HK1169110B - Novel (6-oxo-1, 6-dihydro-pyrimidin-2-yl)-amide derivatives, preparation thereof, and pharmaceutical use thereof as akt phosphorylation inhibitors - Google Patents

Description

The present invention relates to new chemical compounds (6-oxo-1,6-dihydro-pyrimidine-2-yl) amide), derived from pyrimidinones, their preparation process, the new intermediates obtained, their application as medicinal products, the pharmaceutical compositions containing them and the new use of such derivatives.

The present invention thus also concerns the use of the said derivatives for the preparation of a medicinal product for human use.

In particular, the invention relates to novel pyrimidine derivatives and their pharmaceutical use for the prevention and treatment of diseases that can be modulated by inhibition of the PI3K/AKT/mTOR pathway. AKT is a key player in this signaling pathway. A high level of AKT phosphorylation is the marker of pathway activation that is found in many human cancers. The products of the present invention may be used for the prevention or treatment of conditions that can be modulated by inhibition of AKT phosphorylation (P-AKT), inhibition of P-AKT may be achieved by inhibition of the PI3K/AKT/mTOR pathway, and in particular by inhibition of kinases belonging to this pathway such as receptor tyrosine kinase activity such as EGFR, IGFR, ErbB2, 3'-phosphoinositide-dependent protein kinase-1 (PDK1), serine serine kinase PI3K, serine-threonine kinase, AKTOR kinase. In particular, the inhibition and regulation of the PI3K/AKT/mTOR pathway is a novel and powerful mechanism of action for the treatment of a large number of cancers including solid and liquid tumours, such as solid and liquid human tumours.

The role of the PI3K/AKT/mTOR pathway

The PI3K/AKT/mTOR signaling pathway is a complex network that regulates multiple cell functions, such as cell growth, survival, proliferation and motility, which are key processes in tumor genesis.

This signaling pathway is an important target in cancer treatment because most of its effectors are altered in human tumors. The main effectors contributing to the activation of the pathway are (i) oncogenes such as ErbB1 (EGFR), ErbB2 (HER2), PIK3CA and AKT that are activated by mutation, amplification or overexpression; (ii) deficiency of tumor suppressor genes such as PTEN, TSC1/2, LKB and PML that are inactivated by mutations or deletions (Jiang L-Z & Liu L-Z, Biochim Biophys Acta, 2008, 1784:150; Vivanco & I Sawyers, CL Cancer, 2002, 2:489 M; Cully et al., Nature Rev., 2006, 6:18; Rev. 1, 1984; Rev. 2, 2008);

Activation of oncogenes in this signaling pathway is found in many human cancers. The study also found that PIK3CA-activating mutations are present in 15-30% of cancers of the colon, breast, endometrium, liver, ovaries and prostate (TL Yuan and LC Cantley, Oncogene, 2008, 27:5497; Y. Samuels et al. Science, 2004, 304:554; KE Bachman et al. Cancer Biol Ther, 2004, 3:772; DA Levine et al. Clin Canc. 2005, 11:2875; C. Hartmann et al. Acta Neuropathol, 2005, 109:639).The use of the active substance in the food is not recommended for the treatment of patients with severe liver disease (see section 4.4). Deficiency of tumor suppressor genes of this signaling pathway is also found in many human cancers: o PTEN deletion in 50% of cancers of the lung (NSCLC), liver, kidney,The mutations of TSC1/2 in more than 50% of tuberous sclerosis patients (Maxwell GL et al. Canc. Res. 1998, 58:2500; Zhou X-P et al. Amer. J. Pathol., 2002, 161:439; Endersby R & Baker SJ, Oncogene, 2008, 27:5416; Li et al. Science, 1997, 275:1943; Steack PA et al., Nat. Genet., 1997, 15:356) o mutations or deletions of LKB1 (or STK11) which predispose to gastrointestinal tract and pancreatic cancers and which are particularly found in 10-38% of adenocarcinomas of the lung (Shah U.The results of the study were published in the Journal of Clinical Molecular Biology and the Journal of Molecular Biology and the Journal of Molecular Biology, and were published in the journal Physiology and Biology. In addition, this signaling pathway is a major factor in resistance to chemotherapy, radiation therapy and targeted therapies such as EGFR and HER2 inhibitors for example (C. Sawyers et al. Nat Rev 2002).

Role of AKT

AKT (protein kinase B; PKB) is a serine-threonine kinase that plays a central role in one of the major cell signaling pathways, the PI3K/AKT pathway. AKT is involved in tumor cell growth, proliferation and survival. AKT activation is in two steps (i) by phosphorylation of threonine 308 (P-T308) by PDK1 and (2) by phosphorylation of serine 473 (P-S473) by mTORC2 (or mTOR-Rictor complex), resulting in total activation. AKT in turn regulates a large number of target proteins mTORT (mammal of Rapamy), BAD, BAD, GSK23, pFOK1, pRL27, or FOX1 (MAMC, BD, Lanning & Cantley, PRL27, or PRL17, or BD).In particular, AKT controls the initiation of protein synthesis through a cascade of interactions that proceeds via TSC1/2 (tuberous sclerosis complex), Rheb, and TOR to result in two critical targets of the signaling pathway, p70S6K and 4EBP. AKT also induces inhibitory phosphorylation of the Forkhead transcription factor and inactivation of GSK3β which lead to inhibition of apoptosis and cell cycle progression (Franke Oncogene, 2008, TF 27:6473).AKT is therefore a target for anti-cancer therapy and inhibition of AKT activation by inhibition of its phosphorylation may induce apoptosis of malignant cells and thereby present a treatment for cancer.

Receptors with tyrosine kinase activity such as IGF1R

Abnormally high levels of protein kinase activity have been implicated in many diseases resulting from abnormal cell function. This may be either directly or indirectly due to a malfunction in the mechanisms controlling kinase activity, for example due to mutation, over-expression or inappropriate enzyme activation, or by over- or under-production of cytokines or growth factors, also involved in upstream or downstream transduction of signals from kinases. In all these cases, selective inhibition of kinase action is expected to be beneficial. Insulin-like growth factor receptor type 1 (IGF-I-R) is a transmembrane receptor with tyrosine kinase activity that binds primarily to IGFI but also to IGFII and insulin with a lower affinity.The IGF1 receptor binds to its receptor, leading to oligomerization of the receptor, activation of tyrosine kinase, intermolecular autophosphorylation and phosphorylation of cell substrates (main substrates: IRS1 and Shc). Several clinical reports highlight the important role of the IGF-I pathway in the development of human cancers: IGF-I-R is often found to be overexpressed in many tumor types (breast, colon, lung, sarcoma, prostate, multiple myeloma) and its presence is often associated with a more aggressive phenotype.- What? High levels of circulating IGF1 are strongly correlated with a risk of prostate, lung and breast cancer. In addition, IGF-I-R has been widely documented to be necessary for the establishment and maintenance of the transformed phenotype in vitro as well as in vivo [Baserga R, Exp. Cell. Res., 1999, 253, pp. 1-6]. IGF-I-R kinase activity is essential for the transformation activity of several oncogenes: EGFR, PDGFR, the large T antigen of SV40 virus, activated Ras, Raf, and v-Src. Expression of IGF-I-R in normal fibroblasts can then induce a neoplastic phenotype, which can lead to tumor formation in vivo.IGF-I-R has also been shown to be a protector in chemotherapy-induced apoptosis, radiation, and cytokine-induced apoptosis. In addition, inhibition of endogenous IGF-I-R by a negative dominant, triple helix formation, or antisense expression causes suppression of transforming activity in vitro and decreased tumor growth in animal models.

PDK1

3'-phosphoinositide-dependent protein kinase-1 (PDK1) is one of the essential components of the PI3K-AKT signaling pathway. It is a serine-threonine (Ser/Thr) kinase whose role is to phosphorylate and activate other Ser/Thr kinases of the AGC family involved in the control of cell growth, proliferation, survival and in the regulation of metabolism. These kinases include protein kinase B (PKB or AKT), SGK (serum and glucocorticoid regulated kinase), RSK (p90 ribosomal S6 kinase), p70S6K (p70 ribosomal S6 kinase) as well as various kinases of protein kinase C (PKC) (Vanha B., Alessi & J. B., J. J. & J.One of the key roles of PDK1 is therefore activation of AKT: in the presence of PIP3, the second messenger generated by PI3K, PDK-1 is recruited to the plasma membrane via its PH domain (plekstrin homology) and phosphorylates AKT on threonine 308 located in the activation loop, a key modification of AKT activation. PDK1 is ubiquitously expressed and is a constitutively active kinase. PDK1 is a key component in the PI3K/AKT signaling pathway for the regulation of key processes in tumor proliferation and cell survival.PDK1 is a target for anticancer therapy, and inhibition of PDK1 is expected to result in effective inhibition of cancer cell proliferation and survival and thus provide a therapeutic benefit for human cancers (Bayascas JR, Cell cycle, 2008, 7 :2978; Peifer C. & Alessi DR, ChemMedChem, 2008, 3 :1810).

The phosphoinositide-3 kinases (PI3Ks) are

The PI3K lipid kinase is an important target in this signaling pathway for oncology. Class I PI3Ks are divided into class la (PI3Kα,β,δ) activated by tyrosine kinase activity receptors (RTKs), G protein coupled receptors (GPCRs), Rho family GTPases, p21-Ras and class Ib (PI3Kγ) activated by GPCRs and by p21-Ras. Class Ia PI3Ks are heterodimers that consist of a catalytic p110α, β or δ subunit and a regulatory p85 or p55 subunit. Class (p110γ) is monomeric.These class I PI3Ks phosphorylate phosphatidylinositol 4,5 diphosphate (PIP2) at the 3 position of the inositol to give phosphatidylinositol 3,4,5 triphosphate (PIP3), a key secondary messenger of this signaling pathway. In turn, PIP3 recruits AKT and PDK1 to the membrane where they bind to their pleckstrin homologous domain (PH domain), leading to activation of AKT by phosphorylation of PDK1 on threonine 308.And this is the key to cell growth and survival and angiogenesis.

PI3Ks of class I are involved in human cancers: somatic mutations of the PI3Kα gene encoding PIK3CA are found in 15-35% of human tumors, including two major oncogenic mutations H1047R (in the kinase domain) and E545K/E542K (in the helical domain) (Y. Samuels et al. Science, 2004, 304:554; TL Yuan and LC Cantley, Oncogene, 2008, 27:5497). PI3K inhibitors are expected to be effective in the treatment of many human cancers with genetic alterations leading to activation of the PI3K/AKT/mTOR pathway (Vogt P. et al., Virology, 2006, 34431 & Zhao L; Vogt Oncogene, PK, 2008, 27:548).

Morpholino pyrimidinones kinase inhibitor derivatives are known to the art world.

Application WO2008/148074 describes products that have mTOR inhibitory activity, which are pyrido[1,2-a]pyrimidine-4-ones that differ from the products of the present invention by their entirely aromatic nature and substitutions.

Application WO2008/064244 describes the use of PI3Kβ inhibitors TGX-221 and TGX-155 useful in the treatment of cancer, including breast cancer, which are pyrido[1,2-a]pyrimidine-4-ones previously described in applications WO2004/016607 and WO2001/053266 and which differ from products of the present invention by their entirely aromatic nature and substitution.

Applications WO2006/109081, WO2006/109084 and WO2006/126010 describe DNA-PK inhibitors useful for the treatment of ATM-deficient cancers. These products are pyrido[1,2-a]pyrimidine-4-ones which differ from the products of the present invention by their entirely aromatic nature and substitution properties.

Application WO2003/024949 describes DNA-PK inhibitors useful for the treatment of ATM-deficient cancers. These products are pyrido[1,2-a]pyrimidine-4-ones which differ from the products of the present invention by their entirely aromatic nature and substitutions

Morpholino pyrimidine derivatives inhibiting kinases are also known to man.

Applications WO2009/007748, WO2009/007749, WO2009/007750 and WO2009/007751 describe products that have inhibitory activity of mTOR and/or PI3K for the treatment of cancer. The purpose of the present invention is to manufacture products of formula (I): - What? in which: R1 is an aryl or heteroaryl radical which may be replaced by one or more identical or different radicals selected from the halogen atoms and the hydroxyl, CN, nitro,-COOH, -COOalk, -NRxRy, -CONRxRy, -NRxCORy, -CORy, -NRxCO2Rz, alcohols, phenoxys, alkyl alcohols, alkyl alkyl, alkynyl, cycloalkyl, O-cycloalkyl, heterocycloalkyl; aryl and heteroaryl; the latter alcohols, phenoxys, alkyl alcohols, alkyl alcohols, alkyl alcohols, alkynyl alcohols, heterocycloalkyl alcohols, aryl alcohols and heteroalkyl alcohols, each possibly substituted by one or more identical or different radicals from among the total atoms of radiogens and hydroxyl alcohols; NRR, heterocycloalkyl alcohols; heterocycloalkyl alcohols; or heterocycloalkyl alcohols; or alternatively a mixture of these or a mixture of several other radioactive or radioactive elements, possibly a radioactive or a radioactive or a radioactive heterogeneous or a radioactive heterogeneous or aerosol; and/or alternatively a radioactive or heterogeneous or aerosol or a radioactive heterogeneous or aerosol, possibly a radioactive or a radioactive or aerosol or a radioactive aerosol, possibly a radioactive or aerosol or aerosol, possibly a radioactive or a radioactive or aerosol, possibly a radioactive or aerosol or aerosol, and/or a radioactive aerosol, or aerosol or aerosol, or aerosol or aerosol, and/or aerosol, or aerosol or aerosol or aerosol, and/or, or aerosol or aerosol or aerosol or aerosol or aerosol, and/or, and/or, or aerosol or aerosol or aerosol or aerosol or aerosol or aerosol or aerosol or aerosol or aerosol or aerosol or aerosol or aerosol or aerosol or aerosol or aerosol or aS, N, NH and Nalk, whereby this bicyclic radical may be substituted by one or more identical or different radicals chosen from among the halogen atoms and the CO-NH2, hydroxyl, alkyl and alkoxy radicals; whereas the latter alkyl radical may itself be substituted by a hydroxyl, alkoxy, NH2, NHAlk or Nalk radical; whereas R2, R3, which are identical or different, independently represent a hydrogen atom, a halogen atom or an alkyl radical which may be substituted by one or more halogen atoms; whereas R4 represents a hydrogen atom; R5 represents a hydrogen atom or an alkyl radical which may be substituted by one or more halogen atoms; whereas Rw represents a hydrogen atom or an alkyl radical which may be substituted by one or more NRw; whereas Rw represents a hydrogen atom or an alkyl radical which may be substituted by one or more halogen atoms;a cycloalkyl, CO2alk or an alkyl radical possibly substituted by one or more identical or different radicals chosen from the hydroxyl, alkoxy, NRvRw and heterocycloalkyl radicals; either Rx and Ry form with the nitrogen atom to which they are bound a cyclic radical containing 3 to 10 chains and possibly one or more other heteroatoms selected from O, S, NH and N-alkyl, this cyclic radical possibly substituted;NRvRw being such that Rv represents one hydrogen atom or an alkyl radical and Rw represents one hydrogen atom, one cyclic or alkyl radical possibly substituted by one or more identical or different hydroxyl radicals,alcohol, heterocycloalkyl; either Rv and Rw form with the nitrogen atom to which they are bound a cyclic radical containing 3 to 10 chains and possibly one or more other heteroatoms chosen from O, S, NH and N-alkyl, this cyclic radical being possibly substituted;the cyclic radicals which Rx and Ry or Rv and Rw respectively can form with the nitrogen atom to which they are bound, being possibly substituted by one or more identical or different radicals chosen from the halogen atoms; the alcohol alkyl, hydroxyl, oxo, oxy, NH2, NH2 and Nalk;Ry and Rz in the radicals -NRxCORy, -CORy and NRxCO2Rz being chosen from the meanings given above for Rx, Ry, and Rz;all the alkyl (alk), alkoxy and alkylthio radicals above being linear or branched and containing 1 to 6 carbon atoms,the said products of formula (I) being in all possible racemic, enantiomeric and diastomeric isomeric forms, and the addition salts with the mineral and organic acids or with the mineral and organic bases of said products of formula (I). The products of formula (I) according to the present invention are therefore as follows: R is H and R1 is an aryl or heteroaryl radical, possibly substituted, as defined above or below,R forms with R1 a saturated or partially or totally unsaturated 5- or 6-chain ring fused to an aryl or heteroaryl residue and possibly containing one or more other heteroatoms chosen from O, S, N, NH and Nalk, this bicyclic radical being possibly substituted as defined above or below, the substituents R2, R3, R4 and R5 of the above products of formula (I) having the definitions given above. the products of formula (I) are in all possible racemic, enantiomeric and diastereoisomeric isomeric forms, and the salts are added with the mineral and organic acids or with the mineral and organic bases of the products of formula (I).- What? The present invention thus relates to products of formula (I) as defined above in which: R1 is a phenyl, pyridine, thienyl, benzoxazolyl, benzofuryl, indazolyl, indoyl, benzothienyl, benzimidazolyl, benzoxazinyl, tetrahydroquinolyl radical, possibly substituted by one or more identical or different radicals selected from the halogen atoms and the CN, nitro, -COOH, -COOalk, -NRxRy, alcohol, alkyl, alkynyl and cycloalkyle radicals; the latter are alcohol, alkylyl and alkynyl radicals, possibly themselves substituted by one or more different or identical radicals from the hydrogen atoms and hydroxyl radicals, NRR, NRw; piperyl, -COOH, -COOalk, -NRxRy; and possibly a hydroxy, alkylyl and cycloalkyl radical; R1 is a hydroxy or hydroxy radical, possibly substituted by a hydroxy or more than one hydroxy; and R1 is a hydroxy or hydroxy radical, possibly a hydroxy or a hydroxy; and R1 is a hydroxy or hydroxy, possibly a hydroxy, and a hydroxy;dihydroindolyl, tetrahydroisoquinolyl, tetrahydroquinolyl, dihydropyrrolopyridyl, where these cycles may be replaced by one or more identical or different radicals chosen from among the halogen atoms and the CO-NH2, hydroxyl, alkyl and alkoxy radicals; where the latter alkyl radical may itself be replaced by a hydroxyl, alkoxy, NH2, NHAlk or N(alk) 2 ;R2, R3, identical or different, independently represent one hydrogen atom, one fluorine atom or one alkyl radical;R4 represents one hydrogen atom;R5 represents one hydrogen atom or one alkyl radical;RyxRyx represents one hydrogen atom or one alkyl radical and RyxRyx represents one or more hydrogen atoms and RyxRyx represents one or more alkyl atoms, and Ryx is a radical and Ryx is a ring of atoms;S, NH and N-alkyl, this cyclic radical being possibly substituted;NRvRw being such that Rv represents a hydrogen atom or an alkyl radical and Rw represents a hydrogen atom or an alkyl radical;all the alkyl (alk) and alkoxy radicals above being linear or branched and containing 1 to 6 carbon atoms,the said products of formula (I) being in all possible racemic, enantiomeric and diastereoisomeric isomeric forms,as well as the addition salts with the mineral and organic acids or with the mineral and organic bases of the said products of formula (I). The purpose of the present invention is to manufacture products of formula (I): - What? in which: R1 is an aryl or heteroaryl radical possibly substituted by one or more identical or different radicals selected from the halogen atoms and hydroxyl radicals,CN, nitro, -COOH, -COOalk, -NRxRy, -CONRxRy, -NRxCORy, -CORy, -NRxCO2Rz, alcohol, phenoxy, alkylthio, alkyl, alkenyl, alkynyl, cycloalkyl, O-cycloalkyl, heterocycloalkyl; aryl and heteroaryl; the latter radicals alcohol, phenoxy, -COOH, -NRxRy, -CONRxRy, -NRxCORy, -CORy, -NRxCO2Rz, alcohol, phenoxy, alkylthio, alkylthio, alkylthio and heteroaryl, each of which may be substituted by one or more identical or different radicals from the total hydrogen atoms and the heterogeneous hydroxyl radicals, NRRw and heteroxygen; or alternatively, a renin or a heterocyclohalyl or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy; or alternatively, a renin or a heteroxy or a heteroxy or a heteroxy or a heteroxy and possibly a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a and possibly a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroxy or a and possibly a heteroxy or a heteroxy or a heteroxy or a heteroxy or a heteroS, N, NH and Nalk, whereby this bicyclic radical is possibly substituted by one or more identical or different radicals chosen from among the halogen atoms and the hydroxyl, alkyl and alkoxy radicals;R2, R3, identical or different, independently represent one hydrogen atom, one halogen atom or one alkyl radical possibly substituted by one or more halogen atoms;R4 represents one hydrogen atom;R5 represents one hydrogen atom or one alkyl radical possibly substituted by one or more halogen atoms;NRxRy whereas Rx represents one hydrogen atom or one alkyl radical and Ry represents one hydrogen atom, one cyclic or possibly alkyl radical or one hydroxyl radical possibly substituted by several different hydroxyl radicals;alcohols, NRvRw and heterocycloalkyls; either Rx and Ry form with the nitrogen atom to which they are bound a cyclic radical containing 3 to 10 chains and possibly one or more other heteroatoms chosen from O, S, NH and N-alkyl, this cyclic radical being possibly substituted;NRvRw being such that Rv represents a hydrogen atom or an alkyl radical and Rw represents a hydrogen atom, a cycloalkyl radical or an alkyl radical possibly substituted by one or more identical or different shock radicals or chosen from among the hydroxy, S, NH and N-alkyl alcohols; or they are possibly bound to a radical or a heterogeneous radical and Rv and Rw are selected from among 3 to 10 other hydroxy, O and Rw;S, NH and N-alkyl, this cyclic radical being possibly substituted;the cyclic radicals which can form Rx and Ry or Rv and Rw respectively with the nitrogen atom to which they are bound, possibly being substituted by one or more identical or different radicals chosen from among the halogen atoms, the alkyl, hydroxyl, oxo, alcohol radical, NH2;alk and N ((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((((())))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))))Enantiomers and diastereoisomers, and salts of addition with mineral and organic acids or with mineral and organic bases of the said products of formula (I). In products of formula (I): the term alkyl radical (or alk) means linear and where appropriate branched radicals, methyl, ethyl, propyl, isopropyl, butyl, isobutyl, dry-butyl, tert-butyl, pentyl, isopentyl, hexyl, isohexyl and also heptyl, octyl, non-alkyl and decyl and their linear or branched isomers: the preference is given to alkyl radicals containing 1 to 6 carbon atoms and in particular to the alkyl radicals containing 1 to 4 carbon atoms in the above list; the term alcoholic radical means linear and where appropriate branched radicals,: the alkoxy radicals containing 1 to 4 carbon atoms from the above list are preferred; the term alkyl radical means the linear radicals and where applicable branched, methyl, ethyl, propyl, isopropyl, butyl, methyl, secondary or tertiary, pentyl or hexyl and their isomers of secondary or branched positions: the term alkyl radical means the 1 to 4 carbon atoms from the above list; the term chlorine atom is preferred;The term cycloalkyl radical refers to a saturated carbocyclic radical containing 3 to 10 carbon atoms and thus includes in particular the cyclopropyl, cyclobutyl, cyclopentyl and cyclohexyl radicals and in particular the cyclopropyl, cyclopentyl and cyclohexyl radicals; in the O-cycloalkyl radical, cycloalkyl is defined as above; the term heterocycloalkyl radical refers to a monocyclic or bicyclic carbocyclic radical, containing 3 to 10 interlaced rings of one or more different heteroatoms, or one or more identical atoms, such as morphine, morphine, or sulphonyl nitrate:The following are to be considered as radicals, where all of them may be substituted: thiomorpholinyl, homomorpholinyl, aziridyl, azetidyl, piperazinyl, piperidyl, homopiperazinyl, pyrrolidinyl, imidazolidinyl, pyrazolidinyl, tetrahydrofuryl, tetrahydrothynyl, tetrahydropyrran, oxodihydropyridinyl, or even oxetanyl; these radicals may include morpholinyl, thiomorpholinyl, homomorpholinyl, piperazinyl, piperidyl, homoperazinyl or even pyrrolidinyl, containing aryl and heterocyclic, which are different in nature or in different forms, respectively, carbocyclic and heterocyclic, or, where necessary, monocyclic or bicyclic, containing more than one or several different elements; or, where necessary, containing a single or a combination of the following: The term aryl radical thus refers to monocyclic or bicyclic radicals containing 6 to 12 chains, such as phenyl radicals,The following is a list of the most commonly used chemicals: naphthyl, biphenyl, indenyl, fluorenyl and anthracenyl, especially the phenyl and naphthyl radicals and even more particularly the phenyl radical. The term heteroarylic radical thus refers to monocyclic or bicyclic radicals containing 5 to 12 chains: monocyclic heteroarylic radicals such as thienyl radicals such as 2-thienyl and 3-thienyl, furyl such as 2-furyl, 3-furyl, pyrannyl, pyrrolyl, pyrrolinyl, pyrazolinyl, imidazolyl, pyrazolyl, pyridyl such as 2-pyridyl, 3-pyridyl and 4-pyridyl, pyrazinyl, pyrimidinyl, pyridyl, oxazolyl, thiazolyl, isothiazol, diazolyl, thiadiazol, thiatriazol, oxadiazol, isoxazol, 4-xazol such as 3-isozol, orwhereas all these radicals may be substituted for free tetrazolyl, free tetrazolyl or salicylated radicals, all of which may be substituted for such radicals as thienyl radicals such as 2-thienyl and 3-thienyl, thiazolyl, furyl such as 2-furyl, pyrrolyl, pyrrolinyl, pyrazolinyl, imidazolyl, pyrazolyl, oxazolyl, isoxazolyl, pyridyl, pyridazinyl, all of which may be substituted for bicyclic heterocyclic radicals such as for example the benzopropothiel radicals (benzoprophen) such as 3-benzopropotylen, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediopropyl, tediol, tediopropyl, tediol, tediol, tediol, tediol, tediol, tediol, tediol, tediol, tediol, tediol, tediol, tediol, tediol, tediol, tediol, t As examples of heteroarytic or bicyclic radicals,In particular, pyrimidinyl, pyridyl, pyrrolyl, azaindolyl, indazolyl or pyrazolyl, benzothiazolyl or benzimidazolyl radicals may be substituted with one or more of the same or different substituents as indicated above. The carboxy radical (s) of formula (I) products may be salified or esterified by the various groups known to the professional, including, for example: among the salivation compounds, mineral bases such as, for example, an equivalent of sodium, potassium, lithium, calcium, magnesium or ammonium or organic bases such as, for example, methyllamine, propylamine, trimethyllamine,ethylene, triethylene, N,N-dimethylethanolamine, tris (hydroxy-methyl) amino methane, ethanolamine, pyridine, picoline, dicyclohexylamine, morpholine, benzylamine, procaine, lysine, arginine, histidine, N-methylglucamine, amongst the esterification compounds, alkyl radicals to form hydroxy carbonyl groups such as, for example, methoxycarbonyl, ethoxycarbonyl, tert-butoxycarbonyl or benzyloxycarbonyl, these alkyl groups can be substituted by radioactive compounds such as athoxy or diethylamine, diethylamine, methyl, acyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl, methyl

Addition salts with mineral or organic acids of formula (I) products may be, for example, salts formed with hydrochloric, bromic, iodic, nitric, sulphuric, phosphoric, propionic, acetic, trifluoroacetic, formic, benzoic, maleic, fumaric, succinic, tartaric, citric, oxalic, glyoxylic, aspartic, ascorbic acids, alcohol monosulfonic acids such as arythresulfonic acid, ethersulfonic acid, propulsed acid, acidsulfonic acids such as methacetic acid, alpha-beta-acids, acidsulfonic acids such as methacetic acid, acidsulfonic acids such as methacetic acid and acylsulfonic acids.

It may be recalled that stereoisomerism can be defined in its broad sense as the isomerism of compounds having the same developed formulas, but whose different groups are arranged differently in space, such as in monosubstituted cyclohexanes whose substituent may be in the axial or equatorial position, and the different possible rotational conformations of ethane derivatives.- What? The present invention relates to products of formula (I) as defined above in which: R1 is a phenyl, pyridine, thienyl, benzoxazole-4-yl and indazole-6-yl radical, possibly substituted by one or more identical or different radicals chosen from the halogen atoms and the radicals CN, nitro, -COOH, -COOalk, -NRxRy, alcohol, alkyl, alkynyl and cycloalkyl; the latter radicals are alcohol, alkyl and alkynyl, possibly themselves substituted by one or more identical or different radicals chosen from the halogen atoms and the alcohols are halogen, hydroxy NRvRw and phenyl and heteroxy radicals, possibly further substituted by one or more alkynyl and cyclohydrogen; R1 is a hydrogen or hydrogen atom with a ring shape;4-benzoxazine-4-yl or 2,3-dihydro-indol-1-yl, where these cycles may be replaced by one or more identical or different radicals chosen from the halogen atoms and the hydroxyl, alkyl and alkoxy radicals;R2, R3, identical or different, independently represent a hydrogen atom, a fluorine atom or an alkyl radical;R4 represents a hydrogen atom;R5 represents a hydrogen atom or an alkyl radical;NRxRy such that Rx represents a hydrogen atom or an alkyl radical and represents a hydrogen atom or an alkyl radical;Ry is any heterogeneous and forms with the nitrogen atom they are linked to a cyclically ringed radical and possibly to a number of other R10 and 3 O atoms,S, NH and N-alkyl, this cyclic radical being possibly substituted;NRvRw being such that Rv represents a hydrogen atom or an alkyl radical and Rw represents a hydrogen atom or an alkyl radical;all the alkyl (alk) and alkoxy radicals above being linear or branched and containing 1 to 6 carbon atoms,the said products of formula (I) being in all possible racemic, enantiomeric and diastereoisomeric isomeric forms,as well as the addition salts with the mineral and organic acids or with the mineral and organic bases of the said products of formula (I). In particular, when NRxRy or NRvRw forms a cycle as defined above,such an amino cycle may be chosen from amongst, inter alia, the pyrrolidinyl, pyrazolidinyl, pyrazolinyl, piperidyl, azepinyl, morpholinyl, homomorpholinyl, piperazinyl or homopiperazinyl radicals, which may themselves be substituted as indicated above or below. The NRxRy or NRvRw cycle may be chosen from among the pyrrolidinyl radicals, morpholinyl possibly substituted by one or two alkyl radicals or piperazinyl possibly substituted on the second nitrogen atom by an alkyl, phenyl, or CH2-phenyl radical, which may themselves be substituted by one or more identical or different radicals chosen from the halogen atoms and the alkyl, hydroxyl and alcohol radicals. The invention is particularly concerned with products of formula (I) as defined above which meet the following formulae: The following substances are to be classified in the same category as the active substance:2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl and salts of addition with mineral and organic acids or with mineral and organic bases of the said products of formula (I). The invention is particularly concerned with products of formula (I) as defined above which meet the following formulae: 2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl and salts of addition with mineral and organic acids or with mineral and organic bases of the said products of formula (I). The present invention also covers any process for the preparation of formula (I) products as defined above.

The products of the invention can be prepared using conventional organic chemistry methods.

Preparation of compounds of formula (I)

The products of general formula (I) according to the present invention may be prepared as shown in General Schemes 1A-1C below, and as such the methods described cannot constitute a limitation of the scope of the invention as regards the methods of preparation of the claimed compounds.

The preparations of the examples of the present invention illustrate the diagrams below.

Such synthesis schemes are part of the present invention: the present invention thus also covers the processes for preparing products of formula C to (I) d as defined in General Schemes 1A to 1C below. - What?

In the General Scheme 1A: Amino ketene B can be obtained from the amino ether A or its commercial amino acrylate tautomer by reaction with morpholine in a solvent such as ethanol at a temperature between 0 °C and the boiling point of the solvent, according to the process described by Landwehr J. et al. in J. Med. Chem. 2006, 49, 4327-4332.

The C ester can be obtained by reaction of aminal cetene B with the amino-ether A, or its amino-acrylate tautomer, in a solvent such as ethanol, at a temperature between 20°C and the boiling point of the solvent.

Alternatively, ester C can be obtained by reaction one-pot between morpholine and an excess (e.g. 3 equivalents) of amino-ether A (or its amino-acrylate tautomer), in a solvent such as ethanol, at a temperature between 20°C and the boiling point of the solvent.

Carboxylate D can be obtained by hydrolysis of ester C in the presence of a base such as soda or lithine in a solvent such as tetrahydrofuran or methanol at a temperature of 0 to 30 °C

(I) -a amides can be obtained from carboxylate D by condensation of an amine R1-NH2 in the presence of a peptide coupling agent such as, for example, EDCI (ethyl dimethylaminopropyl carbodiimide), DMT-MM [4-(4,6-dimethyloxy-1,2,3-triazin-2-yl) 4-methylmorpholinium chloride], BOP [benzotriazol-1-yl tri-dimethylamino phosphonium hexafluorophosphate], PyBOP [benzotriazol-1-yl dimethylamino phosphate], PyBROP [benzotriazol-1-yl tri-dimethylamino pyramid tetramethyl], or in a mixture of water or phosphorus such as methylamine, in the form of a mixture of methylamine and dimethylamine, such as methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methylamine, methy

(I) -a amides can also be obtained from ester C by reaction of an amine R1-NH2 in the presence of an agent such as trimethyl aluminium or potassium tertiobutylate in a solvent such as toluene, tetrahydrofuran or N,N-dimethylformamide at a temperature between 20°C and 150°C, as for example under the conditions described by Perreux L. et al. in Tetrahedron 2003 (59) 2185-2189 and by Auzeloux, P. et al. in J. Med. Chem. 2000,43 (2), 190-197. - What? In the General Scheme 1B: E esters can be obtained from ester C by reaction with a compound R5-X (X=Cl, Br, I or triphlate), in the presence of a base such as soda, potassium tertiobutylate or caesium carbonate, in a solvent such as methanol, ethanol or dioxane, at a temperature between 0°C and 50°C, depending for example on the process described by Noël D. D'Angelo et al. in J. Med. Chem. 2008, 51, 5766-5779.

Carboxylates F can be obtained by hydrolysis of E esters in the presence of a base such as soda or lithine in a solvent such as tetrahydrofuran or methanol at a temperature of 0 to 30 °C

(I) -b amides can be obtained from carboxylates F by condensation of an amine R1-NH2 in the presence of a peptide coupling agent such as, for example, EDCI (ethyl dimethylaminopropyl carbodiimide), DMT-MM [4-(4,6-dimethyloxy-1,2,3-triazin-2-yl) 4-methylmorpholinium chloride], BOP [benzotriazol-1-yl-hexafluorophosphate tris-dimethylamino phosphonium], PyBOP [benzotriazol-1-yl-hexafluorophosphate tris-pyrrolidine Tetramethonium], PyROP [benzotriazol-1-yl-bromide trioxide trioxide], or phosphorotrifluorophosphate [benzotriazol-1-yl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-

Amides (I) -b can also be obtained from esters E by reaction of an amine R1-NH2 in the presence of an agent such as trimethyl aluminium in a solvent such as toluene at a temperature between 20°C and the boiling point of the solvent, as for example under the conditions described by Auzeloux, P et al. in J. Med. Chem. 2000,43 (2), 190-197. - What? In the General Scheme 1C: The ester G can be obtained from the ester C by reaction with (Boc) 2O (tertiobutyl dicarbonate), in a solvent such as N,N-dimethylformamide, dioxane, acetonitrile or dichloromethane, in the presence of a base such as sodium hydride, triethylamine, N,N-diisopropylethylamine or pyridine, at a temperature between 0°C and 60°C, for example according to the process described by Hioki K. and Coll. Synthesis 2006, 12, 1931-1933

H products can be obtained from ester G by reaction with R2-X and then possibly with R3-X (X = Cl, Br, I or OTf and R2 and R3 are alkyl groups), in the presence of a base such as soda, potassium tertiobutylate or caesium carbonate, in a solvent such as methanol, ethanol or dioxane, at a temperature between 0 °C and 100 °C, for example according to the process described by Noël D. D'Angelo et al. in J. Med. Chem. 2008, 51, 5766-5779.

The product H where R2 = R3 = F can be obtained by reaction of product G with N-fluorobenzenesulfonimide in the presence of a base such as the potassium salt of hexamethyl disyllazanes in a solvent such as tetrahydrofuran at a temperature of -78°C to 20°C, using, for example, the process described by Christopher S. Burgey et al. in J. Med. Chem. 2003, 46, 461-473.

J esters where R2 and R3 are alkyl radicals can be obtained from ester C in the same way as H products, in the presence of a base such as butyllithium, sodium hydride, potassium tertiobutylate or caesium carbonate in a solvent such as methanol, ethanol, tetrahydrofuran, N,N-dimethylformamide or dioxane, at a temperature between 0°C and 50°C.

(I) -c amides can be obtained from H or J esters by reaction of an amine R1-NH2 in the presence of an agent such as trimethyl aluminium in a solvent such as toluene at a temperature between 20°C and the boiling point of the solvent, as for example under the conditions described by Auzeloux, P et al. in J. Med. Chem. 2000,43 (2), 190-197.

Amides (I) -d can be obtained from amides (I) -c by reaction with a compound R5-X (X=Cl, Br, I or triphlate), in the presence of a base such as soda, potassium tertiobutylate or cesium carbonate, in a solvent such as methanol, ethanol or dioxane, at a temperature between 0 °C and 50 °C, for example by the process described by Noel D'Angelo et al. in J. Med. Chem. 2008, 51, 5766-5779.

Alternatively, (I) -d amides can be obtained from K esters by reaction of an amine R1-NH2 in the presence of an agent such as trimethyl aluminium in a solvent such as toluene at a temperature between 20°C and the boiling point of the solvent, as for example under the conditions described by Auzeloux, P et al. in J. Med. Chem. 2000,43 (2), 190-197.

K esters can be obtained from J esters by reaction with a compound R5-X (X=Cl, Br, I or triphlate), in the presence of a base such as soda, potassium tertiobutylate or caesium carbonate, in a solvent such as methanol, ethanol or dioxane, at a temperature between 0°C and 50°C, depending for example on the process described by Noël D. D'Angelo et al. in J. Med. Chem. 2008, 51, 5766-5779.

Some of the products of formula A or B are known and can be obtained either commercially or by the usual methods known to the professional, for example from commercial products. It is understood by the professional that, for the implementation of the processes of the invention described above, it may be necessary to introduce protective groups of amino, carboxyl and alcohol functions in order to avoid side reactions. The following non-exhaustive list of examples of reactive function protection may be cited: hydroxyl groups may be protected by e.g. alkyl radicals such as tert-butyl, trimethylsilyl, tert-butyldimethylsilyl, methoxymethyl, tetrahydropyranyl, benzyl or acetyl,amino groups may be protected by e.g. acetyl, trityl, benzyl, tert-butoxycarbonyl, BOC, benzyloxycarbonyl, phthalimido or other radicals known in peptide chemistry, Acid functions can be protected, for example, as esters formed with easily cleasable esters such as benzyl esters or butyl ter esters or esters known in peptide chemistry. A list of the various protective groups which can be used can be found in the handbooks known to the professional and for example in patent BF 2 499 995.

It may be noted that intermediate products or products of formula (I) thus obtained by the above processes may, if desired and if necessary, be subjected to one or more reactions of transformation known to the professional, for example: (a) an esterification reaction of acid function, (b) a saponification reaction of ester function of acid function, (c) a reduction reaction of the free carboxy function or esterified function of alcohol function, (d) a transformation reaction of alcohol function into hydroxyl function, or of hydroxyl function into alcohol function,(e) a reaction to remove protective groups which may be carried by the protected reactive functions; (f) a reaction to salivate with a mineral or organic acid or base to obtain the corresponding salt; (g) a reaction to split racemic forms into split products; The products of formula (I) thus obtained are in all possible racemic, enantiomeric and diasteroisomeric isomeric forms. Reactions a) to g) can be carried out under normal conditions known to the professional, such as those shown below. (a) The products described above may, if desired, be subjected to esterification reactions on the carboxy functions, if any, which can be carried out by the usual methods known to the professional.(b) Any transformation of ester functions into acid functions of the products described above may, if desired, be carried out under the usual conditions known to the professional, in particular by acid or alkaline hydrolysis, e.g. by soda or potash in an alcoholic medium such as, for example, in methanol or by hydrochloric or sulphuric acid. The saponification reaction may be carried out by the usual methods known to the professional, such as in a solvent such as methanol or ethanol, dioxane or dimethoxyethane, in the presence of sodium or potassium.(c) Any free or esterified carboxy functions of the products described above may, if desired, be reduced to alcohol by methods known to the tradesman: any esterified carboxy functions may, if desired, be reduced to alcohol by methods known to the tradesman and in particular by lithium and aluminium hydride in a solvent such as tetrahydrofuran or dioxane or ethyl ether. The possible free carboxy functions of the products described above may, if desired, be reduced to alcohol function, in particular by boron hydride.(e) The removal of protective groups such as those described above may be carried out under the usual conditions known to the professional, in particular by acid hydrolysis with an acid such as hydrochloric acid, sulphonic benzene or para-sulphonic para-toluene, formic or trifluoroacetic acid or by catalysis.- What? The phthalimide group can be removed by hydrazine. (f) The products described above may, if desired, be subjected to salicylation reactions e.g. by a mineral or organic acid or by a mineral or organic base according to the usual methods known to the trade: such a salicylation reaction may be carried out e.g. in the presence of hydrochloric acid, e.g. or tartaric acid, citric acid or methane sulphate, in an alcohol such as ethanol or methanol. (g) The optically active forms of the products described above may be prepared by double-dipping racemics according to the usual methods known to the trade.- What? The formula (I) products as defined above and their salts of addition with acids have interesting pharmacological properties, in particular due to their kinase inhibitory properties as indicated above. The products of the present invention are particularly useful in the treatment of tumours.

The products of the invention may also thus enhance the therapeutic effects of commonly used anti-tumor agents.

These properties justify their therapeutic application and the invention is particularly intended as a medicinal product, the products of formula (I) as defined above, the said products of formula (I) being in all possible racemic, enantiomeric and diastereoisomeric isomeric forms, and the addition salts with the mineral and organic acids or with the pharmaceutically acceptable mineral and organic bases of said products of formula (I).

The invention relates in particular to products which meet the following formulae as medicinal products: 2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl and salts of addition with the mineral and organic acids or with the pharmaceutically acceptable mineral and organic bases of these products of formula (I).

The invention also relates to pharmaceutical formulations containing as an active ingredient at least one of the products of formula (I) as defined above or a pharmaceutically acceptable salt of that product and, if applicable, a pharmaceutically acceptable medium.

The invention thus extends to pharmaceutical compositions containing as active ingredient at least one of the medicinal products as defined above.

Such pharmaceutical formulations of the present invention may also contain, if necessary, active ingredients of other antimyototic drugs such as taxol, cisplatin, DNA intercalators and others.

These pharmaceutical formulations may be administered orally, parenterally or topically as a topical application to the skin and mucous membranes or as an intravenous or intramuscular injection.

These compounds may be solid or liquid and may take all forms of medicinal products commonly used in human medicine, such as simple or dried tablets, pills, tablets, capsules, drops, granules, injections, ointments, creams or gels, and may be prepared by the usual methods. The active substance may be incorporated into excipients commonly used in these pharmaceutical compounds, such as talc, gum arabic, lactose, starch, magnesium stearate, cocoa butter, carrier bodies or not, animal or vegetable fats, paraffinic residues, glycols, various dispersants or dispersions, preservatives, etc.

The usual dose, which varies according to the product used, the subject treated and the condition, may be, for example, 0.05 to 5 g per day in adults, or preferably 0.1 to 2 g per day.

Such a medicinal product may be intended for the treatment or prevention of a disease in a mammal.

The use of a formula (I) product as defined above for the preparation of a medicinal product for the prevention or treatment of diseases associated with uncontrolled proliferation is also described.

The present invention is thus particularly intended for use in the preparation of a product of formula (I) as defined above for the treatment or prevention of oncological diseases and, in particular, for the treatment of cancers.

These cancers include solid and liquid tumours, and cytotoxically resistant cancers. Products of the present invention may be used for the treatment of primary and/or metastatic tumours, particularly in gastric, liver, kidney, ovarian, colon, prostate, endometrial, lung (NSCLC and SCLC), glioblastoma, thyroid, bladder, breast, lymphoma, lymphopoetic or myeloid metastases, sarcomas, brain, larynx, cancer of the bone system, and pancreatic, hamartoma.

The present invention also concerns the use of formula (I) products as defined above for the preparation of drugs for cancer chemotherapy. The present invention thus relates to formula (I) products as defined above for use in the treatment of cancer. The present invention is intended for use with formula (I) products as defined above for the treatment of solid or liquid tumours. The present invention therefore concerns formula (I) products as defined above for use in the treatment of cytotoxically resistant cancers.- What? The present invention therefore covers formula (I) products as defined above for use in the treatment of primary and/or metastatic tumors, particularly in gastric, hepatic, renal, ovarian, colon, prostate, endometrial, lung cancers (NSCLC and SCLC), glioblastomas, thyroid, bladder, breast cancers, melanoma, lymphoid or myeloid haematopoietic tumors, sarcomas, cancers of the brain, larynx, lymphatic system, bone and pancreas, and hamartomas. The present invention therefore concerns formula (I) products as defined above for use in cancer chemotherapy.- What? Such drugs for cancer chemotherapy may be used alone or in combination. The present invention therefore covers formula (I) products as defined above for use in cancer chemotherapy, alone or in combination.

The products covered by this application may be administered alone or in combination with chemotherapy or radiotherapy or, for example, in combination with other therapeutic agents.

Such therapeutic agents may be commonly used antitumor agents.

The present invention also covers as new industrial products the intermediates for the synthesis of formulae C, D, E and F as defined above and referred to below: where R5 has the definition given in any of claims 1 to 2.

The following examples, which are products of formula (I), illustrate the invention without limiting it.

The experimental part

The classification of the compounds of the present invention has been carried out with ACDLABS version 10.0.

The microwave oven used is a Biotage device, InitiatorTM 2.0, 400W max, 2450 MHz.

The NMR spectra of 1H at 400 MHz and 1H at 500 MHz were performed on BRUKER AVANCE DRX-400 or BRUKER AVANCE DPX-500 spectrometer with chemical displacements (δ in ppm) in the dimethylsulfoxide-d6 (DMSO-d6) solvent referenced at 2.5 ppm at 303K.

The mass spectra (SM) were obtained by either method A or method B:

Method A:

WATERS UPLC-SQD apparatus; Ionisation: electrospray in positive and / or negative mode (ES+/-); Chromatographic conditions: Column: ACQUITY BEH C18 1.7 μm - 2.1 x 50 mm; Solvents: A: H2O (0.1% formic acid) B: CH3CN (0.1% formic acid) Column temperature: 50 °C; Flow rate: 1 ml/min Gradient (2 min) : 5 to 50%; B in 0.8 min 1.2 min: 100 % of B; 1.85 min: 100 % of B; 1.95 : 5 % of B Retention time = Tr (min).

Method B:

WATERS ZQ apparatus ; Ionisation : electrospray in positive and / or negative mode (ES+/-) ; Chromatographic conditions: Column : XBridge C18 2.5 μm - 3 x 50 mm ; Solvents : A: H2O (0.1 % formic acid) B: CH3CN (0.1 % formic acid) ; Column temperature: 70 ° C ; Rate of flow: 0.9 ml / min ; Gradient (7 min) : from 5 to 100% of B in 5.3 min ; 5.5 min ; 100 % of B: 6.3 min 5 % of B ; Retention time = Tr (min).

The following is a list of the active substances in the active substance: Step one:

To a 25 g solution of morpholine in 400 mL of ethanol heated to 95 °C, add 168.5 mL of ethyl 3-ethyoxy-3-iminopropanoate hydrochloride, then 155 mL of N,N-diisopropylethilamine in 200 mL of ethanol. The reaction mixture is heated to 95 °C for 30 hours and then allowed to return to room temperature. The precipitate formed is filtered on a glass sintered pan and then washed with 100 mL of ethanol, 2 times 500 mL of water and 500 mL of ethyl ether. Finally, the solid is emptied to give 35 g of [4-dioxyl-morphyl-4-dioxy-hydropolin-2-hydropyrimidine] acetate in the form of white solids, the characteristics of which are as follows: The frequency range of the spectrum is as follows: 1.19 (t, J=7.1 Hz, 3 H); 3.38 to 3.44 (m, 4 H); 3.56 (s, 2 H); 3.61 (dd, J=4.0 and 5.7 Hz, 4 H); 4.12 (q, J=7.1 Hz, 2 H); 5.20 (s, 1 H); 11.69 (s wide, 1 H) Mass spectrometry: method ATemps of retention Tr (min) = 0.48; [M+H]+ ; m/z 268 [M-H]-: m/z 266

Step two:

To a 10 g solution of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]ethyl acetate prepared in step 1 of example 1 in 300 mL of tetrahydrofuran, 18.7 mL of 2M sodium is added. The reaction mixture is agitated for 48 hours at room temperature. The precipitate formed is filtered on fritted glass, washed with ethyl acetate and rinsed several times with ethyl ether. The resulting solid is then dried in the rotary evaporator to give 8.7 g of [4-morpholin-4-phyl) -6-oxo-1,6-dihydropyrimidine-2-acetyr]ethyl sodium in the form of a white solid with the following characteristics: The maximum value of the measurement is the value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured

Step two:

A 2 g solution of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]ethyl acetate prepared in step 1 of example 1 in 75 mL of methanol is added to 7.5 mL of water and 197 mg of lithium hydroxide. After 48 hours of stirring at room temperature the reaction mixture is concentrated under reduced pressure. 50 mL of water is added. The aqueous phase is then washed with lyophilized ethyl acetate. 1.73 g of [4- ((morpholin-4-() -6-oxo-1,6-dihydropyrimidine-2-yl]ethyl lithium acetate is obtained in the form of a white solid, with similar characteristics to the product in step 2.

Step three:

To a 200 mg solution of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl) sodium acetate prepared in step 2 of example 1 in 3 mL of N,N-dimethylformamide, add 370 mg of benzotriazol-1-yloxytris ((dimethylamino) phosphonium hexafluorophosphate, 113 mg of 1-hydroxybenzotriazole and 0.140 mL of aniline. The reaction mixture is agitated at room temperature for 3 hours, then under reduced pressure. Water and ethyl acetate are added and agitated for 30 minutes. The solidified solid is filtered and rotated in the separator. After purification by chromatography of white colorant, the following characteristics are obtained: 2- (dihydroxybenzotriazole-1-yl) -1-dimethyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl- The spectrum of the NMR 1 H :3,38 to 3,44 (m, 4 H); 3,56 to 3,63 (m, 6 H); 5,20 (s, 1 H); 7,06 (t, J=7,8 Hz, 1 H); 7,31 (t, J=8,6 Hz, 2 H); 7,56 (d, J=8,6 Hz, 2 H); 10,14 (s, 1 H); 11,64 (s wide, 1 H) :Mass spectrometry method ATemps of retention Tr (min) = 0.55; [M+H]+ ; m/z 315 [M-H-]: m/z 313

The following is a list of the active substances in the active substance:

The product is prepared in the manner described in step 3 of example 1 from 300 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl] sodium acetate prepared in step 2 of example 1, 595 mg of benzotriazol-1-yloxytris dimethylamino) phosphonium hexafluorophosphate, 182 mg of 1-hydroxybenzotriazole and 0.235 mL of 4-fluoroaniline in place of aniline. 110 mg of N- ((4- ((morpholin-4-oxo-1,6-dihydropyrimidine-2-yl) -acetamide is obtained as a white solid with the following characteristics: The maximum value of the measurement is the value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured value of the measured

The following is the list of active substances in the active substance:

The product is prepared by following the procedure described in step 3 of example 1 from 300 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]lithium acetate obtained in step 2' of example 1 and 0.235 mL of 3-chlororoaniline instead of aniline. After purification by silica chromatography, the emulsifier : dichloromethane/methanol/acetonite 90/5/5 is obtained from 71 mg of N- (((3-chlorophephnyl) [2-4- ((morpholin-4-yl) -6-o-1,6-dihydropyrimidine-2-yl]acetamide with the following characteristics: The following is a list of the most commonly used methods for the determination of the frequency of the emission of light emitting particles:

The following is the list of active substances in the active substance:

To a 250 mg solution of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl) sodium acetate prepared in step 2 of example 1 in 4 mL N,N-dimethylformamide add 0.160 mL of pyridine, 240 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride and 400 mg of N,N-dimethyl-m-phenylenediamine. Stir at room temperature for 1 night, then concentrate the reaction mixture under reduced pressure. Add water and acetone steam and repeat this process for 30 minutes. The mixture is precipitated, filtered in a distillator and distilled in a thiophenol etheric solution, then obtained by a solid chromatograph using dichloromethane 95/05, and then washed in a distilled liquid.The solid is filtered and dried to obtain 30 mg of N-[3- ((dimethylamino) phenyle]-2-[4- ((morpholin-4-yl)-6-oxo-1 ,6-dihydropyrimidine-2-yl]acetamide in the form of a yellow solid with the following characteristics: The spectrum of the NMR 1 H is 2.86 (s, 6 H); 3.41 (t, J=5.0 Hz, 4 H); 3.57 (s, 2 H); 3.60 (t, J=4.9 Hz, 4 H); 5.19 (s, 1 H); 6.44 (d, J=9.3 Hz, 1 H); 6.86 (d, J=7.8 Hz, 1 H); 7.01 (s, 1 H); 7.09 (t, J=8.3 Hz, 1 H); 9.98 (s wide, 1 H); 11.61 (s wide, 1 H) Mass spectrometry: method BT Retention time Tr (min) =0.

The following is a list of the active substances in the active substance:

To a 260 mg solution of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl) sodium acetate prepared in step 2 of example 1 in 2 mL of N,N-dimethylformamide, 2.5 mL of pyridine, 233 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide chloride and 400 mg of 2,4-difluoroaniline are added. The reaction mixture is agitated at room temperature for 16 hours, then in reduced pressure. Water and ethyl acetate are added and agitated for 30 minutes. The solid is pre-filtered, rosinated in water, ether and petroleum. The following properties of on-2-dimethyl-methyl-methyl-methyl-fluoride are obtained: The spectrum of the NMR 1 H :3,43 (t, J=5,0 Hz, 4 H); 3,61 (t, J=5,0 Hz, 4 H); 3,66(s, 2 H); 5,20 (s, 1 H); 7,01 to 7,13 (m, 1 H); 7,25 to 7,40 (m, 1 H); 7,83 (q, J=7,1 Hz, 1 H); 9,97 (s wide, 1 H); 11,67 (s wide, 1 H) Mass spectrometry method: BT Retention time (min) = 0,59; [M+H]+: m/z 351 ; [M-H]-: m/z 349

The following is a list of the active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 260 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium and 400 mg of 3,4-difluoroaniline instead of 2,4-difluoroaniline. 210 mg of N- ((3,4-difluorophenyl) -2-[4-(morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetamide is obtained as a white solid with the following characteristics: The frequency range of the measurement is as follows: 1.H (400 MHz): 3.41 (t, J=4.9 Hz, 4 H); 3.54 to 3.64 (m, 6 H); 5.20 (s, 1 H); 7.27 (d, J=8.8 Hz,1 H); 7.39 (dt, J=9.0 and 10.6 Hz, 1 H); 7.64 to 7.79 (m, 1 H); 10.38 (s, 1 H); 11.66 (s wide, 1 H) Mass spectrometry: method ATTemps of retention Tr (min) = 0.64; [M+H]+: m/z 351 ; [M-H-]: m/z 349

The following is the list of active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 250 mg of [4-morpholin-4-yl]-6-oxo-1,6-dihydropyrimidine-2-yl] sodium acetate and 400 mg of 3-aminothiophene hydrochloride instead of 2,4-difluoroaniline. 252 mg of 2-[4-morpholin-4-yl)-6-oxo-1,6-dihydropyrimidine-2-yl]-N-(thiophene-3-yl) acetamide is obtained as a beige solid with the following characteristics: The maximum value of the measurement is the value of the measurement of the mass of the sample, which is the mass of the sample.

The following is the list of active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 250 mg of [4-morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl] sodium acetate and 520 mg of 4-fluoro-3-methoxyaniline instead of 2,4-difluoroaniline. 262 mg of N-(4-fluoro-3-methoxyphenyl) -2-[4-morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetamide is obtained as a white solid with the following characteristics: The frequency range of the measurement is as follows: 1.H (400MHz) : 3.41 (t, J=4.9 Hz, 4 H); 3.56 to 3.62 (m, 6 H); 3.79 (s, 3H); 5.20 (s, 1 H); 7.02 to 7.09 (m, 1 H); 7.10 to 7.17 (m, 1 H); 7.47 (dd, J=2.4 and 8.1 Hz, 1 H); 10.20 (s, 1 H); 11.64 (s wide, 1 H) Mass spectrometry: method ATemps of retention Tr (min) = 0.60; [M+H]+: m/z 363 ; [M-H]: m/z 361

The following is the list of active substances in the active substance:

In a microwave tube, 300 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl) ethyl acetate prepared in step 1 of sample 1 is introduced into 1 mL of N,N-dimethylformamide, 623 mg of 2-fluoroaniline and 378 mg of potassium tert-butylate. Then 2 mL of N,N-dimethylformamide is added. The tube is then microwaved to 150 °C for 20 minutes. The reaction mixture is concentrated under reduced pressure. 30 mL of water and 10 mL of ethephal acetate are added and stirred to 1 H30.6-dihydropyrimidin-2-yl]acetamide in the form of a white solid having the following characteristics: The spectrum of the NMR 1 H :3,42 (t, J=4,9 Hz, 4 H); 3,61 (t, J=4,6 Hz, 4 H); 3,67 (s, 2 H); 5,19 (s, 1 H); 7,12 to 7,20 (m, 2 H); 7,21 to 7,32 (m, 1 H); 7,81 to 7,98 (m, J=8,3 and 8,3 Hz, 1 H); 10,00 (s wide, 1 H); 11,66 (s wide, 1 H) Mass spectrometry: method AT Retention time (min) = 0.

The following is the list of active substances in the active substance:

The product is prepared following the procedure described in Example 9 from 300 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]ethyl acetate prepared in Step 1 of Example 1 and 582 mg of 2-methylaniline instead of 2-fluoroaniline. 76 mg of N- ((2-methylphenyl) -2-[4-(morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetamide is obtained as a white solid with the following characteristics: The spectrum of the NMR is given by the following equations: 1. H, 2.21 (s, 3 H); 3.43 (t, J=5.0 Hz, 4 H); 3.55 to 3.67 (m, 6 H); 5.18 (s, 1 H); 7.08 (t, J=7.8 Hz, 1 H); 7.16 (t, J=7.8 Hz, 1 H); 7.21 (d, J=7.8 Hz, 1 H); 7.42 (d, J=7.8 Hz, 1 H); 9.65 (s wide, 1 H); 11.70 (s, 1 H) Mass spectrometry: method BT Retention Tremps (min) = 2.81; [M+H]+: m/z 329 ; [M-H]- m/z 327 melting point (Kofler) 194°C:

The following is the list of active substances in the active substance:

The product is prepared as described in Example 9 from 300 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]ethyl acetate prepared in Step 1 of Example 1 in 2 mL of N,N-dimethylformamide, 637 mg of 2-methoxyaniline instead of 2-fluoroaniline and 300 mg of tert-butylate of potassium. 3 mL of N,N-dimethylformamide is added and the tube is microwaved at 150°C for 20 minutes. The reaction mixture is concentrated under reduced pressure. 15 mL of water and 5 mL of L-acetate are added and agitated for 2 hours. The phase is extracted with 5 mL of L-acetate of L-acetate.The combined organic phases are dried on magnesium sulphate, filtered and concentrated under reduced pressure. After purification of the solid obtained on a preparation plate (thickness: 2 mm), elevating by a mixture of dichloromethane and methanol (90/10 vol) produces 7 mg of N- ((2-methoxyphenyle)-2-[4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetamide in the form of a pink solid with the following characteristics: The frequency range of the EMF is 1 H :3,43 (t, J=4,9 Hz, 4 H); 3,59 to 3,65 (m, 4 H); 3,69 (s, 2 H); 3,83 (s, 3 H); 5,20 (s, 1 H); 6,90 (ddd, J=2,2 and 6,5 and 8,2 Hz, 1 H); 6,99 to 7,13 (m,2 H); 7,The method of mass spectrometry is as follows:

The following is the list of active substances in the active substance:

The product is prepared following the procedure described in Example 9 from 300 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]ethyl acetate prepared in Step 1 of Example 1 and 840 mg of 2,3-difluoroaniline instead of 2-fluoroaniline. 83 mg of N- ((2,3-difluorophenyl) -2-[4-(morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-inyl]acetamide is obtained as a white solid with the following characteristics: The spectrum of the NMR is given by the following equations:

The following is the list of active substances in the active substance:

The product is prepared following the procedure described in Example 9 from 300 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]ethyl acetate prepared in Step 1 of Example 1 and 780 mg of 3,5-difluoroaniline instead of 2-fluoroaniline. 133 mg of N- ((3,5-difluorophenyl) -2-[4-(morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-inyl]acetamide is obtained as a white solid with the following characteristics: The spectrum of the NMR 1 H :3,41 (t, J=4,9 Hz, 4 H); 3,56 to 3,65 (m, 6 H); 5,20 (s, 1 H); 6,92 (t, J=9,3 Hz, 1 H); 7,28 (dd, J=2,2 and 9,5 Hz, 2 H); 10,55 (s wide, 1 H); 11,66(s wide, 1 H) Mass spectrometry: method Retention time Tr (min) = 0.66; [M+H]+ : m/z 351 ; [M-H]- m/z 349 Melting point (Kofler) > 260°C

The following is the list of active substances in the active substance:

The product is prepared following the procedure described in Example 9 from 250 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]ethyl acetate prepared in Step 1 of Example 1 and 0.90 mL of 3-fluoroaniline instead of 2-fluoroaniline. 160 mg of N- ((3-fluorophenyl) -2-[4-(morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetamide is obtained as a white solid with the following characteristics: The frequency range of the spectrum is from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz, from 1 Hz to 1 Hz, from 1 Hz to 1 Hz, from 1 Hz, from 1 Hz to 1 Hz, from 1 Hz, from 1 Hz to 1 Hz, from 1 Hz, from 1 Hz to 1 Hz, from 1 Hz, from 1 Hz to 1 Hz, from 1 Hz, from 1 Hz to 1 Hz, from 1 Hz, from 1 Hz, from 1 Hz to 1 Hz, from 1 Hz, from 1 Hz, from 1 Hz to 1 Hz, from 1 Hz, from 1 Hz, from 1 Hz to 1 Hz, from 1 Hz, from 1 to 1 Hz, from 1 Hz, from 1 Hz, from 1 Hz, from 1 to 1 Hz, from 1 Hz, from 1 Hz, from 1 to 1 Hz, from 0 to 1 Hz, from 0 to 1 Hz

The following is the list of active substances in the active substance:

The product is prepared following the procedure described in Example 9 from 250 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]ethyl acetate prepared in Step 1 of Example 1 and 1.193 g of 4-chloroaniline instead of 2-fluoroaniline. 140 mg of N- ((4-chlorophenyl) -2-[4-(morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetamide is obtained as a white solid with the following characteristics: The spectrum of the NMR 1 H :3,37 to 3,46 (m, J=4,9 Hz, 4 H); 3,51 to 3,66 (m, 6 H); 5,21 (s, 1 H); 7,38 (d, J=8,8 Hz, 2 H); 7,60 (d, J=8,8 Hz, 2 H); 10,34 (s wide, 1 H); 11,71 (s wide, 1 H) Mass spectrometry: method Retention time Tr (min) = 0,68; [M+H]+: m/z 349 ; [M-H]- m/z 347

The following table shows the results of the analysis of the chemical composition of the product:

The product is prepared following the procedure described in Example 9 from 300 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]ethyl acetate prepared in Step 1 of Example 1 and 1.254 mL of 3-methoxyaniline instead of 2-fluoroaniline. 56 mg of N- ((3-methoxyphenyl) -2-[4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetamide is obtained as a white solid with the following characteristics: The spectrum of the NMR 1 H :3,41 (t, J=5,0 Hz, 4 H); 3,55 to 3,63 (m, 6 H); 3,72 (s, 3 H); 5,20 (s, 1 H); 6,64 (dd, J=2,4 and 8,1 Hz, 1 H); 7,08 (ddd, J=0,9 and 1,0 and 8,1 Hz, 1 H); 7,21 (t, J=8,3 Hz,1 H); 7,27 (s, 1 H); 10,14 (s wide, 1 H); 11,63 (s wide, 1 H) Mass spectrometry: method ATemps of retention (min) = 0,58; [M+H] +: m/z 345 ; [M-H]- m/z 343

The following is the list of active substances in the active substance:

The product is prepared following the procedure described in Example 9 from 300 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]ethyl acetate prepared in Step 1 of Example 1 and 0.705 mL of 3- ((trifluoromethyl) aniline instead of 2-fluoroaniline. 228 mg of 2-[4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]-N-[3- ((trifluoromethyl) phenyl) acetamide is obtained as a white solid with the following characteristics: The spectrum of the NMR 1 H is 3,37 to 3,46 (m, 4 H); 3,54 to 3,66 (m, 6 H); 5,21 (width, 1 H); 7,42 (d, J=8,1 Hz, 1 H); 7,57 (t, J=8,1 Hz, 1 H); 7,75 (d, J=8,3 Hz, 1 H); 8,05 (s wide, 1 H); 10,50 (s wide, 1 H); 11,67 (s wide, 1 H) Mass spectrometry: method ATemps of retention Tr (min) = 3.39; [M+H]+: m/z 383 ; [M-H]-: m/z 381

The following is the list of active substances in the active substance:

The product is prepared following the procedure described in Example 9 from 300 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]ethyl acetate prepared in Step 1 of Example 1 in and 0.61 mL of 3-bromoaniline instead of 2-fluoroaniline. 105 mg of N- ((3-bromophenyl) -2-[4-(morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetamide is obtained as a white solid with the following characteristics: The frequency range of the spectrum is as follows: 1.H (400MHz): 3.37 to 3.46 (m, 4H); 3.54 to 3.66 (m, 6H); 5.20 (width, 1H); 7.15 to 7.34 (m, 2H); 7.47 (d, J=8.1 Hz, 1H); 7.91 (s width, 1H); 10.33 (s width, 1H); 11.66 (width, 1H): Mass spectrometry method ATemps of retention Tr (min) = 0.70; [M+H]+: m/z 395 ; [M-H]-: m/z 393

The following is the list of active substances in the active substance:

To a 261 mg solution of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl] sodium acetate prepared in step 2 of example 1 in 10 mL of methanol, 224 mg of 3- ((tert-butyl) aniline is added. The reaction mixture is stirred at room temperature for 5 minutes and then 442 mg of 4- ((4,6-dimethoxy-1,3,5-triazin-2-yl) -4-methylmorpholin-4-ium hydrate chloride is added. It is stirred for 30 minutes at room temperature. The concentrated reaction is then reduced to steam. The residue of onamide is then re-vaporized by 10 mL of water and 10 mL of acetyl-L-ethyl acetate. The following is a list of the most commonly used methods for the determination of the frequency of the emission of light emitting particles:

The following table shows the results of the analysis of the chemical composition of the product:

The product is prepared as described in Example 19 from 653 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium prepared in Step 2 of Example 1 and 567 mg of 3-aminobenzoate of methyl instead of 3-(tert-butyl) aniline. 400 mg of 3- (( (([4-morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetyl}amino) methylbenzoate is obtained as a white solid with the following characteristics: The spectrum of the NMR 1 H :3,41 (dd, J=4,8 and 5,3 Hz, 4 H); 3,53 to 3,68 (m, 6 H); 3,85 (s wide, 3 H); 5,21 (s wide, 1 H); 7,47 (t, J=8,1 Hz, 1 H); 7,66 (d, J=8,1 Hz, 1 H); 7,80 (d, J=8,3 Hz, 1 H); 8,24 (s, 1 H); 10,00 to 10,64 (m, 1 H); 11,67 (s wide, 1 H) Mass spectrometry: method ATemps of retention (min) = 0.59; [M+H] +: m/z 373 ; [M-H]- m/z 371 Purity: 95 %

The following is the list of active substances in the active substance:

The evaporation residue is then removed in 50 mL of water. The aqueous phase is extracted to acidified ethyl acetate (pH=6) by addition of a solution of hydrochloric acid 1 N. The precipitate formed is then filtered under vacuum in the solid form with 20 mL of water, 5 mL of ethyl acetate and 20 mL of ether. The characteristics of the white ether are: 3-methyl ether and 3-methyl ether-acetate (PH=6) and 3-methyl ether-acetate (PH-6). The frequency range of the spectrum is as follows: 1.H (400 MHz): 3.42 (t, J=4.9 Hz, 4 H); 3.52 to 3.72 (m, 6 H); 5.21 (s, 1H); 7.43 (t, J=7.9 Hz, 1 H); 7.64 (d, J=7.8 Hz, 1 H); 7.79 (ddd, J=1.5 and 1.6 and 8.2 Hz, 1 H); 8.19 (s, 1 H); 10.36 (s, 1 H); 11.77 (s wide, 1 H); 12.94 (s wide, 1 H) Mass spectrometry: method ATemps of retention Tr (min) = 0.46; [M+H]+: m/z 359 [M-H- ]: m/z 357

The following is the list of active substances in the active substance:

The product is prepared as described in Example 19 from 653 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium prepared in Step 2 of Example 1 using a mixture of 10 mL of water and 2 mL of tetrahydrofuran instead of methanol and 270 mg of isopropylaniline instead of 3- ((tert-butyl) aniline. 235 mg of 2- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]-N-[3-propan-2-yl) phenylacetamide is obtained as a white solid with the following characteristics: The following is a list of the most commonly used types of radiation therapy:

The following is the list of active substances in the active substance:

The product is prepared following the procedure described in Example 19 from 261 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium prepared in Step 2 of Example 1 using a mixture of 1 mL of water and 9 mL of ethanol instead of methanol and 214 mg of 3-methyl-aniline instead of 3-(tert-butyl) aniline. 196 mg of N- ((3-methylphenyl) -2-[4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetamide is obtained in the form of a white solid with the following characteristics: The following is a list of the most commonly used methods for the determination of the frequency of the emission of light emitting particles:

The following is the list of active substances in the active substance:

The product is prepared as described in Example 19 from 261 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium prepared in Step 2 of Example 1 and 163 mg of 5-amino-2-fluorobenzonitrile instead of 3- ((tert-butyl) aniline. The reaction mixture is concentrated dry under reduced pressure and the residue is purified by silica column chromatography by electrolysis with a gradient of electrolyte CH2Cl2/MeOH: 90/10 in dichloromethane of 0% to 100%. 81 mg of N- (((anocy-4-fluorobenzonitrile) -2-[4- ((tert-butyl-1,6-dihydropyrimidine-2-oxo-2-ambremide) is obtained in the solid form with the following characteristics: The spectrum of the NMR 1 H :3,34 to 3,47 (m, 4 H); 3,53 to 3,67 (m, 6 H); 5,21 (s, 1 H); 7,51 (t, J=9,2 Hz, 1 H); 7,73 to 7,89 (m, 1 H); 8,07 ((dd, J=2,8 and 5,7 Hz, 1 H); 10,53 (s, 1 H); 11,68 (s wide, 1 H) :Mass spectrometry method Retention time Tr (min) = 0,60; [M+H]+ : m/z 358 ; [M-H- ]: m/z 356Purity: 95 %

The following table shows the results of the analysis of the chemical composition of the product:

The product is prepared as described in Example 19 from 261 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl] sodium acetate prepared in Step 2 of Example 1 and 280 mg of 1-Boc-6-amino-indazole instead of 3- ((tert-butyl) aniline. The reaction mixture is concentrated at reduced pressure and taken up into 13 mL of 1,4-dioxane and 3 mL of hydrochloric acid 1 N, microwaved for 10 minutes at 100°C. After cooling at room temperature, the reaction mixture is concentrated at reduced pressure and taken up into 30 mL of water and a saturated sodium bicarbonate solution is added to obtain a pH close to 8.The precipitate formed is filtered and washed with water, ethyl acetate and ethyl ether. After silica chromatography purification by elevating with a gradient of the elevant CH2Cl2/MeOH: 70/30 in dichloromethane from 0% to 100%, 20 mg of N-(1H-indazol-6-yl)-2-[(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide is obtained as a white solid with the following characteristics: The following are the parameters to be taken into account for the calculation of the frequency range:The method of mass spectrometry is as follows:

The following is the list of active substances in the active substance:

The product is prepared as described in Example 19 from 261 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium prepared in Step 2 of Example 1 using a mixture of 6 mL of water and 1 mL of ethyl acetate instead of methanol and 118 mg of 3-aminobenzonitrile instead of 3-(tert-butyl) aniline. 120 mg of N-3-cyanopyrimidine-2-yl) [4- ((morpholin-4-oxo-1,6-dihydropyrimidine-2-yl) acetamide is obtained as a broken white solid with the following characteristics: The spectrum of the NMR 1 H :3,41 (t, J=4,8 Hz, 4 H); 3,60 (dd, J=4,8 and 5,3 Hz, 4 H); 3,63 (s, 2 H); 5,21 (s, 1 H); 7,49 to 7,59 (m, 2 H); 7,78 (dt, J=2,3 and 6,8 Hz, 1 H); 8,04 (s, 1 H); 10,51 (s wide, 1 H); 11,69 (s wide, 1 H) Mass spectrometry: method ATemps of retention Tr (min) = 0,55; [M+H]+: m/z 340 ; [M-H]-: m/z 338

The following is the list of active substances in the active substance:

The product is prepared following the procedure described in Example 19 from 261 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium prepared in Step 2 of Example 1 using a mixture of 7 mL of water and 1.5 mL of tetrahydrofuran instead of methanol and 134 mg of 2-amino-5-fluoropyridine instead of 3-(tert-butyl) aniline. After 1 H30 of stirring at room temperature, a precipitate is obtained. The reaction mixture is filtered onto broken solid glass. The solvent is washed with water, ethylene acetate and white ether. The following characteristics of onty-methyl-2-hydroxy-1-methyl-2-oxy-2-oxy-2-oxy-2-oxy-1-oxy-1-oxy-2-oxy-2-oxy-2-oxy-1-oxy-2-oxy-methyl are: The spectrum of the NMR 1 H :3,36 to 3,46 (m, 4 H); 3,60 (t, J=5,0 Hz, 4 H); 3,67 (s, 2 H); 5,20 (s, 1 H); 7,75 (td, J=2,7 and 6,1 Hz, 1 H); 8,07 (dd, J=9,4 and 4 Hz, 1 H); 8,33 (d, J=2,7 Hz, 1 H); 10,80 (s, 1 H); 11,66 (s wide, 1 H) Mass spectrometry: method AT Retention time (min) = 2,67; [M+H]+: m/z 334 ; [M-H]- m/z 332

The following is the list of active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 250 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetate sodium and 240 mg of 4-fluoro-3-methylaniline instead of 2,4-difluoroaniline. 204 mg of N- ((4-fluoro-3-methylphenyle) -2-[4-(morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetamide is obtained as a white solid with the following characteristics: The following is a list of the most commonly used methods for the determination of the mass spectrometry:

The following is the list of active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 250 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetate sodium and 278 mg of 3-chloro-4-fluoroaniline instead of 2,4-difluoroaniline. 218 mg of N- ((3-chloro-4-fluorophenyl) -2-[4-(morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetamide is obtained as a white solid with the following characteristics: The following is a list of the most commonly used methods for the determination of the concentration of a substance in a sample:

The following is the list of active substances in the active substance:

The product is prepared following the procedure described in Example 5 from 250 mg of [4-morpholin-4-yl]-6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium and 427 mg of 3-aminopyridine instead of 2,4-difluoroaniline. 168 mg of 2-[4-morpholin-4-yl)-6-oxo-1,6-dihydropyrimidine-2-yl]-N-(pyridin-3-yl) acetamide is obtained as a white solid with the following characteristics: The spectrum of the NMR 1 H is 3,39 to 3,46 (m, 4 H); 3,56 to 3,66 (m, 6 H); 5,20 (width, 1 H); 7,35 (s width, 1 H); 8,00 (d, J=8,6 Hz, 1 H); 8,28 (s width, 1 H); 8,71 (s width, 1 H); 10,37 (width, 1 H); 11,67 (s width, 1 H) Mass spectrometry method: AT Retention time Tr (min) =0,25; [M+H]+: m/z 316 ; [M-H]-: m/z 314

The following is the list of active substances in the active substance:

The product is prepared following the procedure described in Example 5 from 200 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium prepared in Step 2 of Example 1 and 278 mg of 4-fluoro-2-methylaniline instead of 2,4-difluoroaniline. 92 mg of N- ((4-fluoro-2-methylphenyl) -2) [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetamide is obtained as a pink solid with the following characteristics: The spectrum of the NMR is 1 H :2,21 (s, 3 H); 3,44 (t, J=4,9 Hz, 4 H); 3,57 to 3,66 (m, 6 H); 5,19 (s, 1 H); 6,99 (td, J=3,2 and 8,6 Hz, 1 H); 7,08 (dd, J=3,1 and 9,7 Hz, 1 H); 7,36 (dd, J=5,6 and 8,6 Hz,1 H); 9,56 (s wide, 1 H); 11,67 (s wide, 1 H) Mass spectrometry: method AT Temps of retention Tr (min) = 0,59; [M+H]+: m/z 347 ; [M-H]-: m/z 345

The following is the list of active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 250 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetate sodium and 418 mg of 3-aminophenol instead of 2,4-difluoroaniline. 210 mg of N- ((3-hydroxyphenyl) -2-[4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetamide is obtained as a pink solid with the following characteristics: The spectrum of the NMR 1 H is 3,37 to 3,47 (m, 4 H); 3,51 to 3,63 (m, 6 H); 5,20 (s, 1 H); 6,45 (d, J=8,6 Hz, 1 H); 6,93 (d, J=8,6 Hz, 1 H); 7,07 (t, J=8,6 Hz, 1 H); 7,12 (s wide, 1 H); 9,36 (s wide, 1 H); 10,00 (s wide, 1 H); 11,63 (s wide, 1 H) Mass spectrometry: method ATemps of retention Tr (min) = 0.43;[M+H]+: m/z 331 ; [M-H]-: m/z 329

The following is the list of active substances in the active substance:

The product is prepared as described in Example 19 from 261 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium prepared in Step 2 of Example 1 using a mixture of 7 mL of water and 1.5 mL of tetrahydrofuran instead of methanol and 190 mg of 3-bromo-4-fluoroaniline instead of 3-(tert-butyl) aniline. 266 mg of N- ((bromo-4-fluorofenyl) [-2- ((morpholin-4-oxo-1,6-dihydropyrimidine-2-yl) -6-oxo-1,6-dihydropyrimidine-2-acetamide in white solid form is obtained, with the following characteristics: The spectrum of the NMR 1 H is 3,41 (t, J=4,9 Hz, 4 H); 3,55 to 3,65 (m, 6 H); 5,20 (s, 1 H); 7,34 (t, J=8,8 Hz, 1 H); 7,44 to 7,53 (m, 1 H); 8,00 (dd, J=2,2 and 6,1 Hz, 1 H); 10,35 (s wide, 1 H); 11,67 (s wide, 1 H) Mass spectrometry: method AT Retention time Tr (min) = 3,30 [M+H]+: m/z 411; [M-H]-: m/z 409

The following is the list of active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 200 mg of [4-morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl] sodium acetate and 113 mg of 3,4,5-trifluoroaniline instead of 2,4-difluoroaniline. 33 mg of 2-[4-morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]-N-(3,4,5-trifluorophenyl) acetamide with the following characteristics is obtained: The frequency range of the measurement is as follows:

The following is the list of active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 250 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetate sodium and 525 mg of (5-amino-2-fluorophenyl) methanol instead of 2,4-difluoroaniline. 218 mg of N-[4-fluoro-3-(hydroxymethyl) phenyl]-2-[4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetamide is obtained as a beige solid with the following characteristics: The spectrum of the NMR 1 H is 3,42 (d, J=4,9 Hz, 4 H); 3,55 to 3,64 (m, 6 H); 4,51 (d, J=6,1 Hz, 2 H); 5,20 (s wide, 1 H); 5,27 (t, J=6,0 Hz, 1 H); 7,08 (t, J=9,4 Hz, 1 H); 7,46 to 7,54 (m, 1 H); 7,63 (d, J=7,3 Hz, 1 H); 10,18 (s wide, 1 H); 11,64 (s wide, 1 H) Mass spectrometry: method ATemps of retention Tr (min) = 0,46 [M+H] + m/z 363 ; [M-H]- m/z 361 > 260°C

The following is the list of active substances in the active substance:

The product is prepared by the following method: 250 mg of [4- ((morpholin-4-yl) -6-oxo-1 ,6-dihydropyrimidin-2-yl]acetate sodium and 395 mg of 3-cyclopropyleaniline (prepared according to Wallace et al. in Tetrahedron Lett. 2002, 43, 6987) instead of 2,4-difluoroaniline. 225 mg of N- ((3-cyclopropylephenyl) -2-[4- ((morpholin-4-yl) -6-oxo-1 ,6-dihydropyrimidin-2-yl) acetamide is obtained as a white solid with the following characteristics: The spectrum of the NMR 1 H is: 0.50 to 0.68 (m, J=2.0 and 4.9 Hz, 2 H); 0.88 to 1.02 (m, 2 H); 1.79 to 1.94 (m, J=4.4 and 4.4 Hz, 1 H); 3.42 (t, J=5.1 Hz, 4 H); 3.51 to 3.68 (m, 6 H); 5.20 (s, 1 H); 6.80 (d, J=8.3 Hz, 1 H); 7.17 (t, J=7.8 Hz, 1 H); 7.26 to 7.36 (m, 2 H); 10.06 (s wide, 1 H); 11.63 (s wide, 1 H) Mass spectrometry: Retention method: AT Tremps (min) = 0.72[M+H] + 35 m/z: [M-H] + 35 m/z: 35 m/z (Kofler) = 24°C

The following is the list of active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 500 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetate sodium and 278 mg of 2-aminophenol instead of 2,4-difluoroaniline. 370 mg of N- ((2-hydroxyphenyl) -2-[4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetamide is obtained as a white solid with the following characteristics: The spectrum of the NMR is given by the following equations: 1.H :3,45 (t, J=5,0 Hz, 4 H); 3.59 to 3.65 (m, 4 H); 3.69 (s, 2 H); 5.21 (s, 1 H); 6.76 (t, J=7,8 Hz, 1 H); 6.87 (d, J=7,8 Hz, 1 H); 6.92 (t, J=8,5 Hz, 1 H); 7.86 (d, J=7,3 Hz, 1 H); 9.46 (s wide, 1 H); 9.82 (s wide, 1 H); 11.63 (s wide, 1 H) Mass spectrometry: Retention time Tr (min) = 2.58; [M+H] + method: m/z 331 [M-H]- m/z 329

The following is the list of active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 200 mg of [4-morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]sodium acetate and 520 mg of 3-difluoromethoxy-aniline instead of 2,4-difluoromethoxy-aniline. 135 mg of N-[3-difluoromethoxy-phenyl]-2-[4-morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetamide is obtained as a white solid with the following characteristics: The frequency range of the spectrum is as follows: 1.H (400MHz): 3.36 to 3.48 (m, 4H); 3.54 to 3.65 (m, 6H); 5.20 (width, 1H); 6.88 (s width, 2H); 7.17 (t, J=69.0 Hz, 1H); 7.36 (s, 1H); 7.48 to 7.57 (m, 1H); 10.34 (s width,1H); 11.66 (s width, 1H) Mass spectrometry: method ATTemps of retention Tr (min) = 0.67; [M+H]+: m/z 381 ; [M-H]-: m/z 379

The following is the list of active substances in the active substance:

Step one:

88 mg sodium hydride is added to a 535 mg solution of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]ethyl acetate prepared in step 1 of example 1 in 9 mL N,N-dimethylformamide under argon. The reaction mixture is then stirred for 5 minutes at room temperature, then a 655 mg solution of di-tert-butyl-dicarbonate in 2 mL N,N-dimethylformamide is added. After 1 night of stirring at room temperature, the mixture is reduced to concentrated pressure. A 10 mL water solution of N-dimethylformamide hydrochloride is added to a pH close to 6.

Step two:

To a 700 mg solution of [4- ((({(2-methylpropan-2-yl) oxy]carbonyl}oxy)-6- ((morpholin-4-yl) pyrimidin-2-yl]ethyl acetate in 8 mL of N,N-dimethylformamide under argon, 84 mg of sodium hydride is added. The reaction mixture is then stirred for 15 minutes at 0 °C. Then 0.130 mL of methane iodide is added and stirred at a cleansing temperature for 1 night. 0.5 mL of water is added and the reaction mixture is concentrated at dry ambient pressure. After chromatography on silica by elucidation with a heptane/acetate gradient of 0% and 100%, the heptane/acetate is then combined with 2-methylpropan-2-yl-2-yl-methylpropanoate.

Step three:

To a 145 mg solution of 2-[4-({[2-methylpropan-2-yl) oxy]carbonyl}oxy)-6-(morpholin-4-yl) pyrimidine-2-yl]ethylpropanoate in 5 mL of tetrahydrofuran, 0.190 mL of sodium 1 M is added. After 1 night of stirring at room temperature, the reaction mixture is concentrated dry under reduced pressure. 100 mg of 2-[4-(methylmorpholin-4-yl) 6-morpholin-4-oxo-1,6-dihydropyropyropyropyr-2-yl]propanoate sodium is obtained as a solid used as a base.

Step four:

The product is prepared by following the procedure described in Example 5 from 100 mg of 2-[4-(morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]propanoate sodium and 195 mg of 4-fluoro-3-methoxyaniline instead of 2,4-difluoroaniline. 30 mg of N-(4-fluoro-3-methoxyphenyl) -2-[4-morphol in-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]propanamide is obtained as a white solid with the following characteristics: The frequency range of the spectrum is as follows: 1.44 (d, J=7.1 Hz, 3 H); 3.36 to 3.47 (m, 4 H); 3.50 to 3.65 (m, 4 H); 3.71 (q, J=6.8 Hz, 1 H); 3.79 (s, 3 H); 5.19 (s wide, 1 H); 7.01 to 7.18 (m, 2 H); 7.47 (dd, J=2.0 and 7.8 Hz, 1 H); 10.00 (s, 1 H); 11.55 (s wide, 1 H) Mass spectrometry: method ATemps of retention Tr (min) = 0.65 (M+H) + m/z 377 ; [M-H]- m/z 375

The following is the list of active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 260 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetate sodium and 242 mg of 2,3-dimethylaniline instead of 2,4-difluoroaniline. 190 mg of N- ((2,3-d imethylphenyl) -2-[4-(morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetamide is obtained as a white solid with the following characteristics: The spectrum of the NMR is 1 H,08 (s, 3 H); 2.24 (s, 3 H); 3.41 to 3.47 (m, 4 H); 3.58 to 3.65 (m, 6 H); 5.20 (s, 1 H); 6.99 to 7.08 (m, 2 H); 7.13 (d, J=7.6 Hz, 1 H); 9.57 (s, 1 H); 11.67 (s wide, 1 H) Mass spectrometry: method Retention time Tr (min) = 0.62 [M+H]+ ; m/z 343 :2 [M-H-]: m/z 341

The following is the list of active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 260 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetate sodium and 250 mg of 2-fluoro-3-methylaniline instead of 2,4-difluoroaniline. 208 mg of N- ((2-fluoro-3-methylphenyle) -2-[4-(morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetamide is obtained as a white solid with the following characteristics: The spectrum of the NMR is 1 H,24 (s wide, 3 H); 3.37 to 3.48 (m, 4 H); 3.56 to 3.72 (m, 6 H); 5.20 (s wide, 1 H); 6.97 to 7.08 (m, 2 H); 7.71 (s wide, 1 H); 9.89 (s wide, 1 H); 11.66 (s wide, 1 H) Mass spectrometry: method Retention time Tr (min) = 0.65 [M+H]+: m/z 347 ; [M-H]-: m/z 345

The following table shows the results of the analysis of the chemical composition of the product:

The product is prepared by following the procedure described in Example 5 from 260 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetate sodium and 268 mg of 1,3-benzoxazol-4-amine instead of 2,4-difluoroaniline. 193 mg of N- ((1,3-benzoxazol-4-yl) -2-[4-(morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetamide is obtained in solid form from the scruff with the following characteristics: The frequency range of the measurement is as follows: 1. m, 4 h; 3.62 (t, J=4.9 Hz, 4 h); 3.80 (s, 2 h); 5.21 (s, 1 h); 7.36 to 7.42 (m, 1 h); 7.49 (d, J=8.3 Hz, 1 h); 8.08 (d, J=7.8 Hz, 1 h); 8.78 (s, 1 h); 10.44 (s) wide, 1 h; 11.73 (s) wide, 1 h.

The following is the list of active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 250 mg of [4-morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium and 270 mg of 3-trifluoromethoxy) aniline instead of 2,4-difluoromethoxy. 230 mg of 2-[4-morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]-N-[3-trifluoromethoxy) phenyl]acetamide is obtained as a white solid with the following characteristics: The spectrum of the NMR 1 H :3,37 to 3,44 (m, 4 H); 3,54 to 3,64 (m, 6 H); 5,20 (s, 1 H); 7,05 (d, J=6,6 Hz, 1 H); 7,41 to 7,48 (m, 2 H); 7,74 (s, 1 H); 10,45 (s wide, 1 H); 11,66 (s wide, 1 H) Mass spectrometry: method ATemps of retention Tr (min) = 0,78; [M+H]+: m/z 399 ; [M-H]-: m/z 397

The following is the list of active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 250 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium and 572 mg of 3-isopropoxyaniline instead of 2,4-difluoroaniline. 228 mg of 2-[4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]-N-[3- ((propan-2-yloxy) phenyl]acetamide is obtained as a white solid with the following characteristics: The spectrum of the NMR 1 H :3,35 (t, J=5,0 Hz, 4 H); 3,56 (t, J=4,9 Hz, 4 H); 4,25 (s, 2 H); 5,25 (s wide, 1 H); 7,31 to 7,40 (m, 2 H); 7,62 to 7,74 (m, 2 H); 11,92 (s wide, 1 H) Mass spectrometry: method ATemps of retention Tr (min) = 0,60; [M+H]+: m/z 313 ; [M-H]-: m/z 311

The following is the list of active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 250 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetate sodium and 460 mg of 4-fluoro-2-methoxyaniline instead of 2,4-difluoroaniline. 245 mg of N- ((4-fluoro-2-methoxyphenyl) -2-[4-morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetamide is obtained as a pink solid with the following characteristics: The following are the parameters to be used for the calculation of the mass spectrometry:

The following is the list of substances which are to be used in the preparation of the product:

The product is prepared in the manner described in Example 5 from 250 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium and 930 mg of [2- ((3-aminophenyl) ethyl) 2-methylpropan-2-yl]carbamate instead of 2,4-difluoroaniline to obtain 285 mg of {2-[3-{[[4-(morpholin-yl) -6-oxo-1,6-hydropyrimidine-2-yl]acetyl}amino) -methyl]oxo-1,6-dihydropyrimidine-2-yl}carbamate of 2-methylpropan-2-yl in solid form with the following characteristics:

The following is the list of active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 260 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetate sodium and 358 mg of 4-fluoro-3- ((trifluoromethylaniline) instead of 2,4-difluoromethylaniline. 222 mg of N-[4-fluoro-3-(trifluoromethyl)phenyl]-2-[4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetamide is obtained as a white solid with the following characteristics: The following are the parameters to be used for the calculation of the mass spectrometry:

The following is the list of active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 260 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium and 201 mg of 3-aminophenyl acetylene instead of 2,4-difluoroaniline. 190 mg of N- (((3-ethynylphenyl) -2-[4-(morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetamide is obtained as a white solid with the following characteristics: The following are the parameters to be used for the calculation of the frequency range:

The following is the list of active substances in the active substance:

The product is prepared following the procedure described in Example 5 from 260 mg of [4-morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl] sodium acetate and 354 mg of 3-cyclopentyloxy-aniline instead of 2,4-difluoroaniline. 269 mg of N-[3-cyclopentyloxy-phenyl]-2-[4-morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetamide is obtained as a white solid with the following characteristics: The spectrum of the NMR 1 H is from 1:50 to 1,75 (m, 6 H) ; 1,83 to 1,96 (m, 2 H) ; 3,39 to 3,44 (m, 4 H) ; 3,54 to 3,63 (m, 6 H) ; 4,73 (m, 1 H) ; 5,20 (s, 1 H) ; 6,60 (dd, J=2,0 and 8,3 Hz, 1 H) ; 7,03 (wide, J=8,3 Hz, 1 H) ; 7,18 (t, J=8,3 Hz, 1 H) ; 7,26 (t, J=2,2 Hz, 1 H) ; 10,10 (s, 1 H) ; 11,64 (s, 1 H) Mass spectrometry method Retention time: Tr (min) = 0,84 [M+H] : 399 m/z; 399 m/z; 399 m/z; 399 m/z.

The following is the list of active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 500 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium and 815 mg of 2-amino-5-fluorophenol instead of 2,4-difluoroaniline. After purification by silica chromatography, the eluent : CH2Cl2/MeOH 95/5 is obtained from 149 mg of N- ((4-fluoro-2-hydroxyphenyle) -2-[4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetamide in a grey solid form with the following characteristics: The frequency range of the measurement is as follows: 1 H :3,41 to 3,47 (m, 4 H) ; 3.59 to 3,64 (m, 4 H) ; 3.67 (s, 2 H) ; 5.20 (s, 1 H) ; 6.58 (dt, J=2,8 and 8,8 Hz, 1 H) ; 6.66 (dd, J=2,8 and 10,4 Hz, 1 H) ; 7.80 (dd, J=6,4 and 8,8 Hz, 1 H) ; 8.66 to 12,13 (m spread, 3 H) Mass spectrometry: method BT retention tremps (min) = 2,74 [M+H+] : m/z 349 ; [M-H]-: m/z 347

The following is a list of the active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 260 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetate of sodium and 238 mg of indoline instead of 2,4-difluoroaniline to obtain 230 mg of 2-[2-(2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-6- ((morpholin-yl) pyrimidin-4(3H) -one as a pale pink solid with the following characteristics:Spectre RMN 1 H 17 (t, J=8,3 Hz, 2 H) 3,41 (dm, 4 H) 3,60 (m, 4 H) 3,75 (s) 2 Hz; 4,14 (s) 4 Hz; 4,14 (s) 4 Hz; 4,14 (s) 4 Hz; 5,21 (s) 5 Hz; 4,21 (s) 6 Hz; 7,01 (s) 7 Hz; 7,01 (s) 7 Hz; 7,01 (s) 7 Hz; 7,01 (s) 7 Hz; 7,01 (s) 7 Hz; 7,01 (s) 7 Hz; 7,01 (s) 7 Hz; 7,01 (s) 7 Hz; 7,01 (s) 7,01 (s) 7,01 (s) 7,01 (s) 7,01 (s) 7,01 (s) 7,01 (s) 11,06 (s) 7,01 (s) 7,01 (s) 7,01 (s) 7,01 (s) 7,01 (s) 11,01 (s) 7,01 (s) 11,01 (s) 7,01 (s) 11,01 (s) 7,01 (s) 11,1 (s) 7,01 (s) 13, (s) 13, (s) 13, (s) 13, (s) 13, (s) 13, (s) 13, (s) 13, (s) 13, (s) 13, (s) 13, (s) 13, (s) 13, (s) 13, (s) 13, (s) 13, (s) 13, (s (s) 13, (s) 13, (s) 13, (s) 13, (s) 13, (s) 13, (s) 13, (s) (s) 13, (s (s) 13, (s) (s) 13, (s) (s) (s) (s) 13, (s) (s)

The following is the list of active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 260 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetate sodium and 302 mg of 3-cyclopropyl-4-fluoroaniline (prepared according to US patent application 2007/0185058.) instead of 2,4-difluoroaniline. 225 mg of N- (((3-cyclopropyl-4-fluorophenyl) [2-dimid4-(morpholin-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetamide is obtained as a pale yellow solid with the following characteristics: The following are the parameters for the measurement of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emission of the emis

The following is a list of the active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 260 mg of [4-morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl] sodium acetate and 294 mg of 2,3,4-trifluoroaniline instead of 2,4-difluoroaniline. 195 mg of 2-[4-morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]-N-(2,3,4-trifluorophenyl) acetamide is obtained as a white solid with the following characteristics: The spectrum of the NMR 1 H :3,43 (m, 4 H) ; 3.61 (m, 4 H) ; 3.67 (s, 2 H) ; 5.20 (s, 1 H) ; 7.24 to 7.35 (m, 1 H) ; 7.56 to 7.67 (m, 1 H) ; 10.18 (s wide, 1 H) ; 11.67 (s wide, 1 H) Mass spectrometry: method ATTemps of retention Tr (min) = 0.65 [M+H]+ : m/z 369 ; [M-H]-: m/z 367

The following is the list of active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 250 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium and 270 mg of 4-fluoro-3- ((trifluoromethoxy) aniline instead of 2,4-difluoromethoxyaniline. 270 mg of N-[4-fluoro-3-(trifluoromethoxy)phenyl]-2-[4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetamide is obtained as a white solid with the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The following are the methods used to determine the mass spectrometry: method ATemps of retention Tr (min) = 0.80 [M+H]+: m/z 417: [M-H]-; m/z 415

The following is the list of active substances in the active substance:

The product is prepared following the procedure described in Example 5 from 260 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetate sodium and 294 mg of 2- ((3-aminophenoxy) -ethanol instead of 2,4-difluoroaniline. 180 mg of N-[3- ((2-hydroxyethhoxy) phenyl]-2-[4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetamide is obtained as a pink solid with the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: In this batch, we observe broad signals with: 3.42 (m, 4 H) ; 3.59 (m, 6 H) ; 3.70 (m, 2 H) ; 3.93 (m, 2 H) ; 4.82 (m, 1 H) ; 5.20 (s, 1 H) ; 6.64 (d, J=8.1 Hz, 1 H) ; 7.07 (d, J=8.1 Hz, 1 H) ; 7.15 to 7.23 (t, J=8.1 Hz, 1 H) ; 7.28 (s, 1 H) ; 10.12 (s, 1 H) ; 11.65 (s, 1 H) Mass spectrometry: AT method Retention time (min) = 0.46 [M+H] +: m/z For 375 [M-H] : m/z3

The following is the list of active substances in the active substance:

The product is prepared following the procedure described in Example 5 from 268 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetate sodium and 324 mg of 3-iodoaniline instead of 2,4-difluoroaniline. 345 mg of N- (((3-iodophenyl) -2-[4-(morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetamide is obtained as a white solid with the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The following are the main characteristics of the test method: 3,41 (m, 4 H) ; 3,58 to 3,64 (m, 6 H) ; 5,20 (s, 1 H) ; 7,12 (t, J=8,1 Hz, 1 H) ; 7,42 (d, J=8,1 Hz, 1 H) ; 7,50 (d, J=8,1 Hz, 1 H) ; 8,06 (s, 1 H) ; 10,26 (s wide, 1 H) ; 11,66 (s wide, 1 H) Mass spectrometry: method BT Retention temps (min) = 3,41[M+H]+: m/z 441; [M-H-: m/z 439].

The following is the list of active substances which are to be classified in the Annex to this Regulation:

The product is prepared by following the procedure described in Example 5 from 500 mg of [4-morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl] sodium acetate and 466 mg of 5-amino-2-fluorobenzoate methyl instead of 2,4-difluoroaniline. 625 mg of 2-fluoro-5- (([4-morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetyl}amino) methyl benzoate is obtained as a pink solid with the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The following are the methods used for the determination of the mass spectrometry: method ATems of retention Tr (min) = 0,59 [M+H]+: m/z 391; [M-H]-: m/z 389

The following is the list of active substances in the active substance:

The product is prepared as described in Example 5 from 250 mg of [4-morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl] sodium acetate and 540 mg of 3-ethoxyaniline instead of 2,4-difluoroaniline. 235 mg of N- (4-morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl) acetamide is obtained as a white solid with the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The following are the parameters to be taken into account for the calculation of the mass spectrometry: mass spectrometry: AT method: retention time: Tr (min) = 0,66; M+H: m/z 359; M-H: 357+m/z 357

The following is the list of active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 260 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetate sodium and 318 mg of 2,4-difluoro-3-methoxyaniline instead of 2,4-difluoroaniline. 255 mg of N- ((2,4-difluoro-3-methoxyphenyl) -2-[4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetamide is obtained as a white solid with the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The following are the values of the measurements to be performed: 3,43 (m, 4 H) ; 3,61 (m, 4 H) ; 3,66 (s, 2 H) ; 3,93 (s, 3 H) ; 5,20 (s, 1 H) ; 7,11 (ddd, J=2,1 and 9,0 and 10,9 Hz, 1 H) ; 7,50 (dt, J=5,5 and 9,0 Hz, 1 H) ; 10,00 (s, 1 H) ; 11,65 (s wide, 1 H) Mass spectrometry: method BT Retention rates Tr (min) = 3,01 [M+H]+: m/z 381 ; [M-H-: m/z 379].

The following is a list of the active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 260 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium and 294 mg of 2,4,5-trifluoroaniline instead of 2,4-difluoroaniline. 230 mg of 2-[4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]-N-(2,4,5-trifluorophenyl) acetamide is obtained as a white solid with the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The following are the methods used for the determination of the mass spectrometry: mass spectrometry: method BT Retention time Tr (min) = 3,10 [M+H]+: m/z 369; [M-H]-: m/z 367

The following is the list of active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 260 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium and 360 mg of 3,5-dichloro-4-fluoroaniline instead of 2,4-difluoroaniline. 259 mg of N- ((3,5-dichloro-4-fluorophenyl) -2-[4-morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetamide is obtained as a white solid with the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The measurement of the mass of the sample is carried out by measuring the mass of the sample and the sample is then measured at a rate of approximately 1 Hz.

The following is a list of the active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 260 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetate sodium and 270 mg of 3,4-dihydro-2H-1,4-benzoxazine instead of 2,4-difluoroaniline. After purification by silica chromatography, CH2Cl2/OHMe 95/05 is released, 150 mg of 2-[2-(2,3-dihydro-4H-1,4-benzoxazin-4-yl) -2-oxoethyl]-6- ((morpholin-4-yl) pyrimidin-4(3H) -one is obtained as a white solid with the following characteristics: The frequency range of the measurement is defined as the frequency range of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measur

The following is the list of active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 500 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetate sodium and 510 mg of 4-fluoro-3-nitroaniline instead of 2,4-difluoroaniline. 339 mg of N- ((4-fluoro-3-nitrophenyl) -2-[4-(morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetamide is obtained as a white solid with the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The following are the values of the measurements to be performed: 3,41 (m, 4 H) ; 3,58 to 3,62 (m, 4 H) ; 3,64 (s, 2 H) ; 5,21 (s, 1 H) ; 7,56 (dd, J=9,0 and 11,2 Hz, 1 H) ; 7,83 to 7,88 (ddd, J=2,9 and 4,0 and 9,0 Hz, 1 H) ; 8,47 (dd, J=2,9 and 6,8 Hz, 1 H) ; 10,63 (s wide, 1 H) ; 11,69 (s wide, 1 H) Mass spectrometry: method AT Retention Tremps (min) = 0,63 [M+H]+: m/z 378 ; [M-H]: m/z 376

The following table shows the results of the analysis of the chemical composition of the product:

After a night of stirring at room temperature, 0.4 mL of 2M soda is added again and brought to the reflux for 3 hours. After cooling, the reaction mixture is concentrated under reduced pressure. The erosion residue is re-absorbed by water. The aqueous phase is extracted with ethyl acetate, then acidified with a solution of hydrochloric acid 1 N (Hp = 5). The chloride is then reduced to a concentrated solution of water and re-absorbed by a water filter of 1 N.The precipitate formed is filtered, rinsed with petroleum ether and concentrated dry under reduced pressure. 52 mg of 2-fluoro-5- (({[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetyl}amino) benzoic acid is obtained in the form of a pale pink solid with the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The following are the methods used for the determination of the mass spectrometry:

The following is the list of active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 1 g of [4-morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl] sodium acetate and 466 mg of 2-amino-4-fluorophenol instead of 2,4-difluoroaniline. 795 mg of 2 N- ((5-fluoro-2-hydroxyphenyle) -2-[4-morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetamide is obtained in the form of a brown solid with the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The following are the methods used for the determination of the mass spectrometry: method ATems of retention Tr (min) = 0.55 [M+H]+: m/z 349; [M-H]-: m/z 347

The following is the list of active substances in the active substance:

The product is prepared by following the procedure described in Example 5 from 250 mg of [4-morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl] sodium acetate and 260 mg of 2-bromo-4-fluoroaniline instead of 2,4-difluoroaniline. 310 mg of N-bromo-4-fluorophenyl) -2-[4-morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetamide is obtained in the form of a brown solid with the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: For this batch all signals are wide with: 3.44 (m, 4 H) ; 3.62 (m, 4 H) ; 3.65 (s, 2 H) ; 5.20 (s, 1 H) ; 7.22 to 7.32 (m, 1 H) ; 7.58 to 7.67 (m, 2 H) ; 9.73 (s, 1 H) ; 11.68 (s, 1 H) Mass spectrometry: method Retention time Tr (min) = 0.65[M+H]+: m/z 411; [M-H]-: m/z 409

The following is the list of active substances in the active substance: Step one:

A solution of 500 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl) ethyl acetate prepared in step 1 of example 1 prepared in step 1 of example 1 in 1.5 mL of dioxane, 330 mg of potassium carbonate and 150 mL of methyl iodide. The reaction mixture is heated to 40 °C for 16 minutes and then cooled to room temperature. The suspension is filtered on a fritted glass and then rinsed with dioxane and the wire is concentrated under reduced pressure. The residue is purified by chromatography in the form of a silicon column, emulsifying with a mixture of dichromethane, aclorin and white acrylonitrile. The following characteristics are obtained: (91/01/01/02/01/01/02/01/01/02/01/02/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/04/ The test method is based on the following equation:

Step two:

- What? To a 190 mg solution of [1-methyl-4-(morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]ethyl acetate prepared in step 1 of sample 67 in 10 mL of toluene, 0.135 mL of 4-fluoroaniline and 0.670 mL of a 2M trimethyl aluminium solution are added. After stirring for 30 minutes at room temperature, 10 mL of toluene is added. After 4 hours of stirring at room temperature, the reaction mixture is poured over with water and a 1 M solution of potassium phosphate is added. The precipitate is filtered over a fritter rinse with the chlorethyl acetate. The glass is then saturated with sodium chloride solution.The organic phase is extracted and then dried on magnesium sulphate, filtered on sintered glass and concentrated under reduced pressure. After purification of the residue by chromatography on a silica column by elevating with a mixture of dichloromethane and methanol (95/05, V/V), 20 mg of N-(4-fluorophenyl)-2-[1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide is obtained as a white solid with the following characteristics: The frequency range of the measurement is defined as the frequency range of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurThe test is performed at a frequency of 0 Hz, 2 H); 10.25 (s, 1 H) Mass spectrometry: method

The following is the list of active substances in the active substance: Step one:

To a 1.62 g solution of [1-methyl-4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]ethyl acetate prepared in step 1 of example 67, in 20 mL of tetrahydrofuran, 2.88 mL of 2M sodium are added. The reaction mixture is agitated for 48 hours at room temperature. The precipitate formed is filtered on sintered glass, washed with ethyl acetate and rinsed several times with ethyl ether. The resulting solid is then dried in the rotary evaporator. 730 mg of [1-methyl-4- ((morpholin-4-morpholin) -6-o-1-hydropyrimidine-2-yl]ethyl sodium is obtained in the form of a white solid, the characteristics of which are as follows: The test chemical is used to determine the concentration of the test chemical in the test medium.

Step two:

A 200 mg solution of [1-methyl-4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium in 2.5 mL N,N-dimethylformamide is added to 120 mL pyridine, 182 mg N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide chlorhydrate and 210 mg 3-chloro-4-fluoroaniline. It is stirred at room temperature for 1 night, then the reaction mixture is concentrated under reduced pressure. Water is added, then extracted from the ethyl acetate, washed with water and concentrated under reduced pressure. The following shall be used for the calculation of the frequency of the radio frequency spectrum: The method of measurement is based on the following equations: 3,34 (s, 3 H) ; 3,37 to 3,42 (m, 4 H) ; 3,55 to 3,60 (m, 4 H); 3,91 (s, 2 H) ; 5,36 (s, 1 H) ; 7,38 (t, J=9,0 Hz, 1 H) ; 7,41 to 7,47 (m, 1 H) ; 7,87 (dd, J=2,4 and 6,8 Hz, 1 H) ; 10,42 (s, 1 H) Mass spectrometry: method ATTemps of retention Tr (min) = 0,75[M+H]+: m/z 381 ; [M-H]-: m/z 379

The following is the list of active substances in the active substance:

The product is prepared following the procedure described in Example 68 from 200 mg of [1-methyl-4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium and 257 mg of 3-bromoaniline. 51 mg of N-(3-bromophenyl)-2-[1-methyl-4-(morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetamide is obtained as a white solid with the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The method of measurement is based on the following equations: 3,34 (s, 3 H) ; 3,37 to 3,42 (m, 4 H) ; 3,58 (m, 4 H) ; 3,92 (s, 2 H) ; 5,36 (s, 1 H) ; 7,19 to 7,33 (m, 2 H) ; 7,45 (m, 1 H) ; 7,91 (s, 1 H) 10,37 (s, 1 H) Mass spectrometry: method Retention time Tr (min) = 0,75 [M+H] : m/z 407+; [M-H]-: m/z 405 Melting point (Kofler): 266°C

The following is the list of active substances in the active substance: Step one:

The product is prepared by following the procedure described in Example 67 from 600 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]ethyl acetate prepared in Step 1 of Example 1 and 0.23 mL of ethyl iodide instead of methyl iodide and replacing the potassium carbonate with caesium carbonate. After purification by silica column chromatography, eluting: CH22/CH3CN/OH Me, 96/02/02, 190 mg of [1-ethyl-4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]ethyl acetate in the form of a white solid with the following characteristics is obtained: The test chemical is used to determine the concentration of the test chemical in the sample.

Step two:

To a 0.13 mL solution of 4-fluoroaniline in 4 mL of toluene are added successively 0.640 mL of a 2M trimethylaluminium solution in toluene drop by drop, then after 40 minutes of stirring at room temperature, a 190 mg solution of [1-ethyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]ethyl acetate in 6 mL of toluene. The reaction mixture is heated at 80°C for 4 hours, cooled using an ice bath and poured over water. A 1 M solution of potassium phosphate and potassium ethyl acetate is then extracted, then the organic phase is washed, with a new solution of 1 Myl phosphate on dried magnesium sulphate, then addedAfter purification by chromatography on a silica column, by electrolysis of CH2Cl2/ CH3CN/ MeOH, 98/01/01 and then, 96/02/02, 60 mg of 2-[1-ethyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidine-2-yl]-N-(4-fluorophenyl) acetamide is obtained as a white solid having the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The following are the methods used to determine the mass spectrometry: AT method Retention time Tr (min) = 0,

The following is the list of active substances in the active substance:

Step one:

The product is prepared by following the procedure described in Example 5 from 500 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium and 445 mg of 4-amino-1H-indole-1-carboxylate 2-methylpropan-2-yl instead of 2,4-difluoroaniline. 500 mg of 4- (([4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetyl}amino) -1-H-indole-1-carboxylate 2-methylpropan-2-yl is obtained as a brown solid with the following characteristics: The test chemical is used to determine the concentration of the test chemical in the test medium.

Step two:

After 3 days of stirring at room temperature, the reaction medium is concentrated under reduced pressure, taken up by toluene and concentrated under reduced pressure. After purification by silica column chromatography, eluting: CH2Cl2/OH, 90/10, 48 N- (H) -indiol-4-methyl-2-methyl-4-methyl-4-methyl-1-methyl-6-hydroxyethyl-2-amide are obtained, the characteristics of which are as follows: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The following are the values of the measurements to be performed: 3,43 (m, 4 H) ; 3,60 (m, 4 H) ; 3,73 (s, 2 H) ; 5,21 (s, 1 H) ; 6,68 (s wide, 1 H) ; 7,01 (t, J=7,9 Hz, 1 H) ; 7,16 (d, J=7,9 Hz, 1 H) ; 7,30 (t, J=2,4 Hz, 1 H) ; 7,55 (d, J=7,9 Hz, 1 H) ; 9,80 (s wide, 1 H) ; 11,11 (s wide, 1 H) ; 11,67 (m spread, 1 H) Mass spectrometry: AT method Retention temps (min) = 0,48 (MH) + m/z 354 (M-H+) m/z 352

The following is the list of active substances in the active substance: Step one:

The product is prepared by following the procedure described in Example 67 from 600 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]ethyl acetate prepared in Step 1 of Example 1 prepared in Step 1 of Example 1 and 0.29 mL 2-iodopropane in place of methyl iodide and replacing the potassium carbonate with caesium carbonate. After purification by silica column chromatography, resulting in: CH22/Cl CH3CN/OH Me, 90/05/05, 20 mg of 3-methyl-2-[4- ((morpholin-4-oxo) -6-hydropyrimidin-2-butyl]ethyl] is obtained in the form of a white solid with the following characteristics: The test chemical is used to determine the concentration of the test chemical in the test medium.

Step two:

The product is prepared in the manner described in Example 70 from 0.023 mL of 4-fluoroaniline and 36 mg of 3-methyl-2-[4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]ethyl butanoate instead of [1-ethyl-4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]ethyl acetate. After purification by silica chromatography on a column of eluting: CH2Cl2/CH3CN/MeOH, 94/03/03, 15 mg of N- ((4-morpholin-4-yl) -3-oxo-1,6-dihydropyrimidin-2-yl) sub-methyl-2-butanoate is obtained, the white solid form of which has the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The following are the values of the measurements to be performed: 0,87 (d, J=6,6 Hz, 3 H) ; 0,97 (d, J=6,6 Hz, 3 H) ; 2,53 to 2,57 (m, 1 H) ; 3,24 (d, J=10,3 Hz, 1 H) ; 3,42 to 3,47 (m, 4 H) ; 3,59 to 3,65 (m, 4 H) ; 5,21 (s, 1 H) ; 7,15 (t, J=8,8 Hz, 2 H) ; 7,59 (dd, J=5,1 and 8,8 Hz, 2 H) ; 10,09 (s wide, 1 H) ; 11,30 (s wide, 1 H) Mass spectrometry: AT method Retention time Tr (min) = 0,76[M+H] + m/z 375 [M-H]: 37 m/z3 melting point (Kofler: 26°C)

The following is the list of active substances in the active substance:

Step one:

In a balloon, 374 mg of 60% sodium hydride is introduced into 10 mL of tetrahydrofuran, 1 g of (5-amino-2-fluorophenyl) methanol and 0.441 mL of methyl iodide. After an hour of stirring at room temperature, a solution of sodium chloride and diethyl ether is added. The organic phase is extracted and washed with water until pH = 7. It is then dried on magnesium sulfate, filtered and concentrated at reduced pressure. 900 mg of 4-fluoro-3- ((methoxymethyl) aniline is obtained in black oil form used as such in the next step.

Step two:

The product is prepared following the procedure described in Example 5 from 250 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium and 900 mg of 4-fluoro-3- ((methoxymethyl) aniline previously prepared instead of 2,4-difluoroaniline. 168 mg of N-[4-fluoro-3-(methoxymethyl) ((phenyl) -2-[4-morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetamide is obtained as a white solid with the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The following is a list of the main components of the test chemical: 3,31 (s partially masked, 3 H) ; 3,41 (m, 4 H) ; 3,59 (m, 6 H) ; 4,43 (s, 2 H) ; 5,20 (s, 1 H) ; 7,14 (t, J=9,3 Hz, 1 H) ; 7,51 (m, 1 H) ; 7,63 (m, 1 H) ; 10,21 (s wide, 1 H) ; 11,63 (s wide, 1 H) Mass spectrometry: AT method Retention time Tr (min) = 0,60[M+H]+: m/z 377 ; [M-H]-: m/z 375 Melting point (Kofler): 220°C

The following is the list of active substances in the active substance:

Step one:

After 1 hour of reflux heating, the reaction mixture is filtered and the organic extracts are evaporated. The evaporation residue is taken up in a mixture of water and dichloromethane. The aqueous phase is extracted with 3 times the dichloromethane. The extra organic reducts are concentrated, concentrated on magnesium sulfate under pressure and under secrite. 840 mg of 4-fluoro-3-iodoaniline are obtained, the characteristics of which are as follows: The test chemical is used to determine the concentration of the test chemical in the test medium.

Step two:

The product is prepared by following the procedure described in Example 5 from 300 mg of [4-morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl] sodium acetate and 272 mg of 4-fluoro-3-iodoaniline. 309 mg of N-(4-fluoro-3-iodophenyl)-2-[4-morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetamide is obtained with the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The following are the values of the measurements to be performed: 3,42 (m, 4 H) ; 3,57 to 3,63 (m, 6 H) ; 5,21 (s, 1 H) ; 7,23 (t, J=8,6 Hz, 1 H) ; 7,52 (ddd, J=2,5 and 4,4 and 8,6 Hz, 1 H) ; 8,12 (dd, J=2,5 and 5,4 Hz, 1 H) ; 10,29 (s wide, 1 H) ; 11,65 (s wide, 1 H) Mass spectrometry: method

The following is a list of the active substances in the active substance:

The product is prepared as described in Example 5 from 250 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetate sodium, 300 mg of 3- ((1,1,2,2-tetrafluoroethy) aniline, 300 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 2 mL pyridine and 2 mL of N,N-dimethylformamide. 300 mg of 2-[4- ((morpholin-4-yl) -6-dihydropyrimidin-1-yl]acetate-N- ((1,1,1,2,2-tetrafluoroethy) acetylphenylate in a white solid form is obtained, which has the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The signal is transmitted at a frequency of approximately 1 Hz, with a maximum of 1 Hz, and a maximum of 1 Hz, with a maximum of 1 Hz, and a maximum of 1 Hz, with a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of 1 Hz, and a maximum of one and a maximum of one and a maximum of one and a maximum of one and a maximum of two seconds.

The following is the list of active substances in the active substance:

Step one:

After 3h30 agitation at 20°C 300 mL of an aqueous solution saturated in sodium hydrocarbonate are slowly added. After one hour agitation, the organic phase is washed with 40 mL of water, then dried on anhydrous magnesium sulphate, filtered and concentrated under dry pressure. The following characteristics are obtained: 3.6 g 2-fluoro-thyromethane-1-difluorobenzene in the form of a yellow liquid: Mass spectrometry: spectra were obtained by direct introduction on a WATERS GCTof apparatus (direct introduction without LC): El: [M]+.m/z = 191

Step two:

The reaction mixture is agitated for 1 hour at the reflux, then cooled to room temperature. 20 mL of ethyl acetate is then added and the reaction medium is filtered on Clarcel, rinsed with ethyl acetate and then concentrated dry under reduced pressure. The residue is taken up by 100 mL of ethyl acetate and filtered again on Clarcel and under reduced pressure. After using the residual liquid purifier, such as CH2OH, a mixture of 3-OH, 95-Cl, a mixture of 1-OH, a mixture of 3-OH, and a reducing fluid is used.

Step three:

The product is prepared as described in Example 5 from 250 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetate sodium, 1.1 g of 3- ((difluoromethyl) -4-fluoroaniline (step 2), and 300 mg of N- ((dimethylamino) propyl) -N'-ethylcarbodiene hydrochloride in a mixture of 2 mL pyridine and 2 mL N,N-dimethylformamide. 260 mg of N- ((difluoromethyl) -4-fluorofenyl) -2-[4- ((difluoromethyl) -4-oxo-6-hydropyrimidin-1-yl-2-amide) is obtained in the following white solid form: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The method of mass spectrometry is based on the following equation:

The following is the list of active substances in the active substance:

Step one:

To a 570 mg solution of 1,1,1,3,3,3-hexamethyldisilazan-2-ide potassium in 9 mL tetrahydrofuran placed at - 78°C and under argon, add 350 mg of [4- ((({[2-methylpropan-2-yl) oxy]carbonyl}oxy)-6- ((morpholin-4-yl) pyrimidine-2-yl]ethyl acetate previously dissolved in 6 mL tetrahydrofuran. After 45 min agitation at this temperature, add 409 mg of manganese dibromide2+). After 30 minutes agitation of the resulting suspension at - 78°C, add 847 mg of N-morpholine-benzyl-fluorocarbonyl acetate. After 20°C, the sodium bicarbonate is returned to a saturated suspension.The organic phase is washed by an aqueous solution saturated with sodium chloride, dried on anhydrous magnesium sulphate, filtered and dry concentrated under reduced pressure. The residue is picked up by 10 mL of methylene chloride and then the insoluble is filtered and washed to 5 mL of methylene chloride three times. The filtrate is dry concentrated under reduced pressure and after purification on a silica column of the oil residue, eluting: CH2Cl2/O, 95/05, Acetyl 95/05, 278 mg of diforo[4-[[2-[methylenpropan-2-y]carbonyl-oxy--6-[4-methylenmorol-pyrimidine]acetyl-2-oxy] is obtained, the characteristics of which are as follows: Mass spectrometry: method ATR (min) = 1,

Step two:

A 0.136 mL solution of 4-fluoroaniline in 5 mL of toluene at a temperature of 0°C to 10°C is slowly introduced into the toluene, 0.756 mL of an aluminium trichloride (2N) solution is slowly introduced into the toluene. After 40 min of stirring at a temperature of about 20°C, 271 mg of difluoro[4-((([[2-methylpropan-2-yl) oxy]carbonyl}oxy)-6-morpholine-4-yl) pyrimid-2-inyl]ethyl acetate are slowly added to the solution, then dissolved in 6 mL of toluene. After 2h30 of reflux, a reflux phase of about 20°C to 0°C is returned to 26 mL of water and 26 mL of sodium dihydrophosphoric acid is added slowly.After purification on a silica column of the residue, the eluting agent CH2Cl2/MeOH, 95/05, the solid is taken up by 5 mL of dichloromethane, the mixture is heated to 40°C for 5 minutes and then returned to a temperature of about 20°C. The insoluble is squeezed, washed in 1 mL of dichloromethane three times, then vacuum dried. 28 mg of 2,2-difluoro-N- ((4-fluoro-2-ethyl) [4-morpholine-4-amyl) -6-oxo-1,6-dihydropinamid-2-acetyl] is obtained as a white powder having the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: 3,51 (m, 4 H) ; 3,58 to 3,The following are the methods used for the determination of the mass spectrometry:

The following is the list of active substances in the active substance:

The product is prepared as described in Example 5 from 250 mg of [1-methyl-4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl] sodium acetate prepared in Step 1 of Example 68, 169 mg of 3,4-difluoroaniline, and 285 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide chloride in a mixture of 2 mL of pyridine and 2 mL of N,N-dimethylformamide. 180 mg of N-3,4-dihydropyrimidine-2-yl) [1-methyl-4- ((morpholin-4-oxo) -6-hydropyrimidine-1-yl] is obtained in the form of a white solid with the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The following is a list of the most commonly used methods of measuring the mass of a liquid: 3,33 (s, 3H) ; 3,39 (m, 4H) ; 3,58 (m, 4H) ; 3,91 (s, 2H) ; 5,36 (s, 1H) ; 7,26 (m, 1H) ; 7,39 (q, J=9,5 Hz, 1H) ; 7,73 (ddd, J=2,2 and 7,5 and 13,0 Hz, 1H) ; 10,43 (s, 1H) :Mass spectrometry method ATemps of retention Tr (min) = 0,69[M+H]+ : m/z 365 [M-H]-: m/z 363

The following is the list of active substances in the active substance:

The product is prepared as described in Example 5 from 200 mg of [1-methyl-4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl] sodium acetate prepared in Step 1 of Example 68, 174 mg of 2,3-dihydro-1H-indole, and 185 mg of N-[3-dimethylamino) propyl]-N'-ethylcarbodiimide chloride in a mixture of 0.12 mL of pyridine and 3 mL of N,N-dimethylformamide. After heating on a silicon column, the solid is purified by CH2Cl2/OH, 93/07 Me, the solid is recrystallized by 4 mL of methanol and acetone. The suspension is heated to a temperature of 80 °C, then the solid is recrystallized and filtered at a temperature of 20 °C.52 mg of 2-[2-(2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-3-methyl-6-(morpholin-4-yl)pyrimidine-4(3H) -one is obtained in the form of white crystals having the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The following are the methods used to determine the mass spectrometry: mass spectrometry: method AT retention time Tr (min) = 0,

The following is the list of active substances in the active substance:

The product is prepared as described in Example 5 from 200 mg of [1-methyl-4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl] sodium acetate prepared in Step 1 of Example 68, 199 mg of 3-bromo-4-fluoroaniline, and 228 mg of N-[3-dimethylamino) propyl]-N'-ethylcarbodiimide chlorate in a mixture of 1.5 mL pyridine and 1.5 mL N,N-dimethylformamide. 185 mg of N- ((3-bromo-4-dihydropyrimidine-2-yl) [1-methyl-4-morpholin-4-oxo-1-hydropyrimidine-1-yl] in the form of a white solid are obtained, which have the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The method of measurement is based on the following equations: 3,34 (s, 3 H) ; 3,39 (m, 4 H) ; 3,58 (m, 4 H) ; 3,91 (s, 2 H) ; 5,36 (s, 1 H) ; 7,30 to 7,38 (t, J=8,9 Hz, 1 H) ; 7,48 (ddd, J=2,7 and 4,4 and 8,9 Hz, 1 H) ; 7,99 (dd, J=2,7 and 6,4 Hz, 1 H) ; 10,40 (s, 1 H) Mass spectrometry: method Retention time Tr (min) = 0,76 [M+H]+ : m/z 425 ; [M-H]-Point m/z 423 melting (Kofler): greater than 262°C.

The following is the list of active substances in the active substance:

The product is prepared as described in Example 5 from 250 mg of [1-methyl-4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]sodium acetate prepared in Step 1 of Example 68, 184 mg of (5-amino-2-fluorophenyl) methanol, and 285 mg of N-[3-dimethylamino) -propyl]-Nethylcarbodiimide chlorhydrate in a mixture of 2 mL pyridine and 2 mL N,N-dimethylformamide. 157 mg of N-[4-fluoro-3-dihydropyrimidine-2-yl][4-methyl-4-methyl-4-methyl-1-fluorophenyl] is obtained, the following characteristics of which are given below: The spectrum of the NMR is 1 H (400 MHz):3,34 (s, 3 H) ; 3,40 (m, 4 H) ; 3,59 (m, 4 H) ; 3,90 (s, 2 H) ; 4,52 (d, J=5,6 Hz, 2 H) ; 5,27 (t, J=5,6 Hz, 1 H) ; 5,35 (s, 1 H) ; 7,08 (t, J=9,3 Hz, 1 H) ; 7,43 to 7,53 (m, 1 H) ; 7,64 (dd, J=2,7 and 6,6 Hz, 1 H) ; 10,23 (s, 1 H) Mass spectrometry: AT method Retention time (min) = 0,49 [M+H] : m/z 377+ [M-H] / 375 m /z 375 m (Kfler) ; 22°C to higher

The following is the list of active substances in the active substance:

The product is prepared as described in Example 5 from 200 mg of [1-methyl-4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl] sodium acetate prepared in Step 1 of Example 68, 194 mg of 3-cyclopropyleaniline (prepared according to Wallace et al. in Tetrahedron Lett. 2002, 43, 6987), and 185 mg of N-[3-dimethylamino) propyl]N'-ethylcarbodiimide chloride in a mixture of 0.12 mL pyridine and 4 mL N,N-dimethyl-2-amide. After extraction of the purification acetate from a white residue, the following characteristics are obtained: CH2-OH, CH2-OH, CH2-OH, N2-methyl-4-methyl-2-amide, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH2-OH, CH-OH, CH2-OH The following shall be used for the calculation of the maximum value of the measurement of the measured value:The measurements shall be performed at a frequency of ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1 Hz, ± 1

The following is the list of active substances in the active substance:

The product is prepared as described in Example 5 from 200 mg of [1-methyl-4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl] sodium acetate prepared in Step 1 of Example 68, 205 mg of 4-fluoro-3-methoxyaniline, and 185 mg of N-[3-dimethylamino) propyl]-N'-ethylcarbodiimide chlorate in a mixture of 0.12 mL pyridine and 3 mL N,N-dimethylformamide. After extraction in ethyl acetate and solidification on white silica column, the following residues are obtained: CH2Cl2O2-methyl, CH2OH5O1-methyl, CH5O5-methyl, CH5O5-methyl, CH5O5-methyl, CH5O5-methyl, CH5O4-methyl, CH5O4-methyl, CH5O4-methyl, CH5O4-methyl, CH5O4-methyl, CH5O4-methyl, CH5O4-methyl, CH5O4-methyl, CH5O4-methyl, CH5O4-methyl, CH5O4-methyl, CH5O4-methyl, CH5O4-methyl, CH5O4-methyl, CH5O4-methyl, CH5O4-methyl, CH5O4-methyl, CH5O4-methyl, CH5O4-methyl, CH5O4-methyl, CH5O4-methyl, CH5O4-methyl, CH5O4-methyl, CH5O4-methyl, CH5O4-methyl, CH5O4-methyl, CH5O2-methyl, CH5O2-methyl, CH5O2-methyl, CH5O2-methyl, CH5O2-methyl, CH5O2-methyl, CH5O2-methyl, CH5O2-methyl, CH5O2-methyl, CH5O2-methyl, CH4O2-methyl, CH4O2-methyl, CH4O2-methyl, CH4O2-methyl, CH4O2-methyl, CH4O2-methyl, CH4O2-methyl, CH4O2-methyl, CH4O2-meth The measurement of the mass of the sample is performed by measuring the mass of the sample and the sample is measured by measuring the mass of the sample and the sample is measured by measuring the mass of the sample.

The following is the list of active substances in the active substance:

The product is prepared as described in Example 5 from 250 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium, 178 mg of 1-benzofuran-4-amine, 300 mg of N-[3- ((dimethylamino) propyl) -N'-ethylcarbodiimide hydrochloride in a mixture of 2 mL pyridine and 3 mL of N,N-dimethylformamide. 275 mg of 2-[1-methyl-4-(morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]N-phenylacetamide is obtained as a white solid with the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The following are the methods used for the determination of the mass spectrometry: mass spectrometry: method BT retention time: Tr (min) = 2.96 [M+H]+ m/z 355 ; method BT [M-H]-m/z 353 Melting point (Kofler): greater than 260°C

The following is the list of active substances in the active substance:

The product is prepared as described in Example 5 from 200 mg of [1-methyl-4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]sodium acetate prepared in Step 1 of Example 68, 134 mg of aniline, and 180 mg of N-[3-dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 0.12 mL pyridine and 2.5 mL N,N-dimethylformamide. 95 mg of 2-[1-methyl-4-(morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-]N-amylamide-lacethylene is obtained as a solid with the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The following is a list of the most commonly used methods of measuring the mass of a liquid: 3,35 (s, 3 H) ; 3,41 (m, 4 H) ; 3,58 (m, 4 H) ; 3,91 (s, 2 H) ; 5,35 (s, 1 H) ; 7,06 (t, J=7,8 Hz, 1 H) ; 7,31 (t, J=7,8 Hz, 2 H) ; 7,55 (d, J=7,8 Hz, 2 H) ; 10,19 (s, 1 H) :Mass spectrometry method BTRetention time Tr (min) = 2,87[M+H]+ : m/z 329 ; [M-H]-: m/z 327

The following is the list of active substances in the active substance:

Stage 1

To a 950 mg solution of 3-bromo-4-fluoroaniline in 20 mL tolene under agitation and argon, add 558 mg of cyclopropylboronic acid, 3.7 g of potassium tribasic phosphonate, 70 mg of tricyclohexylphosphane and 56 mg of palladium diacetate in 1.5 mL of water. The mixture is degassed and then heated to 100°C. After 15 hours, the reaction medium is cooled to a temperature of 20°C, then heated in 100 mL of water, then extracted four times from 60 mL of diethyl oxide. The following organic phases are obtained by seeping on magnesium sulphate, filtered and reduced in the form of marble. The residues are purified on a concentrated solution of cyclopropyl acrylate, containing 70 mg/m3 of diethyl sulphate: The test shall be carried out on the test vessel in accordance with the requirements of paragraphs 6.2.3.3 and 6.2.3.4 of this annex.

Stage 2

The product is prepared as described in Example 5 from 200 mg of [1-methyl-4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl] sodium acetate prepared in Step 1 of Example 68, 220 mg of 3-cyclopropyl-4-fluoroaniline, and 180 mg of N-[3-dimethylamino) propyl]-N'-ethylcarbodiimide chlorate in a mixture of 0.12 mL of pyridine and 2.5 mL of N,N-dimethylformamide. After extraction with ethyl acetate and pre-purification on the following solid silica column: CH2Cl2/MeOH-10, the residue is recovered by 10 mL of dihydroxypropyl-N-dimethyl-propyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl- The following shall be used for the calculation of the frequency of the radio frequency spectrum: 0,The following are the values of the measurements to be performed: 57 to 0.66 (m, 2 H) ; 0.94 to 1.03 (m, 2 H) ; 1.93 to 2.08 (m, 1 H) ; 3.33 (s, 3 H) ; 3.37 to 3.42 (m, 4 H) ; 3.55 to 3.62 (m, 4 H) ; 3.87 (s, 2 H) ; 5.35 (s, 1 H) ; 7.07 (dd, J=8.8 and 10.3 Hz, 1 H) ; 7.16 (dd, J=2.6 and 7.0 Hz, 1 H) ; 7.29 to 7.38 (m, 1 H) ; 10.16 (s, 1 H) Mass spectrometry: BT method Retention time (min) = 3,

The following is the list of active substances in the active substance:

The product is prepared as described in Example 5 from 500 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium, 357 mg of 2-amino-6-fluorophenol, 600 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 4 mL pyridine and 4 mL of N,N-dimethylformamide. 335 mg of N- ((4- ((morpholin-4-dihydropyrimidine-2-yl) -2-oxo-1,6-dihydropyrimidine-2-acetamide is obtained in the form of a beige solid with the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The method of measurement is based on the following equations: 3,44 (m, 4 H) ; 3,62 (m, 4 H) ; 3,71 (s, 2 H) ; 5,21 (s, 1 H) ; 6,78 (dt, J=6,0 and 8,1 Hz, 1 H) ; 6,94 (t wide, J=8,1 Hz, 1 H) ; 7,64 (d wide, J=8,1 Hz, 1 H) ; 9,55 to 10,10 (m spread, 2 H) ; 11,69 (m spread, 1 H) Mass spectrometry: method BT Retention time (min) = 2,66[M+H]+ : m/z 349 ; [M-H]- m/z 347 melting point (Kofler) at: 260°C or higher:

The following is a list of the active substances in the active substance:

The product is prepared as described in Example 5 from 261 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium, 274 mg of 4-fluoro-2,3-dihydro-1H-indole, 254 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 0.16 mL pyridine and 4 mL of N,N-dimethylformamide. 249 mg of 2-[2- ((fluoro-2,3-dihydropyrimidine-1-H-indol-1-oxo-2-yl) -6-morpholin-4-dimethyl-4-hydro-4H-indole) are obtained in the form of a white solid with the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The following are the main characteristics of the product: the characteristics of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality of the product, the quality, the quality of the product, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality, the quality,

The following is a list of the active substances in the active substance:

The product is prepared as described in Example 5 from 261 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium, 307 mg of 4-chloro-2,3-dihydro-1H-indole, 254 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 0.16 mL pyridine and 4 mL of N,N-dimethylformamide . 247 mg of 2-[2- ((chloro-2,3-dihydro-1H-indol-1-oxo-2-yl) -morpholine-4-dimethyl-4-hydropyrimidine-4-H) in a white solid form are obtained, which have the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The following are the main components of the test method: 3,18 (t, J=8,4 Hz, 2 H) ; 3,41 (m, 4 H) ; 3,60 (m, 4 H) ; 3,76 (s, 2 H) ; 4,20 (t, J=8,4 Hz, 2 H) ; 5,21 (s, 1 H) ; 7,09 (d, J=8,1 Hz, 1 H) ; 7,22 (t, J=8,1 Hz, 1 H) ; 7,97 (d, J=8,1 Hz, 1 H) 11,62 (s wide, 1 H) ; Mass spectrometry: method BT Retention time (min) = 3,46 ; [M+H]+ : m/z 375 [M-H]-m/z 373 Melting point (Kofler): greater than 260°C:

The following is the list of active substances in the active substance:

Step one:

After 4 hours and 30 minutes at 100°C, the reaction medium is cooled and the insoluble is filtered on a sintered glass. The filtrate is concentrated under reduced pressure. After two purifications on an eluting column of Acce Silica: Heptane/AcO, 90/10 Heptane/O, 95/5, 460 of these solids are obtained: Mass spectrometry: spectra were obtained by direct introduction on a WATERS GCTof apparatus (direct introduction without LC):El: [M]+. m/z 237; base peak: m/z 222

Stage 2

After three and a half hours of reflux, the medium is cooled and then filtered on silica, dry concentrated at reduced pressure. The residue is taken up by diethyl oxide, the insoluble filtered and then the concentrated wire at reduced pressure. 370 mg of 4-fluoro-3-[trimethyl]ethyl]aniline is obtained in the form of a hydrate, the characteristics of which are as follows: Mass spectrometry: method ATTemps of retention Tr (min) = 1.11[M+H]+: m/z 208; base peak: m/z 249

Stage 3

After a night's agitation under argon and at a temperature of about 20°C, the medium is concentrated dry under reduced pressure and then taken up again in 8 mL of water, neutralized with a few drops of hydrochloric acid (1 N) extracted three times by diethyl oxide. The combined organic phases are dried on anhydrous magnesium sulfate, filtered and concentrated dry under diethyl pressure. 225 mg of 3-thynyl-fluoroaniline is obtained in the form of a brown oil with the following characteristics: The test chemical is used to determine the concentration of the test chemical in the test medium.

Stage 4

The product is prepared as described in Example 5 from 204 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium, 211 mg of 3-ethynyl-4-fluoroaniline, 195 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide chlorhydrate in a mixture of 0.126 mL of pyridine and 3 mL of N,N-dimethylformamide. 200 mg of N-3-ethynyl-4-fluoroethinyl) -2-[4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-acetamide are obtained as a white solid with the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The method of measurement is based on the following equations: 3,41 (m, 4 H) ; 3,60 (m, 6 H) ; 4,48 (s, 1 H) ; 5,20 (s, 1 H) ; 7,27 (t, J=9,0 Hz, 1 H) ; 7,56 (m, 1 H) ; 7,78 (dd, J=1,5 and 5,9 Hz, 1 H) ; 10,31 (m spread, 1 H) ; 11,66 (m spread, 1 H) Mass spectrometry: method AT Retention time Tr (min) = 0,75[M+H]+: m/z 357 ; [M-H]-: m/z 355 Melting point (Kofler): greater than 260°C

The following is a list of the active substances in the active substance:

The product is prepared as described in Example 5 from 261 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium, 270 mg of 2,3-dihydro-1H-indol-4-ol, 254 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 0.16 mL pyridine and 4 mL of N,N-dimethylformamide. 205 mg of 2-[2- ((hydroxy-2,3-dihydro-1H-indol-1-yl) -2-oxoethyl]-6- ((morpholin-4-dimethyl) pyrimidine-4-H3)) is obtained in the form of a solid with the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The method of mass spectrometry is as follows: retention time Tr (min) = 0.57 M+H+: 357 m/z [M-H]-: 355 m/z 355 melting point (Kofler): greater than 260°C.

The following is a list of the active substances in the active substance:

The product is prepared as described in Example 5 from 261 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium, 310 mg of 4,6-difluoro-2,3-dihydro-1H-indole, 254 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 0.16 mL of pyridine and 4 mL of N,N-dimethylformamide . 225 mg of 2-[2- ((fluoro-4,6-dihydropyrimidine-2,3-dihydro-1H-indol-1-yl) -2-oxo-2-morphyl]-6-(dimethyl-dimethyl-4H-indol) in a white solid is obtained, the characteristics of which are as follows: The following shall be used for the calculation of the frequency range: The method of mass spectrometry: retention time Tr (min) = 0.73 [M+H]+: m/z 377; [M-H]-: m/z 375 melting point (Kofler): greater than 260°C. The method of mass spectrometry is based on the following equation:

The following is the list of active substances in the active substance:

The product is prepared by following the procedure described in Example 68 from 200 mg of [1-methyl-4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium and 210 mg of 3-iodo-4-fluoroaniline. 186 mg of N-(3-iodo-4-fluorophenyl)-2-[1-methyl-4-(morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetamide is obtained as a white solid with the following characteristics: The frequency range of the measurement is defined as the frequency range of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measur

The following is a list of the active substances in the active substance:

The product is prepared as described in Example 5 but starting from 261 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl] sodium acetate prepared in Step 2 of Example 1, 383 mg of 4.5-difluoro-2,3-dihydro-1H-indole hydrochloride, 254 mg of N-[3- ((dimethylamino) propyl]'-Nethylcarbodiimide hydrochloride in a mixture of 0.32 mL pyridine and 4 mL N,N-dimethylamide. 210 mg of 2- ((4- ((dihydropyrimidine-2-yl) -1-dihydro-2,3-dihydro-1-dihydro-2-oxo-2-yl) -6-)) - ((dimethylamino) -4-propyl) -4-morphyl) -H-4-hydroxylamide are obtained in powdered form, the solid characteristics of which are as follows: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The following are the methods used for the determination of the mass spectrometry: retention time; method Tr (min) = 3.30; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT; method BT

The following is a list of the active substances in the active substance:

The product is prepared as described in Example 5 but starting from 200 mg of (4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium prepared in Step 2 of Example 1, 210 mg of 6-fluoro-2,3-dihydro-1H-indole, 194 mg of N-[3-dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 0.12 mL pyridine and 3 mL N,N-dimethylformamide. 184 mg of 2-[6- ((fluoro-2,3-dihydropyrimidine-1-H-indol)-2-oxo-2-ethyl]-6- ((dimethyl-4-hydropyrimidine-4-H) is obtained, which has the following characteristics: The following shall be used for the calculation of the frequency of the radio frequency spectrum: The following are the methods used for the determination of the mass spectrometry: 3,14 (t, J=8,3 Hz, 2 H) ; 3,37 to 3,45 (m, 4 H) ; 3,54 to 3,64 (m, 4 H) ; 3,76 (s, 2 H) ; 4,19 (t, J=8,3 Hz, 2 H) ; 5,21 (s, 1 H) ; 6,83 (dt, J=2,0 and 8,6 Hz, 1 H) ; 7,19 to 7,31 (m, 1 H) ; 7,77 (dd, J=2,6 and 10,8 Hz, 1 H) ; 11,61 (m spread, 1 H) Mass spectrometry: method ATTemps of retention (min) ; Tr = 0,67[M+H]: m/z 359 + [M-H]-m/z 357 Melting point (Kofler): greater than 260°C

The following is the list of active substances in the active substance:

The product is prepared as described in Example 5 from 500 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium, 510 mg of 2-methyl-2,3-dihydro-1H-indole, 487 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 0.308 mL pyridine and 8 mL of N,N-dimethylformamide. 400 mg of 2-[2- ((methyl-2,3-dihydro-1H-indol-1-oxo-2-morphyl]-6- ((methyl-2,3-dimethyl) pyrimidine-4-H3)) is obtained in the form of a white powder with the following characteristics: The frequency range of the NMR is 1 H (400 MHz):1,26 (d, J=6,1 Hz, 3 H) ; 2,65 to 2,72 (m, 1 H) ; 3,18 to 3,44 (m partially masked, 5 H) ; 3,54 to 3,63 (m, 4 H) ; 3,72 (d, J=15,7 Hz, 1 H) ; 3,92 (d, J=15,7 Hz, 1 H) ; 4,71 (m, 1 H) ; 5,20 (s, 1 H) ; 7,04 (t, J=7,8 Hz, 1 H) ; 7,18 (t, J=7,8 Hz, 1 H) ; 7,29 (d, J=7,8 Hz, 1 H) ; 7,96 (d, J=7,8 Hz, 1 H) 11,69 (m-scaled, 1 H) ; Mass spectrometry: method of retention: 0,70 m; M-Tz = 35°; M-Tz = 35°; M-Tz = 170 m (M+H) ; M-Tz = 35° (M-C) [M-C]

The following is the list of active substances in the active substance:

The product is prepared following the procedure described in Example 5 but starting from 275 mg of [1-methyl-4- ((morpholine-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]sodium acetate prepared in Step 1 of Example 68, 322 mg of 3- ((difluoromethyl) -4-fluoroaniline (Step 76 Example 2), and 250 mg of N-[3- ((dimethyl) -amino) propyl) -N'-ethylcarbodiimide chlorate in a mixture of 0.16 mL pyridine and 4 mL N,N-dihydropyrimidine-2-yl. 98 mg of N-[3- ((dihydropyrimidine-4-fluoropyrimidine-2-yl) -amino[1- ((dihydropyrimidine-4-hydropyramid-2-yl-1-yl-1-yl-1-oxo-4-acetyl) -amino-2-yl) are obtained in the following solid form: The frequency range of the measurement is defined as the frequency range of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measur

The following is the list of active substances in the active substance:

The product is prepared as described in Example 68 from 200 mg of [1-methyl-4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl] sodium acetate, 214 mg of 3,4,5-trifluoroaniline, 180 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 0,12 mL pyridine and 2,5 mL N,N-dimethylformamide. 72 mg of 2-(1-methyl-4-morpholin-4-yl-6-oxo-1,6-dihydro-pyrimidine-2-yl) -N-(3,4,5-trifluoro-nyl) acetate is obtained in a solid form with the following characteristics: The frequency range of the radio spectrum is defined as the frequency range of the radio spectrum, which is the frequency range of the radio spectrum.

The following is the list of active substances in the active substance:

To a 250 mg solution of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium prepared in step 2 of example 1 in 2 mL of N,N-dimethylformamide, 2 mL of pyridine, 300 mg of N-[3- ((dimethyl) amino) propyl]-N'-ethylcarbodiimide chloride and 272 mg of 1-methyl-1H-indol-4-ylamine are added to a 250 mg solution. The reaction mixture is agitated at room temperature for 15 hours, then reduced in concentrated pressure. The frequency range of the NEMS is defined as the frequency range of the NEMS, which is the frequency range of the NEMS.

The following is a list of the active substances in the active substance:

The product is prepared as described in Example 5 from 261 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium, 339 mg of 4-methyl-indoline hydrochloride, 254 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 241 μL of pyridine and 4.0 mL of N,N-dimethylformamide. 22 mg of 2-[2- ((methyl-2,3-dihydro-1H-indol-1-yl) -2-oxoethyl]-6- ((morpholin-4-dimethyl) -4-propyl-4-H3)) is obtained in the form of a crystalline powder with the following characteristics: The frequency range of the NFM is defined as the frequency range of the frequency range of the NFM 1 H (400 MHz): 2.21 (s, 3 H) ; 3.08 (t, J=8.3 Hz, 2 H) ; 3.42 (m, 4 H); 3.61 (m, 4 H) ; 3.75 (s, 2 H) ; 4.15 (t, J=8.3 Hz, 2 H) ; 5.20 (s, 1 H) ; 6.85 (d, J=8.0 Hz, 1 H) ; 7.07 (t, J=8.0 Hz, 1 H) ; 7.85 (d, J=8.0 Hz, 1 H) ; 11.62 (m spread, 1 H) Mass spectrometry: BT method Retention time Tr (min) = 3.31[M+H] +: m/z 355 [M-H] +: m/z 353 Fusion point (K) ; higher than 260°C;

The following is a list of the active substances in the active substance:

The product is prepared as described in Example 5 from 500 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl) sodium acetate, 170 mg of 3-methyl-indoline, 487 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide chloride hydrate in a mixture of 310 μL pyridine and 6,0 mL of N,N-dimethylformamide. 367 mg of 2-[2- ((methyl-2,3-dihydro-1H-indol-1-yl) -2-oxoethyl) -6-sub-morpholin-4-dimethyl) -4-pyrimidine-4-H-one is obtained in a white crystalline powder with the following characteristics: The frequency range of the NEMS is defined as the frequency range of the radio spectrum, measured at the frequency bands of the frequency spectrum, and the frequency range of the radio spectrum.

The following is a list of the active substances in the active substance:

The product is prepared as described in Example 68 from 275 mg of [1-methyl-4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium, 274 mg of 4-fluoro-indoline, 254 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide chlorhydrate in a mixture of 161 μL pyridine and 4.0 mL of N,N-dimethylformamide. 102 mg of 2-[2- ((4-fluoro-2,3-dihydro-1H-morphol-1-) -2-oxo-indyl]-3-methyl-6- ((dimethyl-4-dimethyl) pyrimidine-4-propyl) -H-morphone is obtained in the form of a pink powder with the following characteristics: The frequency range of the radio spectrum is defined as the frequency range of the radio spectrum, measured at the frequency bands of the frequency spectrum.

The following is added to the list of substances which are to be used in the preparation of the additive:

The product is prepared as described in Example 5 from 261 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium, 274 mg of 5-fluoro-indoline, 254 mg of N-[3- ((dimethylamino) propyl) -N'-ethylcarbodiimide chloride hydrate in a mixture of 0.16 mL pyridine and 4 mL dimethylamide. 197 mg of 2-[2- ((morpholin-2-yl) -2-dihydro-indol-2-) -3-oxo-ethyl]-6-morpholin-4-dihydropyrimidine-4-one is obtained in a very pale powder form with the following characteristics: The frequency range of the measurement is defined as the frequency range of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measur

The following is a list of the active substances in the active substance:

The product is prepared as described in Example 68 from 275 mg of [1-methyl-4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium, 307 mg of 4-chloro-indoline, 254 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 161 μL pyridine and 4.0 mL of N,N-dimethylformamide. 84 mg of 2-[2- ((chloro-2,3-dihydro-1H-ol-1-) -2-oxo-morphyl]-3-methyl-6- ((dimethyl-4-dimethyl) pyrimidine-4-propyl) -H-morphone is obtained in a slightly powdered form with the following characteristics: The frequency range of the radio spectrum is defined as the frequency range of the radio spectrum, which is the frequency range of the radio spectrum.

The following is the list of active substances in the active substance:

To a 250 mg solution of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl) sodium acetate prepared in step 2 of example 1 in 2 mL of N,N-dimethylformamide, 2 mL of pyridine, 257 mg of N-[3- ((dimethyl) amino) propyl]-N'-ethylcarbodiimide chloride and 223 mg of benzo[B]thiophenylamide-4-ylamine are added to a 250 mg solution. The reaction mixture is agitated at room temperature for 15 hours, then reduced in concentrate. The frequency range of the NFM is defined as the frequency range of the frequency spectrum of the NFM, measured at the frequency of the NFM.

The following is a list of the active substances in the active substance:

The product is prepared as described in Example 5 from 261 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium, 298 mg of 2,3-dihydro-1H-indol-2-yl methanol, 249 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 322 μL of pyridine and 4.0 mL of N,N-dimethylformamide. 212 mg of 2- ((2- (([2-dimethylamidine-2-yl) -2-dihydro-1,3-H-indol]oxo-2-yl)) -6- ((dimethyl-dimethyl-pyrimidine-4-propyl) -N'-ethylcarbodiimide hydrochloride in a pink powder form are obtained, which have the following characteristics: The frequency range of the NEMS is 1.H (400 MHz): 2.86 (d, J=16.1 Hz, 1 H) ; 3.25 (dd, J=8.6 and 16.1 Hz, 1 H) ; 3.34 to 3.43 (m, 5 H) ; 3.51 (m, 1 H) ; 3.60 (m, 4 H) ; 3.81 (d, J=15.9 Hz, 1 H) ; 4.01 (d, J=15.9 Hz, 1 H) ; 4.64 (m, 1 H) ; 5.13 (m wide, 1 H) ; 5.20 (s, 1 H) ; 7.03 (t, J=7.8 Hz, 1 H) ; 7.16 (t, J=7.8 Hz, 1 H) ; 7.26 (d, J=7.8 Hz, 1 H) ; 7.94 (d, J=7.8 Hz, 1 H) ; 11.63 (m H) ; 1.K; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 2.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 2.M; 1.M; 2.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 2.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 1.M; 2.M; 1.M; 2.M; 1.M; 1.M; 1.M; 2.M; 1.M; 1.M;

The following is the list of active substances in the active substance:

The product is prepared as described in Example 5 from 250 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetate sodium, 303 mg of 2- ((2-pipéridine-1-yl-ethoxy) -phenylamine, 300 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 2 mL pyridine and 2 mL dimethylformamide. 255 mg of 2- ((4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl) -N2- ((2- ((piperidine-1-yl) -ethoxyphenyl) acetate is obtained in a beige solid with the following characteristics: The frequency range of the NEMS is defined as the frequency range of the NEMS, which is the frequency range of the NEMS, and the frequency range of the NEMS, which is the frequency range of the NEMS.

The following is the list of active substances in the active substance:

To a 250 mg solution of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium prepared in step 2 of example 1 in 2 mL of N,N-dimethylformamide, 2 mL of pyridine, 300 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide chloride and 303 mg of 2- (((2-methylamino-ethylamino) phenylamide are added to a 250 mg solution. The reaction mixture is agitated at room temperature for 15 hours, then concentrated under reduced pressure. The frequency range of the NFM is 1 H (400 MHz) : 3.19 to 3.33 (s partially masked, 3 H) ; 3.43 (m, 4 H) ; 3.61 (m, 4 H) ; 3.67 to 3.72 (m, 4 H) ; 4.16 (t, J=4.5 Hz, 2 H) ; 5.21 (s, 1 H) ; 6.94 (m, 1 H) ; 7.02 to 7.13 (m, 2 H) ; 7.95 (d, J=8.1 Hz, 1 H) ; 9.25 (s, 1 H) ; 11.67 (m spread, 1 H) Mass spectrometry: BT method Retention time (min) = 3.00[M+H] +: m/z 387 [M-H] +: m/z 389

The following is a list of the active substances in the active substance:

The product is prepared as described in Example 68 from 275 mg of [1-methyl-4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl) sodium acetate, 270 mg of indoline-4-ol, 254 mg of N-[3-{dimethylamino) propyl]-N'-ethylcarbodiimide chlorhydrate in a mixture of 161 μL pyridine and 4.0 mL of N,N-dimethylformamide. 85 mg of 2-[2-hydroxy-2,3-dihydro-1H-ol-1-) 2-oxo-2-morphyl]-3-methyl-6- ((dimethyl-4-dimethylpropyl) pyrimidine-4-H3 (((morpholine) is obtained in the form of a powder with the following characteristics: The frequency range of the NFM is defined as the frequency range of the frequency range of the NFM 1 H (400 MHz): 3,01 (t, J=8,6 Hz, 2 H) ; 3,31 (s masked, 3 H) ; 3,40 (m, 4 H) ; 3,58 (m, 4 H) ; 4,07 (s, 2 H) ; 4,16 (t, J=8,6 Hz, 2 H) ; 5,36 (s, 1 H) ; 6,50 (d, J=8,2 Hz, 1 H) ; 6,97 (t, J=8,2 Hz, 1 H) ; 7,49 (d, J=8,2 Hz, 1 H) ; 9,47 (s wide, 1 H) Mass spectrometry: AT method Retention time (min) = 0,49[MH] +: m/z 371+ [M-H] : m/z 369 m (K) of melting point: higher than 260 °C;

The following is a list of the active substances in the active substance:

The product is prepared as described in Example 68 from 275 mg of [1-methyl-4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl) sodium acetate, 298 mg of 4-methoxy-indoline, 254 mg of N-[3-dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 161 μL pyridine and 4.0 mL of N,N-dimethylformamide. 107 mg of 2-[2-(methoxy-2,3-dihydro-1H-indol-1-yl) saxo-2-ethyl]-3-methyl-6- ((morpholin-4-dimethyl) pyrimidine-4-H3 ((H3)) saxo-hydride is obtained in a powdered form with the following characteristics: The frequency range of the radio spectrum is defined as the frequency range of the radio spectrum, measured at the frequency bands of the frequency spectrum, and the frequency range of the radio spectrum measured at the frequency bands of the frequency spectrum.

The following is a list of the active substances in the active substance:

The product is prepared as described in Example 70 from 304 μL of 1,2,3,4-tetrahydroisoquinoline, 300 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]ethyl acetate prepared in Step 1 of Example 1 and 1,3 mL of a 2M trimethyl aluminium solution in a mixture of 21 mL of toluene and 10 mL of tetrahydrofuran, in a mixture of which 130 mg of 2-[2- (((3,4-dihydroisoquinoline-2-(1 H) -yl) 2-oxoethyl]-6- ((morpholin-4-yl) -pyrimidine-4- ((3H) -one in the form of a white meringue has the following characteristics: The frequency range of the signal is approximately 1 H (400 MHz) for this batch, all signals are broad with: 2.86 (m, 2 H) ; 3.33 (m, 4 H) ; 3.56 (m, 4 H) ; 3.72 (m, 4 H) ; 4.67 (s, 2 H) ; 5.13 (s, 1 H) ; 7.18 (s, 4 H) ; 11.23 (m spread, 1 H) : Mass spectrometry method ATT Retention time Tr (min) = 0.62 ; [M+H]+ : m/z 355 ; [M-H]- : m/z 353 Fusion point (Kofler) 107.5°C:

The following is a list of the active substances in the active substance:

To a 250 mg solution of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl) sodium acetate prepared in step 2 of example 1 in 2 mL N,N-dimethylformamide, add 2 mL of pyridine, 300 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride and 273 mg of 2-(2-pyrrolidine-1-yl-ethoxy) phenylamine. The reaction mixture is agitated at room temperature for 2 days, then concentrated under reduced pressure.

After purification on a silica column by elevating by a mixture of dichloromethane and methanol (95/05 by volume), 45 mg of 2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidine-2-yl]-N-{2-[2-(pyrrolidin-1-yl) ethoxy]phenyl}acetamide is obtained as a white solid with the following characteristics: The frequency spectrum of the NMR is defined as the frequency range of the frequency spectrum of the radio frequency spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spe

The following is the list of active substances in the active substance:

To a 250 mg solution of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium prepared in step 2 of example 1 in 2 mL of N,N-dimethylformamide, 2 mL of pyridine, 300 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride, and 366 mg of 2- ((pyridin-3-methylmethoxy) -phenylamine are added to a 250 mg solution. The reaction mixture is agitated at room temperature for 20 hours, concentrated under reduced pressure. 1 H (400 MHz) NMR spectrum: all signals are broad with: 3,The following are the values of the measurements to be performed: 37 (m, 4 H) 3,55 (m, 4 H) ; 3,70 (s, 2 H) ; 5,19 (s, 1 H) ; 5,26 (s, 2 H) ; 6,93 (t, J=7,6 Hz, 1 H) ; 7,07 (t, J=7,6 Hz, 1 H) ; 7,14 (d, J=7,6 Hz, 1 H) ; 7,40 (m, 1 H) ; 7,88 (m, 2 H) ; 8,53 (d, J=5,2 Hz, 1 H) ; 8,70 (s, 1 H) 9,47 (s, 1 H) ; 11,66 (m spread, 1 H) Mass spectrometry: AT method Retention thresholds (min) = 0,

The following is a list of the active substances in the active substance:

The product is prepared as described in Example 68 from 275 mg of [1-methyl-4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium, 339 mg of 4-methyl-indoline hydrochloride, 254 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 240 μL of pyridine and 4.0 mL of N,N-dimethylformamide. 93 mg of 3-methyl-2-[2-4-thyl-2,3-dihydro-1H-indol-1-) -2-oxo-methyl]-6- ((morpholin-4-dimethyl) pyrimidine-4-H3 ((H3)) is obtained in the form of a powder with the following characteristics: The frequency range of the radio spectrum is defined as the frequency range of the radio spectrum in the frequency spectrum of the vehicle.

The following is a list of the active substances in the active substance:

Stage 1

The reaction medium is thrown into 50 g of ice and alkalized by 30% soda, then extracted by four times 30 mL of ethyl acetate. The organic phase is then washed with 20 mL of water, dried on magnesium sulphate, filtered dry at reduced pressure in concentrated form. After collation on electrolytic silicon: Cl22/MeCH, 85/15v/OH, the following characteristics are obtained: 6-1,360 mg (2-3,3H-hydroxymethyl-dimethyl-methyl) anhydride: Mass spectrometry: method ATTemps of retention Tr (min) = 0.16; mixing with expected[M+H]+: m/z 177

Stage 2

The product is prepared as described in Example 5 from 220 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium, 300 mg of (2,3-dihydro-1H-indol-3-yl-methyl) -dimethyl-amine, 210 mg of N-[3- ((dimethylamino) propyl) -N'-ethylcarbodiimide hydrochloride in a mixture of 0,14 mL of pyridine and 2,5 mL of N,N-dimethylformamide. 206 mg of 2-[2- ((dimethylaminomethyl-2,3-dihydro-1-indol-2-oxo-2-oxo-ethyl]-6-dimethyl-4-phyl-3-Hyropyrimidine-4-morphol) are obtained, which have the following characteristics: The frequency range of the NEMS is defined as the frequency range of the radio spectrum, which is the frequency range of the radio spectrum, and the frequency range of the radio spectrum, which is the frequency range of the radio spectrum.

The following is a list of the active substances in the active substance:

The product is prepared as described in Example 68 from 275 mg of [1-methyl-4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium, 352 mg of 4-bromo-indoline hydrochloride, 254 mg of N-[3-dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 201 μL pyridine and 4.0 mL of N,N-dimethylformamide. 161 mg of 2-[2-(bromo-2,3-dihydro-1H-indol-1-yl) -2-oxoethyl]-3-methyl-6- ((morpholin-4-dimethyl) pyrimidine-4-H3 ((H3)) is obtained in the form of a pink powder with the following characteristics: The frequency range of the radio spectrum is defined as the frequency range of the radio spectrum in the frequency spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum

Examples 117 and 118 : Separation of 2-{2-[(2S)-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(morpholin-4-yl)pyrimidine-4(3H) -one and 2-{2-[(2R)-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(morpholin-4-yl)pyrimidine-4(3H) -one

The products were obtained by chiral chromatographic separation of 311 mg of 2-{2-[(2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(morpholin-4-yl) pyrimidine-4(3H) -one (Example 96) on chiral column Chiralpak T304 20 μm (1080 g, 20 μm, 8/35 cm), with elution: Acetonyl/Isopropanol : 90/10; flow rate: 185 mL/min. After purification, 160 mg of (+) {2-[(2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-4-morpholin-4-morphyl) amorphimidine-4H3 (H) is obtained as the first enantiomer in the form of a solid with the following characteristics: The signal spectrum is 1 H (400 MHz): for this batch the signals are broad with: 1.26 (d, J=6.8 Hz, 3 H) ; 2.44 (m partially masked, 1 H) ; 2.69 (d, J=15.2 Hz, 1 H) ; 3.42 (m, 4 H) ; 3.60 (m, 4 H) ; 3.72 (d, J=15.7 Hz, 1 H) ; 3.92 (d, J=15.7 Hz, 1 H) ; 4.72 (m, 1 H) ; 5.20 (s, 1 H) ; 7.04 (t, J=7.8 Hz, 1 H) ; 7.18 (t, J=7.8 Hz, 1 H) ; 7.28 (d, J=7.8 Hz, 1 H) ; 7.96 (d, J=7.8 Hz, 1 H) ; 11.67 (m), 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1 m; 1

Then the second enantiomer, namely: 143 mg of (-)-2-{2-[(2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(morpholin-4-yl)pyrimidine-4(3H) -one in the form of a white amorphous solid having the following characteristics: The signal spectrum is broad with: 1.26 (d, J=6.8 Hz, 3 H) ; 2.45 (m partially masked, 1 H) ; 2.69 (m, 1 H) ; 3.41 (m, 4 H) ; 3.61 (m, 4 H) ; 3.72 (d, J=15.7 Hz, 1 H) ; 3.92 (d, J=15.7 Hz, 1 H) ; 4.70 (m, 1 H) ; 5.20 (s, 1 H) ; 7.04 (t, J=7.8 Hz, 1 H) ; 7.18 (t, J=7.8 Hz, 1 H) = 7.28 (d, J=7.8 Hz, 1 H) ; 7.96 (d, J=7.8 Hz, 1 H) ; 11.64 (m, 1 L) ; Masometry: H; Spectral range: H; +/- 0.5 m; Rotation: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter: Meter

The following is a list of the active substances in the active substance:

The product is prepared as described in Example 68 from 275 mg of [1-methyl-4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium, 254 mg of 3-methyl-indoline hydrochloride, 254 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 161 μL of pyridine and 4.0 mL of N,N-dimethylformamide. 96 mg of 3-methyl-2-[2-3-methyl-2,3-dihydro-1H-indol-1-) -2-oxo-methyl]-6- ((morpholin-4-dimethyl) pyrimidine-4-H3 ((H3)) is obtained in the form of a powder with the following characteristics: The frequency range of the NEMS is defined as the frequency range of the NEMS, which is the frequency range of the NEMS, and the frequency range of the NEMS, which is the frequency range of the NEMS.

The following is a list of the active substances in the active substance:

The product is prepared as described in Example 5 from 261 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium, 326 mg of 2- ((methoxymethyl) indole, 249 mg of N-[3- ((dimethylamino) propyl) -N'-ethylcarbodiimide hydrochloride in a mixture of 162 μL of pyridine and 4.0 mL of N,N-dimethylformamide. 143 mg of 2-{2-[2- ((methoxymethyl) -2-dihydro-1H-indol-1-yl]oxo-2-ethyl-6- ((morpholin-4-dimethyl) pyrimidine-4-H3)) is obtained in powder form with the following characteristics: The frequency range of the spectrum is defined as the frequency range of the radio spectrum, which is the frequency range of the radio spectrum, and the frequency range of the radio spectrum, which is the frequency range of the radio spectrum.

The following is a list of the active substances in the active substance:

The product is prepared by the procedure described in Example 5 from 261 mg of [4-morpholin-4-yl) -6-dihydropyrimidine-2-yl]acetate of sodium, 163 mg of 4-ethylamino-indoline, 249 mg of N-[3-dimethylamino-propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 162 μL of pyridine and 4.0 mL of N,N-dimethylformamide, starting from 260 mg of 2-[4-morpholin-4-yl]acetate of sodium, 163 mg of 4-ethylamino-indoline, 249 mg of N-[3-dimethylamino-propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 162 μL of pyridine and 4.0 mL of N,N-dimethylformamide, and ending with 260 mg of 2-[2-morpholin-4-yl]acetate of sodium, 163 mg of 4-ethylamino-indoline, 249 mg of N-[3-dimethylamino-propyl]-N-N'-ethylamine-N-N'-N'-ethylamine in a white powder form, the following characteristics: 1 , 1 , 2 , 3 , 3 , 4 , 4 , 4 , 4 , 6 , 6 , 8 , 8 , 8 , 8 , 8 , 8 , 8 , 8 , 8 , 8 , 8 , 8 , 8 , 8 , 8 , 8 , 8 , 8 , 8 , 9 , 9 , 9 , 9 , 9 , 9 , 10 , 10 , 10 , 10 , 11 , 11 , 11 , 12 , 12 , 12 , 12 , 12 , 12 , 12 , 12 , 12 , 12 , 13 , 13 , 13 , 13 , 13 , 13 , 13 , 13 , 13 , 13 , 13 , 14 , 14 , 18 , 18 , 18 , 18 , 18 , 18 , 18 , 19 , 19 , 19 , 19 , 19 , 19 , 19 , 19 , 19 , 19 , 19 , 19 , 19 , 19 , 19 , 19 , 19 , 19 , 19 , 19 , 19 , 19 , 19 , 19 , 19 , 19 , 19 , 19 , 20 , 20 , 20 , 21 , 21 , 21 , 21 , 21 ,

The following is a list of the active substances in the active substance:

The product is prepared as described in Example 5 from 261 mg of [4-morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium, 324 mg of 2-carboxamidine-indoline, 249 mg of N-[3-dimethylamino) propyl]-N'-ethylcarbodiimide chlorhydrate in a mixture of 162 μL of pyridine and 4.0 mL of N,N-dimethylformamide. 93 mg of 1-{4-morpholin-4-yl) -6-dihydropyrimidine-1-yl]acetate is obtained in the form of a white powder with the following characteristics: The frequency range of the NEMS is 1 H (400 MHz): 3,11 (d, J=16,9 Hz, 1 H) ; 3,36 to 3,47 (m, 5 H) ; 3,54 to 3,63 (m, 5 H) ; 3,77 (d, J=15,7 Hz, 1 H) ; 5,07 (dd, J=3,8 and 9,1 Hz, 1 H) ; 5,20 (s, 1 H) ; 7,02 (t, J=7,8 Hz, 1 H) ; 7,18 (t, J=7,8 Hz, 1 H) ; 7,23 (d, J=7,8 Hz, 1 H) ; 7,36 (s wide, 1 H) ; 7,76 (s wide, 1 H) ; 8,01 (d, J=7,8 Hz, 1 H) ; 11,59 (m spread, 1 H) Spectrometry of the higher frequency range: Mass of emission: 0,50 m; (M+K) ; 38 m; (M+H) ; Atz-Point of fusion: 38°C (M) + 260 °C (M)

The following is a list of the active substances in the active substance:

The product is prepared as described in Example 68 from 550 mg of [1-methyl-4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium, 400 mg of 2-methyl-indoline, 500 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 320 μL pyridine and 8,0 mL of N,N-dimethylformamide. 37 mg of 3-methyl[2- ((methyl-2-dimethyl-2,3-dihydro-1H-indol-1-oxoethyl) -6- ((dimethyl-4-morphine-pyrimidine-4-H3)) pyrimidine is obtained in the form of a powder with the following characteristics: The frequency range of the NEMS is 1 H (400 MHz, 1,28 (d, J=6,8 Hz, 3 H) ; 2,70 (d, J=1,5,9 Hz, 1 H) ; 3,23 to 3,30 (s masked, 3 H) ; 3,40 (m, 5 H) ; 3,60 (m, 4 H) ; 4,02 (d, J=16,9 Hz, 1 H) ; 4,29 (d, J=16,9 Hz, 1 H) ; 4,70 (m, 1 H) ; 5,36 (s, 1 H) ; 7,05 (t, J=7,8 Hz, 1 H) ; 7,29 (d, J=7,8 Hz, 1 H); 7,95 (d, J=7,8 Hz, 1 H) AT spectrometry: Masses of retention: 0,75 m; (M+K) ; Spectroscopy: 36 m; (M+H) ; 36 m; (M+K) / 36 m; (M+H) / 36 m (M-Z) [Fusion Point: 36°C]

The following table shows the results of the analysis of the chemical composition of the compound:

The product is prepared as described in Example 68 from 275 mg of [1-methyl-4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl) sodium acetate, 205 mg of 6-fluoro-indoline, 254 mg of N-[3- ((dimethylamino) propyl) -N'-ethylcarbodiimide hydrochloride in a mixture of 161 μL pyridine and 4.0 mL of N,N-dimethylformamide. 140 mg of 2-[2- ((6-morpholin-2,3-dihydro-1H-fluoro-1-ol) -2-oxo-3-methyl) sub-methyl-6- ((morpholin-4-dimethyl) -4-propyl) -H3 is obtained in a very pink powder form with the following characteristics: The frequency range of the radio spectrum is defined as the frequency range of the radio spectrum, measured at the frequency bands of the frequency spectrum, and the frequency range of the radio spectrum measured at the frequency bands of the frequency spectrum.

Examples 125 and 126 : Separation of 2-{2-[(3S) -3-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6- ((morpholin-4-yl) pyrimidine-4(3H) -one and 2-{2-[(3R) -3-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6- ((morpholin-4-yl) pyrimidine-4(3H) -one

The products were obtained by chiral chromatographic separation of 369 mg of 2-{2-[3-methyl-2,3-dihydro-1H-indo)-1-yl]-2-oxoethyl}-6-(morpholin-4-yl) pyrimidine-4(3H) -one (Example 101) on chiral column Chiralpak T304 20 μm (1100 g, 20 μm, 8/35 cm), by the emulsion of: heptane/ethanol/methanol : 25/40/35 ; flow rate: :200 mL/min. After purification, 168 mg of (+)-2-{2-[3-methyl-2,3-dihydro-1H-dihydro-1-indol-1-methyl]-oxoethyl-2-H-powder, in the form of a white powder, with the following characteristics, is obtained as the first enantiomer: The frequency range of the NMR is 1 H (400 MHz) : 1.29 (d, J=6.8 Hz, 3 H) ; 3.42 (m, 4 H) ; 3.49 (m, 1 H) ; 3.60 (m, 4 H) ; 3.68 (dd, J=6.6 and 10.1 Hz, 1 H) ; 3.75 (s, 2 H) ; 4.33 (t, J=10.1 Hz, 1 H) ; 5.21 (s, 1 H) ; 7.04 (t, J=8.0 Hz, 1 H) ; 7.18 (t, J=8.0 Hz, 1 H) ; 7.27 (d, J=8.0 Hz, 1 H) ; 8.01 (d, J=8.0 Hz, 1 H) ; 11.61 (m, 1 H) ; Mass spectrometer: ATL method of emission: 0.72 mL (m) ; +M (m) ; +M (m) +O (m) = 35 mg/L (m) ; +P (m) = 0.565 mL (m) ; +M (m) = 0.565 mL (m) ; +M (m) = 0.565 mL (m) ; +O (m) = 0.5 m (m) +O (m) +O (m) +O (m) +O) +O (m (m) +O) +O) +O (m (m) +O) +O) +O (m (m) +O) +O) +O) +O (m (m (m) +O) +O) +O) +O (O) +O) +O) +O (O) +O) +O (O) +O) +O (O) +O) +O) +O (O) +O) +O (O) +O) +O) +O (O) +O) +O (O) +O) +O) +O (O) +O) +O (O) +O) +O) +O (O) +O) +O (O) +O) +O) +O (O) +O) +O; +O (O) +O) +O; +O (O) +O) +O; +O; +O; +O;

Then the second enantiomer, which is: 164 mg of (-)-2-{2-[3-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(morpholin-4-yl)pyrimidine-4(3H) -one in the form of a white powder having the following characteristics: The frequency range of the NMR is defined as the frequency range of the frequency range of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, measured at the frequency of the NMR, meas

The following is a list of the active substances in the active substance:

The product is prepared as described in Example 68 from 275 mg of [1-methyl-4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl) sodium acetate, 232 mg of 5,6-difluoro-indoline, 254 mg of N-[3-dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 161 μL pyridine and 4,0 mL of N,N-dimethylformamide. 167 mg of 2-[2-(5,6-difluoro-2,3-dihydro-1H-indol-1-yl) -2-oxoethyl]-3-methyl-6- ((dimethyl-dimethyl-morpholin-4-pyrimidine-4-H3)) is obtained in the form of a white powder with the following characteristics: The frequency range of the radio spectrum is defined as the frequency range of the radio spectrum in the frequency spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum

The following is a list of the active substances in the active substance:

The product is prepared as described in Example 68 from 275 mg of [1-methyl-4- ((morpholin-4-yl) - 6-oxo-1,6-dihydropyrimidine-2-yl) sodium acetate, 287 mg of 4,5-difluoro-indoline hydrochloride, 254 mg of N-[3-dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 241 μL of pyridine and 4,0 mL of N,N-dimethylformamide. 155 mg of 2-[(1-methyl-4-dimethyl-dihydropyrimidine-2-yl]acetate, 287 mg of 4,5-difluoro-indoline hydrochloride, 254 mg of N-[3-dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 241 μL of pyridine and 4,0 mL of N,N-dimethylformamide are obtained. The following are the characteristics of 2-[2-(4-dimethyl-dihydropyrimidine-2-yl-hydrochloride-1-indol-1-yl) - 2-oxo-3-methyl-methyl-dimethyl-methyl-methyl-6-methyl-methyl-methyl-methyl: 0,3·methyl-dimethyl-dimethyl-propyl-propyl: 0,3·pyrimidine; 4,9Hydrin; 4,9H; 4,9H; 4,9H; 4,9H; 4,9H; 4,9H; 4,9H; 2,9H; 2,9H; 3,9H; 3,9H; 4,9H; 3,9H; 3,9H; 3,9H; 3,9H; 3,8H; 3,9H; 3,9H; 3,9H; 3,9H; 3,9H; 3,9H; 3,9H; 3,8H; 3,9H; 3,9H; 3,9H; 3,9H; 3,9H; 3,9H; 3,8H; (H) (H) (H) (H) (H) (H) (H) (H) (H) (H) (H) (H) (H) (H)

The following table shows the results of the analysis of the chemical composition of the compound:

The product is prepared as described in Example 70 from 250 mg of isohindoline, 267 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]ethyl acetate prepared in Step 1 of Example 1 and 1,15 mL of a 2M trimethyl aluminium solution in a mixture of 20 mL of toluene and 10 mL of tetrahydrofuran, in a mixture of 20 mL of toluene and 10 mL of tetrahydrofuran, to obtain 80 mg of 2-[2- ((1,3-dihydro-2H-indol) -oh-2-iso-2-ethyl]-6- ((morpholin-4-yl) -pyrimidine-43 (((H) -oxone in the form of a white powder having the following characteristics: The frequency range of the test chemical is defined as the frequency range of the test chemical, which is the frequency of the test chemical.

The following is the list of active substances in the active substance:

The product is prepared as described in Example 68 from 551 mg of [1-methyl-4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl acetate sodium, 328 mg of benzo[b]thiophen-4-ylamine, 498 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 324 μL of pyridine and 8.0 mL of N,N-dimethylformamide. 110 mg of N- (((1-methyl-4-benzothiophen-4-dihydropyrimidine-2-yl) -4-methyl-4- ((morpholin-4-dihydropyrimidine-6-oxo-1,6-dihydropyrimidine-2-yl) acetate is obtained in a white powder with the following characteristics: The frequency range of the NFM is 1 H (400 MHz): 3,38 (s, 3 H) ; 3,41 (m, 4 H) ; 3,57 (m, 4 H) ; 4,05 (s, 2 H) ; 5,36 (s, 1 H) ; 7,34 (t, J=7,9 Hz, 1 H) ; 7,63 (d, J=5,6 Hz, 1 H) ; 7,72 to 7,81 (m, 3 H) ; 10,14 (m spread out, 1 H) Mass spectrometry: method ATTemps of retention Tr (min) = 0,71 [M+H]+: m/z 385 ; [M-H]-point m/z 383 of melting (Kofler): 254°C.

The following is a list of the active substances in the active substance:

The product is prepared as described in Example 5 from 261 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium, 184 mg of 5-chloro-1,2,3,4-tetrahydroquinoline (can be prepared according to WO2004/0116388), 249 mg of N-[3- ((dimethylamino) propyl) -N'-ethylcarbodiimide chlorate in a mixture of 162 μL of pyridine and 4.0 mL of N,N-dimethylformamide. 141 mg of 2-[2- ((morpholin-4-yl) -3-dihydropyrimidine-1- (2-dihydropyrimidine-3-dihydroquinoline) -4-oxo-2-ethyl) -6- ((dimethyl-4-propyl) -H-pyrimidine-4) is obtained in the following white powder form: The frequency range of the NFM is defined as the frequency range of the frequency spectrum of the NFM 1 H (400 MHz): 1.96 (m, 2 H) ; 2.77 (t, J=6.8 Hz, 2 H) ; 3.41 (m, 4 H) ; 3.61 (m, 4 H) ; 3.70 (t, J=6.8 Hz, 2 H) ; 3.79 (s, 2 H) ; 5.16 (s, 1 H) ; 7.21 (t, J=8.0 Hz, 1 H) ; 7.27 (d, J=8.0 Hz, 1 H) ; 7.55 (d wide, J=8.0 Hz, 1 H); 11.57 (m spread, 1 H) Mass spectrometry: method AT Retention time (min) = 0.78 [M+H] + m/z 389 [M-H] : m/z 387 m/z of fusion (Kofler: 23°C) ;

The following is a list of the active substances in the active substance:

The product is prepared as described in Example 5 from 261 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium, 173 mg of 4- ((hydroxymethyl) -indoline, 254 mg of N-[3- ((dimethylamino) propyl) -N'-ethylcarbodiimide hydrochloride in a mixture of 161 μL of pyridine and 4.0 mL of N,N-dimethylformamide. 288 mg of 2-{2-[4- ((hydroxymethyl) -2,3-dihydroxymethyl-1H-indol-1-]-2-oxo-methyl-6-morpholin-4-dimethyl) -pyrimidine-4-H3 ((H3)) are obtained in powder form, the characteristics of which are as follows: The frequency range of the radio spectrum is defined as the frequency range of the radio spectrum in the frequency spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum

The following is the list of active substances in the active substance:

Step one:

To a 500 mg solution of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl) sodium acetate prepared in step 2 of example 1 3 mL of N,N-dimethylformamide are added to 3 mL of pyridine, 500 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide chloride and 930 mg of 4- (((amino-5-fluoro-phenoxymethyl) -pipéridine-1-carboxylic acid tert-butyl) is reduced. The following reactive agonists are mixed at room temperature under pressure for 2 days and then concentrated in tert-butyl acid. After purification on silica collagen, by mixing a mixture of dichloromethane and dichloromethyl-methylamine-1-butyl (95-dimethylamino-1-methylamine-1-butyl) in the following volumes: 4- ((amino-5-fluoro-fluoro-methylamine-2-butyl) -4-dimethyl-butyl) is obtained: The test chemical is used to determine the concentration of the test chemical in the test medium.

Step two:

After 20 hours of stirring at room temperature, the reaction medium is concentrated under reduced pressure, taken up with a solution of ammonia in methanol and then concentrated again to dry. After purification by silicon neck chromatography, the following are obtained: CH22/Cl/OH, 90/10, 1.5 mg of N-fluoropyridine: [N-fluoropyridine: 2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-methyl-2-meth-2-meth-2-meth-2-meth-2-meth-2-meth-2-meth-2-meth-2-meth-2-meth-2-meth-2-meth-2-meth-2-meth-2-meth-2-meth-2-meth-2-meth-2-meth-2-meth-2-meth-2-meth-2- The frequency spectrum of the NMR is defined as the frequency range of the radio frequency spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectrum of the radio spectr

The following is added to the list of substances which are to be used in the preparation of the additive:

The product is prepared as described in Example 5 from 261 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium, 307 mg of 5-chloro-indoline, 254 mg of N-[3- ((dimethylamino) propyl) -N'-ethylcarbodiimide chlorhydrate in a mixture of 0.16 mL pyridine and 4 mL dimethyformylamide. 255 mg of 2-[2- ((5-chloro-2,3-dihydro-indol-1-) -2-oxo-ethyl]-6-morpholin-4-dimethyl-3H-pyrimidine-4-one is obtained as a white powder with the following characteristics: The frequency range of the test chemical is defined as the frequency range of the test chemical, measured at the start of the test, and the frequency range of the test chemical.

The following is added to the list of substances which are to be used in the preparation of the additive:

The product is prepared as described in Example 5 from 261 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium, 402 mg of 4-bromo-indoline, 254 mg of N-[3- ((dimethylamino) propyl) -N'-ethylcarbodiimide chloride hydrate in a mixture of 0.16 mL pyridine and 4 mL dimethylamide. 303 mg of 2-[2- ((bromo-2,3-dihydro-indo)-1-yl) -2-oxo-ethyl]-6-morpholin-4-bromo-3-H-pyrimidine-4-one is obtained in the form of a white powder with the following characteristics: The frequency range of the measurement is defined as the frequency range of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measur

Examples 136 and 137: Separation of 2-(2-{(3S)-3-[(dimethylamino) methyl]-2,3-dihydro-1H-indol-1-yl}-2-oxoethyl)-6- ((morpholin-4-yl) pyrimidine-4(3H) -one and 2-((2-{(3R)-3-[dimethylamino) methyl]-2,3-dihydro-1H-indol-1-yl}-2-oxoethyl)-6- ((morpholin-4-yl) pyrimidine-4(3H) -one

The products were obtained by chiral chromatographic separation of 500 mg of 2-[2-(3-dimethylaminomethyl-2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-6-morpholin-4-yl-3H-pyrimidine-4-one (Example 115) on chiral column chiralpak AD 20μm (lot CFB003) (1200g, 20μM, 80/35mm), eluting : Heptane/Methanol/Ethanol : 50/20/30 ; flow rate :160 ml/min. After purification, 226 mg of (+) [2-(3-dimethylaminomethyl-2,3-dihydro-indol-1-yl) 2-oxo-ethyl]-6-dimethyl-4-phyrimidine-3-morphone is obtained as the first enantiomer, in solid form, with the following characteristics: The frequency range of the measurement is defined as the frequency range of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measur

Then the second enantiomer, namely: 239 mg of (-)-2-[2-(3-dimethylaminomethyl-2,3-dihydro-indol-1-yl)-2-oxo-ethyl]-6-morpholine-4-yl-3H-pyrimidine-4-one in the form of a yellow solid with the following characteristics: The frequency range of the measurement is defined as the frequency range of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measur

The following is the list of active substances in the active substance:

To a 500 mg solution of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium prepared in step 2 of example 1 3 mL of N,N-dimethylformamide is added to 3 mL of pyridine, 500 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide chloride and 590 mg of 4- ((fluoro-2-methyloxy-ethoxy) -phenyllamine. The reaction mixture is agitated at room temperature for 15 hours, then concentrated under solid pressure. Water and rosemary acetate are added and agitated for 30 minutes. The frequency of the measurement shall be determined by the measurement method.The measurements are based on the following equations: 17 to 3.33 (m partially masked, 3 H); 3.43 (m, 4 H); 3.62 (m, 4 H); 3.68 (m, 4 H); 4.21 (m, 2 H); 5.21 (s, 1 H); 6.75 (dt, J=2.7 and 8.8 Hz, 1 H); 7.02 (dd, J=2.7 and 10.8 Hz, 1 H); 7.85 (dd, J=6.8 and 8.8 Hz, 1 H); 9.28 (s wide, 1 H); 11.65 (m spread, 1 H) Mass spectrometry: BT method Retention time Tr (min) = 3.

The following is the list of active substances in the active substance:

The product is prepared as described in Example 5 from 130 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium, 113 mg of 4-amino-benzimidazole dichlorohydrate, 127 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 80 μL of pyridine and 2.0 mL of N,N-dimethylformamide. 112 mg of N- ((1H-benzimidazole-4-yl) -2- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-amide acetate is obtained in a white powder with the following characteristics: The frequency range of the NFM is defined as the frequency range of the frequency spectrum of the NFM, measured at the frequency of the NFM, measured at the frequency of the NFM, measured at the frequency of the NFM.

Example 140: Synthesis of methyl 2-hydroxy-3- (([[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetyl}amino) benzoate

To a 1g solution of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium prepared in step 2 of example 1 in 6 mL of N,N-dimethylformamide are added 6 mL of pyridine, 1g of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide chloride and 1g of methyl 3-amino-2-hydroxybenzoate. The reaction mixture is agitated at room temperature for 15 hours, then concentrated under reduced pressure. The frequency range of the NFM is defined as the frequency range of the frequency spectrum of the NFM: 1.

The following shall be reported for the product concerned:

The product is prepared as described in Example 5 from 261 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl) sodium acetate, 308 mg of 4-methoxy-indoline, 254 mg of N-[3- ((dimethylamino) propyl) -N'-ethylcarbodiimide hydrochloride in a mixture of 0.16 mL pyridine and 4 mL dimethylformamide. 269 mg of 2-[2- ((methoxy-2,3-dihydro-indol-1-yl) -2-oxo-ethyl]-6-morpholin-4-yl-3H-pyrimidine-4-hydride is obtained in a pink powder with the following characteristics: The frequency range of the test chemical is defined as the frequency range of the test chemical, which is the frequency of the test chemical, and the frequency range of the test chemical.

The following is added to the list of active substances:

A 500 mg solution of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl) sodium acetate prepared in step 2 of example 1 in 4 mL of pyridine, 600 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide chlorhydrate and 550 mg of 2-amino-6-bromophenol. The reaction mixture is agitated at room temperature for 20 hours, then concentrated under reduced pressure. Water and ethyl acetate are added and agitated for 30 minutes. The precipitate formed is filtered, rinsed under water, ether and petroleum ether. The solid is obtained in the following form. The frequency range of the measurement is defined as the frequency range of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measur

The following is the list of active substances in the active substance:

The product is prepared as described in Example 5 from 261 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium, 166 mg of 3,4-dihydro-2H-1,4-benzoxazine-8-ylamine, 249 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 162 μL of pyridine and 4.0 mL of N,N-dimethylformamide. 100 mg of N- ((3,4-dihydro-2H-1,4-benzoxazine-8-yl) -2- ((morpholin-4-dihydro-1,6-oxo-1-hydropyrimidine-2-yl) acetate in a white powder form are obtained, which have the following characteristics: The frequency range of the NFM is 1 H (400 MHz): 3,32 (m partially masked, 2 H) ; 3,44 (m, 4 H) ; 3,62 (m, 6 H) ; 4,08 (m, 2 H) ; 5,08 (m, 1 H) ; 5,19 (s, 1 H) ; 6,49 (t, J=7,8 Hz, 1 H) ; 6,56 (dd, J=1,5 and 7,8 Hz, 1 H) ; 6,80 (dd, J=1,5 and 7,8 Hz, 1 H) ; 9,43 (m spread, 1 H) ; 11,63 (m spread, 1 H) ; Mass spectrometry: method AT Retention time (min) = 2,64; [M+H] :+ m/z 372 [M-H] : 370 m/z fusion point (Kofler: 24°C)

The following is added to the list of substances which are to be used in the preparation of the additive:

The product is prepared as described in Example 5 from 300 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetate of sodium, 303 mg of 2-amino-5-fluorobenzoate of methyl, 308 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 2 mL of pyridine and 2 mL of dimethylformamide. 310 mg of 5-fluoro-2-yle{[4- ((morpholin-4-oxo-1,6-dihydropyrimidin-2-yl]acetyl}amino) benzoate is obtained as a white solid with the following characteristics: The frequency range of the radio spectrum is defined as the frequency range of the radio spectrum, measured at the frequency bands of the frequency spectrum.

The following is a list of the active substances in the active substance:

Stage 1

To a solution of 0.5 g diethyl- (((1H-indol-3-ylmethyl) -amine (prepared according to Synth. Commun. 2006, 1829) in 10 mL of argon-cooled trifluoroacetic acid in an ice bath, 0.48 g of sodium cyanoborohydride is gradually added, and then stirred for half an hour at 0 °C and 3 h at room temperature. The reaction medium is then thrown into 100 mL of water and alkalized by soda at 30%. After adding 100 mL of ethyl acetate, stirred for 10 min at room temperature, then the mixer is decarboxylated and the aqueous phase is extracted by 50 mL of organic phyl acetate, three times.The organic phase is dried on anhydrous magnesium sulphate, filtered and dry concentrated under reduced pressure. The residue is taken up by 20 mL of 2N sodium, plus 40 mL of water and 60 mL of ethyl acetate, stirred for 5 min, then decanted. The aqueous phase is extracted by two times 40 mL of ethyl acetate and the organic phases are collected, dried on anhydrous magnesium sulphate, filtered and dry concentrated under reduced pressure. After a silica column purification, emulsifying: CH2Cl2/OH/NH4OH, 89/10/1, 246 mg (2-hydro-1,3-H-3-dihydro-dihydro-diethyl-methyl) is obtained in the form of a yellow: The mass spectrometry method is used for the determination of the mass of the test substance.

Stage 2

The product is prepared as described in Example 5 from 150 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium, 238 mg of (2,3-dihydro-1H-indol-3-yl-methyl) -diethyl-amine, 140 mg of N-[3- ((dimethylamino) propyl) -N'-ethylcarbodiimide chlorhydrate in a mixture of 0,1 mL of pyridine and 3 mL of N,N-dimethylformamide. 108 mg of 2-2-{dihydropyrimidine-2-yl]-2,3-dihydro-1H-indol-1-oxo-2-amine are obtained, the following solid characteristics being: The frequency range of the NEMS is defined as the frequency range of the NEMS, which is the frequency range of the NEMS, and the frequency range of the NEMS, which is the frequency range of the NEMS.

The following is a list of the active substances in the active substance:

Stage 1

The residue is purified by chromatography on a cartridge of 70 g silica 15-40 μm, eluting with pure dichloromethane and then with a dichloromethane/methanol 99/1 v/v mixture at a flow rate of 80 mL/min, on a cartridge of 30 g 15-40 μm, eluting with pure dichloromethane and then in a solid form of 0.18 g silica at 63°C (a jaundice of 0.18 g).

Stage 2

The product is prepared as described in Example 5 from 350 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium, 177 mg of 4-aza-indoline, 340 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide chlorhydrate in a mixture of 216 μL pyridine and 6.5 mL of N,N-dimethylamide. 252 mg of 2-[2-(morpholin-4-dimethylamino) pyrimidine-4-hydro-1H-pyrrolo[3,2-b]pyrid in-2-oxo-2-ethyl]-6- ((morpholin-4-dimethyl) pyrimidine-4- (((H3)) is obtained in a white powder with the following characteristics: The frequency range of the NFM is 1 H (400 MHz): 3,24 to 3,37 (m partially masked, 2H) ; 3,41 (m, 4 H) ; 3,60 (m, 4 H) ; 3,79 (s, 2 H) ; 4,19 (t, J=8,3 Hz, 2 H) ; 5,21 (s, 1 H) ; 7,17 (dd, J=4,4 and 8,3 Hz, 1 H) ; 8,13 (d, J=4,4 Hz, 1 H) ; 8,19 (d, J=8,3 Hz, 1 H) ; 11,63 (m spread, 1 H) Mass spectrometry: AT method Retention time (min) = 0,37 ; [MH]+/z 342 m [M-H] + 342 m /z: 340 K Fusion point (ofler): greater than 260 °C;

The following is added to the list of substances which are to be used in the preparation of the additive:

The product is prepared by the procedure described in Example 5 from 261 mg of [4- ((morpholin-4-yl) -6-dihydropyrimidine-2-yl) acetate of sodium, 310 mg of 4-methoxy-indoline, 254 mg of N-[3- ((dimethylamino) propyl) -N'-ethylcarbodiimide hydrochloride in a mixture of 0,16 mL of pyridine and 4 mL of dimethylformamide, starting from 245 mg of 2-[4- ((morpholin-4-yl) -6-dihydropyrimidine-2-yl) -6-dihydroxo-1,3-dihydropyrimidine-2-yl) acetate, 310 mg of 4-methoxy-indoline, 254 mg of N-[3- ((dimethylamino) propyl) -N'-ethylcarbodiimide hydrochloride in a mixture of 0,16 mL of pyridine and 4 mL of dimethylformamide, obtained by the following method: 2-[2- ((morpholin-4-yl) -5-dihydropyrimidine-2-yl) acetate, 3- (dimethylamino) -3-methyl-3-methyl) -4-methyl-dihydropyridine-4-methyl) -245 mg of N-[3- ((dimethylamino) -propyl) -propyl) -N'-N'-N'-N'-ethyl) -N'-ethyl-methyl-propyl) -N'-N'-N'-N'-N'-N'-N'-N'-Ethyl-methyl-methyl-carbonyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl-methyl

The following is a list of the active substances in the active substance:

The product is prepared as described in Example 5 from 340 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]acetate of sodium, 212 mg of 8-amino-1,2,3,4-tetrahydroquinoline, 330 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 210 μL of pyridine and 5,0 mL of N,N-dimethylformamide. 243 mg of 2-[4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidin-2-yl]-N- ((1,2,3,4-tetrahydroquinoline-8-acetyl) is obtained as a powder with the following characteristics: The frequency range of the NEMS is defined as the frequency range of the radio spectrum, measured at the frequency bands of the frequency spectrum, and the frequency range of the radio spectrum.

The following is the list of active substances in the active substance:

The product is prepared as described in Example 5 from 220 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium, 157 mg of 8-chloro-2H-benzo[b][1,4]oxazine (which can be prepared according to WO 2008/100463), 214 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 135 μL of pyridine and 3.5 mL of N,N-dimethylformamide. 140 mg of 2-[2- (((chloro-2,3-dihydropyrimidine-4H-1,4-dihydro-4-benzoxazine) 2-oxo-ethyl]-6- ((dimethyl-4-propyl) -morphol-4-morphol) is obtained, the sub-form of which has the following characteristics: RMN spectrum 1 H (400MHz): for this batch, all signals are broad with: 3.41 (m, 4 H) ; 3.57 (m, 4 H) ; 3.88 (m, 4 H) ; 4.42 (m, 2 H) ; 5.17 (s, 1 H) ; 6.88 (m, 1 H) ; 7.24 (m, 1 H) ; 7.71 (m widely spread, 1 H) ; 11.57 (m widely spread, 1 H) Mass spectrometry: AT method; Retention time (min) = 0.71[M+H]+ : m/z 391 ; [M-H]- m/z 389 melting point: (Kofler): above 260°C.

The following is the list of active substances in the active substance:

The product is prepared as described in Example 5 from 1 g of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium, 680 mg of 6-amino-2-methylphenol, 1,2 g of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 6 mL of pyridine and 8 mL of N,N-dimethylformamide. 1,1 g of N- ((2-hydroxy-3-methylphenyle) -2-[4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-]acetamide is obtained in the form of a beige solid with the following characteristics: The frequency range of the NFM is defined as the frequency range of the frequency spectrum of the NFM, measured at the frequency of the NFM.

The following is added to the list of active substances:

The product is prepared as described in Example 5 from 1 g of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium, 590 mg of 2-amino-6-nitrophenol, 734 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 5 mL pyridine and 6 mL of N,N-dimethylformamide. 976 mg of N-2-hydroxy-3-nitrophenyl) -2- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-]acetamide is obtained in a solid form with the following characteristics: The frequency range of the measurement is defined as the frequency range of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measur

The following is added to the list of substances which are to be used in the preparation of the product:

The product is prepared as described in Example 5 from 1 g of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate of sodium, 513 mg of 3-amino-2-hydroxybenzonitrile, 734 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 5 mL of pyridine and 5 mL of N,N-dimethylformamide. 257 mg of N- ((cyano-2-hydroxyphenyl) -4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-]acetamide is obtained as a white solid with the following characteristics: The frequency range of the NMR is defined as the frequency range of the frequency spectrum of the NMR, which is the frequency of the NMR, and the frequency range of the NMR, which is the frequency of the NMR, which is the frequency of the NMR.

The following is added to the list of substances which are to be used in the preparation of the product:

The product is prepared as described in Example 5 from 1 g of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium, 978 mg of 2-hydroxy-3- ((trifluoromethyl) aniline, 1.2 g of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide hydrochloride in a mixture of 6 mL pyridine and 8 mL of N,N-dimethylformamide . 600 mg of N-[2-hydroxy-3-trifluoromethyl]acetate is obtained in a beige solid form with the following characteristics: The frequency range of the measurement is defined as the frequency range of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measurement of the measur

The following is a list of the active substances in the active substance:

The product is prepared as described in Example 5 from 177 mg of [4- ((morpholin-4-yl) -6-oxo-1,6-dihydropyrimidine-2-yl]acetate sodium, 236 mg of 3,3-dimethylindoline (which can be prepared according to T.W. Ramsay et al. Synth. Commun. 1995, 25, 4029), 169 mg of N-[3- ((dimethylamino) propyl]-N'-ethylcarbodiimide chloride hydrate in a mixture of 0.11 mL pyridine and 5 mL N,N-dimethylformamide. The reaction mixture is agitated for 15 hours at room temperature, concentrated at room temperature. The remaining 40 mL of water is added to the mixture which is then cooled to a temperature of 40 °C and filtered to form a dichlorobutane/methane.After dry concentration at reduced pressure, the raw product is purified by chromatography on a 30 g silica column (0.02-0.045 mm), eluting dichloromethane/methanol 90/10 v/v. After evaporation of the various fractions, the pink solid residue is crushed in 10 mL diisopropyl ether, filtered and then dried under a bell (1h/40°C/20 mbar). This results in 134 mg of 2-[(2-3,3-dimethyl-2,3-dihydro-1-indolyl)-2-oxo-ethyl]-6-morpholin-4-yl-3H-pyrimidine-4-one in pink solid form with the following characteristics: The frequency range of the radio spectrum is defined as the frequency range of the radio spectrum.The method of mass spectrometry is based on the following equation:

Example 93: Pharmaceutical composition

Tablets have been prepared with the following formula: Example product 1 0.2 g Excipient for a 1 g tablet (Details of the excipient: lactose, talc, starch, magnesium stearate)

Example 1 is taken as an example of a pharmaceutical preparation, which can be made if desired with other products in the examples in this application.

Pharmacological part: The test protocols In vitro experimental procedures

The inhibitory activity of the molecules on AKT phosphorylation is measured either by western blotting by the technique described below or by the MSD Multi-spot Biomarker Detection Meso Scale Discovery technique also described below.

Study of pAKT expression in human prostate cancer PC3 cells measured by western blotting (Test A):

This test is based on measurement of expression of the AKT phosphorylated protein on serine 473. AKT phosphorylation (pAKT) is measured by western blotting in the human PC3 prostate cancer lineage (ATCC CRL-1435), using an antibody that specifically recognizes pAKT-S473.

On day 1, the PC3 cells are seeded in 6-well plates (TPP, #92006) at a concentration of 0.8x106 cells/well in 1800 μl DMEM medium (DMEM Gibco #11960-044) containing 10% foetal calf serum (SVF Gibco, #10500-056) and 1% Glutamine (L-Glu Gibco #25030-024), and incubated at 37°C, 5% CO2, for one night.

On day 2, the cells are incubated with or without test products for 1-2 hours at 37°C in the presence of 5% CO2. The molecules diluted in dimethyl sulfoxide (DMSO Sigma #D2650) are added from a concentrated parent solution 10 times, with the final percentage of DMSO being 0.1. The molecules are tested either at a single concentration less than or equal to 10μM or at increasing concentrations in a range of less than 1 nM to 10μM.

After this incubation, the cells are lysed for protein preparation. After aspiration of the culture medium, the cells are rinsed with 1 ml of PBS (DPBS Gibco, #14190-094), recovered by scraping in 200μl of complete HNTG buffer and transferred to 96-well plate (Greiner #651201), and lysed for 1 H on ice. The HNTG buffer is composed of the following mixture: Hepes 50 mM, NaCl 150 mM, Triton 1%, Glycerol 10%, with the addition of a protonated Protease Inhibitor Cocktail Mini (Roche 1836153) and a Phosphatase Inhibitor Cocktail (Roche104906837001) for 10 ml buffer.

The lysate is centrifuged 10 min at 6000 RPM. 155 μl of surfactant is recovered. 150 μl is incubated for denaturation for 5 min at 95°C in the presence of NuPAGE LDS Sample Buffer 4X buffer 4 times diluted (Ref InVitrogen NP0007) and NuPAGE Sample Reducing Agent 10X 10 times diluted (Ref InVitrogen NP0009). These samples are then frozen at -20°C. 5 μl are dosed by the microBCA technique according to the MicroBCA Protein Assay Kit data sheet (Pierce #23235).

For protein separation, 20μg of protein is deposited on NU-PAGE gel 4-12% Bis Tris Gel 12 wells (Ref InVitrogen NP0322BOX) and migration is carried out for 1 h 30 in NU-PAGE MOPS SDS Running Buffer 20X migration buffer diluted 20 times (Ref InVitrogen NP0001), at 150 Volts.

The gel is then transferred to an Invitrolon PVDF membrane (Invitrogen #LC2007) which has been previously permeable for a few seconds in ethanol (Ethanol Fischer Scientific #E/0600DF/15).

The transfer is carried out in a Biorad tank at 30 volts overnight or 60 volts for 3 hours, in the presence of a NUPAGE Transfer Buffer 20X transfer buffer diluted 20 times (Ref InVitrogen NP0006).

The membrane is then saturated with a saturation solution consisting of TBS (Tris Buffer Saline 10x, Sigma #T5912 Sigma, diluted 10 times), Tween 20 0.1% (#P5927 Sigma) and BSA 3% (Bovine Albumin Serum Fraction V, Sigma #A4503) for 6 hours after an overnight transfer or for 1 hour after a 3 hour transfer.

The primary antibodies are diluted to 1/1000th of the antiphospho antibody AKT-Ser473 (193H2, rabbit monoclonal, cat#4058 from Cell Signaling Technology (Abcam)), in a saturation solution composed of PBS, Tween 20 0.1%, BSA 3%, and then stirred overnight at 4°C. Two 5-minute rinse times in a wash solution composed of TBS, Tween 20 0.1% are performed before hybridization of the secondary antibodies.

The secondary antibodies are diluted to 1/10000th for Rabbit anti-Mouse IgG HRP antibody (W402 Promega) and to 1/10000th for Goat anti-Rabbit IgG HRP antibody (W401 Promega) in a saturation solution and then agitated for 1 hour at room temperature.

Two 30 min rinse in washing solution and then 5 min rinse in H2O to remove the remaining Tween 20.

The exposure solution is prepared volume by volume according to the specification of the Western Lightning Chemiluminescence Reagent Plus (Western Lightning Chemiluminescence Reagent Plus Perkin Elmer #NEL104).

The membrane is placed for 1 min in the exposure solution, drained, inserted between two transparencies and then placed in the measuring apparatus for reading the luminescence and quantifying the signal.

The FUJI device measures the total luminescence signal (AU) obtained for each selected band. It then subtracts the background noise (BG) proportional to the size of the selected band (Area), background noise calculated from a specific background noise band, to obtain the specific signal (AU-BG) for each band. The band obtained in the absence of product and in the presence of 0.1% DMSO is considered to be 100% of the signal. The software calculates the specific activity percentage (Ratio) obtained for each selected band as a function of this 100% of the signal. The inhibition percentage is calculated for each concentration according to the formula (100% - Ratio).

2 independent experiments to calculate the average of the inhibition percentages obtained at a given concentration for the products tested at a concentration only.

If applicable, the activity of the products is translated into approximate Cl50 from a dose-response curve of different tested concentrations representing the dose giving 50% specific inhibition (absolute CI50).

Study of pAKT expression in human prostate cancer PC3 cells measured by the MSD Multi-spot Biomarker Detection of Meso Scale Discovery (Test B):

The test is based on measurement of expression of the serine 473 (P-AKT-S473) phosphorylated AKT protein in the PC3 human prostate cancer lineage by the sandwich-based immunoassay technique using the MSD Multi-spot Biomarker Detection Meso Scale Discovery kit: phospho-Akt (Ser473) whole cell lysate (#K151CAD) or phospho-Akt (Ser473)/Total Akt cell lysate (#K151OOD). The primary antibody specific to P-AKT-S473 (Kit #K151CAD) is coated on an electrode in each well plate: after 96 well plates of lysate are detected in each well kit, the secondary antibody is detected in the test kit by a decryption of the composition of the antibodies.

On day 1, the PC3 cells are seeded in 96 well plates (TPP, #92096) at a concentration of 35000 cells/well in 200 μl DMEM medium (DMEM Gibco #11960-044) containing 10% foetal calf serum (SVF Gibco, #10500-056) and 1% Glutamine (L-Glu Gibco #25030-024) and incubated at 37°C, 5% CO2 for one night.

On day 2, the cells are incubated with or without test products for 1-2 hours at 37°C in the presence of 5% CO2. The molecules diluted in dimethyl sulfoxide (DMSO Sigma #D2650) are added from a concentrated parent solution 20 times, with the final percentage of DMSO being 0.1%. The molecules are tested either at a single concentration less than or equal to 10μM or at increasing concentrations in a range of less than 1 nM to 10μM.

After this incubation, the cells are lysed for protein preparation, for which, after aspiration from the culture medium, 50 μl of Tris Lysis Buffer complete lysine buffer from the MSD kit containing protease and phosphatase inhibitor solutions is added to the wells and the cells are lysed for 1 h at 4 °C under agitation.

The wells of the 96 well plates of the MSD kit are saturated for 1h at room temperature with the blocking solution of the MSD kit. Four washes are performed with 150μl of Tris Wash Buffer washing solution from the MSD kit. The previously prepared lysates are transferred to the Multi-spot 96 well plates of the MSD kit and incubated for 1h at room temperature, under agitation. Four washes are performed with 150μl of Tris Wash Buffer washing solution from the MSD kit. 25μl of the MSD sulfo-tag antibody detection solution are added to the wells and incubated for 1h at room temperature, under agitation. Four washes are performed with 150μl of Tris Wash Buffer washing solution. 150μl of buffer are removed from the MSD S12 and the MSD S400 read-out plates are added to the MSD Meso-discovery kit immediately.

The apparatus measures a signal for each well. Cell-free wells containing the lysis buffer are used to determine the background noise to be subtracted from all measurements (min). Wells containing cells in the absence of product and in the presence of 0.1% DMSO are considered to be 100% of the signal (max). The percentage of inhibition is calculated for each concentration of test product according to the following formula: (1- ((test-min) / ((max-min))) x100.

The activity of the product is expressed as Cl50 from a dose-response curve of different tested concentrations and representing the dose giving 50% specific inhibition (absolute Cl50).

The results obtained for the sample products in the experimental part are given in the following pharmacological result table: - What? :

exemple	Test A	Test B
Exemple 1	102
Exemple 2	321
Exemple 3	100
Exemple 4		145
Exemple 5		51
Exemple 6	23
Exemple 7		23
Exemple 8	318
Exemple 9	727
Exemple 10	3498
Exemple 11	632
Exemple 12	737
Exemple 13		71
Exemple 14	570	74
Exemple 15	1420
Exemple 16	850
Exemple 17	1481
Exemple 18	23
Exemple 19		42
Exemple 20	1314
Exemple 21	10000
Exemple 22	305
Exemple 23	39
Exemple 24		247
Exemple 25
Exemple 26	2287
Exemple 27		71
Exemple 28	171
Exemple 29	116
Exemple 30		1030
Exemple 31		58
Exemple 32	3635
Exemple 33	93
Exemple 34	609
Exemple 35	10000
Exemple 36	200
Exemple 37	10000
Exemple 38	480
Exemple 39	1763
Exemple 40	1494
Exemple 41	290	60
Exemple 42	400	148
Exemple 43	549
Exemple 44	308
Exemple 45	261
Exemple 46	2498
Exemple 47	346
Exemple 48	184
Exemple 49		146
Exemple 50	6721
Exemple 51	133
Exemple 52	227
Exemple 53		66
Exemple 54	807	67
Exemple 55	10000
Exemple 56	137
Exemple 57	5865
Exemple 58	760	71
Exemple 59	417	50
Exemple 60		290
Exemple 61		77
Exemple 62	530
Exemple 63	6155
Exemple 64		10000
Exemple 65	6460
Exemple 66		131
Exemple 67	2207
Exemple 68	202	79
Exemple 69	250
Exemple 70		195
Exemple 71	5375	120
Exemple 72		89
Exemple 73	650
Exemple 74		10
Exemple 75		69
Exemple 76		77
Exemple 77		698
Exemple 78		129
Exemple 79		20
Exemple 80		94
Exemple 81		1940
Exemple 82		133
Exemple 83		115
Exemple 84		17
Exemple 85		340
Exemple 86		26
Exemple 87		75
Exemple 88		5
Exemple 89		3
Exemple 90		14
Exemple 91		71
Exemple 92		57
Exemple 93		63
Exemple 94		11
Exemple 95		35
Exemple 96		6
Exemple 97		260
Exemple 98		219
Exemple 99		666
Exemple 100		3
Exemple 101		13
Exemple 102		43
Exemple 103		7
Exemple 104		42
Exemple 105		15
Exemple 106		27
Exemple 107		24
Exemple 108		56
Exemple 109		43
Exemple 110		278
Exemple 111		301
Exemple 112		23
Exemple 113		664
Exemple 114		26
Exemple 115		10
Exemple 116		51
Exemple 117		19
Exemple 118		12
Exemple 119		194
Exemple 120		11
Exemple 121		44
Exemple 122		503
Exemple 123		77
Exemple 124		124
Exemple 125		16
Exemple 126		57
Exemple 127		61
Exemple 128		69
Exemple 129		1000
Exemple 130		70
Exemple 131		41
Exemple 132		533
Exemple 133		174
Exemple 134		124
Exemple 135		1
Exemple 136		26
Exemple 137		68
Exemple 138		35
Exemple 139		3000
Exemple 140		302
Exemple 141		60
Exemple 142		22
Exemple 143		473
Exemple 144		432
Exemple 145		38
Exemple 146		180
Exemple 147		4
Exemple 148		234
Exemple 149		43
Exemple 150		189
Exemple 151		29
Exemple 152		938
Exemple 153		49
Exemple 154		28

:

Claims (17)

1. Products of formula (I): in which:

   R1 represents an aryl or heteroaryl radical optionally substitutes with one or more radicals, which may be identical or different, chosen from halogen atoms and hydroxyl, CN, nitro, -COOH, -COOalk, -CONRxRy, -NRxCORy, -CORy, -NRxCO₂Rz, alkoxy, phenoxy, alkylthio, alkyl, alkenyl, alkynyl, cycloalkyl, O-cycloalkyl, heterocycloalkyl, aryl and heteroaryl radicals;

   the latter alkoxy, phenoxy, alkylthio, alkyl, alkenyl, alkynyl, heterocycloalkyl, aryl and heteroaryl radicals being themselves optionally substituted with one or more radicals, which may be identical or different, chosen from halogen atoms and hydroxyl, alkoxy, NRvRw, heterocycloalkyl or heteroaryl radicals;

   the aryl and heteroaryl radicals being, in addition, optionally substituted with one or more alkyl and alkoxy radicals, themselves optionally substituted with one or more halogen atoms;

   it being possible for the heterocycloalkyl and heteroaryl radicals to additionally contain an oxo radical;

   R represents a hydrogen atom or else forms, with R1, a saturated or partially or totally unsaturated 5- or 6-membered ring fused to an aryl or heteroaryl residue and optionally containing one or more other heteroatoms chosen from O, S, N, NH and Nalk, this bicyclic radical being optionally substituted with one or more radicals, which may be identical or different, chosen from halogen atoms and CO-NH₂, hydroxyl, alkyl and alkoxy radicals; the latter alkyl radical being itself optionally substituted with a hydroxyl, alkoxy, NH₂, NHalk or N(alk)₂ radical;

   R2 and R3, which may be identical or different, independently represent a hydrogen atom, a halogen atom or an alkyl radical optionally substituted with one or more halogen atoms;

   R4 represents a hydrogen atom;

   R5 represents a hydrogen atom or an alkyl radical optionally substituted with one or more halogen atoms;

   NRxRy being such that Rx represents a hydrogen atom or an alkyl radical and Ry represents a hydrogen atom or a cycloalkyl radical or an alkyl radical optionally substituted with one or more radicals, which may be identical or different, chosen from hydroxyl, alkoxy, NRvRw and heterocycloalkyl radicals; or Rx and Ry form, with the nitrogen atom to which they are attached, a cyclic radical containing from 3 to 10 ring members and optionally one or more other heteroatoms chosen from O, S, NH and N-alkyl, this radical being optionally substituted;

   NRvRw being such that Rv represents a hydrogen atom or an alkyl radical and Rw represents a hydrogen atom or a cycloalkyl radical, CO₂alk, or an alkyl radical optionally substituted with one or more radicals, which may be identical or different, chosen from hydroxyl, alkoxy and heterocycloalkyl radicals; or Rv and Rw form, with the nitrogen atom to which they are attached, a cyclic radical containing from 3 to 10 ring members and optionally one or more other heteroatoms chosen from O, S, NH and N-alkyl, this cyclic radical being optionally substituted;

   the cyclic radicals that Rx and Ry or Rv and Rw, respectively, can form, with the nitrogen atom to which they are attached, being optionally substituted with one or more radicals, which may be identical or different, chosen from halogen atoms and alkyl, hydroxyl, oxo, alkoxy, NH₂; NHalk and N(alk)₂ radicals;

   Rz represents the values of Ry except for hydrogen;

   Rx, Ry and Rz in the -NRxCORy, -CORy and CO₂Rz radicals being chosen from the meanings indicated above for Rx, Ry and Rz;

   all the above alkyl (alk), alkoxy and alkylthio, radicals being linear or blanched and containing from 1 to 6 carbon atoms,

   said products of formula (I) being in all the possible racemic, enantiomeric and diastereoisomeric stereoisomer forms, and also the addition salts with inorganic and organic acids or with inorganic and organic bases, of said products of formula (I).
2. Products of formula (I) as defined in Claim 1, in which:

   R₁ represents a phenyl, pyridine, thienyl, benzoxazolyl, benzofuryl, indazolyl, indolyl, benzothienyl, benzimidazolyl, benzoxazinyl or tetrahydroquinolyl radical, optionally substituted with one or more radicals, which may be identical or different, chosen from halogen atoms and CN, nitro, - COOH, -COOalk, -NRxRy, alkoxy, alkyl, alkynyl and cycloalkyl radicals;

   the latter alkoxy, alkyl and alkynyl radicals being themselves optionally substituted with one or more radicals, which may be identical or different, chosen from halogen atoms and hydroxyl, alkoxy, NRvRw, piperidyl, pyrrolidinyl or heteroaryl radicals;

   the phenyl and heteroaryl radicals being, in addition, optionally substituted with one or more alkyl and alkoxy radicals;

   R represents a hydrogen atom or else forms, with R₁ a benzoxazinyl, dihydroindolyl, tetrahydroisoquinolyl, tetrahydroquinolyl or dihydropyrrolopyridyl ring, these rings being optionally substituted with one or more radicals, which may be identical or different, chosen from halogen atoms and CO-NH₂, hydroxyl, alkyl and alkoxy radicals;

   the latter alkyl radical being itself optionally substituted with a hydroxyl, alkoxy, NH₂, NHalk or N(alk)₂ radical;

   R2 and R3, which may be identical or different, independently represent a hydrogen atom, a fluorine atom or an alkyl radical;

   R4 represents a hydrogen atom;

   R5 represents a hydrogen atom or an alkyl radical;

   NRxRy being such that Rx represents a hydrogen atom or an alkyl radical and Ry represents a hydrogen atom or an alkyl radical; or Rx and Ry form, with the nitrogen atom to which they are attached, a cyclic radical containing from 3 to 10 ring members and optionally one or more other heteroatoms chosen from O, S, NH and N-alkyl, this cyclic radical being optionally substituted;

   NRvRw being such that Rv represents a hydrogen atom or an alkyl radical and Rw represents a hydrogen atom or an alkyl radical;

   all the above alkyl (alk) and alkoxy radicals being linear or blanched and containing from 1 to 6 carbon atoms,

   said products of formula (I) being in all the possible racemic, enantiomeric and diastereoisomeric stereoisomer forms, and also the addition salts with inorganic and organic acids or with inorganic and organic bases, of said products of formula (I).
3. Products of formula (I) as defined in either one of Claims 1 and 2, corresponding to the following formulae:

   - 2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]-N-phenylacetamide

   - N-(4-fluorophenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(3-chlorophenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-[3-(dimethylamino)phenyl]-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydroyrimidin-2-yl]acetamide

   - N-(2,4-difluorophenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(3,4-difluorophenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - 2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]-N-(thiophen-3-yl)acetamide

   - N-(4-fluoro-3-methoxyphenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(2-fluorophenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(2-methylphenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(2-methoxyphenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(2,3-difluorophenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(3,5-difluorophenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(3-fluorophenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(4-chlorophenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(3-methoxyphenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - 2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]-N-[3-(trifluoromethyl)phenyl]acetamide

   - N-(3-bromophenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-[3-(2-methylpropan-2-yl)phenyl]-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - methyl 3-({[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetyl}amino)benzoate

   - 3-({[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetyl}amino)benzoic acrid

   - 2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]-N-[3-(propan-2-yl)phenyl]acetamide

   - N-(3-methylphenyl-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(3-cyano-4-fluorophenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(1H-indazol-6-yl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(3-cyanophenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(5-fluoropyridin-2-yl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(4-fluoro-3-methylphenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(3-chloro-4-fluorophenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - 2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]-N-(pyridin-3-yl)acetamide

   - N-(4-fluoro-2-methylphenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(3-hydroxyphenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(3-bromo-4-fluorophenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - 2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]-N-(3,4,5-trifluorophenyl)acetamide

   - N-[4-fluoro-3-(hydroxymethyl)phenyl]-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(3-cyclopropylephenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(2-hydroxyphenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-[3-(difluoromethoxy)phenyl]-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(4-fluoro-3-methoxyphenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]propanamide

   - N-(2,3-dimethylphenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(2-fluoro-3-methylphenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(1,3-benzoxazol-4-yl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - 2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]-N-[3-(trifluoromethoxy)phenyl]acetamide

   - 2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]-N-[3-(propan-2-yloxy)phenyl]acetamide

   - N-(4-fluoro-2-methoxyphenyl)-2-[4-(morpholin-4-yl)-5-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - 2-methylpropan-2-yl {2-[3-({[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetyl}amino)phenyl]ethyl}carbamate

   - N-[4-fluoro-3-(trifluoromethyl)phenyl]-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(3-ethynylphenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-[3-(cyclopentyloxy)phenyl]-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(4-fluoro-2-hydroxyphenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - 2-[2-(2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - N-(3-cyclopropyl-4-fluorophenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - 2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl-N-2,3,4-trifluorophenyl)acetamide

   - N-[4-fluoro-3-(trifluoromethoxy)phenyl]-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-[3-(2-hydroxyethoxy)phenyl]-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(3-iodophenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - methyl 2-fluoro-5-({[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetyl}amino)benzoate

   - N-(3-ethoxyphenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(2,4-difluoro-3-methoxyphenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - 2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]-N-(2,4,5-trifluorophenyl)acetamide

   - N-(3,5-dichloro-4-fluorophenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - 2-[2-(2,3-dihydro-4H-1,4-benzoxazin-4-yl)-2-oxoethyl]-6-(morpholin-4-yl)pyrimidin-4(3)-one

   - N-(4-fluoro-3-nitrophenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - 2-fluoro-5-({[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetyl}amino)benzoic acid

   - N-(5-fluoro-2-hydroxyphenyl)-2-[4-morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(2-bromo-4-fluorophenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(4-fluorophenyl)-2-[1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(3-chloro-4-fluorophenyl)-2-[1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(3-bromophenyl)-2-[1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - 2-[1-ethyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]-N-(4-fluorophenyl)acetamide

   - N-(1H-indol-4-yl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(4-fluorophenyl)-3-methyl-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]butanamide

   - N-[4-fluoro-3-(methoxymethyl)phenyl]-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(4-fluoro-3-iodophenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - 2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]-N-[3-(1,1,2,2-tetrafluoroethoxy)phenyl]acetamide

   - N-[3-(difluoromethyl)-4-fluorophenyl]-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - 2,2-difluoro-N-(4-fluorophenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(3,4-difluorophenyl)-2-[1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - 2-[2-(2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-3-methyl-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - N-(3-bromo-4-fluorophenyl)-2-[1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-[4-fluoro-3-(hydroxymethyl)phenyl]-2-[1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(3-cyclopropylphenyl)-2-[1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(4-fluoro-3-methoxyphenyl)-2-[1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(1-benzofur-4-yl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - 2-[1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]-N-phenylacetamide

   - N-(3-cyclopropyl-4-fluorophenyl)-2-[1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(3-fluoro-2-hydroxyphenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - 2-[2-(4-fluoro-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - 2-[2-(4-chloro-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - N-(3-ethynyl-4-fluorophenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - 2-[2-(4-hydroxy-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - 2-[2-(4,6-difluoro-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - N-(4-fluoro-3-iodophenyl)-2-(1-methyl-4-morpholin-4-yl-6-oxo-1,6-dihydropyrimidin-2-yl)acetamide

   - 2-[2-(4,5-difluoro-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - 2-[2-(6-fluoro-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - 2-[2-(2-methyl-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - N-3-(difluoromethyl)-4-fluorophenyl]-2-[1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - 2-[1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]-N-(3,4,5-trifluorophenyl)acetamide

   - N-(1-methyl-1H-indol-4-yl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - 2-[2-(4-methyl-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - 2-[2-(3-methyl-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - 2-[2-(4-fluoro-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-3-methyl-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - 2-[2-(5-fluoro-2,3-dihydroindol-1-yl)-2-oxoethyl]-6-morpholin-4-yl-3H-pyrimidin-4-one

   - 2-[2-(4-chloro-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-3-methyl-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - N-(1-benzothiophen-4-yl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - 2-{2-[2-(hydroxymethyl)-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - 2-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]-N-{2-[2-(piperidin-1-yl)ethoxy]phenyl}acetamide

   - N-[2-(2-methoxyethoxy)phenyl]-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - 2-[2-(4-hydroxy-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-3-methyl-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - 2-[2-(4-methoxy-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-3-methyl-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - 2-[2-(3,4-dihydroisoquinolin-2(1H)-yl)-2-oxoethyl]-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - 2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]-N-{2-[2-(pyrrolidin-1-yl)ethoxy]phenyl}acetamide

   - 2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]-N-[2-(pyridin-3-ylmethoxy)phenyl]acetamide

   - 3-methyl-2-[2-(4-methyl-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - 2-(2-{3-[(dimethylamino)methyl]-2,3-dihydro-1H-indol-1-yl}-2-oxoethyl)-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - 2-[2-(4-bromo-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-3-methyl-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - 2-{2-[(2S)-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - 2-{2-[(2R)-2-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - 3-methyl-2-[2-(3-methyl-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - 2-{2-[2-(methoxymethyl)-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - 2-[2-(4-ethoxy-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - 1-{[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetyl}-2,3-dihydro-1H-indole-2-carboxamide

   - 3-methyl-2-[2-(2-methyl-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - 2-[2-(6-fluoro-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-3-methyl-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - 2-{2-[(3S)-3-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - 2-{2-[(3R)-3-methyl-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(morpholin-4-yl)pyrimidin-4(3H)-one 2-[2-(5,6-difluoro-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-3-methyl-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - 2-[2-(4,5-difluoro-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-3-methyl-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - 2-[2-(1,3-dihydro-2H-isoindol-2-yl)-2-oxoethyl]-6-(morpholin-4-yl)pyrimidin-4-(3H)-one

   - N-(1-benzothiophen-4-yl)-2-[1-methyl-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - 2-[2-(5-chloro-3,4-dihydroquinolin-1(2H)-yl)-2-oxoethyl]-6-morpholin-4-yl)pyrimidin-4(3H)-one

   - 2-{2-[4-(hydroxymethyl)-2,3-dihydro-1H-indol-1-yl]-2-oxoethyl}-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - N-[4-fluoro-2-(piperidin-4-ylmethoxy)phenyl]-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - 2-[2-(5-chloro-2,3-dihydroindol-1-yl)-2-oxoethyl]-6-morpholin-4-yl-3H-pyrimidin-4-one

   - 2-[2-(4-bromo-2,3-dihydroindol-1-yl)-2-oxoethyl]-6-morpholin-4-yl-3H-pyrimidin-4-one

   - 2-(2-{(3S)-3-[(dimethylamino)methyl]-2,3-dihydro-1H-indol-1-yl}-2-oxoethyl)-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - 2-(2-{(3R)-3-[(dimethylamino)methyl]-2,3-dihydro-1H-indol-1-yl}-2-oxoethyl)-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - N-[4-fluoro-2-(2-methoxyethoxy)phenyl]-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(1H-benzimidazol-4-yl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-diydroyrimidin-2-yl]acetamide

   - methyl 2-hydroxy-3-({[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetyl}amino)benzoate

   - 2-[2-(4-methoxy-2,3-dihydroindol-1-yl)-2-oxoethyl]-6-morpholin-4-yl-3H-pyrimidin-4-one

   - N-(3-bromo-2-hydroxyphenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(3,4-dihydro-2H-1,4-benzoxazin-8-yl)-2-[4-(morpholin-4-yl)-6-oxo-1,G-dihydropyrimidin-2-yl]acetamide

   - methyl 5-fluoro-2-({[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetyl}amino)benzoate

   - 2-(2-{3-[(diethylamino)methyl]-2,3-dihydro-1H-indol-1-yl}-2-oxoethyl)-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - 2-[2-(2,3-dihydro-1H-pyrrolo[3,2-b]pyridin-1-yl)-2-oxoethyl]-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - 2-[2-(5,6-difluoro-2,3-dihydroindol-1-yl)-2-oxoethyl]-6-morpholin-4-yl-3H-pyrimidin-4-one

   - 2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]-N-[1,2,3,4-tetrahydroquinolin-8-yl)acetamide

   - 2-[2-(8-chloro-2,3-dihydro-4H-1,4-benzoxazin-4-yl)-2-oxoethyl]-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   - N-(2-hydroxy-3-methylphenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(2-hydroxy-3-nitrophenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-(3-cyano-2-hydroxyphenyl)-2-[4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - N-[2-hydroxy-3-(trifluoromethyl)phenyl]-2-4-(morpholin-4-yl)-6-oxo-1,6-dihydropyrimidin-2-yl]acetamide

   - 2-[2-(3,3-dimethyl-2,3-dihydro-1H-indol-1-yl)-2-oxoethyl]-6-(morpholin-4-yl)pyrimidin-4(3H)-one

   and also the addition salts with inorganic and organic acids or with inorganic and organic bases, of said products of formula (I).
4. Process for prepaying the products of formula (I) as define in any one of Claims 1 to 3, according to scheme 1A as defined hereinafter: in which the substituent R1 has the meanings indicated in either one of Claims 1 and 2.
5. Process for preparing the products of formula (I) as defined in any one of Claims 1 to 3, according to scheme 1B as defined hereinafter: in which the substituents R1 and R5 have the meanings indicated in either one of Claims 1 and 2.
6. Process for preparing the products of formula (I) as define in any one of Claims 1 to 3 according to scheme 1C as defined hereinafter: in which the substituents R1, R2, R3 and R5 have the meanings indicated in either one of Claims 1 and 2.
7. Products of formula (I) as defined in any one of Claims 1 to 3, and also the pharmaceutically acceptable addition salts with inorganic an organic acids or with inorganic and organic bases, of said products of formula (I), for their use as medicaments.
8. Products of formula (I) as defined in Claim 3, and also the pharmaceutically acceptable addition salts with inorganic organic acids or it inorganic and organic bases, of said products of formula (I), for their use as medicaments.
9. Pharmaceutical compositions containing, as active ingredient, at least one of the products of formula (I) as defined in any one of Claims 1 to 3, or a pharmaceutically acceptable salt of this product, and a pharmaceutically acceptable carrier.
10. Products of formula (I) as defined in any one of Claims 1 to 3, for their use in the treatment of cancers.
11. Products of formula (1) as defined in any one of Claims 1 to 3, for their use in the treatment of solid or liquid tumours.
12. Products of formula (1) as defined in any one of Claims 1 to 3, for their use in the treatment of cancers résistant to cytotoxic agents.
13. Products of formula (1) as defined in any one of Claims 1 to 3, for their use in the treatment of primary tumours and/or of metastases, in particular in gastric, hepatic, renal, ovarian, colon, prostate, endometrial and lung (NSCLC and SCLC) cancers, glioblastomas, thyroid, bladder and breast cancers, in melanoma, in lymphoid or yeloid hematopoietic tumours, in sarcomas, in brain, larynx and lymphatic system cancers, bone and pancreatic cancers, and in hamartomas.
14. Products of formula (I) as defined in any one of Claims 1 to 3, for their use in cancer chemotherapy.
15. Products of formula (I) as defined in any one of Claims 1 to 3, for their use in cancer chemotherapy, alone or in combination.
16. Products of formula (I) as defined in any one of Claims 1 to 3, as inhibitors of AKT (PKB) phosphorylation.
17. Synthesis intermediates of formulae C, D, E and F as defined in Claim 4 and recalled below: in which R5 has the definition indicated in either one of Claims 1 and 2.