoromethyl)-6-(4-methoxy-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민 [(]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [( SS )-1-((2-(difluoromethyl)-6-(4-methoxy-1)-1-((2-(difluoromethyl)-6-(4-methoxy-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

실시예 59를 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 59 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: (S)-1-((2-(다이플루오로메틸)-6-(4-메톡시-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민(S)-1-((2-(difluoromethyl)-6-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine

이 화합물은 tert-부틸 (S)-(1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-4-메틸펜탄-2-일)카바메이트 (100.0 mg, 0.24 mmol) (실시예 57, B 파트) 및 tert-부틸 4-메톡시-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (132.6 mg, 0.35 mmol)를 사용하여 제조하였고, 아이보리색 분말 (19.5 mg, 21.1%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.12 (d, 1H), 8.01 (d, 1H), 7.65 (s, 1H), 7.61 (d, 1H), 6.90-7.12 (m, 1H), 6.76 (d, 1H), 4.22-4.24 (m, 1H), 4.03-4.06 (m, 1H), 3.97 (s, 3H), 3.47-3.49 (m, 1H), 1.77-1.81 (m, 1H), 1.53-1.61 (m, 1H), 1.47-1.51 (m, 1H), 0.99 (t, 6H). LC-MS (ESI+) m/z 391.4 [(M+H)+, calcd. C20H24F2N4O2 m/z 390.1].This compound was prepared using tert -butyl ( S )-(1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 57, Part B) and tert -butyl 4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (132.6 mg, 0.35 mmol) to obtain an ivory powder (19.5 mg, 21.1%). 1H NMR (500 MHz, MeOD) δ 8.12 (d, 1H), 8.01 (d, 1H), 7.65 (s, 1H), 7.61 (d, 1H), 6.90-7.12 (m, 1H), 6.76 (d, 1H), 4.22-4.24 (m, 1H), 4.03-4.06 (m, 1H), 3.97 (s, 3H), 3.47-3.49 (m, 1H), 1.77-1.81 (m, 1H), 1.53-1.61 (m, 1H), 1.47-1.51 (m, 1H), 0.99 (t, 6H). LC-MS (ESI+) m/z 391.4 [(M+H) + , calcd. C 20 H 24 F 2 N 4 O 2 m/z 390.1].

실시예 60: (Example 60: ( SS )-1-((2-(다이플루오로메틸)-6-(1)-1-((2-(difluoromethyl)-6-(1 HH -피라졸-4-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민 [(-pyrazol-4-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [( SS )-1-((2-(difluoromethyl)-6-(1)-1-((2-(difluoromethyl)-6-(1 HH -pyrazol-4-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]-pyrazol-4-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

실시예 60을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 60 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: (S)-1-((2-(다이플루오로메틸)-6-(1H-피라졸-4-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민(S)-1-((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine

이 화합물은 tert-부틸 (S)-(1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-4-메틸펜탄-2-일)카바메이트 (100.0 mg, 0.24 mmol) (실시예 57, B 파트) 및 tert-부틸 4-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피라졸-1-카복실레이트 (104.2 mg, 0.35 mmol)를 사용하여 제조하였고, 아이보리색 분말 (16.7 mg, 22.7%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.11 (br, 2H), 7.75 (d, 1H), 7.58 (d, 1H), 6.85-7.06 (m, 1H), 4.13-4.15 (m, 1H), 3.92-3.95 (m, 1H), 3.32-3.34 (m, 1H), 1.79-1.81 (m, 1H), 1.40-1.48 (m, 2H), 0.96-0.99 (m, 6H). LC-MS (ESI+) m/z 311.3 [(M+H)+, calcd. C15H20F2N4O m/z 310.1].This compound was prepared using tert -butyl ( S )-(1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 57, Part B) and tert -butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole-1-carboxylate (104.2 mg, 0.35 mmol) and an ivory powder (16.7 mg, 22.7%) was obtained. 1H NMR (500 MHz, MeOD) δ 8.11 (br, 2H), 7.75 (d, 1H), 7.58 (d, 1H), 6.85-7.06 (m, 1H), 4.13-4.15 (m, 1H), 3.92-3.95 (m, 1H), 3.32-3.34 (m, 1H), 1.79-1.81 (m, 1H), 1.40-1.48 (m, 2H), 0.96-0.99 (m, 6H). LC-MS (ESI+) m/z 311.3 [(M+H) + , calcd. C 15 H 20 F 2 N 4 O m/z 310.1].

실시예 61: 1-((4-(다이플루오로메틸)-6-(1Example 61: 1-((4-(difluoromethyl)-6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민 [1-((4-(difluoromethyl)-6-(1]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((4-(difluoromethyl)-6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]

실시예 61을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 61 was prepared according to a procedure similar to that described for Example 57.

B 파트: Part B: terttert -부틸 (1-((6-브로모-4-(다이플루오로메틸)피리딘-3-일)옥시)-2-메틸프로판-2-일)카바메이트-Butyl (1-((6-bromo-4-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-yl)carbamate

이 화합물은 tert-부틸 (1-하이드록시-2-메틸프로판-2-일)카바메이트 (1.1 g, 5.97 mmol) 및 2-브로모-4-(다이플루오로메틸)-5-플루오로피리딘 (0.5 g, 2.21 mmol) (실시예 30, A 파트)을 사용하여 제조하였고, 투명한 액체 (0.4 g, 45.7%)를 얻었다. LC-MS (ESI+) m/z 395.1 [(M+H)+, calcd. C15H21BrF2N2O3 m/z 394.0].This compound was prepared using tert -butyl (1-hydroxy-2-methylpropan-2-yl)carbamate (1.1 g, 5.97 mmol) and 2-bromo-4-(difluoromethyl)-5-fluoropyridine (0.5 g, 2.21 mmol) (Example 30, Part A) and a clear liquid (0.4 g, 45.7%) was obtained. LC-MS (ESI+) m/z 395.1 [(M+H) + , calcd. C 15 H 21 BrF 2 N 2 O 3 m/z 394.0].

C 파트: Part C: 1-((4-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민1-((4-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine

이 화합물은 tert-부틸 (1-((6-브로모-4-(다이플루오로메틸)피리딘-3-일)옥시)-2-메틸프로판-2-일)카바메이트 (100.0 mg, 0.25 mmol) (실시예 61, B 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (130.6 mg, 0.38 mmol)를 사용하여 제조하였고, 연한-황색 분말 (29.5 mg, 35.0%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.41 (d, 1H), 8.75 (s, 1H), 8.58 (d, 1H), 8.48 (s, 1H), 8.25 (s, 1H), 7.74-7.77 (m, 1H), 7.27-7.48 (m, 1H), 4.40 (s, 2H), 1.55 (s, 6H). LC-MS (ESI+) m/z 000.0 [(M+H)+, calcd. C17H18F2N4O m/z 332.1].This compound was prepared using tert -butyl (1-((6-bromo-4-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.25 mmol) (Example 61, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (130.6 mg, 0.38 mmol) to obtain a pale-yellow powder (29.5 mg, 35.0%). 1H NMR (500 MHz, MeOD) δ 9.41 (d, 1H), 8.75 (s, 1H), 8.58 (d, 1H), 8.48 (s, 1H), 8.25 (s, 1H), 7.74-7.77 (m, 1H), 7.27-7.48 (m, 1H), 4.40 (s, 2H), 1.55 (s, 6H). LC-MS (ESI+) m/z 000.0 [(M+H) + , calcd. C 17 H 18 F 2 N 4 O m/z 332.1].

실시예 62: 1-((4-(다이플루오로메틸)-6-(5-플루오로-1Example 62: 1-((4-(difluoromethyl)-6-(5-fluoro-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민 [1-((4-(difluoromethyl)-6-(5-fluoro-1]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((4-(difluoromethyl)-6-(5-fluoro-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]

실시예 62를 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 62 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: 1-((4-(다이플루오로메틸)-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민1-((4-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine

이 화합물은 tert-부틸 (S)-(1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-4-메틸펜탄-2-일)카바메이트 (100.0 mg, 0.25 mmol) (실시예 61, B 파트) 및 tert-부틸 5-플루오로-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (137.4 mg, 0.38 mmol)를 사용하여 제조하였고, 연한-황색 분말 (52.8 mg, 59.5%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.70 (s, 1H), 8.44-8.52 (m, 3H), 8.35 (s, 1H), 7.31-7.53 (m, 1H), 4.43 (s, 2H), 1.54 (s, 6H). LC-MS (ESI+) m/z 351.2 [(M+H)+, calcd. C17H17F3N4O m/z 350.1].This compound was prepared using tert -butyl ( S )-(1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.25 mmol) (Example 61, Part B) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (137.4 mg, 0.38 mmol) to obtain a pale-yellow powder (52.8 mg, 59.5%). 1H NMR (500 MHz, MeOD) δ 8.70 (s, 1H), 8.44-8.52 (m, 3H), 8.35 (s, 1H), 7.31-7.53 (m, 1H), 4.43 (s, 2H), 1.54 (s, 6H). LC-MS (ESI+) m/z 351.2 [(M+H) + , calcd. C 17 H 17 F 3 N 4 O m/z 350.1].

실시예 63: 1-((5-(다이플루오로메틸)-6-(1Example 63: 1-((5-(difluoromethyl)-6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민 [1-((5-(difluoromethyl)-6-(1]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((5-(difluoromethyl)-6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]

실시예 63을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 63 was prepared according to a procedure similar to that described for Example 57.

B 파트: Part B: tert-부틸 (1-((6-브로모-5-(다이플루오로메틸)피리딘-3-일)옥시)-2-메틸프로판-2-일)카바메이트tert-Butyl (1-((6-bromo-5-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-yl)carbamate

이 화합물은 tert-부틸 (1-하이드록시-2-메틸프로판-2-일)카바메이트 (0.9 g, 4.87 mmol) 및 2-브로모-3-(다이플루오로메틸)-5-플루오로피리딘 (1.0 g, 4.42 mmol) (실시예 33, A 파트)를 사용하여 제조하였고, 투명한 액체 (0.3 g, 17.1%)를 얻었다. LC-MS (ESI+) m/z 395.3 [(M+H)+, calcd. C15H21BrF2N2O3 m/z 394.0].This compound was prepared using tert -butyl (1-hydroxy-2-methylpropan-2-yl)carbamate (0.9 g, 4.87 mmol) and 2-bromo-3-(difluoromethyl)-5-fluoropyridine (1.0 g, 4.42 mmol) (Example 33, Part A) and a clear liquid (0.3 g, 17.1%) was obtained. LC-MS (ESI+) m/z 395.3 [(M+H) + , calcd. C 15 H 21 BrF 2 N 2 O 3 m/z 394.0].

C 파트: Part C: 1-((5-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민1-((5-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine

이 화합물은 tert-부틸 (1-((6-브로모-5-(다이플루오로메틸)피리딘-3-일)옥시)-2-메틸프로판-2-일)카바메이트 (100.0 mg, 0.25 mmol) (실시예 63, B 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (130.6 mg, 0.38 mmol)를 사용하여 제조하였고, 회백색 분말 (23.3 mg, 27.7%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.96 (d, 1H), 8.76 (s, 1H), 8.56 (d, 1H), 8.09 (s, 1H), 7.98 (s, 1H), 7.69 (t, 1H), 6.83-7.04 (m, 1H), 4.30 (s, 2H), 1.51 (s, 6H) LC-MS (ESI+) m/z 333.5 [(M+H)+, calcd. C17H18F2N4O m/z 332.1].This compound was prepared using tert -butyl (1-((6-bromo-5-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.25 mmol) (Example 63, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (130.6 mg, 0.38 mmol) to obtain an off-white powder (23.3 mg, 27.7%). 1H NMR (500 MHz, MeOD) δ 8.96 (d, 1H), 8.76 (s, 1H), 8.56 (d, 1H), 8.09 (s, 1H), 7.98 (s, 1H), 7.69 (t, 1H), 6.83-7.04 (m, 1H), 4.30 (s, 2H), 1.51 (s, 6H) LC-MS (ESI+) m/z 333.5 [(M+H) + , calcd. C17H18F2N4O m/z 332.1].

실시예 64: 1-((5-(다이플루오로메틸)-6-(1Example 64: 1-((5-(difluoromethyl)-6-(1 HH -피롤로[3,2--Pyrrolo[3,2- bb ]피리딘-1-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민 [1-((5-(difluoromethyl)-6-(1]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((5-(difluoromethyl)-6-(1 HH -pyrrolo[3,2--pyrrolo[3,2- bb ]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]

실시예 64는 tert-부틸 (1-((6-브로모-5-(다이플루오로메틸)피리딘-3-일)옥시)-2-메틸프로판-2-일)카바메이트 (100.0 mg, 0.25 mmol) (실시예 63, B 파트), 1H-피롤로[3,2-b]피리딘 (29.8 mg, 0.25 mmol)을 사용하여 실시예 10에 대하여 설명한 것과 유사한 절차에 따라 중간체로 제조하였다. 정제 후 염산 (1.0 M EtOAc 용액, 10 mL)을 첨가하고, tert-부톡시 카르보닐기의 탈보호를 위해 실온에서 교반하였다. 반응 진행은 HPLC로 모니터링하였다. 반응이 완료된 후, 생성물을 EtOAc 및 10% NaOH 용액 (aq.)으로 추출하였다. 분리된 유기층을 물과 염수로 세척하고 황산마그네슘으로 건조시킨 후 농축하였다. 잔류물을 테트라하이드로퓨란 및 n-헥산으로 세척하여 회백색 분말 (17.4 mg, 20.6%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.72 (d, 1H), 8.60 (d, 1H), 8.50 (d, 1H), 8.30 (d, 1H), 8.03 (d, 1H), 7.76-7.79 (m, 1H), 7.14 (d, 1H), 6.69-6.90 (m, 1H), 4.31 (s, 2H), 1.53 (m, 6H). LC-MS (ESI+) m/z 333.5 [(M+H)+, calcd. C17H18F2N4O m/z 332.1].Example 64 was prepared as an intermediate according to a procedure similar to that described for Example 10 using tert -butyl (1-((6-bromo-5-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.25 mmol) (Example 63, Part B) and 1 H -pyrrolo[3,2- b ]pyridine (29.8 mg, 0.25 mmol). After purification, hydrochloric acid (1.0 M EtOAc solution, 10 mL) was added and stirred at room temperature for deprotection of the tert -butoxy carbonyl group. The progress of the reaction was monitored by HPLC. After the reaction was completed, the product was extracted with EtOAc and 10% NaOH solution (aq.). The separated organic layer was washed with water and brine, dried over magnesium sulfate, and concentrated. The residue was washed with tetrahydrofuran and n -hexane to give an off-white powder (17.4 mg, 20.6%). 1 H NMR (500 MHz, MeOD) δ 8.72 (d, 1H), 8.60 (d, 1H), 8.50 (d, 1H), 8.30 (d, 1H), 8.03 (d, 1H), 7.76-7.79 (m, 1H), 7.14 (d, 1H), 6.69-6.90 (m, 1H), 4.31 (s, 2H), 1.53 (m, 6H). LC-MS (ESI+) m/z 333.5 [(M+H) + , calcd. C 17 H 18 F 2 N 4 O m/z 332.1].

실시예 65: 1-(((2-(다이플루오로메틸)-6-(1Example 65: 1-(((2-(difluoromethyl)-6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민 [1-(((2-(difluoromethyl)-6-(1]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((2-(difluoromethyl)-6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

실시예 65를 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 65 was prepared according to a procedure similar to that described for Example 57.

B 파트: Part B: tert-부틸 (1-(((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)메틸)사이클로프로필)카바메이트tert-butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate

이 화합물은 tert-부틸 (1-(하이드록시메틸)사이클로프로필)카바메이트 (372.8 mg, 1.99 mmol) 및 6-브로모-2-(다이플루오로메틸)-3-플루오로피리딘 (300.0 mg, 1.32 mmol) (실시예 13, A 파트)을 사용하여 제조하였고, 회백색 분말 (387.5 mg, 74.2%)을 얻었다. LC-MS (ESI+) m/z 393.1 [(M+H)+, calcd. C15H19BrF2N2O3 m/z 392.0].This compound was prepared using tert -butyl (1-(hydroxymethyl)cyclopropyl)carbamate (372.8 mg, 1.99 mmol) and 6-bromo-2-(difluoromethyl)-3-fluoropyridine (300.0 mg, 1.32 mmol) (Example 13, Part A) and an off-white powder (387.5 mg, 74.2%) was obtained. LC-MS (ESI+) m/z 393.1 [(M+H) + , calcd. C 15 H 19 BrF 2 N 2 O 3 m/z 392.0].

C 파트: Part C: 1-(((2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민1-(((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

이 화합물은 tert-부틸 (1-(((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)메틸)사이클로프로필)카바메이트 (100.0 mg, 0.25 mmol) (실시예 65, B 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (131.3 mg, 0.38 mmol)를 사용하여 제조하였고, 아이보리색 분말 (17.2 mg, 20.4%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.64 (d, 1H), 8.48 (d, 1H), 8.34 (s, 1H), 8.07 (d, 1H), 7.68-7.71 (m, 2H), 7.16-7.38 (m, 1H), 4.32 (s, 2H), 1.15-1.19 (m, 4H). LC-MS (ESI+) m/z 331.3 [(M+H)+, calcd. C17H16F2N4O m/z 330.1].This compound was prepared using tert -butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 65, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (131.3 mg, 0.38 mmol) to obtain an ivory powder (17.2 mg, 20.4%). 1H NMR (500 MHz, MeOD) δ 9.64 (d, 1H), 8.48 (d, 1H), 8.34 (s, 1H), 8.07 (d, 1H), 7.68-7.71 (m, 2H), 7.16-7.38 (m, 1H), 4.32 (s, 2H), 1.15-1.19 (m, 4H). LC-MS (ESI+) m/z 331.3 [(M+H) + , calcd. C 17 H 16 F 2 N 4 O m/z 330.1].

실시예 66: 1-(((2-(다이플루오로메틸)-6-(1Example 66: 1-(((2-(difluoromethyl)-6-(1 HH -피라졸-4-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민 [1-(((2-(difluoromethyl)-6-(1-pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((2-(difluoromethyl)-6-(1 HH -pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]-pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

실시예 66을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 66 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: 1-(((2-(다이플루오로메틸)-6-(1H-피라졸-4-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민1-(((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

이 화합물은 tert-부틸 (1-(((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)메틸)사이클로프로필)카바메이트 (100.0 mg, 0.25 mmol) (실시예 65, B 파트) 및 tert-부틸 4-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피라졸-1-카복실레이트 (112.2 mg, 294.2 mmol)를 사용하여 제조하였고, 회백색 분말 (24.2 mg, 33.9%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.68 (s, 2H), 7.94 (d, 1H), 7.70 (d, 1H), 7.07-7.28 (m, 1H), 4.30 (s, 2H), 1.12-1.27 (m, 4H). LC-MS (ESI+) m/z 000.0 [(M+H)+, calcd. C13H14F2N4O m/z 280.1].This compound was prepared using tert -butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 65, Part B) and tert -butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole-1-carboxylate (112.2 mg, 294.2 mmol) to obtain an off-white powder (24.2 mg, 33.9%). 1H NMR (500 MHz, MeOD) δ 8.68 (s, 2H), 7.94 (d, 1H), 7.70 (d, 1H), 7.07-7.28 (m, 1H), 4.30 (s, 2H), 1.12-1.27 (m, 4H). LC-MS (ESI+) m/z 000.0 [(M+H) + , calcd. C 13 H 14 F 2 N 4 O m/z 280.1].

실시예 67: 1-(((2-(다이플루오로메틸)-6-(2Example 67: 1-(((2-(difluoromethyl)-6-(2 HH -1,2,3-트리아졸-4-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민 [1-(((2-(difluoromethyl)-6-(2-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((2-(difluoromethyl)-6-(2 HH -1,2,3-triazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

실시예 67을 실시예 8에 대하여 설명한 것과 유사한 절차에 따라 제조하였다.Example 67 was prepared according to a procedure similar to that described for Example 8.

B 파트: Part B: 1-(((2-(다이플루오로메틸)-6-(2H-1,2,3-트리아졸-4-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민1-(((2-(difluoromethyl)-6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

이 화합물은 tert-부틸 (1-(((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)메틸)사이클로프로필)카바메이트 (100.0 mg, 0.25 mmol) (실시예 65, B 파트) 및 2-(테트라하이드로-2H-피란-2-일)-4-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-2H-1,2,3-트리아졸 (106.4 mg, 0.38 mmol)을 사용하여 제조하였고, 회백색 분말 (17.1 mg, 23.9%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.42 (s, 1H), 8.13 (d, 1H), 7.72 (d, 1H), 7.06-7.28 (m, 1H), 4.31 (s, 2H), 1.12-1.22 (m, 4H). LC-MS (ESI+) m/z 282.3 [(M+H)+, calcd. C12H13F2N5O m/z 281.1].This compound was prepared using tert -butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 65, Part B) and 2-(tetrahydro-2 H -pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2 H -1,2,3-triazole (106.4 mg, 0.38 mmol) to obtain an off-white powder (17.1 mg, 23.9%). 1H NMR (500 MHz, MeOD) δ 8.42 (s, 1H), 8.13 (d, 1H), 7.72 (d, 1H), 7.06-7.28 (m, 1H), 4.31 (s, 2H), 1.12-1.22 (m, 4H). LC-MS (ESI+) m/z 282.3 [(M+H) + , calcd. C 12 H 13 F 2 N 5 O m/z 281.1].

실시예 68: 1-(((2-(다이플루오로메틸)-6-(5-플루오로-1Example 68: 1-(((2-(difluoromethyl)-6-(5-fluoro-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민 [1-(((2-(difluoromethyl)-6-(5-fluoro-1]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((2-(difluoromethyl)-6-(5-fluoro-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

실시예 68을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 68 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: 1-(((2-(다이플루오로메틸)-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민1-(((2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

이 화합물은 tert-부틸 (1-(((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)메틸)사이클로프로필)카바메이트 (100.0 mg, 0.25 mmol) (실시예 65, B 파트) 및 tert-부틸 5-플루오로-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (138.1 mg, 0.38 mmol)를 사용하여 제조하였고, 연한-황색 분말 (34.1 mg, 38.5%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.10 (d, 1H), 8.43 (s, 1H), 8.27 (s, 1H), 7.98 (d, 1H), 7.64 (d, 1H), 7.12-7.34 (m, 1H), 4.28 (s, 2H), 1.11-1.18 (m, 4H). LC-MS (ESI+) m/z 349.3 [(M+H)+, calcd. C17H15F3N4O m/z 348.1].This compound was prepared using tert -butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 65, Part B) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (138.1 mg, 0.38 mmol) to obtain a pale-yellow powder (34.1 mg, 38.5%). 1H NMR (500 MHz, MeOD) δ 9.10 (d, 1H), 8.43 (s, 1H), 8.27 (s, 1H), 7.98 (d, 1H), 7.64 (d, 1H), 7.12-7.34 (m, 1H), 4.28 (s, 2H), 1.11-1.18 (m, 4H). LC-MS (ESI+) m/z 349.3 [(M+H) + , calcd. C 17 H 15 F 3 N 4 O m/z 348.1].

실시예 69: 1-(((2-(다이플루오로메틸)-6-(1Example 69: 1-(((2-(difluoromethyl)-6-(1 HH -피롤로[3,2--Pyrrolo[3,2- bb ]피리딘-1-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민 [1-(((2-(difluoromethyl)-6-(1]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((2-(difluoromethyl)-6-(1 HH -pyrrolo[3,2--pyrrolo[3,2- bb ]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

실시예 69는 tert-부틸 (1-(((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)메틸)사이클로프로필)카바메이트 (100.0 mg, 0.25 mmol) (실시예 65, B 파트) 및 1H-피롤로[3,2-b]피리딘 (30.0 mg, 0.25 mmol)을 사용하여 실시예 64에 대하여 설명한 것과 유사한 절차에 따라 제조하였고, 회백색 분말 (15.4 mg, 18.3%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.54 (d, 1H), 8.70-8.74 (m, 2H), 8.04 (d, 1H), 7.95 (d, 1H), 7.84-7.86 (m, 1H), 7.21-7.43 (m, 1H), 7.14 (d, 1H), 4.38 (s, 2H), 1.15-1.22 (m, 4H). LC-MS (ESI+) m/z 331.5 [(M+H)+, calcd. C17H16F2N4O m/z 330.1].Example 69 was prepared according to a similar procedure as described for Example 64 using tert -butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 65, part B) and 1 H -pyrrolo[3,2- b ]pyridine (30.0 mg, 0.25 mmol) to obtain an off-white powder (15.4 mg, 18.3%). 1H NMR (500 MHz, MeOD) δ 9.54 (d, 1H), 8.70-8.74 (m, 2H), 8.04 (d, 1H), 7.95 (d, 1H), 7.84-7.86 (m, 1H), 7.21-7.43 (m, 1H), 7.14 (d, 1H), 4.38 (s, 2H), 1.15-1.22 (m, 4H). LC-MS (ESI+) m/z 331.5 [(M+H) + , calcd. C 17 H 16 F 2 N 4 O m/z 330.1].

실시예 70: 1-(((6-(1Example 70: 1-(((6-(1 HH -피라졸-4-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민 [1-(((6-(1-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((6-(1 HH -pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

실시예 70을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 70 was prepared according to a procedure similar to that described for Example 57.

B 파트: Part B: tert-부틸 (1-(((6-브로모-2-(트리플루오로메틸)피리딘-3-일)옥시)메틸)사이클로프로필)카바메이트tert-butyl (1-(((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate

이 화합물은 tert-부틸 (1-(하이드록시메틸)사이클로프로필)카바메이트 (253.2 mg, 1.35 mmol) 및 6-브로모-3-플루오로-2-(트리플루오로메틸)피리딘 (300.0 mg, 1.23 mmol)을 사용하여 제조하였고, 회백색 분말 (290.7 mg, 59.8%)을 얻었다. LC-MS (ESI+) m/z 411.1 [(M+H)+, calcd. C15H18BrF3N2O3 m/z 410.0].This compound was prepared using tert -butyl (1-(hydroxymethyl)cyclopropyl)carbamate (253.2 mg, 1.35 mmol) and 6-bromo-3-fluoro-2-(trifluoromethyl)pyridine (300.0 mg, 1.23 mmol) and an off-white powder (290.7 mg, 59.8%) was obtained. LC-MS (ESI+) m/z 411.1 [(M+H) + , calcd. C15H18BrF3N2O3 m/z 410.0].

C 파트: Part C: 1-(((6-(1H-피라졸-4-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민1-(((6-(1H-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

이 화합물은 tert-부틸 (1-(((6-브로모-2-(트리플루오로메틸)피리딘-3-일)옥시)메틸)사이클로프로필)카바메이트 (100.0 mg, 0.24 mmol) (실시예 70, B 파트) 및 tert-부틸 4-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피라졸-1-카복실레이트 (107.3 mg, 0.36 mmol)를 사용하여 제조하였고, 연한-갈색 분말 (38.2 mg, 52.6%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.65 (br, 2H), 8.06 (d, 1H), 7.83 (d, 1H), 4.37 (s, 2H), 1.15-1.23 (m, 4H). LC-MS (ESI+) m/z 299.3 [(M+H)+, calcd. C13H13F3N4O m/z 298.1].This compound was prepared using tert -butyl (1-(((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.24 mmol) (Example 70, Part B) and tert -butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole-1-carboxylate (107.3 mg, 0.36 mmol) to obtain a pale-brown powder (38.2 mg, 52.6%). 1H NMR (500 MHz, MeOD) δ 8.65 (br, 2H), 8.06 (d, 1H), 7.83 (d, 1H), 4.37 (s, 2H), 1.15-1.23 (m, 4H). LC-MS (ESI+) m/z 299.3 [(M+H) + , calcd. C 13 H 13 F 3 N 4 O m/z 298.1].

실시예 71: 1-((5-(다이플루오로메틸)-6-(1Example 71: 1-((5-(difluoromethyl)-6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민 [1-((5-(difluoromethyl)-6-(1]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine [1-((5-(difluoromethyl)-6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine]

실시예 71을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 71 was prepared according to a procedure similar to that described for Example 57.

B 파트: Part B: tert-부틸 (1-(((6-브로모-5-(다이플루오로메틸)피리딘-3-일)옥시)메틸)사이클로프로필)카바메이트tert-butyl (1-(((6-bromo-5-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate

이 화합물은 tert-부틸 (1-(하이드록시메틸)사이클로프로필)카바메이트 (273.4 mg, 1.46 mmol) 및 2-브로모-3-(다이플루오로메틸)-5-플루오로피리딘 (300.0 mg, 1.33 mmol) (실시예 33, A 파트)을 사용하여 제조하였고, 회백색 분말 (253.1 mg, 48.4%)을 얻었다. LC-MS (ESI+) m/z 393.1 [(M+H)+, calcd. C15H19BrF2N2O3 m/z 392.0].This compound was prepared using tert -butyl (1-(hydroxymethyl)cyclopropyl)carbamate (273.4 mg, 1.46 mmol) and 2-bromo-3-(difluoromethyl)-5-fluoropyridine (300.0 mg, 1.33 mmol) (Example 33, Part A) and an off-white powder (253.1 mg, 48.4%) was obtained. LC-MS (ESI+) m/z 393.1 [(M+H) + , calcd. C 15 H 19 BrF 2 N 2 O 3 m/z 392.0].

C 파트: Part C: 1-((5-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민1-((5-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine

이 화합물은 tert-부틸 (1-(((6-브로모-5-(다이플루오로메틸)피리딘-3-일)옥시)메틸)사이클로프로필)카바메이트 (100.0 mg, 0.25 mmol) (실시예 71, B 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (131.3 mg, 0.38 mmol)를 사용하여 제조하였고, 회백색 분말 (33.9 mg, 40.3%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.96 (d, 1H), 8.68 (d, 1H), 8.54 (d, 1H), 7.93-7.96 (m, 2H), 7.65-7.68 (m, 1H), 6.82-7.04 (m, 1H), 4.31 (s, 2H), 1.12-1.19 (m, 4H). LC-MS (ESI+) m/z 331.3 [(M+H)+, calcd. C17H16F2N4O m/z 330.1].This compound was prepared using tert -butyl (1-(((6-bromo-5-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 71, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (131.3 mg, 0.38 mmol) to obtain an off-white powder (33.9 mg, 40.3%). 1H NMR (500 MHz, MeOD) δ 8.96 (d, 1H), 8.68 (d, 1H), 8.54 (d, 1H), 7.93-7.96 (m, 2H), 7.65-7.68 (m, 1H), 6.82-7.04 (m, 1H), 4.31 (s, 2H), 1.12-1.19 (m, 4H). LC-MS (ESI+) m/z 331.3 [(M+H) + , calcd. C 17 H 16 F 2 N 4 O m/z 330.1].

실시예 72: 1-(((5-(다이플루오로메틸)-6-(5-플루오로-1Example 72: 1-(((5-(difluoromethyl)-6-(5-fluoro-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민 [1-(((5-(difluoromethyl)-6-(5-fluoro-1]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((5-(difluoromethyl)-6-(5-fluoro-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

실시예 72를 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 72 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: 1-(((5-(다이플루오로메틸)-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민1-(((5-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

이 화합물은 tert-부틸 (1-(((6-브로모-5-(다이플루오로메틸)피리딘-3-일)옥시)메틸)사이클로프로필)카바메이트 (100.0 mg, 0.25 mmol) (실시예 71, B 파트) 및 tert-부틸 5-플루오로-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (138.1 mg, 0.38 mmol)를 사용하여 제조하였고, 회백색 분말 (35.7 mg, 40.3%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.64 (d, 1H), 8.26 (s, 1H), 8.01-8.05 (m, 2H), 7.78 (s, 1H), 6.77-6.99 (m, 1H), 4.38 (s, 2H), 1.12-1.20 (m, 4H). LC-MS (ESI+) m/z 349.3 [(M+H)+, calcd. C17H15F3N4O m/z 348.1].This compound was prepared using tert -butyl (1-(((6-bromo-5-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 71, Part B) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (138.1 mg, 0.38 mmol) to obtain an off-white powder (35.7 mg, 40.3%). 1H NMR (500 MHz, MeOD) δ 8.64 (d, 1H), 8.26 (s, 1H), 8.01-8.05 (m, 2H), 7.78 (s, 1H), 6.77-6.99 (m, 1H), 4.38 (s, 2H), 1.12-1.20 (m, 4H). LC-MS (ESI+) m/z 349.3 [(M+H) + , calcd. C 17 H 15 F 3 N 4 O m/z 348.1].

실시예 73: 1-(((2-(다이플루오로메틸)-6-(1Example 73: 1-(((2-(difluoromethyl)-6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로부탄-1-아민 [1-(((2-(difluoromethyl)-6-(1]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine [1-(((2-(difluoromethyl)-6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine]]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine]

실시예 73을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 73 was prepared according to a procedure similar to that described for Example 57.

B 파트: Part B: tert-부틸 (1-(((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)메틸)사이클로부틸)카바메이트tert-butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutyl)carbamate

이 화합물은 tert-부틸 (1-(하이드록시메틸)사이클로부틸)카바메이트 (489.8 mg, 2.43 mmol) 및 2-브로모-3-(다이플루오로메틸)-5-플루오로피리딘 (500.0 mg, 2.21 mmol) (실시예 13, A 파트)을 사용하여 제조하였고, 회백색 분말 (677.6 mg, 75.2%)을 얻었다. LC-MS (ESI+) m/z 407.3 [(M+H)+, calcd. C16H21BrF2N2O3 m/z 406.0].This compound was prepared using tert -butyl (1-(hydroxymethyl)cyclobutyl)carbamate (489.8 mg, 2.43 mmol) and 2-bromo-3-(difluoromethyl)-5-fluoropyridine (500.0 mg, 2.21 mmol) (Example 13, Part A) and an off-white powder (677.6 mg, 75.2%) was obtained. LC-MS (ESI+) m/z 407.3 [(M+H) + , calcd. C 16 H 21 BrF 2 N 2 O 3 m/z 406.0].

C 파트: Part C: 1-(((2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로부탄-1-아민1-(((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine

이 화합물은 tert-부틸 (1-(((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)메틸)사이클로부틸)카바메이트 (100.0 mg, 0.25 mmol) (실시예 73, B 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (126.7 mg, 0.37 mmol)를 사용하여 제조하였고, 연한-갈색 분말 (34.6 mg, 40.9%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.65 (d, 1H), 8.50 (d, 1H), 8.37 (s, 1H), 8.12 (d, 1H), 7.81 (d, 1H), 7.69-7.72 (m, 1H), 7.12-7.33 (m, 1H), 4.44 (s, 2H), 2.36-2.48 (m, 4H), 2.09-2.14 (m, 2H). LC-MS (ESI+) m/z 345.3 [(M+H)+, calcd. C18H18F2N4O m/z 344.1].This compound was prepared using tert -butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutyl)carbamate (100.0 mg, 0.25 mmol) (Example 73, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (126.7 mg, 0.37 mmol) to obtain a pale-brown powder (34.6 mg, 40.9%). 1H NMR (500 MHz, MeOD) δ 9.65 (d, 1H), 8.50 (d, 1H), 8.37 (s, 1H), 8.12 (d, 1H), 7.81 (d, 1H), 7.69-7.72 (m, 1H), 7.12-7.33 (m, 1H), 4.44 (s, 2H), 2.36-2.48 (m, 4H), 2.09-2.14 (m, 2H). LC-MS (ESI+) m/z 345.3 [(M+H) + , calcd. C 18 H 18 F 2 N 4 O m/z 344.1].

실시예 74: 1-(((2-(다이플루오로메틸)-6-(1Example 74: 1-(((2-(difluoromethyl)-6-(1 HH -피라졸-4-일)피리딘-3-일)옥시)메틸)사이클로부탄-1-아민 [1-(((2-(difluoromethyl)-6-(1-pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine [1-(((2-(difluoromethyl)-6-(1 HH -pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine]-pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine]

실시예 74를 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 74 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: 1-(((2-(다이플루오로메틸)-6-(1H-피라졸-4-일)피리딘-3-일)옥시)메틸)사이클로부탄-1-아민1-(((2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine

이 화합물은 tert-부틸 (1-(((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)메틸)사이클로부틸)카바메이트 (100.0 mg, 0.25 mmol) (실시예 73, B 파트) 및 tert-부틸 4-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피라졸-1-카복실레이트 (108.3 mg, 0.37 mmol)를 사용하여 제조하였고, 아이보리색 분말 (30.7 mg, 42.4%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.70 (s, 2H), 7.98 (d, 1H), 7.82 (d, 1H), 7.02-7.24 (m, 1H), 4.43 (s, 2H), 2.35-2.47 (m, 4H), 2.07-2.12 (m, 2H). LC-MS (ESI+) m/z 295.4 [(M+H)+, calcd. C14H16F2N4O m/z 294.1].This compound was prepared using tert -butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutyl)carbamate (100.0 mg, 0.25 mmol) (Example 73, Part B) and tert -butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole-1-carboxylate (108.3 mg, 0.37 mmol) and an ivory powder (30.7 mg, 42.4%) was obtained. 1H NMR (500 MHz, MeOD) δ 8.70 (s, 2H), 7.98 (d, 1H), 7.82 (d, 1H), 7.02-7.24 (m, 1H), 4.43 (s, 2H), 2.35-2.47 (m, 4H), 2.07-2.12 (m, 2H). LC-MS (ESI+) m/z 295.4 [(M+H) + , calcd. C 14 H 16 F 2 N 4 O m/z 294.1].

실시예 75: 1-(((2-(다이플루오로메틸)-6-(2Example 75: 1-(((2-(difluoromethyl)-6-(2 HH -1,2,3-트리아졸-4-일)피리딘-3-일)옥시)메틸)사이클로부탄-1-아민 [1-(((2-(difluoromethyl)-6-(2-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine [1-(((2-(difluoromethyl)-6-(2 HH -1,2,3-triazol-4-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine]-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine]

실시예 75를 실시예 8에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 75 was prepared according to a procedure similar to that described for Example 8.

B 파트: Part B: 1-(((2-(다이플루오로메틸)-6-(2H-1,2,3-트리아졸-4-일)피리딘-3-일)옥시)메틸)사이클로부탄-1-아민1-(((2-(difluoromethyl)-6-(2H-1,2,3-triazol-4-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine

이 화합물은 (1-(((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)메틸)사이클로부틸)카바메이트 (100.0 mg, 0.25 mmol) (실시예 73, B 파트) 및 2-(테트라하이드로-2H-피란-2-일)-4-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-2H-1,2,3-트리아졸 (102.8 mg, 0.37 mmol)을 사용하여 제조하였고, 연한-황색 분말 (36.6 mg, 50.4%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.54 (s, 1H), 8.19 (d, 1H), 7.85 (d, 1H), 7.03-7.24 (m, 1H), 4.44 (s, 2H), 2.35-2.45 (m, 4H), 2.08-2.12 (m, 2H). LC-MS (ESI+) m/z 296.3 [(M+H)+, calcd. C13H15F2N5O m/z 295.1].This compound was prepared using (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutyl)carbamate (100.0 mg, 0.25 mmol) (Example 73, Part B) and 2-(tetrahydro-2 H -pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2 H -1,2,3-triazole (102.8 mg, 0.37 mmol) to obtain a pale-yellow powder (36.6 mg, 50.4%). 1H NMR (500 MHz, MeOD) δ 8.54 (s, 1H), 8.19 (d, 1H), 7.85 (d, 1H), 7.03-7.24 (m, 1H), 4.44 (s, 2H), 2.35-2.45 (m, 4H), 2.08-2.12 (m, 2H). LC-MS (ESI+) m/z 296.3 [(M+H) + , calcd. C 13 H 15 F 2 N 5 O m/z 295.1].

실시예 76: 1-(((2-(다이플루오로메틸)-6-(1Example 76: 1-(((2-(difluoromethyl)-6-(1 HH -피롤로[3,2--Pyrrolo[3,2- bb ]피리딘-1-일)피리딘-3-일)옥시)메틸)사이클로부탄-1-아민 [1-(((2-(difluoromethyl)-6-(1]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine [1-(((2-(difluoromethyl)-6-(1 HH -pyrrolo[3,2--pyrrolo[3,2- bb ]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine]]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine]

실시예 76은 tert-부틸 (1-(((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)메틸)사이클로부틸)카바메이트 (100.0 mg, 0.25 mmol) (실시예 73, B 파트), 및 1H-피롤로[3,2-b]피리딘 (29.0 mg, 0.25 mmol)을 사용하여 실시예 64에 대하여 설명한 것과 유사한 절차에 따라 제조하였고, 회백색 분말 (18.7 mg, 22.1%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.55 (d, 1H), 8.71-8.76 (m, 2H), 8.07-8.08 (m, 2H), 7.84-7.87 (m, 1H), 7.15-7.38 (m, 2H), 4.50 (s, 2H), 2.38-2.47 (m, 4H), 2.10-2.15 (m, 2H). LC-MS (ESI+) m/z 345.4 [(M+H)+, calcd. C18H18F2N4O m/z 344.1].Example 76 was prepared according to a similar procedure as that described for Example 64 using tert -butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutyl)carbamate (100.0 mg, 0.25 mmol) (Example 73, Part B) and 1 H -pyrrolo[3,2- b ]pyridine (29.0 mg, 0.25 mmol) to obtain an off-white powder (18.7 mg, 22.1%). 1H NMR (500 MHz, MeOD) δ 9.55 (d, 1H), 8.71-8.76 (m, 2H), 8.07-8.08 (m, 2H), 7.84-7.87 (m, 1H), 7.15-7.38 (m, 2H), 4.50 (s, 2H), 2.38-2.47 (m, 4H), 2.10-2.15 (m, 2H). LC-MS (ESI+) m/z 345.4 [(M+H) + , calcd. C 18 H 18 F 2 N 4 O m/z 344.1].

실시예 77: 1-(((6-(1Example 77: 1-(((6-(1 HH -피라졸-4-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)메틸)사이클로부탄-1-아민 [1-(((6-(1-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine [1-(((6-(1 HH -pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine]-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine]

실시예 77을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 77 was prepared according to a procedure similar to that described for Example 57.

B 파트: Part B: tert-부틸 (1-(((6-브로모-2-(트리플루오로메틸)피리딘-3-일)옥시)메틸)사이클로부틸)카바메이트tert-butyl (1-(((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutyl)carbamate

이 화합물은 tert-부틸 (1-(하이드록시메틸)사이클로부틸)카바메이트 (453.7 mg, 2.25 mmol) 및 6-브로모-3-플루오로-2-(트리플루오로메틸)피리딘 (500.0 mg, 2.05 mmol)을 사용하여 제조하였고, 회백색 분말 (734.8 mg, 84.3%)을 얻었다. LC-MS (ESI+) m/z 425.1 [(M+H)+, calcd. C16H20BrF3N2O3 m/z 424.0].This compound was prepared using tert -butyl (1-(hydroxymethyl)cyclobutyl)carbamate (453.7 mg, 2.25 mmol) and 6-bromo-3-fluoro-2-(trifluoromethyl)pyridine (500.0 mg, 2.05 mmol) and an off-white powder (734.8 mg, 84.3%) was obtained. LC-MS (ESI+) m/z 425.1 [(M+H) + , calcd. C 16 H 20 BrF 3 N 2 O 3 m/z 424.0].

C 파트: Part C: 1-(((6-(1H-피라졸-4-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)메틸)사이클로부탄-1-아민1-(((6-(1H-pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine

이 화합물은 tert-부틸 (1-(((6-브로모-2-(트리플루오로메틸)피리딘-3-일)옥시)메틸)사이클로부틸)카바메이트 (100.0 mg, 0.24 mmol) (실시예 77, B 파트) 및 tert-부틸 4-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피라졸-1-카복실레이트 (103.7 mg, 0.35 mmol)를 사용하여 제조하였고, 연한-갈색 분말 (42.6 mg, 58.0%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.63 (br, 2H), 8.07 (d, 1H), 7.90 (d, 1H), 4.43 (s, 2H), 2.40-2.44 (m, 4H), 2.07-2.10 (m, 2H). LC-MS (ESI+) m/z 313.4 [(M+H)+, calcd. C14H15F3N4O m/z 312.1].This compound was prepared using tert -butyl (1-(((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutyl)carbamate (100.0 mg, 0.24 mmol) (Example 77, Part B) and tert -butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole-1-carboxylate (103.7 mg, 0.35 mmol) to obtain a pale-brown powder (42.6 mg, 58.0%). 1H NMR (500 MHz, MeOD) δ 8.63 (br, 2H), 8.07 (d, 1H), 7.90 (d, 1H), 4.43 (s, 2H), 2.40-2.44 (m, 4H), 2.07-2.10 (m, 2H). LC-MS (ESI+) m/z 313.4 [(M+H) + , calcd. C 14 H 15 F 3 N 4 O m/z 312.1].

실시예 78: 1-(((6-(2Example 78: 1-(((6-(2 HH -1,2,3-트리아졸-4-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)메틸)사이클로부탄-1-아민 [1-(((6-(2-1,2,3-triazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine [1-(((6-(2 HH -1,2,3-triazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine]-1,2,3-triazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine]

실시예 78을 실시예 8에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 78 was prepared according to a procedure similar to that described for Example 8.

B 파트: Part B: 1-(((6-(2H-1,2,3-트리아졸-4-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)메틸)사이클로부탄-1-아민1-(((6-(2H-1,2,3-triazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine

이 화합물은 tert-부틸 (1-(((6-브로모-2-(트리플루오로메틸)피리딘-3-일)옥시)메틸)사이클로부틸)카바메이트 (100.0 mg, 0.24 mmol) (실시예 77, B 파트) 및 2-(테트라하이드로-2H-피란-2-일)-4-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-2H-1,2,3-트리아졸 (98.4 mg, 0.35 mmol)을 사용하여 제조하였고, 연한-황색 분말 (58.4 mg, 79.2%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.44 (s, 1H), 8.28 (d, 1H), 7.95 (d, 1H), 4.45 (s, 2H), 2.41-2.44 (m, 4H), 2.07-2.10 (m, 2H). LC-MS (ESI+) m/z 314.3 [(M+H)+, calcd. C13H14F3N5O m/z 313.1].This compound was prepared using tert -butyl (1-(((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutyl)carbamate (100.0 mg, 0.24 mmol) (Example 77, Part B) and 2-(tetrahydro-2 H -pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2 H -1,2,3-triazole (98.4 mg, 0.35 mmol) to obtain a pale-yellow powder (58.4 mg, 79.2%). 1H NMR (500 MHz, MeOD) δ 8.44 (s, 1H), 8.28 (d, 1H), 7.95 (d, 1H), 4.45 (s, 2H), 2.41-2.44 (m, 4H), 2.07-2.10 (m, 2H). LC-MS (ESI+) m/z 314.3 [(M+H) + , calcd. C 13 H 14 F 3 N 5 O m/z 313.1].

실시예 79: 1-((2-(다이플루오로메틸)-6-(1Example 79: 1-((2-(difluoromethyl)-6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)-2-메틸프로판-2-올 [1-((2-(difluoromethyl)-6-(1]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-ol [1-((2-(difluoromethyl)-6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-ol]]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-ol]

실시예 79를 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 79 was prepared according to a procedure similar to that described for Example 13.

B 파트: Part B: 1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-2-메틸프로판-2-올1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-ol

이 화합물은 2-메틸프로판-1,2-다이올 (219.3 mg, 2.43 mmol) 및 6-브로모-2-(다이플루오로메틸)-3-플루오로피리딘 (500.0 mg, 2.21 mmol) (실시예 13, A 파트)을 사용하여 제조하였고, 투명한 액체 (295.7 mg, 45.1%)를 얻었다. LC-MS (ESI+) m/z 296.1 [(M+H)+, calcd. C10H12BrF2NO2 m/z 295.0].This compound was prepared using 2-methylpropane-1,2-diol (219.3 mg, 2.43 mmol) and 6-bromo-2-(difluoromethyl)-3-fluoropyridine (500.0 mg, 2.21 mmol) (Example 13, Part A) and a clear liquid (295.7 mg, 45.1%) was obtained. LC-MS (ESI+) m/z 296.1 [(M+H) + , calcd. C 10 H 12 BrF 2 NO 2 m/z 295.0].

C 파트: Part C: 1-((2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2-메틸프로판-2-올1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-ol

이 화합물은 1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-2-메틸프로판-2-올 (100.0 mg, 0.34 mmol) (실시예 79, B 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (174.3 mg, 0.51 mmol)를 사용하여 제조하였고, 연한-황색 분말 (43.3 mg, 38.4%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.58 (d, 1H), 8.44 (d, 1H), 8.25 (s, 1H), 7.98 (d, 1H), 7.61-7.65 (m, 2H), 7.02-7.24 (m, 1H), 3.92 (s, 2H), 1.33 (s, 6H). LC-MS (ESI+) m/z 334.4 [(M+H)+, calcd. C17H17F2N3O2 m/z 333.1].This compound was prepared using 1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-ol (100.0 mg, 0.34 mmol) (Example 79, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (174.3 mg, 0.51 mmol) to obtain a pale-yellow powder (43.3 mg, 38.4%). 1H NMR (500 MHz, MeOD) δ 9.58 (d, 1H), 8.44 (d, 1H), 8.25 (s, 1H), 7.98 (d, 1H), 7.61-7.65 (m, 2H), 7.02-7.24 (m, 1H), 3.92 (s, 2H), 1.33 (s, 6H). LC-MS (ESI+) m/z 334.4 [(M+H) + , calcd. C 17 H 17 F 2 N 3 O 2 m/z 333.1].

실시예 80: 1-((2-(다이플루오로메틸)-6-(1Example 80: 1-((2-(difluoromethyl)-6-(1 HH -피롤로[3,2--Pyrrolo[3,2- bb ]피리딘-1-일)피리딘-3-일)옥시)-2-메틸프로판-2-올 [1-((2-(difluoromethyl)-6-(1]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-ol [1-((2-(difluoromethyl)-6-(1 HH -pyrrolo[3,2--pyrrolo[3,2- bb ]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-ol]]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-ol]

실시예 80은 1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)옥시)-2-메틸프로판-2-올 (100.0 mg, 0.34 mmol) (실시예 79, B 파트), 1H-피롤로[3,2-b]피리딘 (39.9 mg, 0.34 mmol)을 사용하여 실시예 10에 대하여 설명한 것과 유사한 절차에 따라 제조하였고, 아이보리색 분말 (31.2 mg, 27.7%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.87 (d, 1H), 8.40 (d, 1H), 8.18 (d, 1H), 7.78 (s, 2H), 7.30-7.33 (m, 1H), 7.03-7.25 (m, 1H), 6.84 (d, 1H), 3.95 (s, 2H), 1.35 (m, 6H). LC-MS (ESI+) m/z 334.4 [(M+H)+, calcd. C17H17F2N3O2 m/z 333.1].Example 80 was prepared according to a similar procedure as described for Example 10 using 1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-ol (100.0 mg, 0.34 mmol) (Example 79, Part B), 1 H -pyrrolo[3,2- b ]pyridine (39.9 mg, 0.34 mmol) to obtain an ivory powder (31.2 mg, 27.7%). 1H NMR (500 MHz, MeOD) δ 8.87 (d, 1H), 8.40 (d, 1H), 8.18 (d, 1H), 7.78 (s, 2H), 7.30-7.33 (m, 1H), 7.03-7.25 (m, 1H), 6.84 (d, 1H), 3.95 (s, 2H), 1.35 (m, 6H). LC-MS (ESI+) m/z 334.4 [(M+H) + , calcd. C 17 H 17 F 2 N 3 O 2 m/z 333.1].

실시예 81: (Example 81: ( SS )-1-(4-(1)-1-(4-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)펜옥시)-2,4-다이메틸펜탄-2-아민 [(]pyridin-3-yl)phenoxy)-2,4-dimethylpentan-2-amine [( SS )-1-(4-(1)-1-(4-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)phenoxy)-2,4-dimethylpentan-2-amine]]pyridin-3-yl)phenoxy)-2,4-dimethylpentan-2-amine]

A 파트: Part A: (S)-1-(4-요오도펜옥시)-2,4-다이메틸펜탄-2-아민(S)-1-(4-iodophenoxy)-2,4-dimethylpentan-2-amine

1-플루오로-4-요오도벤젠 (200.0 mg, 0.90 mmol), (S)-2-아미노-2,4-다이메틸펜탄-1-올 (130.0 mg, 0.99 mmol) 및 칼륨 tert-부톡사이드 (505.4 mg, 4.50 mmol)의 테트라하이드로퓨란 (8 mL) 용액을 120°C의 마이크로파에서 1시간 동안 조사하였다. TLC와 HPLC로 반응의 진행을 모니터링하였다. 반응이 완료된 후, EtOAc와 물로 희석하였다. 분리된 유기층을 물과 염수로 세척하고, 황산마그네슘으로 건조시킨 후 농축하였다. 잔류물을 MPLC (실리카겔, CH2Cl2 : MeOH = 10 : 1, v/v로 용출)로 정제하여 연한-황색 액체를 얻었다. LC-MS (ESI+) m/z 334.1 [(M+H)+, calcd. C13H20INO m/z 333.0].A solution of 1-fluoro-4-iodobenzene (200.0 mg, 0.90 mmol), ( S )-2-amino-2,4-dimethylpentan-1-ol (130.0 mg, 0.99 mmol), and potassium tert -butoxide (505.4 mg, 4.50 mmol) in tetrahydrofuran (8 mL) was irradiated in a microwave at 120°C for 1 h. The progress of the reaction was monitored by TLC and HPLC. After the reaction was completed, the mixture was diluted with EtOAc and water. The separated organic layer was washed with water and brine, dried over magnesium sulfate, and concentrated. The residue was purified by MPLC (silica gel, eluted with CH 2 Cl 2 : MeOH = 10 : 1, v/v ) to obtain a pale-yellow liquid. LC-MS (ESI+) m/z 334.1 [(M+H) + , calcd. C 13 H 20 INO m/z 333.0].

실시예 81을 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 81 was prepared according to a procedure similar to that described for Example 13.

C 파트: Part C: (S)-1-(4-(1H-피롤로[2,3-b]피리딘-3-일)펜옥시)-2,4-다이메틸펜탄-2-아민(S)-1-(4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2,4-dimethylpentan-2-amine

이 화합물은 (S)-1-(4-요오도펜옥시)-2,4-다이메틸펜탄-2-아민 (100.0 mg, 0.30 mmol) (실시예 81, A 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (154.9 mg, 0.45 mmol)를 사용하여 제조하였고, 진한-아이보리색 분말 (41.3 mg, 42.5%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.92 (d, 1H), 8.48 (d, 1H), 7.90 (s, 1H), 7.63-7.70 (m, 3H), 7.21 (d, 2H), 4.07-4.18 (m, 2H), 1.83-1.87 (m, 2H), 1.68-1.70 (m, 1H), 1.50 (s, 3H), 1.07 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+) m/z 324.2 [(M+H)+, calcd. C20H25N3O m/z 323.1].This compound was prepared using ( S )-1-(4-iodophenoxy)-2,4-dimethylpentan-2-amine (100.0 mg, 0.30 mmol) (Example 81, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (154.9 mg, 0.45 mmol) to obtain a dark-ivory powder (41.3 mg, 42.5%). 1H NMR (500 MHz, MeOD) δ 8.92 (d, 1H), 8.48 (d, 1H), 7.90 (s, 1H), 7.63-7.70 (m, 3H), 7.21 (d, 2H), 4.07-4.18 (m, 2H), 1.83-1.87 (m, 2H), 1.68-1.70 (m, 1H), 1.50 (s, 3H), 1.07 (d, 3H), 1.02 (d, 3H). LC-MS (ESI+) m/z 324.2 [(M+H) + , calcd. C 20 H 25 N 3 O m/z 323.1].

실시예 82: (Example 82: ( SS )-1-((6-(5-플루오로-1)-1-((6-(5-fluoro-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민 [(]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [( SS )-1-((6-(5-fluoro-1)-1-((6-(5-fluoro-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

A 파트: Part A: tert-부틸 (S)-(1-((6-요오도피리딘-3-일)옥시)-4-메틸펜탄-2-일)카바메이트tert-Butyl (S)-(1-((6-iodopyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate

다이이소프로필 아조다이카복실레이트 (6.2 mL, 31.67 mmol)를 6-요오도피리딘-3-올 (3.5 g, 15.84 mmol), tert-부틸 (S)-(1-하이드록시-4-메틸펜탄-2-일)카바메이트 (8.6 g, 39.59 mmol) 및 트리페닐 포스핀 (8.3 g, 31.67 mmol)의 테트라하이드로퓨란 (100 mL) 용액에 점적하였다. 반응 혼합물을 실온에서 2시간 동안 교반하였다. TLC와 HPLC로 반응의 진행을 모니터링하였다. 반응이 완료된 후, 물 및 EtOAc를 넣었다. 분리된 유기층을 물과 염수로 세척하고, 황산마그네슘으로 건조시킨 후 농축하였다. 잔류물을 MPLC (실리카겔, eluted with EtOAc in n-hexane from 0 to 20%)로 정제하고 회백색 분말 (5.7 g, 85.6%)을 얻었다. LC-MS (ESI+) m/z 421.3 [(M+H)+, calcd. C16H25IN2O3 m/z 420.0].Diisopropyl azodicarboxylate (6.2 mL, 31.67 mmol) was added dropwise to a solution of 6-iodopyridin-3-ol (3.5 g, 15.84 mmol), tert -butyl ( S )-(1-hydroxy-4-methylpentan-2-yl)carbamate (8.6 g, 39.59 mmol), and triphenyl phosphine (8.3 g, 31.67 mmol) in tetrahydrofuran (100 mL). The reaction mixture was stirred at room temperature for 2 h. The progress of the reaction was monitored by TLC and HPLC. After the reaction was completed, water and EtOAc were added. The separated organic layer was washed with water and brine, dried over magnesium sulfate, and concentrated. The residue was purified by MPLC (silica gel, eluted with EtOAc in n -hexane from 0 to 20%) to give an off-white powder (5.7 g, 85.6%). LC-MS (ESI+) m/z 421.3 [(M+H) + , calcd. C 16 H 25 IN 2 O 3 m/z 420.0].

실시예 82를 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 82 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: (S)-1-((6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민(S)-1-((6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine

이 화합물은 tert-부틸 (S)-(1-((6-요오도피리딘-3-일)옥시)-4-메틸펜탄-2-일)카바메이트 (100.0 mg, 0.24 mmol) (실시예 82, A 파트) 및 tert-부틸 5-플루오로-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (129.2 mg, 0.36 mmol)를 사용하여 제조하였고, 연한-황색 분말 (15.6 mg, 19.9%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.39-8.44 (m, 2H), 8.16 (s, 1H), 7.99 (s, 1H), 7.76 (d, 1H), 7.49-7.52 (m, 1H), 4.30-4.35 (m, 1H), 4.11-4.15 (m, 1H), 3.64-3.66 (m, 1H), 1.79-1.84 (m, 1H), 1.58-1.69 (m, 2H), 1.03 (t, 6H). LC-MS (ESI+) m/z 329.2 [(M+H)+, calcd. C18H21FN4O m/z 328.1].This compound was prepared using tert -butyl ( S )-(1-((6-iodopyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 82, Part A) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (129.2 mg, 0.36 mmol) to obtain a pale-yellow powder (15.6 mg, 19.9%). 1H NMR (500 MHz, MeOD) δ 8.39-8.44 (m, 2H), 8.16 (s, 1H), 7.99 (s, 1H), 7.76 (d, 1H), 7.49-7.52 (m, 1H), 4.30-4.35 (m, 1H), 4.11-4.15 (m, 1H), 3.64-3.66 (m, 1H), 1.79-1.84 (m, 1H), 1.58-1.69 (m, 2H), 1.03 (t, 6H). LC-MS (ESI+) m/z 329.2 [(M+H) + , calcd. C 18 H 21 FN 4 O m/z 328.1].

실시예 83: (Example 83: ( SS )-1-((6-(4-메톡시-1)-1-((6-(4-methoxy-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민 [(]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [( SS )-1-((6-(4-methoxy-1)-1-((6-(4-methoxy-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

실시예 83을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 83 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: (S)-1-((6-(4-메톡시-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민(S)-1-((6-(4-methoxy-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine

이 화합물은 tert-부틸 (S)-(1-((6-요오도피리딘-3-일)옥시)-4-메틸펜탄-2-일)카바메이트 (100.0 mg, 0.24 mmol) (실시예 82, A 파트) 및 tert-부틸 4-메톡시-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (133.5 mg, 0.36 mmol)를 사용하여 제조하였고, 아이보리색 분말 (17.8 mg, 21.9%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.23 (m, 1H), 8.12 (d, 1H), 7.80 (d, 1H), 7.48-7.51 (m, 2H), 6.74 (d, 1H), 4.24-4.26 (m, 1H), 4.06-4.09 (m, 1H), 3.95 (s, 3H), 3.55-3.57 (m, 1H), 1.79-1.82 (m, 1H), 1.55-1.63 (m, 2H), 1.00 (t, 6H). LC-MS (ESI+) m/z 341.7 [(M+H)+, calcd. C19H24N4O2 m/z 340.1].This compound was prepared using tert -butyl ( S )-(1-((6-iodopyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 82, Part A) and tert -butyl 4-methoxy-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (133.5 mg, 0.36 mmol) to obtain an ivory powder (17.8 mg, 21.9%). 1H NMR (500 MHz, MeOD) δ 8.23 (m, 1H), 8.12 (d, 1H), 7.80 (d, 1H), 7.48-7.51 (m, 2H), 6.74 (d, 1H), 4.24-4.26 (m, 1H), 4.06-4.09 (m, 1H), 3.95 (s, 3H), 3.55-3.57 (m, 1H), 1.79-1.82 (m, 1H), 1.55-1.63 (m, 2H), 1.00 (t, 6H). LC-MS (ESI+) m/z 341.7 [(M+H) + , calcd. C 19 H 24 N 4 O 2 m/z 340.1].

실시예 84: (Example 84: ( SS )-1-((6-(1)-1-((6-(1 HH -피라졸-4-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민 [(-pyrazol-4-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [( SS )-1-((6-(1)-1-((6-(1 HH -pyrazol-4-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]-pyrazol-4-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

실시예 84를 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 84 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: (S)-1-((6-(1H-피라졸-4-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민(S)-1-((6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine

이 화합물은 tert-부틸 (S)-(1-((6-요오도피리딘-3-일)옥시)-4-메틸펜탄-2-일)카바메이트 (100.0 mg, 0.24 mmol) (실시예 82, A 파트) 및 tert-부틸 4-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피라졸-1-카복실레이트 (133.5 mg, 0.36 mmol)를 사용하여 제조하였고, 아이보리색 분말 (23.3 mg, 37.6%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.28 (d, 1H), 8.09 (b, 2H), 7.68 (d, 1H), 7.51-7.53 (m, 1H), 4.33-4.35 (m, 1H), 4.15-4.18 (m, 1H), 3.69-3.71 (m, 1H), 1.79-1.82 (m, 1H), 1.64-1.72 (m, 2H), 1.02 (t, 6H). LC-MS (ESI+) m/z 261.6 [(M+H)+, calcd. C14H20N4O m/z 260.1].This compound was prepared using tert -butyl (S)-(1-((6-iodopyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 82, Part A) and tert -butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole-1-carboxylate (133.5 mg, 0.36 mmol) to obtain an ivory powder (23.3 mg, 37.6%). 1H NMR (500 MHz, MeOD) δ 8.28 (d, 1H), 8.09 (b, 2H), 7.68 (d, 1H), 7.51-7.53 (m, 1H), 4.33-4.35 (m, 1H), 4.15-4.18 (m, 1H), 3.69-3.71 (m, 1H), 1.79-1.82 (m, 1H), 1.64-1.72 (m, 2H), 1.02 (t, 6H). LC-MS (ESI+) m/z 261.6 [(M+H) + , calcd. C 14 H 20 N 4 O m/z 260.1].

실시예 85: (Example 85: ( SS )-1-((6-(1)-1-((6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민 [(]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [( SS )-1-((6-(1)-1-((6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

실시예 85를 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 85 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: (S)-1-((6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민(S)-1-((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine

이 화합물은 tert-부틸 (S)-(1-((6-요오도피리딘-3-일)옥시)-4-메틸펜탄-2-일)카바메이트 (100.0 mg, 0.24 mmol) (실시예 82, A 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (122.8 mg, 0.36 mmol)를 사용하여 제조하였고, 아이보리색 분말 (16.7 mg, 22.6%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.03 (d, 1H), 8.52-8.58 (m, 2H), 8.37 (s, 1H), 8.25 (d, 1H), 8.13 (d, 1H), 7.62-7.64 (m, 1H), 4.51-4.53 (m, 1H), 4.34-4.37 (m, 1H), 3.78-3.79 (m, 1H), 1.76-1.86 (m, 1H), 1.67-1.76 (m, 2H), 1.05 (d, 3H), 1.04 (d, 3H). LC-MS (ESI+) m/z 311.5 [(M+H)+, calcd. C18H22N4O m/z 310.1].This compound was prepared using tert -butyl ( S )-(1-((6-iodopyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 82, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (122.8 mg, 0.36 mmol) to obtain an ivory powder (16.7 mg, 22.6%). 1H NMR (500 MHz, MeOD) δ 9.03 (d, 1H), 8.52-8.58 (m, 2H), 8.37 (s, 1H), 8.25 (d, 1H), 8.13 (d, 1H), 7.62-7.64 (m, 1H), 4.51-4.53 (m, 1H), 4.34-4.37 (m, 1H), 3.78-3.79 (m, 1H), 1.76-1.86 (m, 1H), 1.67-1.76 (m, 2H), 1.05 (d, 3H), 1.04 (d, 3H). LC-MS (ESI+) m/z 311.5 [(M+H) + , calcd. C 18 H 22 N 4 O m/z 310.1].

실시예 86: (Example 86: ( SS )-1-((6-(4-플루오로-1)-1-((6-(4-fluoro-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민 [(]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [( SS )-1-((6-(4-fluoro-1)-1-((6-(4-fluoro-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

실시예 86을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 86 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: (S)-1-((6-(4-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민(S)-1-((6-(4-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine

이 화합물은 tert-부틸 (S)-(1-((6-요오도피리딘-3-일)옥시)-4-메틸펜탄-2-일)카바메이트 (100.0 mg, 0.24 mmol) (실시예 82, A 파트) 및 tert-부틸 4-플루오로-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (129.2 mg, 0.36 mmol)를 사용하여 제조하였고, 갈색 분말 (36.5 mg, 46.7%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.30 (d, 1H), 8.21-8.23 (m, 1H), 7.76 (d, 2H), 7.50-7.52 (m, 1H), 6.93-6.96 (m, 1H), 4.18-4.21 (m, 1H), 3.99-4.03 (m, 1H), 3.44-3.49 (m, 1H), 1.77-1.83 (m, 1H), 1.49-1.58 (m, 2H), 0.97-1.00 (m, 6H). LC-MS (ESI+) m/z 329.6 [(M+H)+, calcd. C18H21FN4O m/z 328.1].This compound was prepared using tert -butyl ( S )-(1-((6-iodopyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 82, Part A) and tert -butyl 4-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (129.2 mg, 0.36 mmol) to obtain a brown powder (36.5 mg, 46.7%). 1H NMR (500 MHz, MeOD) δ 8.30 (d, 1H), 8.21-8.23 (m, 1H), 7.76 (d, 2H), 7.50-7.52 (m, 1H), 6.93-6.96 (m, 1H), 4.18-4.21 (m, 1H), 3.99-4.03 (m, 1H), 3.44-3.49 (m, 1H), 1.77-1.83 (m, 1H), 1.49-1.58 (m, 2H), 0.97-1.00 (m, 6H). LC-MS (ESI+) m/z 329.6 [(M+H) + , calcd. C 18 H 21 FN 4 O m/z 328.1].

실시예 87: (Example 87: ( SS )-1-((6-(6-플루오로-1)-1-((6-(6-fluoro-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민 [(]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [( SS )-1-((6-(6-fluoro-1)-1-((6-(6-fluoro-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

실시예 87을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 87 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: (S)-1-((6-(6-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민(S)-1-((6-(6-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine

이 화합물은 tert-부틸 (S)-(1-((6-요오도피리딘-3-일)옥시)-4-메틸펜탄-2-일)카바메이트 (100.0 mg, 0.24 mmol) (실시예 82, A 파트) 및 tert-부틸 6-플루오로-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (129.2 mg, 0.36 mmol)를 사용하여 제조하였고, 연한-갈색 분말 (28.7 mg, 36.7%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.50-8.53 (m, 2H), 8.25-8.30 (m, 2H), 8.17 (s, 1H), 6.98 (d, 1H), 4.51-4.54 (m, 1H), 4.34-4.37 (m, 1H), 3.77-3.79 (m, 1H), 1.74-1.85 (m, 1H), 1.63-1.71 (m, 2H), 1.02-1.04 (m, 6H). LC-MS (ESI+) m/z 329.4 [(M+H)+, calcd. C18H21FN4O m/z 328.1].This compound was prepared using tert -butyl ( S )-(1-((6-iodopyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 82, Part A) and tert -butyl 6-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrrolo[2,3-b]pyridine-1-carboxylate (129.2 mg, 0.36 mmol) to obtain a pale-brown powder (28.7 mg, 36.7%). 1H NMR (500 MHz, MeOD) δ 8.50-8.53 (m, 2H), 8.25-8.30 (m, 2H), 8.17 (s, 1H), 6.98 (d, 1H), 4.51-4.54 (m, 1H), 4.34-4.37 (m, 1H), 3.77-3.79 (m, 1H), 1.74-1.85 (m, 1H), 1.63-1.71 (m, 2H), 1.02-1.04 (m, 6H). LC-MS (ESI+) m/z 329.4 [(M+H) + , calcd. C 18 H 21 FN 4 O m/z 328.1].

실시예 88: (Example 88: ( SS )-1-((6-(6-플루오로-1)-1-((6-(6-fluoro-1 HH -피롤로[3,2--Pyrrolo[3,2- bb ]피리딘-1-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민 [(]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [( SS )-1-((6-(6-fluoro-1)-1-((6-(6-fluoro-1 HH -pyrrolo[3,2--pyrrolo[3,2- bb ]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

실시예 88은 tert-부틸 (S)-(1-((6-요오도피리딘-3-일)옥시)-4-메틸펜탄-2-일)카바메이트 (100.0 mg, 0.24 mmol) (실시예 82, A 파트) 및 6-플루오로-1H-피롤로[3,2-b]피리딘 (32.3 mg, 0.24 mmol)을 사용하여 실시예 64에 대하여 설명한 것과 유사한 절차에 따라 제조하였고, 연한-갈색 분말 (27.6 mg, 35.3%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.33 (d, 1H), 8.89 (d, 1H), 8.67 (d, 1H), 8.44 (d, 1H), 7.77-7.85 (m, 2H), 7.11 (d, 1H), 4.24-4.44 (m, 2H), 3.74-3.75 (m, 1H), 1.65-1.83 (m, 3H), 1.03-1.05 (m, 6H). LC-MS (ESI+) m/z 329.3 [(M+H)+, calcd. C18H21FN4O m/z 328.1].Example 88 was prepared according to a similar procedure as that described for Example 64 using tert -butyl ( S )-(1-((6-iodopyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 82, Part A) and 6-fluoro-1 H -pyrrolo[3,2- b ]pyridine (32.3 mg, 0.24 mmol) to obtain a pale-brown powder (27.6 mg, 35.3%). 1H NMR (500 MHz, MeOD) δ 9.33 (d, 1H), 8.89 (d, 1H), 8.67 (d, 1H), 8.44 (d, 1H), 7.77-7.85 (m, 2H), 7.11 (d, 1H), 4.24-4.44 (m, 2H), 3.74-3.75 (m, 1H), 1.65-1.83 (m, 3H), 1.03-1.05 (m, 6H). LC-MS (ESI+) m/z 329.3 [(M+H) + , calcd. C 18 H 21 FN 4 O m/z 328.1].

실시예 89: (Example 89: ( SS )-1-((6-(1)-1-((6-(1 HH -피롤로[3,2--Pyrrolo[3,2- bb ]피리딘-1-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민 [(]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [( SS )-1-((6-(1)-1-((6-(1 HH -pyrrolo[3,2--pyrrolo[3,2- bb ]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

실시예 89는 tert-부틸 (S)-(1-((6-요오도피리딘-3-일)옥시)-4-메틸펜탄-2-일)카바메이트 (100.0 mg, 0.24 mmol) (실시예 82, A 파트) 및 1H-피롤로[3,2-b]피리딘 (28.1 mg, 0.24 mmol)을 사용하여 실시예 64에 대하여 설명한 것과 유사한 절차에 따라 제조하였고, 아이보리색 분말 (13.5 mg, 18.2%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.39 (d, 1H), 8.66-8.70 (m, 2H), 8.45 (d, 1H), 7.79-7.86 (m, 3H), 7.12 (d, 1H), 4.25-4.45 (m, 2H), 3.73-3.77 (m, 1H), 1.66-1.84 (m, 3H), 1.03-1.05 (m, 6H). LC-MS (ESI+) m/z 311.6 [(M+H)+, calcd. C18H22N4O m/z 310.1].Example 89 was prepared according to a similar procedure as described for Example 64 using tert -butyl ( S )-(1-((6-iodopyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 82, Part A) and 1 H -pyrrolo[3,2- b ]pyridine (28.1 mg, 0.24 mmol) to obtain an ivory powder (13.5 mg, 18.2%). 1H NMR (500 MHz, MeOD) δ 9.39 (d, 1H), 8.66-8.70 (m, 2H), 8.45 (d, 1H), 7.79-7.86 (m, 3H), 7.12 (d, 1H), 4.25-4.45 (m, 2H), 3.73-3.77 (m, 1H), 1.66-1.84 (m, 3H), 1.03-1.05 (m, 6H). LC-MS (ESI+) m/z 311.6 [(M+H) + , calcd. C 18 H 22 N 4 O m/z 310.1].

실시예 90: (Example 90: ( SS )-1-((6-(1)-1-((6-(1 HH -피롤로[2,3--Pyrrolo[2,3- cc ]피리딘-1-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민 [(]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [( SS )-1-((6-(1)-1-((6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- cc ]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

실시예 90은 tert-부틸 (S)-(1-((6-요오도피리딘-3-일)옥시)-4-메틸펜탄-2-일)카바메이트 (100.0 mg, 0.24 mmol) (실시예 82, A 파트) 및 1H-피롤로[2,3-c]피리딘 (28.1 mg, 0.24 mmol)을 사용하여 실시예 64에 대하여 설명한 것과 유사한 절차에 따라 제조하였고, 아이보리색 분말 (17.3 mg, 23.4%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.99 (s, 1H), 8.76 (d, 1H), 8.45 (d, 1H), 8.38 (d, 1H), 8.24 (d, 1H), 7.91 (d, 1H), 7.79-7.81 (m, 1H), 7.21 (d, 1H), 4.25-4.45 (m, 2H), 3.75-3.77 (m, 1H), 1.66-1.84 (m, 3H), 1.03-1.05 (m, 6H). LC-MS (ESI+) m/z 311.3 [(M+H)+, calcd. C18H22N4O m/z 310.1].Example 90 was prepared according to a similar procedure as described for Example 64 using tert -butyl ( S )-(1-((6-iodopyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 82, Part A) and 1 H -pyrrolo[2,3- c ]pyridine (28.1 mg, 0.24 mmol) to obtain an ivory powder (17.3 mg, 23.4%). 1H NMR (500 MHz, MeOD) δ 9.99 (s, 1H), 8.76 (d, 1H), 8.45 (d, 1H), 8.38 (d, 1H), 8.24 (d, 1H), 7.91 (d, 1H), 7.79-7.81 (m, 1H), 7.21 (d, 1H), 4.25-4.45 (m, 2H), 3.75-3.77 (m, 1H), 1.66-1.84 (m, 3H), 1.03-1.05 (m, 6H). LC-MS (ESI+) m/z 311.3 [(M+H) + , calcd. C 18 H 22 N 4 O m/z 310.1].

실시예 91: (Example 91: ( SS )-1-((6-(1)-1-((6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-1-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민 [(]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [( SS )-1-((6-(1)-1-((6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

실시예 91은 tert-부틸 (S)-(1-((6-요오도피리딘-3-일)옥시)-4-메틸펜탄-2-일)카바메이트 (100.0 mg, 0.24 mmol) (실시예 82, A 파트) 및 1H-피롤로[2,3-b]피리딘 (28.1 mg, 0.24 mmol)을 사용하여 실시예 64에 대하여 설명한 것과 유사한 절차에 따라 제조하였고, 아이보리색 분말 (19.8 mg, 23.4%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.82 (d, 1H), 8.61 (d, 1H), 8.51 (d, 1H), 8.46 (d, 1H), 7.99 (d, 1H), 7.83-7.85 (m, 1H), 7.75-7.79 (m, 1H), 7.16 (d, 1H), 4.11-4.31 (m, 2H), 3.75-3.76 (m, 1H), 1.61-1.74 (m, 3H), 1.02-1.04 (m, 6H). LC-MS (ESI+) m/z 311.1 [(M+H)+, calcd. C18H22N4O m/z 310.1].Example 91 was prepared according to a similar procedure as described for Example 64 using tert -butyl ( S )-(1-((6-iodopyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 82, Part A) and 1 H -pyrrolo[2,3- b ]pyridine (28.1 mg, 0.24 mmol) to obtain an ivory powder (19.8 mg, 23.4%). 1H NMR (500 MHz, MeOD) δ 8.82 (d, 1H), 8.61 (d, 1H), 8.51 (d, 1H), 8.46 (d, 1H), 7.99 (d, 1H), 7.83-7.85 (m, 1H), 7.75-7.79 (m, 1H), 7.16 (d, 1H), 4.11-4.31 (m, 2H), 3.75-3.76 (m, 1H), 1.61-1.74 (m, 3H), 1.02-1.04 (m, 6H). LC-MS (ESI+) m/z 311.1 [(M+H) + , calcd. C 18 H 22 N 4 O m/z 310.1].

실시예 92: (Example 92: ( SS )-1-((6-(1)-1-((6-(1 HH -피롤로[3,2--Pyrrolo[3,2- cc ]피리딘-1-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민 [(]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine [( SS )-1-((6-(1)-1-((6-(1 HH -pyrrolo[3,2--pyrrolo[3,2- cc ]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine]

실시예 92는 tert-부틸 (S)-(1-((6-요오도피리딘-3-일)옥시)-4-메틸펜탄-2-일)카바메이트 (100.0 mg, 0.24 mmol) (실시예 82, A 파트) 및 1H-피롤로[3,2-c]피리딘 (28.1 mg, 0.24 mmol)을 사용하여 실시예 64에 대하여 설명한 것과 유사한 절차에 따라 제조하였고, 아이보리색 분말 (15.6 mg, 21.1%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.25 (s, 1H), 8.73 (d, 1H), 8.45-8.47 (m, 2H), 8.35 (d, 1H), 7.78-7.85 (m, 2H), 7.28 (d, 1H), 4.24-4.44 (m, 2H), 3.74-3.76 (m, 1H), 1.64-1.83 (m, 3H), 1.02-1.04 (m, 6H). LC-MS (ESI+) m/z 311.2 [(M+H)+, calcd. C18H22N4O m/z 310.1].Example 92 was prepared according to a similar procedure as described for Example 64 using tert -butyl ( S )-(1-((6-iodopyridin-3-yl)oxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 82, Part A) and 1 H -pyrrolo[3,2- c ]pyridine (28.1 mg, 0.24 mmol) to obtain an ivory powder (15.6 mg, 21.1%). 1H NMR (500 MHz, MeOD) δ 9.25 (s, 1H), 8.73 (d, 1H), 8.45-8.47 (m, 2H), 8.35 (d, 1H), 7.78-7.85 (m, 2H), 7.28 (d, 1H), 4.24-4.44 (m, 2H), 3.74-3.76 (m, 1H), 1.64-1.83 (m, 3H), 1.02-1.04 (m, 6H). LC-MS (ESI+) m/z 311.2 [(M+H) + , calcd. C 18 H 22 N 4 O m/z 310.1].

실시예 93: (Example 93: ( SS )-1-(4-(5-플루오로-1)-1-(4-(5-fluoro-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)펜옥시)-4-메틸펜탄-2-아민 [(]pyridin-3-yl)phenoxy)-4-methylpentan-2-amine [( SS )-1-(4-(5-fluoro-1)-1-(4-(5-fluoro-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)phenoxy)-4-methylpentan-2-amine]]pyridin-3-yl)phenoxy)-4-methylpentan-2-amine]

실시예 93을 실시예 82에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 93 was prepared according to a procedure similar to that described for Example 82.

A 파트: Part A: tert-부틸 (S)-(1-(4-요오도펜옥시)-4-메틸펜탄-2-일)카바메이트tert-butyl (S)-(1-(4-iodophenoxy)-4-methylpentan-2-yl)carbamate

이 화합물은 4-요오도페놀 (100.0 mg, 0.45 mmol) 및 tert-부틸 (S)-(1-하이드록시-4-메틸펜탄-2-일)카바메이트 (198.0 mg, 0.91 mmol)를 사용하여 100oC에서 제조하였고, 아이보리색 분말 (134.3 mg, 70.4%)을 얻었다. LC-MS (ESI+) m/z 420.1 [(M+H)+, calcd. C17H26INO3 m/z 419.0].This compound was prepared at 100 o C using 4-iodophenol (100.0 mg, 0.45 mmol) and tert -butyl ( S )-(1-hydroxy-4-methylpentan-2-yl)carbamate (198.0 mg, 0.91 mmol) and ivory powder (134.3 mg, 70.4%) was obtained. LC-MS (ESI+) m/z 420.1 [(M+H) + , calcd. C 17 H 26 INO 3 m/z 419.0].

실시예 93을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 93 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: (S)-1-(4-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)펜옥시)-4-메틸펜탄-2-아민(S)-1-(4-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-4-methylpentan-2-amine

이 화합물은 tert-부틸 (S)-(1-(4-요오도펜옥시)-4-메틸펜탄-2-일)카바메이트 (100.0 mg, 0.24 mol) (실시예 93, A 파트) 및 tert-부틸 5-플루오로-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (129.5 mg, 0.36 mmol)를 사용하여 제조하였고, 아이보리색 분말 (15.3 mg, 19.5%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.13 (s, 1H), 7.94-7.97 (m, 1H), 7.62 (s, 1H), 7.54 (d, 2H), 7.04 (d, 2H), 3.99-4.02 (m, 1H), 3.80-3.83 (m, 1H), 3.25-3.28 (m, 1H), 1.78-1.82 (m, 1H), 1.37-1.43 (m, 2H), 0.98 (d, 3H), 0.96 (d, 3H). LC-MS (ESI+) m/z 328.4 [(M+H)+, calcd. C19H22FN3O m/z 327.1].This compound was prepared using tert -butyl ( S )-(1-(4-iodophenoxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.24 mol) (Example 93, Part A) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (129.5 mg, 0.36 mmol) to obtain an ivory powder (15.3 mg, 19.5%). 1H NMR (500 MHz, MeOD) δ 8.13 (s, 1H), 7.94-7.97 (m, 1H), 7.62 (s, 1H), 7.54 (d, 2H), 7.04 (d, 2H), 3.99-4.02 (m, 1H), 3.80-3.83 (m, 1H), 3.25-3.28 (m, 1H), 1.78-1.82 (m, 1H), 1.37-1.43 (m, 2H), 0.98 (d, 3H), 0.96 (d, 3H). LC-MS (ESI+) m/z 328.4 [(M+H) + , calcd. C 19 H 22 FN 3 O m/z 327.1].

실시예 94: (Example 94: ( SS )-1-(4-(5-플루오로-1)-1-(4-(5-fluoro-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)-2-(트리플루오로메틸)펜옥시)-4-메틸펜탄-2-아민 [(]pyridin-3-yl)-2-(trifluoromethyl)phenoxy)-4-methylpentan-2-amine [( SS )-1-(4-(5-fluoro-1)-1-(4-(5-fluoro-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)-2-(trifluoromethyl)phenoxy)-4-methylpentan-2-amine]]pyridin-3-yl)-2-(trifluoromethyl)phenoxy)-4-methylpentan-2-amine]

실시예 94를 실시예 82에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 94 was prepared according to a procedure similar to that described for Example 82.

A 파트: Part A: tert-부틸 (S)-(1-(4-브로모-2-(트리플루오로메틸)펜옥시)-4-메틸펜탄-2-일)카바메이트tert-Butyl (S)-(1-(4-bromo-2-(trifluoromethyl)phenoxy)-4-methylpentan-2-yl)carbamate

이 화합물은 4-브로모-2-(트리플루오로메틸)페놀 (300.0 mg, 1.24 mmol) 및 tert-부틸 (S)-(1-하이드록시-4-메틸펜탄-2-일)카바메이트 (217.3 mg, 2.49 mmol)를 사용하여 제조하였고, 아이보리색 분말 (293.3 mg, 53.5%)을 얻었다. LC-MS (ESI+) m/z 440.4 [(M+H)+, calcd. C18H25BrF3NO3 m/z 439.0].This compound was prepared using 4-bromo-2-(trifluoromethyl)phenol (300.0 mg, 1.24 mmol) and tert -butyl ( S )-(1-hydroxy-4-methylpentan-2-yl)carbamate (217.3 mg, 2.49 mmol) and the resulting ivory powder (293.3 mg, 53.5%) was obtained. LC-MS (ESI+) m/z 440.4 [(M+H) + , calcd. C 18 H 25 BrF 3 NO 3 m/z 439.0].

실시예 94를 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 94 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: (S)-1-(4-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)-2-(트리플루오로메틸)펜옥시)-4-메틸펜탄-2-아민(S)-1-(4-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(trifluoromethyl)phenoxy)-4-methylpentan-2-amine

이 화합물은 tert-부틸 (S)-(1-(4-브로모-2-(트리플루오로메틸)펜옥시)-4-메틸펜탄-2-일)카바메이트 (100.0 mg, 0.23 mmol) (실시예 94, A 파트) 및 tert-부틸 5-플루오로-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (123.4 mg, 0.34 mmol)를 사용하여 제조하였고, 황색 분말 (32.6 mg, 36.3%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.30-8.38 (m, 2H), 7.86-7.92 (m, 3H), 7.38 (d, 1H), 4.23-4.40 (m, 2H), 3.70-3.72 (m, 1H), 1.75-1.80 (m, 2H), 1.61-1.64 (m, 1H),0.99-1.01 (m, 6H). LC-MS (ESI+) m/z 396.3 [(M+H)+, calcd. C20H21F4N3O m/z 395.1].This compound was prepared using tert -butyl ( S )-(1-(4-bromo-2-(trifluoromethyl)phenoxy)-4-methylpentan-2-yl)carbamate (100.0 mg, 0.23 mmol) (Example 94, Part A) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (123.4 mg, 0.34 mmol) and a yellow powder (32.6 mg, 36.3%) was obtained. 1H NMR (500 MHz, MeOD) δ 8.30-8.38 (m, 2H), 7.86-7.92 (m, 3H), 7.38 (d, 1H), 4.23-4.40 (m, 2H), 3.70-3.72 (m, 1H), 1.75-1.80 (m, 2H), 1.61-1.64 (m, 1H),0.99-1.01 (m, 6H). LC-MS (ESI+) m/z 396.3 [(M+H) + , calcd. C 20 H 21 F 4 N 3 O m/z 395.1].

실시예 95: 1-(((6-(2Example 95: 1-(((6-(2 HH -1,2,3-트리아졸-4-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민 [1-(((6-(2-1,2,3-triazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((6-(2 HH -1,2,3-triazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]-1,2,3-triazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

실시예 95를 실시예 8에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 95 was prepared according to a procedure similar to that described for Example 8.

B 파트: Part B: 1-(((6-(2H-1,2,3-트리아졸-4-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민1-(((6-(2H-1,2,3-triazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

이 화합물은 tert-부틸 (1-(((6-브로모-2-(트리플루오로메틸)피리딘-3-일)옥시)메틸)사이클로프로필)카바메이트 (100.0 mg, 0.24 mol) (실시예 70, B 파트) 및 tert-부틸 2-(테트라하이드로-2H-피란-2-일)-4-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-2H-1,2,3-트리아졸 (101.8 mg, 0.36 mmol)을 사용하여 제조하였고, 아이보리색 분말 (44.4 mg, 61.0%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.37 (s, 1H), 8.23 (d, 1H), 7.83 (d, 1H), 4.36 (s, 2H), 1.13-1.20 (m, 4H). LC-MS (ESI+) m/z 300.2 [(M+H)+, calcd. C12H12F3N5O m/z 299.0].This compound was prepared using tert -butyl (1-(((6-bromo-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.24 mol) (Example 70, Part B) and tert -butyl 2-(tetrahydro-2 H -pyran-2-yl)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2 H -1,2,3-triazole (101.8 mg, 0.36 mmol) and an ivory powder (44.4 mg, 61.0%) was obtained. 1H NMR (500 MHz, MeOD) δ 8.37 (s, 1H), 8.23 (d, 1H), 7.83 (d, 1H), 4.36 (s, 2H), 1.13-1.20 (m, 4H). LC-MS (ESI+) m/z 300.2 [(M+H) + , calcd. C 12 H 12 F 3 N 5 O m/z 299.0].

실시예 96: 1-(((6-(1Example 96: 1-(((6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민 [1-(((6-(1]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

실시예 96을 실시예 82에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 96 was prepared according to a procedure similar to that described for Example 82.

A 파트: Part A: tert-부틸 (1-(((6-브로모피리딘-3-일)옥시)메틸)사이클로프로필)카바메이트tert-butyl (1-(((6-bromopyridin-3-yl)oxy)methyl)cyclopropyl)carbamate

이 화합물은 6-브로모피리딘-3-올 (100.0 mg, 0.57 mol) 및 tert-부틸 (1-(하이드록시메틸)사이클로프로필)카바메이트 (215.2 mg, 1.15 mmol)를 사용하여 제조하였고, 회백색 분말 (54.0 mg, 27.3%)을 얻었다. LC-MS (ESI+) m/z 343.6 [(M+H)+, calcd. C14H19BrN2O3 m/z 342.0].This compound was prepared using 6-bromopyridin-3-ol (100.0 mg, 0.57 mol) and tert -butyl (1-(hydroxymethyl)cyclopropyl)carbamate (215.2 mg, 1.15 mmol) and an off-white powder (54.0 mg, 27.3%) was obtained. LC-MS (ESI+) m/z 343.6 [(M+H) + , calcd. C 14 H 19 BrN 2 O 3 m/z 342.0].

실시예 96을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 96 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: 1-(((6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민1-(((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

이 화합물은 tert-부틸 (1-(((6-브로모피리딘-3-일)옥시)메틸)사이클로프로필)카바메이트 (100.0 mg, 0.29 mol) (실시예 96, A 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (150.4 mg, 0.44 mmol)를 사용하여 제조하였고, 갈색 분말 (30.6 mg, 37.4%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.07 (d, 1H), 8.59 (d, 2H), 8.44 (s, 1H), 8.24-8.34 (m, 2H), 7.71-7.73 (m, 1H), 4.44 (s, 2H), 1.15-1.20 (m, 4H). LC-MS (ESI+) m/z 281.3 [(M+H)+, calcd. C16H16N4O m/z 280.1].This compound was prepared using tert -butyl (1-(((6-bromopyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.29 mol) (Example 96, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (150.4 mg, 0.44 mmol) to obtain a brown powder (30.6 mg, 37.4%). 1H NMR (500 MHz, MeOD) δ 9.07 (d, 1H), 8.59 (d, 2H), 8.44 (s, 1H), 8.24-8.34 (m, 2H), 7.71-7.73 (m, 1H), 4.44 (s, 2H), 1.15-1.20 (m, 4H). LC-MS (ESI+) m/z 281.3 [(M+H) + , calcd. C 16 H 16 N 4 O m/z 280.1].

실시예 97: 1-(((6-(1Example 97: 1-(((6-(1 HH -피라졸-4-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민 [1-(((6-(1-pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((6-(1 HH -pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]-pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

실시예 97을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 97 was prepared according to a procedure similar to that described for Example 57.

C 파트: 1-(((6-(1H-피라졸-4-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민Part C: 1-(((6-(1H-pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

이 화합물은 tert-부틸 (1-(((6-브로모피리딘-3-일)옥시)메틸)사이클로프로필)카바메이트 (100.0 mg, 0.29 mmol) (실시예 96, A 파트) 및 tert-부틸 4-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피라졸-1-카복실레이트 (128.5 mg, 0.44 mmol)를 사용하여 제조하였고, 연한-황색 분말 (20.2 mg, 30.1%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.39-8.43 (m, 3H), 8.21-8.27 (m, 2H), 4.40 (s, 2H), 1.13-1.19 (m, 4H). LC-MS (ESI+) m/z 231.4 [(M+H)+, calcd. C12H14N4O m/z 230.1].This compound was prepared using tert -butyl (1-(((6-bromopyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.29 mmol) (Example 96, Part A) and tert -butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole-1-carboxylate (128.5 mg, 0.44 mmol) to obtain a pale-yellow powder (20.2 mg, 30.1%). 1 H NMR (500 MHz, MeOD) δ 8.39-8.43 (m, 3H), 8.21-8.27 (m, 2H), 4.40 (s, 2H), 1.13-1.19 (m, 4H). LC-MS (ESI+) m/z 231.4 [(M+H) + , calcd. C 12 H 14 N 4 O m/z 230.1].

실시예 98: 1-(((6-(1Example 98: 1-(((6-(1 HH -피롤로[3,2--Pyrrolo[3,2- bb ]피리딘-1-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민 [1-(((6-(1]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((6-(1 HH -pyrrolo[3,2--pyrrolo[3,2- bb ]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

실시예 98은 tert-부틸 (1-(((6-브로모피리딘-3-일)옥시)메틸)사이클로프로필)카바메이트 (100.0 mg, 0.29 mmol) (실시예 96, A 파트) 및 1H-피롤로[3,2-b]피리딘 (34.4 mg, 0.29 mmol)을 사용하여 실시예 64에 대하여 설명한 것과 유사한 절차에 따라 제조하였고, 아이보리색 분말 (15.1 mg, 18.4%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.35 (d, 1H), 8.65-8.71 (m, 2H), 7.91-7.95 (m, 1H), 7.82-7.85 (m, 1H), 7.75 (d, 1H), 7.13 (d, 1H), 4.40 (s, 2H), 1.13-1.19 (m, 4H). LC-MS (ESI+) m/z 281.3 [(M+H)+, calcd. C16H16N4O m/z 280.1].Example 98 was prepared according to a similar procedure as described for Example 64 using tert -butyl (1-(((6-bromopyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.29 mmol) (Example 96, Part A) and 1 H -pyrrolo[3,2- b ]pyridine (34.4 mg, 0.29 mmol) to obtain an ivory powder (15.1 mg, 18.4%). 1H NMR (500 MHz, MeOD) δ 9.35 (d, 1H), 8.65-8.71 (m, 2H), 7.91-7.95 (m, 1H), 7.82-7.85 (m, 1H), 7.75 (d, 1H), 7.13 (d, 1H), 4.40 (s, 2H), 1.13-1.19 (m, 4H). LC-MS (ESI+) m/z 281.3 [(M+H) + , calcd. C 16 H 16 N 4 O m/z 280.1].

실시예 99: 1-(((2-플루오로-6-(1Example 99: 1-(((2-Fluoro-6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민 [1-(((2-fluoro-6-(1]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((2-fluoro-6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

실시예 99를 실시예 82에 대하여 설명한 것과 유사한 절차에 따라 제조하였다.Example 99 was prepared according to a procedure similar to that described for Example 82.

A 파트: Part A: tert-부틸 (1-(((6-브로모-2-플루오로피리딘-3-일)옥시)메틸)사이클로프로필)카바메이트tert-butyl (1-(((6-bromo-2-fluoropyridin-3-yl)oxy)methyl)cyclopropyl)carbamate

이 화합물은 6-브로모-2-플루오로피리딘-3-올 (1.0 g, 5.21 mmol) 및 tert-부틸 (1-(하이드록시메틸)사이클로프로필)카바메이트 (1.9 g, 10.42 mmol)를 사용하여 제조하였고, 회백색 분말 (0.72 g, 38.2%)을 얻었다. LC-MS (ESI+) m/z 361.5 [(M+H)+, calcd C14H18BrFN2O3 m/z 360.0].This compound was prepared using 6-bromo-2-fluoropyridin-3-ol (1.0 g, 5.21 mmol) and tert -butyl (1-(hydroxymethyl)cyclopropyl)carbamate (1.9 g, 10.42 mmol) and an off-white powder (0.72 g, 38.2%) was obtained. LC-MS (ESI+) m/z 361.5 [(M+H) + , calcd C 14 H 18 BrFN 2 O 3 m/z 360.0].

실시예 99를 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 99 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: 1-(((2-플루오로-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민1-(((2-fluoro-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

이 화합물은 tert-부틸 (1-(((6-브로모피리딘-3-일)옥시)메틸)사이클로프로필)카바메이트 (100.0 mg, 0.28 mol) (실시예 96, A 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (142.9 mg, 0.42 mmol)를 사용하여 제조하였고, 황색 분말 (28.5 mg, 34.5%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.46 (d, 1H), 8.48 (d, 1H), 8.29 (s, 1H), 7.80 (d, 1H), 7.66-7.81 (m, 2H), 4.29 (s, 2H), 1.11-1.19 (m, 4H). LC-MS (ESI+) m/z 299.5 [(M+H)+, calcd C16H15FN4O m/z 298.1].This compound was prepared using tert -butyl (1-(((6-bromopyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.28 mol) (Example 96, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (142.9 mg, 0.42 mmol) and a yellow powder (28.5 mg, 34.5%) was obtained. 1H NMR (500 MHz, MeOD) δ 9.46 (d, 1H), 8.48 (d, 1H), 8.29 (s, 1H), 7.80 (d, 1H), 7.66-7.81 (m, 2H), 4.29 (s, 2H), 1.11-1.19 (m, 4H). LC-MS (ESI+) m/z 299.5 [(M+H) + , calcd C 16 H 15 FN 4 O m/z 298.1].

실시예 100: 1-(((2-플루오로-6-(5-플루오로-1Example 100: 1-(((2-Fluoro-6-(5-Fluoro-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민 [1-(((2-fluoro-6-(5-fluoro-1]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((2-fluoro-6-(5-fluoro-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

실시예 100을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 100 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: 1-(((2-플루오로-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민1-(((2-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

이 화합물은 (1-(((6-브로모-2-플루오로피리딘-3-일)옥시)메틸)사이클로프로필)카바메이트 (100.0 mg, 0.28 mmol) (실시예 99, A 파트) 및 tert-부틸 5-플루오로-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (150.4 mg, 0.42 mmol)를 사용하여 제조하였고, 연한-황색 분말 (23.9 mg, 27.9%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.87-8.89 (m, 1H), 8.40 (t, 1H), 8.21 (s, 1H), 7.70 (d, 1H), 7.60-7.64 (m, 1H), 4.23 (s, 2H), 1.07-1.15 (m, 4H). LC-MS (ESI+) m/z 317.3 [(M+H)+, calcd C16H14F2N4O m/z 316.1].This compound was prepared using (1-(((6-bromo-2-fluoropyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.28 mmol) (Example 99, Part A) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (150.4 mg, 0.42 mmol) to obtain a pale-yellow powder (23.9 mg, 27.9%). 1H NMR (500 MHz, MeOD) δ 8.87-8.89 (m, 1H), 8.40 (t, 1H), 8.21 (s, 1H), 7.70 (d, 1H), 7.60-7.64 (m, 1H), 4.23 (s, 2H), 1.07-1.15 (m, 4H). LC-MS (ESI+) m/z 317.3 [(M+H) + , calcd C 16 H 14 F 2 N 4 O m/z 316.1].

실시예 101: 1-(((2-플루오로-6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민 [1-(((2-fluoro-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]Example 101: 1-(((2-fluoro-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((2-fluoro-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

실시예 101은 tert-부틸 (1-(((6-브로모피리딘-3-일)옥시)메틸)사이클로프로필)카바메이트 (100.0 mg, 0.28 mmol) (실시예 99, A 파트) 및 1H-피롤로[3,2-b]피리딘 (32.7 mg, 0.28 mmol)을 사용하여 실시예 64에 대하여 설명한 것과 유사한 절차에 따라 제조하였고, 회백색 분말 (10.1 mg, 12.2%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.35 (d, 1H), 8.65-8.71 (m, 2H), 7.91-7.95 (m, 1H), 7.82-7.85 (m, 1H), 7.75 (d, 1H), 7.13 (d, 1H), 4.35 (s, 2H), 1.14-1.21 (m, 4H). LC-MS (ESI+) m/z 299.3 [(M+H)+, calcd. C16H15FN4O m/z 298.1].Example 101 was prepared according to a similar procedure as described for Example 64 using tert -butyl (1-(((6-bromopyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.28 mmol) (Example 99, Part A) and 1 H -pyrrolo[3,2- b ]pyridine (32.7 mg, 0.28 mmol) to obtain an off-white powder (10.1 mg, 12.2%). 1H NMR (500 MHz, MeOD) δ 9.35 (d, 1H), 8.65-8.71 (m, 2H), 7.91-7.95 (m, 1H), 7.82-7.85 (m, 1H), 7.75 (d, 1H), 7.13 (d, 1H), 4.35 (s, 2H), 1.14-1.21 (m, 4H). LC-MS (ESI+) m/z 299.3 [(M+H) + , calcd. C 16 H 15 FN 4 O m/z 298.1].

실시예 102: 1-(((4-플루오로-6-(1Example 102: 1-(((4-Fluoro-6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민 [1-(((4-fluoro-6-(1]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((4-fluoro-6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

실시예 102를 실시예 82에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 102 was prepared according to a procedure similar to that described for Example 82.

A 파트: Part A: terttert -부틸 (1-(((6-브로모-4-플루오로피리딘-3-일)옥시)메틸)사이클로프로필)카바메이트-Butyl (1-(((6-bromo-4-fluoropyridin-3-yl)oxy)methyl)cyclopropyl)carbamate

이 화합물은 6-브로모-4-플루오로피리딘-3-올 (0.5 g, 2.60 mmol) 및 tert-부틸 (1-(하이드록시메틸)사이클로프로필)카바메이트 (0.7 g, 3.91 mmol)를 사용하여 제조하였고, 회백색 분말 (0.89 g, 94.9%)을 얻었다. LC-MS (ESI+) m/z 361.4 [(M+H)+, calcd C14H18BrFN2O3 m/z 360.0].This compound was prepared using 6-bromo-4-fluoropyridin-3-ol (0.5 g, 2.60 mmol) and tert -butyl (1-(hydroxymethyl)cyclopropyl)carbamate (0.7 g, 3.91 mmol) and an off-white powder (0.89 g, 94.9%) was obtained. LC-MS (ESI+) m/z 361.4 [(M+H) + , calcd C 14 H 18 BrFN 2 O 3 m/z 360.0].

실시예 102를 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 102 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: 1-(((4-플루오로-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민1-(((4-fluoro-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

이 화합물은 tert-부틸 (1-(((6-브로모-4-플루오로피리딘-3-일)옥시)메틸)사이클로프로필)카바메이트 (100.0 mg, 0.28 mmol) (실시예 102, A 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (142.9 mg, 0.42 mmol)를 사용하여 제조하였고, 회백색 분말 (36.7 mg, 44.4%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.23 (d, 1H), 8.76 (d, 1H), 8.62 (d, 1H), 8.49 (s, 1H), 8.25 (d, 1H), 7.76-7.79 (m, 1H), 4.51 (s, 2H), 1.17-1.23 (m, 4H). LC-MS (ESI+) m/z 299.6 [(M+H)+, calcd C16H15FN4O m/z 298.1].This compound was prepared using tert -butyl (1-(((6-bromo-4-fluoropyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.28 mmol) (Example 102, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (142.9 mg, 0.42 mmol) to obtain an off-white powder (36.7 mg, 44.4%). 1H NMR (500 MHz, MeOD) δ 9.23 (d, 1H), 8.76 (d, 1H), 8.62 (d, 1H), 8.49 (s, 1H), 8.25 (d, 1H), 7.76-7.79 (m, 1H), 4.51 (s, 2H), 1.17-1.23 (m, 4H). LC-MS (ESI+) m/z 299.6 [(M+H) + , calcd C 16 H 15 FN 4 O m/z 298.1].

실시예 103: 1-(((4-플루오로-6-(5-플루오로-1Example 103: 1-(((4-Fluoro-6-(5-Fluoro-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민 [1-(((4-fluoro-6-(5-fluoro-1]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((4-fluoro-6-(5-fluoro-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

실시예 103을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 103 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: 1-(((4-플루오로-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민1-(((4-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

이 화합물은 tert-부틸 (1-(((6-브로모-4-플루오로피리딘-3-일)옥시)메틸)사이클로프로필)카바메이트 (100.0 mg, 0.28 mmol) (실시예 102, A 파트) 및 tert-부틸 5-플루오로-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (150.4 mg, 0.42 mmol)를 사용하여 제조하였고, 연한-갈색 분말 (44.4 mg, 50.7%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.66 (d, 1H), 8.41 (s, 1H), 8.35-8.37 (m, 2H), 8.24 (d, 1H), 4.50 (s, 2H), 1.16-1.24 (m, 4H). LC-MS (ESI+) m/z 317.3 [(M+H)+, calcd C16H14F2N4O m/z 316.1].This compound was prepared using tert -butyl (1-(((6-bromo-4-fluoropyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.28 mmol) (Example 102, Part A) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (150.4 mg, 0.42 mmol) to obtain a pale-brown powder (44.4 mg, 50.7%). 1H NMR (500 MHz, MeOD) δ 8.66 (d, 1H), 8.41 (s, 1H), 8.35-8.37 (m, 2H), 8.24 (d, 1H), 4.50 (s, 2H), 1.16-1.24 (m, 4H). LC-MS (ESI+) m/z 317.3 [(M+H) + , calcd C 16 H 14 F 2 N 4 O m/z 316.1].

실시예 104: 1-(((5-플루오로-6-(1Example 104: 1-(((5-Fluoro-6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민 [1-(((5-fluoro-6-(1]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((5-fluoro-6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

실시예 104를 실시예 82에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 104 was prepared according to a procedure similar to that described for Example 82.

A 파트: Part A: tert-부틸 (1-(((6-브로모-5-플루오로피리딘-3-일)옥시)메틸)사이클로프로필)카바메이트tert-butyl (1-(((6-bromo-5-fluoropyridin-3-yl)oxy)methyl)cyclopropyl)carbamate

이 화합물은 6-브로모-5-플루오로피리딘-3-올 (500.0 mg, 2.60 mmol) 및 tert-부틸 (1-(하이드록시메틸)사이클로프로필)카바메이트 (975.2 mg, 5.21 mmol)를 사용하여 제조하였고, 회백색 분말 (650.0 mg, 69.1%)을 얻었다. LC-MS (ESI+) m/z 361.5 [(M+H)+, calcd C14H18BrFN2O3 m/z 360.0].This compound was prepared using 6-bromo-5-fluoropyridin-3-ol (500.0 mg, 2.60 mmol) and tert -butyl (1-(hydroxymethyl)cyclopropyl)carbamate (975.2 mg, 5.21 mmol) and an off-white powder (650.0 mg, 69.1%) was obtained. LC-MS (ESI+) m/z 361.5 [(M+H) + , calcd C 14 H 18 BrFN 2 O 3 m/z 360.0].

실시예 104를 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 104 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: 1-(((5-플루오로-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민1-(((5-fluoro-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

이 화합물은 tert-부틸 (1-(((6-브로모-5-플루오로피리딘-3-일)옥시)메틸)사이클로프로필)카바메이트 (100.0 mg, 0.28 mmol) (실시예 104, A 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (000.0 mg, 0.6 mmol)를 사용하여 제조하였고, 연한-황색 분말 (24.8 mg, 30.0%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.56 (d, 1H), 8.54 (d, 1H), 8.44 (d, 1H), 8.22 (d, 1H), 7.70-7.72 (m, 1H), 7.57-7.60 (m, 1H), 4.32 (s, 2H), 1.11-1.20 (m, 4H). LC-MS (ESI+) m/z 299.6 [(M+H)+, calcd C16H15FN4O m/z 298.1].This compound was prepared using tert -butyl (1-(((6-bromo-5-fluoropyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.28 mmol) (Example 104, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (000.0 mg, 0.6 mmol) to obtain a pale-yellow powder (24.8 mg, 30.0%). 1H NMR (500 MHz, MeOD) δ 9.56 (d, 1H), 8.54 (d, 1H), 8.44 (d, 1H), 8.22 (d, 1H), 7.70-7.72 (m, 1H), 7.57-7.60 (m, 1H), 4.32 (s, 2H), 1.11-1.20 (m, 4H). LC-MS (ESI+) m/z 299.6 [(M+H) + , calcd C 16 H 15 FN 4 O m/z 298.1].

실시예 105: 1-(((5-플루오로-6-(5-플루오로-1Example 105: 1-(((5-Fluoro-6-(5-Fluoro-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민 [1-(((5-fluoro-6-(5-fluoro-1]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine [1-(((5-fluoro-6-(5-fluoro-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine]

실시예 105를 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 105 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: 1-(((5-플루오로-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민1-(((5-fluoro-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine

이 화합물은 tert-부틸 tert-부틸 (1-(((6-브로모-5-플루오로피리딘-3-일)옥시)메틸)사이클로프로필)카바메이트 (100.0 mg, 0.28 mmol) (실시예 104, A 파트) 및 tert-부틸 5-플루오로-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (150.4 mg, 0.42 mmol)를 사용하여 제조하였고, 갈색 분말 (16.1 mg, 18.3%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.88 (d, 1H), 8.50 (s, 1H), 8.42 (d, 1H), 8.22 (d, 1H), 7.74-7.77 (m, 1H), 4.33 (s, 2H), 1.11-1.19 (m, 4H). LC-MS (ESI+) m/z 317.1 [(M+H)+, calcd C16H14F2N4O m/z 316.1].This compound was prepared using tert -butyl tert -butyl (1-(((6-bromo-5-fluoropyridin-3-yl)oxy)methyl)cyclopropyl)carbamate (100.0 mg, 0.28 mmol) (Example 104, Part A) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (150.4 mg, 0.42 mmol) to obtain a brown powder (16.1 mg, 18.3%). 1H NMR (500 MHz, MeOD) δ 8.88 (d, 1H), 8.50 (s, 1H), 8.42 (d, 1H), 8.22 (d, 1H), 7.74-7.77 (m, 1H), 4.33 (s, 2H), 1.11-1.19 (m, 4H). LC-MS (ESI+) m/z 317.1 [(M+H) + , calcd C 16 H 14 F 2 N 4 O m/z 316.1].

실시예 106: 1-(((6-(1Example 106: 1-(((6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로부탄-1-아민 [1-(((6-(1]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine [1-(((6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine]]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine]

실시예 106을 실시예 82에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 106 was prepared according to a procedure similar to that described for Example 82.

A 파트: Part A: tert-부틸 (1-(((6-요오도피리딘-3-일)옥시)메틸)사이클로부틸)카바메이트tert-butyl (1-(((6-iodopyridin-3-yl)oxy)methyl)cyclobutyl)carbamate

이 화합물은 6-요오도피리딘-3-올 (500.0 mg, 2.26 mmol) 및 tert-부틸 (1-(하이드록시메틸)사이클로부틸)카바메이트 (910.7 mg, 4.52 mmol)를 사용하여 제조하였고, 회백색 분말 (103.5 mg, 11.3%)을 얻었다. LC-MS (ESI+) m/z 405.4 [(M+H)+, calcd. C15H21IN2O3 m/z 404.2].This compound was prepared using 6-iodopyridin-3-ol (500.0 mg, 2.26 mmol) and tert -butyl (1-(hydroxymethyl)cyclobutyl)carbamate (910.7 mg, 4.52 mmol) and an off-white powder (103.5 mg, 11.3%) was obtained. LC-MS (ESI+) m/z 405.4 [(M+H) + , calcd. C 15 H 21 IN 2 O 3 m/z 404.2].

실시예 106을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 106 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: 1-(((6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로부탄-1-아민1-(((6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine

이 화합물은 tert-부틸 (1-(((6-요오도피리딘-3-일)옥시)메틸)사이클로부틸)카바메이트 (100.0 mg, 0.25 mmol) (실시예 106, A 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (127.7 mg, 0.37 mmol)를 사용하여 제조하였고, 갈색 분말 (11.8 mg, 16.2%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.01 (d, 1H), 8.49 (d, 1H), 8.43 (d, 1H), 8.20 (s, 1H), 8.04 (d, 1H), 7.82 (d, 1H), 7.49-7.51 (m, 1H), 4.44 (s, 2H), 2.37-2.43 (m, 4H), 2.09-2.14 (m, 2H). LC-MS (ESI+) m/z 000.0 [(M+H)+, calcd. C17H18N4O m/z 294.1].This compound was prepared using tert -butyl (1-(((6-iodopyridin-3-yl)oxy)methyl)cyclobutyl)carbamate (100.0 mg, 0.25 mmol) (Example 106, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)- 1 H-pyrrolo[2,3- b ]pyridine-1-carboxylate (127.7 mg, 0.37 mmol) to obtain a brown powder (11.8 mg, 16.2%). 1H NMR (500 MHz, MeOD) δ 9.01 (d, 1H), 8.49 (d, 1H), 8.43 (d, 1H), 8.20 (s, 1H), 8.04 (d, 1H), 7.82 (d, 1H), 7.49-7.51 (m, 1H), 4.44 (s, 2H), 2.37-2.43 (m, 4H), 2.09-2.14 (m, 2H). LC-MS (ESI+) m/z 000.0 [(M+H) + , calcd. C 17 H 18 N 4 O m/z 294.1].

실시예 107: 1-(2-(다이플루오로메틸)-4-(1Example 107: 1-(2-(difluoromethyl)-4-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)펜옥시)-2-메틸프로판-2-아민 [1-(2-(difluoromethyl)-4-(1]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine [1-(2-(difluoromethyl)-4-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine]]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine]

A 파트: Part A: tert-부틸 (1-(4-브로모-2-(다이플루오로메틸)펜옥시)-2-메틸프로판-2-일)카바메이트tert-butyl (1-(4-bromo-2-(difluoromethyl)phenoxy)-2-methylpropan-2-yl)carbamate

탄산칼륨 (1.5 g, 11.06 mmol)을 tert-부틸 (1-하이드록시-2-메틸프로판-2-일)카바메이트 (2.0 g, 11.06 mmol) 및 4-브로모-2-(다이플루오로메틸)-1-플루오로벤젠 (1.0 g, 4.42 mmol)의 디메틸설폭시드 (4 mL) 용액에 넣었다. 반응 혼합물을 120oC의 마이크로파에서 5시간 동안 조사하였다. TLC와 HPLC로 반응의 진행을 모니터링하였다. 반응이 완료된 후, EtOAc와 물로 희석하였다. 분리된 유기층을 물과 염수로 세척하고, 황산마그네슘으로 건조시킨 후 농축하였다. 잔류물을 MPLC (실리카겔, 0 내지 20%의 n-헥산 중 EtOAc로 용출)로 정제하고, 회백색 분말 (0.24 g, 13.9%)을 얻었다. LC-MS (ESI+) m/z 394.6 [(M+H)+, calcd. C16H22BrF2NO3 m/z 393.0].Potassium carbonate (1.5 g, 11.06 mmol) was added to a solution of tert -butyl (1-hydroxy-2-methylpropan-2-yl)carbamate (2.0 g, 11.06 mmol) and 4-bromo-2-(difluoromethyl)-1-fluorobenzene (1.0 g, 4.42 mmol) in dimethyl sulfoxide (4 mL). The reaction mixture was irradiated in a microwave at 120 o C for 5 h. The progress of the reaction was monitored by TLC and HPLC. After the reaction was completed, the mixture was diluted with EtOAc and water. The separated organic layer was washed with water and brine, dried over magnesium sulfate, and concentrated. The residue was purified by MPLC (silica gel, eluted with 0-20% EtOAc in n -hexane) to obtain an off-white powder (0.24 g, 13.9%). LC-MS (ESI+) m/z 394.6 [(M+H) + , calcd. C 16 H 22 BrF 2 NO 3 m/z 393.0].

실시예 107을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 107 was prepared according to a procedure similar to that described for Example 57.

C 파트: 1-(2-(다이플루오로메틸)-4-(1H-피롤로[2,3-b]피리딘-3-일)펜옥시)-2-메틸프로판-2-아민Part C: 1-(2-(difluoromethyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine

이 화합물은 tert-부틸 (1-(4-브로모-2-(다이플루오로메틸)펜옥시)-2-메틸프로판-2-일)카바메이트 (100.0 mg, 0.25 mmol) (실시예 107, A 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (130.9 mg, 0.38 mmol)를 사용하여 제조하였고, 연한-황색 분말 (19.8 mg, 23.5%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.87 (d, 1H), 8.48 (d, 1H), 7.96 (s, 1H), 7.87 (d, 2H), 7.64-7.66 (m, 1H), 7.15-7.37 (m, 2H), 4.17 (s, 2H), 1.51 (s, 6H). LC-MS (ESI+) m/z 332.6 [(M+H)+, calcd. C18H19F2N3O m/z 331.1].This compound was prepared using tert -butyl (1-(4-bromo-2-(difluoromethyl)phenoxy)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.25 mmol) (Example 107, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (130.9 mg, 0.38 mmol) to obtain a pale-yellow powder (19.8 mg, 23.5%). 1H NMR (500 MHz, MeOD) δ 8.87 (d, 1H), 8.48 (d, 1H), 7.96 (s, 1H), 7.87 (d, 2H), 7.64-7.66 (m, 1H), 7.15-7.37 (m, 2H), 4.17 (s, 2H), 1.51 (s, 6H). LC-MS (ESI+) m/z 332.6 [(M+H) + , calcd. C 18 H 19 F 2 N 3 O m/z 331.1].

실시예 108: Example 108: NN 11 -(2-(다이플루오로메틸)-6-(1-(2-(difluoromethyl)-6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)-2-메틸프로판-1,2-다이아민 []pyridin-3-yl)pyridin-3-yl)-2-methylpropane-1,2-diamine [ NN 11 -(2-(difluoromethyl)-6-(1-(2-(difluoromethyl)-6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)-2-methylpropane-1,2-diamine]]pyridin-3-yl)pyridin-3-yl)-2-methylpropane-1,2-diamine]

실시예 108을 실시예 107에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 108 was prepared according to a procedure similar to that described for Example 107.

A 파트: Part A: tert-부틸 (1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)아미노)-2-메틸프로판-2-일)카바메이트tert-Butyl (1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)amino)-2-methylpropan-2-yl)carbamate

이 화합물은 tert-부틸 (1-아미노-2-메틸프로판-2-일)카바메이트 (1.2 g, 6.64 mmol) 및 6-브로모-2-(다이플루오로메틸)-3-플루오로피리딘 (1.0 g, 4.42 mmol) (실시예 13, A 파트)을 사용하여 제조하였고, 회백색 분말 (0.52 g, 29.8%)을 얻었다. LC-MS (ESI+) m/z 394.3 [(M+H)+, calcd. C15H22BrF2N3O2 m/z 393.0].This compound was prepared using tert -butyl (1-amino-2-methylpropan-2-yl)carbamate (1.2 g, 6.64 mmol) and 6-bromo-2-(difluoromethyl)-3-fluoropyridine (1.0 g, 4.42 mmol) (Example 13, Part A) and an off-white powder (0.52 g, 29.8%) was obtained. LC-MS (ESI+) m/z 394.3 [(M+H) + , calcd. C 15 H 22 BrF 2 N 3 O 2 m/z 393.0].

실시예 108을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 108 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: NN 11 -(2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)-2-메틸프로판-1,2-다이아민-(2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)-2-methylpropane-1,2-diamine

이 화합물은 tert-부틸 (1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)아미노)-2-메틸프로판-2-일)카바메이트 (100.0 mg, 0.25 mmol) (실시예 108, A 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (130.9 mg, 0.38 mmol)를 사용하여 제조하였고, 연한-황색 분말 (36.9 mg, 43.9%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.60 (d, 1H), 8.45 (d, 1H), 8.21 (s, 1H), 7.90 (d, 1H), 7.64-7.67 (m, 1H), 7.52 (d, 1H), 6.90-7.12 (m, 1H), 3.49 (s, 2H), 1.41 (s, 6H). LC-MS (ESI+) m/z 332.4 [(M+H)+, calcd. C17H19F2N5 m/z 331.1].This compound was prepared using tert -butyl (1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)amino)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.25 mmol) (Example 108, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (130.9 mg, 0.38 mmol) to obtain a pale-yellow powder (36.9 mg, 43.9%). 1H NMR (500 MHz, MeOD) δ 9.60 (d, 1H), 8.45 (d, 1H), 8.21 (s, 1H), 7.90 (d, 1H), 7.64-7.67 (m, 1H), 7.52 (d, 1H), 6.90-7.12 (m, 1H), 3.49 (s, 2H), 1.41 (s, 6H). LC-MS (ESI+) m/z 332.4 [(M+H) + , calcd. C 17 H 19 F 2 N 5 m/z 331.1].

실시예 109: Example 109: NN 11 -(2-(다이플루오로메틸)-6-(1-(2-(difluoromethyl)-6-(1 HH -피롤로[3,2--Pyrrolo[3,2- bb ]피리딘-1-일)피리딘-3-일)-2-메틸프로판-1,2-다이아민 []pyridin-1-yl)pyridin-3-yl)-2-methylpropane-1,2-diamine [ NN 11 -(2-(difluoromethyl)-6-(1-(2-(difluoromethyl)-6-(1 HH -pyrrolo[3,2--pyrrolo[3,2- bb ]pyridin-1-yl)pyridin-3-yl)-2-methylpropane-1,2-diamine]]pyridin-1-yl)pyridin-3-yl)-2-methylpropane-1,2-diamine]

실시예 109는 tert-부틸 (1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)아미노)-2-메틸프로판-2-일)카바메이트 (100.0 mg, 0.25 mmol) (실시예 108, A 파트) 및 1H-피롤로[3,2-b]피리딘 (29.9 mg, 0.25 mmol)을 사용하여 실시예 64에 대하여 설명한 것과 유사한 절차에 따라 제조하였고, 연한-황색 분말 (19.6 mg, 23.3%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.63 (d, 1H), 8.37 (d, 1H), 8.07 (d, 1H), 7.63 (d, 1H), 7.56 (d, 1H), 7.25-7.28 (m, 1H), 6.78-6.801 (m, 2H), 3.27 (s, 2H), 1.25 (m, 6H). LC-MS (ESI+) m/z 332.3 [(M+H)+, calcd. C17H19F2N5 m/z 331.1].Example 109 was prepared according to a similar procedure as described for Example 64 using tert -butyl (1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)amino)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.25 mmol) (Example 108, Part A) and 1 H -pyrrolo[3,2- b ]pyridine (29.9 mg, 0.25 mmol) to obtain a pale-yellow powder (19.6 mg, 23.3%). 1H NMR (500 MHz, MeOD) δ 8.63 (d, 1H), 8.37 (d, 1H), 8.07 (d, 1H), 7.63 (d, 1H), 7.56 (d, 1H), 7.25-7.28 (m, 1H), 6.78-6.801 (m, 2H), 3.27 (s, 2H), 1.25 (m, 6H). LC-MS (ESI+) m/z 332.3 [(M+H) + , calcd. C 17 H 19 F 2 N 5 m/z 331.1].

실시예 110: Example 110: NN 11 -(6-(1-(6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)-2-(트리플루오로메틸)피리딘-3-일)-2-메틸프로판-1,2-다이아민 []pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)-2-methylpropane-1,2-diamine [ NN 11 -(6-(1-(6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)-2-methylpropane-1,2-diamine]]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)-2-methylpropane-1,2-diamine]

실시예 110을 실시예 107에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 110 was prepared according to a procedure similar to that described for Example 107.

A 파트: Part A: tert-부틸 (1-((6-브로모-2-(트리플루오로메틸)피리딘-3-일)아미노)-2-메틸프로판-2-일)카바메이트tert-Butyl (1-((6-bromo-2-(trifluoromethyl)pyridin-3-yl)amino)-2-methylpropan-2-yl)carbamate

이 화합물은 6-브로모-3-플루오로-2-(트리플루오로메틸)피리딘 (500.0 mg, 2.05 mmol) 및 tert-부틸 (1-아미노-2-메틸프로판-2-일)카바메이트 (578.7 mg, 3.07 mmol)를 사용하여 제조하였고, 회백색 분말 (574.6 mg, 76.2%)을 얻었다. LC-MS (ESI+) m/z 412.3 [(M+H)+, calcd. C15H21BrF3N3O2 m/z 411.0].This compound was prepared using 6-bromo-3-fluoro-2-(trifluoromethyl)pyridine (500.0 mg, 2.05 mmol) and tert -butyl (1-amino-2-methylpropan-2-yl)carbamate (578.7 mg, 3.07 mmol) and an off-white powder (574.6 mg, 76.2%) was obtained. LC-MS (ESI+) m/z 412.3 [(M+H) + , calcd. C 15 H 21 BrF 3 N 3 O 2 m/z 411.0].

실시예 110을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 110 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: NN 11 -(6-(1H-피롤로[2,3-b]피리딘-3-일)-2-(트리플루오로메틸)피리딘-3-일)-2-메틸프로판-1,2-다이아민-(6-(1H-pyrrolo[2,3-b]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)-2-methylpropane-1,2-diamine

이 화합물은 tert-부틸 (1-((6-브로모-2-(트리플루오로메틸)피리딘-3-일)아미노)-2-메틸프로판-2-일)카바메이트 (100.0 mg, 0.24 mmol) (실시예 110, A 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (125.2 mg, 0.36 mmol)를 사용하여 제조하였고, 황색 분말 (33.1 mg, 39.0%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.54 (d, 1H), 8.45 (d, 1H), 8.25 (s, 1H), 7.98 (d, 1H), 7.60-7.67 (m, 2H), 3.52 (s, 2H), 1.39 (s, 6H). LC-MS (ESI+) m/z 350.6 [(M+H)+, calcd. C17H18F3N5 m/z 349.1].This compound was prepared using tert -butyl (1-((6-bromo-2-(trifluoromethyl)pyridin-3-yl)amino)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 110, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (125.2 mg, 0.36 mmol) to obtain a yellow powder (33.1 mg, 39.0%). 1H NMR (500 MHz, MeOD) δ 9.54 (d, 1H), 8.45 (d, 1H), 8.25 (s, 1H), 7.98 (d, 1H), 7.60-7.67 (m, 2H), 3.52 (s, 2H), 1.39 (s, 6H). LC-MS (ESI+) m/z 350.6 [(M+H) + , calcd. C 17 H 18 F 3 N 5 m/z 349.1].

실시예 111: Example 111: NN 11 -(2-(다이플루오로메틸)-4-(1-(2-(difluoromethyl)-4-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)페닐)-2-메틸프로판-1,2-다이아민 []pyridin-3-yl)phenyl)-2-methylpropane-1,2-diamine [ NN 11 -(2-(difluoromethyl)-4-(1-(2-(difluoromethyl)-4-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)phenyl)-2-methylpropane-1,2-diamine]]pyridin-3-yl)phenyl)-2-methylpropane-1,2-diamine]

실시예 111을 실시예 107에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 111 was prepared according to a procedure similar to that described for Example 107.

A 파트: Part A: tert-부틸 (1-((4-브로모-2-(다이플루오로메틸)페닐)아미노)-2-메틸프로판-2-일)카바메이트tert-butyl (1-((4-bromo-2-(difluoromethyl)phenyl)amino)-2-methylpropan-2-yl)carbamate

이 화합물은 4-브로모-2-(다이플루오로메틸)-1-플루오로벤젠 (1.0 g, 4.42 mmol) 및 tert-부틸 (1-아미노-2-메틸프로판-2-일)카바메이트 (1.6 g, 8.85 mmol)를 사용하여 제조하였고, 연한-황색 분말 (146.7 mg, 8.4%)을 얻었다. LC-MS (ESI+) m/z 393.2 [(M+H)+, calcd. C16H23BrF2N2O2 m/z 392.0].This compound was prepared using 4-bromo-2-(difluoromethyl)-1-fluorobenzene (1.0 g, 4.42 mmol) and tert -butyl (1-amino-2-methylpropan-2-yl)carbamate (1.6 g, 8.85 mmol) and a pale-yellow powder (146.7 mg, 8.4%) was obtained. LC-MS (ESI+) m/z 393.2 [(M+H) + , calcd. C 16 H 23 BrF 2 N 2 O 2 m/z 392.0].

실시예 111을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 111 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: NN 11 -(2-(다이플루오로메틸)-4-(1H-피롤로[2,3-b]피리딘-3-일)페닐)-2-메틸프로판-1,2-다이아민-(2-(difluoromethyl)-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenyl)-2-methylpropane-1,2-diamine

이 화합물은 tert-부틸 (1-((4-브로모-2-(다이플루오로메틸)페닐)아미노)-2-메틸프로판-2-일)카바메이트 (100.0 mg, 0.25 mmol) (실시예 111, A 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (131.2 mg, 0.38 mmol)를 사용하여 제조하였고, 황색 분말 (13.5 mg, 16.0%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.23-8.27 (m, 2H), 7.66-7.69 (m, 2H), 7.57 (s, 1H), 7.17-7.20 (m, 1H), 6.87-7.09 (m, 2H), 3.45 (s, 2H), 1.43 (s, 6H). LC-MS (ESI+) m/z 331.6 [(M+H)+, calcd. C18H20F2N4 m/z 330.1].This compound was prepared using tert -butyl (1-((4-bromo-2-(difluoromethyl)phenyl)amino)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.25 mmol) (Example 111, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (131.2 mg, 0.38 mmol) to obtain a yellow powder (13.5 mg, 16.0%). 1H NMR (500 MHz, MeOD) δ 8.23-8.27 (m, 2H), 7.66-7.69 (m, 2H), 7.57 (s, 1H), 7.17-7.20 (m, 1H), 6.87-7.09 (m, 2H), 3.45 (s, 2H), 1.43 (s, 6H). LC-MS (ESI+) m/z 331.6 [(M+H) + , calcd. C 18 H 20 F 2 N 4 m/z 330.1].

실시예 112: Example 112: NN -((1-아미노사이클로프로필)메틸)-2-(다이플루오로메틸)-6-(5-플루오로-1-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(5-fluoro-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-아민 []pyridin-3-yl)pyridin-3-amine [ NN -((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(5-fluoro-1-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(5-fluoro-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-amine]]pyridin-3-yl)pyridin-3-amine]

실시예 112를 실시예 107에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 112 was prepared according to a procedure similar to that described for Example 107.

A 파트: Part A: tert-부틸 (1-(((6-브로모-2-(다이플루오로메틸)피리딘-3-일)아미노)메틸)사이클로프로필)카바메이트tert-butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)amino)methyl)cyclopropyl)carbamate

이 화합물은 6-브로모-2-(다이플루오로메틸)-3-플루오로피리딘 (500.0 mg, 2.21 mmol) (실시예 13, A 파트) 및 tert-부틸 (1-(아미노메틸)사이클로프로필)카바메이트 (618.1 mg, 3.32 mmol)를 사용하여 제조하였고, 연한-황색 분말 (340.5 mg, 35.0%)을 얻었다. LC-MS (ESI+) m/z 392.1 [(M+H)+, calcd. C15H20BrF2N3O2 m/z 391.0].This compound was prepared using 6-bromo-2-(difluoromethyl)-3-fluoropyridine (500.0 mg, 2.21 mmol) (Example 13, Part A) and tert -butyl (1-(aminomethyl)cyclopropyl)carbamate (618.1 mg, 3.32 mmol) to obtain a pale-yellow powder (340.5 mg, 35.0%). LC-MS (ESI+) m/z 392.1 [(M+H) + , calcd. C 15 H 20 BrF 2 N 3 O 2 m/z 391.0].

실시예 112를 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 112 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: N-((1-아미노사이클로프로필)메틸)-2-(다이플루오로메틸)-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-아민N-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine

이 화합물은 tert-부틸 (1-(((6-브로모-2-(다이플루오로메틸)피리딘-3-일)아미노)메틸)사이클로프로필)카바메이트 (100.0 mg, 0.25 mmol) (실시예 112, A 파트) 및 tert-부틸 5-플루오로-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (138.5 mg, 0.38 mmol)를 사용하여 제조하였고, 연한-오렌지색 분말 (33.4 mg, 37.7%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.05-9.07 (m, 1H), 8.48 (t, 1H), 8.23 (s, 1H), 7.92 (d, 1H), 7.54 (d, 1H), 6.96-7.17 (m, 1H), 3.62 (s, 2H), 1.01-1.03 (m, 4H). LC-MS (ESI+) m/z 348.3 [(M+H)+, calcd. C17H16F3N5 m/z 347.1].This compound was prepared using tert -butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)amino)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 112, Part A) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (138.5 mg, 0.38 mmol) to obtain a pale-orange powder (33.4 mg, 37.7%). 1H NMR (500 MHz, MeOD) δ 9.05-9.07 (m, 1H), 8.48 (t, 1H), 8.23 (s, 1H), 7.92 (d, 1H), 7.54 (d, 1H), 6.96-7.17 (m, 1H), 3.62 (s, 2H), 1.01-1.03 (m, 4H). LC-MS (ESI+) m/z 348.3 [(M+H) + , calcd. C 17 H 16 F 3 N 5 m/z 347.1].

실시예 113: Example 113: NN -((1-아미노사이클로프로필)메틸)-2-(다이플루오로메틸)-6-(1-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1 HH -피라졸-4-일)피리딘-3-아민 [-pyrazol-4-yl)pyridin-3-amine [ NN -((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1 HH -pyrazol-4-yl)pyridin-3-amine]-pyrazol-4-yl)pyridin-3-amine]

실시예 113을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 113 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: N-((1-아미노사이클로프로필)메틸)-2-(다이플루오로메틸)-6-(1H-피라졸-4-일)피리딘-3-아민N-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1H-pyrazol-4-yl)pyridin-3-amine

이 화합물은 tert-부틸 (1-(((6-브로모-2-(다이플루오로메틸)피리딘-3-일)아미노)메틸)사이클로프로필)카바메이트 (100.0 mg, 0.25 mmol) (실시예 112, A 파트) 및 tert-부틸 4-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피라졸-1-카복실레이트 (112.4 mg, 0.38 mmol)를 사용하여 제조하였고, 황색 분말 (30.5 mg, 42.8%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.53 (s, 2H), 7.82 (d, 1H), 7.53 (d, 1H), 6.80-7.02 (m, 1H),3.60 (s, 2H), 0.95-1.02 (m, 4H). LC-MS (ESI+) m/z 280.1 [(M+H)+, calcd. C13H15F2N5 m/z 279.1].This compound was prepared using tert -butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)amino)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 112, Part A) and tert -butyl 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrazole-1-carboxylate (112.4 mg, 0.38 mmol) to obtain a yellow powder (30.5 mg, 42.8%). 1H NMR (500 MHz, MeOD) δ 8.53 (s, 2H), 7.82 (d, 1H), 7.53 (d, 1H), 6.80-7.02 (m, 1H), 3.60 (s, 2H), 0.95-1.02 (m, 4H). LC-MS (ESI+) m/z 280.1 [(M+H) + , calcd. C 13 H 15 F 2 N 5 m/z 279.1].

실시예 114: Example 114: NN -((1-아미노사이클로프로필)메틸)-2-(다이플루오로메틸)-6-(1-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-아민 []pyridin-3-yl)pyridin-3-amine [ NN -((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-amine]]pyridin-3-yl)pyridin-3-amine]

실시예 114를 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 114 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: N-((1-아미노사이클로프로필)메틸)-2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-아민N-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine

이 화합물은 tert-부틸 (1-(((6-브로모-2-(다이플루오로메틸)피리딘-3-일)아미노)메틸)사이클로프로필)카바메이트 (100.0 mg, 0.25 mmol) (실시예 112, A 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (131.6 mg, 0.38 mmol)를 사용하여 제조하였고, 아이보리색 분말 (19.3 mg, 22.9%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.56 (d, 1H), 8.43 (d, 1H), 8.19 (s, 1H), 7.89 (d, 1H), 7.61-7.63 (m, 1H), 7.43 (d, 1H), 6.87-7.08 (m, 1H), ,3.59 (s, 2H), 0.97-1.03 (m, 4H). LC-MS (ESI+) m/z 330.5 [(M+H)+, calcd. C17H17F2N5 m/z 329.1].This compound was prepared using tert -butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)amino)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 112, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (131.6 mg, 0.38 mmol) to obtain an ivory powder (19.3 mg, 22.9%). 1H NMR (500 MHz, MeOD) δ 9.56 (d, 1H), 8.43 (d, 1H), 8.19 (s, 1H), 7.89 (d, 1H), 7.61-7.63 (m, 1H), 7.43 (d, 1H), 6.87-7.08 (m, 1H), ,3.59 (s, 2H), 0.97-1.03 (m, 4H). LC-MS (ESI+) m/z 330.5 [(M+H) + , calcd. C 17 H 17 F 2 N 5 m/z 329.1].

실시예 115: Example 115: NN -((1-아미노사이클로프로필)메틸)-2-(다이플루오로메틸)-6-(1-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1 HH -피롤로[3,2--Pyrrolo[3,2- bb ]피리딘-1-일)피리딘-3-아민 []pyridin-1-yl)pyridin-3-amine [ NN -((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1-((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1 HH -pyrrolo[3,2--pyrrolo[3,2- bb ]pyridin-1-yl)pyridin-3-amine]]pyridin-1-yl)pyridin-3-amine]

실시예 115는 tert-부틸 (1-(((6-브로모-2-(다이플루오로메틸)피리딘-3-일)아미노)메틸)사이클로프로필)카바메이트 (100.0 mg, 0.25 mmol) (실시예 112, A 파트) 및 1H-피롤로[3,2-b]피리딘 (30.1 mg, 0.25 mmol)을 사용하여 실시예 64에 대하여 설명한 것과 유사한 절차에 따라 제조하였고, 황색 분말 (18.5 mg, 22.0%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.37 (d, 1H), 8.60-8.67 (m, 2H), 7.76-7.85 (m, 2H), 7.63 (d, 1H), 6.89-7.10 (m, 2H), 3.63 (s, 2H), 1.03 (s, 4H). LC-MS (ESI+) m/z 330.4 [(M+H)+, calcd. C17H17F2N5 m/z 329.1].Example 115 was prepared according to a similar procedure as that described for Example 64 using tert -butyl (1-(((6-bromo-2-(difluoromethyl)pyridin-3-yl)amino)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 112, Part A) and 1 H -pyrrolo[3,2- b ]pyridine (30.1 mg, 0.25 mmol) to obtain a yellow powder (18.5 mg, 22.0%). 1H NMR (500 MHz, MeOD) δ 9.37 (d, 1H), 8.60-8.67 (m, 2H), 7.76-7.85 (m, 2H), 7.63 (d, 1H), 6.89-7.10 (m, 2H), 3.63 (s, 2H), 1.03 (s, 4H). LC-MS (ESI+) m/z 330.4 [(M+H) + , calcd. C 17 H 17 F 2 N 5 m/z 329.1].

실시예 116: Example 116: NN -((1-아미노사이클로프로필)메틸)-6-(1-((1-aminocyclopropyl)methyl)-6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-아민 []pyridin-3-yl)pyridin-3-amine [ NN -((1-aminocyclopropyl)methyl)-6-(1-((1-aminocyclopropyl)methyl)-6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-amine]]pyridin-3-yl)pyridin-3-amine]

실시예 116을 실시예 107에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 116 was prepared according to a procedure similar to that described for Example 107.

A 파트: Part A: tert-부틸 (1-(((6-브로모피리딘-3-일)아미노)메틸)사이클로프로필)카바메이트tert-butyl (1-(((6-bromopyridin-3-yl)amino)methyl)cyclopropyl)carbamate

이 화합물은 2-브로모-5-플루오로피리딘 (1.0 g, 5.68 mmol) 및 tert-부틸 (1-(아미노메틸)사이클로프로필)카바메이트 (2.1 g, 11.3 mmol)를 사용하여 제조하였고, 회백색 분말 (213.8 mg, 10.9%)을 얻었다. LC-MS (ESI+) m/z 342.6 [(M+H)+, calcd. C14H20BrN3O2 m/z 341.0].This compound was prepared using 2-bromo-5-fluoropyridine (1.0 g, 5.68 mmol) and tert -butyl (1-(aminomethyl)cyclopropyl)carbamate (2.1 g, 11.3 mmol) and an off-white powder (213.8 mg, 10.9%) was obtained. LC-MS (ESI+) m/z 342.6 [(M+H) + , calcd. C 14 H 20 BrN 3 O 2 m/z 341.0].

실시예 116을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 116 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: N-((1-아미노사이클로프로필)메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-아민N-((1-aminocyclopropyl)methyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine

이 화합물은 tert-부틸 (1-(((6-브로모피리딘-3-일)아미노)메틸)사이클로프로필)카바메이트 (100.0 mg, 0.29 mmol) (실시예 116, A 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (150.8 mg, 0.44 mmol)를 사용하여 제조하였고, 황색 분말 (25.4 mg, 31.1%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.84 (d, 1H), 8.54 (d, 1H), 8.28 (s, 1H), 8.12-8.15 (m, 2H), 7.95-9.97 (m, 1H), 7.61-7.64 (m, 1H). 3.60 (s, 2H), 1.02-1.09 (m, 4H). LC-MS (ESI+) m/z 280.3 [(M+H)+, calcd. C16H17N5 m/z 279.1].This compound was prepared using tert -butyl (1-(((6-bromopyridin-3-yl)amino)methyl)cyclopropyl)carbamate (100.0 mg, 0.29 mmol) (Example 116, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (150.8 mg, 0.44 mmol) to obtain a yellow powder (25.4 mg, 31.1%). 1H NMR (500 MHz, MeOD) δ 8.84 (d, 1H), 8.54 (d, 1H), 8.28 (s, 1H), 8.12-8.15 (m, 2H), 7.95-9.97 (m, 1H), 7.61-7.64 (m, 1H). 3.60 (s, 2H), 1.02-1.09 (m, 4H). LC-MS (ESI+) m/z 280.3 [(M+H) + , calcd. C 16 H 17 N 5 m/z 279.1].

실시예 117: Example 117: NN -((1-아미노사이클로프로필)메틸)-6-(5-플루오로-1-((1-aminocyclopropyl)methyl)-6-(5-fluoro-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-아민 []pyridin-3-yl)pyridin-3-amine [ NN -((1-aminocyclopropyl)methyl)-6-(5-fluoro-1-((1-aminocyclopropyl)methyl)-6-(5-fluoro-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-amine]]pyridin-3-yl)pyridin-3-amine]

실시예 117을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 117 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: N-((1-아미노사이클로프로필)메틸)-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-아민N-((1-aminocyclopropyl)methyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine

이 화합물은 tert-부틸 (1-(((6-브로모피리딘-3-일)아미노)메틸)사이클로프로필)카바메이트 (100.0 mg, 0.29 mmol) (실시예 116, A 파트) 및 tert-부틸 5-플루오로-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (158.7 mg, 0.44 mmol)를 사용하여 제조하였고, 황색 분말 (16.8 mg, 19.3%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.30 (s, 1H), 8.15-8.06 (m, 2H), 8.03-8.08 (m, 2H), 7.91-7.93 (m, 1H), 3.57 (s, 2H), 1.01-1.08 (m, 4H). LC-MS (ESI+) m/z 298.2 [(M+H)+, calcd. C16H16FN5 m/z 297.1].This compound was prepared using tert -butyl (1-(((6-bromopyridin-3-yl)amino)methyl)cyclopropyl)carbamate (100.0 mg, 0.29 mmol) (Example 116, Part A) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (158.7 mg, 0.44 mmol) to obtain a yellow powder (16.8 mg, 19.3%). 1H NMR (500 MHz, MeOD) δ 8.30 (s, 1H), 8.15-8.06 (m, 2H), 8.03-8.08 (m, 2H), 7.91-7.93 (m, 1H), 3.57 (s, 2H), 1.01-1.08 (m, 4H). LC-MS (ESI+) m/z 298.2 [(M+H) + , calcd. C 16 H 16 FN 5 m/z 297.1].

실시예 118: Example 118: NN -((1-아미노사이클로프로필)메틸)-4-(다이플루오로메틸)-6-(1-((1-aminocyclopropyl)methyl)-4-(difluoromethyl)-6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-아민 []pyridin-3-yl)pyridin-3-amine [ NN -((1-aminocyclopropyl)methyl)-4-(difluoromethyl)-6-(1-((1-aminocyclopropyl)methyl)-4-(difluoromethyl)-6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-amine]]pyridin-3-yl)pyridin-3-amine]

실시예 118을 실시예 107에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 118 was prepared according to a procedure similar to that described for Example 107.

A 파트: Part A: tert-부틸 (1-(((6-브로모-4-(다이플루오로메틸)피리딘-3-일)아미노)메틸)사이클로프로필)카바메이트tert-butyl (1-(((6-bromo-4-(difluoromethyl)pyridin-3-yl)amino)methyl)cyclopropyl)carbamate

이 화합물은 2-브로모-4-(다이플루오로메틸)-5-플루오로피리딘 (0.5 g, 2.21 mmol) (실시예 30, A 파트) 및 tert-부틸 (1-(아미노메틸)사이클로프로필)카바메이트 (1.0 g, 5.53 mmol)를 사용하여 제조하였고, 황색 분말 (351.3 mg, 40.4%)을 얻었다. LC-MS (ESI+) m/z 392.3 [(M+H)+, calcd. C15H20BrF2N3O2 m/z 391.0].This compound was prepared using 2-bromo-4-(difluoromethyl)-5-fluoropyridine (0.5 g, 2.21 mmol) (Example 30, Part A) and tert -butyl (1-(aminomethyl)cyclopropyl)carbamate (1.0 g, 5.53 mmol) and a yellow powder (351.3 mg, 40.4%) was obtained. LC-MS (ESI+) m/z 392.3 [(M+H) + , calcd. C 15 H 20 BrF 2 N 3 O 2 m/z 391.0].

실시예 118을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 118 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: N-((1-아미노사이클로프로필)메틸)-4-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-아민N-((1-aminocyclopropyl)methyl)-4-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine

이 화합물은 tert-부틸 (1-(((6-브로모-4-(다이플루오로메틸)피리딘-3-일)아미노)메틸)사이클로프로필)카바메이트 (100.0 mg, 0.25 mmol) (실시예 118, A 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (131.6 mg, 0.38 mmol)를 사용하여 제조하였고, 황색 분말 (32.2 mg, 38.3%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.06 (d, 1H), 8.62 (d, 1H), 8.49 (s, 1H), 8.41 (s, 1H), 8.26 (s, 1H), 7.74-7.77 (m, 1H), 7.17-7.92 (m, 1H), 3.79 (s, 2H), 1.08-1.10 (m, 4H). LC-MS (ESI+) m/z 330.2 [(M+H)+, calcd. C17H17F2N5 m/z 329.1].This compound was prepared using tert -butyl (1-(((6-bromo-4-(difluoromethyl)pyridin-3-yl)amino)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 118, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (131.6 mg, 0.38 mmol) to obtain a yellow powder (32.2 mg, 38.3%). 1H NMR (500 MHz, MeOD) δ 9.06 (d, 1H), 8.62 (d, 1H), 8.49 (s, 1H), 8.41 (s, 1H), 8.26 (s, 1H), 7.74-7.77 (m, 1H), 7.17-7.92 (m, 1H), 3.79 (s, 2H), 1.08-1.10 (m, 4H). LC-MS (ESI+) m/z 330.2 [(M+H) + , calcd. C 17 H 17 F 2 N 5 m/z 329.1].

실시예 119: Example 119: NN -((1-아미노사이클로프로필)메틸)-5-(다이플루오로메틸)-6-(1-((1-aminocyclopropyl)methyl)-5-(difluoromethyl)-6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-아민 []pyridin-3-yl)pyridin-3-amine [ NN -((1-aminocyclopropyl)methyl)-5-(difluoromethyl)-6-(1-((1-aminocyclopropyl)methyl)-5-(difluoromethyl)-6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-amine]]pyridin-3-yl)pyridin-3-amine]

실시예 119를 실시예 107에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 119 was prepared according to a procedure similar to that described for Example 107.

A 파트: Part A: terttert -부틸 (1-(((6-브로모-5-(다이플루오로메틸)피리딘-3-일)아미노)메틸)사이클로프로필)카바메이트-Butyl (1-(((6-bromo-5-(difluoromethyl)pyridin-3-yl)amino)methyl)cyclopropyl)carbamate

이 화합물은 2-브로모-3-(다이플루오로메틸)-5-플루오로피리딘 (1.0 g, 4.42 mmol) (실시예 33, A 파트) 및 tert-부틸 (1-(아미노메틸)사이클로프로필)카바메이트 (2.0 g, 11.0 mmol)를 사용하여 제조하였고, 아이보리색 분말 (264.5 mg, 15.2%)을 얻었다. LC-MS (ESI+) m/z 392.4 [(M+H)+, calcd. C15H20BrF2N3O2 m/z 391.0].This compound was prepared using 2-bromo-3-(difluoromethyl)-5-fluoropyridine (1.0 g, 4.42 mmol) (Example 33, Part A) and tert -butyl (1-(aminomethyl)cyclopropyl)carbamate (2.0 g, 11.0 mmol) and the resulting product was an ivory powder (264.5 mg, 15.2%). LC-MS (ESI+) m/z 392.4 [(M+H) + , calcd. C 15 H 20 BrF 2 N 3 O 2 m/z 391.0].

실시예 119를 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 119 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: N-((1-아미노사이클로프로필)메틸)-5-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-아민N-((1-aminocyclopropyl)methyl)-5-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-amine

이 화합물은 tert-부틸 (1-(((6-브로모-5-(다이플루오로메틸)피리딘-3-일)아미노)메틸)사이클로프로필)카바메이트 (100.0 mg, 0.25 mmol) (실시예 119, A 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (131.6 mg, 0.38 mmol)를 사용하여 제조하였고, 아이보리색 분말 (35.0 mg, 41.6%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.69-8.71 (m, 1H), 8.60 (d, 1H), 8.45 (s, 1H), 8.09-8.12 (m, 2H), 7.66-7.70 (m, 1H), 6.74-6.96 (m, 1H), 3.70 (s, 2H), 1.08-1.12 (m, 4H). LC-MS (ESI+) m/z 330.4 [(M+H)+, calcd. C17H17F2N5 m/z 329.1].This compound was prepared using tert -butyl (1-(((6-bromo-5-(difluoromethyl)pyridin-3-yl)amino)methyl)cyclopropyl)carbamate (100.0 mg, 0.25 mmol) (Example 119, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (131.6 mg, 0.38 mmol) to obtain an ivory powder (35.0 mg, 41.6%). 1H NMR (500 MHz, MeOD) δ 8.69-8.71 (m, 1H), 8.60 (d, 1H), 8.45 (s, 1H), 8.09-8.12 (m, 2H), 7.66-7.70 (m, 1H), 6.74-6.96 (m, 1H), 3.70 (s, 2H), 1.08-1.12 (m, 4H). LC-MS (ESI+) m/z 330.4 [(M+H) + , calcd. C 17 H 17 F 2 N 5 m/z 329.1].

실시예 120: 1-((2-(다이플루오로메틸)-6-(1Example 120: 1-((2-(difluoromethyl)-6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)아미노)-2-메틸프로판-2-올 [1-((2-(difluoromethyl)-6-(1]pyridin-3-yl)pyridin-3-yl)amino)-2-methylpropan-2-ol [1-((2-(difluoromethyl)-6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)amino)-2-methylpropan-2-ol]]pyridin-3-yl)pyridin-3-yl)amino)-2-methylpropan-2-ol]

실시예 120을 실시예 107에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 120 was prepared according to a procedure similar to that described for Example 107.

A 파트: Part A: 1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)아미노)-2-메틸프로판-2-올1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)amino)-2-methylpropan-2-ol

이 화합물은 6-브로모-2-(다이플루오로메틸)-3-플루오로피리딘 (1.0 g, 4.42 mmol) (실시예 13, A 파트) 및 1-아미노-2-메틸프로판-2-올 (0.6 mL, 6.64 mmol)를 사용하여 제조하였고, 연한-황색 액체 (700.0 mg, 53.6%)를 얻었다. LC-MS (ESI+) m/z 296.4 [(M+H)+, calcd. C10H13BrF2N2O m/z 294.0].This compound was prepared using 6-bromo-2-(difluoromethyl)-3-fluoropyridine (1.0 g, 4.42 mmol) (Example 13, Part A) and 1-amino-2-methylpropan-2-ol (0.6 mL, 6.64 mmol) to obtain a pale-yellow liquid (700.0 mg, 53.6%). LC-MS (ESI+) m/z 296.4 [(M+H) + , calcd. C 10 H 13 BrF 2 N 2 O m/z 294.0].

실시예 120을 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 120 was prepared according to a procedure similar to that described for Example 13.

C 파트: Part C: 1-((2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)아미노)-2-메틸프로판-2-올1-((2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)amino)-2-methylpropan-2-ol

이 화합물은 1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)아미노)-2-메틸프로판-2-올 (100.0 mg, 0.34 mmol) (실시예 120, A 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (174.9 mg, 0.51 mmol)를 사용하여 제조하였고, 황색 분말 (30.6 mg, 27.1%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.56 (d, 1H), 8.43 (d, 1H), 8.14 (s, 1H), 7.82 (d, 1H), 7.62-7.65 (m, 1H), 7.34 (d, 1H), 6.81-7.03 (m, 1H), 3.19 (s, 2H), 1.29 (s, 6H). LC-MS (ESI+) m/z 333.3 [(M+H)+, calcd. C17H18F2N4O m/z 332.1].This compound was prepared using 1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)amino)-2-methylpropan-2-ol (100.0 mg, 0.34 mmol) (Example 120, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (174.9 mg, 0.51 mmol) and a yellow powder (30.6 mg, 27.1%) was obtained. 1H NMR (500 MHz, MeOD) δ 9.56 (d, 1H), 8.43 (d, 1H), 8.14 (s, 1H), 7.82 (d, 1H), 7.62-7.65 (m, 1H), 7.34 (d, 1H), 6.81-7.03 (m, 1H), 3.19 (s, 2H), 1.29 (s, 6H). LC-MS (ESI+) m/z 333.3 [(M+H) + , calcd. C 17 H 18 F 2 N 4 O m/z 332.1].

실시예 121: 1-((2-(다이플루오로메틸)-6-(1Example 121: 1-((2-(difluoromethyl)-6-(1 HH -피롤로[3,2--Pyrrolo[3,2- bb ]피리딘-1-일)피리딘-3-일)아미노)-2-메틸프로판-2-올 [1-((2-(difluoromethyl)-6-(1]pyridin-1-yl)pyridin-3-yl)amino)-2-methylpropan-2-ol [1-((2-(difluoromethyl)-6-(1 HH -pyrrolo[3,2--pyrrolo[3,2- bb ]pyridin-1-yl)pyridin-3-yl)amino)-2-methylpropan-2-ol]]pyridin-1-yl)pyridin-3-yl)amino)-2-methylpropan-2-ol]

실시예 121은 1-((6-브로모-2-(다이플루오로메틸)피리딘-3-일)아미노)-2-메틸프로판-2-올 (100.0 mg, 0.34 mmol) (실시예 120, A 파트) 및 1H-피롤로[3,2-b]피리딘 (40.3 mg, 0.34 mmol)을 사용하여 실시예 10에 대하여 설명한 것과 유사한 절차에 따라 제조하였고, 황색 분말 (29.6 mg, 26.2%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.59 (d, 1H), 8.36 (d, 1H), 8.05 (d, 1H), 7.59 (d, 1H), 7.47 (d, 1H), 7.25-7.28 (m, 1H), 6.73-6.94 (m, 2H), 3.19 (s, 2H), 1.29 (m, 6H). LC-MS (ESI+) m/z 333.6 [(M+H)+, calcd. C17H18F2N4O m/z 332.1].Example 121 was prepared according to a similar procedure as described for Example 10 using 1-((6-bromo-2-(difluoromethyl)pyridin-3-yl)amino)-2-methylpropan-2-ol (100.0 mg, 0.34 mmol) (Example 120, Part A) and 1 H -pyrrolo[3,2- b ]pyridine (40.3 mg, 0.34 mmol) to obtain a yellow powder (29.6 mg, 26.2%). 1H NMR (500 MHz, MeOD) δ 8.59 (d, 1H), 8.36 (d, 1H), 8.05 (d, 1H), 7.59 (d, 1H), 7.47 (d, 1H), 7.25-7.28 (m, 1H), 6.73-6.94 (m, 2H), 3.19 (s, 2H), 1.29 (m, 6H). LC-MS (ESI+) m/z 333.6 [(M+H) + , calcd. C 17 H 18 F 2 N 4 O m/z 332.1].

실시예 122: 1-(2-클로로-4-(1Example 122: 1-(2-chloro-4-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)펜옥시)-2-메틸프로판-2-아민 [1-(2-chloro-4-(1]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine [1-(2-chloro-4-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine]]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine]

A 파트: Part A: tert-부틸 (1-(4-브로모-2-클로로펜옥시)-2-메틸프로판-2-일)카바메이트tert-butyl (1-(4-bromo-2-chlorophenoxy)-2-methylpropan-2-yl)carbamate

탄산칼륨 (0.8 g, 5.78 mmol)을 4-브로모-2-클로로페놀 (0.6 g, 2.89 mmol) 및 tert-부틸 4,4-다이메틸-1,2,3-옥사티아졸리딘-3-카복실레이트 2,2-다이옥사이드 (1.1 g, 4.34 mmol)의 N,N-다이메틸포름아미드 (5 mL) 용액에 넣었다. 반응 혼합물을 100oC의 마이크로파에서 1.5시간 동안 조사하였다. TLC와 HPLC로 반응의 진행을 모니터링하였다. 반응이 완료된 후, EtOAc와 물로 희석하였다. 분리된 유기층을 물과 염수로 세척하고, 황산마그네슘으로 건조시킨 후 농축하였다. 잔류물을 MPLC (실리카겔, 0 내지 20%의 n-헥산 중 EtOAc로 용출)로 정제하고 회백색 분말을 얻었다. LC-MS (ESI+) m/z 378.6 [(M+H)+, calcd. C15H21BrClNO3 m/z 377.0].Potassium carbonate (0.8 g, 5.78 mmol) was added to a solution of 4-bromo-2-chlorophenol (0.6 g, 2.89 mmol) and tert -butyl 4,4-dimethyl-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide (1.1 g, 4.34 mmol) in N , N -dimethylformamide (5 mL). The reaction mixture was irradiated in a microwave at 100 o C for 1.5 h. The progress of the reaction was monitored by TLC and HPLC. After the reaction was completed, the mixture was diluted with EtOAc and water. The separated organic layer was washed with water and brine, dried over magnesium sulfate, and concentrated. The residue was purified by MPLC (silica gel, eluted with 0–20% EtOAc in n -hexane) to obtain an off-white powder. LC-MS (ESI+) m/z 378.6 [(M+H) + , calcd. C 15 H 21 BrClNO 3 m/z 377.0].

실시예 122를 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 122 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: 1-(2-클로로-4-(1H-피롤로[2,3-b]피리딘-3-일)펜옥시)-2-메틸프로판-2-아민1-(2-chloro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine

이 화합물은 tert-부틸 (1-(4-브로모-2-클로로펜옥시)-2-메틸프로판-2-일)카바메이트 (100.0 mg, 0.26 mmol) (실시예 122, A 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (136.3 mg, 0.40 mmol)를 사용하여 제조하였고, 연한-황색 분말 (30.5 mg, 36.5%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.90 (d, 1H), 8.48 (d, 1H), 7.95 (s, 1H), 7.78 (d, 1H), 7.63-7.67 (m, 2H), 7.30 (d, 1H), 4.14 (s, 2H), 1.52 (s, 6H). LC-MS (ESI+) m/z 316.3 [(M+H)+, calcd. C17H18ClN3O m/z 315.1].This compound was prepared using tert -butyl (1-(4-bromo-2-chlorophenoxy)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.26 mmol) (Example 122, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (136.3 mg, 0.40 mmol) to obtain a pale-yellow powder (30.5 mg, 36.5%). 1H NMR (500 MHz, MeOD) δ 8.90 (d, 1H), 8.48 (d, 1H), 7.95 (s, 1H), 7.78 (d, 1H), 7.63-7.67 (m, 2H), 7.30 (d, 1H), 4.14 (s, 2H), 1.52 (s, 6H). LC-MS (ESI+) m/z 316.3 [(M+H) + , calcd. C 17 H 18 ClN 3 O m/z 315.1].

실시예 123: 1-(2-플루오로-4-(1Example 123: 1-(2-Fluoro-4-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)펜옥시)-2-메틸프로판-2-아민 [1-(2-fluoro-4-(1]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine [1-(2-fluoro-4-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine]]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine]

실시예 123을 실시예 122에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 123 was prepared according to a procedure similar to that described for Example 122.

A 파트: Part A: terttert -부틸 (1-(4-브로모-2-플루오로펜옥시)-2-메틸프로판-2-일)카바메이트-Butyl (1-(4-bromo-2-fluorophenoxy)-2-methylpropan-2-yl)carbamate

이 화합물은 4-브로모-2-플루오로페놀 (200.0 mg, 1.05 mmol) 및 tert-부틸 4,4-다이메틸-1,2,3-옥사티아졸리딘-3-카복실레이트 2,2-다이옥사이드 (394.7 mg, 1.57 mmol)를 사용하여 제조하였고, 회백색 분말 (309.0 mg, 54.9%)을 얻었다. LC-MS (ESI+) m/z 362.2 [(M+H)+, calcd. C15H21BrFNO3 m/z 361.0].This compound was prepared using 4-bromo-2-fluorophenol (200.0 mg, 1.05 mmol) and tert -butyl 4,4-dimethyl-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide (394.7 mg, 1.57 mmol) and an off-white powder (309.0 mg, 54.9%) was obtained. LC-MS (ESI+) m/z 362.2 [(M+H) + , calcd. C 15 H 21 BrFNO 3 m/z 361.0].

실시예 123을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 123 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: 1-(2-플루오로-4-(1H-피롤로[2,3-b]피리딘-3-일)펜옥시)-2-메틸프로판-2-아민1-(2-fluoro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine

이 화합물은 tert-부틸 (1-(4-브로모-2-플루오로펜옥시)-2-메틸프로판-2-일)카바메이트 (100.0 mg, 0.28 mmol) (실시예 123, A 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (142.5 mg, 0.41 mmol)를 사용하여 제조하였고, 연한-황색 분말 (31.3 mg, 37.8%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.91 (d, 1H), 8.48 (d, 1H), 7.94 (s, 1H), 7.62-7.65 (m, 1H), 7.50-7.56 (m, 2H), 7.30 (t, 1H), 4.13 (s, 2H), 1.49 (s, 6H). LC-MS (ESI+) m/z 300.3 [(M+H)+, calcd. C17H18FN3O m/z 299.1].This compound was prepared using tert -butyl (1-(4-bromo-2-fluorophenoxy)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.28 mmol) (Example 123, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (142.5 mg, 0.41 mmol) to obtain a pale-yellow powder (31.3 mg, 37.8%). 1H NMR (500 MHz, MeOD) δ 8.91 (d, 1H), 8.48 (d, 1H), 7.94 (s, 1H), 7.62-7.65 (m, 1H), 7.50-7.56 (m, 2H), 7.30 (t, 1H), 4.13 (s, 2H), 1.49 (s, 6H). LC-MS (ESI+) m/z 300.3 [(M+H) + , calcd. C 17 H 18 FN 3 O m/z 299.1].

실시예 124: 1-(2,5-다이클로로-4-(1Example 124: 1-(2,5-Dichloro-4-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)펜옥시)-2-메틸프로판-2-아민 [1-(2,5-dichloro-4-(1]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine [1-(2,5-dichloro-4-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine]]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine]

실시예 124를 실시예 122에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 124 was prepared according to a procedure similar to that described for Example 122.

A 파트: Part A: terttert -부틸 (1-(4-브로모-2,5-다이클로로펜옥시)-2-메틸프로판-2-일)카바메이트-Butyl (1-(4-bromo-2,5-dichlorophenoxy)-2-methylpropan-2-yl)carbamate

이 화합물은 4-브로모-2,5-다이클로로페놀 (200.0 mg, 0.83 mmol) 및 tert-부틸 4,4-다이메틸-1,2,3-옥사티아졸리딘-3-카복실레이트 2,2-다이옥사이드 (311.6 mg, 1.24 mmol)를 사용하여 제조하였고, 회백색 분말 (179.0 mg, 52.4%)을 얻었다. LC-MS (ESI+) m/z 412.1 [(M+H)+, calcd. C15H20BrCl2NO3 m/z 411.0].This compound was prepared using 4-bromo-2,5-dichlorophenol (200.0 mg, 0.83 mmol) and tert -butyl 4,4-dimethyl-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide (311.6 mg, 1.24 mmol) and an off-white powder (179.0 mg, 52.4%) was obtained. LC-MS (ESI+) m/z 412.1 [(M+H) + , calcd. C 15 H 20 BrCl 2 NO 3 m/z 411.0].

실시예 124를 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 124 was prepared according to a procedure similar to that described for Example 57.

C 파트: 1-(2,5-다이클로로-4-(1Part C: 1-(2,5-Dichloro-4-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)펜옥시)-2-메틸프로판-2-아민]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine

실시예 124는 tert-부틸 (1-(4-브로모-2,5-다이클로로펜옥시)-2-메틸프로판-2-일)카바메이트 (100.0 mg, 0.24 mmol) (실시예 124, A 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (131.5 mg, 0.36 mmol)을 사용하여 실시예 64에 대하여 설명한 것과 유사한 절차에 따라 제조하였고, 아이보리색 분말 (15.8 mg, 19.1%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.59(d, 1H), 8.36(d, 1H), 8.05(d, 1H), 7.59(d, 2H), 7.47(d, 1H), 4.13(s, 2H), 1.49(s, 6H). LC-MS (ESI+) m/z 350.3 [(M+H)+, calcd. C17H17Cl2N3O m/z 349.0].Example 124 was prepared according to a similar procedure as that described for Example 64 using tert -butyl (1-(4-bromo-2,5-dichlorophenoxy)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.24 mmol) (Example 124, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (131.5 mg, 0.36 mmol) to obtain an ivory powder (15.8 mg, 19.1%). 1H NMR (500 MHz, MeOD) δ 8.59(d, 1H), 8.36(d, 1H), 8.05(d, 1H), 7.59(d, 2H), 7.47(d, 1H), 4.13(s, 2H), 1.49(s, 6H). LC-MS (ESI+) m/z 350.3 [(M+H) + , calcd. C 17 H 17 Cl 2 N 3 O m/z 349.0].

실시예 125: 2-메틸-1-(2-메틸-4-(1Example 125: 2-Methyl-1-(2-methyl-4-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)펜옥시)프로판-2-아민 [2-methyl-1-(2-methyl-4-(1]pyridin-3-yl)phenoxy)propan-2-amine [2-methyl-1-(2-methyl-4-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)phenoxy)propan-2-amine]]pyridin-3-yl)phenoxy)propan-2-amine]

실시예 125를 실시예 122에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 125 was prepared according to a procedure similar to that described for Example 122.

A 파트: Part A: tert-부틸 (1-(4-브로모-2-메틸펜옥시)-2-메틸프로판-2-일)카바메이트tert-butyl (1-(4-bromo-2-methylphenoxy)-2-methylpropan-2-yl)carbamate

이 화합물은 4-브로모-2-메틸페놀 (200.0 mg, 1.07 mmol) 및 tert-부틸 4,4-다이메틸-1,2,3-옥사티아졸리딘-3-카복실레이트 2,2-다이옥사이드 (403.0 mg, 1.60 mmol)를 사용하여 제조하였고, 회백색 분말 (213.3 mg, 55.6%)을 얻었다. LC-MS (ESI+) m/z 358.3 [(M+H)+, calcd. C16H24BrNO3 m/z 357.0].This compound was prepared using 4-bromo-2-methylphenol (200.0 mg, 1.07 mmol) and tert -butyl 4,4-dimethyl-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide (403.0 mg, 1.60 mmol) and an off-white powder (213.3 mg, 55.6%) was obtained. LC-MS (ESI+) m/z 358.3 [(M+H) + , calcd. C 16 H 24 BrNO 3 m/z 357.0].

실시예 125를 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 125 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: 2-메틸-1-(2-메틸-4-(1H-피롤로[2,3-b]피리딘-3-일)펜옥시)프로판-2-아민2-Methyl-1-(2-methyl-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)propan-2-amine

이 화합물은 tert-부틸 (1-(4-브로모-2-메틸펜옥시)-2-메틸프로판-2-일)카바메이트 (100.0 mg, 0.28 mmol) (실시예 125, A 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (144.1 mg, 0.42 mmol)를 사용하여 제조하였고, 황색 분말 (27.5 mg, 33.7%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.88 (d, 1H), 8.44 (d, 1H), 7.85 (s, 1H), 7.60-7.63 (m, 1H), 7.51 (d, 2H), 7.08 (d, 1H), 4.05 (s, 2H), 2.37 (s, 3H), 1.50 (s, 6H). LC-MS (ESI+) m/z 296.3 [(M+H)+, calcd. C18H21N3O m/z 295.1].This compound was prepared using tert -butyl (1-(4-bromo-2-methylphenoxy)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.28 mmol) (Example 125, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (144.1 mg, 0.42 mmol) and a yellow powder (27.5 mg, 33.7%) was obtained. 1H NMR (500 MHz, MeOD) δ 8.88 (d, 1H), 8.44 (d, 1H), 7.85 (s, 1H), 7.60-7.63 (m, 1H), 7.51 (d, 2H), 7.08 (d, 1H), 4.05 (s, 2H), 2.37 (s, 3H), 1.50 (s, 6H). LC-MS (ESI+) m/z 296.3 [(M+H) + , calcd. C 18 H 21 N 3 O m/z 295.1].

실시예 126: 1-(2,6-다이플루오로-4-(1Example 126: 1-(2,6-Difluoro-4-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)펜옥시)-2-메틸프로판-2-아민 [1-(2,6-difluoro-4-(1]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine [1-(2,6-difluoro-4-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine]]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine]

실시예 126을 실시예 122에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 126 was prepared according to a procedure similar to that described for Example 122.

A 파트: Part A: tert-부틸 (1-(4-브로모-2,6-다이플루오로펜옥시)-2-메틸프로판-2-일)카바메이트tert-butyl (1-(4-bromo-2,6-difluorophenoxy)-2-methylpropan-2-yl)carbamate

이 화합물은 4-브로모-2,6-다이플루오로페놀 (200.0 mg, 0.96 mmol) 및 tert-부틸 4,4-다이메틸-1,2,3-옥사티아졸리딘-3-카복실레이트 2,2-다이옥사이드 (360.7 mg, 1.44 mmol)를 사용하여 제조하였고, 회백색 분말 (265.3 mg, 72.9%)을 얻었다. LC-MS (ESI+) m/z 380.2 [(M+H)+, calcd. C15H20BrF2NO3 m/z 379.0].This compound was prepared using 4-bromo-2,6-difluorophenol (200.0 mg, 0.96 mmol) and tert -butyl 4,4-dimethyl-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide (360.7 mg, 1.44 mmol) and an off-white powder (265.3 mg, 72.9%) was obtained. LC-MS (ESI+) m/z 380.2 [(M+H) + , calcd. C 15 H 20 BrF 2 NO 3 m/z 379.0].

실시예 126을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 126 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: 1-(2,6-다이플루오로-4-(1H-피롤로[2,3-b]피리딘-3-일)펜옥시)-2-메틸프로판-2-아민1-(2,6-difluoro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine

이 화합물은 tert-부틸 (1-(4-브로모-2,6-다이플루오로펜옥시)-2-메틸프로판-2-일)카바메이트 (100.0 mg, 0.26 mmol) (실시예 126, A 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (135.7 mg, 0.39 mmol)를 사용하여 제조하였고, 연한-황색 분말 (28.6 mg, 34.2%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.94 (d, 1H), 8.50 (d, 1H), 8.03 (s, 1H), 7.64-7.67 (m, 1H), 7.46 (d, 2H), 4.16 (s, 2H), 1.47 (s, 6H). LC-MS (ESI+) m/z 318.5 [(M+H)+, calcd. C17H17F2N3O m/z 317.1].This compound was prepared using tert -butyl (1-(4-bromo-2,6-difluorophenoxy)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.26 mmol) (Example 126, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (135.7 mg, 0.39 mmol) to obtain a pale-yellow powder (28.6 mg, 34.2%). 1H NMR (500 MHz, MeOD) δ 8.94 (d, 1H), 8.50 (d, 1H), 8.03 (s, 1H), 7.64-7.67 (m, 1H), 7.46 (d, 2H), 4.16 (s, 2H), 1.47 (s, 6H). LC-MS (ESI+) m/z 318.5 [(M+H) + , calcd. C 17 H 17 F 2 N 3 O m/z 317.1].

실시예 127: 1-(2,5-다이플루오로-4-(1Example 127: 1-(2,5-Difluoro-4-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)펜옥시)-2-메틸프로판-2-아민 [1-(2,5-difluoro-4-(1]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine [1-(2,5-difluoro-4-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine]]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine]

실시예 127을 실시예 122에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 127 was prepared according to a procedure similar to that described for Example 122.

A 파트: Part A: tert-부틸 (1-(4-브로모-2,5-다이플루오로펜옥시)-2-메틸프로판-2-일)카바메이트tert-butyl (1-(4-bromo-2,5-difluorophenoxy)-2-methylpropan-2-yl)carbamate

이 화합물은 4-브로모-2,5-다이플루오로페놀 (200.0 mg, 0.96 mmol) 및 tert-부틸 4,4-다이메틸-1,2,3-옥사티아졸리딘-3-카복실레이트 2,2-다이옥사이드 (360.7 mg, 1.44 mmol)를 사용하여 제조하였고, 회백색 분말 (182.6 mg, 50.1%)을 얻었다. LC-MS (ESI+) m/z 380.3 [(M+H)+, calcd. C15H20BrF2NO3 m/z 379.0].This compound was prepared using 4-bromo-2,5-difluorophenol (200.0 mg, 0.96 mmol) and tert -butyl 4,4-dimethyl-1,2,3-oxathiazolidine-3-carboxylate 2,2-dioxide (360.7 mg, 1.44 mmol) and an off-white powder (182.6 mg, 50.1%) was obtained. LC-MS (ESI+) m/z 380.3 [(M+H) + , calcd. C 15 H 20 BrF 2 NO 3 m/z 379.0].

실시예 127을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 127 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: 1-(2,5-다이플루오로-4-(1H-피롤로[2,3-b]피리딘-3-일)펜옥시)-2-메틸프로판-2-아민1-(2,5-difluoro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine

이 화합물은 tert-부틸 (1-(4-브로모-2,5-다이플루오로펜옥시)-2-메틸프로판-2-일)카바메이트 (100.0 mg, 0.26 mmol) (실시예 127, A 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (135.7 mg, 0.39 mmol)를 사용하여 제조하였고, 연한-황색 분말 (25.8 mg, 30.9%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.76 (d, 1H), 8.51 (d, 1H), 7.94 (s, 1H), 7.63-7.66 (m, 1H), 7.53-7.57 (m, 1H), 7.23-7.27 (m, 1H), 4.16 (s, 2H), 1.50 (s, 6H). LC-MS (ESI+) m/z 318.3 [(M+H)+, calcd. C17H17F2N3O m/z 317.1].This compound was prepared using tert -butyl (1-(4-bromo-2,5-difluorophenoxy)-2-methylpropan-2-yl)carbamate (100.0 mg, 0.26 mmol) (Example 127, Part A) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (135.7 mg, 0.39 mmol) to obtain a pale-yellow powder (25.8 mg, 30.9%). 1H NMR (500 MHz, MeOD) δ 8.76 (d, 1H), 8.51 (d, 1H), 7.94 (s, 1H), 7.63-7.66 (m, 1H), 7.53-7.57 (m, 1H), 7.23-7.27 (m, 1H), 4.16 (s, 2H), 1.50 (s, 6H). LC-MS (ESI+) m/z 318.3 [(M+H) + , calcd. C 17 H 17 F 2 N 3 O m/z 317.1].

실시예 128: 5-플루오로-3-(4-(피페라진-1-일)페닐)-1Example 128: 5-Fluoro-3-(4-(piperazin-1-yl)phenyl)-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘 [5-fluoro-3-(4-(piperazin-1-yl)phenyl)-1]pyridine [5-fluoro-3-(4-(piperazin-1-yl)phenyl)-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridine]]pyridine]

실시예 128을 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 128 was prepared according to a procedure similar to that described for Example 13.

C 파트: Part C: 5-플루오로-3-(4-(피페라진-1-일)페닐)-1H-피롤로[2,3-b]피리딘5-Fluoro-3-(4-(piperazin-1-yl)phenyl)-1H-pyrrolo[2,3-b]pyridine

이 화합물은 1-(4-브로모페닐)피페라진 (100.0 mg, 0.41 mmol) 및 tert-부틸 5-플루오로-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (225.3 mg, 0.62 mmol)를 사용하여 제조하였고, 아이보리색 분말 (30.8 mg, 25.1%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.33 (s, 1H), 8.26-8.28 (m, 1H), 7.78 (s, 1H), 7.63 (d, 2H), 7.18 (d, 2H), 3.42-3.50 (m, 8H). LC-MS (ESI+) m/z 297.2 [(M+H)+, calcd. C17H17FN4 m/z 296.1].This compound was prepared using 1-(4-bromophenyl)piperazine (100.0 mg, 0.41 mmol) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (225.3 mg, 0.62 mmol) and an ivory powder (30.8 mg, 25.1%) was obtained. 1 H NMR (500 MHz, MeOD) δ 8.33 (s, 1H), 8.26-8.28 (m, 1H), 7.78 (s, 1H), 7.63 (d, 2H), 7.18 (d, 2H), 3.42-3.50 (m, 8H). LC-MS (ESI+) m/z 297.2 [(M+H) + , calcd. C 17 H 17 FN 4 m/z 296.1].

실시예 129: 5-플루오로-3-(4-(4-메틸피페라진-1-일)페닐)-1Example 129: 5-Fluoro-3-(4-(4-methylpiperazin-1-yl)phenyl)-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘 [5-fluoro-3-(4-(4-methylpiperazin-1-yl)phenyl)-1]pyridine [5-fluoro-3-(4-(4-methylpiperazin-1-yl)phenyl)-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridine]]pyridine]

실시예 129를 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 129 was prepared according to a procedure similar to that described for Example 13.

C 파트: Part C: 5-플루오로-3-(4-(4-메틸피페라진-1-일)페닐)-1H-피롤로[2,3-b]피리딘5-Fluoro-3-(4-(4-methylpiperazin-1-yl)phenyl)-1H-pyrrolo[2,3-b]pyridine

이 화합물은 1-(4-브로모페닐)-4-메틸피페라진 (100.0 mg, 0.39 mmol) 및 tert-부틸 5-플루오로-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (212.9 mg, 0.59 mmol)를 사용하여 제조하였고, 회백색 분말 (18.5 mg, 15.2%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.15 (s, 1H), 7.99-8.01 (m, 1H), 7.64 (s, 1H), 7.56 (d, 2H), 7.10 (d, 2H), 3.26-3.28 (m, 4H), 2.67-2.69 (m, 4H), 2.39 (s, 3H). LC-MS (ESI+) m/z 311.1 [(M+H)+, calcd. C18H19FN4 m/z 310.1].This compound was prepared using 1-(4-bromophenyl)-4-methylpiperazine (100.0 mg, 0.39 mmol) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (212.9 mg, 0.59 mmol) and an off-white powder (18.5 mg, 15.2%) was obtained. 1H NMR (500 MHz, MeOD) δ 8.15 (s, 1H), 7.99-8.01 (m, 1H), 7.64 (s, 1H), 7.56 (d, 2H), 7.10 (d, 2H), 3.26-3.28 (m, 4H), 2.67-2.69 (m, 4H), 2.39 (s, 3H). LC-MS (ESI+) m/z 311.1 [(M+H) + , calcd. C 18 H 19 FN 4 m/z 310.1].

실시예 130: 4-(4-(5-플루오로-1Example 130: 4-(4-(5-fluoro-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)페닐)모폴린 [4-(4-(5-fluoro-1]pyridin-3-yl)phenyl)morpholine [4-(4-(5-fluoro-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)phenyl)morpholine]]pyridin-3-yl)phenyl)morpholine]

실시예 130을 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 130 was prepared according to a procedure similar to that described for Example 13.

C 파트: Part C: 4-(4-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)페닐)모폴린4-(4-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)phenyl)morpholine

이 화합물은 4-(4-브로모페닐)모폴린 (100.0 mg, 0.41 mmol) 및 tert-부틸 5-플루오로-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (224.4 mg, 0.62 mmol)를 사용하여 제조하였고, 아이보리색 분말 (20.1 mg, 16.4%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.35 (s, 1H), 8.24-8.28 (m, 3H), 8.17-8.21 (m, 3H), 3.90-3.92 (m, 4H), 3.43-3.45 (m, 4H). LC-MS (ESI+) m/z 298.3 [(M+H)+, calcd. C17H16FN3O m/z 297.1].This compound was prepared using 4-(4-bromophenyl)morpholine (100.0 mg, 0.41 mmol) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (224.4 mg, 0.62 mmol) and an ivory powder (20.1 mg, 16.4%) was obtained. 1 H NMR (500 MHz, MeOD) δ 8.35 (s, 1H), 8.24-8.28 (m, 3H), 8.17-8.21 (m, 3H), 3.90-3.92 (m, 4H), 3.43-3.45 (m, 4H). LC-MS (ESI+) m/z 298.3 [(M+H) + , calcd. C 17 H 16 FN 3 O m/z 297.1].

실시예 131: 5-플루오로-3-(5-(피페라진-1-일)피리딘-2-일)-1Example 131: 5-Fluoro-3-(5-(piperazin-1-yl)pyridin-2-yl)-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘 [5-fluoro-3-(5-(piperazin-1-yl)pyridin-2-yl)-1]pyridine [5-fluoro-3-(5-(piperazin-1-yl)pyridin-2-yl)-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridine]]pyridine]

실시예 131을 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 131 was prepared according to a procedure similar to that described for Example 13.

C 파트: Part C: 5-플루오로-3-(5-(피페라진-1-일)피리딘-2-일)-1H-피롤로[2,3-b]피리딘5-Fluoro-3-(5-(piperazin-1-yl)pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridine

이 화합물은 1-(6-브로모피리딘-3-일)피페라진 (100.0 mg, 0.41 mmol) 및 tert-부틸 5-플루오로-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (224.4 mg, 0.62 mmol)를 사용하여 제조하였고, 아이보리색 분말 (24.6 mg, 20.0%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.32 (s, 1H), 8.25-8.28 (m, 2H), 7.78 (s, 1H), 7.63 (d, 1H), 7.18 (d, 1H), 3.42-3.50 (m, 8H). LC-MS (ESI+) m/z 298.3 [(M+H)+, calcd. C16H16FN5 m/z 297.1].This compound was prepared using 1-(6-bromopyridin-3-yl)piperazine (100.0 mg, 0.41 mmol) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (224.4 mg, 0.62 mmol) and an ivory powder (24.6 mg, 20.0%) was obtained. 1H NMR (500 MHz, MeOD) δ 8.32 (s, 1H), 8.25-8.28 (m, 2H), 7.78 (s, 1H), 7.63 (d, 1H), 7.18 (d, 1H), 3.42-3.50 (m, 8H). LC-MS (ESI+) m/z 298.3 [(M+H) + , calcd. C 16 H 16 FN 5 m/z 297.1].

실시예 132: 5-플루오로-3-(5-(4-메틸피페라진-1-일)피리딘-2-일)-1Example 132: 5-Fluoro-3-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘 [5-fluoro-3-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)-1]pyridine [5-fluoro-3-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridine]]pyridine]

실시예 132를 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 132 was prepared according to a procedure similar to that described for Example 13.

C 파트: Part C: 5-플루오로-3-(5-(4-메틸피페라진-1-일)피리딘-2-일)-1H-피롤로[2,3-b]피리딘5-Fluoro-3-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridine

이 화합물은 1-(6-브로모피리딘-3-일)-4-메틸피페라진 (100.0 mg, 0.39 mmol) 및 tert-부틸 5-플루오로-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (212.1 mg, 0.59 mmol)를 사용하여 제조하였고, 아이보리색 분말 (34.8 mg, 28.6%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.37-8.39 (m, 1H), 8.32 (d, 1H), 8.17 (s, 1H), 7.95 (s, 1H), 7.67 (d, 1H), 7.46-7.48 (m 1H), 3.31-3.33 (m, 4H), 2.67-2.69 (m, 4H), 2.39 (s, 3H). LC-MS (ESI+) m/z 312.1 [(M+H)+, calcd. C17H18FN5 m/z 311.1].This compound was prepared using 1-(6-bromopyridin-3-yl)-4-methylpiperazine (100.0 mg, 0.39 mmol) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (212.1 mg, 0.59 mmol) and an ivory powder (34.8 mg, 28.6%) was obtained. 1H NMR (500 MHz, MeOD) δ 8.37-8.39 (m, 1H), 8.32 (d, 1H), 8.17 (s, 1H), 7.95 (s, 1H), 7.67 (d, 1H), 7.46-7.48 (m 1H), 3.31-3.33 (m, 4H), 2.67-2.69 (m, 4H), 2.39 (s, 3H). LC-MS (ESI+) m/z 312.1 [(M+H) + , calcd. C 17 H 18 FN 5 m/z 311.1].

실시예 133: 4-(6-(5-플루오로-1Example 133: 4-(6-(5-Fluoro-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)모폴린 [4-(6-(5-fluoro-1]pyridin-3-yl)pyridin-3-yl)morpholine [4-(6-(5-fluoro-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)morpholine]]pyridin-3-yl)pyridin-3-yl)morpholine]

실시예 133을 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 133 was prepared according to a procedure similar to that described for Example 13.

C 파트: Part C: 4-(6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)모폴린4-(6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)morpholine

이 화합물은 4-(6-브로모피리딘-3-일)모폴린 (100.0 mg, 0.41 mmol) 및 tert-부틸 5-플루오로-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (223.4 mg, 0.62 mmol)를 사용하여 제조하였고, 아이보리색 분말 (30.8 mg, 25.1%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.37 (s, 1H), 8.25-8.26 (m, 2H), 8.17-8.21 (m, 3H), 3.90-3.92 (m, 4H), 3.43-3.45 (m, 4H). LC-MS (ESI+) m/z 299.6 [(M+H)+, calcd. C16H15FN4O m/z 298.1].This compound was prepared using 4-(6-bromopyridin-3-yl)morpholine (100.0 mg, 0.41 mmol) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (223.4 mg, 0.62 mmol) and an ivory powder (30.8 mg, 25.1%) was obtained. 1H NMR (500 MHz, MeOD) δ 8.37 (s, 1H), 8.25-8.26 (m, 2H), 8.17-8.21 (m, 3H), 3.90-3.92 (m, 4H), 3.43-3.45 (m, 4H). LC-MS (ESI+) m/z 299.6 [(M+H) + , calcd. C 16 H 15 FN 4 O m/z 298.1].

실시예 134: 4-(2-(다이플루오로메틸)-6-(5-플루오로-1Example 134: 4-(2-(difluoromethyl)-6-(5-fluoro-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)모폴린 [4-(2-(difluoromethyl)-6-(5-fluoro-1]pyridin-3-yl)pyridin-3-yl)morpholine [4-(2-(difluoromethyl)-6-(5-fluoro-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)morpholine]]pyridin-3-yl)pyridin-3-yl)morpholine]

실시예 134를 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 134 was prepared according to a procedure similar to that described for Example 13.

A 파트: Part A: 3-브로모-6-클로로-2-(다이플루오로메틸)피리딘3-bromo-6-chloro-2-(difluoromethyl)pyridine

이 화합물은 3-브로모-6-클로로피콜린알데히드 (2.0 g, 9.07 mmol) 및 디에틸아미노황 삼불화물 (2.6 mL, 18.14 mmol)을 사용하여 제조하였고, 회백색 분말 (2.0 g, 90.9%)을 얻었다. LC-MS (ESI+) m/z 242.4 [(M+H)+, calcd. C6H3BrClF2N m/z 240.9].This compound was prepared using 3-bromo-6-chloropicolinaldehyde (2.0 g, 9.07 mmol) and diethylaminosulfur trifluoride (2.6 mL, 18.14 mmol) and an off-white powder (2.0 g, 90.9%) was obtained. LC-MS (ESI+) m/z 242.4 [(M+H) + , calcd. C 6 H 3 BrClF 2 N m/z 240.9].

B 파트: Part B: 4-(6-클로로-2-(다이플루오로메틸)피리딘-3-일)모폴린4-(6-chloro-2-(difluoromethyl)pyridin-3-yl)morpholine

3-브로모-6-클로로-2-(다이플루오로메틸)피리딘 (100.0 mg, 0.41 mmol) (실시예 134, A 파트), 모폴린 (35.9 mg, 0.41 mmol), 트리스(다이벤질리덴아세톤)다이팔라듐(0) (75.5 mg, 0.08 mmol), 다이사이클로헥실(2',6'-다이메톡시-[1,1'-바이페닐]-2-일)포스핀 (25.4 mg, 0.06 mmol) 및 나트륨 tert-부톡사이드 (59.4 mg, 0.62 mmol)의 톨루엔 (5 mL) 용액을 80°C의 마이크로파에서 2.0시간 동안 조사하였다. TLC와 HPLC로 반응의 진행을 모니터링하였다. 반응이 완료된 후, EtOAc와 물로 희석하였다. 분리된 유기층을 물과 염수로 세척하고, 황산마그네슘으로 건조시킨 후 농축하였다. 잔류물을 MPLC (실리카겔, 0 내지 30%의 n-헥산 중 EtOAc로 용출)로 정제하고 아이보리색 분말 (18.7 mg, 18.2%)을 얻었다. LC-MS (ESI+) m/z 249.6 [(M+H)+, calcd. C10H11ClF2N2O m/z 248.0].A solution of 3-bromo-6-chloro-2-(difluoromethyl)pyridine (100.0 mg, 0.41 mmol) (Example 134, Part A), morpholine (35.9 mg, 0.41 mmol), tris(dibenzylideneacetone)dipalladium(0) (75.5 mg, 0.08 mmol), dicyclohexyl(2',6'-dimethoxy-[1,1'-biphenyl]-2-yl)phosphine (25.4 mg, 0.06 mmol), and sodium tert -butoxide (59.4 mg, 0.62 mmol) in toluene (5 mL) was irradiated in a microwave at 80 °C for 2.0 h. The progress of the reaction was monitored by TLC and HPLC. After the reaction was completed, the mixture was diluted with EtOAc and water. The separated organic layer was washed with water and brine, dried over magnesium sulfate, and concentrated. The residue was purified by MPLC (silica gel, eluted with 0–30% EtOAc in n -hexane) to give an ivory powder (18.7 mg, 18.2%). LC-MS (ESI+) m/z 249.6 [(M+H) + , calcd. C 10 H 11 ClF 2 N 2 O m/z 248.0].

실시예 134를 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 134 was prepared according to a procedure similar to that described for Example 13.

C 파트: Part C: 4-(2-(다이플루오로메틸)-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)모폴린4-(2-(difluoromethyl)-6-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)morpholine

이 화합물은 4-(6-클로로-2-(다이플루오로메틸)피리딘-3-일)모폴린 (100.0 mg, 0.40 mmol) (실시예 134, B 파트) 및 tert-부틸 5-플루오로-3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (218.5 mg, 0.60 mmol)를 사용하여 제조하였고, 연한-갈색 분말 (35.4 mg, 25.3%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 8.36-8.40 (m, 1H), 8.34 (d, 1H), 8.19 (s, 1H), 7.95 (s, 1H), 7.67 (d, 1H), 7.46-7.48 (m 1H), 3.90-3.92 (m, 4H), 3.43-3.45 (m, 4H). LC-MS (ESI+) m/z 349.8 [(M+H)+, calcd. C17H15F3N4O m/z 348.1].This compound was prepared using 4-(6-chloro-2-(difluoromethyl)pyridin-3-yl)morpholine (100.0 mg, 0.40 mmol) (Example 134, Part B) and tert -butyl 5-fluoro-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (218.5 mg, 0.60 mmol) to obtain a pale-brown powder (35.4 mg, 25.3%). 1H NMR (500 MHz, MeOD) δ 8.36-8.40 (m, 1H), 8.34 (d, 1H), 8.19 (s, 1H), 7.95 (s, 1H), 7.67 (d, 1H), 7.46-7.48 (m 1H), 3.90-3.92 (m, 4H), 3.43-3.45 (m, 4H). LC-MS (ESI+) m/z 349.8 [(M+H) + , calcd. C 17 H 15 F 3 N 4 O m/z 348.1].

실시예 135: 4-(2-(다이플루오로메틸)-6-(1Example 135: 4-(2-(difluoromethyl)-6-(1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘-3-일)피리딘-3-일)-2,2-다이메틸모폴린 [4-(2-(difluoromethyl)-6-(1]pyridin-3-yl)pyridin-3-yl)-2,2-dimethylmorpholine [4-(2-(difluoromethyl)-6-(1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridin-3-yl)pyridin-3-yl)-2,2-dimethylmorpholine]]pyridin-3-yl)pyridin-3-yl)-2,2-dimethylmorpholine]

실시예 135를 실시예 134에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 135 was prepared according to a procedure similar to that described for Example 134.

B 파트: Part B: 4-(6-클로로-2-(다이플루오로메틸)피리딘-3-일)-2,2-다이메틸모폴린4-(6-chloro-2-(difluoromethyl)pyridin-3-yl)-2,2-dimethylmorpholine

이 화합물은 3-브로모-6-클로로-2-(다이플루오로메틸)피리딘 (1.0 g, 4.12 mmol) (실시예 134, A 파트) 및 2,2-다이메틸모폴린 (475.0 mg, 4.12 mmol)을 사용하여 제조하였고, 연한-갈색 액체 (150.4 mg, 13.1%)를 얻었다. LC-MS (ESI+) m/z 277.1 [(M+H)+, calcd. C12H15ClF2N2O m/z 276.0].This compound was prepared using 3-bromo-6-chloro-2-(difluoromethyl)pyridine (1.0 g, 4.12 mmol) (Example 134, Part A) and 2,2-dimethylmorpholine (475.0 mg, 4.12 mmol) to obtain a pale-brown liquid (150.4 mg, 13.1%). LC-MS (ESI+) m/z 277.1 [(M+H) + , calcd. C 12 H 15 ClF 2 N 2 O m/z 276.0].

실시예 135를 실시예 13에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 135 was prepared according to a procedure similar to that described for Example 13.

C 파트: Part C: 4-(2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)-2,2-다이메틸모폴린4-(2-(difluoromethyl)-6-(1H-pyrrolo[2,3-b]pyridin-3-yl)pyridin-3-yl)-2,2-dimethylmorpholine

이 화합물은 4-(6-클로로-2-(다이플루오로메틸)피리딘-3-일)-2,2-다이메틸모폴린 (100.0 mg, 0.36 mmol) (실시예 135, B 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (181.1 mg, 0.54 mmol)를 사용하여 제조하였고, 연한-적색 분말 (26.8 mg, 20.7%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.02 (d, 1H), 8.27 (d, 1H), 8.08 (s, 1H), 7.93 (d, 1H), 7.78 (d, 1H), 7.12-7.33 (m, 2H), 3.93-3.94 (m, 2H), 2.95-2.97 (m, 2H), 1.38 (s, 6H), 1.30-1.31 (m, 2H). LC-MS (ESI+) m/z 359.5 [(M+H)+, calcd. C19H20F2N4O m/z 358.1].This compound was prepared using 4-(6-chloro-2-(difluoromethyl)pyridin-3-yl)-2,2-dimethylmorpholine (100.0 mg, 0.36 mmol) (Example 135, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (181.1 mg, 0.54 mmol) to obtain a pale-red powder (26.8 mg, 20.7%). 1H NMR (500 MHz, MeOD) δ 9.02 (d, 1H), 8.27 (d, 1H), 8.08 (s, 1H), 7.93 (d, 1H), 7.78 (d, 1H), 7.12-7.33 (m, 2H), 3.93-3.94 (m, 2H), 2.95-2.97 (m, 2H), 1.38 (s, 6H), 1.30-1.31 (m, 2H). LC-MS (ESI+) m/z 359.5 [(M+H) + , calcd. C 19 H 20 F 2 N 4 O m/z 358.1].

실시예 136: 3-(6-(다이플루오로메틸)-5-(3,3-다이메틸피페라진-1-일)피리딘-2-일)-1Example 136: 3-(6-(difluoromethyl)-5-(3,3-dimethylpiperazin-1-yl)pyridin-2-yl)-1 HH -피롤로[2,3--Pyrrolo[2,3- bb ]피리딘 [3-(6-(difluoromethyl)-5-(3,3-dimethylpiperazin-1-yl)pyridin-2-yl)-1]Pyridine [3-(6-(difluoromethyl)-5-(3,3-dimethylpiperazin-1-yl)pyridin-2-yl)-1 HH -pyrrolo[2,3--pyrrolo[2,3- bb ]pyridine]]pyridine]

실시예 136을 실시예 134에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 136 was prepared according to a procedure similar to that described for Example 134.

B 파트: Part B: tert-부틸 4-(6-클로로-2-(다이플루오로메틸)피리딘-3-일)-2,2-다이메틸피페라진-1-카복실레이트tert-Butyl 4-(6-chloro-2-(difluoromethyl)pyridin-3-yl)-2,2-dimethylpiperazine-1-carboxylate

이 화합물은 3-브로모-6-클로로-2-(다이플루오로메틸)피리딘 (300.0 mg, 1.24 mmol) (실시예 134, A 파트) 및 tert-부틸 2,2-다이메틸피페라진-1-카복실레이트 (265.1 mg, 1.24 mmol)를 사용하여 제조하였고, 아이보리색 분말 (115.3 mg, 24.7%)을 얻었다. LC-MS (ESI+) m/z 376.2 [(M+H)+, calcd. C17H24ClF2N3O2 m/z 375.1].This compound was prepared using 3-bromo-6-chloro-2-(difluoromethyl)pyridine (300.0 mg, 1.24 mmol) (Example 134, Part A) and tert -butyl 2,2-dimethylpiperazine-1-carboxylate (265.1 mg, 1.24 mmol) to obtain an ivory powder (115.3 mg, 24.7%). LC-MS (ESI+) m/z 376.2 [(M+H) + , calcd. C 17 H 24 ClF 2 N 3 O 2 m/z 375.1].

실시예 136을 실시예 57에 대하여 설명한 것과 유사한 절차에 따라 제조하였다. Example 136 was prepared according to a procedure similar to that described for Example 57.

C 파트: Part C: 3-(6-(다이플루오로메틸)-5-(3,3-다이메틸피페라진-1-일)피리딘-2-일)-1H-피롤로[2,3-b]피리딘3-(6-(difluoromethyl)-5-(3,3-dimethylpiperazin-1-yl)pyridin-2-yl)-1H-pyrrolo[2,3-b]pyridine

이 화합물은 tert-부틸 4-(6-클로로-2-(다이플루오로메틸)피리딘-3-일)-2,2-다이메틸피페라진-1-카복실레이트 (100.0 mg, 0.27 mmol) (실시예 136, B 파트) 및 tert-부틸 3-(4,4,5,5-테트라메틸-1,3,2-다이옥사보롤란-2-일)-1H-피롤로[2,3-b]피리딘-1-카복실레이트 (137.3 mg, 0.40 mmol)를 사용하여 제조하였고, 연한-황색 분말 (17.0 mg, 18.5%)을 얻었다. 1H NMR (500 MHz, MeOD) δ 9.46 (d, 1H), 8.45 (d, 1H), 8.34 (s, 1H), 8.08 (d, 1H), 7.93 (d, 1H), 7.56-7.58 (m, 1H), 7.13-7.35 (m, 1H), 3.68 (s, 2H), 3.50-3.51 (m, 2H), 3.25-3.27 (m, 2H), 1.58 (s, 6H). LC-MS (ESI+) m/z 358.3 [(M+H)+, calcd. C19H21F2N5 m/z 357.1].This compound was prepared using tert -butyl 4-(6-chloro-2-(difluoromethyl)pyridin-3-yl)-2,2-dimethylpiperazine-1-carboxylate (100.0 mg, 0.27 mmol) (Example 136, Part B) and tert -butyl 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1 H -pyrrolo[2,3- b ]pyridine-1-carboxylate (137.3 mg, 0.40 mmol) to obtain a pale-yellow powder (17.0 mg, 18.5%). 1H NMR (500 MHz, MeOD) δ 9.46 (d, 1H), 8.45 (d, 1H), 8.34 (s, 1H), 8.08 (d, 1H), 7.93 (d, 1H), 7.56-7.58 (m, 1H), 7.13-7.35 (m, 1H), 3.68 (s, 2H), 3.50-3.51 (m, 2H), 3.25-3.27 (m, 2H), 1.58 (s, 6H). LC-MS (ESI+) m/z 358.3 [(M+H) + , calcd. C 19 H 21 F 2 N 5 m/z 357.1].

실험예 1. AAK1 키나아제 분석Experimental Example 1. AAK1 Kinase Analysis

분석은 U-바닥 384웰 플레이트에서 수행하였다. 최종 분석 부피는 분석 완충액(10mM Tris-HCl pH 7. 4, 10 mM MgCl2. 0.01% TWEEN20 및 1.0 mM DTT)에 효소 및 기질(형광화 펩타이드(5-FAM)-Aha-KEEQSQITSQVTGQIGWR-NH2 및 ATP) 및 시험 화합물을 15μL 첨가하여 제조된 30μL였다. 반응은 박테리아로 발현된 GST-Xa-hAAK1과 기질 및 테스트 화합물의 조합에 의해 시작되었다. 반응은 실온에서 3시간 동안 인큐베이션하고 각 샘플에 35 mM EDTA 버퍼 60 μL를 추가하여 종결시켰다. 반응은 형광 기질 및 인산화된 생성물을 전기영동 분리하여 Caliper LabChip 3000 (Caliper, Hopkinton, Ma)에서 분석하였다. 억제 데이터는 EDTA 퀜칭 대조군 반응을 100% 억제, 및 비히클 단독 반응을 0% 억제와 비교하여 계산하였다. 분석에 사용된 시약의 최종 농도는 ATP, 22 μM; (5-FAM)-Aha-KEEQSQITSQVTGQIGWR-NH2, 1.5 μM; GST-Xa-hAAk1, 3.5 nM; 및 DMSO, 1.6%이다. 키나아제 활성의 50%를 억제하는 데 필요한 농도 (IC50)를 결정하기 위해 용량 반응 곡선을 생성하였다. 화합물은 디메틸설폭시드(DMSO)에 10 mM로 용해하고 11개 농도에서 평가하였다. IC50 값은 비선형 회귀 분석을 통해 도출되었다(표 1).Assays were performed in U-bottom 384-well plates. The final assay volume was 30 μL, prepared by adding 15 μL of enzyme and substrate (fluorescent peptide (5-FAM)-Aha-KEEQSQITSQVTGQIGWR-NH2 and ATP) and test compounds to assay buffer (10 mM Tris-HCl pH 7.4, 10 mM MgCl 2 , 0.01% TWEEN 20, and 1.0 mM DTT). The reaction was initiated by combining bacterially expressed GST-Xa-hAAK1 with substrate and test compounds. The reaction was incubated at room temperature for 3 h and terminated by adding 60 μL of 35 mM EDTA buffer to each sample. The reaction was analyzed on a Caliper LabChip 3000 (Caliper, Hopkinton, MA) by electrophoretically separating the fluorescent substrate and phosphorylated products. Inhibition data were calculated by comparing the EDTA-quenched control reaction with 100% inhibition and the vehicle-only reaction with 0% inhibition. The final concentrations of reagents used in the assay were ATP, 22 μM; (5-FAM)-Aha-KEEQSQITSQVTGQIGWR-NH2, 1.5 μM; GST-Xa-hAAk1, 3.5 nM; and DMSO, 1.6%. A dose-response curve was generated to determine the concentration required to inhibit 50% of kinase activity (IC 50 ). Compounds were dissolved in dimethyl sulfoxide (DMSO) at 10 mM and evaluated at 11 concentrations. IC 50 values were derived by nonlinear regression analysis (Table 1).

활성이 "A"로 지정된 화합물(실시예)은 IC50 <100 nM, 활성이 "B"로 지정된 화합물(실시예)은 IC50 > 100 nM을 나타내었다.Compounds designated as "A" (Example) exhibited IC 50 <100 nM, and compounds designated as "B" (Example) exhibited IC 50 >100 nM.

화합물compound A < 100 nM
B > 100 nMA < 100 nM
B > 100 nM 화합물compound A < 100 nM
B > 100 nMA < 100 nM
B > 100 nM 11 AA 6969 AA 22 AA 7070 BB 33 BB 7171 BB 44 BB 7272 AA 55 BB 7373 AA 66 AA 7474 AA 77 BB 7575 BB 88 BB 7676 AA 99 BB 7777 BB 1010 AA 7878 BB 1111 AA 7979 AA 1212 AA 8080 BB 1313 AA 8181 AA 1414 BB 8282 AA 1515 BB 8383 BB 1616 AA 8484 BB 1717 BB 8585 AA 1818 BB 8686 AA 1919 BB 8787 BB 2020 AA 8888 AA 2121 AA 8989 AA 2222 AA 9090 BB 2323 BB 9191 BB 2424 AA 9292 BB 2525 AA 9393 AA 2626 AA 9494 AA 2727 AA 9595 BB 2828 AA 9696 AA 2929 AA 9797 BB 3030 AA 9898 BB 3131 AA 9999 AA 3232 AA 100100 BB 3333 BB 101101 BB 3434 AA 102102 BB 3535 AA 103103 BB 3636 AA 104104 BB 3737 BB 105105 AA 3838 AA 106106 AA 3939 BB 107107 BB 4040 BB 108108 BB 4141 AA 109109 AA 4242 BB 110110 BB 4343 AA 111111 BB 4444 BB 112112 AA 4545 AA 113113 BB 4646 AA 114114 AA 4747 AA 115115 AA 4848 AA 116116 BB 4949 BB 117117 AA 5050 AA 118118 AA 5151 BB 119119 BB 5252 BB 120120 AA 5353 BB 121121 BB 5454 BB 122122 AA 5555 BB 123123 AA 5656 AA 124124 AA 5757 AA 125125 AA 5858 AA 126126 AA 5959 AA 127127 AA 6060 AA 128128 BB 6161 AA 129129 BB 6262 AA 130130 BB 6363 AA 131131 BB 6464 BB 132132 BB 6565 AA 133133 BB 6666 BB 134134 AA 6767 BB 135135 AA 6868 AA 136136 BB

합성된 실시예 1 ~ 실시예 136 화합물은 모두 AAK1에 대하여 우수한 저해 활성을 나타내었다.All of the synthesized compounds of Examples 1 to 136 exhibited excellent inhibitory activity against AAK1.

전술한 본 발명의 설명은 예시를 위한 것이며, 본 발명이 속하는 기술분야의 통상의 지식을 가진 자는 본 발명의 기술적 사상이나 필수적인 특징을 변경하지 않고서 다른 구체적인 형태로 쉽게 변형이 가능하다는 것을 이해할 수 있을 것이다. 그러므로 이상에서 기술한 실시예들은 모든 면에서 예시적인 것이며 한정적이 아닌 것으로 이해해야만 한다. 예를 들어, 단일형으로 설명되어 있는 각 구성 요소는 분산되어 실시될 수도 있으며, 마찬가지로 분산된 것으로 설명되어 있는 구성 요소들도 결합된 형태로 실시될 수 있다.The foregoing description of the present invention is for illustrative purposes only, and those skilled in the art will readily appreciate that the present invention can be readily modified into other specific forms without altering the technical spirit or essential characteristics of the present invention. Therefore, the embodiments described above should be understood as illustrative in all respects and not restrictive. For example, each component described as a single entity may be implemented in a distributed manner, and similarly, components described as distributed may be implemented in a combined manner.

본 발명의 범위는 후술하는 청구범위에 의하여 나타내어지며, 청구범위의 의미 및 범위 그리고 그 균등 개념으로부터 도출되는 모든 변경 또는 변형된 형태가 본 발명의 범위에 포함되는 것으로 해석되어야 한다.The scope of the present invention is indicated by the claims set forth below, and all changes or modifications derived from the meaning and scope of the claims and their equivalent concepts should be interpreted as being included in the scope of the present invention.

Claims (15)

하기 화학식 1로 표시되는 헤테로아릴 유도체 화합물, 이의 수화물, 이의 용매화물 또는 이의 약학적으로 허용가능한 염:A heteroaryl derivative compound represented by the following chemical formula 1, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof: <화학식 1><Chemical Formula 1> 상기 식에서, In the above formula, A는 CH 또는 N이고,A is CH or N, B1, B3, B4 및 B5는 C, CH, N 또는 NH이고,B 1 , B 3 , B 4 and B 5 are C, CH, N or NH, B2는 C, CH, N, NH 또는 O이고,B 2 is C, CH, N, NH or O, B 고리는 N 및 O 중에서 선택되는 1 내지 4개의 헤테로원자를 포함하는 5원의 방향족 헤테로사이클이고,The B ring is a 5-membered aromatic heterocycle containing 1 to 4 heteroatoms selected from N and O, Y는 NH, NR6 또는 O이고,Y is NH, NR 6 or O, R2는 H 또는 할로겐이고,R 2 is H or halogen, R4는 H, C1-4 알킬, 할로겐 또는 C1-4 할로알킬이고,R 4 is H, C 1-4 alkyl, halogen or C 1-4 haloalkyl, R5는 C1-9 직쇄 또는 분지쇄 알킬로서 C3-5 사이클로알킬을 포함하거나 포함하지 않고; 또는 R6와 연결되어, R5 및 R6에 연결된 N을 포함하고, N 또는 O를 추가로 포함하는, 5원 내지 7원의 비방향족 헤테로사이클을 형성하고,R 5 is a C 1-9 straight or branched chain alkyl, optionally including a C 3-5 cycloalkyl; or is connected to R 6 to form a 5- to 7-membered non-aromatic heterocycle, comprising N connected to R 5 and R 6 , and further comprising N or O, 상기 R5는 단수 또는 복수의 R5a로 치환되거나 치환되지 않고,wherein R 5 is substituted or unsubstituted with singular or plural R 5a , 상기 R5a는 C1-4 알킬, 아미노 또는 하이드록시이고,wherein R 5a is C 1-4 alkyl, amino or hydroxy, R6는 R5와 연결되어, R5 및 R6에 연결된 N을 포함하고, N 또는 O를 추가로 포함하는, 5원 내지 7원의 비방향족 헤테로사이클을 형성하고,R 6 is connected to R 5 to form a 5- to 7-membered non-aromatic heterocycle containing N connected to R 5 and R 6 , and further containing N or O, 상기 B1은 Rb1으로 치환되거나 치환되지 않고,The above B 1 is substituted or not substituted with R b1 , 상기 Rb1은 C1-4 알킬이거나; Rb2와 연결되어 0개 내지 2개의 N을 포함하고 B 고리와 융합된 C 고리를 형성하고,wherein R b1 is C 1-4 alkyl or is connected to R b2 to form a C ring containing 0 to 2 N and fused with the B ring, 상기 B2는 Rb2로 치환되거나 치환되지 않고,The above B 2 is substituted or not substituted with R b2 , 상기 Rb2는 Rb1과 연결되어 0개 내지 2개의 N을 포함하고 B 고리와 융합된 C 고리를 형성하고,The above R b2 is connected to R b1 to form a C ring containing 0 to 2 N and fused with the B ring, 상기 B4는 Rb4로 치환되거나 치환되지 않고,The above B 4 is substituted or not substituted with R b4 , 상기 Rb4는 C1-4 알킬 또는 할로겐이고,wherein R b4 is C 1-4 alkyl or halogen, 상기 B 고리와 C 고리의 융합 고리는 1 내지 4개의 N을 포함하는 2개환의 융합 고리로서, Rf로 치환되거나 치환되지 않고,The fused ring of the above B ring and C ring is a fused ring of two rings containing 1 to 4 N, which is substituted or unsubstituted with R f , 상기 Rf는 할로겐, C1-4 할로알킬 또는 C1-4 알콕시이다.wherein R f is halogen, C 1-4 haloalkyl or C 1-4 alkoxy. 제1항에 있어서, 상기 B 고리가 피롤릴, 피라졸릴, 이미다졸릴, 이속사졸릴 또는 트리아졸릴인 것을 특징으로 하는 화합물, 이의 수화물, 이의 용매화물 또는 이의 약학적으로 허용가능한 염.A compound, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof, characterized in that the B ring in claim 1 is pyrrolyl, pyrazolyl, imidazolyl, isoxazolyl, or triazolyl. 제1항에 있어서, 상기 R2가 H, 플루오로 또는 클로로인 것을 특징으로 하는 화합물, 이의 수화물, 이의 용매화물 또는 이의 약학적으로 허용가능한 염.A compound, a hydrate thereof, a solvate thereof or a pharmaceutically acceptable salt thereof, characterized in that R 2 is H, fluoro or chloro in the first paragraph. 제1항에 있어서, 상기 R4가 H, 메틸, 플루오로, 클로로, 다이플루오로메틸 또는 트리플루오로메틸인 것을 특징으로 하는 화합물, 이의 수화물, 이의 용매화물 또는 이의 약학적으로 허용가능한 염.A compound, a hydrate thereof, a solvate thereof or a pharmaceutically acceptable salt thereof, characterized in that R 4 is H, methyl, fluoro, chloro, difluoromethyl or trifluoromethyl in the first paragraph. 제1항에 있어서, 상기 R5가 에틸, 2-메틸-프로필-, 4-메틸-펜틸-, 2,4-다이메틸펜틸-, 사이클로프로필-메틸- 또는 사이클로부틸-메틸-인 것을 특징으로 하는 화합물, 이의 수화물, 이의 용매화물 또는 이의 약학적으로 허용가능한 염.A compound, a hydrate thereof, a solvate thereof or a pharmaceutically acceptable salt thereof, characterized in that in claim 1, R 5 is ethyl, 2-methyl-propyl-, 4-methyl-pentyl-, 2,4-dimethylpentyl-, cyclopropyl-methyl- or cyclobutyl-methyl-. 제1항에 있어서, 상기 R5 및 R6가 연결되어 형성하는 비방향족 헤테로사이클이 피페라지닐 또는 모폴리노인 것을 특징으로 하는 화합물, 이의 수화물, 이의 용매화물 또는 이의 약학적으로 허용가능한 염.A compound, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof, characterized in that the non-aromatic heterocycle formed by connecting R 5 and R 6 in claim 1 is piperazinyl or morpholino. 제1항에 있어서, 상기 R5a가 메틸, 아미노 또는 하이드록시인 것을 특징으로 하는 화합물, 이의 수화물, 이의 용매화물 또는 이의 약학적으로 허용가능한 염.A compound, a hydrate thereof, a solvate thereof or a pharmaceutically acceptable salt thereof, characterized in that R 5a is methyl, amino or hydroxy in the first paragraph. 제1항에 있어서, 상기 Rb1가 메틸인 것을 특징으로 하는 화합물, 이의 수화물, 이의 용매화물 또는 이의 약학적으로 허용가능한 염.A compound, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof, characterized in that R b1 is methyl in the first paragraph. 제1항에 있어서, 상기 B 고리와 C 고리의 융합 고리가 하기 화학식으로 구성되는 군으로부터 선택되는 어느 하나인 것을 특징으로 하는 화합물, 이의 수화물, 이의 용매화물 또는 이의 약학적으로 허용가능한 염:A compound, characterized in that the fused ring of the B ring and the C ring in the first paragraph is one selected from the group consisting of the following chemical formulas, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof: . . 제1항에 있어서, 상기 Rb4가 메틸 또는 플루오로인 것을 특징으로 하는 화합물, 이의 수화물, 이의 용매화물 또는 이의 약학적으로 허용가능한 염.A compound, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof, characterized in that R b4 is methyl or fluoro in the first paragraph. 제1항에 있어서, 상기 Rf가 플루오로, 클로로, 트리플루오로메틸 또는 메톡시인 것을 특징으로 하는 화합물, 이의 수화물, 이의 용매화물 또는 이의 약학적으로 허용가능한 염.A compound, a hydrate thereof, a solvate thereof or a pharmaceutically acceptable salt thereof, characterized in that R f is fluoro, chloro, trifluoromethyl or methoxy in the first paragraph. 제1항에 있어서, 상기 화학식 1로 표시되는 화합물이 하기 화합물로 구성된 군으로부터 선택되는 어느 하나인 것을 특징으로 하는 화합물, 이의 수화물, 이의 용매화물 또는 이의 약학적으로 허용가능한 염:In claim 1, a compound characterized in that the compound represented by the chemical formula 1 is any one selected from the group consisting of the following compounds, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof: [1] (S)-1-((6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[1] ( S )-1-((6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [2] (S)-1-((6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[2] (S)-1-((6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [3] (S)-1-((6-(1H-피롤로[3,2-c]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[3] ( S )-1-((6-(1 H -pyrrolo[3,2- c ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [4] (S)-1-((6-(1H-피롤로[2,3-c]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[4] ( S )-1-((6-(1 H -pyrrolo[2,3- c ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [5] (S)-1-((6-(7-플루오로이미다조[1,2-a]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[5] ( S )-1-((6-(7-fluoroimidazo[1,2- a ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [6] (S)-1-((6-(1H-피라졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[6] ( S )-1-((6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [7] (S)-1-((6-(1H-피롤-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[7] ( S )-1-((6-(1 H -pyrrol-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [8] (S)-1-((6-(2H-1,2,3-트리아졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[8] ( S )-1-((6-(2 H -1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [9] (S)-1-((6-(3,5-다이메틸-1H-피라졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[9] ( S )-1-(( 6 -( 3 , 5 -dimethyl-1 H -pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [10] (S)-1-((6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[10] ( S )-1-((6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [11] (S)-1-((6-(6-플루오로-1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[11] ( S )-1-((6-(6-fluoro-1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [12] (S)-1-((6-(6-클로로-1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[12] ( S )-1-((6-(6-chloro-1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [13] (S)-1-((2-(다이플루오로메틸)-6-(1H-피라졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[13] ( S )-1-((2-(difluoromethyl)-6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [14] (S)-1-((2-(다이플루오로메틸)-6-(이속사졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[14] ( S )-1-((2-(difluoromethyl)-6-(isoxazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [15] (S)-1-((2-(다이플루오로메틸)-6-(1H-이미다졸-1-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[15] ( S )-1-((2-(difluoromethyl)-6-(1 H -imidazol-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [16] (S)-1-((2-(다이플루오로메틸)-6-(3-플루오로-1H-피라졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[16] ( S )-1-((2-(difluoromethyl)-6-(3-fluoro-1 H -pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [17] (S)-1-((2-(다이플루오로메틸)-6-(1H-이미다졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[17] ( S )-1-((2-(difluoromethyl)-6-(1 H -imidazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [18] (S)-1-((2-(다이플루오로메틸)-6-(1H-피롤-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[18] ( S )-1-((2-(difluoromethyl)-6-(1 H -pyrrol-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [19] (S)-1-((2-(다이플루오로메틸)-6-(1H-피라졸-5-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[19] ( S )-1-((2-(difluoromethyl)-6-(1 H -pyrazol-5-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [20] (S)-1-((2-(다이플루오로메틸)-6-(2H-1,2,3-트리아졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[20] ( S )-1-((2-(difluoromethyl)-6-(2 H -1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [21] (S)-1-((2-(다이플루오로메틸)-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[21] ( S )-1-((2-(difluoromethyl)-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [22] (S)-1-(2-(다이플루오로메틸)-4-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)펜옥시)-2,4-다이메틸펜탄-2-아민,[22] ( S )-1-(2-(difluoromethyl)-4-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)phenoxy)-2,4-dimethylpentan-2-amine, [23] (S)-1-((2-(다이플루오로메틸)-6-(5-(트리플루오로메틸)-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[23] ( S )-1-((2-(difluoromethyl)-6-(5-(trifluoromethyl)-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [24] (S)-1-((2-(다이플루오로메틸)-6-(4-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[24] ( S )-1-((2-(difluoromethyl)-6-(4-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [25] ((S)-1-((2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[25] (( S )-1-((2-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [26] (S)-1-((6-(5-클로로-1H-피라졸로[3,4-b]피리딘-3-일)-2-(다이플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[26] ( S )-1-((6-(5-chloro-1 H -pyrazolo[3,4- b ]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [27] (S)-1-((2-(다이플루오로메틸)-6-(4-메톡시-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[27] ( S )-1-((2-(difluoromethyl)-6-(4-methoxy-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [28] (S)-1-((2-(다이플루오로메틸)-6-(6-플루오로-1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[28] ( S )-1-((2-(difluoromethyl)-6-(6-fluoro-1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [29] (S)-1-((2-(다이플루오로메틸)-6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[29] (S)-1-((2-(difluoromethyl)-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [30] (S)-1-((4-(다이플루오로메틸)-6-(1H-피라졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[30] ( S )-1-((4-(difluoromethyl)-6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [31] (S)-1-((4-(다이플루오로메틸)-6-(2H-1,2,3-트리아졸-4-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[31] ( S )-1-((4-(difluoromethyl)-6-(2 H -1,2,3-triazol-4-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [32] ((S)-1-((4-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[32] (( S )-1-((4-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [33] (S)-1-((5-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[33] ( S )-1-((5-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [34] (S)-1-((6-(1H-피라졸-4-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[34] ( S )-1-((6-(1 H -pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [35] (S)-1-((6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[35] ( S )-1-((6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [36] (S)-1-((5-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민,[36] ( S )-1-((5-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine, [37] (S)-1-((3-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민,[37] ( S )-1-((3-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine, [38] (S)-1-((4-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민,[38] ( S )-1-((4-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine, [39] (S)-1-((6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민,[39] ( S )-1-((6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine, [40] (S)-1-((4-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[40] ( S )-1-((4-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [41] (S)-1-((5-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[41] ( S )-1-((5-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [42] (S)-1-((3-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-4-일)옥시)-2,4-다이메틸펜탄-2-아민,[42] ( S )-1-((3-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine, [43] (S)-1-((2-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-4-일)옥시)-2,4-다이메틸펜탄-2-아민,[43] ( S )-1-((2-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-4-yl)oxy)-2,4-dimethylpentan-2-amine, [44] (S)-1-((2-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[44] ( S )-1-((2-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [45] 1-((2-(다이플루오로메틸)-6-(1H-피라졸-4-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민,[45] 1-((2-(difluoromethyl)-6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine, [46] 1-((2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민,[46] 1-((2-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine, [47] 1-((2-(다이플루오로메틸)-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민,[47] 1-((2-(difluoromethyl)-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine, [48] 1-((2-(다이플루오로메틸)-6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민,[48] 1-((2-(difluoromethyl)-6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine, [49] 1-((6-(1H-피라졸-4-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)-2-메틸프로판-2-아민,[49] 1-((6-(1 H -pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine, [50] 1-((6-(1H-피롤로[2,3-b]피리딘-3-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)-2-메틸프로판-2-아민,[50] 1-((6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)-2-methylpropan-2-amine, [51] 2-((6-(5-클로로-1H-피라졸로[3,4-b]피리딘-3-일)-2-(다이플루오로메틸)피리딘-3-일)옥시)에탄-1-올,[51] 2-((6-(5-chloro-1 H -pyrazolo[3,4- b ]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-ol, [52] 2-((6-(5-클로로-1H-피라졸로[3,4-b]피리딘-3-일)-2-(다이플루오로메틸)피리딘-3-일)옥시)에탄-1-아민,[52] 2-((6-(5-chloro-1 H -pyrazolo[3,4- b ]pyridin-3-yl)-2-(difluoromethyl)pyridin-3-yl)oxy)ethan-1-amine, [53] (S)-1-((4-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민,[53] ( S )-1-((4-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine, [54] (S)-1-((5-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)-2,4-다이메틸펜탄-2-아민,[54] ( S )-1-((5-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2,4-dimethylpentan-2-amine, [55] (S)-1-((5-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-2-일)옥시)-2,4-다이메틸펜탄-2-아민,[55] ( S )-1-((5-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-2-yl)oxy)-2,4-dimethylpentan-2-amine, [56] (S)-1-(4-(1H-피롤로[3,2-b]피리딘-1-일)펜옥시)-2,4-다이메틸펜탄-2-아민,[56] ( S )-1-(4-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)phenoxy)-2,4-dimethylpentan-2-amine, [57] (S)-1-((2-(다이플루오로메틸)-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[57] ( S )-1-((2-(difluoromethyl)-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [58] (S)-1-((2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[58] ( S )-1-((2-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [59] (S)-1-((2-(다이플루오로메틸)-6-(4-메톡시-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[59] ( S )-1-((2-(difluoromethyl)-6-(4-methoxy-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [60] (S)-1-((2-(다이플루오로메틸)-6-(1H-피라졸-4-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[60] ( S )-1-((2-(difluoromethyl)-6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [61] 1-((4-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민,[61] 1-((4-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine, [62] 1-((4-(다이플루오로메틸)-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민,[62] 1-((4-(difluoromethyl)-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine, [63] 1-((5-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민,[63] 1-((5-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine, [64] 1-((5-(다이플루오로메틸)-6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민,[64] 1-((5-(difluoromethyl)-6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine, [65] 1-(((2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[65] 1-(((2-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [66] 1-(((2-(다이플루오로메틸)-6-(1H-피라졸-4-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[66] 1-(((2-(difluoromethyl)-6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [67] 1-(((2-(다이플루오로메틸)-6-(2H-1,2,3-트리아졸-4-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[67] 1-(((2-(difluoromethyl)-6-(2 H -1,2,3-triazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [68] 1-(((2-(다이플루오로메틸)-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[68] 1-(((2-(difluoromethyl)-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [69] 1-(((2-(다이플루오로메틸)-6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[69] 1-(((2-(difluoromethyl)-6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [70] 1-(((6-(1H-피라졸-4-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[70] 1-(((6-(1 H -pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [71] 1-((5-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2-메틸프로판-2-아민,[71] 1-((5-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-amine, [72] 1-(((5-(다이플루오로메틸)-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[72] 1-(((5-(difluoromethyl)-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [73] 1-(((2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로부탄-1-아민,[73] 1-(((2-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine, [74] 1-(((2-(다이플루오로메틸)-6-(1H-피라졸-4-일)피리딘-3-일)옥시)메틸)사이클로부탄-1-아민,[74] 1-(((2-(difluoromethyl)-6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine, [75] 1-(((2-(다이플루오로메틸)-6-(2H-1,2,3-트리아졸-4-일)피리딘-3-일)옥시)메틸)사이클로부탄-1-아민,[75] 1-(((2-(difluoromethyl)-6-(2 H -1,2,3-triazol-4-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine, [76] 1-(((2-(다이플루오로메틸)-6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)메틸)사이클로부탄-1-아민,[76] 1-(((2-(difluoromethyl)-6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine, [77] 1-(((6-(1H-피라졸-4-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)메틸)사이클로부탄-1-아민,[77] 1-(((6-(1 H -pyrazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine, [78] 1-(((6-(2H-1,2,3-트리아졸-4-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)메틸)사이클로부탄-1-아민,[78] 1-(((6-(2 H -1,2,3-triazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine, [79] 1-((2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-2-메틸프로판-2-올,[79] 1-((2-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-2-methylpropan-2-ol, [80] 1-((2-(다이플루오로메틸)-6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)-2-메틸프로판-2-올,[80] 1-((2-(difluoromethyl)-6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-2-methylpropan-2-ol, [81] (S)-1-(4-(1H-피롤로[2,3-b]피리딘-3-일)펜옥시)-2,4-다이메틸펜탄-2-아민,[81] ( S )-1-(4-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)phenoxy)-2,4-dimethylpentan-2-amine, [82] (S)-1-((6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[82] ( S )-1-((6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [83] (S)-1-((6-(4-메톡시-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[83] ( S )-1-((6-(4-methoxy-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [84] (S)-1-((6-(1H-피라졸-4-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[84] ( S )-1-((6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [85] (S)-1-((6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[85] ( S )-1-((6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [86] (S)-1-((6-(4-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[86] ( S )-1-((6-(4-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [87] (S)-1-((6-(6-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[87] ( S )-1-((6-(6-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [88] (S)-1-((6-(6-플루오로-1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[88] ( S )-1-((6-(6-fluoro-1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [89] (S)-1-((6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[89] ( S )-1-((6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [90] (S)-1-((6-(1H-피롤로[2,3-c]피리딘-1-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[90] ( S )-1-((6-(1 H -pyrrolo[2,3- c ]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [91] (S)-1-((6-(1H-피롤로[2,3-b]피리딘-1-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[91] ( S )-1-((6-(1 H -pyrrolo[2,3- b ]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [92] (S)-1-((6-(1H-피롤로[3,2-c]피리딘-1-일)피리딘-3-일)옥시)-4-메틸펜탄-2-아민,[92] ( S )-1-((6-(1 H -pyrrolo[3,2- c ]pyridin-1-yl)pyridin-3-yl)oxy)-4-methylpentan-2-amine, [93] (S)-1-(4-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)펜옥시)-4-메틸펜탄-2-아민,[93] ( S )-1-(4-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)phenoxy)-4-methylpentan-2-amine, [94] (S)-1-(4-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)-2-(트리플루오로메틸)펜옥시)-4-메틸펜탄-2-아민,[94] ( S )-1-(4-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)-2-(trifluoromethyl)phenoxy)-4-methylpentan-2-amine, [95] 1-(((6-(2H-1,2,3-트리아졸-4-일)-2-(트리플루오로메틸)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[95] 1-(((6-(2 H -1,2,3-triazol-4-yl)-2-(trifluoromethyl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [96] 1-(((6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[96] 1-(((6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [97] 1-(((6-(1H-피라졸-4-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[97] 1-(((6-(1 H -pyrazol-4-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [98] 1-(((6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[98] 1-(((6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [99] 1-(((2-플루오로-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[99] 1-(((2-fluoro-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [100] 1-(((2-플루오로-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[100] 1-(((2-fluoro-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [101] 1-(((2-플루오로-6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[101] 1-(((2-fluoro-6-(1H-pyrrolo[3,2-b]pyridin-1-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [102] 1-(((4-플루오로-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[102] 1-(((4-fluoro-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [103] 1-(((4-플루오로-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[103] 1-(((4-fluoro-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [104] 1-(((5-플루오로-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[104] 1-(((5-fluoro-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [105] 1-(((5-플루오로-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로프로판-1-아민,[105] 1-(((5-fluoro-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclopropan-1-amine, [106] 1-(((6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)옥시)메틸)사이클로부탄-1-아민,[106] 1-(((6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)oxy)methyl)cyclobutan-1-amine, [107] 1-(2-(다이플루오로메틸)-4-(1H-피롤로[2,3-b]피리딘-3-일)펜옥시)-2-메틸프로판-2-아민,[107] 1-(2-(difluoromethyl)-4-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine, [108] N 1-(2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)-2-메틸프로판-1,2-다이아민,[108] N 1 -(2-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)-2-methylpropane-1,2-diamine, [109] N 1-(2-(다이플루오로메틸)-6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)-2-메틸프로판-1,2-다이아민,[109] N 1 -(2-(difluoromethyl)-6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)-2-methylpropane-1,2-diamine, [110] N 1-(6-(1H-피롤로[2,3-b]피리딘-3-일)-2-(트리플루오로메틸)피리딘-3-일)-2-메틸프로판-1,2-다이아민,[110] N 1 -(6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)-2-(trifluoromethyl)pyridin-3-yl)-2-methylpropane-1,2-diamine, [111] N 1-(2-(다이플루오로메틸)-4-(1H-피롤로[2,3-b]피리딘-3-일)페닐)-2-메틸프로판-1,2-다이아민,[111] N 1 -(2-(difluoromethyl)-4-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)phenyl)-2-methylpropane-1,2-diamine, [112] N-((1-아미노사이클로프로필)메틸)-2-(다이플루오로메틸)-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-아민,[112] N -((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-amine, [113] N-((1-아미노사이클로프로필)메틸)-2-(다이플루오로메틸)-6-(1H-피라졸-4-일)피리딘-3-아민,[113] N -((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1 H -pyrazol-4-yl)pyridin-3-amine, [114] N-((1-아미노사이클로프로필)메틸)-2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-아민,[114] N -((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-amine, [115] N-((1-아미노사이클로프로필)메틸)-2-(다이플루오로메틸)-6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-아민,[115] N -((1-aminocyclopropyl)methyl)-2-(difluoromethyl)-6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-amine, [116] N-((1-아미노사이클로프로필)메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-아민,[116] N -((1-aminocyclopropyl)methyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-amine, [117] N-((1-아미노사이클로프로필)메틸)-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-아민,[117] N -((1-aminocyclopropyl)methyl)-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-amine, [118] N-((1-아미노사이클로프로필)메틸)-4-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-아민,[118] N -((1-aminocyclopropyl)methyl)-4-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-amine, [119] N-((1-아미노사이클로프로필)메틸)-5-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-아민,[119] N -((1-aminocyclopropyl)methyl)-5-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-amine, [120] 1-((2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)아미노)-2-메틸프로판-2-올,[120] 1-((2-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)amino)-2-methylpropan-2-ol, [121] 1-((2-(다이플루오로메틸)-6-(1H-피롤로[3,2-b]피리딘-1-일)피리딘-3-일)아미노)-2-메틸프로판-2-올,[121] 1-((2-(difluoromethyl)-6-(1 H -pyrrolo[3,2- b ]pyridin-1-yl)pyridin-3-yl)amino)-2-methylpropan-2-ol, [122] 1-(2-클로로-4-(1H-피롤로[2,3-b]피리딘-3-일)펜옥시)-2-메틸프로판-2-아민,[122] 1-(2-chloro-4-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine, [123] 1-(2-플루오로-4-(1H-피롤로[2,3-b]피리딘-3-일)펜옥시)-2-메틸프로판-2-아민,[123] 1-(2-fluoro-4-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine, [124] 1-(2,5-다이클로로-4-(1H-피롤로[2,3-b]피리딘-3-일)펜옥시)-2-메틸프로판-2-아민,[124] 1-(2,5-dichloro-4-(1H-pyrrolo[2,3-b]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine, [125] 2-메틸-1-(2-메틸-4-(1H-피롤로[2,3-b]피리딘-3-일)펜옥시)프로판-2-아민,[125] 2-methyl-1-(2-methyl-4-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)phenoxy)propan-2-amine, [126] 1-(2,6-다이플루오로-4-(1H-피롤로[2,3-b]피리딘-3-일)펜옥시)-2-메틸프로판-2-아민,[126] 1-(2,6-difluoro-4-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine, [127] 1-(2,5-다이플루오로-4-(1H-피롤로[2,3-b]피리딘-3-일)펜옥시)-2-메틸프로판-2-아민,[127] 1-(2,5-difluoro-4-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)phenoxy)-2-methylpropan-2-amine, [128] 5-플루오로-3-(4-(피페라진-1-일)페닐)-1H-피롤로[2,3-b]피리딘,[128] 5-Fluoro-3-(4-(piperazin-1-yl)phenyl)-1 H -pyrrolo[2,3- b ]pyridine, [129] 5-플루오로-3-(4-(4-메틸피페라진-1-일)페닐)-1H-피롤로[2,3-b]피리딘,[129] 5-Fluoro-3-(4-(4-methylpiperazin-1-yl)phenyl)-1 H -pyrrolo[2,3- b ]pyridine, [130] 4-(4-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)페닐)모폴린,[130] 4-(4-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)phenyl)morpholine, [131] 5-플루오로-3-(5-(피페라진-1-일)피리딘-2-일)-1H-피롤로[2,3-b]피리딘,[131] 5-Fluoro-3-(5-(piperazin-1-yl)pyridin-2-yl)-1 H -pyrrolo[2,3- b ]pyridine, [132] 5-플루오로-3-(5-(4-메틸피페라진-1-일)피리딘-2-일)-1H-피롤로[2,3-b]피리딘,[132] 5-Fluoro-3-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)-1 H -pyrrolo[2,3- b ]pyridine, [133] 4-(6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)모폴린,[133] 4-(6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)morpholine, [134] 4-(2-(다이플루오로메틸)-6-(5-플루오로-1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)모폴린,[134] 4-(2-(difluoromethyl)-6-(5-fluoro-1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)morpholine, [135] 4-(2-(다이플루오로메틸)-6-(1H-피롤로[2,3-b]피리딘-3-일)피리딘-3-일)-2,2-다이메틸모폴린, 및[135] 4-(2-(difluoromethyl)-6-(1 H -pyrrolo[2,3- b ]pyridin-3-yl)pyridin-3-yl)-2,2-dimethylmorpholine, and [136] 3-(6-(다이플루오로메틸)-5-(3,3-다이메틸피페라진-1-일)피리딘-2-일)-1H-피롤로[2,3-b]피리딘.[136] 3-(6-(difluoromethyl)-5-(3,3-dimethylpiperazin-1-yl)pyridin-2-yl)-1 H -pyrrolo[2,3- b ]pyridine. 제1항 내지 제12항 중 어느 한 항의 헤테로아릴 유도체 화합물, 이의 수화물, 이의 용매화물 또는 이의 약학적으로 허용가능한 염을 유효성분으로 포함하는, AAK1 억제 관련 질환의 예방 또는 치료용 약학 조성물.A pharmaceutical composition for preventing or treating a disease related to AAK1 inhibition, comprising a heteroaryl derivative compound of any one of claims 1 to 12, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof as an active ingredient. 제13항에 있어서, 상기 AAK1 억제 관련 질환이 급성 통증, 만성 통증, 염증성 통증, 신경병증성 통증, 파킨슨병, 알츠하이머병, 조현병, 조울증, 근이영양증 및 바이러스 감염 질환인 것을 특징으로 하는 약학 조성물.A pharmaceutical composition according to claim 13, characterized in that the disease associated with AAK1 inhibition is acute pain, chronic pain, inflammatory pain, neuropathic pain, Parkinson's disease, Alzheimer's disease, schizophrenia, bipolar disorder, muscular dystrophy, and viral infection disease. 제1항 내지 제12항 중 어느 한 항의 헤테로아릴 유도체 화합물, 이의 수화물, 이의 용매화물 또는 이의 약학적으로 허용가능한 염과, 약제학적으로 허용가능한 첨가제를 포함하는 약학 조성물.A pharmaceutical composition comprising a heteroaryl derivative compound of any one of claims 1 to 12, a hydrate thereof, a solvate thereof, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable additive.
PCT/KR2025/005735 2024-04-29 2025-04-28 Novel heteroaryl derivatives and use thereof in inhibiting aak1 Pending WO2025230262A1 (en)

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