EA037563B1 - New (hetero)aryl-substituted piperidinyl derivatives, process for their preparation and pharmaceutical compositions containing them - Google Patents

Abstract

Compounds of formula (I)wherein R1, R2, J, K, L, n and W are as defined in the description. Medicaments.

Description

The invention relates to new (hetero) aryl-substituted piperidinyl derivatives, to a method for their preparation and to pharmaceutical compositions containing them.

The compounds of the present invention are novel and have very valuable pharmacological characteristics in the fields of apoptosis and oncology.

Ubiquitination is a process that controls basic cellular functions such as protein metabolism and homeostasis, protein activation and localization. Ubiquitin is a 76 amino acid polypeptide that is covalently attached to post-translationally modified protein substrates through an isopeptide bond. Deubiquitinizing enzymes (DUB) are mostly cysteine proteases that cleave the ubiquitin-ubiquitin bond or the ubiquitin-protein bond at the Cter of ubiquitin glycine. Approximately 100 DUBs regulate thousands of ubiquitinated proteins, and even some overregulation of deubiquitinase substrates has been observed.

DUB dysregulation has been associated with several diseases such as neurodegenerative and infectious diseases (Edelman et al., Expert Rev. Mol. Med. 2011, 13, 1-17), and human malignancies (Pal et al., Cancer Res. 2014, 74, 4955-4966). Accordingly, overexpression of DUB or an increase in their activity is associated with numerous types of malignant diseases (Luise et al., Plos One 2011, 6, e15891; Rolen et al., Mol. Carcinog. 2006, 45, 260-269) and poor prognosis.

Ubiquitin-specific protease 7 (USP7), also known as the herpes-associated ubiquitin-specific protease (HAUSP), belongs to the family of deubiquitinizing enzymes. USP7 has been reported to stabilize numerous oncogenes involved in survival and proliferation by regulating cell cycle progression, apoptosis, DNA repair, DNA replication, and epigenetic factors (Nicholson et al. Cell Biochem. Biophys. 2011, 60, 61-68). In addition, USP7 has been shown to regulate the immune response through inflammation and Treg modulation (Van Loosdregt et al., Immunity 2013, 39, 259-27; Colleran et al., Proc. Natl. Acad. Sci. USA 2013, PO, 618-623). USP7 is also implicated in other pathological conditions such as neurodevelopmental disorders (Hao et al., Mol. Cell 2015, 59, 956-969) and viral infection (Holowaty et al., Biochem. Soc. Trans. 2004, 32, 731 -732).

Overexpression of USP7 has been associated with advanced cancer and poor prognosis in lung cancer, neuroblastoma, myeloma, prostate, colon and breast cancer. Although some inhibitors have been published in the literature, most of them were not selective and to date, USP7 inhibitors have not been included in clinical practice (Kemp et al., Progress in Medicinal Chemistry 2016, 55, 149-192). Therefore, there is a therapeutic need for compounds that inhibit the activity of the USP7 protein.

In addition to being novel, the compounds of the present invention have pro-apoptotic and / or antiproliferative properties, which allows their use in pathologies in which a defect in apoptosis is involved, such as for the treatment of malignant neoplasms and immunopathological and autoimmune diseases.

More specifically, the present invention relates to compounds of formula (I)

where R ₁ represents an aryl group or a heteroaryl group,

R ₂ represents a hydrogen atom or a halogen atom, n represents an integer equal to 0, 1 or 2,

J represents -C (O) -group, -CH (R ₃ ) -group or -SO ₂ -group,

R ₃ represents a hydrogen atom or a linear or branched _(C1-C6) alkyl group,

K represents a bond or -Cy ₁ -group,

L is a -Cy ₂ -group or -CH ₂ -Cy ₂ -group, W is a group

where A is a heteroaryl ring,

X represents a carbon atom or a nitrogen atom,

R4 represents a hydrogen atom, a halogen atom, a linear or branched _(C1-C6) alkyl group, a linear or branched (C ₂ -C ₆₎ alkenyl group, a linear or branched (C ₂ -C ₆₎ alkynyl group, -Y ₁ -NR ₆ R ₇ -group, -Y ₁ -OR ₆ -group, linear or branched halogen (C1-C ₆ ) alkyl group, oxo group, -Y ₁ -Cy ₃ -group, -Cy ₃ -R ₇ -group, -Cy ₃ -OR ₇ -group, or -Y1- 1 037563

NR ₆ -C (O) -R ₇ -groupy,

R5 represents a hydrogen atom, a halogen atom or a linear or branched (C ₁ -C ₆₎ alkyl group,

R ₆ represents a hydrogen atom or a linear or branched (C ₁ -C ₆ ) alkyl group,

R7 represents a hydrogen atom, a linear or branched (C ₁ -C ₆ ) alkyl group, or -Y2-Cy4-group,

Y1 and Y2 each independently represent a bond or a linear or branched (C1C ₄₎ alkilenovyyu group,

Cy1 represents a cycloalkyl group, a heterocycloalkyl group, an aryl group, or a heteroaryl group that is attached to the J group and to the L group,

Cy ₂ , Cy ₃ and Cy ₄ independently of each other represent a cycloalkyl group, a heterocycloalkyl group, an aryl group, or a heteroaryl group, it should be understood that aryl means a phenyl, naphthyl or indanyl group, heteroaryl means any mono- or fused bicyclic a group of 5-10 ring members containing at least one aromatic moiety and containing from 1 to 3 heteroatoms selected from oxygen, sulfur and nitrogen, cycloalkyl means any mono- or fused bicyclic non-aromatic carbocyclic group containing from 3 to 7 ring members, heterocycloalkyl means any non-aromatic mono- or fused bicyclic group containing from 3 to 10 ring members and containing from 1 to 3 heteroatoms selected from oxygen, sulfur and nitrogen, with aryl, heteroaryl, cycloalkyl and heterocycloalkyl groups defined in this way can be substituted with 1-4 groups selected and from linear or branched (C ₁ -C ₆ ) alkyl, linear or branched (C ₂ -C ₆ ) alkenyl, linear or branched (C ₂ -C ₆ ) alkynyl, linear or branched halogen (C1-C ₆ ) alkyl, -Y1-OR ', -Yj-NR'R, -Yj-S (O) _m -R', oxo (or N-oxide, as appropriate), nitro, cyano, -C (O) -R ', -C (O) -OR ', -OC (O) -R', -C (O) -NR'R, -Yj-NR'-C (O) -R, -Yj-NR'-C (O ) -OR, halogen, cyclopropyl, and pyridinyl, which may be substituted by a linear or branched (C ₁ -C ₆ ) alkyl group, it being understood that R 'and R independently of each other represent a hydrogen atom, linear or branched (C ₁ -C ₆ ) alkyl group, linear or branched (C ₂ -C ₆ ) alkenyl group, linear or branched (C1 -C ₆ ) alkoxy group, linear or branched halogen (C ₁ -C ₆ ) alkyl group, linear or branched hydroxy (C ₁ -C ₆ ) alkyl group, linear or branched (C ₁ -C ₆ ) alkoxy (C ₁ -C ₆ ) alkyl group, phenyl group, cyclopropylmethyl a radical group, a tetrahydropyranyl group, or substituents of the pair (R ', R) together with the nitrogen atom carrying them, form a non-aromatic ring consisting of 5-7 ring members, which may contain, in addition to the nitrogen atom, a second heteroatom selected from oxygen and nitrogen, it should be understood that the second considered nitrogen may be substituted by 1-2 groups representing a hydrogen atom or a linear or branched (C ₁ -C ₆ ) alkyl group, and it should be understood that m means an integer equal to 0, 1 or 2, their enantiomers, diastereoisomers and their addition salts with a pharmaceutically acceptable acid or base.

Among the pharmaceutically acceptable acids, there may be mentioned, without implying any limitation, hydrochloric acid, hydrobromic acid, sulfuric acid, phosphonic acid, acetic acid, trifluoroacetic acid, lactic acid, pyruvic acid, malonic acid, succinic acid, glutaric acid, fumaric acid, tartaric acid, maleic acid, citric acid, ascorbic acid, oxalic acid, methanesulfonic acid, camphoric acid, etc.

Among the pharmaceutically acceptable bases, there may be mentioned, without implying any limitation, sodium hydroxide, potassium hydroxide, triethylamine, tert-butylamine, etc.

Among heteroaryl groups, there may be mentioned, without implying any limitation, pyrrolyl, furyl, thienyl, thiazolyl, isothiazolyl, oxazolyl, isoxazolyl, pyrazolyl, imidazolyl, pyridinyl (also known as pyridyl), pyrazinyl, pyridazinyl, pyrimidinyl, pyolidinyl dihydroindolyl, dihydroisoindolyl, indazolyl, digidrotsiklopentatienil, benzothienyl, tetragidrobenzotienil, benzofuranyl, imidazopyridinyl, benzotriazolyl, benzodioxolyl, dihydrobenzodioxinyl, quinolinyl, isoquinolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, quinoxalinyl, dihydroquinoxaline, digidrotienodioksinil, quinazolinone, pyrrolopyridazine, digidropirrolizinil, tetragidroindolizinil etc.

Among the cycloalkyl groups, there may be mentioned, without implying any limitation, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, etc.

Among the heterocycloalkyl groups, pyrrolidinyl, tetrahydropyranyl, piperidinyl, piperazinyl, morpholinyl, etc. may be mentioned without implying any limitation.

In another embodiment of the invention, W is preferably a group o

where R4, R5 and A are as defined for formula (I).

More specific,

represents

In particular,

represents

It is beneficial if

represents

Preferably

- 3 037563

In another embodiment, W is preferably a group

where R4, R5 and A are as defined for formula (I). More specifically is

R1 is preferably a phenyl group or a thienyl group. More preferably, R ₁ is a phenyl group.

Preferably, the compounds of formula (I) exhibit the trans configuration as indicated below:

or

More preferably, the compounds of formula (I) exhibit the trans configuration as follows:

Preferably R2 is a hydrogen atom or a fluorine atom. More preferably R2 is a hydrogen atom. Preferably the - (R2) n group is a heme difluoro group.

In some preferred embodiments of the invention, R3 is a hydrogen atom or a methyl group. More preferably, R3 is a hydrogen atom.

In preferred compounds of the invention, J is a —C (O) —group or —CH2— group. Preferably J is a —C (O) - group. Preferably J is a —CH ₂ group.

K is preferably a bond or a -Cy ₁ group selected from a phenyl group, a pyrrolyl group, a thienyl group, a thiazolyl group, a pyridinyl group, a tetrahydrobenzothienyl group, a dihydrothienodioxynyl group, a cyclopropyl group, a cyclobutyl group, or a pyrrolidinyl group. More preferably, K is preferably a bond or a -Cy1 group selected from a thienyl group, a thiazolyl group, or a pyridinyl group.

Preferably L is a —Cy ₂ —group. More preferably Cy ₂ is a co-4 037563 phenyl group, indanyl group, pyrrolyl group, furyl group, thienyl group, thiazolyl group, isothiazolyl group, oxazolyl group, isoxazolyl group, pyrazolyl group, pyridinyl group, pyrazinyl group, pyridazinyl group piridinonilnuyu group, an indolyl group, a dihydroindolyl group, digidroizoindolilnuyu group, indazolyl group, digidrotsiklopentatienilnuyu group, a tetrahydrobenzothienyl group, a benzofuranyl group, imidazopyridinyl group, a benzotriazolyl group, a benzodioxolyl group, a dihydrobenzodioxinyl group, a quinolinyl group, tetrahydroquinolinyl group, tetrahydroisoquinolinyl group, quinoxalinyl group, a dihydroquinoxalinyl group, a quinazolinonyl group, or a pyrrolidinyl group.

Even more preferably, Cy2 is a phenyl group, a pyrrolyl group, a furyl group, a thienyl group, a thiazolyl group, an oxazolyl group, an isoxazolyl group, a pyrazolyl group, a pyridinyl group, a pyrazinyl group, a pyridazinyl group, a pyrimidinyl group, or an imidazopyridinyl group.

Preferably Cy2 is a cycloalkyl group, a heterocycloalkyl group, an aryl group, or a heteroaryl group which are substituted with 1 or 2 groups selected from linear or branched (C ₁ -C ₆ ) alkyl, linear or branched halo (C1-C ₆ ) alkyl, -Y1OR ', -Y ₁ -NR'R, N-oxide, cyano, -C (O) -OR', -C (O) -NR'R, halogen, where R 'and R independently of each other represent a hydrogen atom, a linear or branched (C ₁ -C ₆ ) alkyl group, a linear or branched (C ₁ -C ₆ ) alkoxy group, a tetrahydropyranyl group, or substituents of a pair (R ', R) together with the nitrogen atom carrying them form a non-aromatic ring of 5-7 ring members, which may contain, in addition to the nitrogen atom, a second heteroatom selected from oxygen and nitrogen, it being understood that the second considered nitrogen may be substituted with a linear or branched (C1-C6) alkyl group ...

In some preferred embodiments, K is a thienyl group, a thiazolyl group, or a pyridinyl group, and L is a pyrrolyl group, a furyl group, a thienyl group, a pyrazolyl group, a pyridinyl group, a pyrimidinyl group, or an imidazopyridinyl group, and each said heteroaryl group may be substituted with 1 or 2 groups selected from linear or branched (C ₁ C ₆ ) alkyl, linear or branched halogen (C ₁ -C ₆ ) alkyl, -Y1-OR ', -Y1-NR'R, N-oxide, cyano , -C (O) -NR'R, halogen, where R 'and R independently of each other represent a hydrogen atom, linear or branched (C ₁ -C ₆ ) alkyl group, linear or branched (C ₁ -C ₆ ) an alkoxy group, a linear or branched (C ₁ -C ₆ ) alkoxy (C ₁ -C ₆ ) alkyl group, a tetrahydropyranyl group, or substituents of the pair (R ', R) together with the nitrogen atom carrying them form a non-aromatic ring consisting of 5-7 ring members enov, which may contain, in addition to the nitrogen atom, a second heteroatom selected from oxygen and nitrogen. More preferably, K is a thiazolyl group and L is a pyridinyl group.

Other compounds of the invention that are preferred are those wherein K is a bond and L is a phenyl group, a thiazolyl group, an oxazolyl group, an isoxazolyl group, a pyrazolyl group, a pyridinyl group, a pyrazinyl group, a pyridazinyl group or a pyrimidinyl group, each of which is the group may be substituted by 1 or 2 groups selected from linear or branched (C1 -C ₆ ) alkyl, -Y 1 OR ', -Y1-NR'R, cyano, -C (O) -OR', halogen, while it should be understood that R 'and R independently of each other represent a hydrogen atom, a linear or branched (C ₁ -C ₆ ) alkyl group, or the substituents of the pair (R', R) together with the nitrogen atom carrying them form a non-aromatic ring consisting of 5-7 ring members, which may contain, in addition to the nitrogen atom, a second heteroatom selected from oxygen and nitrogen, it should be understood that the second considered nitrogen may be substituted by 1-2 groups, pre representing a hydrogen atom or a linear or branched (C ₁ -C ₆ ) alkyl group.

In a preferred embodiment, the —JKL group attached to the piperidinyl ring is defined such that J is —C (O) —group, K is —Cy _1, and L is —Cy ₂ —group.

In another preferred embodiment, the —JKL group is defined such that J is —CH ₂ —group, K is a bond, and L is —Cy ₂ —group.

In another preferred embodiment, the —JKL group is defined such that J is —C (O) —group, K is a bond, and L is —Cy ₂ —group.

In another preferred embodiment, the —JKL group is defined such that J is —CH ₂ —group, K is —Cy1— and L is —Cy ₂ .

In preferred compounds of the invention, R4 represents a halogen atom, a linear or branched _(C1-C6) alkyl group, or -Y1-Cy ₃ group. Preferably R ₄ is a bromine atom, a methyl group or a -Cy ₃ group.

- 5 037563

Preferably Cy ₃ is a phenyl group, a naphthyl group, a pyrrolyl group, a furyl group, a thienyl group, a thiazolyl group, a pyrazolyl group, an imidazolyl group, a pyridinyl group, a pyrimidinyl group, a pyridinonyl group, an indolyl group, a benzodioxolyl group, a dihydroxydioxy group a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a pyrrolidinyl group, a tetrahydropyranyl group, or a piperidinyl group.

Cy _{3 is} preferably a cycloalkyl group, a heterocycloalkyl group, an aryl group or a heteroaryl group which is substituted by 1-3 groups selected from linear or branched (C ₁ -C ₆ ) alkyl, linear or branched halogen (C ₁ -C ₆ ) alkyl , -Y1-OR ', -Y1NR'R, cyano, halogen, where R' and R independently of each other represent a hydrogen atom or a linear or branched (C ₁ -C ₆ ) α-alkyl group, or substituents of the pair (R ', R) together with the nitrogen atom carrying them form a non-aromatic ring of 5-7 ring members, which may contain, in addition to the nitrogen atom, a second heteroatom selected from oxygen and nitrogen.

Preferably R5 is a hydrogen atom or a methyl group. More preferably, R5 is a hydrogen atom.

In preferred compounds of the invention, R ₆ represents a hydrogen atom or a methyl group.

R _{7 is} preferably a hydrogen atom, a methyl group or —CH ₂ —Cy ₄ —group.

Preferably Cy ₄ is a phenyl group or a dihydroindolyl group.

Preferred compounds of the invention are

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[3-methyl-5- (pyridin-4-yl) thiophen-2yl] carbonyl} -3-phenylpiperidine-4- yl] carbonyl} piperidin-4-yl) methyl] -7methyl-3,7-dihydro-4/7-pyrrolo [2,3- <7] pyrimidin-4-one;

3 - [(1 - {[(3 ", 47?) - 1 - {[5- (6-aminopyridin-3-yl) -3-fluorothiophen-2yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl } -4-hydroxypiperidin-4yl) methyl] -7-methyl-3,7-dihydro-4/7-pyrrolo [2,3- <7] pyrimidin-4-one;

7-cyclopropyl-3 - [(1 - {[(37?, 47?) - 1 - {[3-fluoro-5- (pyridin-4-yl) thiophene-2yl] carbonyl} -3-phenylpiperidine-4- yl] carbonyl} -4-hydroxypiperidin-4yl) methyl] -3,7-dihydro-4 // - pyrrolo [2,3-b7] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7-phenyl-3,7-dihydro-4/7-pyrrolo [2,3- <7] pyrimidin-4-one;

- 6 037563

3 - [(1 - {[(37?, 47?) - 1 - {[3-fluoro-5- (6-methylpyridin-3-yl) thiophen-2yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperid in-4yl) methyl] -7-phenyl-3,7-dihydro-4 // - pyrrolo [2,3-dG | pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl3,7-dihydro-4 // - pyrrolo [2,3-dG | pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7- (pyridin-3-yl) -3,7-dihydro-4 // - pyrrolo [2,3-dG | pyrimidin-4- is he;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7- (thiophen-3-yl) -3,7-dihydro-4 // - pyrrolo [2,3-b7] pyrimidine-4- is he;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7- (naphthalen-2-yl) -3,7-dihydro-4 // - pyrrolo [2,3-dG | pyrimidine-4- is he;

7- (4-chlorophenyl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6methylpyridin-3-yl) -1,3- thiazol-5-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4 // - pyrrolo [2,3-dG | pyrimidin 4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-4 // - pyrrolo [2,3-dG | pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7- (3-methyl phenyl) -3,7-dihydro-4 // - pyrrolo [2,3-b7] pyrimidin-4-one ;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7- (4-methylphenyl) -3,7-dihydro-4 // - pyrrolo [2,3-b7] pyrimidin-4-one;

7- (3-chlorophenyl) -3 - [(4-hydroxy-1 - {[(ZL, 4L) -1 - {[4-methyl-2- (6methylpyridin-3-yl) -1,3-thiazole- 5-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4/7-pyrrolo [2,3 - </ | pyrimidin 4-one;

7- (furan-3-yl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6methylpyridin-3-yl) -1, 3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-7 037563 yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4 // - pyrrolo [2,3 -d \ pyrimidine

4th;

7- (2-fluorophenyl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6methylpyridin-3-yl) -1,3- thiazol-5-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4 // - pyrrolo [2, 3-J] pyrimidin 4-one;

7- (2-chlorophenyl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6methylpyridin-3-yl) -1,3- thiazol-5-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4 // - pyrrolo [2, 3-J] pyrimidin 4-one;

7- [4- (dimethylamino) phenyl] -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2 (6-methylpyridin-3-yl) - 1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4 // - pyrrolo [2, 3-J] pyrimidine 4 -is he;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7- [4- (4-methylpiperazin-1-yl) phenyl] -3,7-dihydro-4 // - pyrrolo [2,3g7 ] pyrimidin-4-one;

7- [3- (dimethylamino) phenyl] -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2 (6-methylpyridin-3-yl) - 1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4 // - pyrrolo [2, 3-J] pyrimidine 4 -is he;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7- (1/7-pyrrol-1-yl) -3,7-dihydro-4/7-pyrrolo [2,3- <7 ] pyrimidin-4-one;

3 - {[1 - ({(37?, 47?) - 1 - [(2-bromo-4-methyl-1,3-thiazol-5-yl) carbonyl] -3phenylpiperidin-4-yl} carbonyl) - 4-hydroxypiperidin-4-yl] methyl} -7-phenyl3,7-dihydro-4/7-pyrrolo [2,3- <7] pyrimidin-4-one;

5- (5 - {[(37?, 47?) - 4 - ({4-hydroxy-4 - [(4-oxo-7-phenyl-4,7-dihydro-ZN pyrrolo [2,3-b /] pyrimidin-3-yl) methyl] piperidin-1-yl} carbonyl) -3phenylpiperidin-1-yl] carbonyl} -4-methyl-1,3-thiazol-2-yl) pyridine-2carbonitrile;

3 - [(1 - {[(37?, 47?) - 1 - ({2- [6- (dimethylamino) pyridin-3-yl] -4-methyl-1,3thiazol-5-yl} carbonyl) - 3-phenylpiperidin-4-yl] carbonyl} -4-8 037563 hydroxypiperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4/7-pyrrolo [2,3 <7] pyrimidine-4- is he;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - ({4-methyl-2- [6- (trifluoromethyl) pyridin3-yl] -1,3-thiazol-5-yl } carbonyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin4-yl) methyl] -7-phenyl-3,7-dihydro-477-pyrrolo [2,3- <7] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methoxypyridin-3-yl) -4-methyl1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7-phenyl-3,7-dihydro-477-pyrrolo [2,3- <7] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7- (3-methoxyphenyl) -3,7-dihydro-477-pyrrolo [2,3- <7] pyrimidin-4-one;

7- (3-fluorophenyl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6methylpyridin-3-yl) -1,3- thiazol-5-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-477-pyrrolo [2,3- <7] pyrimidin4-one;

3 - [(1 - {[(37?, 47?) - 1 - ({2- [6- (dimethylamino) pyridin-3-yl] -1,3-thiazol-5yl} methyl) -3-phenylpiperidine- 4-yl] carbonyl} -4-hydroxypiperidin-4yl) methyl] -7-phenyl-3,7-dihydro-477-pyrrolo [2,3- <7] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl 3,7-dihydro-4/7-pyrrolo [2,3- <7] pyrimidin-4-one;

7- (4-fluorophenyl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6methylpyridin-3-yl) -1,3- thiazol-5-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-477-pyrrolo [2,3- <7] pyrimidin4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (thiophen-3-yl) -3,7-dihydro-47 / -pyrrolo [2,3-b7] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - ({2- [6- (morpholin-4-yl) pyridin-3-yl] 1,3-thiazol-5- yl} methyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7-phenyl-3,7-dihydro-477-pyrrolo [2,3- <7] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3methylphenyl) -3,7-dihydro-477-pyrrolo [2,3- <7] pyrimidin-4-one;

- 9 037563

3 - [(4-hydroxy-1- {[(37?, 47?) - 1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4methylphenyl) -3,7-dihydro-477-pyrrolo [2,3-dH | pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4methoxyphenyl) -3,7-dihydro-47) pyrrolo [2,3-D] pyrimidin-4-one;

3 - [(1 - {[(37?, 47?) - 1 - ({2- [6- (dimethylamino) pyridin-3-yl] -1,3-thiazol-5yl} methyl) -3-phenylpiperidine- 4-yl] carbonyl} -4-hydroxypiperidin-4yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-477-pyrrolo [2,3-dH | pyrimidin-4-one;

7- (4-chlorophenyl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methylpyridin-3yl) -1,3-thiazole-5- yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -3,7-dihydro-47 / -pyrrolo [2,3-D] pyrimidin-4-one;

7- (4-chlorophenyl) -3 - [(1 - {[(37?, 47?) - 1 - ({2- [6- (dimethylamino) pyridin-3yl] -1,3-thiazol-5-yl } methyl) -3-phenylpiperidin-4-yl] carbonyl} -4hydroxypiperidin-4-yl) methyl] -3,7-dihydro-47 / -pyrrolo [2,3-D] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -6,8-dimethylpyrimido [5 ', 4': 4,5] pyrrolo [1,2-b] pyridazin-4 (377) -one ;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7- [3- (morpholin-4-yl) phenyl] -3,7-dihydro-477-pyrrolo [2,3D] pyrimidine-4 -is he;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7- [4- (morpholin-4-yl) phenyl] -3,7-dihydro-477-pyrrolo [2,3D] pyrimidine-4 -is he;

7- (3-chlorophenyl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methylpyridin-3yl) -1,3-thiazole-5- yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -3,7-dihydro-477-pyrrolo [2,3-d] pyrimidin-4-one;

- [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methyl-1-oxidopyridin3-yl) -1,3-thiazol-5-yl ] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin4-yl) methyl] -7-phenyl-3,7-dihydro-477-pyrrolo [2,3-dG | pyrimidin-4-one;

- 10 037563

3 - [(4-hydroxy-1 - {[(37?, 47?) - 3-phenyl-1 - ({2- [6- (piperazin-1yl) pyridin-3-yl] -1,3-thiazole -5-yl} methyl) piperidin-4-yl] carbonyl} piperidin4-yl) methyl] -7-phenyl-3,7-dihydro-4 // - pyrrolo [2,3-dG | pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 3-phenyl-1 - ({2- [6- (trifluoromethyl) pyridin3-yl] -1,3-thiazol-5-yl } methyl) piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] 7- (4-methoxyphenyl) -3,7-dihydro-4 // - pyrrolo [2,3-b /] pyrimidin-4- is he;

7- (3,4-dichlorophenyl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6methylpyridin-3-yl) -1, 3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4/7-pyrrolo [2,3- <7] pyrimidine 4- is he;

5- (5 - {[(37?, 47?) - 4 - ({4-hydroxy-4 - [(4-oxo-7-phenyl-4,7-dihydro-3 // pyrrolo [2,3- d /] pyrimidin-3-yl) methyl] piperidin-1-yl} carbonyl) -3phenylpiperidin-1-yl] methyl} -1,3-thiazol-2-yl) pyridine-2-carbonitrile;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3methoxyphenyl) -3,7-dihydro-4 // - pyrrolo [2,3-b] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7- (pyridin-2-yl) -3,7-dihydro-4/7-pyrrolo [2,3- <7] pyrimidine-4 -is he;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7- [4- (hydroxymethyl) phenyl] -3,7-dihydro-4 // - pyrrolo [2,3g /] pyrimidine-4- is he;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7- (thiophen-2-yl) -3,7-dihydro-4 // - pyrrolo [2,3-b /] pyrimidine-4 -is he;

7- (3,4-dimethoxyphenyl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6methylpyridin-3-yl) -1, 3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4/7-pyrrolo [2,3- <7] pyrimidine 4- is he;

7- (3,4-dimethoxyphenyl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6methylpyridin-3-yl) -1,3-thiazole- 5-yl] methyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4/7-pyrrolo [2,3- <7] pyrimidin 4-one;

- 11 037563

3 - [(4-hydroxy-1- {[(37?, 47?) - 1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7 (pyridin-3-yl) -3,7-dihydro-477-pyrrolo [2,3- <7] pyrimidin-4-one;

5 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -1-phenyl1,5-dihydro-477-pyrazolo [3,4- <7] pyrimidin-4-one;

7- (3,5-dimethoxyphenyl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6methylpyridin-3-yl) -1, 3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-477-pyrrolo [2,3- <7] pyrimidin 4-one;

7- (3,5-dimethoxyphenyl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6methylpyridin-3-yl) -1,3-thiazole- 5-yl] methyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-477-pyrrolo [2,3- <7] pyrimidin 4-one;

7- (4-fluorophenyl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methylpyridin-3yl) -1,3-thiazole-5- yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -3,7-dihydro-477-pyrrolo [2,3-b7] pyrimidin-4-one;

4- {3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] methyl} - 3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] 4-oxo-3,4-dihydro-777-pyrrolo [2,3-b7] pyrimidin-7-yl} benzonitrile;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7- (1-methyl-177-pyrazol-4-yl) -3,7-dihydro-477-pyrrolo [2,3 <Dpyrimidine- 4th;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (1methyl-177-pyrazol-4-yl) -3,7-dihydro-477-pyrrolo [2,3- <7] pyrimidine-4 -is he;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7- [3- (hydroxymethyl) phenyl] -3,7-dihydro-47 / -pyrrolo [2,3 <Dpyrimidin-4-one;

7- [3- (hydroxymethyl) phenyl] -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6methylpyridin-3-yl) -1,3-thiazole -5-yl] methyl} -3-phenylpiperidin-4- 12 037563 yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4 // - pyrrolo [2,3-J] pyrimidine

4th;

7- (4-chloro-3-fluorophenyl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - Г {[4-methyl-2- (6methylpyridin-3-yl) -1 , 3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4/7-pyrrolo [2,3- <7] pyrimidine 4 -is he;

5 - [(4-hydroxy-1 - {[(37?, 47?) - G {[4-methyl-2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] carbonyl} - 3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -1-phenyl-1,5-dihydro-4/7-pyrazolo [3,4- <7] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - G {[2- (6-methoxypyridin-3-yl) -1,3-thiazol5-yl] methyl} -3-phenylpiperidine- 4-yl] carbonyl} piperidin-4-yl) methyl] -7- (1methyl-1/7-pyrazol-4-yl) -3,7-dihydro-4/7-pyrrolo [2,3- <7] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - G {[2- (6-methoxypyridin-3-yl) -1,3-thiazol5-yl] methyl} -3-phenylpiperidine- 4-yl] carbonyl} piperidin-4-yl) methyl] -7- [3 (hydroxymethyl) phenyl] -3,7-dihydro-4/7-pyrrolo [2,3- <7] pyrimidin-4-one;

7- (4-fluorophenyl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - Г {[2- (6-methoxypyridin 3-yl) -1,3-thiazol-5- yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -3,7-dihydro-4 // - pyrrolo [2,3-b] pyrimidin-4-one;

7- (4-chloro-3-fluorophenyl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - Г {[2- (6methylpyridin-3-yl) -1,3-thiazole -5-yl] methyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4/7-pyrrolo [2,3- <7] pyrimidin 4-one;

7- (3-chloro-5-methoxyphenyl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - Г {[4-methyl-2 (6-methylpyridin-3-yl) - 1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4/7-pyrrolo [2,3- <7] pyrimidine 4th;

7- (3-chloro-5-methoxyphenyl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - Г {[2- (6methylpyridin-3-yl) -1,3-thiazole -5-yl] methyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4/7-pyrrolo [2,3- <7] pyrimidin 4-one;

7- (4-fluoro-3-methoxyphenyl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - Г {[4-methyl-2 (6-methylpyridin-3-yl) - 1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4/7-pyrrolo [2,3- <7] pyrimidine 4th;

- 13 037563

7- (4-fluoro-3-methoxyphenyl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1- {[2- (6methylpyridin-3-yl) -1,3- thiazol-5-yl] methyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4/7-pyrrolo [2,3- <7] pyrimidine

4th;

7- (4-fluoro-3-methoxyphenyl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6methoxypyridin-3-yl) -1,3- thiazol-5-yl] methyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4/7-pyrrolo [2,3-dG | pyrimidin 4-one;

7- (4-chloro-3-methoxyphenyl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2 (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4/7-pyrrolo [2,3-dG | pyrimidin 4-one;

7- (4-chloro-3-methoxyphenyl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6methylpyridin-3-yl) -1,3- thiazol-5-yl] methyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4/7-pyrrolo [2,3-dG | pyrimidin 4-one;

7- (4-chlorophenyl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methoxypyridin · 3-yl) -1,3-thiazole- 5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -3,7-dihydro-4 // - pyrrolo [2,3-b7] pyrimidin-4-one;

7- (5-chlorothiophen-2-yl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6methylpyridin-3-yl) - 1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4 // - pyrrolo [2,3-d] pyrimidine 4 -is he;

7- (5-chlorothiophen-2-yl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6methylpyridin-3-yl) -1,3- thiazol-5-yl] methyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4/7-pyrrolo [2,3- <7] pyrimidin 4-one;

7-bromo-3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methylpyridin-3yl) -1,3-thiazole-5- yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] pyrrolo [2,1 -f] [1,2,4] triazin-4 (377) -one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7- (5-methylthiophen-2-yl) -3,7-dihydro-4 // - pyrrolo [2,3-0] pyrimidine- 4on;

- 14 037563

3 - [(4-hydroxy-1- {[(37?, 47?) - 1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (5methylthiophen-2-yl) -3,7-dihydro-477-pyrrolo [2,3- <7] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (5methylthiophen-2-yl) -3,7-dihydro-477-pyrrolo [2,3- <7] pyrimidin-4-one;

7- [4- (hydroxymethyl) phenyl] -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6methylpyridin-3-yl) -1,3-thiazole -5-yl] methyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-47 / -pyrrolo [2,3-dH | pyrimidin4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- [4 (hydroxymethyl) phenyl] -3,7-dihydro-477-pyrrolo [2,3- <7] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7phenylpyrrolo [2,1-f] [1,2,4] triazin-4 (377) -one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7-phenyl pyrrole o [2, lf] [1, 2,4] triazin-4 (377) -one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (thiophen 2-yl) -3,7-dihydro-47 / -pyrrolo [2,3-b7] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7 (thiophen-2-yl) -3,7-dihydro-477-pyrrolo [2,3- <7] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7-phenylthieno [3,4-b7] pyrimidin-4 (377) -one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7phenylthieno [3,4-b7] pyrimidin-4 (377) -one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7-phenyl-3,5-dihydro-477-pyrrolo [3,2- <7] pyrimidin-4-one;

- 15 037563

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl3,5-dihydro-477-pyrrolo [3,2- <7] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl 3,5-dihydro-477-pyrrolo [3,2- <7] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3methylphenyl) -3,7-dihydro-477-pyrrolo [2,3- <7] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4methylphenyl) -3,7-dihydro-477-pyrrolo [2,3- <7] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7 (thiophen-3-yl) -3,7-dihydro-477-pyrrolo [2,3- <7] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- [3 (morpholin-4-yl) phenyl] -3,7-dihydro-47 / -pyrrolo [2,3-b7] pyrimidine-4 -is he;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- [3 (morpholin-4-yl) phenyl] -3,7-dihydro-47 / -pyrrolo [2,3-b7] pyrimidine-4 -is he;

3 - {[1 - ({(37?, 47?) - 1 - [(2-bromo-1,3-thiazol-5-yl) methyl] -3-phenylpiperidin4-yl} carbonyl) -4-hydroxypiperidine- 4-yl] methyl} -7-phenyl-3,7-dihydro-477pyrrolo [2,3-b /] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7- (4-hydroxyphenyl) -3,7-dihydro-47 / -pyrrolo [2,3-b7] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4hydroxyphenyl) -3,7-dihydro-47 / -pyrrolo [2,3-b7] pyrimidin-4-one;

- [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-hydroxypyridin-3-yl) -1,3thiazol-5-yl] methyl} -3-phenylpiperidine- 4-yl] carbonyl} piperidin-4-yl) methyl] 7- (4-hydroxyphenyl) -3,7-dihydro-477-pyrrolo [2,3- <7] pyrimidin-4-one;

- 16 037563

- [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-hydroxypyridin-3-yl) -1,3thiazol-5-yl] methyl} -3-phenylpiperidine-4- yl] carbonyl} piperidin-4-yl) methyl] 7-phenyl-3,7-dihydro-4/7-pyrrolo [2,3-dH | pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - ({2- [6- (hydroxymethyl) pyridin-3-yl] 1,3-thiazol-5-yl} methyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7-phenyl-3,7-dihydro-4 // - pyrrolo [2,3-D | pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7- [3- (trifluoromethyl) phenyl] -3,7-dihydro-4H-pyrrolo [2,3D] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- [3 (trifluoromethyl) phenyl] -3,7-dihydro-4 // - pyrrolo [2,3-dG | pyrimidin-4-one;

7- [4- (difluoromethyl) phenyl] -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2 (6-methylpyridin-3-yl) - 1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4/7-pyrrolo [2,3-dG | pyrimidin 4-one;

7- [4- (difluoromethyl) phenyl] -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6methylpyridin-3-yl) -1,3-thiazole -5-yl] methyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-477-pyrrolo [2,3-D | pyrimidin 4-one;

7- [4- (difluoromethyl) phenyl] -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6methoxypyridin-3-yl) -1,3-thiazole -5-yl] methyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4/7-pyrrolo [2,3-dG | pyrimidin 4-one;

7- [1 - (difluoromethyl) -1 // - pyrazol-4-yl] -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 {[4-methyl-2- ( 6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4 / 7pyrrolo [2 , 3-D] pyrimidin-4-one;

7- [1 - (difluoromethyl) -1 // - pyrazol-4-yl] -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 {[2- (6-methylpyridine- 3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4/7-pyrrolo [2,3 -yG | pyrimidin 4-one;

- 17 037563

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (3-methyl-377-imidazo [4,5-b] pyridin6-yl) -1,3- thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7-phenyl-3,7-dihydro-4/7-pyrrolo [2,3- <7] pyrimidine -4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3methoxyphenyl) -3,7-dihydro-4 // - pyrrolo [2,3-b7] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4methoxyphenyl) -3,7-dihydro-4 // - pyrrolo [2,3-b7] pyrimidin-4-one;

7- [3- (dimethylamino) phenyl] -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6methylpyridin-3-yl) -1,3-thiazole -5-yl] methyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3- <7] pyrimidin 4-one;

7- (3-fluorophenyl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methylpyridin-3yl) -1,3-thiazole-5- yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -3,7-dihydro-4 // - pyrrolo [2,3-b7] pyrimidin-4-one;

3 - [(1 - {[(37?, 47?) - 1 - {[2- (5-fluoro-6-hydroxypyridin-3-yl) -1,3-thiazol-5yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} -4-hydroxypiperidin-4yl) methyl] -7-phenyl-3,7-dihydro-4/7-pyrrolo [2,3- <7] pyrimidin-4-one;

5- (5 - {[(37?, 47?) - 4 - ({4-hydroxy-4 - [(4-oxo-7-phenyl-4,7-dihydro-3/7-pyrrolo [2,3-r7 ] pyrimidin-3-yl) methyl] piperidin-1-yl} carbonyl) -3phenylpiperidin-1-yl] methyl} -1,3-thiazol-2-yl) pyridine-3-carboxamide;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - ({2- [5- (hydroxymethyl) pyridin-3-yl] 1,3-thiazol-5-yl} methyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7-phenyl-3,7-dihydro-477-pyrrolo [2,3- <7] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 3-phenyl-1 - ({2- [6- (tetrahydro-277-pyran-4yloxy) pyridin-3-yl] -1 , 3-thiazol-5-yl} methyl) piperidin-4yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4 // - pyrrolo [2,3g7] pyrimidine-4- is he;

3 - [(1 - {[(37?, 47?) - 1 - {[2- (5-amino-6-methoxypyridin-3-yl) -1,3-thiazol-5yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} -4-hydroxypiperidin-4yl) methyl] -7-phenyl-3,7-dihydro-4/7-pyrrolo [2,3- <7] pyrimidin-4-one;

- 18 037563

3 - {[1 - ({(37?, 47?) - 1 - [(2-bromo-1,3-thiazol-5-yl) methyl] -3-phenylpiperidin4-yl} carbonyl) -4-hydroxypiperidine- 4-yl] methyl} -7- (4-methoxyphenyl) -3,7 dihydro-47) pyrrolo [2,3-b7] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 3-phenyl-1 - {[2- (thiophen-2-yl) -1,3-thiazol-5yl] methyl} piperidine- 4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4methoxyphenyl) -3,7-dihydro-477-pyrrolo [2,3 - </] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 3-phenyl-1 - {[2- (pyrimidin-5-yl) -1,3thiazol-5-yl] methyl} piperidine- 4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4methoxyphenyl) -3,7-dihydro-477-pyrrolo [2,3 - </] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (1-methyl-177-pyrazol-5-yl) -1,3thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] 7- (4-methoxyphenyl) -3,7-dihydro-47 / -pyrrolo [2,3-b7] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (1-methyl-177-pyrazol-4-yl) -1,3thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] 7- (4-methoxyphenyl) -3,7-dihydro-47 / -pyrrolo [2,3-b7] pyrimidin-4-one;

3 - [(4-hydroxy-1- {[(37 ?, 47?) - 1 - {[2- (1-methyl-177-pyrrol-3-yl) -1,3-thiazol 5-yl] methyl } -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4methoxyphenyl) -3,7-dihydro-47 / pyrrolo [2,3-b7] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 3-phenyl-1 - {[2- (thiophen-3-yl) -1,3-thiazol-5yl] methyl} piperidine- 4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4methoxyphenyl) -3,7-dihydro-47 / pyrrolo [2,3-b7] pyrimidin-4-one;

7- (2,3-dihydro-1,4-benzodioxin-6-yl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 {[4-methyl-2- ( 6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-477pyrrolo [2,3 -b /] pyrimidin-4-one;

7- (2,3-dihydro-1,4-benzodioxin-6-yl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 {[2- (6-methylpyridine- 3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-47 / -pyrrolo [2,3- (1] pyrimidin4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3hydroxyphenyl) -3,7-dihydro-47 / -pyrrolo [2,3-b7] pyrimidin-4-one;

- 19 037563

3 - {[1 - ({(37?, 47?) - 1 - [(2-bromopyridin-4-yl) carbonyl] -3phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidin-4-yl] methyl] -7-phenyl3,7-dihydro-477-pyrrolo [2,3-b7] pyrimidin-4-one;

3 - {[1 - ({(37?, 47?) - 1 - [(5-bromopyridin-3-yl) carbonyl] -3phenylpiperidin-4-yl] carbonyl) -4-hydroxypiperidin-4-yl] methyl} -7-phenyl3,7-dihydro-4 // - pyrrolo [2,3-dG | pyrimidin-4-one;

7- (3-chlorophenyl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6hydroxypyridin-3-yl) -1,3-thiazole-5- yl] methyl] -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-477-pyrrolo [2,3- <7] pyrimidin4-one;

3 - [(1 - {[(37?, 47?) - 1 - {[2- (furan-3-yl) -1,3-thiazol-5-yl] methyl} -3phenylpiperidin-4-yl] carbonyl } -4-hydroxypiperidin-4-yl) methyl] -7- (4methoxyphenyl) -3,7-dihydro-477-pyrrolo [2,3-b7] pyrimidin-4-one;

3 - [(1 - {[(37?, 47?) - 1 - {[2- (furan-2-yl) -1,3-thiazol-5-yl] methyl} -3phenylpiperidin-4-yl] carbonyl } -4-hydroxypiperidin-4-yl) methyl] -7- (4methoxyphenyl) -3,7-dihydro-477-pyrrolo [2,3-b7] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 3-phenyl-1 - {[2- (thiophen-2-yl) -1,3-thiazol-5yl] methyl] piperidine- 4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3methoxyphenyl) -3,7-dihydro-477-pyrrolo [2,3-b7] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 3-phenyl-1 - {[2- (pyrimidin-5-yl) -1,3thiazol-5-yl] methyl] piperidine- 4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3methoxyphenyl) -3,7-dihydro-477-pyrrolo [2,3- <Dpyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (1-methyl-1H-pyrazol-5-yl) -1,3thiazol-5-yl] methyl] -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] 7- (3-methoxyphenyl) -3,7-dihydro-4/7-pyrrolo [2,3-b7] pyrimidin-4-one ;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (1-methyl-1/7-pyrazol-4-yl) -1,3thiazol-5-yl]] methyl] -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] 7- (3-methoxyphenyl) -3,7-dihydro-4/7-pyrrolo [2,3-b7] pyrimidine-4 -is he;

3 - [(4-hydroxy-1- {[(37 ?, 47?) - 1 - {[2- (1-methyl-177-pyrrol-3-yl) -1,3-thiazol 5-yl] methyl } -3-phenylpiperidin-4-yl] carbonyl] piperidin-4-yl) methyl] -7- (3methoxyphenyl) -3,7-dihydro-477-pyrrolo [2,3-b7] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 3-phenyl-1 - {[2- (thiophen-3-yl) -1,3-thiazol-5yl] methyl] piperidine- 4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3methoxyphenyl) -3,7-dihydro-477-pyrrolo [2,3-b7] pyrimidin-4-one;

- 20 037563

3 - [(1 - {[(37?, 47?) - 1 - {[2- (furan-3-yl) -1,3-thiazol-5-yl] methyl} -3phenylpiperidin-4-yl] carbonyl } -4-hydroxypiperidin-4-yl) methyl] -7- (3methoxyphenyl) -3,7-dihydro-4 // - pyrrolo [2,3-b] pyrimidin-4-one;

3 - [(1 - {[(37?, 47?) - 1 - {[2- (furan-2-yl) -1,3-thiazol-5-yl] methyl} -3phenylpiperidin-4-yl] carbonyl } -4-hydroxypiperidin-4-yl) methyl] -7- (3methoxyphenyl) -3,7-dihydro-4 // - pyrrolo [2,3 - </] pyrimidin-4-one;

7- (2,3-dihydro-1,4-benzodioxin-6-yl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 {[2- (6-methoxypyridine- 3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4/7-pyrrolo [2,3 - <7] pyrimidin 4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3,4,5trimethoxyphenyl) -3,7-dihydro-4 // - pyrrolo [2,3-b /] pyrimidin-4-one ;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3,4,5 · trimethoxyphenyl) -3,7-dihydro-4 // - pyrrolo [2,3-b /] pyrimidine-4 -is he;

7- (1,3-benzodioxol-5-yl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2 (6-methylpyridin-3- yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4/7-pyrrolo [2,3- < 7] pyrimidin 4-one;

7- (1,3-benzodioxol-5-yl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6methylpyridin-3-yl) -1, 3-thiazol-5-yl] methyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4/7-pyrrolo [2,3- <7] pyrimidine 4- is he;

7- (1,3-benzodioxol-5-yl) -3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6methoxypyridin-3-yl) -1, 3-thiazol-5-yl] methyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4/7-pyrrolo [2,3- <7] pyrimidine 4- is he;

3 - {[1 - ({(37?, 47?) - 1 - [(5-bromopyridin-3-yl) methyl] -3-phenylpiperidin-4yl} carbonyl) -4-hydroxypiperidin-4-yl] methyl} -7-phenyl-3,7-dihydro-4 // pyrrolo [2,3 - </] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-21 037563 yl) methyl] -7- (3,4,5-trimethoxyphenyl) -3,7-dihydro-477-pyrrolo [2,3 - </ ] pyrimidin4-one;

3 - [(4-hydroxy-1- {[(37?, 47?) - 3-phenyl-1- (pyridin-3-ylmethyl) piperidin4-yl] carbonyl} piperidin-4-yl) methyl] -7- phenyl-3,7-dihydro-4 // - pyrrolo [2,3r7] pyrimidin-4-one;

3 - {[4-hydroxy-1 - ({(37?, 47?) - 1 - [(6'-methyl-3,3'-bipyridin-5yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl ) piperidin-4-yl] methyl} -7phenyl-3,7-dihydro-4 // - pyrrolo [2,3-b /] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7- (3-hydroxyphenyl) -3,7-dihydro-4 // - pyrrolo [2,3-b /] pyrimidin-4-one ;

3 - [(4-hydroxy-1- {[(37?, 47?) - 3-phenyl-1- (pyridin-4-ylmethyl) piperidin4-yl] carbonyl} piperidin-4-yl) methyl] -7- phenyl-3,7-dihydro-477-pyrrolo [2,3- <7] pyrimidin-4-one;

5- [5 - ({(37?, 47?) - 4 - [(4-hydroxy-4 - {[7- (3-methoxyphenyl) -4-oxo-4,7 dihydro-37 / -pyrrolo [2, 3-b7] pyrimidin-3-yl] methyl} piperidin-1-yl) carbonyl] -3phenylpiperidin-1-yl} methyl) -1,3-thiazol-2-yl] pyridine-2-carbonitrile;

5- [5 - ({(37?, 47?) - 4 - [(4 - {[7- (4-chlorophenyl) -4-oxo-4,7-dihydro-377pyrrolo [2,3-r7] pyrimidine -3-yl] methyl} -4-hydroxypiperidin-1-yl) carbonyl] -3-phenylpiperidin-1-yl} methyl) -1,3-thiazol-2-yl] pyridine-2-carbonitrile;

5- [5 - ({(37?, 47?) - 4 - [(4-hydroxy-4 - {[7- (4-methoxyphenyl) -4-oxo-4,7 dihydro-3 // - pyrrolo [2 , 3-b /] pyrimidin-3-yl] methyl} piperidin-1-yl) carbonyl] -3phenylpiperidin-1-yl} methyl) -1,3-thiazol-2-yl] pyridine-2-carbonitrile;

- [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (morpholin-4-yl) -1,3-thiazol5-yl] carbonyl} -3- phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7phenyl-3,7-dihydro-477-pyrrolo [2,3-b7] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - ({2- [6- (2-methoxyethoxy) pyridin-3-yl] 1,3-thiazol-5-yl}) methyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7-phenyl-3,7-dihydro-477-pyrrolo [2,3- <7] pyrimidin-4-one;

- [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (4-methylpiperazin-1-yl) - 1,3-thiazol5-yl] methyl} -3-phenylpiperidine- 4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl 3,7-dihydro-477-pyrrolo [2,3- <7] pyrimidin-4-one;

- 22 037563

- [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-hydroxypyridin-3-yl) -1,3thiazol-5-yl] methyl} -3-phenylpiperidine- 4-yl] carbonyl} piperidin-4-yl) methyl] 7- (3-hydroxyphenyl) -3,7-dihydro-477-pyrrolo [2,3- <7] pyrimidin-4-one;

3 - {[4-hydroxy-1 - ({(37?, 47?) - 1 - [(4-methyl-1,3-thiazol-5-yl) carbonyl] -3phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7-phenyl-3,7-dihydro477-pyrrolo [2,3 - <7] pyrimidin-4-one;

3 - {[4-hydroxy-1 - ({(37?, 47?) - 1 - [(2-methyl-1,3-thiazol-5-yl) carbonyl] -3phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7-phenyl-3,7-dihydro477-pyrrolo [2,3 - <7] pyrimidin-4-one;

3 - {[1 - ({(37?, 47?) - 1 - [(2-chloro-1,3-thiazol-5-yl) carbonyl] -3phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidine- 4-yl] methyl} -7-phenyl3,7-dihydro-477-pyrrolo [2,3- <7] pyrimidin-4-one;

3 - [(4-hydroxy-1- {[(37 ?, 47?) - 3-phenyl- 1- (pyrazin-2-ylmethyl) piperidin 4-yl] carbonyl} piperidin-4-yl) methyl] -7 -phenyl-3,7-dihydro-47) -pyrrolo [2,3r7] pyrimidin-4-one;

3 - [(4-hydroxy-1 - {[(37?, 47?) - 3-phenyl-1- (1,3-thiazol-5ylmethyl) piperidin-4-yl] carbonyl} piperidin-4-yl) methyl ] -7-phenyl-3,7-dihydro-47) -pyrrolo [2,3-b7] pyrimidin-4-one;

5- [5 - ({(37?, 47?) - 4 - [(4 - {[7- (4-fluorophenyl) -4-oxo-4,7-dihydro-377pyrrolo [2,3- <7] pyrimidin-3-yl] methyl} -4-hydroxypiperidin-1-yl) carbonyl] -3phenylpiperidin-1-yl} methyl) -1,3-thiazol-2-yl] pyridine-2-carbonitrile;

methyl 3 - {[(37?, 47?) - 4 - ({4-hydroxy-4 - [(4-oxo-7-phenyl-4,7-dihydro-377pyrrolo [2,3-b /] pyrimidine- 3-yl) methyl] piperidin-1-yl} carbonyl) -3phenylpiperidin-1-yl] carbonyl} benzoate;

5 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -1- (4methoxyphenyl) -1,5-dihydro-477-pyrazolo [3,4- <7] pyrimidin-4-one;

5 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -1- (4methoxyphenyl) -1,5-dihydro-477-pyrazolo [3,4- <7] pyrimidin-4-one;

5 - [(4-hydroxy-1 - {[(37?, 47?) - 1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -1- (4-methoxyphenyl) -1,5-dihydro-47 / -pyrazolo [3,4-b7] pyrimidin-4-one;

- 23 037563

3 - {[4-hydroxy-1 - ({(37?, 47?) - 1 - [(2- {6 - [(2-methoxyethyl) amino] pyridin3-yl} -1,3-thiazol-5- yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) piperidin-4yl] methyl} -7-phenyl-3,7-dihydro-4 // - pyrrolo [2,3-b7] pyrimidin-4-one;

3 - {[4-hydroxy-1 - ({(37?, 47?) - 1 - [(1-methyl-177-pyrazol-4-yl) methyl] -3phenylpiperidin-4-yl} carbonyl) piperidin-4 -yl] methyl} -7- (4-methoxyphenyl) 3,7-dihydro-4 // - pyrrolo [2,3-b] pyrimidin-4-one;

3 - [(4-hydroxy-1- {[(37?, 47?) - 3-phenyl-1- (pyrazin-2-ylmethyl) piperidin 4-yl] carbonyl} piperidin-4-yl) methyl] -7 - (4-methoxyphenyl) -3,7-dihydro-4 / 7pyrrolo [2,3-g7] pyrimidin-4-one;

3 - {[4-hydroxy-1 - ({(37?, 47?) - 1 - [(5-methyl-1,3-thiazol-2-yl) methyl] -3phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7- (4-methoxyphenyl) 3,7-dihydro-4 // - pyrrolo [2,3-b] pyrimidin-4-one;

3 - {[1 - ({(37?, 47?) - 1 - [(5-bromopyridin-3-yl) methyl] -3-phenylpiperidin-4yl} carbonyl) -4-hydroxypiperidin-4-yl] methyl} -7- (4-methoxyphenyl) -3,7 dihydro-4 // - pyrrolo [2,3-b7] pyrimidin-4-one;

methyl 5 - {[(37?, 47?) - 4 - ({4-hydroxy-4 - [(4-oxo-7-phenyl-4,7-dihydro-37 / pyrrolo [2,3-r7] pyrimidine -3-yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-Pyl] carbonyl} pyridine-3-carboxylate;

1- (2,3-dihydro-1,4-benzodioxin-6-yl) -5 - [(4-hydroxy-1 - {[(37?, 47?) - 1 {[4-methyl-2- ( 6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -1,5-dihydro-4 / 7pyrazolo [3 , 4- <7] pyrimidin-4-one;

1- (2,3-dihydro-1,4-benzodioxin-6-yl) -5 - [(4-hydroxy-1 - {[(37?, 47?) - 1 {[2- (6-methylpyridine- 3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-yl) methyl] -1,5-dihydro-4 // - pyrazolo [3,4g7 ] pyrimidin-4-one;

3 - {[4-hydroxy-1 - ({(37?, 47?) - 1 - [(5-methyl-1,3-thiazol-2-yl) methyl] -3phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7-phenyl-3,7-dihydro4 // - pyrrolo [2,3 - <7] pyrimidin-4-one;

3 - {[4-hydroxy-1 - ({(37?, 47?) - 1 - [(3-methyl-1,2-oxazol-5-yl) methyl] -3phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7-phenyl-3,7-dihydro4 // - pyrrolo [2,3 - <7] pyrimidin-4-one;

- 24 037563

3 - {[1 - ({(37?, 47?) - 1 - [(2,4-dimethyl-1,3-thiazol-5-yl) methyl] -3phenylpiperidin-4-yl) carbonyl) -4- hydroxypiperidin-4-yl] methyl) -7- (4methoxyphenyl) -3,7-dihydro-47) pyrrolo [2,3-b7] pyrimidin-4-one;

- [(4-hydroxy-1 - {[(37?, 47?) - 1 - (1,3-oxazol-4-ylmethyl) -3phenylpiperidin-4-yl] carbonyl) piperidin-4-yl) methyl] - 7- (4-methoxyphenyl) 3,7-dihydro-47 / -pyrrolo [2,3- <7] pyrimidin-4-one;

3 - {[4-hydroxy-1 - ({(37?, 47?) - 1 - [(5-methyl-1,3-oxazol-2-yl) methyl] -3phenylpiperidin-4-yl) carbonyl) piperidine -4-yl] methyl) -7- (4-methoxyphenyl) 3,7-dihydro-477-pyrrolo [2,3- <7] pyrimidin-4-one;

5 - {[(37?, 47?) - 4 - ({4-hydroxy-4 - [(4-oxo-7-phenyl-4,7-dihydro-377pyrrolo [2,3-b /] pyrimidine-3 -yl) methyl] piperidin-1-yl} carbonyl) -3phenylpiperidin-1-yl] methyl) pyrid-yn-2-carbonitrile;

3- [[4-hydroxy- 1 - [(37?, 47?) - 1- [4-methyl-2- (6-methyl-3-pyrid yl) thiazole-5 carbonyl] -3-phenylpiperidine-4- carbonyl] -4-piperidyl] methyl] -7- [4 (hydroxymethyl) phenyl] pyrrolo [2,1 -f \ [1,2,4] triazin-4-one;

3- [[4-hydroxy- 1 - [(37?, 47?) - 1- [4-methyl-2- (6-methyl-3-pyrid yl) thiazole-5 carbonyl] -3-phenylpiperidine-4- carbonyl] -4-piperidyl] methyl] -7- [4 (hydroxymethyl) phenyl] thieno [3,4- <7] pyrimidin-4-one;

3 - [[4-hydroxy-1 - [(37?, 47?) - 1- [2- (6-methyl-3-pyridyl) thiazole-5carbonyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl ] methyl] -7- (3methoxyphenyl) pyrrolo [2,3- <7] pyrimidin-4-one;

3 - [[3,3-difluoro-4-hydroxy-1 - [(37?, 47?) - 1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3- phenylpiperidin-4-carbonyl] -4-piperidyl] methyl] -7-phenylpyrrolo [2,3-b7] pyrimidin-4-one;

3 - [[3,3-difluoro-4-hydroxy-1 - [(37?, 47?) - 1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3- phenylpiperidin-4-carbonyl] -4piperidyl] methyl] -7- (4-methoxyphenyl) pyrrolo [2,3- <7] pyrimidin-4-one;

3 - [[4-hydroxy-1 - [(37?, 47?) - 1 - [(2-methoxypyrimidin-4-yl) methyl] -3phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7- phenylpyrrolo [2,3 <7] pyrimidin-4-one;

3 - [[4-hydroxy-1 - [(37?, 47?) - 1 - [(2-methoxypyrimidin-4-yl) methyl] -3phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7- (4methoxyphenyl) pyrrolo [2,3- <7] pyrimidin-4-one;

- 25 037563

3- [[4-hydroxy-l - [(37?, 47?) - l - [(5-methylpyrazin-2-yl) methyl] -3phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7- phenylpyrrolo [2,3b /] pyrimidin-4-one;

3 - [[4-hydroxy-1 - [(37?, 47?) - 1 - [(5-methylpyrazin-2-yl) methyl] -3phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7- (4methoxyphenyl) pyrrolo [2,3- <Apyrimidin-4-one;

- [[4-hydroxy-1 - [(37?, 47?) - 3-phenyl-1 - (pyrimidin-2ylmethyl) piperidine-4-carbonyl] -4-piperid yl] methyl] -7-phenylpyrrolo [2, 3b7] pyrimidin-4-one;

- [[4-hydroxy-1 - [(37?, 47?) - 3-phenyl-1 - (pyrimidin-2ylmethyl) piperidine-4-carbonyl] -4-piperidyl] methyl] -7- (4methoxyphenyl) pyrrolo [ 2,3-bH | pyrimidin-4-one;

3 - [[4-hydroxy-1 - [(37?, 47?) - 1 - [(2-methylpyrimidin-4-yl) methyl] -3phenylpiperidin-4-carbonyl] -4-piperidyl] methyl] -7- phenylpyrrolo [2,3b7] pyrimidin-4-one;

3 - [[4-hydroxy-1 - [(37 ?, 47?) - 1 - [(2-methylpyrimidin-4-yl) methyl] -3 phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7 - (4methoxyphenyl) pyrrolo [2,3-07] pyrimidin-4-one;

3 - [[4-hydroxy-1 - [(37?, 47?) - 1 - [(6-methoxypyrid azin-3-yl) methyl] -3phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7 - (4methoxyphenyl) pyrrolo [2,3-07] pyrimidin-4-one;

3 - [[4-hydroxy-1 - [(37?, 47?) - 1 - [(5-methylpyrazin-2-yl) methyl] -3phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7- phenylthieno [3.4 </] pyrimidin-4-one;

3 - [[4-hydroxy-1 - [(37?, 47?) - 1 - [(2-methylpyrimidin-4-yl) methyl] -3phenylpiperidin-4-carbonyl] -4-piperidyl] methyl] -7- phenylthieno [3,4 "?] pyrimidin-4-one.

The invention also relates to a process for the preparation of compounds of formula (I), which is characterized in that a compound of formula (II)> p (P) is used as the starting material, where R2 and n are as defined for formula (I), which is subjected to combination with a compound of formula (III)

where R1 is as defined for formula (I) and PG is an amine protecting group to give a compound of formula (IV) / PG

O R _x where R1, R ₂ , n and PG are as defined above, the compound of formula (IV) is then converted to an epoxy compound of formula (V)

- 26 037563 where R1, R _2, n and PG are as defined above, the compound of formula (V) is then coupled with a compound of formula (VI):

(VI) where W is as defined for formula (I) to give a compound of formula (VII)

wherein R1, R _2, n, W and PG are as defined above, the compound of formula (VII), after deprotection PG, is then subjected to a combination of a compound of formula (VIII) wherein J is as defined for formula (I), K 'is a —Cy ₁ —group, Y is a hydroxy group or a halogen atom, and Z is a halogen atom, to give a compound of formula (IX)

where R1, R ₂ , J, K ', n, W and Z are as defined above and the compound of formula (IX) is then coupled with a compound of formula (X)

where L is as defined for formula (I), and RB1 and R _B2 represent a hydrogen atom, a linear or branched (C ₁ -C ₆ ) alkyl group, or R _B1 and R _{B2 are} joined by a linear or branched (C ₂ - C ₆ ) an alkylene group, to give a compound of formula (Ia), a particular case of compounds of formula (I)

wherein R1, R _2, J, K ', L, n and W are as defined above, or a combination with a compound of formula (XI)

Where J, K and L are as defined for formula (I) and Y is a hydroxy group or a halogen atom to give a compound of formula (I), a compound of formula (I) or a compound of formula (Ia) which is particular in the case of a compound of formula (I), can then be purified according to conventional separation techniques, converted, if necessary, into its addition salts with a pharmaceutically acceptable acid or base, and optionally separated into its isomers according to conventional separation techniques, it being understood that that at any time deemed appropriate during the process described above, some groups (hydroxy, amino ...) of the starting reagents or synthesis intermediates can be protected, subsequently deprotected and functionalized as required by the synthesis.

In another embodiment of the invention, compounds of formula (I) can be prepared using an alternative process, characterized in that a compound of formula (XII) is used as starting material:

- 27 037563 where R1 is as defined for formula (I) and PG is a protecting group of the carboxylic acid function which is either combined with a compound of formula (VIII)

Y ^{/ J} \ ^{/ Z (VIII)} 'where J is as defined for formula (I), K' is a -Cy ₁ -group, Y is a hydroxy group or a halogen atom and Z is a halogen atom, to give a compound formulas (XIII)

where R1, J, K ', Z and PG are as defined above and the compound of formula (XIII) is then coupled with a compound of formula (X)

where L is as defined for formula (I), and RB1 and R _B2 represent a hydrogen atom, a linear or branched (C ₁ -C ₆ ) alkyl group, or R _B1 and R _{B2 are} joined by a linear or branched (C ₂ - C ₆ ) an alkylene group to give a compound of formula (XIV)

where R1, J, K ', L and PG are as defined above, or in combination with a compound of formula (XI):

where J, K and L are as defined for formula (I) and Y is hydroxy or a halogen atom to give a compound of formula (XV)

where R1, J, K, L and PG are as defined above, compounds of formulas (XIV) and (XV), after deprotection reaction PG, are then coupled with a compound of formula (II) to give a compound of formula (XVI) ):

wherein R1, R _2, J, L and n are as defined above, and K is either K ', or K, as defined above, the compound of formula (XVI) is then converted into an epoxy compound of formula (XVII)

where R1, R2, J, K ″, L and n are as defined above and the compound of formula (XVII) is then coupled with a compound of formula (VI) (VI), where W is as defined for formula ( I) to provide a compound of formula (I) which can be purified according to conventional separation techniques, converted, if necessary, into its addition salts with a pharmaceutically acceptable acid or base, and optionally resolved into its isomers according to conventional separation techniques, wherein it should be understood that at any time deemed appropriate during the process described above, some groups (hydroxy, amino ...) of the starting reagents or synthesis intermediates can be protected, subsequently deprotected and functionalized as required by the synthesis.

Compounds of formulas (II), (III), (VI), (VIII), (X), (XI) and (XII) are either commercially available or

- 28 037563 can be obtained by a person skilled in the art using conventional chemical reactions described in the literature.

Pharmacological studies of the compounds of the invention have shown pro-apoptotic and / or antiproliferative properties. The ability to reactivate the apoptotic process in cancer cells is of great therapeutic interest for the treatment of malignant diseases and immunopathological and autoimmune diseases.

Among the targeted anticancer therapies, there may be mentioned, without implying any limitation, therapies for bladder, brain, breast and uterine cancers, chronic lymphoid leukemia, colon, esophagus and liver cancers, lymphoblastic leukemia, acute myeloid leukemia, lymphomas, melanomas, malignant blood diseases, myelomas, ovarian cancer, non-small cell lung cancer, prostate cancer, pancreatic cancer and small cell lung cancer. More specifically, the compounds according to the invention will be useful in the treatment of chemotherapy-resistant, targeted therapy or radiotherapy-resistant cancers.

The present invention also relates to pharmaceutical compositions containing at least one compound of formula (I) in combination with one or more pharmaceutically acceptable excipients.

Among the pharmaceutical compositions according to the invention, there may be mentioned more particularly those suitable for oral, parenteral, nasal, transdermal, transdermal, rectal, perlingual, ophthalmic or respiratory administration, especially tablets or dragees, sublingual tablets, sachets, sachets, capsules, glossets, lozenges, suppositories, creams, ointments, skin gels, and drinking or injectable ampoules.

Pharmaceutical compositions according to the invention contain one or more fillers or carriers selected from diluents, lubricants, binders, disintegrating agents, stabilizers, preservatives, absorbents, colorants, sweeteners, flavors, etc. As a non-limiting example, the following may be mentioned:

as diluents: lactose, dextrose, sucrose, mannitol, sorbitol, cellulose, glycerin, as lubricants: silica, talc, stearic acid and its magnesium and calcium salts, polyethylene glycol, as binders: magnesium aluminum silicate, starch, gelatin , tragacanth, methylcellulose, sodium carboxymethylcellulose and polyvinylpyrrolidone, as disintegrants: agar, alginic acid and its sodium salt, effervescent mixtures.

The dosage varies depending on the gender, age and weight of the patient, the route of administration, the nature of the therapeutic indication, or any concomitant treatment, and ranges from 0.01 mg to 1 g in 24 hours in one or more administrations.

In addition, the present invention also relates to the combination of a compound of formula (I) with antineoplastic agents selected from genotoxic agents, mitotic poisons, antimetabolites, proteasome inhibitors, kinase inhibitors, protein-protein interaction inhibitors, immunomodulators, E3 ligase inhibitors, T therapy β-cells with chimeric antigen receptors and antibodies, as well as pharmaceutical compositions containing this type of combination, and their use for the manufacture of medicaments for use in the treatment of malignant neoplasms.

The combination of a compound of formula (I) with an antineoplastic agent can be administered simultaneously or sequentially. The preferred route of administration is oral, and the corresponding pharmaceutical compositions can provide immediate or delayed release of the active components. In addition, the compounds of the combination can be administered as two separate pharmaceutical compositions, each containing one of the active ingredients, or as one pharmaceutical composition in which the active ingredients are in admixture.

For the treatment of cancer, the compounds of formula (I) can also be used in combination with radiotherapy.

The following Syntheses and Examples illustrate the invention, but do not limit it in any way.

General techniques

All reagents obtained from commercial sources were used without further purification. Anhydrous solvents were obtained from commercial sources and used without additional drying.

Flash chromatography was performed on an ISCO CombiFlash Rf 200i instrument with pre-filled silica gel cartridges (RediSep®R _f Gold High Performance).

Thin layer chromatography was performed on 5x10 cm plates coated with Merck Type 60 F254 silica gel.

Microwave heating was performed in an Anton Parr MonoWave or CEM Dis-29 037563 cover® device.

Preparative HPLC purification operations were performed on a HANBON NP7000 Liquid Chromatography System with Gemini-NX® 5 μm C18, 250 mm x 50 mm id. column, operating at a flow rate of 99.9 ml min ^-1 with UV detection on a diode array (210-400 nm), using 5 mM aqueous NH ₄ HCO ₃ solution and MeCN as eluents, unless otherwise indicated.

Analytical LC-MS: Compounds of the present invention were characterized by high performance liquid chromatography-mass spectroscopy (HPLC-MS) on an Agilent HP1200 instrument with an Agilent 6140 quadrupole LC / MS operating with electrospray ionization in positive or negative ion mode. The scan range of molecular weights was from 100 to 1350. Parallel UV detection was performed at 210 nm and 254 nm. Samples were injected as a 1 mM solution in MeCN, or in a THF / H ₂ O mixture (1: 1) using a 5 μL loop dispenser. LCMS analyzes were performed on two instruments, one of which worked with basic and the other with acidic eluents.

Basic LCMS: Gemini-NX, 3 μm, C18, 50 mm x 3.00 mm in. e. column at 23 ° C, flow rate 1 ml min ^-1 , using 5 mM ammonium bicarbonate (Solvent A) and acetonitrile (Solvent B) with a gradient starting with 100% Solvent A and ending with 100% Solvent B for various / specific periods of time.

Acidic LCMS: ZORBAX Eclipse XDB-C18, 1.8 μm, 50 mm x 4.6 mm id. column at 40 ° C, with a flow rate of 1 ml min ^-1 , using 0.02% v / v. aqueous formic acid (Solvent A) and 0.02% v / v. formic acid in acetonitrile (Solvent B) with a gradient starting with 100% Solvent A and finishing with 100% Solvent B for various / defined times.

¹ H-NMR studies were performed on a Bruker Avance III 500 MHz spectrometer and a Bruker Avance III 400 MHz spectrometer using DMSO-d ₆ or CDCl ₃ as solvent. 1H NMR data are presented as delta values reported in parts per million (ppm) using the residual solvent peak (2.50 ppm for DMSO-d ₆ and 7.26 ppm for CDCl ₃ ) as internal standard. Splitting patterns are designated as: s (singlet), d (doublet), t (triplet), q (quartet), quint (quintet), sept (septet), m (multiplet), brs (broad singlet), brd (broad doublet), brt (wide triplet), brq (wide quartet), brm (wide multiplet), vbrs (very wide singlet), dd (doublet of doublets), td (triplet of doublets), dt (doublet of triplets), dq (doublet of quartets ), ddd (doublet of doublet of doublets), dm (doublet of multiplets), tm (triplet of multiplets), qm (quartet of multiplets).

Gas chromatography combined with low resolution mass spectrometry was performed on an Agilent 6850 gas chromatograph and an Agilent 5975C mass spectrometer using a 15 mx 0.25 mm column with 0.25 μm HP-5MS coating and helium as carrier gas. Ion source: EI +, 70 eV, 230 ° C, quadrupole: 150 ° C, interface: 300 ° C.

MCBP data were determined on a Shimadzu IT-TOF instrument, ion source temperature 200 ° C, ESI +/-, ionization voltage: (+ -) 4.5 kV. Mass resolution min. 10000.

Elementary analyzes were performed on a Thermo Flash EA 1112 elemental analyzer.

List of abbreviations

Abbreviation - designation:

abs. - absolute;

aq. - water;

Ar is argon;

AtaPhos * PdCl ₂ - bis (di-tert-butyl (4-dimethylaminophenyl) phosphine) dichloropalladium (II);

Boc is tert-butoxycarbonyl;

conc. - concentrated;

DCM - dichloromethane;

DEE - diethyl ether;

DIPO - diisopropyl oxide;

disp. - variance;

DMEDA - N, N'-dimethylethylenediamine;

DMF - dimethylformamide;

EDC.HCl = N- (3-dimethylaminopropyl) -N'-ethylcarbodiimide hydrochloride;

EEO - ethyl ethanoate;

eq. - equivalent;

LC - liquid chromatography;

LDA - lithium diisopropylamide;

mCPBA, meta-chloroperbenzoic acid;

MeCN - acetonitrile;

MSM for methylsulfinylmethane;

MTBE = tert-butyl methyl ether;

NMP is N-methylpyrrolidone;

- 30 037563

PDO - n-dioxane;

Ph.D. - room temperature;

saturate - saturated;

SEM, trimethylsilylethoxymethyl;

TBAF - tetrabutylammonium fluoride;

TFA - trifluoroacetic acid;

THF - tetrahydrofuran;

TMP.MgCl.LiCl - complex 2,2,6,6-tetramethylpiperidine-magnesium chloride-lithium chloride (1: 1).

General procedure 1.

Stage 1.

To a stirred solution of 4-chloro-7H-pyrrolo [2,3-d] pyrimidine (Synthesis compound R1a; 1.84 g, 12 mmol, 1 eq.) In abs. DMF (15 ml) was added sodium hydride (720 mg, 60% dispers. In mineral oil, 18 mmol, 1.5 eq.), And the mixture was stirred for 10 min at RT. under Ar. An alkylating agent (13.18 mmol) was added to the reaction mixture and stirred for 1-6 h at rt. The mixture was poured into water (150 ml), then it was extracted with EEO (3x150 ml). The combined organic layers were washed with water, brine, dried over MgSO ₄ and evaporated.

Stage 2.

A portion of the compound from Step 1 above (1.36 mmol) and lithium hydroxide monohydrate (571 mg, 13.62 mmol, 10 eq.) Were stirred in PDO-water (40 mL, 1: 1 v / v) at 110 ° C for 7-36 hours, the Reaction mixture was neutralized with 1N. aq. HCl solution and the resulting precipitate was filtered off, washed with water and dried.

General procedure 2.

Stage 1.

Synthesis compound R1a (460 mg, 3 mmol, 1 eq.), Heteroaryl / aryl boronic acid (7.5 mmol), and copper (II) acetate (817 mg, 4.5 mmol) were stirred in pyridine (10 ml) at 50-60 ° C for 16-72 hours.

Isolation of the reaction product, route 1.

The mixture was evaporated, applied to celite and purified by flash chromatography (heptane-EEO, gradient).

Isolation of the reaction product, route 2.

The mixture was filtered and the resulting filtrate was purified by preparative LC (5 μm C-18 Gemini-NX column, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient).

Stage 2.

The compound obtained in the above Step 1 (1.36 mmol) and lithium hydroxide monohydrate (571 mg, 13.62 mmol, 10 eq.) Were stirred in a PDO-water mixture (40 ml, 1: 1 v / v) at 110 ° C in for 7-24 hours, the Reaction mixture was neutralized with 1N. aq. HCl solution, the resulting precipitate was filtered off, washed with water, and dried.

General procedure 3.

Stage 1.

Synthesis compound R1b (746 mg, 5 mmol, 1 eq.), Heteroaryl / aryl iodide (10 mmol), CuI (286 mg, 1.5 mmol, 0.3 eq.), R, R-diaminocyclohexane (171 mg, 1.5 mmol, 0.3 eq. .) and anhydrous K ₃ PO ₄ (4.24 g, 20 mmol, 4 equiv.) were stirred in diglyme (15 ml) for 6-16 h at 120 ° C in an N2 atmosphere.

Isolation of the reaction product, route 1:

After completion of the reaction, the mixture was diluted with water (200 ml) (or 25% aq. NH ₃ ) and cooled to rt. The mixture was filtered, washed with water (3x30 ml), aq. NH ₃ solution (40 ml, 25%), water (3x50 ml), heptane (50, then 30 ml), and dried in vacuo.

Isolation of the reaction product, route 2.

The reaction mixture was evaporated, loaded onto celite and purified by flash chromatography (heptane: EEO, gradient).

Stage 2.

The corresponding 4-methoxy-7-heteroaryl / arylpyrrolo [2,3-d] pyrimidine obtained in Step 1 above (61.3 mmol, 1 eq.), Conc. an aqueous solution of HCl (10 ml, ~ 12.2 M, 122.5 mmol, 2 eq.) and PDO (70 ml) were stirred at 100 ° C for 0.5-2 h. After the completion of the reaction, the mixture was partially evaporated. The resulting slurry was filtered and the filter solid was washed with water and dried.

General procedure 4.

Stage 1.

Synthesis Compound R1a (154 mg, 1 mmol, 1 eq.), Di-tert-butyl diazodicarboxylate (690 mg, 3 mmol, 3 eq.), Triphenylphosphine (786 mg, 3 mmol, 3 eq.) And the corresponding alcohol ( 3 mmol, 3 eq.) Was stirred in abs. Toluene (10 ml) in an Ar atmosphere at 50 ° C for 2 h.The reaction mixture was evaporated, introduced into THF, and purified by preparative LC (on a C-18 Gemini-NX 5 μm column, 5 mM aqueous NH4HCO3-MeCN, gradient ).

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Stage 2.

A portion of 4-chloro-7-aryl / alkylpyrrolo [2,3-d] pyrimidine from Step 1 above (1.36 mmol) and lithium hydroxide monohydrate (571 mg, 13.62 mmol) were stirred in PDO-water (40 ml , 1: 1 v / v) at 110 ° C for 7-24 hours, the Reaction mixture was neutralized with 1N. aq. HCl solution, the resulting precipitate was filtered off, washed with water and dried.

General procedure 5.

Stage 1.

The pyrimidin-4-one derivative (1 mmol), the epoxy compound of the Synthesis of R1f (1 mmol) and K ₂ CO ₃ (276.4 mg, 2 mmol, 2 eq.) Were stirred in DMF (5 ml) at 75 ° C for 2- 8 h

Isolation of the reaction product, route 1.

The mixture was poured into ice-water and the resulting precipitate was filtered off, washed with water and dried.

Isolation of the reaction product, route 2.

The reaction mixture was filtered and the solid was washed with DMF. The resulting filtrate was purified by preparative LC (C-18 Gemini-NX 5 μm column, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient).

Stage 2.

Part of the compound obtained in the above Step 1 (1 mmol) was stirred in aq. a solution of HCl (1N, 10 ml, 10 mmol, 10 eq.) and PDO (5 ml) for 1-3 h at 75 ° C.

Isolation of the reaction product, route 1.

The mixture was cooled to about 0-5 ° C with an ice bath and the white precipitate was filtered and dried in vacuo (resulting in the HCl salt).

Isolation of the reaction product, route 2.

The mixture was completely evaporated and used in the next step (resulting in the HCl salt).

Isolation of the reaction product, route 3.

The mixture was purified by prep LC (5 µm Gemini-NX C-18 column, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient to give the free base).

General procedure 6.

The compound obtained by performing General Procedure 5, (1 mmol, 1 eq.), Aryl / heteroaryl CH ₂ -X (1 mmol, 1 eq .; where X is a halogen atom) and K ₂ CO ₃ (483 mg, 3.5 mmol , 3.5 equiv.) Was stirred in DMF (10 ml) at rt. within 4-16 hours.

Isolation of the reaction product, route 1.

The mixture was poured into ice-water and the resulting precipitate was filtered off, washed with water and dried.

Isolation of the reaction product, route 2.

The mixture was filtered and the filtrate was injected onto preparative LC (on a C-18 Gemini-NX 5 μm column, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient).

General procedure 7.

The compound obtained by performing General Procedure 5, (2.7 mmol), EDC.HCl (1.183 g, 6.172 mmol) and the corresponding carboxylic acid (2.7 mmol) were stirred in pyridine (25 ml) at RT. within 16 hours.

Isolation of the reaction product, route 1.

The reaction mixture was evaporated, the residue was taken up in DMF and introduced into preparative LC (on a C-18 Gemini-NX 5 μm column, 5 mM aqueous NH4HCO3-MeCN, gradient).

Isolation of the reaction product, route 2.

The reaction mixture was evaporated. The residue was triturated with water and the resulting solid was filtered off.

General procedure 8.

The compound obtained by performing General Procedure 5, (1 mmol, 1 eq.), The corresponding sulfonyl chloride (2 mmol, 2 eq.) And K ₂ CO ₃ (553 mg, 4 mmol, 4 eq.) Were stirred in DMF (10 ml ) at c.t. within 4-28 hours.

The mixture was evaporated, applied to celite and purified by flash chromatography (eluent: DCMMeOH).

General procedure 9.

The corresponding halogenated component (0.15 mmol, 1 eq.), The corresponding boronic acid (0.375 mol, 2.5 eq.), ATAphos * PdCl ₂ (10.6 mg, 0.015 mmol, 0.1 eq.) And Cs ₂ CO ₃ (171 mg, 0.525 mmol , 3.5 equiv.) Was diluted with THF (2.5 ml) and water (2.5 ml). The mixture was purged with nitrogen and stirred in a microwave reactor at 80 ° C for 100-150 minutes. The reaction mixture was injected through a syringe filter onto a preparative LC column (C-18 Gemini-NX 5 μm column, 5 mM aqueous NH4HCO3MeCN, gradient).

General procedure 10.

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Boron tribromide (0.3 ml, 440 mg, 1.7 mmol, 10 eq.) Was added dropwise to a stirred solution of the corresponding-O-benzyl- or-O-methyl-containing compound (0.17 mmol) in DCM (5 ml) at

Ph.D. After 3 h stirring, the reaction mixture was quenched with EtOH and evaporated. The residue was purified by preparative LC (on a C-18 Gemini-NX 5 µm column, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient).

General procedure 11.

This procedure is similar to that described in General Procedure 5 using the Synthesis compound R1m as the epoxy component. The residue was purified by preparative LC (on a C-18 Gemini-NX 5 µm column, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient).

General procedure 12.

A mixture of nitro compound (1.45 mmol), tin (II) chloride dihydrate (1.64 g, 7.45 mmol, 5 eq.) In EtOH (30 ml) and HCl (1N, 5 ml, aq.) Was stirred for 20 h at 80 ° C. To the reaction mixture was added sat. aqueous NaHCO ₃ (50 ml), then the mixture was evaporated, applied to celite and purified by flash chromatography (DCM-MeOH).

General procedure 13.

Iodomethane (10 μL) was added to a stirred mixture of the amino / amide compound (0.105 mmol), K ₂ CO ₃ (22 mg, 0.158 mmol, 1.5 eq.) In DMF (1 ml) at RT. After 18 h stirring, the reaction mixture was filtered and injected into preparative LC (on a C-18 Gemini-NX 5 μm column, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient).

General procedure 14.

The N-Boc compound (0.1 mmol) was stirred in aq. a solution of HCl (1N, 3 ml, 3 mmol, 30 eq.) and PDO (2 ml) for 2-5 h at 75 ° C. The mixture was purified by prep LC (on a 5 μm Gemini-NX C-18 column, 5 mM aqueous NH4HCO3-MeCN, gradient to give the free amine base).

General procedure 15.

A mixture of the corresponding methoxy compound (0.44 mmol), conc. HCl (aq. 37%, 1.1 ml, 13 mmol, 30 eq.) And PDO (7 ml) were stirred at 100 ° C for 3 h. A NaOH solution (aq. 2 M, 6.6 ml) was added to the reaction mixture. The solid compound was filtered off, then purified by preparative LC (on a C-18 Gemini-NX 5 μm column, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient).

Synthesis of R1b: 4-methoxy-7H-pyrrolo [2,3-d] pyrimidine.

Synthesis compound R1a (100 g, 0.651 mol, 1 eq.), NaOH (31.26 g, 0.781 mol, 1.2 eq.), And MeOH (400 ml) were stirred at 90 ° C for 24 h. The mixture was quenched with water (1200 ml) and cooled to rt. using an ice bath. The mixture was stirred for 30 min and filtered through a glass filter. The precipitate was washed with water (3 x 100 ml) then dried and the Synthesis compound R1b was obtained as a white solid. MCBP: calculated for C ₇ H ₇ N ₃ O: 149.0589, found: 150.0667 [(M + H) + form].

¹ H-NMR (400 MHz, MSM-d6): δ = 12.02 (vbrs, 1H), 8.37 (s, 1H), 7.35 (d, 1H), 6.47 (d, 1H), 4.02 (s, 3H). ¹³ C-NMR (100 MHz, MSM-d6) δ ppm. 162.6, 152.9, 150.8, 124.6, 104.8, 98.3, 53.7.

Synthesis of R1c: 5- [5- (chloromethyl) -1,3-thiazol-2-yl] -2-methylpyridine.

Step 1. [2- (6-Methylpyridin-3-yl) -1,3-thiazol-5-yl] methanol.

2-Bromothiazole-5-methanol (20 g, 0.103 mol, 1 eq.), 2-methylpyridine-5-boronic acid (18.3 g, 0.134 mol, 1.3 eq.), ATAphos * PdCl ₂ (3.65 g, 5.152 mmol, 0.05 eq.) And Cs ₂ CO ₃ (67.14 g, 0.206 mol, 2 eq.) Were dissolved in THF (800 ml) and water (800 ml). The mixture was purged with nitrogen and stirred at 80 ° C for 3 hours. The mixture was cooled to rt. and diluted with EEO (300 ml). The layers were separated, the aqueous layer was extracted with EEO (3x 100 ml), the combined organic layer was dried over MgSO ₄ and, after filtration, was evaporated. The residue was crystallized from EEO / DIPO, filtered and dried in vacuo to give a brown solid. MCBP calculated for C ₁₀ H ₁₀ N ₂ OS: 206.0514, found: 207.0591 [(M + H) + form].

1H-NMR (500 MHz, MSM-d6): δ = 2.52 (s, 3H), 4.72 (d, J = 10.4 Hz, 2H), 5.67 (t, J = 11.0 Hz, 1H), 7.38 (d, J = 16.3 Hz, 1H), 7.77 (s, 1H), 8.14 (dd, J = 16.0, 4.8 Hz, 1H), 8.96 (d, J = 4.5 Hz, 1H).

Step 2. Compound Synthesis of R1c.

[2- (6-Methyl-3-pyridyl) thiazol-5-yl] methanol (18.23 g, 88.38 mmol, 1 eq.) Was dissolved in abs. DMF (1.37 ml, 1.29 g, 17.68 mmol, 0.2 eq.) And dry DCM (400 ml). _{SOCl 2} (8.36 ml, 13.67 g, 114.9 mmol, 1.3 equiv.) In the form of DCM (50 ml) solution at RT was added dropwise to the reaction mixture (~ 15 min). The mixture was stirred at 50 ° C for 2 h. The mixture was cooled to rt. Water (50 ml) was slowly added to the mixture, then it was neutralized with sat. NaHCO ₃ solution (250 ml, pH 7-8). The layers were separated. The aqueous layer was extracted with DCM (4 x 50 ml). The combined organic layer was dried over MgSO ₄ , filtered. The solution was diluted with EEO (300 ml) and filtered through a pad of silica gel (~ 20 g). The mixture was evaporated to give Synthesis compound R1c as a yellow solid. MCBP: calculated for C ₁₀ H ₉ ClN ₂ S: 224.0175, found: 225.0247 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6): δ = 2.53 (s, 3H), 5.17 (s, 2H), 7.41 (d, J = 16.5 Hz, 1H), 7.98 (s, 1H), 8.17 (dd, J = 16.0, 5.0 Hz, 1H), 8.99 (d, J = 5.0 Hz, 1H). ¹³ C-NMR (125 MHz, MSM-d6): δ (ppm) 24.5, 38.4, 124.1, 134.4, 144.4, 146.7.

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Synthesis of R1d: 4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazole-5-carboxylic acid.

Step 1: ethyl 4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazole-5-carboxylate.

Ethyl 2-bromo-4-methylthiazole-5-carboxylate (26.9 g, 107.6 mmol, 1 eq.), 2-methylpyridine-5boronic acid (19.2 g, 139.8 mmol, 1.3 eq.), ATAphos * PdCl ₂ (3.05 g, 4.3 mmol, 0.04 eq.) And Na ₂ CO ₃ (34.2 g, 322.65 mmol, 3 eq.) Were dissolved in THF (250 ml) and water (250 ml). The mixture was purged with nitrogen and stirred at 80 ° C for 2 hours. After completion of the reaction, the mixture was cooled to rt. and diluted with EEO (250 ml). The layers were separated and the aqueous layer was extracted with EEO (2x50 ml). The combined organic layer was dried over MgSO ₄ and, after filtration, was evaporated. The crude product was dissolved in DCM / EEO / heptane (1: 1: 1 v / v, 600 ml) and filtered through silica gel (~ 30 g) and washed with DCM / EEO / heptane (1: 1: 1 v / v). / vol., 100 ml). The mixture was evaporated. The residue was recrystallized from DIPO (100 ml) and dried in vacuo to give a beige solid. MCBP: calculated for CBH14N2O2S: 262.0776, found: 263.0852 [(M + H) + form].

1H NMR (500 MHz, MSM-d ₆ ): δ = 1.31 (t, J = 17.5 Hz, 3H), 2.54 (s, 3H), 2.70 (s, 3H), 4.30 (q, J = 17.8 Hz, 2H ), 7.42 (d, J = 20.3 Hz, 1H), 8.24 (dd, J = 20.4, 6.1 Hz, 1H), 9.04 (d, J = 5.4 Hz, 1H).

Step 2. Compound Synthesis of R1d.

Ethyl 4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carboxylate (21.07 g, 80.33 mmol, 1 eq.) Was dissolved in EtOH (40 ml). NaOH (4.82 g, 120.49 mmol, 1.5 equiv.) Was dissolved in water (80 ml). Aq. NaOH was added to the organic mixture and stirred at 80 ° C for 45 min. After completion of the reaction, the mixture was cooled to rt. After 1 week, a black precipitate was observed. The mixture was filtered through a pad of silica gel / celite. The mixture was acidified with conc. HCl solution (to pH ~ 1) and the resulting precipitate was filtered off, washed with water (50 ml) and dried in vacuo to give Synthesis compound R1d as an off-white solid. MCBP: calculated for C ₁₁ H ₁₀ N ₂ O ₂ S: 234.0463, found: 235.0533 [(M + H) ⁺ form].

¹ H NMR (500 MHz, MSM-d ₆ ): δ = 2.52 (s, 3H), 2.63 (s, 3H), 7.36 (d, J = 16.2 Hz, 1H), 8.14 (dd, J = 16.2, 4.8 Hz, 1H), 8.95 (d, J = 4.8 Hz, 1H).

Synthesis of R1e. tert-Butyl 1-oxa-6-azaspiro [2.5] octane-6-carboxylate.

Trimethylsulfoxonium iodide (20.0 g, 150 mmol) was dissolved in abs. MSM (75 ml) was then sequentially added to a dispersion of sodium hydride (60% in mineral oil, 6 g, 150 mmol) and stirred for 20 min at RT. To the mixture was added a solution of N-Boc-piperidin-4-one (20.0 g, 100 mmol) in MSM (75 ml, abs.) And stirred for 15 h at rt. The reaction mixture was poured into ice-water (200 ml) and extracted with diethyl ether (4 x 200 ml). The combined organic layer was washed with water, brine, then dried over MgSO ₄ and evaporated to give Synthesis compound R1e. MCBP: calculated for C _n H ₁₉ NO ₃ : 213.1365, found: 158.0811 [(M + H-tBu) + form].

1H NMR (500 MHz, MSM-d6): δ ppm. 3.5 / 3.37 (brm + brm, 4H), 2.65 (s, 2H), 1.64 / 1.38 (m + m, 4H), 1.4 (s, 9H). ¹³ C NMR (125 MHz, MSM-d6): δ ppm. 154.3, 79.3, 57.4, 53.3, 42.7, 33, 28.5.

Synthesis of R1f: tert-butyl (3R, 4R) -4- (1-oxa-6-azaspiro [2.5] oct-6-ylcarbonyl) -3-phenylpiperidine-1carboxylate.

Step 1 tert-Butyl (3R, 4R) -4 - [(4-oxopiperidin-1-yl) carbonyl] -3-phenylpiperidine-1-carboxylate.

4-piperidone hydrochloride hydrate (0.969 g, 6.3 mmol), EDC.HCl (3.623 g, 18.9 mmol) and (3R, 4R) -1 tert-butoxycarbonyl-3-phenylpiperidine-4-carboxylic acid (1.928 g, 6.3 mmol) were dissolved in pyridine (10 ml) and stirred at rt. over 16 hours. The reaction mixture was evaporated, loaded onto celite and purified by flash chromatography (DCM: MeOH, gradient) to give the title product. MCBP: calculated for C ₂₂ H ₃₀ N ₂ O ₄ : 386.2206, found: 409.2093 [(M + Na) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ): δ 1.42 (s, 9H), 4.14-1.50 (m, 16H), 7.32-7.15 (m, 5H).

Step 2. Compound Synthesis of R1f.

tert-Butyl (3R, 4R) -4 - [(4-oxopiperidin-1-yl) carbonyl] -3-phenylpiperidine-1-carboxylate (60 g, 155 mmol 1 eq.) and trimethylsulfoxonium iodide (85.41 g, 388 mmol , 2.5 eq.) Was loaded into a round bottom flask and dissolved / suspended in MeCN (150 ml) and MTBE (150 ml). Simultaneously, NaOH (15.5 g, 388 mmol, 2.5 equiv.) Was dissolved in water (21.6 mL) (~ 40% solution). Aq. NaOH solution was added to the reaction mixture and stirred at 60 ° C for 2 h. After completion of the reaction, the mixture was cooled to rt, filtered through celite pad and the filter cake was washed with MTBE (2x60 ml). Water (150 ml) was added to the organic layer and, after extraction, the layers were separated. Aq. the layer was extracted with additional MTBE (2 x 60 ml). The combined organic layers were dried over MgSO4 and, after filtration, evaporated to give Synthesis compound R1f as a beige solid foam. MCBP: calculated for C ₂₃ H ₃₂ N ₂ O ₄ : 400.2362, found: 423.2247 [(M + Na) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ): δ = 1.41 (s, 9H), 1.79-0.86 (m, 6H), 2.61-2.51 (m, 2H), 4.16-2.73 (m, 10H), 7.33- 7.18 (m, 5H).

Synthesis of R1g. 3-Fluoro-5-iodothiophene-2-carboxylic acid.

Stage 1. 3-Fluoro-5-iodothiophene-2-carboxylate and methyl 3-fluoro-4,5-diiodothiophene-2-carboxylate.

To a solution of methyl 3-fluorothiophene-2-carboxylate (2.42 g, 15.1 mmol) in THF (10 ml), TMP.MgCl.LiCl (1N, in a mixture of THF / toluene, 25 ml, 25 mmol ) at -45 ° C for 5 min. After stirring for 30 min, iodine (4.04 mg, 15.9 mmol) in THF (10 ml) was added to the mixture at -45 ° C. After heating (1 h), sat. NH ₄ Cl solution (50 ml, aq.). The mixture was extracted with EEO (5x10 ml). The combined organic layer was evaporated. The residue was purified using preparative LC (on a C-18 Gemini-NX column 5 μm, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient) to obtain 3-fluoro-5-iodothiophene-2-carboxylate and methyl 3-fluoro-4 , 5-diiodothiophene-2-carboxylate, separately from each other.

Methyl 3-fluoro-5-iodothiophene-2-carboxylate.

GC-MS: calculated for C ₆ H ₄ FiO ₂ S: 285.8961, found: 285.9 [(M, EI) form]. % NMR (500 MHz, MSM-de): δ ppm. 7.52 (s, 1H), 3.78 (s, 3H). ¹³ C NMR (125 MHz, MSM-d6): δ ppm. 159.4, 158.8, 128.5, 117.2, 86.4, 52.8.

Methyl 3-fluoro-4,5-diiodothiophene-2-carboxylate.

GC-MS: calculated for C6H4FIO2S: 411.7927, found: 411.9 [(M, EI) form]. % NMR (500 MHz, MSM-d ₆ ): δ ppm. 3.8 (s, 3H). ¹³ C NMR (125 MHz, MSM-d ₆ ): δ ppm. 159, 158.2, 117.4, 96.1, 90.6, 53.1.

Step 2. Compound Synthesis of R1g.

Methyl 3-fluoro-5-iodothiophene-2-carboxylate (1.188 g, 4.135 mmol) and lithium hydroxide monohydrate (867 mg, 20.7 mmol) were stirred in methanol (10 ml) and water (10 ml) at 70 ° C for 1 am The mixture was partially evaporated and the aqueous residue was acidified with 1N. HCl (25 ml, aq.). The resulting precipitate was filtered off, washed with water and dried to give Synthesis compound R1g. GC-MS calculated for C5H ₂ FIO ₂ S: 271.8804, found: 271.9 [(M, EI) form].

1H NMR (500 MHz, MSM-d6): δ ppm. 13.48 (brs), 7.74 (s, 1H). ¹³ C NMR (125 MHz, MSM-d6): δ ppm. 160.4, 158.3, 128.5, 119, 85.1.

Synthesis of R1h: 3-fluoro-4,5-diiodothiophene-2-carboxylic acid.

Methyl 3-fluoro-4,5-diiodothiophene-2-carboxylate (614 mg, 1.49 mmol) and lithium hydroxide monohydrate (256 mg, 6 mmol) were stirred in methanol (8 ml) and water (8 ml) at rt. for 5 h. The mixture was partially evaporated and the aqueous residue was acidified with 1N. HCl (10 ml, aq.). The resulting precipitate was filtered off, washed with water and dried to give Synthesis compound R1h. MCBP: calculated for C5HFI2O2S: 397.7771, found: 352.7798 [(M-H-CO2) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ): δ ppm. 13.72 (brs, 1H). ¹³ C NMR (125 MHz, MSM-d ₆ ): δ ppm. 160, 157.7, 119.1, 95.1, 90.5.

Synthesis of R1i: 3-fluoro-4-iodo-5-methylthiophene-2-carboxylic acid.

Stage 1. Methyl 3-fluoro-4-iodo-5-methylthiophene-2-carboxylate.

To a solution of methyl 3-fluoro-5-iodothiophene-2-carboxylate, the compound of the synthesis R1g, (286 mg, 1 mmol) in THF (3 ml), TMP.MgCl.LiCl (1N, in a THF / toluene mixture, 1.5 ml, 1.5 mmol) at -45 ° C for 5 min. After 60 min stirring, iodomethane (123 ml, 282 mg, 2 mmol) in THF (2 ml) was added to the mixture at -45 ° C and stirred for 2 h at -40 ° C. After heating, sat. Was added to the mixture with stirring. NH4Cl solution (5 ml, aq.). The mixture was extracted with EEO (4 x 10 ml). The combined organic layer was evaporated. The residue was purified by prep LC (5 µm Gemini-NX C-18 column, 5 mM aqueous NH ₄ HCO ₃ -MeCN gradient) to afford the title product. MCBP: calculated for C ₇ H ^ 10 ^: 299.9117; 300.9200 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ): δ ppm. 3.8 (s, 3H), 2.43 (s, 3H). ¹³ C NMR (125 MHz, MSM-d ₆ ): δ ppm. 159.8, 158.5, 145.1, 109.6, 77.2, 52.8, 19.1.

Step 2. Compound Synthesis of R1i.

Methyl 3-fluoro-4-iodo-5-methylthiophene-2-carboxylate (40 mg, 0.133 mmol) and lithium hydroxide monohydrate (11 mg, 0.266 mmol) were stirred in methanol (1 ml) and water (1 ml) at room temperature. t. for 3 h. The mixture was partially evaporated and the aqueous residue was acidified with 1N. HCl (3 ml, aq.). The resulting precipitate was filtered off, washed with water and dried to give Synthesis compound R1i. 1H NMR (500 MHz, MSM-d6): δ ppm. 13.41 (brs, 1H), 2.41 (s, 3H).

¹³ C NMR (125 MHz, MSM-d ₆ ): δ ppm. 160.8, 158, 144.2, 76.9, 19.1.

Synthesis of R1j: 3-chloro-5-iodothiophene-2-carboxylic acid.

Stage 1. Complex methyl ester of 3-chloro-5-iodo-thiophene-2-carboxylic acid.

To a solution of 3-chlorothiophene-2-carboxylic acid methyl ester (353 g, 2 mmol) in THF (5 ml) was added TMP.MgCl.LiCl (1N, in a mixture of THF / toluene, 3 ml, 3 mmol) dropwise at -45 ° C. After 20 min stirring, iodine (507 mg, 4 mmol) in THF (2 ml) was added to the mixture at -45 ° C. After heating, sat. Was added to the mixture with stirring. NH ₄ Cl solution (5 ml, aq.) and Na2S2O ₃ solution (5 ml, 10% aq.). The mixture was extracted with EEO (4 x 10 ml). The combined organic layer was evaporated. The residue was purified by prep LC (5 µm Gemini-NX C-18 column, 5 mM aqueous NH ₄ HCO ₃ -MeCN gradient) to afford the title product. MCBP calculated for C6H4CHO2S: 301.8665, found: 301.9000 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ): δ ppm. 37.55 (s, 1H), 3.8 (s, 3H). ¹³ C NMR (125 MHz, MSM-d ₆ ): δ ppm. 159.5, 139.4, 130.9, 130.6, 86.8, 53.

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Step 2. Compound Synthesis of R1j.

Methyl 3-chloro-5-iodothiophene-2-carboxylic acid methyl ester (477 mg, 1.58 mmol) and lithium hydroxide monohydrate (132 mg, 3.16 mmol) were stirred in methanol (5 ml) and water (5 ml) at 50 ° C for 2.5 h. The mixture was partially evaporated and the aqueous residue was acidified with 1N. HCl solution (4 ml, aq.). The resulting precipitate was filtered off, washed with water and dried to give Synthesis compound R1j. GC-MS calculated for C ₅ H ₂ ClIO ₂ S: 287.8509, found: 243.8 [(M-CO ₂ , EI) form].

¹ H NMR (500 MHz, MSM-de): δ ppm. 13.6 (brs, 1H), 7.51 (s, 1H). ¹³ C NMR (125 MHz, MSM-de): δ ppm. 160.6, 139.3, 132.4, 130.1, 85.8.

Synthesis of R1k: 5-chloro-3-fluoro-4-iodothiophene-2-carboxylic acid.

Stage 1. Methyl 5-chloro-3-fluoro-4-iodothiophene-2-carboxylate.

To a solution of methyl 3-fluoro-5-iodothiophene-2-carboxylate (286 mg, 1 mmol) in THF (5 ml), TMP.MgCl.LiCl (1N, in a THF / toluene mixture, 1.5 ml, 1.5 mmol ) at -45 ° C for 5 min. After stirring for 30 min, hexachloroethane (236 mg, 1 mmol) in THF (2 ml) was added to the mixture at -45 ° C. After heating, sat. Was added to the mixture with stirring. NH4Cl solution (5 ml, aq.). The mixture was extracted with EEO (4x10 ml) and the combined organic layers were evaporated. The residue was purified by prep LC (5 µm Gemini-NX C-18 column, 5 mM aqueous NH ₄ HCO ₃ -MeCN gradient) to afford the title product. GC-MS calculated for C ₆ H ₃ ClFIO ₂ S: 319.8571, found: 319.9 [(M, EI) form].

¹ H NMR (500 MHz, MSM-d6): δ ppm. 3.82 (s, 3H). ¹³ C NMR (125 MHz, MSM-d6): δ ppm. 159.1, 157.9, 135.9, 111.7, 81.1, 53.2.

Step 2. Compound Synthesis of R1k.

Methyl 5-chloro-3-fluoro-4-iodothiophene-2-carboxylate (76 mg, 0.237 mmol) and lithium hydroxide monohydrate (20 mg, 0.474 mmol) were stirred in methanol (4 ml) and water (4 ml) at room temperature. t. for 2 h. The mixture was partially evaporated and the aqueous residue was acidified with 1N. HCl (2 ml, aq.). The resulting precipitate was filtered off, washed with water and dried to give Synthesis compound R1k. 1H NMR (400 MHz, MSM-d ₆ ): δ ppm. 13.88 (brs, 1H).

¹⁹ F NMR (376.5 MHz, MSM-d6): δ ppm. -101.7. ¹³ C NMR (100 MHz, MSM-d6): δ ppm. 157.4.

Synthesis of R1l: 5-chloro-3-fluoro-4-methylthiophene-2-carboxylic acid.

Stage 1. Methyl 5-chloro-3-fluorothiophene-2-carboxylate.

To a solution of methyl 3-fluorothiophene-2-carboxylate (1826 mg, 11.4 mmol) in THF (5 ml) was added TMP.MgCl.LiCl (1N, in a THF / toluene mixture, 21 ml, 21 mmol) dropwise at -45 ° C for 5 min. After stirring for 30 min at -45 ° C, hexachloroethane (2.7 g, 11.4 mmol) was added to the mixture at -45 ° C and stirred for 1 h at -40 ° C. After heating, sat. Was added to the mixture with stirring. NH4Cl solution (10 ml, aq.). The mixture was extracted with EEO (4x10 ml) and the combined organic layers were evaporated. The residue was purified by prep LC (5 µm Gemini-NX C-18 column, 5 mM aqueous NH ₄ HCO ₃ -MeCN gradient) to afford the title product. GC-MS calculated for C ₆ H ₄ ClFO ₂ S: 193.9604, found: 193.9 [(M, EI) form].

1H NMR (500 MHz, MSM-d6): δ ppm. 7.46 (s, 1H), 3.81 (s, 3H). ¹³ C NMR (125 MHz, MSM-d6): δ ppm. 159.5, 157.5, 135.3, 120.2, 111.5, 53.

Step 2. Methyl 5-chloro-3-fluoro-4-methylthiophene-2-carboxylate.

To a solution of methyl 5-chloro-3-fluorothiophene-2-carboxylate (579 mg, 3 mmol) in THF (3 ml) was added TMP.MgCl.LiCl (1N, in a mixture of THF / toluene, 6 ml, 6 mmol ) at -45 ° C for 5 min. After 60 min stirring, iodomethane (1.3 ml, 2964 mg, 20.9 mmol) in THF (2 ml) was added to the mixture at -45 ° C and stirred for 2 h at -40 ° C. After heating, sat. Was added to the mixture with stirring. NH ₄ Cl solution (5 ml, aq.). The mixture was extracted with EEO (4x10 ml) and the combined organic layers were evaporated. The residue was purified by prep LC (5 µm Gemini-NX C-18 column, 5 mM aqueous NH4HCO3-MeCN gradient) to afford the title product. GC-MS calculated for C ₇ H ₆ ClFO ₂ S: 207.9761, found: 207.9 [(M, EI) form].

1H NMR (500 MHz, MSM-d ₆ ): δ ppm. 3.81 (s, 3H), 2.09 (s, 3H). ¹³ C NMR (125 MHz, MSM-d ₆ ): δ ppm. 159.7, 156.4, 130.8, 127, 109.6, 53, 10.5.

Step 3. Compound Synthesis of R1l.

Methyl 5-chloro-3-fluoro-4-methylthiophene-2-carboxylate (316 mg, 1.62 mmol) and lithium hydroxide monohydrate (271 mg, 6.46 mmol) were stirred in methanol (5 ml) and water (5 ml) at r. t. for 4 h. The mixture was partially evaporated and the aqueous residue was acidified with 1N. HCl (2 ml, aq.). The resulting precipitate was filtered off, washed with water and dried to give Synthesis compound R1l.

1H NMR (500 MHz, MSM-d6): δ ppm. 13.57 (brs, 1H), 2.07 (s, 3H). ¹³ C NMR (125 MHz, MSM-d6): δ ppm. 160.7, 155.9, 129.8, 126.9, 111.4, 10.5

Synthesis of R1m: [4-methyl-2- (6-methyl-3-pyridyl) thiazol-5-yl] - [(3R, 4R) -4- (2-oxa-6-azaspiro [2.5] octane6-carbonyl) -3-phenyl-1-piperidyl] methanone.

Stage 1. Ethyl (3R, 4R) -3-phenylpiperidine-4-carboxylate hydrochloride.

1-tert-Butyl 4-ethyl (3R, 4R) -3-phenylpiperidine-1,4-dicarboxylate (10 g, 30 mmol) was stirred in

- 36 037563 mixtures of MeCN (100 ml) and conc. HCl solution (7.38 ml, 90 mmol, aq.) at 80 ° C for 30 min. The reaction mixture was evaporated and dried in vacuo to give the title product.

Step 2. Ethyl (3R, 4R) -1 - [(2-bromo-4-methyl-1,3-thiazol-5-yl) carbonyl] -3-phenylpiperidine-4carboxylate.

Ethyl (3R, 4R) -3-phenylpiperidine-4-carboxylate hydrochloride (7.89 g, 29.9 mmol), 2-bromo-4methylthiazole-5-carboxylic acid (6.64 g, 29.9 mmol) and EDC.HCl (17.2 g, 89.7 mmol ) was dissolved in pyridine (200 ml) and stirred at rt. over 23 hours. The reaction mixture was evaporated. Water (200 ml) was added to the residue and extracted with DCM (3x50 ml). The combined organic layer was dried over MgSO ₄ and evaporated to give the title product. MCBP: calculated for C ₁₉ H ₂₁ BrN ₂ O ₃ S: 436.0456, found: 437.0546 [(M + H) + form].

Ή NMR (500 MHz, MSM-d ₆ ): δ ppm 7.36-7.19 (m, 5H), 4.96-2.74 (vbrs, 4H), 3.82 (q, 2H), 3.03 (m, 1H), 2.87 (m, 1H), 2.34 (s, 3H), 1.98 / 1.62 ( m + m, 2H), 0.86 (t, 3H). ¹³ C NMR (125 MHz, MSM-d ₆ ): δ ppm. 160.5, 151.6, 136.3, 129.2, 60.1, 47.3, 45.3, 29.2, 16.4, 14.2.

Stage 3. Ethyl (3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidine-4-carboxylate ...

In 8 separate microwave tubes, ethyl (3R, 4R) -1 - [(2-bromo-4-methyl-1,3-thiazol-5yl) carbonyl] -3-phenylpiperidine-4-carboxylate (8x1.87 g , 34.2 mmol), 2-methylpyridine-5-boronic acid (8x1.17 g, 68.4 mmol), ATAphos * PdCl ₂ (8x303 mg, 3.4 mmol) and Cs ₂ CO ₃ (8x4.18 g, 102.6 mmol) were dissolved in THF (8x25 ml) and water (8x15 ml). 8 tubes were immediately exposed to microwave irradiation at 80 ° C for 2 h (Anton-Paar Multiwave Pro). The organic layers of 8 tubes were combined, partially evaporated and purified by preparative LC (on a C-18 Gemini-NX column 5 μm, 5 mM aqueous NH4HCO3-MeCN, gradient) to afford the title product. MCBP: calculated for C ₂₅ H ₂₇ N ₃ O ₃ S: 449.1773, found: 450.1860 [(M + H) ⁺ form].

1H NMR (400 MHz, MSM-d6): δ ppm. 8.98 (d, 1H), 8.17 (dd, 1H), 7.4 (d, 1H), 7.36-7.16 (m, 5H), 5-2.75 (vbrs, 4H), 3.83 (q, 2H), 3.05 (m, 1H), 2.87 (m, 1H), 2.53 (s, 3H), 2.43 (s, 3H), 2.01 / 1.64 (dm + qm, 2H), 0.87 (t, 3H). ¹³ C NMR (100 MHz, MSM-d6): δ ppm. 146.7, 134.4, 124, 60.1, 47.3, 45.5, 29.2, 24.3, 16.5, 14.2.

Step 4. (3R, 4R) -1 - {[4-Methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidine-4-carboxylic acid ...

Ethyl (3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidine 4-carboxylate (7.48 g, 16.64 mmol) and lithium hydroxide hydrate (1.75 g, 41.6 mmol) were stirred in a mixture of EtOH (30 ml) and water (10 ml) at 75 ° C for 3.5 h. The reaction mixture was partially evaporated, the residue was acidified (to pH = 4.5-5.5 ) HCl solution (1N, aq.) and the resulting suspension was filtered. The solid compound on the filter was washed with water and dried to give the title product. MCBP: calculated for C ₂₃ H ₂₃ N ₃ O ₃ S: 421.146, found: 422.1544 [(M + H) ⁺ form].

1H NMR (400 MHz, MSM-d ₆ ): δ ppm. 11.82 (brs, 1H), 8.97 (d, 1H), 8.15 (dd, 1H), 7.39 (d, 1H), 7.35-7.18 (m, 5H), 4.34-4.05 (brm, 4H), 3.01-2.84 ( m, 2H), 2.54 (s, 3H), 2.44 (s, 3H), 2.06 / 1.66 (m + m, 2H). ¹³ C NMR (100 MHz, MSM-d ₆ ): δ ppm. 146.8, 134.4, 123.8, 29.5, 24.3, 16.5.

Step 5. 1- {[(3R, 4R) -1- {[4-Methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidine- 4-yl] carbonyl} piperidin-4-one.

(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidine-4carboxylic acid (3786 mg, 8.98 mmol), piperidin-4-one hydrochloride hydrate (1518 mg, 9.88 mmol), and EDC.HCl (5.16 g, 26.94 mmol) were stirred in pyridine (30 mL) at RT. for 16 h. The reaction mixture was evaporated, the residue was taken up in MeOH (20 ml) and poured into water (120 ml) and extracted with DCM (3 x 60 ml). The combined organic layer was washed with water, brine, dried over MgSO ₄ and evaporated to give the title product. MCBP: calculated for C ₂₃ H ₂₃ N ₃ O ₃ S: 502.2039, found: 503.2088 [(M + H) ⁺ form].

1H NMR (400 MHz, MSM-d6): δ ppm. 8.98 (brs, 1H), 8.17 (dd, 1H), 7.4 (d, 1H), 7.36-7.13 (m, 5H), 4.922.76 (m, 10H), 2.53 (s, 3H), 2.45 (s, 3H), 2.25-1.52 (m, 6H).

Step 6. Compound Synthesis of R1m.

- {[(3R, 4R) -1- {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} piperidin-4-one (3.89 g, 7.74 mmol) and trimethylsulfoxonium iodide (2.09 g, 9.3 mmol) were stirred in MeCN (19 ml) at RT. and a solution of NaOH (309 mg, 9.3 mmol) in water (0.4 ml) was added to the mixture. The reaction mixture was then stirred at 70 ° C for 2 h. The reaction mixture was poured into water (200 ml) and neutralized with aqueous HCl (1N, 9 ml) and extracted with DCM (3 x 80 ml). The combined organic layer was washed with water and brine and evaporated to give Synthesis compound R1m as a solid foam. MCBP calculated for C ₂₉ H ₃₂ N ₄ O ₃ S: 516.2195, found: 517.2267 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6): δ ppm. 8.98 (brs, 1H), 8.17 (dd, 1H), 7.4 (d, 1H), 7.37-7.15 (brs / brs, 5H), 3.82-0.88 (m, 14H), 3.53 (m, 1H), 2.97 ( brm, 1H), 2.56 (m, 2H), 2.53 (s, 3H), 2.44 (s, 3H). ¹³ C NMR (125 MHz, MSM-d6): δ ppm. 164.1, 160.8, 152.4, 146.8, 134.5, 125.6, 124.1, 57.4 / 57.1, 53.4 / 53.1, 42.9 / 42.8, 24.5, 16.7.

Synthesis of R1n. 3 - [[4-Hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7- (2- 37 037563 trimethylsilylethoxymethyl) pyrrolo [2,3-d] pyrimidin-4-one.

Step 1. 2 - [(4-Chloropyrrolo [2,3-d] pyrimidin-7-yl) methoxy] ethyltrimethylsilane.

Synthesis compound R1a (2.81 g, 18.3 mmol) was dissolved in THF (25 ml), cooled to 0 ° C, and NaH (60% disp., 1.1 g, 27.4 mmol) was added to the mixture and stirred for 1 h. the mixture was added SEM-C1 (8.1 ml, 45.76 mmol) and allowed to warm to rt. After 2.5 h, water (25 ml) was added to the reaction mixture and extracted with EEO (2x30 ml). The combined organic layer was dried over MgSO ₄ and evaporated. The residue was purified by flash chromatography (220 g Silica Gold column, heptane-EEO, gradient) to afford the title product.

Step 2. 7- (2-Trimethylsilylethoxymethyl) -3H-pyrrolo [2,3-d] pyrimidin-4-one.

2 - [(4-Chloropyrrolo [2,3-d] pyrimidin-7-yl) methoxy] ethyltrimethylsilane (3.5 g, 12.3 mmol) and lithium hydroxide hydrate (5.17 g, 123 mmol) were stirred at 100 ° C for 116 h in a mixture of PDO (20 ml) and water (20 ml). The reaction mixture was filtered, the filtrate was acidified with aqueous HCl (1N, 80 ml) and the resulting solid was filtered off, washed with water and dried to give the title product.

Step 3. tert-Butyl 4-hydroxy-4 - [[4-oxo-7- (2-trimethylsilylethoxymethyl) pyrrolo [2,3-d] pyrimidin-3-yl] methyl] piperidine-1-carboxylate.

7- (2-Trimethylsilylethoxymethyl) -3H-pyrrolo [2,3-d] pyrimidin-4-one (3.11 g, 11.7 mmol), Synthesis compound R1e (2.75 g, 2.9 mmol) and K ₂ CO ₃ (1.78 g, 12.9 mmol) was stirred in DMF (70 ml) at 60 ° C for 40 h. Water was added to the reaction mixture, the resulting solid was filtered off and washed with water to give the title product. MCBP: calculated for C ₂₃ H ₃₈ N ₄ O ₅ Si 478.2611, found: 479.2694 [(M + H) + form].

Step 4. 3 - [(4-Hydroxy-4-piperidyl) methyl] -7- (2-trimethylsilylethoxymethyl) pyrrolo [2,3-d] pyrimidin-4-one.

tert-Butyl 4-hydroxy-4 - [[4-oxo-7- (2-trimethylsilylethoxymethyl) pyrrolo [2,3-d] pyrimidin-3-yl] methyl] piperidine-1-carboxylate (1.84 g, 3.86 mmol) dissolved in DCM (50 ml) and added formic acid (5 ml) and TFA (1317 mg, 0.885 ml, 11.58 mmol), and then the mixture was stirred for 4 days at rt. An aqueous sodium hydroxide solution (1N, 100 ml) was added to the reaction mixture, followed by extraction with DCM (50 ml). The organic layer was dried over MgSO ₄ , filtered, and evaporated to give the title product. MCBP: calculated for C ₁₈ H ₃₀ N ₄ O ₃ Si: 378.2087, found: 379.2176 [(M + H) ⁺ form].

Step 5. tert-Butyl (3R, 4R) -4- [4-hydroxy-4 - [[4-oxo-7- (2-trimethylsilylethoxymethyl) pyrrolo [2,3-d] pyrimidin-3-yl] methyl] piperidine-1-carbonyl] -3-phenylpiperidine-1 -carboxylate.

3 - [(4-Hydroxy-4-piperidyl) methyl] -7- (2-trimethylsilylethoxymethyl) pyrrolo [2,3-d] pyrimidin-4one (1.527 g, 3.77 mmol), (3R, 4R) -1-tert β-butoxycarbonyl-3-phenylpiperidine-4-carboxylic acid (1.152 g, 3.77 mmol) and EDC.HCl (1.446 g, 7.54 mmol) were stirred in pyridine (15 ml) overnight at rt. The reaction mixture was evaporated, loaded onto celite, and purified by flash chromatography (DCM-MeOH) to give the title product. MCBP: calculated for C ₃ 5H5iN ₅ O ₆ Si: 665.3609, found: 666.3696 [(M + H) ⁺ form].

Step 6. Compound Synthesis of R1n.

A solution of tert-butyl (3R, 4R) -4- [4-hydroxy-4 - [[4-oxo-7- (2-trimethylsilylethoxymethyl) pyrrolo [2,3d] pyrimidin-3-yl] methyl] piperidin-1- carbonyl] -3-phenylpiperidine-1-carboxylate (1.6 g, 2.4 mmol), formic acid (3 ml) and TFA (820 mg, 0.55 ml, 7.2 mmol) in DCM (30 ml) were stirred at rt. within 4 days. Potassium carbonate (15 g) was added to the reaction mixture as an aqueous solution, and the mixture was extracted with DCM. The organic layer was evaporated to give Synthesis compound R1n. MCBP calculated for C3 ₀ H ₄₃ N ₅ O ₄ Si: 565.3084, found: 566.3138 [(M + H) + form].

Synthesis of R1o: 5-bromo-4- (tert-butoxycarbonylamino) thiophene-2-carboxylic acid.

4-amino-5-bromothiophene-2-carboxylic acid (500 mg, 2.25 mmol) was dissolved in a PDO mixture (2 ml), and water (2 ml) and sodium hydroxide (194 mg, 4.8 mmol ). Then, di-tert-butyl dicarbonate (1768 mg, 8.1 mmol) was added to the mixture and stirred at 0 ° C for 3 h, then the reaction mixture was allowed to warm to rt. and stirred for 116 h. Water was added to the reaction mixture and acidified with aqueous HCl (1N, 4 ml). The resulting solid was filtered off, washed with water and dried. The residue was purified by preparative LC (5 µm Gemini-NX C-18 column, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient yielding ammonium salt) to give Synthesis compound R1o. 1H NMR (500 MHz, MSM-d ₆ ): δ ppm. 8.71 (s, 1H), 7.44 (brs, 4H), 7.24 (s, 1H), 1.44 (s, 9H).

¹³ C NMR (125 MHz, MSM-d6): δ ppm. 125.8, 28.5. ¹⁵ N NMR (470.6 MHz, MSM-d6): δ ppm. 99.

Synthesis of R1p: 4-nitro-5- (4-pyridyl) thiophene-2-carboxylic acid.

Using General Procedure 9, starting from methyl 5-chloro-4-nitrothiophene-2-carboxylate and 4 (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine as reactant, crude the product (200 mg, 0.75 mmol) was stirred with lithium hydroxide hydrate (60 mg, 1.5 mmol) in a mixture of water (2 ml) and methanol (10 ml) at room temperature. for 4 h.The reaction mixture was neutralized with an aqueous solution of HCl (1N, 1.5

- 38 037563 ml). The resulting precipitate was filtered off, washed with water and dried to give Synthesis compound R1p. 1H NMR (500 MHz, MSM-d ₆ ): δ ppm. 14.18 (vbrs, 1H), 8.74 (brs, 2H), 8.19 (s, 1H),

7.65 (m, 2H).

¹³ C NMR (125 MHz, MSM-d ₆ ): δ ppm. 161.8, 150.4, 145.9, 143.6, 138.2, 134.4, 129.2, 124.3.

Synthesis of R1q- (3S, 4R): (3S, 4R) -1-benzyl-3- (2-thienyl) piperidine-4-carboxylic acid and

Synthesis of R1q- (3R, 4S): (3R, 4S) -1-benzyl-3- (2-thienyl) piperidine-4-carboxylic acid.

To a stirred suspension of sodium hydride (60% dispers., 1.4 g, 35.1 mmol) in abs. DEE (135 mL) was added ethyl 1-benzyl-3-oxopiperidine-4-carboxylate hydrochloride (3.54 g, 11.9 mmol) at 0 ° C. After stirring for 30 min, trifluoromethanesulfonic anhydride (3.88 g, 2.28 ml, 13.5 mmol) was added dropwise to the reaction mixture and stirred for 3 h, during which the temperature was allowed to rise to rt. Water (100 ml) was added to the reaction mixture, the layers were separated, the aqueous layer was washed with DEE. The DEE layer was dried over MgSO ₄ and evaporated.

Part of the resulting ethyl 1-benzyl-5- (trifluoromethylsulfonyloxy) -3,6-dihydro-2H-pyridine-4-carboxylate (2.184 g, 5.55 mmol), 2-thienylboronic acid (925 mg, 7.23 mmol), ATAphos * PdCl ₂ (400 mg, 0.55 mmol) and Cs ₂ CO ₃ (3.63 g, 11.1 mol) were dissolved in THF (11 ml) and water (11 ml). The mixture was purged with nitrogen and microwaved at 82 ° C for 140 min. The layers were separated, the organic layer was evaporated, applied to celite and purified by flash chromatography (Heptane-EEO, gradient).

Earlier obtained ethyl 1-benzyl-5- (trifluoromethylsulfonyloxy) -3,6-dihydro-2H-pyridine-4-carboxylate (2.184 g, 5.55 mmol), 2-thienylboronic acid (925 mg, 7.23 mmol), ATAphos * PdCl ₂ (400 mg, 0.55 mmol) and Cs ₂ CO ₃ (3.63 g, 11.1 mol) were dissolved in a mixture of THF (11 ml) and water (11 ml). The mixture was purged with nitrogen and microwaved at 82 ° C for 140 min. The layers were separated, the organic layer was evaporated, applied to celite and purified by flash chromatography (HeptanEEO, gradient).

The resulting ethyl 1-benzyl-5- (2-thienyl) -3,6-dihydro-2H-pyridine-4-carboxylate (2.85 g, 8.7 mmol), Pd on carbon (3x1.5 g, 10%), a solution of HCl (1N in ether, 8.7 ml, 8.7 mmol) and EtOH (65 ml) were loaded into the autoclave. The autoclave was closed, inerted, evacuated and filled with hydrogen (8 bar), and the reaction mixture was stirred in the autoclave at 90 ° C for 420 hours. During the reaction, the catalyst was filtered off and replaced twice with fresh. The reaction mixture was removed from the autoclave and filtered through celite and the filtrate was evaporated. The residue was purified by preparative LC (on a C-18 Gemini-NX 5 µm column, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient).

The resulting methyl cis-1-benzyl-3- (2-thienyl) piperidine-4-carboxylate (664 mg, 2 mmol) was dissolved in a solution of NaOEt (1N, in EtOH, freshly prepared, 10 ml, 10 mmol) and stirred at 75 ° C for 3 hours. Then water (5 ml) was added to the reaction mixture and stirring was continued at 75 ° C for 4 hours. The reaction mixture was partially evaporated, then neutralized with 1N. aqueous HCl solution, the solid was filtered off, washed with water and dried. The two enantiomers were separated by chiral LC to give Synthesis compound R1q- (3S, 4R) and Synthesis compound R1q- (3R, 4S). MCBP: calculated for Ci ₇ Hi ₉ NO ₂ S: 301.1136, found: 302.1217 [(M + H) + form].

1H NMR (400 MHz, MSM-d ₆ ): δ ppm. 12.15 (brs, 1H), 7.37-7.19 (m, 5H), 7.32 (dd, 1H), 6.91 (dd, 1H), 6.88 (dd, 1H), 3.51 (s, 2H), 3.24 (tm, 1H) , 2.9-2.05 (m, 4H), 2.39 (tm, 1H), 1.91-1.67 (dm / qm, 2H).

Synthesis of R1s: (4-methyl-2-phenylthiazol-5-yl) - [(3R, 4R) -4- (2-oxa-6-αzaspiro [2.5] octαn-6-carbonyl) -3phenyl-1-piperidyl] methanone.

Step 1. 1 - [(3R, 4R) -3-Phenylpiperidin-4-carbonyl] piperidin-4-one hydrochloride.

tert-butyl (3R, 4R) -4- (4-oxopiperidine-1-carbonyl) -3-phenylpiperidine-1-carboxylate (obtained from Stage 1 of Synthesis of R1f, 4.77 g, 12.34 mmol) was stirred in PDO (20 ml) and aqueous HCl (20 ml, 1N) at 70 ° C for 1 h. The reaction mixture was evaporated and dried to give the title product. MCBP calculated for C ₁₇ H ₂₂ N ₂ O ₂ : 286.1681, found: 287.1755 [(M + H) + form].

1H NMR (400 MHz, MSM-d6): δ ppm. 9.68 (brd, 1H), 9.14 (brq, 1H), 7.40-7.18 (m, 5H), 3.73 / 3.31 (m / m, 2H), 3.73 / 3.31 (m / m, 2H), 3.56 (m, 1H ), 3.33 / 3.10 (m / m, 2H), 3.31-3.13 (m, 2H), 3.26 (m, 1H), 2.17 / 1.56 (m / m, 2H), 2.15 / 1.81 (m / m, 2H) , 2.03-1.87 (m, 2H).

Stage 2.1 - [(3R, 4R) -1- (4-Methyl-2-phenylmiazole-5-carbonyl) -3-phenylpiperidin-4-carbonyl] piperidin-4-one

1 - [(3R, 4R) -3-phenylpiperidin-4-carbonyl] piperidin-4-one hydrochloride (3.42 g, 10.6 mmol), EDC.HCl (6.64 g, 34.6 mmol) and 4-methyl-2-phenylthiazole- 5-carboxylic acid (2.32 g, 10.6 mmol) was stirred in pyridine (60 ml) at rt. over 20 hours. The reaction mixture was evaporated, loaded onto celite and purified by flash chromatography (DCM-MeOH / DCM gradient) to give the title product. MCBP: calculated for C ₂₈ H ₂₉ N ₃ O ₃ S: 487.1930, found: 488.1991 [(M + H) + form].

Ή NMR (400 MHz, MSM-d6): δ ppm 7.93 / 7.51 (brs / brs, 5H), 7.35 / 7.15 (brs / brs, 5H), 4.80-2.80 (brm, 4H), 3.74 / 3.63 (m / brm, 2H), 3.74 / 3.32 (m / m, 2H), 3.56 (td, 1H), 2.99 (td, 1H), 2.44 (s, 3H), 2.19 / 1.61 (m / m, 2H), 2.16 / 1.84 (m / m, 2H), 1.89 / 1.66 ( brm / brm, 2H).

Step 3. Compound Synthesis of R1s.

- 39 037563

To a stirred suspension of 1 - [(3R, 4R) -1- (4-methyl-2-phenylthiazole-5-carbonyl) -3-phenylpiperidin-4-carbonyl] piperidin-4-one (4.5 g, 9.23 mmol) and iodide trimethylsulfoxonium (2.44 g, 11.1 mmol) in MeCN (25 ml) was added aqueous sodium hydroxide (40 wt%, 443 mg NaOH / 0.664 ml water) at RT. and the mixture was stirred for 160 minutes. The reaction mixture was diluted with water (20 ml) and the MeCN was evaporated. The residue was extracted with DCM and the organic layer was evaporated to give Synthesis compound R1s. MCBP: calculated for C ₂₉ H ₃ iN3O ₃ S: 501.2086, found: 502.2160 [(M + H) + form].

1H NMR (400 MHz, MSM-de): δ ppm. 7.93 (m, 2H), 7.51 (m, 3H), 7.40-7.10 (brs / brs, 5H), 4.88-2.88 (brm, 4H), 3.82-297 (m, 4H), 3.54 (m, 1H), 2.97 (m, 1H), 2.56 (m, 2H), 2.43 (s, 3H), 1.83 / 1.63 (brd / brq, 2H), 1.450.86 (m, 2H).

Synthesis of R1t: 1-ethenyl-1H-indole-2-carboxylic acid.

A mixture of ethyl indole-2-carboxylate (2 g, 10.57 mmol), palladium (II) acetate (119 mg, 0.53 mmol), copper (II) bromide (2.37 g, 10.57 mmol), vinyl acetate (20 ml, 248.7 mmol) and sodium acetate (2.6 g, 31.7 mmol) was heated at 80 ° C for 28 h. The reaction mixture was evaporated, applied to celite and purified by flash chromatography (heptane-EEO, 0-5% gradient).

A mixture of the resulting ester (1.08 g, 5.017 mmol) and lithium hydroxide hydrate (1.05 g, 25.1 mmol) in ethanol and water (10-10 mL) was stirred at 80 ° C for 90 min. The reaction mixture was acidified with an aqueous solution of HCl (1N, 30 ml) at 0-5 ° C, the formed precipitate was filtered off, washed with water (5x20 ml) and dried to give the Synthesis compound R1t.

Ή NMR (400 MHz, MSM-d6): δ ppm 13.22 (s, 1H), 7.75 (m, 3H), 7.51 (m, 1H), 7.22 (t, 1H), 5.48 (d, 1H), 5.28 (d, 1H).

Synthesis of R1u: 5-bromo-1-vinylpyrrole-2-carboxylic acid.

A mixture of methyl 5-bromo-1H-pyrrole-2-carboxylate (1.2 g, 5.88 mmol), palladium (II) acetate (132 mg, 0.588 mmol), copper (II) bromide (2.63 g, 11.76 mmol), vinyl acetate (27 ml, 294 mmol) and sodium acetate (2.9 g, 35.3 mmol) were heated at 80 ° C for 28 h.The reaction mixture was evaporated, applied to celite and purified by flash chromatography (heptane-EEO, 0-25% gradient).

A mixture of the resulting ester (403 mg, 1.75 mmol) and lithium hydroxide hydrate (368 mg, 8.75 mmol) in ethanol and water (4-4 ml) was stirred at 80 ° C for 60 min. The reaction mixture was acidified with aqueous HCl solution (1N, 10 ml) at 0-5 ° C. The formed precipitate was filtered off, washed with water (5x20 ml) and dried to give the Synthesis compound R1u. 1H NMR (400 MHz, MSM-d ₆ ): δ ppm. 12.63 (s, 1H), 7.11 (m, 1H), 6.94 (d, 1H), 6.45 (d, 1H), 5.42 (m, 2H).

Synthesis of R1v: 4-bromo-1-vinylpyrrole-2-carboxylic acid.

A mixture of methyl 4-bromo-1H-pyrrole-2-carboxylate (1.2 g, 5.88 mmol), palladium (II) acetate (132 mg, 0.588 mmol), copper (II) bromide (2.63 g, 11.76 mmol), vinyl acetate (27 ml, 294 mmol) and sodium acetate (2.9 g, 35.3 mmol) were heated at 80 ° C for 21 h.The reaction mixture was evaporated, applied to celite and purified by flash chromatography (heptane-EEO, 0-5% gradient).

A mixture of the resulting ester (338 mg, 1.47 mmol) and lithium hydroxide hydrate (908 mg, 7.35 mmol) in ethanol and water (3.5-3.5 mL) was stirred at 80 ° C for 105 min. The reaction mixture was acidified with aqueous HCl solution (1N, 9 ml) at 0-5 ° C. The formed precipitate was filtered off, washed with water (2x5 ml) and dried to give Synthesis compound R1v. 1H NMR (500 MHz, MSM-d6): δ ppm. 12.93 (brs, 1H), 7.85 (d, 1H), 7.84 (dd, 1H), 6.94 (d, 1H), 5.5 / 4.9 (dd + dd, 2H).

¹³ C NMR (125 MHz, MSM-d6): δ ppm. 131.4, 124.1, 123.4, 120.3, 102.8, 97.9

Synthesis of R1w: 4,5-dichloro-3-fluorothiophene-2-carboxylic acid.

Stage 1: methyl 4,5-dichloro-3-fluorothiophene-2-carboxylate.

To a solution of methyl 3-fluorothiophene-2-carboxylate (1826 mg, 11.4 mmol) in THF (5 ml) was added TMP.MgCl.LiCl (1N, in a THF / toluene mixture, 21 ml, 21 mmol) dropwise at -45 ° C for 5 min. After stirring for 30 min at -45 ° C, hexachloroethane (2.7 g, 11.4 mmol) was added to the mixture at -45 ° C and stirred for 1 h at -40 ° C. After heating, sat. Was added to the mixture with stirring. NH ₄ Cl solution (10 ml, aq.). The mixture was extracted with EEO (4x10 ml). The combined organic layer was evaporated. The residue was purified by prep LC (5 µm Gemini-NX C-18 column, 5 mM aqueous NH4HCO ₃ -MeCN gradient) to afford the title product. GC-MS calculated for C ₆ H3Cl ₂ FO ₂ S: 227.9215, found: 227.9 [(M, EI) form].

1H NMR (500 MHz, MSM-d6): δ ppm. 3.85 (s, 3H). ¹³ C NMR (125 MHz, MSM-d6): δ ppm. 159, 152.8, 130.5, 115.5, 110.8, 53.4.

Step 2. Compound Synthesis of R1w.

Methyl 4,5-dichloro-3-fluorothiophene-2-carboxylate (130 mg, 0.567 mmol) and lithium hydroxide monohydrate (95 mg, 2.27 mmol) were stirred in methanol (3 ml) and water (3 ml) at rt. within 3 h. The mixture was partially evaporated and the aqueous residue was acidified with 1N. HCl (4 ml, aq.). The resulting precipitate was filtered off, washed with water and dried to give Synthesis compound R1w. ¹³ C NMR (125 MHz, MSM-d ₆ ): δ ppm. 160, 152.3, 129.5, 115.3, 112.8.

Synthesis of R1x: 2- (6-methyl-3-pyridyl) thiazole-5-carboxylic acid.

Ethyl 2- (6-methyl-3-pyridyl) thiazole-5-carboxylate (745 mg, 3 mmol) and lithium hydroxide monohydrate

- 40 037563 (630 mg, 15 mmol) was stirred in ethanol (5 ml) and water (5 ml) at rt. for 8 h. The mixture was partially evaporated and the aqueous residue was acidified with 1N. HCl (15 ml, aq.). The resulting precipitate was filtered off, washed with water and dried to give Synthesis compound R1x. MCBP: calculated for C ₁₀ H ₈ N ₂ O ₂ S: 220.0307, found: 221.0379 [(M + H) + form].

¹ H NMR (500 MHz, MSM-de): δ ppm. 13.69 (brs, 1H), 9.07 (d, 1H), 8.45 (s, 1H), 8.26 (dd, 1H), 7.44 (d, 1H), 2.55 (s, 3H). ¹³ C NMR (125 MHz, MSM-de): δ ppm. 149.3, 147.1, 134.9, 124.2, 24.5.

Synthesis of R2b: 7-methyl-3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one Using General Procedure 1, starting from Synthesis compound R1a and iodomethane as alkylating agent, Synthesis compound R2b was obtained. MCBP: calculated for C ₇ H ₇ N ₃ O: 149.0589, found: 150.0668 [(M + H) + form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 11.85 (brs, 1H), 7.88 (brs, 1H), 7.09 (d, 1H), 6.44 (d, 1H), 3.70 (m, 1H).

13C-NMR (125 MHz, MSM-d6): δ (ppm) 158.7, 147.7, 143.8, 125.1, 108.1, 101.7, 31.8.

Synthesis of R2c: 7-ethyl-3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 1, starting from the Synthesis compound R1a and iodoethane as reagents, the Synthesis compound R2c was prepared. MCBP calculated for C8H9N3O: 163.0746, found: 164.0823 [(M + H) + form].

1H NMR (500 MHz, MSM-d ₆ ): δ (ppm) 11.38 (brs, 1H), 7.87 (d, J = 2.0 Hz, 1H), 7.16 (d, J = 3.4 Hz, 1H), 6.45 (d, J = 3.4 Hz, 1H), 4.14 (q, J = 7.1 Hz, 2H), 1.34 (t, J = 7.1 Hz, 3H).

Synthesis of R2d: 7- (propαn-2-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one Using General Procedure 1, starting from the Synthesis compound R1a and 2-iodopropane as reagents, obtained the Synthesis compound R2d. MCBP calculated for C9H11N3O: 177.0902, found: 178.0979 [(M + H) + form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 11.83 (brs, 1H), 7.87 (s, 1H), 7.24 (d, 1H), 6.47 (d, 1H), 4.85 (sept. , 1H), 1.42 (d, 6H). 13C-NMR (125 MHz, MSM-d _6): δ (ppm) 158.8, 146.8, 143.5, 120.7, 108.2, 102, 46.5, ^15, 23. NYAMR (50.6 MHz, MSM-d _6): δ ( ppm) 168.

Synthesis of R2g: 7-cyclopropyl-3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 2, starting from the Synthesis compound R1a and cyclopropylboronic acid as reagents, the Synthesis compound R2g was prepared. MCBP: calculated for C9H9N3O: 175.0746, found: 176.0819 [(M + H) + form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 11.88 (brs, 1H), 7.89 (brs, 1H), 7.05 (d, 1H), 6.4 (d, 1H), 3.53 (m, 1H), 1.06-0.92 (m, 4H). 13C-NMR (125 MHz, MSM-d6): δ (ppm) 158.7, 148.9, 143.8, 123.4, 108.8, 101.6, 27.5, 6.6.

Synthesis of R2h: 7-cyclobutyl-3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 1, starting from Synthesis compound R1a and cyclobutyl bromide as reagents, Synthesis compound R2h was prepared. MCBP: calculated for C ₁₀ H11N ₃ O: 189.0902, found: 190.0974 [(M + H) + form].

1H NMR (500 MHz, MSM-d ₆ ): δ (ppm) 11.85 (brs, 1H), 7.88 (brs, 1H), 7.09 (d, 1H), 6.44 (d, 1H), 3.70 (m , 1H). 13C-NMR (125 MHz, MSM-d ₆ ): δ (ppm) 158.7, 147.7, 143.8, 125.1, 108.1, 101.7, 31.8.

Synthesis of R2i: 7-cyclopentyl-3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 4 starting from the Synthesis compound R1a and cyclopentanol as reagents, the Synthesis compound R2i was prepared. MCBP calculated for C11H ₁₃ N ₃ O: 203.1059, found: 204.1139 [(M + H) + form].

1H NMR (400 MHz, MSM-d ₆ ): δ (ppm) 11.84 (brs, 1H), 7.87 (d, 1H), 7.21 (d, 1H), 6.46 (d, 1H), 4.97 (m , 1H), 2.16-1.57 (m, 8H). 13C-NMR (100 MHz, MSM-d ₆ ): δ (ppm) 143.5, 121.3, 102, 55.6.

Synthesis of R2j: 7-cyclohexyl-3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 4 starting from the Synthesis compound R1a and cyclohexanol as reagents, the Synthesis compound R2j was prepared. MCBP calculated for C ₁₂ H ₁₅ N ₃ O: 217.1215, found: 218.1293 [(M + H) + form].

1H NMR (400 MHz, MSM-d6): δ (ppm) 11.83 (brs, 1H), 7.86 (d, 1H), 7.23 (d, 1H), 6.46 (d, 1H), 4.45 (m, 1H), 1.97-1.13 (m, 10H). 13C-NMR (100 MHz, MSM-d6): δ (ppm) 143.4, 121.1, 101.8, 53.8.

Synthesis of R2k: 7- (1-methylpiperidin-4-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 4, starting from the Synthesis compound of R1a and 4-hydroxy-1-methylpiperidine as reagents, the Synthesis compound of R2k was prepared. MCBP: calculated for C ₁₂ H ₁₆ N ₄ O: 232.1324, found: 233.1405 [(M + H) + form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 11.82 (brs, 1H), 7.86 (d, 1H), 7.29 (d, 1H), 6.46 (d, 1H), 4.44 (m, 1H), 2.89 / 2.05 (m, 4H), 2.22 (s, 3H), 2.02 / 1.82 (m, 4H). 13C-NMR (125 MHz, MSM-d6): δ (ppm) 143.9, 121.2, 102.1, 55.1, 52.1, 46.1, 32.3.

Synthesis of R2l: 7- (tetrahydro-2H-pyran-4-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 4, starting from the Synthesis compound R1a and tetrahydro-4-pyranol as reagents, the Synthesis compound R2l was prepared. MCBP: calculated for C11H ₁₃ N ₃ O ₂ : 219.1008, found: 220.1082 [(M + H) + form].

- 41 037563

Ή NMR (400 MHz, MSM-d ₆ ): δ (ppm) 11.88 (brs, 1H), 7.88 (d, 1H), 7.29 (d, 1H), 6.48 (d, 1H), 4.71 (m ,

1H), 3.98 / 3.49 (m + m, 4H), 2.05 / 1.82 (m + m, 4H). ¹³ C-NMR (100 MHz, MSM-d ₆ ): δ (ppm) 143.5, 121.2, 102,

66.7, 51.3, 33.3.

Synthesis of R2m: 7- (prop-2-yn-1-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 1, starting from the Synthesis compound R1b (instead of the Synthesis compound R1a) and 3-bromoprop-1-yne as reagents (without the hydrolysis step), the crude methoxypyrimidine product (400 mg, 2.3 mmol) was dissolved in PDO (4 ml) and an aqueous HCl solution (37%, 0.18 ml) was added. The mixture was heated at 100 ° C for 30 min in a Schlenk flask. After cooling, DIPO (4 ml) was added to the reaction mixture and the resulting precipitate was filtered off and dried to give Synthesis compound R2m. MCBP calculated for C ₉ H ₇ N ₃ O: 173.0589, found: 174.0665 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 11.98 (brs, 1H), 7.93 (s, 1H), 7.19 (d, 1H), 6.5 (d, 1H), 4.98 (d, 2H), 3.42 (t, 1H). ¹³ C-NMR (125 MHz, MSM-d6): δ (ppm) 158.6, 147.3, 144.3, 123.6, 102.5, 79.4, 76, 34.1.

Synthesis of R2n: 7- (2-methylpropyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 1, starting from the Synthesis compound of R1a and 1-bromo-2-methylpropane as reagents, the Synthesis compound of R2n was prepared. MCBP: calculated for C ₁₀ H ₁₃ N ₃ O: 191.1059, found: 192.1132 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ): δ (ppm) 11.84 (brs, 1H), 7.86 (s, 1H), 7.12 (d, 1H), 6.45 (d, 1H), 3.92 (d , 2H), 2.1 (sept., 1H), 0.82 (d, 6H). ¹³ C-NMR (125 MHz, MSM-d ₆ ): δ (ppm) 158.8, 147.7, 143.7, 124.5, 108, 101.6, 52, 29.6, 20.2.

Synthesis of R2o: 7- (2,2,2-trifluoroethyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 1, starting from the Synthesis compound R1a and 2,2,2-trifluoroethyl trifluoromethanesulfonate as reagents, the Synthesis compound R2o was obtained. MCBP: calculated for C8H6N ₃ OF ₃ : 217.0463, found: 218.0543 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 12.08 (brs, 1H), 7.97 (s, 1H), 7.19 (d, 1H), 6.57 (d, 1H), 5.06 (q, 2H). ¹³ C-NMR (125 MHz, MSM-d6): δ (ppm) 158.5, 148.4, 144.9, 124.7, 124.4, 108.8, 103.2, 45.1. ¹⁹ F-NMR (376.5 MHz, MSM-d6): δ (ppm) -70.3.

Synthesis of R2p: 7- (2,2-difluoroethyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 1, starting from the Synthesis compound R1a and 2-iodo-1,1-difluoroethane as reagents, the Synthesis compound R2p was prepared. MCBP: calculated for C ₈ H ₇ N ₃ OF ₂ : 199.0557, found: 200.0634 ((M + H) ⁺ form].

1H NMR (400 MHz, MSM-d6) δ ppm. 11.99 (brs, 1H), 7.93 (s, 1H), 7.16 (d, 1H), 6.53 (d, 1H), 6.37 (tt, 1H), 4.6 (td, 2H). ¹³ C-NMR (400 MHz, MSM46) δ ppm. 144.4, 124.8, 114.3, 102.5, 46.2.

Synthesis of R2q: 7- (cyclopropylmethyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 1, starting from Synthesis compound R1a and cyclopropylmethyl bromide as reagents, Synthesis compound R2q was prepared. MCBP: calculated for C10H11N3O: 189.0902, found: 190.0980 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ): δ (ppm) 11.84 (s, 1H), 7.87 (s, 1H), 7.2 (d, 1H), 6.45 (d, 1H), 3.97 (d , 2H), 1.21 (m, 1H), 0.52-0.35 (m, 4H). ¹³ C-NMR (125 MHz, MSM-d6): δ (ppm) 158.7, 147.3, 143.7, 124, 108.1, 101.7, 49, 12.3, 4.07.

Synthesis of R2r: 7- (cyclobutylmethyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 1, starting from the Synthesis compound of R1a and (bromomethyl) cyclobutane as reagents, the Synthesis compound of R2r was obtained. MCBP: calculated for CnHi ₃ N ₃ O: 203.1059, found: 204.1134 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ): δ (ppm) 11.83 (brs, 1H), 7.87 (d, 1H), 7.12 (d, 1H), 6.43 (d, 1H), 4.13 (d , 2H), 2.72 (m, 1H), 1.92 / 1.74 (m + m, 4H), 1.82 (m, 2H). ¹³ C-NMR (125 MHz, MSM-d ₆ ): δ (ppm) 143.7, 124.2, 101.7, 49.6, 36, 25.6, 18.

Synthesis of R2s: 7- (buta-2,3-diene-1-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 1, starting from the Synthesis compound R1b (instead of the Synthesis compound R1a) and 4-bromobut-1,2-diene as reagents (without the hydrolysis step), the crude methoxypyrimidine product (300 mg, 1.65 mmol) was dissolved in PDO (4 ml) and an aqueous HCl solution (37%, 0.18 ml) was added. The mixture was heated at 100 ° C for 30 min in a Schlenk flask. After cooling, the reaction mixture was evaporated to give Synthesis compound R2s. MCBP: calculated for C ₁₀ H ₉ N ₃ O: 187.0745, found: 188.0821 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 11.91 (brs, 1H), 7.89 (s, 1H), 7.12 (d, 1H), 6.46 (d, 1H), 5.48 (m, 1H), 4.87 (m, 2H), 4.73 (m, 2H). ¹³ C-NMR (125 MHz, MSM-d6): δ (ppm) 208.3, 158.7, 147.4, 143.9, 123.9, 108.2, 102.1, 88.3, 78.1, 43.

Synthesis of R2t: 7- [3- (dimethylamino) propyl] -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 1, starting from the Synthesis compound R1a and 3-dimethylaminopropyl chloride hydrochloride as reagents, the Synthesis compound R2t was prepared. MCBP: calculated for C11H16N4O: 220.1324, found: 221.1401 [(M + H) ⁺ form].

- 42 037563

Ή NMR (500 MHz, MSM-d ₆ ): δ (ppm) 11.84 (brs, 1H), 7.88 (s, 1H), 7.13 (d, 1H), 6.44 (d, 1H), 4.12 (t ,

2H), 2.15 (t, 2H), 2.1 (s, 6H), 1.85 (quint, 2H). ¹³ C-NMR (125 MHz, MSM-d ₆ ): δ (ppm) 158.8, 147.4, 143.8,

124.2, 108.2, 101.7, 56.4, 45.6, 43, 28.6.

Synthesis of R2u: 7- (2-fluoroethyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one Using General Procedure 1, starting from the Synthesis compound R1a and 1-fluoro-2-iodoethane as reagents, received the compound Synthesis R2u. MCBP: calculated for C8H8NOF: 181.0651, found: 182.0728 [(M + H) + form].

1H NMR (400 MHz, MSM-d6) δ ppm. 11.91 (brs, 1H), 7.9 (s, 1H), 7.17 (d, 1H), 6.49 (d, 1H), 4.74 (dt, 2H), 4.43 (dt, 2H). ¹³ C-NMR (100 MHz, MSM-d6) δ ppm. 144, 124.3, 102, 83.1, 45.1.

Synthesis of R2v: 7- [2- (dimethylamino) ethyl] -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 1, starting from the Synthesis compound R1a and the hydrobromide 2-6pom-N, N-dimethylethylamine as reagents, the Synthesis compound R2v was prepared. MCBP calculated for C ₁₀ H ₁₄ N ₄ O: 206.1168, found: 207.1242 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 11.84 (brs, 1H), 7.88 (brd, 1H), 7.16 (d, 1H), 6.44 (d, 1H), 4.19 (t, 2H), 2.6 (t, 2H), 2.16 (s, 6H). ¹³ C-NMR (125 MHz, MSM-d6): δ (ppm) 158.7, 147.5, 143.7, 124.4, 108.1, 101.7, 59.2, 45.5, 42.6.

Synthesis of R2w: 7- (2-hydroxyethyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 1, starting from the Synthesis compound R1a and 2-chloroethanol as reagents, the Synthesis compound R2w was prepared. 1H NMR (400 MHz, MSM-d ₆ ): δ (ppm) 11.83 (brs, 1H), 7.86 (d, J = 2.4 Hz, 1H), 7.12 (d, J = 3.92 Hz, 1H), 6.43 (d, J = 3.14 Hz, 1H), 4.92 (t, J = 5.49 Hz, 1H), 4.15 (t, J = 6.28 Hz, 2H), 3.68 (q, J = 5.49 Hz, 2H).

Synthesis of R2x: 7 - [(4-chlorophenyl) methyl] -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 1, starting from the Synthesis compound R1a and 4-chlorobenzyl bromide as reagents, the Synthesis compound R2x was prepared. MCBP: calculated for Ci ₃ Hi ₀ ClN ₃ O: 259.0512, found: 260.0583 [(M + H) + form].

1H NMR (400 MHz, MSM-d ₆ ): δ (ppm) 11.93 (s, 7.9 (s, 1H), 7.39 (m, 2H), 7.23 (m, 2H), 7.22 (d, 1H) , 6.51 (d, 1H), 5.34 (s, 2H). ¹³ C-NMR (100 MHz, MSM-d ₆ ): δ (ppm) 158.7, 147.4, 144.2, 137.5, 132.5, 129.5, 129, 124.2, 108.3, 102.4, 47.5.

Synthesis of R2y: 7 - [(3-chlorophenyl) methyl] -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 1, starting from the Synthesis compound R1a and 3-chlorobenzyl bromide as reagents, the Synthesis compound R2y was prepared. MCBP: calculated for C ₁₃ H ₁₀ ClN ₃ O: 259.0512, found: 260.0580 [(M + H) + form].

¹ H-NMR (500 MHz, MSM-d6): δ (ppm) 11.94 (brs, 1H), 7.92 (d, 1H), 7.35 (m, 1H), 7.35 (m, 1H), 7.28 ( t, 1H), 7.25 (d, 1H), 7.16 (dm, 1H), 6.51 (d, 1H), 5.35 (s, 2H). ¹³ C-NMR (125 MHz, MSM-d6): δ (ppm) 158.7, 147.6, 144.3, 140.9, 133.6, 131.1, 128, 127.5, 126.4, 124.3, 108.4, 102.4, 47.5.

Synthesis of R2z: 7-benzyl-3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 1, starting from the Synthesis compound R1a and benzyl bromide as reagents, the Synthesis compound R2z was prepared. MCBP: calculated for C ₁₃ H _n N ₃ O: 225.0902, found: 226.0986 [(M + H) + form].

1H-NMR (400 MHz, MSM-d ₆ ): δ (ppm) 11.91 (brs, 1H), 7.91 (s, 1H), 7.36-7.17 (m, 5H), 7.2 (d, 1H), 6.49 (d, 1H), 5.34 (s, 2H). ¹³ C-NMR (100 MHz, MSM-d ₆ ): δ (ppm) 144.1, 124.3, 102.2, 48.1.

Synthesis of R2aa: 7 - [(2-chlorophenyl) methyl] -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 1, starting from the Synthesis compound R1a and 2-chlorobenzyl bromide as reagents, the Synthesis compound R2aa was obtained. MCBP: calculated for C ₁₃ H ₁₀ ClN ₃ O: 2590512, found: 260.0587 [(M + H) + form].

1H-NMR (400 MHz, MSM-d ₆ ): δ (ppm) 11.95 (brs, 1H), 7.89 (d, 1H), 7.5 (dm, 1H), 7.32 (m, 1H), 7.26 ( m, 1H), 7.17 (d, 1H), 6.72 (dm, 1H), 6.55 (d, 1H), 5.44 (s, 2H). ¹³ C-NMR (100 MHz, MSM-d ₆ ): δ (ppm) 144.3, 129.8, 129.8, 128.8, 128.1, 124.5, 102.5, 46.

Synthesis of R2ab: 7- (2-oxopyrrolidin-1-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one.

Synthesis compound R1b (1.74 g, 11.67 mmol) was dissolved in DMF (80 ml) and cooled to 0 ° C, sodium hydride (60% dispers., 1.87 g, 46.67 mmol) was slowly added and stirred for 30 min at 0 ° C. ... Hydroxylαmun-O-sulfonic acid (2.11 g, 18.67 mmol) was added to the reaction mixture and allowed to warm to rt, and stirred for 20 h. Water (100 ml) was added to the reaction mixture and extracted with DCM (4x50 ml ). The combined organic layer was washed with water and dried over MgSO ₄ and evaporated. The residue was dissolved in MSM and purified by preparative LC (on a C-18 Gemini-NX 5 μm column, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient).

Part of the resulting N-amine compound (500 mg, 3.05 mmol) was dissolved in DCM (20 ml) and TEA (850 μl, 6.09 mmol, 2 eq.) And 4-chlorobutyryl chloride (409 μl, 515 mg, 3.65 mmol, 1.2 eq.), And stirred for 20 h at rt. Then the reaction mixture was evaporated, sat. a solution of NaHCO ₃ (5 ml, aq.), MeCN (20 ml) and water (20 ml) and the mixture was stirred for 3 h at 80 ° C. The reaction mixture was evaporated and water (50 ml) was added. The solution was extracted with DCM (3x10 ml) and the combined organic layers were evaporated. The residue was purified with

- 43 037563 by preparative LC (on a C-18 Gemini-NX 5 μm column, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient).

The resulting pyrrolidone (200 mg, 0.862 mmol) was dissolved in a solution of HCl (4 ml, 1N, aq.) And PDO (80 ml) and stirred at 60 ° C for 6 h. The reaction mixture was evaporated and the residue was purified using Preparative LC (on a C-18 Gemini-NX 5 μm column, 5 mM aqueous NH ₄ HCO ₃ MeCN, gradient) to give Synthesis compound R2ab. MCBP: calculated for C ₁₀ H ₁₀ N ₄ O ₂ : 218.0804, found: 219.0883 [(M + H) + form].

1H NMR (500 MHz, MSM-de): δ (ppm) 12.11 (brs, 1H), 7.91 (s, 1H), 7.2 (d, 1H), 6.53 (d, 1H), 3.77 (t, 2H), 2.47 (t, 2H), 2.17 (quint., 2H). 13C-NMR (125 MHz, MSM-de): δ (ppm) 173.7, 158.4, 146.6, 145.2, 124.2, 107, 101.3, 49.8, 28.4, 16.9.

Synthesis of R2ac: 7- (3,4,5-mrimethoxyphenyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound of R1b and 5-iodo-1,2,3-trimethoxybenzene as reagents, the Synthesis compound of R2ac was obtained. MCBP: calculated for C ₁₅ H ₁₅ N ₃ O ₄ : 301.1063, found: 302.1138 [(M + H) + form].

1H NMR (500 MHz, MSM-d ₆ ): δ (ppm) 12.07 (brs, 1H), 7.95 (d, 1H), 7.49 (d, 1H), 6.99 (s, 2H), 6.66 (d , 1H), 3.82 (s, 6H), 3.7 (s, 3H). 13C-NMR (125 MHz, MSM-d ₆ ): δ (ppm) 144.5, 124.6, 103.2, 103, 60.6, 56.6.

Synthesis of R2ad: 7- (3,5-dichlorophenyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 2, starting from the Synthesis compound of R1a and 3,5-dichlorophenylboronic acid as reagents, the Synthesis compound of R2ad was prepared. MCBP: calculated for C ₁₂ H ₇ Cl ₂ N ₃ O: 278.9966, found: 280.0040 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 12.03 (vbrs, 1H), 8.03 (s, 1H), 7.95 (d, 2H), 7.64 (t, 1H), 7.63 (d, 1H), 6.71 (d, 1H). 13C-NMR (125 MHz, MSM-d6): δ (ppm) 145.3, 126.7, 123.8, 122.7, 104.4.

Synthesis of R2ae: 7- (3-chloro-5-methoxyphenyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 2, starting from the Synthesis compound of R1a and 3-chloro-5methoxyphenylboronic acid as reagents, the Synthesis compound of R2ae was obtained. MCBP: calculated for C ₁₃ H ₁₀ ClN ₃ O ₂ : 275.0461, found: 276.0541 [(M + H) + form].

1H NMR (400 MHz, MSM-d6): δ (ppm) 12.18 (s, 1H), 8 (d, 1H), 7.6 (d, 1H), 7.51 (t, 1H), 7.33 (t, 1H), 7.08 (t, 1H), 6.69 (d, 1H), 3.85 (s, 3H). 13C-NMR (100 MHz, MSM-d6): δ (ppm) 161, 158.7, 147.5, 145, 139.7, 134.5, 124, 116.3, 112.7, 110.2, 109.4, 104, 56.4.

Synthesis of R2af: 7- (3,5-dimethoxyphenyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 2, starting from the Synthesis compound of R1a and 2- (3,5-dimethoxy) phenyl4,4,5,5-tetramethyl- (1,3,2) -dioxaborolane as reagents, the Synthesis compound of R2af was obtained. MCBP: calculated for C ₁₄ H ₁₃ N ₃ O ₃ : 271.0957, found: 272.1030 [(M + H) + form].

1H NMR (500 MHz, MSM-d ₆ ): δ (ppm) 12.11 (s, 1H), 7.95 (d, 1H), 7.52 (d, 1H), 6.91 (d, 2H), 6.66 (d , 1H), 6.54 (t, 1H), 3.8 (s, 6H). 13C-NMR (125 MHz, MSM-d ₆ ): δ (ppm) 144.5, 124.2, 103.5, 103.1, 98.9.

Synthesis of R2ag: 7- (3,4-dichlorophenyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound of R1b and 3,4-dichlorophenylboronic acid as reagents, the Synthesis compound of R2ag was obtained. MSBP calculated for C12H7Cl2N3O: 278.9966, found: 280.003 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ): δ (ppm) 12.21 (brs, 1H), 8.15 (t, 1H), 8.02 (brs, 1H), 7.82 (d, 1H), 7.82 (d , 1H), 7.61 (d, 1H), 6.72 (d, 1H). 13C-NMR (125 MHz, MSM-d ₆ ): δ (ppm) 145.1, 131.5, 125.9, 124.3, 123.8, 104.2.

Synthesis of R2ah: 7- (4-chloro-3-fluorophenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound R1b and 4-chloro-3-fluoroiodobenzene as reagents, the Synthesis compound R2ah was prepared. MCBP: calculated for C ₁₂ H ₇ ClFN ₃ O: 263.0262, found: 264.0339 [(M + H) + form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 12.21 (s, 1H), 8.02 (d, 1H), 7.97 (dd, 1H), 7.77 (dd, 1H), 7.72 (dd, 1H), 7.6 (d, 1H), 6.72 (d, 1H). 13C-NMR (125 MHz, MSM-d6): δ (ppm) 145.1, 131.5, 123.7, 121.5, 112.8, 104.2.

Synthesis of R2ai: 7- (4-chloro-3-methoxyphenyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound of R1b and 2-chloro-5-iodoanisole as reagents, the Synthesis compound of R2ai was obtained. MCBP: calculated for C ₁₃ H ₁₀ ClN ₃ O ₂ : 275.0461, found: 276.0537 [(M + H) + form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 12.15 (brs, 1H), 7.98 (brs, 1H), 7.58 (d, 1H), 7.57 (d, 1H), 7.49 (d, 1H), 7.36 (dd, 1H), 6.7 (d, 1H), 3.93 (s, 3H). 13C-NMR (125 MHz, MSM-d6): δ (ppm) 158.7, 155.3, 147.4, 144.8, 137.7, 130.5, 124.2, 119.8, 117.3, 110, 109.4, 103.7, 56.9.

Synthesis of R2aj: 7- (4-fluoro-3-methoxyphenyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound R1b and 1-fluoro-4-iodo-2-methoxybenzene as reagents, the Synthesis compound R2aj was prepared. MCBP: calculated for C ₁₃ H ₁₀ N ₃ O ₂ F: 259.0757, found: 260.0818 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ): δ (ppm) 12.1 (s, 1H), 7.95 (s, 1H), 7.51 (d, 1H), 7.48 (dd, 1H), 7.38 (dd , 1H), 7.27 (ddd, 1H), 6.68 (d, 1H), 3.9 (s, 3H). 13C-NMR (125 MHz, MSM-d ₆ ): δ (ppm) 144.7, 124.5, 117, 116.5,

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111, 103.4, 56.8.

Synthesis of R2ak: 7- (3,4-dimethoxyphenyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from Synthesis R1b compound and pinacol ester

3,4-dimethoxyphenylboronic acid as reagents gave the Synthesis compound R2ak.

MCBP: calculated for C ₁₄ H ₁₃ N ₃ O ₃ : 271.0957, found: 272.103 [(M + H) + form].

¹ H-NMR (500 MHz, MSM-de): δ (ppm) 7.92 (d, 1H), 7.43 (d, 1H), 7.25 (d, 1H), 7.19 (dd, 1H), 7.08 ( d, 1H), 6.65 (d, 1H), 3.8 (s, 6H). 13C-NMR (125 MHz, MSM-de): δ (ppm) 144.5, 124.6, 116.9, 112.2, 109.3, 103.1, 56.3.

Synthesis of R2am: 7- (4-methylphenyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound R1b and 4-iodotoluene as reagents, the Synthesis compound R2am was prepared. MCBP: calculated for C13H11N3O: 225.0902, found: 226.0987 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ): δ (ppm) 12.06 (brs, 1H), 7.93 (s, 1H), 7.58 (dm, 1H), 7.44 (d, 1H), 7.33 (dm , 1H), 6.66 (d, 1H), 2.37 (s, 3H). 13C-NMR (125 MHz, MSM-d ₆ ): δ (ppm) 158.8, 147.3, 144.5, 136.8, 135.4, 130.1, 124.5, 124.1, 109.6, 103.4.21.

Synthesis of R2an: 4- {4-oxo-3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-7-yl} benzonitrile.

Using General Procedure 3, starting from the Synthesis compound of R1b and 4-iodobenzonitrile as reagents, the Synthesis compound of R2an was prepared. MCBP calculated for C13H8N4O: 236.0698, found: 237.0775 [(M + H) + form].

1H NMR (500 MHz, MSM-d ₆ ): δ (ppm) 12.25 (brs, 1H), 8.05 (m, 2H), 8.03 (m, 2 H), 8.02 (brs, 1H), 7.66 ( d, 1H), 6.75 (d, 1H). 13C-NMR (125 MHz, MSM-d ₆ ): δ (ppm) 147.6, 145.2, 141.5, 134, 124.6, 123.6, 119, 110.6, 109.4, 104.7.

Synthesis of R2ao: 7- [4- (trifluoromethyl) phenyl] -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound of R1b and 4-iodobenzotrifluoride as reagents, the Synthesis compound of R2ao was prepared. MCBP: calculated for C ₁₃ H ₈ F ₃ N ₃ O: 279.0619, found: 280.0691 [(M + H) form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 12.23 (brs, 1H), 8.02 (m, 2H), 8.01 (d, 1H), 7.92 (m, 2H), 7.63 (d, 1H), 6.74 (d, 1H). 13C-NMR (125 MHz, MSM-d6): δ (ppm) 158.7, 147.6, 145.1, 126.9, 124.7, 123.8, 110.4, 104.5 'N-NMR (50.6 MHz, MSM-d ₆ ): δ ( ppm) 170.9.

Synthesis of R2ap: 7- [4- (difluoromethyl) phenyl] -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound of R1b and 1- (difluoromethyl) -4-iodobenzene as reagents, the Synthesis compound of R2ap was prepared. MCBP calculated for C ₁₃ H ₉ F ₂ N ₃ O: 261.0714, found: 262.0784 [(M + H) + form].

1H NMR (500 MHz, MSM-d ₆ ): δ (ppm) 12.17 (brs, 1H), 7.99 (d, 1H), 7.91 (m, 2H), 7.75 (m, 2H), 7.58 (d , 1H), 7.12 (t, 1H), 6.72 (d, 1H). 13C-NMR (125 MHz, MSM-d6): δ (ppm) 144.9, 127.2, 124.7, 123.9, 115.1, 104.1.

Synthesis of R2aq: 7- [4- (hydroxymethyl) phenyl] -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound R1b and 4-iodobenzyl alcohol as reagents, the Synthesis compound R2aq was prepared. MCBP: calculated for C13H11N3O2: 241.0851, found: 242.0925 [(M + H) + form].

1H NMR (500 MHz, MSM-d ₆ ): δ (ppm) 12.07 (brs, 1H), 7.94 (s, 1H), 7.66 (m, 2H), 7.47 (m, 2H), 7.45 (d , 1H), 6.67 (d, 1H), 5.31 (t, 1H), 4.56 (d, 2H). 13C-NMR (125 MHz, MSM-d ₆ ): δ (ppm) 158.9, 147.4, 144.6, 142.2, 136.6, 127.6, 124.3, 124.2, 109.9, 103.5, 62.8.

Synthesis of R2ar: 7- (4-chlorophenyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound of R1b and 1-chloro-4-iodobenzene as reagents, the Synthesis compound of R2ar was obtained. MCBP: calculated for C ₁₂ H ₈ ClN ₃ O: 245.0356, found: 246.0427 [(M + H) + form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 12.15 (brs, 1H), 7.97 (d, 1H), 7.78 (dm, 1H), 7.61 (dm, 1H), 7.53 (d, 1H), 6.7 (d, 1H). 13C-NMR (125 MHz, MSM-d6): δ (ppm) 158.7, 147.3, 144.8, 136.7, 131.7, 129.6, 126.1, 123.9, 109.9, 103.9.

Synthesis of R2as: 7- (4-fluorophenyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound of R1b and 4-fluoroiodobenzene as reagents, the Synthesis compound of R2as was prepared. MCBP calculated for C12H8FN3O: 229.0651, found: 230.0714 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 12.12 (brs, 1H), 7.95 (d, 1H), 7.74 (m, 2H), 7.48 (d, 1H), 7.39 (m, 2H), 6.68 (d, 1H). 13C-NMR (125 MHz, MSM-d6): δ (ppm) 144.7, 126.8, 124.2, 116.4, 103.5.

Synthesis of R2at: 7- [4- (dimethylamino) phenyl] -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 2, starting from the Synthesis compound of R1a and 4- (dimethylamino) phenylboronic acid as reagents, the Synthesis compound of R2at was prepared. MCBP calculated for C14H14N4O: 254.1168, found: 255.1243 [(M + H) ⁺ form].

1H NMR (400 MHz, MSM-d ₆ ): δ (ppm) 11.98 (brs, 1H), 7.89 (d, 1H), 7.43 (m, 2H), 7.33 (d, 1H), 6.82 (m ,

- 45 037563

2H), 6.61 (d, 1H), 2.94 (s, 6H). ¹³ C-NMR (100 MHz, MSM-d ₆ ): δ (ppm) 144.1, 125.6, 124.3, 112.7, 102.7, 40.6.

Synthesis of R2au: 7- [4- (4-methylpiperazin-1-yl) phenyl] -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 2, starting from the Synthesis of R1a compound and a pinacol ester

4- (4-methylpiperazin-1-yl) phenylboronic acid as reagents, the compound of Synthesis

R2au. MCBP calculated for C ₁₇ H ₁₉ N ₅ O: 309.1590, found: 310.1674 [(M + H) + form].

1H NMR (400 MHz, MSM-d6): δ (ppm) 12.01 (brs, 1H), 7.9 (d, 1H), 7.49 (m, 2H), 7.37 (d, 1H), 7.06 (m, 2H), 6.63 (d, 1H), 3.2 (brm, 4H), 2.51 (brm, 4H), 2.27 (s, 3H). 13C-NMR (100 MHz, MSM-d6): δ (ppm) 144.3, 125.4, 124.2, 115.9, 102.9, 54.8, 48.3, 45.9.

Synthesis of R2av: 7- [4- (morpholin-4-yl) phenyl] -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 2, starting from the Synthesis compound of R1a and 4-morpholinophenylboronic acid as reagents, the Synthesis compound of R2av was prepared. MCBP calculated for C ₁₆ H ₁₆ N ₄ O ₂ : 296.1273, found: 297.1361 [(M + H) ⁺ form].

1H NMR (400 MHz, MSM-d6): δ (ppm) 12.01 (brs, 1H), 7.9 (s, 1H), 7.51 (m, 2H), 7.38 (d, 1H), 7.07 (m, 2H), 6.63 (d, 1H), 3.76 (m, 4H), 3.16 (m, 4H). ¹³ C-NMR (100 MHz, MSM-d6): δ (ppm) 484.8, 144.3, 125.4, 124.2, 115.7, 103, 66.5.

Synthesis of R2ax: 7- (4-methoxyphenyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound R1b and 4-iodanisole as reagents, the Synthesis compound R2ax was obtained. MCBP calculated for C13H11N3O2: 241.0851, found: 242.0929 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ): δ (ppm) 12.04 (brs, 1H), 7.92 (d, 1H), 7.58 (dd, 1H), 7.4 (d, 1H), 7.08 (d , 1H), 6.65 (d, 1H), 3.81 (s, 3H). 13C-NMR (125 MHz, MSM-d ₆ ): δ (ppm) 158.8, 158.8, 147.3, 144.4, 130.9, 126.1, 124.4, 114.8, 109.4, 103.1, 55.9.

Synthesis of R2ay: 7- [4- (trifluoromethoxy) phenyl] -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound of R1b and 1-iodo-4- (trifluoromethoxy) benzene as reagents, the Synthesis compound R2ay was prepared. MCBP: calculated for C ₁₃ H ₈ F ₃ N ₃ O ₂ : 295.0569, found: 296.0648 [(M + H) + form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 12.15 (s, 1H), 7.97 (d, 1H), 7.86 (m, 2H), 7.56 (m, 2H), 7.54 (m, 1H), 6.71 (d, 1H). ¹³ C-NMR (125 MHz, MSM-d6): δ (ppm) 144.8, 126.4, 124.1, 122.5, 103.9.

Synthesis of R2az: 7- [4- (benzyloxy) phenyl] -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound of R1b and 4-benzyloxyiodobenzene as reagents, the Synthesis compound of R2az was prepared. MCBP: calculated for C ₁₉ H ₁₅ N ₃ O ₂ : 317.1164, found: 318.1243 [(M + H) + form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 12.05 (brs, 1H), 7.92 (d, 1H), 7.59 (dm, 2H), 7.48 (dm, 2H), 7.41 (d, 1H), 7.41 (tm, 2H), 7.35 (tm, 1H), 7.16 (dm, 2H), 6.65 (d, 1H), 5.18 (s, 2H). ¹³ C-NMR (125 MHz, MSM-d ₆ ): δ (ppm) 158.8, 157.6, 147.3, 144.4, 137.4, 131, 129, 128.4, 128.2, 126.1, 124.3, 115.7, 109.4, 103.1, 69.9 ...

Synthesis of R2ba: 7- (5-methylthiophen-2-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound of R1b and 2-iodo-5-methylthiophene as reagents, the Synthesis compound of R2ba was obtained. MCBP: calculated for C11H9N3OS: 231.0466, found: 232.0541 [(M + H) ⁺ form].

1H NMR (400 MHz, MSM-d ₆ ): δ (ppm) 12.17 (brs, 1H), 7.99 (d, 1H), 7.49 (d, 1H), 7.14 (d, 1H), 6.76 (dq , 1H), 6.67 (d, 1H), 2.46 (d, 3H). 13C-NMR (100 MHz, MSM-d ₆ ): δ (ppm) 145, 124.2, 123.9, 119.4, 103.9, 15.4.

Synthesis of R2bb: 7- (5-chlorothiophen-2-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound of R1b and 2-chloro-5-iodothiophene as reagents, the Synthesis compound of R2bb was prepared. MCBP: calculated for C ₁₀ H ₆ N ₃ OSCl: 250.9920, found: 252.0005 [(M + H) + form].

1H NMR (500 MHz, MSM-d6) δ ppm. 12.28 (brs, 1H), 8.07 (d, 1H), 7.67 (d, 1H), 7.3 (d, 1H), 7.13 (d, 1H), 6.72 (d, 1H). 13C-NMR (125 MHz, MSM-d ₆ ) δ ppm. 158.4, 146.8, 145.6, 136.4, 125.5, 124.6, 123.3, 117.5, 109.3, 104.6

Synthesis of R2bc: 7- (2,3-dihydro-1,4-benzodioxin-6-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine-4one.

Using General Procedure 2, starting from the Synthesis compound of R1a and 1,4-benzodioxane-6-boronic acid as reagents, the Synthesis compound of R2bc was prepared. MCBP: calculated for C14H11N3O3: 269.0800, found: 270.0881 [(M + H) + form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 12.05 (brs, 1H), 7.92 (d, 1H), 7.4 (d, 1H), 7.22 (d, 1H), 7.13 (dd, 1H), 6.99 (d, 1H), 6.63 (d, 1H), 4.33-4.25 (m, 4H). ¹³ C-NMR (125 MHz, MSM-d6): δ (ppm) 144.4, 124.3, 117.7, 117.6, 113.8, 103.2.

Synthesis of R2bd: 7- (2H-1,3-benzodioxol-5-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 2, starting from the Synthesis compound of R1a and 3,4-methylenedioxyphenylboronic acid as reactants, the Synthesis compound of R2bd was obtained. MCBP: calculated for C ₁₃ H ₉ N ₃ O ₃ : 255.0644, found: 256.0719 [(M + H) + form].

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1H NMR (500 MHz, MSM-d ₆ ): δ (ppm) 12.05 (brs, 1H), 7.92 (d, 1H), 7.4 (d, 1H), 7.29 (d, 1H), 7.12 (dd ,

1H), 7.05 (d, 1H), 6.63 (d, 1H), 6.11 (s, 2H). ¹³ C-NMR (125 MHz, MSM-d ₆ ): δ (ppm) 144.5, 124.5, 118.2, 108.7,

106.5, 103.1, 102.2.

Synthesis of R2be: 7- (naphthalen-2-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 2, starting from the Synthesis compound of R1a and 2-naphthalene boronic acid as reagents, the Synthesis compound of R2be was prepared. MCBP: calculated for C ₁₆ H _n N ₃ O: 261.0902, found: 262.0982 [(M + H) + form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 12.14 (s, 1H), 8.25 (d, 1H), 8.09 (d, 1H), 8.01 (m, 1H), 8.01 (m, 1H), 8 (s, 1H), 7.91 (dd, 1H), 7.63 (d, 1H), 7.6 (tm, 1H), 7.57 (tm, 1H), 6.74 (d, 1H). ¹³ C-NMR (125 MHz, MSM-d6): δ (ppm) 158.8, 147.6, 144.8, 135.4, 133.4, 132, 129.4, 128.4, 128.2, 127.4, 126.9, 124.4, 123.5, 122.3, 109.9, 103.8.

Synthesis of R2bf: 7- (3-methylphenyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound of R1b and 3-iodotoluene as reagents, the Synthesis compound of R2bf was obtained. MCBP: calculated for C13H11N3O: 225.0902, found: 226.098 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ): δ (ppm) 12.08 (brs, 1H), 7.95 (d, 1H), 7.52 (brs, 1H), 7.49 (dm, 1H), 7.46 (d , 1H), 7.41 (t, 1H), 7.22 (brd, 1H), 6.67 (d, 1H), 2.39 (s, 3H). 13C-NMR (125 MHz, MSM-d ₆ ): δ (ppm) 158.8, 147.3, 144.6, 139.2, 137.8, 129.5, 128.1, 125.2, 124.2, 121.8, 109.7, 103.5, 21.4.

Synthesis of R2bg: 7- [3- (trifluoromethyl) phenyl] -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound R1b and 3-iodobenzotrifluoride as reagents, the Synthesis compound R2bg was prepared. MCBP: calculated for C ₁₃ H ₈ F ₃ N ₃ O: 279.0620, found: 280.0699 [(M + H) + form].

1H NMR (500 MHz, MSM-d ₆ ): δ (ppm) 12.19 (brs, 1H), 8.18 (brs, 1H), 8.07 (dm, 1H), 8.02 (d, 1H), 7.79 (t , 1H), 7.77 (dm, 1H), 7.65 (d, 1H), 6.73 (d, 1H). ¹³ C-NMR (125 MHz, MSM-d ₆ ): δ (ppm) 145.1, 131.1, 128.3, 124, 123.9, 121, 104.1.

Synthesis of R2bh: 7- {3 - [(4-methylpiperazin-1-yl) methyl] phenyl} -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidine-4one.

Using General Procedure 3, starting from Synthesis compound R1b and 3- (4-methyl-1-piperazinylmethyl) benzene boronic acid pinacol ester as reagents, Synthesis compound R2bh was prepared. MCBP: calculated for C ₁₈ H ₂₁ N ₅ O: 323.1746, found: 324.1828 [(M + H) + form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 12.37 / 12.2 / 11.95 (brs, 3H), 8.04 (brs, 1H), 7.98 (s, 1H), 7.91 (dm, 1H), 7.67 (dm, 1H), 7.63 (d, 1H), 7.62 (t, 1H), 6.72 (d, 1H), 4.49 (brs, 2H), 3.8-3.3 (brm, 8H), 2.8 (brs, 3H) ... ¹³ SNMR (125 MHz, MSM-d6): δ (ppm) 144.8, 130.3, 130, 127.3, 125.7, 124, 103.9, 58.7, 42.7.

Synthesis of R2bi: 7- [3- (hydroxymethyl) phenyl] -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound R1b and 3-iodobenzyl alcohol as reagents, the Synthesis compound R2bi was prepared. MCBP: calculated for Ci ₃ HnN ₃ O ₂ : 241.0851, found: 242.0935 [(M + H) + form].

1H NMR (500 MHz, MSM-d ₆ ): δ (ppm) 12.11 (brs, 1H), 7.95 (d, 1H), 7.64 (brt, 1H), 7.55 (dm, 1H), 7.48 (t , 1H), 7.46 (d, 1H), 7.35 (dm, 1H), 6.68 (d, 1H), 4.58 (s, 2H). 13C-NMR (125 MHz, MSM-d ₆ ): δ (ppm) 158.8, 147.4, 144.6, 144.4, 137.7, 129.4, 125.4, 124.2, 123, 122.5, 109.7, 103.5, 62.9.

Synthesis of R2bj: 7- (3-chlorophenyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound R1b and 1-chloro-3-iodobenzene as reagents, the Synthesis compound R2bj was prepared. MCBP: calculated for C ₁₂ H ₈ ClN ₃ O: 245.0356, found: 246.0437 [(M + H) + form].

1H NMR (400 MHz, MSM-d6): δ (ppm) 12.17 (brs, 1H), 8 (d, 1H), 7.92 (m, 1H), 7.74 (dm, 1H), 7.58 (d, 1H), 7.57 (t, 1H), 7.47 (dm, 1H), 6.7 (d, 1H). 13C-NMR (100 MHz, MSM-d6): δ (ppm) 145, 131.3, 127.2, 124.1, 123.9, 122.9, 104.

Synthesis of R2bk: 7- (3-fluorophenyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound of R1b and 1-fluoro-3-iodobenzene as reagents, the Synthesis compound of R2bk was prepared. MCBP: calculated for C ₁₂ H ₈ N ₃ OF: 229.0651, found: 230.0729 [(M + H) + form].

1H NMR (400 MHz, MSM-d6): δ (ppm) 12.17 (brs, 1H), 7.99 (d, 1H), 7.72 (dm, 1H), 7.64 (m, 1H), 7.58 (d, 1H), 7.58 (m, 1H), 7.25 (m, 1H), 6.71 (d, 1H). 13C-NMR (100 MHz, MSM-d6): δ (ppm) 144.9, 131.4, 130.9, 123.9, 120.2, 114, 111.6. F-NMR (376.5 MHz, MSM-d6): δ (ppm) -111.7.

Synthesis of R2bl: 7- [3- (dimethylamino) phenyl] -3H, 4H, 7H-purrolo [2,3-d] purimidin-4-one.

Using General Procedure 2, starting from the Synthesis compound of R1a and 3- (N, N-dimethylamino) phenylboronic acid as reagents, the Synthesis compound of R2bl was prepared. MCBP calculated for C14H14N4O: 254.1168, found: 255.1229 [(M + H) + form].

1H NMR (500 MHz, MSM-d ₆ ): δ (ppm) 12.04 (brs, 1H), 7.92 (d, 1H), 7.45 (d, 1H), 7.3 (t, 1H), 6.94 (m , 1H), 6.93 (dm, 1H), 6.74 (dm, 1H), 6.65 (d, 1H), 2.95 (s, 6H). 13C-NMR (125 MHz, MSM-d ₆ ): δ (ppm) 144.3,

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129.9, 124.4, 112.4, 111.4, 108.6, 103.1, 40.5.

Synthesis of R2bm: 7- [3- (morpholin-4-yl) phenyl] -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 2, starting from the Synthesis compound of R1a and 3- (morpholino) phenylboronic acid as reagents, the Synthesis compound of R2bm was prepared. 1H NMR (400 MHz, MSM-d ₆ ): δ (ppm) 12.05 (brs, 1H), 7.93 (s, 1H), 7.47 (d, J = 3.53 Hz, 1H), 7.36 (t, J = 8.13 Hz, 1H), 7.19 (t, J = 2.20 Hz, 1H), 7.11 (dd, J = 1.27, 7.93 Hz, 1H), 6.98 (dd, J = 1.96, 8.49 Hz, 1H), 6.65 (d , J = 3.5 Hz, 1H), 3.75 (t, J = 4.61 Hz, 4H), 3.18 (t, J = 4.61 Hz, 4H).

Synthesis of R2bo: 7- (3-methoxyphenyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound of R1b and 3-iodanisole as reagents, the Synthesis compound of R2bo was prepared. MCBP calculated for C13H11N3O2: 241.0851, found: 242.0928 [(M + H) + form].

¹ H NMR (400 MHz, MSM-d ₆ ): δ (ppm) 12.1 (brs, 1H), 7.95 (d, 1H), 7.51 (d, 1H), 7.44 (t, 1H), 7.31 ( m, 1H), 7.3 (m, 1H), 6.98 (dm, 1H), 6.67 (d, 1H), 3.82 (s, 3H).

13C-NMR (100 MHz, MSM-d ₆ ): δ (ppm) 144.6, 130.4, 124.2, 116.7, 112.9, 110.5, 103.5.

Synthesis of R2bp: 7- [3 - (trifluoromethoxy) phenyl] -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound of R1b and 3- (trifluoromethoxy) iodobenzene as reagents, the Synthesis compound of R2bp was obtained. MCBP calculated for C ₁₃ H ₈ F ₃ N ₃ O ₂ : 295.0569, found: 296.0651 [(M + H) + form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 12.91 (s, 1H), 8 (s, 1H), 7.87 (t, 1H), 7.82 (ddd, 1H), 7.68 (t, 1H), 7.6 (d, 1H), 7.41 (ddd, 1H), 6.71 (d, 1H). 13C-NMR (125 MHz, MSM-d ₆ ): δ (ppm) 145.1, 131.5, 123.9, 123.2, 119.5, 117.1, 104.1.

Synthesis of R2bq: 7- [3- (benzyloxy) phenyl] -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound R1b and 1-benzyloxy-3-iodobenzene as reagents, the Synthesis compound R2bq was prepared. MCBP: calculated for C ₁₉ H ₁₅ N ₃ O ₂ : 317.1164, found: 318.1235 [(M + H) + form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 12.1 (brs, 1H), 7.95 (d, 1H), 7.51 (d, 1H), 7.51-7.31 (m, 5H), 7.44 ( t, 1H), 7.41 (m, 1H), 7.32 (dm, 1H), 7.05 (dm, 1H), 6.68 (d, 1H), 5.18 (s, 2H). 13C-NMR (125 MHz, MSM-d6): δ (ppm) 144.6, 130.5, 124.1, 116.8, 113.6, 111.4, 103.6, 70.

Synthesis of R2br: 7- (6-methylpyridin-2-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound of R1b and 2-iodo-6-methylpyridine as reagents, the Synthesis compound of R2br was prepared. MCBP: calculated for C ₁₂ H ₁₀ N ₄ O: 226.0855, found: 227.0933 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ): δ (ppm) 12 (brs, 1H), 8.25 (dm, 1H), 8.05 (s, 1H), 7.9 (t, 1H), 7.88 (d , 1H), 7.25 (dm, 1H), 6.68 (d, 1H), 2.52 (s, 3H). 13C-NMR (125 MHz, MSM-d ₆ ): δ (ppm) 144.9, 139.5, 122, 121.8, 113.8, 103.7, 24.4.

Synthesis of R2bs: 7- (6-methoxypyridin-2-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

A mixture of Synthesis compound R1a (1.0 g, 6.51 mmol), 2-iodo-6-methoxypyridine (2.35 g, 9.77 mmol, 1.5 eq.), Copper (I) iodide (125 mg, 0.65 mmol, 0.1 eq.), Potassium orthophosphate (2.76 g, 13 mmol, 2 eq.) And (1R, 2R) - (-) - 1,2-diaminocyclohexane (74 mg, 0.65 mmol, 0.1 eq.) In PDO (50 ml) were stirred in an inert atmosphere for 4 h at 100 ° C. The inorganic materials were filtered off, the filtrate was evaporated and the resulting residue was purified using flash chromatography (DCM).

The resulting arylated product (920 mg, 3.5 mmol) and lithium hydroxide monohydrate (1.48 g, 35 mmol) were stirred in a mixture of PDO (15 ml) and water (15 ml) at 110 ° C for 24 h. The residue was acidified with aqueous HCl solution ( 1N, 50 ml) and the resulting precipitate was filtered and dried to give Synthesis compound R2bs.

MCBP: calculated for C ₁₂ H ₁₀ N ₄ O ₂ : 242.0804, found: 243.0884 [(M + H) + form].

1H NMR (500 MHz, MSM-d ₆ ): δ (ppm) 12.21 (brs, 1H), 8.08 (dd, 1H), 8.03 (s, 1H), 7.94 (d, 1H), 7.9 (t , 1H), 6.78 (dd, 1H), 6.7 (d, 1H), 3.94 (s, 3H). 13C-NMR (125 MHz, MSM-d ₆ ): δ (ppm) 163.2, 158.5, 147.6, 147.4, 144.9, 141.9, 121.9, 111.2, 108.4, 108.4, 103.8, 53.9.

Synthesis of R2bt: 7- (naphthalen-1-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 2, starting from the Synthesis compound of R1a and 1-naphthalene boronic acid as reagents, the Synthesis compound of R2bt was prepared. MCBP calculated for C16H11N3O: 261.0902, found: 262.0984 [(M + H) + form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 12.04 (s, 1H), 8.12 (d, 1H), 8.09 (d, 1H), 7.78 (d, 1H), 7.67 (t, 1H), 7.61 (dm, 1H), 7.6 (t, 1H), 7.51 (tm, 1H), 7.39 (d, 1H), 7.21 (t, 1H), 6.77 (d, 1H). 13C-NMR (125 MHz, MSMd6): δ (ppm) 158.9, 149.2, 144.6, 134.2, 134.1, 130.4, 129.5, 128.7, 127.8, 127.2, 126.4, 126.3, 126, 123, 108.7, 103.1

Synthesis of R2bu: 7-phenyl-3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound R1b and iodobenzene as reagents, the Synthesis compound R2bu was prepared. MCBP: calculated for C ₁₂ H ₉ N ₃ O: 211.0746, found: 212.083 [(M + H) + form].

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Ή NMR (500 MHz, MSM-d ₆ ): δ (ppm) 12.1 (brs, 1H), 7.95 (d, 1H), 7.71 (m, 2H), 7.54 (m, 2H), 7.5 (d ,

1H), 7.4 (m, 1H), 6.69 (d, 1H). ¹³ C-NMR (125 MHz, MSM-d ₆ ): δ (ppm) 158.8, 147.3, 144.6, 137.8, 129.7, 127.4,

124.6, 124.1, 109.8, 103.6.

Synthesis of R2bv: 7- (2-methylphenyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 2, starting from the Synthesis compound of R1a and 2-methylphenylboronic acid as reagents, the Synthesis compound of R2bv was obtained. MCBP: calculated for C ₁₃ H _n N ₃ O: 225.0902, found: 226.098 [(M + H) + form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 12 (brs, 1H), 7.83 (d, 1H), 7.41 (m, 1H), 7.41 (m, 1H), 7.35 (m, 1H), 7.3 (d, 1H), 7.21 (d, 1H), 6.66 (d, 1H), 2.01 (s, 3H). ¹³ C-NMR (125 MHz, MSM-d6): δ (ppm) 158.9, 148.2, 144.4, 136.9, 135.6, 131.2, 129.2, 128.5, 127.1, 125.3, 108.6, 102.9, 17.9.

Synthesis of R2bw: 7- (2-chlorophenyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 2, starting from the Synthesis compound of R1a and 2-chlorophenylboronic acid as reagents, the Synthesis compound of R2bw was obtained. MCBP: calculated for C ₁₂ H ₈ ClN ₃ O: 245.0356, found: 246.0437 [(M + H) + form].

1H NMR (400 MHz, MSM-d ₆ ): δ (ppm) 12.06 (brs, 1H), 7.86 (d, 1H), 7.73-7.48 (m, 4H), 7.27 (d, 1H), 6.68 (d, 1H). ¹³ C-NMR (100 MHz, MSM-d6): δ (ppm) 144.7, 125.4, 102.2.

Synthesis of R2bx: 7- (2-fluorophenyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 2, starting from the Synthesis compound of R1a and 2-fluorophenylboronic acid as reagents, the Synthesis compound of R2bx was obtained. MCBP: calculated for Q2H8N3OF: 229.0651, found: 230.0730 [(M + H) ⁺ form].

1H NMR (400 MHz, MSM-d ₆ ): δ (ppm) 12.09 (brs, 1H), 7.9 (d, 1H), 7.61 (m, 1H), 7.54 (m, 1H), 7.48 (m , 1H), 7.38 (m, 1H), 7.34 (dd, 1H), 6.7 (d, 1H). ¹³ C-NMR (100 MHz, MSM-d ₆ ): δ (ppm) 144.8, 130.6, 129.6, 125.4, 125.3, 117, 103.5.

Synthesis of R2by: 7- [2- (dimethylamino) phenyl] -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 2, starting from the Synthesis compound R1a and dimethyl [2- (4,4,5,5-tetramethyl1,3,2-dioxaborolan-2-yl) phenyl] amine as reagents, the Synthesis compound R2by was obtained. MCBP: calculated for C ₁₄ H ₁₄ N ₄ O: 254.1168, found: 255.1237 [(M + H) + form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 12 (brs, 1H), 7.85 (d, 1H), 7.36 (m, 1H), 7.24 (dm, 1H), 7.2 (d, 1H), 7.13 (dm, 1H), 7.02 (m, 1H), 6.64 (d, 1H), 2.36 (s, 6H). ¹³ C-NMR (125 MHz, MSM-d6): δ (ppm) 144.4, 130.1, 129.4, 125.5, 121.1, 119, 102.9, 42.4.

Synthesis of R2bz: 7- (2-methoxyphenyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 2, starting from the Synthesis compound of R1a and 2-methoxyphenylboronic acid as reactants, the Synthesis compound of R2bz was obtained. MCBP: calculated for C ₁₃ H _n N ₃ O ₂ : 241.0851, found: 242.092 [(M + H) + form].

1H NMR (400 MHz, MSM-d6): δ (ppm) 11.96 (brs, 1H), 7.82 (d, 1H), 7.46 (m, 1H), 7.37 (dm, 1H), 7.24 (dm, 1H), 7.18 (d, 1H), 7.08 (m, 1H), 6.6 (d, 1H), 3.74 (s, 3H). ¹³ C-NMR (100 MHz, MSM-d6): δ (ppm) 144.2, 130.2, 129.3, 126, 120.8, 113.1, 102.4.

Synthesis of R2ca: 7- (pyridin-2-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound of R1b and 2-iodopyridine as reagents, the Synthesis compound of R2ca was prepared. MCBP: calculated for CnH ₈ N ₄ O: 212.0698, found: 213.0774 [(M + H) ⁺ form].

Ή-NMR (500 MHz, MSM-d ₆ ): δ (ppm) 12.29 (s, 1H), 8.55 (dd, 1H), 8.47 (dd, 1H), 8.06 (brs, 1H), 8.03 ( t, 1H), 7.9 (d, 1H), 7.4 (t, 1H), 6.7 (d, 1H). ¹³ C-NMR (125 MHz, MSM-d6): δ (ppm) 149.1, 145, 139.4, 122.5, 122, 116.9, 104 ¹⁵ N-NMR (50.6 MHz, MSM-d6): δ (m etc.) 171.2.

Synthesis of R2cb: 7- (pyridin-3-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 2, starting from the Synthesis compound of R1a and pyridine-3-boronic acid as reagents, the Synthesis compound of R2cb was prepared. MCBP: calculated for CnH ₈ N ₄ O: 212.0698, found: 213.0774 [(M + H) + form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 12.29 (s, 1H), 8.55 (dd, 1H), 8.47 (dd, 1H), 8.06 (brs, 1H), 8.03 (t, 1H), 7.9 (d, 1H), 7.4 (t, 1H), 6.7 (d, 1H). ¹³ C-NMR (125 MHz, MSM-d6): δ (ppm) 149.1, 145, 139.4, 122.5, 122, 116.9, 104 ¹⁵ N-NMR (50.6 MHz, MSM-d6): δ (m etc.) 171.2.

Synthesis of R2cc: 7- (thiophen-2-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound of R1b and 2-iodothiophene as reagents, the Synthesis compound R2cc was prepared. MCBP: calculated for C ₁₀ H ₇ N ₃ OS: 217.0310, found: 218.0384 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 12.2 (brs, 1H), 8.03 (s, 1H), 7.58 (d, 1H), 7.43 (dd, 1H), 7.39 (dd, 1H), 7.07 (dd, 1H), 6.69 (d, 1H). ¹³ C-NMR (125 MHz, MSM-d6): δ (ppm) 158.5, 147.2, 145.3, 138.7, 126, 124.3, 122.8, 119.2, 109.4, 104.2.

Synthesis of R2cd: 7- (pyridin-4-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 2, starting from the Synthesis of R1a compound and a pinacol ester

- 49 037563 pyridine-4-boronic acid as reagents, the synthesis compound R2cd was obtained. MCBP: calculated for C11H8N ₄ O: 212.0698, found: 213.0773 [(M + H) + form].

1H NMR (500 MHz, MSM-de): δ ppm. 12.31 (brs, 1H), 8.69 (m, 2H), 8.05 (s, 1H), 7.99 (m, 2H), 7.73 (d,

1H), 6.76 (d, 1H). 13C-NMR (125 MHz, MSM-d ₆ ): δ (ppm) 151.3, 145.6, 122.8, 117.3, 105.

Synthesis of R2ce: 7- (furan-3-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 2, starting from the Synthesis compound of R1a and 3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) furan as reagents, the Synthesis compound of R2ce was obtained. MCBP: calculated for C ₁₀ H ₇ N ₃ O ₂ : 201.0538, found: 202.0617 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 12.13 (brs, 1H), 8.32 (dd, 1H), 8 (d, 1H), 7.8 (dd, 1H), 7.52 (d, 1H), 7.17 (dd, 1H), 6.66 (d, 1H). 13C-NMR (125 MHz, MSM-d6): δ (ppm) 158.6, 147.1, 145, 143.9, 133.8, 126, 123, 109.6, 106.5, 103.8.

Synthesis of R2cf: 7- (thiophen-3-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 2, starting from Synthesis compound R1a and thiophene-3-boronic acid pinacol ester as reactants, Synthesis compound R2cf was prepared. MCBP: calculated for C ₁₀ H ₇ N ₃ OS: 217.0310, found: 218.0390 [(M + H) + form].

1H NMR (500 MHz, MSM-d ₆ ): δ (ppm) 12.14 (s, 1H), 7.99 (d, 1H), 7.92 (dd, 1H), 7.71 (dd, 1H), 7.68 (dd , 1H), 7.57 (d, 1H), 6.66 (d, 1H). 13C-NMR (125 MHz, MSM-d ₆ ): δ (ppm) 158.6, 147, 144.8, 136.3, 127, 123.8, 123.3, 115.1, 109.5, 103.5.

Synthesis of R2cg: 7- (1-methyl-1H-imidαzol-4-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis of R1b compound and 4-iodo-1-methyl-1H-imidazole as reagents, the Synthesis of R2cg compound was prepared. MCBP: calculated for C ₁₀ H ₉ N ₅ O: 215.0807, found: 216.0879 [(M + H) + form].

1H NMR (500 MHz, MSM-d ₆ ): δ (ppm) 9.24-7.3 (vbrs, 3H), 7.51 (d, 1H), 6.72 (brs, 1H), 3.77 (s, 3H). ¹³ SNMR (125 MHz, MSM-d ₆ ): δ (ppm) 121.7, 103.5, 35 λ-NMR (50.6 MHz, MSM-d ₆ ): δ (ppm) 153.

Synthesis of R2ch: 7- (1-methyl-1H-pyrαzol-4-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound of R1b and 4-iodo-1-methyl-1H-pyrazole as reagents, the Synthesis compound of R2ch was prepared. MCBP: calculated for C ₁₀ H ₉ N ₅ O: 215.0807, found: 216.0889 [(M + H) + form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 12.12 (brs, 1H), 8.27 (s, 1H), 7.96 (s, 1H), 7.91 (d, 1H), 7.42 (d, 1H), 6.63 (d, 1H), 3.89 (s, 3H). 13C-NMR (125 MHz, MSM-d6): δ (ppm) 158.6, 146.9, 144.7, 132.1, 124.3, 123.4, 121.4, 109, 103.4, 38.5.

Synthesis of R2ci: 7- [1- (difluoromethyl) -1H-pyrazol-4-yl] -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound of R1b and 1- (difluoromethyl) -4-iodo-1Hpyrazole as reagents, the Synthesis compound of R2ci was prepared. MCBP: calculated for C ₁₀ H ₇ F ₂ N ₅ O: 251.0619, found: 252.0682 [(M + H) + form].

1H NMR (500 MHz, MSM-d ₆ ): δ (ppm) 11.88 (brs, 1H), 8.83 (d, 1H), 8.4 (d, 1H), 8.03 (s, 1H), 7.91 (t , 1H), 7.58 (d, 1H), 6.69 (d, 1H). 13C-NMR (125 MHz, MSM-d ₆ ): δ (ppm) 145.2, 136.2, 123.2, 121.3, 111, 104.

Synthesis of R2cj: 7- (pyrimidin-2-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Synthesis compound R1b (300 mg, 2.011 mmol, 1 eq.), 2-chloropyrimidine (2.413 mmol, 1.2 eq.), And anhydrous K ₂ CO ₃ (417 mg, 3.017 mmol, 1.5 eq.) Were heated in DMF (10 ml) at 150 ° C for 2 h. The reaction mixture was filtered and purified by preparative LC (on a C-18 Gemini-NX column 5 μm, 5 mM aqueous NH4HCO3-MCN, gradient) to give 4-methoxy-7-pyrimidine-2 -ylpyrrolo [2,3-d] pyrimidine.

Then the resulting product (0.633 mmol, 1 eq.), 1M aqueous solution of HCl (3 ml) and PDO (60 ml) was stirred at 100 ° C for 1 h. After completion of the reaction, the mixture was evaporated and purified using preparative LC (on column C-18 Gemini-NX 5 μm, 5 mM aqueous NH ₄ HCO ₃ -MCN, gradient) to give Synthesis compound R2cj. MCBP: calculated for C ₁₀ H ₇ N ₅ O: 213.0651, found: 214.0735 [(M + H) + form].

1H NMR (500 MHz, MSM-d6): δ (ppm) 12.19 (brs, 1H), 8.94 (d, 1H), 8.01 (s, 1H), 7.78 (d, 1H), 7.54 (t, 1H), 6.71 (d, 1H). 13C-NMR (125 MHz, MSM-d6): δ (ppm) 159.7, 158.7, 156, 148.1, 145.2, 123.3, 120.1, 111.4, 104.5.

Synthesis of R2ck: 7- (1,3-thiazol-2-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the Synthesis compound R1b and 2-iodothiazole as reagents, the Synthesis compound R2ck was prepared. MCBP: calculated for C9H6N4OS: 218.0262, found: 219.0335 [(M + H) ⁺ form].

1H NMR (500 MHz, MeCN-d ₃ ) δ ppm. 8.5 (s, 1H), 7.62 (d, 1H), 7.52 (d, 1H), 7.22 (d, 1H), 6.51 (d, 1H). 13C-NMR (125 MHz, MeCN-d ₃ ) δ ppm. 154.5, 137.9, 116.8, 114.8, 104.2.

Synthesis of R2cl: 7- (1H-indol-1-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Synthesis compound R1b (1.74 g, 11.67 mmol) was dissolved in DMF (80 ml) and cooled to 0 ° C. Sodium hydride (60% dis., 1.87 g, 46.67 mmol) was added slowly and the mixture was stirred for 30 min at 0 ° C. Hydroxylamine-O-sulfonic acid (2.11 g, 18.67

- 50 037563 mmol), allowed to warm to rt. and stirred for 20 h. Water (100 ml) was added to the reaction mixture and extracted with DCM (4x50 ml). The combined organic layers were washed with water and dried over MgSO ₄ and evaporated. The residue was dissolved in MSM and purified by preparative LC (on a C-18 Gemini-NX 5 μm column, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient).

A portion of the resulting N-amino compound (500 mg, 3.05 mmol) was dissolved in PDO (5 ml) and 2,5-dimethoxytetrahydrofuran (454 ml, 462 mg, 3.5 mmol) was added. The mixture was stirred at 100 ° C for 115 h. The reaction mixture was diluted with an aqueous solution of HCl (5N, 2 ml) and purified using preparative LC (on a C-18 Gemini-NX column 5 μm, 5 mM aqueous NH ₄ HCO ₃ - MeCN, gradient) to give Synthesis compound R2cl. MCBP: calculated for C ₁₄ H ₁₀ N ₄ O: 250.0854, found: 250.2000 [(M form)].

1H NMR (500 MHz, MSM-d ₆ ): δ (ppm) 12.22 (brs, 1H), 7.86 (s, 1H), 7.71 (d, 1H), 7.68 (m, 1H), 7.58 (d , 1H), 7.17 (m, 1H), 7.17 (m, 1H), 6.86 (m, 1H), 6.73 (d, 1H), 6.68 (dd, 1H). 13C-NMR (125 MHz, MSM-d ₆ ): δ (ppm) 158.5, 147.9, 145.9, 137, 129.7, 126.3, 125.4, 123.5, 121.5, 121.5, 109, 107, 102.3, 101.8.

Synthesis of R2cm: 7- (1H-pyrrol-1-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Synthesis compound R1b (1.74 g, 11.67 mmol) was dissolved in DMF (80 ml) and cooled to 0 ° C. Sodium hydride (60% dis., 1.87 g, 46.67 mmol) was added slowly and stirred for 30 min at 0 ° C. To the reaction mixture was added hydroxylamine-O-sulfonic acid (2.11 g, 18.67 mmol) and allowed to warm to rt. and stirred for 20 h. Water (100 ml) was added to the reaction mixture and extracted with DCM (4 x 50 ml). The combined organic layers were washed with water and dried over MgSO4 and evaporated. The residue was dissolved in MSM and purified by preparative LC (on a C-18 Gemini-NX 5 μm column, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient).

A portion of the resulting N-amino compound (500 mg, 3.05 mmol) was dissolved in PDO (5 ml) and 2,5-dimethoxytetrahydrofuran (454 ml, 462 mg, 3.5 mmol) was added. The mixture was stirred at 100 ° C for 115 h. The reaction mixture was diluted with an aqueous solution of HCl (5N, 2 ml) and purified using preparative LC (on a C-18 Gemini-NX column 5 μm, 5 mM aqueous NH ₄ HCO ₃ - MeCN, gradient).

PDO (25 ml) and an aqueous HCl solution (1N, 1.3 ml) were added to a part of the resulting compound (63 mg, 0.294 mmol) and stirred at 60 ° C for 5 h. The reaction mixture was evaporated and the residue was purified using a preparative LC (on a C-18 Gemini-NX 5 μm column, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient) to give Synthesis compound R2cm. MCBP: calculated for C ₁₀ H ₈ N ₄ O: 200.0698, found: 201.0770 [(M + H) + form].

¹ H-NMR (500 MHz, MSM-d ₆ ): δ (ppm) 12.18 (brs, 1H), 7.92 (s, 1H), 7.46 (d, 1H), 7.12 (m, 2H), 6.61 (d, 1H), 6.21 (m, 2H). 13C-NMR (125 MHz, MSM-d ₆ ): δ (ppm) 158.4, 147.4, 145.8, 125.1, 122.8, 108, 106.7, 101.1.

Synthesis of R2de: 6-methyl-7-phenyl-3H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the compound of Synthesis of R1b and iodobenzene as reagents, 4-methoxy-7-phenylpyrrolo [2,3-d] pyrimidine was obtained (without hydrolysis). This crude product (450 mg, 2 mmol) was dissolved in THF (18 ml) stirring at -78 ° C, then LDA solution (1.8 M, 1.7 ml, 3 mmol) was added. After one hour stirring at -78 ° C, a solution of iodomethane (190 μl, 3 mmol) in THF (5 ml) was added and stirring was continued for 90 min. The reaction mixture was then diluted with brine (10 ml) and evaporated, loaded onto celite and purified by flash chromatography (Hexane-EEO = 7 -1).

The resulting crude product (400 mg, 1.6 mmol) was dissolved in conc. aqueous solution of HCl (330 μl, ~ 12.2 M, 4 mmol) and PDO (5 ml), and stirred at 100 ° C for 2 h. After completion of the reaction, the mixture was partially evaporated and the resulting suspension was filtered. The solid on the filter was washed with water and dried to give Synthesis compound R2de. MCBP: calculated for Ci ₃ H _u N ₃ O: 225.0902, found: 226.0985 [(M + H) + form].

1H NMR (500 MHz, MSM-d ₆ ): δ ppm. 11.94 (s, 1H), 7.76 (d, 1H), 7.55 (tm, 2H), 7.49 (tm, 1H), 7.4 (dm, 2H), 6.41 (d, 1H), 2.17 (d, 3H). 13C-NMR (125 MHz, MSM-d ₆ ): δ ppm. 158.4, 143.6, 136.2, 132.6, 129.6, 128.7, 128.5, 100.9, 13.3.

Synthesis of R2df: 9-methyl-3H-πyrimido [4,5-b] indol-4-one.

Synthesis of R1b (500 mg, 3.06 mmol) and 2,5-dimethoxytetrahydrofuran (810 mg, 6.13 mmol, d = 1.02, 795 μL) in PDO (5 mL) was heated to 100 ° C for 102 h, then 1N HCI was added. aqueous HCl solution (5 ml). The mixture was dissolved in DMF and purified by preparative LC (on a C-18 Gemini-NX 5 μm column, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient) to give Synthesis compound R2df. MCBP: calculated for C _n H ₉ N ₃ O: 199.0746, found: 200.0827 [(M + H) + form].

1H NMR (500 MHz, MSM-d6): δ ppm. 12.33 (brs, 1H), 8.21 (s, 1H), 7.63 (dm, 1H), 7.41 (ddd, 1H), 7.29 (td, 1H), 3.86 (s, 3H) ¹³ C-NMR (125 MHz, MSM -d6): δ ppm 158.5, 153.5, 148.1, 137, 124.6, 122, 121.8, 121, 110.7, 100.1, 28.5

Synthesis of R2dg: 6,8-dimethylpyrimido [5,4-b] indolizin-4 (3H) -one.

Synthesis compound R1b (1.74 g, 11.67 mmol) was dissolved in DMF (80 ml) and cooled to 0 ° C. Sodium hydride (60% dis., 1.87 g, 46.67 mmol) was added slowly and stirred for 30 min at 0 ° C. Hydroxylamine-O-sulfonoβy acid (2.11 g, 18.67 mmol) was added to the reaction mixture,

- 51 037563 allowed to warm up to rt. and stirred for 20 h. Water (100 ml) was added to the reaction mixture and extracted with DCM (4x50 ml). The combined organic layers were washed with water, dried over MgSO ₄ and evaporated.

Part of the resulting N-amino compound (300 mg, 1.83 mmol) and acetylacetone (206 μL, 201 mg 2.01 mmol) were dissolved in 5 ml of acetic acid and heated to 120 ° C for 2.5 h, then TFA (5 ml) was added ... The mixture was heated at 120 ° C for 18 hours. Then water (1 ml) and methanol (10 ml) were added and the solution was evaporated. The residue was purified by preparative LC (on a GeminiNX C-18 column 5 μm, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient) to give Synthesis compound R2dg. MCBP: calculated for C11H10N4O: 214.0855, found: 215.0935 [(M + H) + form].

1H NMR (500 MHz, MSM-de) δ ppm. 12.16 (s, 1H), 8 (s, 1H), 6.89 (s, 1H), 6.68 (d, 1H), 2.45 (d, 3H), 2.44 (s, 3H). ¹³ C-NMR (125 MHz, MSM-d6) δ ppm. 159.7, 152.5, 143.4, 141.2, 138.9, 127.7, 115.5, 109.8, 91.2, 21.9, 17.4.

Synthesis of R2dh: 6-chloro-7-phenyl-3H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 3, starting from the compound Synthesis of R1b and iodobenzene as reagents, 4-methoxy-7-phenylpyrrolo [2,3-pyrimidine (no hydrolysis) was obtained. The crude product (394 mg, 1.75 mmol) was dissolved in THF (14 ml) stirred at -78 ° C, then an LDA solution (1.8 M, 1.2 ml, 2.16 mmol) was added. After one hour stirring at -78 ° C, a solution of hexachloroethane (632 mg, 2.63 mmol) in THF (5 ml) was added and stirring was continued for 90 minutes. The reaction mixture was then diluted with brine (10 ml), evaporated, loaded onto celite and purified by flash chromatography (Hexane-EEO = 9-1).

The resulting crude product (110 mg, 0.42 mmol) was dissolved in conc. aqueous solution of HCl (82 μl, ~ 12.2 M, 1 mmol) and PDO (5 ml), and stirred at 100 ° C for 2 h. After completion of the reaction, the mixture was partially evaporated. The resulting slurry was filtered and the filter solid was washed with water and dried to give Synthesis compound R2dh. MCBP: calculated for CuHNsOCl: 245.0356, found: 246.043 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 12.16 (s, 1H), 7.88 (s, 1H), 7.6-7.52 (m, 5H), 6.78 (s, 1H). ¹³ SNMR (125 MHz, MSM-d ₆ ) δ ppm. 157.6, 148.2, 145.3, 101.6.

Synthesis of R2di: 6-iodo-7-methyl-3H-πyrrolo [2,3-d] πyrimidin-4-one.

Stirred solution of the Synthesis compound R1a 8 g, 52.1 mmol) in abs. DMF (50 ml) was cooled to 0 ° C, then sodium hydride (3.13 g, 60% dispers. In mineral oil, 78.2 mmol, 1.5 eq.) Was added and stirred for 20 min at rt. under Ar. Methyl iodide (8.2 g, 57.2 mmol, d = 2.28, 3.6 ml) was added to the reaction mixture and stirred for 1.5 h at rt. The mixture was poured into water (50 ml) to give a solid compound, which was filtered off.

Part of the resulting solid compound (500 mg, 2.98 mmol) was dissolved in 5 ml abs. THF and cooled to -78 ° C. Then 2 M LDA (1.7 ml, 3.4 mmol) was added dropwise. The mixture was stirred at -78 ° C for 1 h, then iodide (757 mg, 2.98 mmol) was added. The solution was allowed to warm to rt. and stirred for 22 hours. Finally, 5 ml of water was added and the formation of a solid compound was observed, which was filtered off to give Synthesis compound R2di. MCBP calculated for C ₇ H ₆ IN ₃ O: 274.9556, found: 275.9634 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 11.97 (s, 1H), 7.85 (s, 1H), 6.79 (s, 1H), 3.64 (s, 3H). 13C-NMR (125 MHz, MSM-d ₆ ) δ ppm. 157.3, 149.1, 144.2, 111.4, 110.3, 80.4, 33.2.

Synthesis of R2dj: 5-fluoro-7-methyl-3H-pyrrolo [2,3-d] pyrimidin-4-one Using General Procedure 1 starting from 4-chloro-5-fluoro-7H-pyrrolo [2,3-d ] pyrimidine (instead of the Synthesis compound R1a) and iodomethane as the alkylating agent, the Synthesis compound R2dj was obtained. MCBP: calculated for C7H6FN3O: 167.0495, found: 168.0574 [(M + H) + form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 11.97 (brs, 1H), 7.88 (s, 1H), 7.07 (s, 1H), 3.64 (s, 3H). ¹³ C-NMR (125 MHz, MSM-d ₆ ) δ ppm. 156.9, 144.6, 144.4, 143.1, 108.1, 97.0, 31.6.

Synthesis of R2dk: 3,6,7,8-tetrahydro-4H-pyrimido [5,4-b] pyrrolizin-4-one.

Step 1. 4-Methoxy-7 - ((2- (mrimethylsilyl) ethoxy) methyl) -7H-pyrrolo [2,3-d] pyrimidine.

In a preheated 100 ml two-necked spherical flask with a magnetic stirrer armature and a gas inlet, the Synthesis compound R1b (2.0 g, 11.4 mmol) was dissolved in abs. THF (45 ml). The solution was cooled to 0 ° C and NaH (0.85 g, 3 eq.) Was added. The mixture was stirred for 1 h, then SEM-Cl (3.55 ml, 1.5 eq.) Was added via a syringe. A yellow solution and a white precipitate formed. The mixture was allowed to warm to rt, during which time the color disappeared. After decolorization, the reaction was quenched with water (30 ml). The mixture was extracted with EEO (3x30 ml) and the collected organic layers were dried over Na ₂ SO ₄ . After filtration, the solvent was evaporated and the crude product was purified by flash chromatography (hexane: EEO = 20: 1-9: 1) to give the title product as a yellowish liquid.

Step 2. 6-Iodo-4-methoxy-7 - ((2- (trimethylsilyl) ethoxy) methyl) -7H-pyrrolo [2, S-d] pyrimidine.

In a preheated 250 ml three-necked spherical flask with a magnetic stirrer armature and a gas inlet, abs. THF (30 ml) and diisopropylamine (2.7 ml, 1.5 eq.) In the atmosphere

- 52 037563 nitrogen. The mixture was cooled to -78 ° C and n-BuLi (8.0 ml, 1.5 eq.) Was added and stirred for 30 min. Then 4-methoxy-7 - ((2- (trimethylsilyl) ethoxy) methyl) -7Hpyrrolo [2,3-d] pyrimidine (3.64 g, 13.05 mmol, 1 eq.), Dissolved in abs. THF (100 ml), and stirring was continued for 1 h. Then iodine (3.95 g, 1.2 eq.), Dissolved in abs. THF (35 ml) and the mixture was stirred for an additional 3 h. Then the cooling bath was removed and the reaction mixture was allowed to warm to rt. Brine (500 ml) was added and the reaction solution was extracted three times with EEO (150 ml). The organic phases were dried, filtered, evaporated and purified by flash chromatography (hexane: EEO 9: 1) to give the title product as a yellowish white powder.

Step 3. 6-Iodo-4-methoxy-7H-pyrrolo [2,3-d] pyrimidine.

In a 100 ml Schlenk flask, 6-iodo-4-methoxy-7 - ((2- (trimethylsilyl) ethoxy) methyl) -7H-pyrrolo [2,3d] pyrimidine (4.72 g, 11.65 mmol) was dissolved in THF (50 ml ). To the solution was added TBAF.3H ₂ O (11.34 g, 3 equiv.) With 4A molecular sieves. The mixture was heated at 95 ° C under nitrogen overnight. After cooling, the mixture was filtered through celite and the solvent was evaporated. Water was added to the resulting brown oil and precipitation of an off-white powder was observed. The precipitate was filtered off, washed with water and MeCN (3x10 ml). After drying, the title product was obtained as an off-white powder.

Step 4. 7-Allyl-6-iodo-4-methoxy-7H-pyrrolo [2,3-d] pyrimidine.

In a preheated two-necked 100 ml spherical flask with a magnetic stirrer arm and a gas inlet, 6-iodo-4-methoxy-7H-pyrrolo [2,3-d] pyrimidine (900 mg, 3.27 mmol) was dissolved in abs. THF (10 ml) under nitrogen. Then triphenylphosphine (1.048 g, 1.2 eq.) Was added. Then, with continuous stirring, allyl alcohol (232 mg, 1.2 equiv.) Was measured into a flask using a syringe. The mixture was cooled to 0 ° C and diisopropyl aza-dicarboxylate (808 mg, 1.2 eq.) Was added dropwise using a syringe. The mixture was allowed to warm to rt and the reaction was monitored by TLC. After completion of the reaction, the solvent was evaporated and the crude product was purified by flash chromatography (hexane: EEO = 10: 1) to give the title product as white crystals.

Step 5. 4-Methoxy-7,8-dihydro-6H-pyrimido [5,4-b] pyrrolysine.

7-allyl-6-iodo-4-methoxy-7H-pyrrolo [2,3-d] pyrimidine (1.60 g, 5.1 mmol) was measured into a preheated 100 ml Schlenk vessel and dissolved in abs. THF (50 ml). 9-Borabicyclo [3.3.1] nonane (1.87 g, 3 equiv.) Was measured in a glove box with a double manifold, dissolved in abs. THF (30 ml) and added to the Schlenk flask with a syringe at 0 ° C. The reaction mixture was allowed to warm to rt. and stirred overnight. Then [1, G-bis (diphenylphosphino) ferrocene] dichloropalladium (P) (366 mg, 0.1 eq.) And K ₂ CO ₃ (4.93 g, 7 eq.) Were measured under nitrogen and added to the solution. The mixture was heated to 85 ° C for 4 hours. After completion of the reaction, the solvent was evaporated and the crude product was purified by flash chromatography (hexane: EEO = 3: 1) to give the title product as a dark red solid.

Step 6. Compound Synthesis of R2dk.

The resulting in Step 5 above, methoxypyrrolysine (69.7 mg, 0.37 mmol) and lithium hydroxide monohydrate (155 mg, 3.7 mmol) were diluted in a mixture of PDO (2 ml) and water (2 ml) and stirred at 110 ° C for for 40 hours. After completion of the reaction, the mixture was evaporated and purified by preparative LC (on a C-18 Gemini-NX 5 μm column, 5 mM aqueous NH4HCO ₃ -MeCN, gradient) to give Synthesis compound R2dk. MS calcd for C9H9N3O: 175.07, found: 175.2 [(M + H) + EI form].

Synthesis of R2dl: 6,7,8,9-tetrahydro-3H-pyrimido [5,4-b] indolizin-4-one.

Step 1. 7- (But-3-en-1-yl) -6-iodo-4-methoxy-7H-pyrrolo [2,3-d] pyrimidine.

In a 100 ml spherical flask, 6-iodo-4-methoxy-7H-pyrrolo [2,3-d] pyrimidine (obtained from Stage 3 of the Synthesis of R2dk, 1.99 g, 7.23 mmol) was dissolved in DMSO (70 ml), and KOH was added (690 mg, 1.7 eq.). The mixture was sonicated for 10 min, then homoallyl bromide (2.15 mL, 3 equiv.) Was added at 0 ° C. After heating to rt, the mixture was stirred until the reaction was complete. After completion of the reaction, water (50 ml) was added and the mixture was extracted with EEO (3x120 ml). The organic phases were collected, dried over sodium sulfate and evaporated. The crude product was purified by flash chromatography (hexane: EEO = 20: 1-5: 1) to afford the title product as a white solid.

Step 2. 4-Methoxy-3,4,6,7,8,9-hexahydropyrimido [5,4-b] indolizine.

7-But-3-enyl-6-iodo-4-methoxypyrrolo [2,3-d] pyrimidine (164 mg, 0.5 mmol) was dissolved in THF (2 ml) in a Schlenk flask under nitrogen atmosphere. The mixture was cooled to 0 ° C, a solution of 9-borabicyclo [3.3.1] nonane (305 mg, 2.5 mmol) in THF (5 ml) was added using a syringe and stirred overnight at RT. [1, G-bis (diphenylphosphino) ferrocene] dichloropalladium (II) (75 mg, 0.1 mmol) and K2CO3 (967 mg, 7 mmol) were added to the reaction mixture and stirred for 3 h at 80 ° C. Then the reaction mixture was evaporated, applied to celite and purified using flash chromatography (hexane-EEO = 3-1).

Step 3. Compound Synthesis of R2dl.

- 53 037563

The resulting Step 2 above, methoxyindolysine (104 mg, 0.51 mmol) and lithium hydroxide monohydrate (215 mg, 5.1 mmol), were diluted in a mixture of PDO (2 ml) and water (2 ml) and stirred at 110 ° C. within 40 hours. After completion of the reaction, the mixture was evaporated and purified by preparative LC (on a C-18 Gemini-NX column 5 μm, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient) to give Synthesis compound R2dl. MS: calculated for C ₁₀ H11N ₃ O: 189.09, found: 190 [(M + H) + EI form].

Synthesis of R3a: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) 3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5 starting from 3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one as reagent, Synthesis compound R3a was obtained. MCBP: calculated for C ₂₄ H ₂₉ N ₅ O ₃ : 435.2270, found: 436.2345 [(M + H) ⁺ form].

¹ H NMR (500 MHz, MSM-d ₆ ) δ ppm. 11.91 / 11.9 (brs, 1H), 9.36 / 8.86 (brd + brq, 2H), 8.03 / 7.97 (s, 1H), 7.32-7.11 (m, 5H), 7.06 / 7.04 (dd, 1H), 6.47 / 6.43 (dd, 1H), 4.09-2.6 (m, 12H), 1.96-0.62 (m, 6H).

Synthesis of R3b: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] nuperidin-4-yl} methyl) -7methyl-3H, 4H, 7H-pyrrolo [2,3 -d] pyrimidin-4-one.

Using General Procedure 5, starting from Synthesis compound R2b as reagent, Synthesis compound R3b was obtained as the HCl salt. MCBP: calculated for C ₂₅ H ₃₁ N ₅ O ₃ : 449.2427, found: 450.2517 [(M + H) + form].

1H NMR (500 MHz, MSM-d6) δ ppm. 9.16 / 8.72 (brd / brq, 2H), 8.02 / 8.07 (s, 1H), 7.34-7.11 (m, 5H), 7.11 / 7.13 (d, 1H), 6.45 / 6.48 (d, 1H), 4.01 / 3.73 (d / s, 1H), 4.00-0.58 (m, 16H), 3.89 (d, 2H), 3.71 (s, 3H).

Synthesis of R3c: 7-ethyl-3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidine-4yl} methyl) -3H, 4H, 7H-pyrrolo [2,3 -d] pyrimidin-4-one.

Using General Procedure 5, starting with Synthesis compound R2c as reagent, Synthesis compound R3c was prepared as the HCl salt. MCBP calculated for C ₂₆ H ₃₃ N ₅ O ₃ : 463.2583, found: 464.2654 [(M + H) + form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.16 / 8.72 (brd / brq, 2H), 8.01 / 8.07 (s, 1H), 7.33-7.09 (m, 5H), 7.18 / 7.19 (d, 1H), 6.45 / 6.49 (d, 1H), 4.13 / 4.15 (q, 2H), 4.01 / 3.73 (d / s, 1H), 4.00-0.58 (m, 16H), 3.89 (d, 2H), 1.34 / 1.35 (t, 3H).

Synthesis of R3d: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidin-4-carbonyl] nuperidin-4-yl} methyl) -7 (npropan-2-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5 starting from Synthesis compound R2d as reagent, Synthesis R3d compound was prepared. MCBP calculated for C ₂₇ H ₃₅ N ₅ O ₃ : 477.274, found: 478.2819 [(M + H) + form].

1H NMR (500 MHz, MSM-d6) δ ppm. 9.4 / 8.89 (brd + brq, 1 + 1H), 8.08 / 8.03 (s / s, 1H), 7.32-7.09 (m, 5H), 7.27 / 7.25 (d / d, 1H), 6.51 / 6.47 (d / d, 1H), 4.84 (m, 1H), 4.05-0.6 (m, 16H), 3.48 / 3.43 (m / m, 1H), 3.22 (m, 1H), 1.43 (d, 6H). 13C-NMR (125 MHz, MSM-d6) δ ppm. 147.4, 121.1 / 121, 102.3 / 102.2, 46.4, 42.6 / 42.4, 41 / 40.6, 23.1.

Synthesis of R3e: 6- [3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperudine-4-carbonyl] piperidin-4-yl} methyl) 4-oxo-3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-7-yl] -1,2-dihydropyridin-2-one.

Using General Procedure 15, starting from Synthesis R3bs compound as reagent, Synthesis R3e compound was obtained as the free base. MCBP calculated for C ₂₉ H ₃₂ N ₆ O ₄ : 528.2485, found: 529.2567 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 8.17 / 8.13 (s / s, 1H), 7.87 / 7.86 (d / d, 1H), 7.83 / 7.8 (d / d, 1H), 7.82 (t, 1H), 7.26-6.99 (m, 5H), 6.71 /6.68 (d / d, 1H), 6.6 (d, 1H), 4.85 (brs, 1H), 4.12-0.75 (m, 16H), 3.21 / 3.15 (t / t, 1H), 2.86 (m, 1H) ... 13C-NMR (125 MHz, MSM-d ₆ ) δ ppm. 148.4, 142, 122.2, 107.9, 107.1, 103.9 / 103.8, 46.4 / 46.3, 43.4 / 42.9.

Synthesis of R3g: 7-cyclopropyl-3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidin-4-carbonyl] piperidin4-yl} methyl) -3H, 4H, 7H-pyrrolo [2,3 -d] pyrimidin-4-one.

Using General Procedure 5, starting from the Synthesis compound R2g as a reagent, the Synthesis compound R3g was obtained as the HCl salt. MCBP: calculated for C ₂₇ H ₃₃ N ₅ O ₃ : 475.2583, found: 476.2668 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.26 / 8.78 (brd + brq, 2H), 8.12-6.38 (m, 8H), 4.05-0.62 (m, 23H).

Synthesis of R3h: 7-cyclobutyl-3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidine-4yl} methyl) -3H, 4H, 7H-pyrrolo [2,3 -d] pyrimidin-4-one.

Using General Procedure 5, starting from Synthesis compound R2h as a reagent, Synthesis compound R3h was prepared. MCBP: calculated for C ₂₈ H ₃₅ N ₅ O ₃ : 489.274, found: 490.2796 ((M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6) δ ppm. 8.92 (vbrs, 2H), 8.06 / 8.01 (s / s, 1H), 7.43 / 7.4 (d / d, 1H), 7.34-7.08 (m, 5H), 6.53 / 6.49 (d / d, 1H), 5.09 (m, 1H), 4.85 (s, 1H), 4.08-0.55 (m, 16H), 3.47 / 3.42 (m / m, 1H), 3.21 (m, 1H), 2.5 / 2.38 (m + m, 4H) , 1.82 (m, 2H). 13C-NMR (500 MHz, MSM-d ₆ ) δ ppm. 147.6 / 147.5, 122 / 121.9, 102.5 / 102.4, 48.5, 42.6 / 42.5, 41 / 40.6, 31, 14.8.

Synthesis of R3k: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidin-4-carbonyl] nuperidin-4-yl} methyl) -7 (1-methylniperidin-4-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from the Synthesis compound R2k as a reagent, the compound

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The synthesis of R3k was obtained as the HCl salt. MCBP: calculated for C ₃₀ H ₄₀ N ₆ O ₃ : 532.3162, found: 267.1658

[(M + 2H) 2+ form].

Ή NMR (500 MHz, MSM-d6) δ ppm 10.87 / 10.67 (brs, 1H), 9.29 / 8.8 (brq + brd, 2H), 8.13 / 8.08 (s, 1H), 7.35-7.11 (m, 5H), 7.14 / 7.12 (d, 1H), 6.57 / 6.53 (d, 1H), 4.82 (brs, 1H), 4.76 (m, 1H), 4.08-2.61 (m, 16H), 2.78 (d, 3H), 2.47-1.96 (m, 4H), 1.95-0.59 (m , 6H).

Synthesis of R3m: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -7 (prop-2-yn-1-yl) - 3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with Synthesis compound R2m as reagent, Synthesis compound R3m was prepared as the HCl salt. MCBP: calculated for C ₂₇ H ₃₁ N ₅ O ₃ : 473.2427, found: 474.2502 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.32 / 8.83 (brd + brq, 2H), 8.12 / 8.06 (s, 1H), 7.33-7.12 (m, 12H), 7.337.12 (m, 5H), 7.22 / 7.2 (d, 1H), 6.55 / 6.51 (d, 1H), 5 / 4.98 (d, 2H), 3.44 / 3.43 (t, 1H), 1.92-0.62 (m, 6H).

Synthesis of R3n: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -7 (2-methylpropyl) -3H, 4H, 7H- pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from the Synthesis compound R2n as a reagent, the Synthesis compound R3n was obtained as the HCl salt. MCBP calculated for C ₂₈ H ₃₇ N ₅ O ₃ : 491.2896, found: 492.2963 [(M + H) ⁺ form].

¹ H NMR (500 MHz, MSM-d6) δ ppm. 9.3 / 8.81 (brd + brq, 2H), 8.07 / 8.01 (s, 1H), 7.33-7.12 (m, 5H), 7.15 / 7.13 (d, 1H), 6.49 / 6.46 (d, 1H), 4.05-2.61 (m, 14H), 2.12 (m, 1H), 1.92-0.61 (m, 6H), 0.84 / 0.83 (d, 6H).

Synthesis of R3o: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -7 (2,2,2-trifluoroethyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with the Synthesis compound R2o as a reagent, the Synthesis compound R3o was obtained as the HCl salt. MCBP: calculated for C ₂₆ H ₃₀ F ₃ N ₅ O ₃ : 517.2301, found: 518.2386 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.11 / 8.67 (brq + brd, 2H), 8.16-6.55 (m, 8H), 5.15-0.6 (m, 20 H), 4.87 (brs, 1H).

Synthesis of R3p: 7- (2,2-difluoroethyl) -3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -3H, 4H , 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with Synthesis compound R2p as reagent, Synthesis compound R3p was obtained as the HCl salt. MCBP: calculated for C ₂₆ H ₃₁ F ₂ N ₅ O ₃ : 499.2395, found: 500.2485 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6) δ ppm. 9.28 / 8.8 (brd + brq., 2H), 8.12 / 8.07 (s / s, 1H), 7.36-7.11 (m, 5H), 7.18 / 7.17 (d / d, 1H), 6.57 / 6.53 (d / d , 1H), 6.39 (tm, 1H), 4.6 (m, 2H), 4.07-0.6 (m, 16H), 3.48 / 3.42 (m / m, 1H), 3.22 (m, 1H). 13C-NMR (125 MHz, MSM-d6) δ ppm. 148.2 / 148.1, 125.2, 114.4, 102.9 / 102.8, 46.1, 42.6 / 42.4, 41 / 40.6.

Synthesis of R3q: 7- (cyclopropylmethyl) -3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidin-4-carbonyl] piperidin-4-yl} methyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with Synthesis compound R2q as a reagent, Synthesis compound R3q was prepared as the HCl salt. MCBP: calculated for C ₂₈ H ₃₅ N ₅ O ₃ : 489.2740, found: 490.2817 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.11 / 8.68 (brq + brd, 2H), 8.06 / 8 (s, 1H), 7.34-7.1 (m, 5H), 7.23 / 7.21 (d, 1H), 6.5 / 6.46 (d, 1H), 4.07-2.6 (m, 14H), 1.92-0.63 (m, 7H), 0.54-0.35 (m, 4H).

Synthesis of R3r: 7- (cyclobumylmethyl) -3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidin-4-carbonyl] piperidin-4-yl} methyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with Synthesis compound R2r as a reagent, Synthesis compound R3r was obtained as an HCl salt. MCBP calculated for C ₂ 9H ₃₇ N ₅ O ₃ : 503.2896, found: 504.2957 [(M + H) ⁺ form].

1H NMR (400 MHz, MSM-d6) δ ppm. 9.45 / 8.92 (brq + brd), 8.09 / 8.03 (s, 1H), 7.34-7.08 (m, 5H), 7.15 / 7.13 (d, 1H), 6.47 / 6.44 (d, 1H), 4.19-2.59 (m , 15H), 2.02-0.56 (m, 12H).

Synthesis of R3s: 7- (buta-2,3-diene-1-yl) -3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidin-4-carbonyl] piperidin-4-yl} methyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with the Synthesis compound R2s as a reagent, the Synthesis compound R3s was obtained as the HCl salt. MCBP: calculated for C ₂₈ H ₃₃ N ₅ O ₃ : 487.2583, found: 488.2657 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6) δ ppm. 9.28 / 8.8 (brd + brq, 2H), 8.09 / 8.03 (s, 1H), 7.34-7.11 (m, 5H), 7.15 / 7.14 (d, 1H), 6.51 / 6.47 (d, 1H), 5.5 (m , 1H), 4.9 (m, 2H), 4.88 (s, 1H), 4.73 (m, 2H), 4.06-2.63 (m, 12H), 1.94-0.6 (m, 6H).

Synthesis of R3t: 7- [3 - (dimethylamino) propyl] -3 - ({4-hydroxy- 1 - [(3R, 4R) -3-phenylpiperidin-4-carbonyl] piperidin-4-yl} methyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with the Synthesis compound R2t as a reagent, the Synthesis compound R3t was obtained as the HCl salt. MCBP: calculated for C ₂₉ H ₄₀ N ₆ O ₃ : 520.3162, found: 261.1666

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[(M + 2H) 2+ form].

Ή NMR (500 MHz, MSM-d ₆ ) δ ppm. 10.53 (brs, 1H), 9.33 / 8.83 (brs + brm, 2H), 8.13 / 8.07 (s / s, 1H), 7.367.14 (m, 5H), 7.23 / 7.21 (d / d, 1H), 6.53 /6.5 (d / d, 1H), 4.2 (m, 2H), 4.06-0.55 (m, 16H), 3.48 / 3.43 (m / m, 1H), 3.22 (m, 1H), 3.02 (m, 2H) , 2.72 / 2.71 (s / s, 6H), 2.17 (m, 2H). ¹³ C-NMR (125 MHz, MSM-d ₆ ) δ ppm. 147.9 / 147.8, 124.4 / 124.3, 102.4, 54.4, 42.6 / 42.4, 42.5, 42, 41 / 40.6, 25.6.

Synthesis of R3u: 7- (2-fluoroethyl) -3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidin-4-carbonyl] piperidin4-yl} methyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from the Synthesis compound R2u as a reagent, the Synthesis compound R3u was obtained as the HCl salt. MCBP: calculated for C25H31FN5O3: 468.2411, found: 482.2555 [(M + H) + form].

1H NMR (500 MHz, MSM-d6) δ ppm. 9.16 / 8.71 (m + m, 2H), 8.08 / 8.03 (s, 1H), 7.34-7.11 (m, 5H), 7.2 / 7.18 (d, 1H), 6.53 / 6.49 (d, 1H), 4.82 (brs , 1H), 4.76 (dt, 2H), 4.44 (dt, 2H), 4.11-2.6 (m, 12H), 1.95-0.6 (m, 6H).

Synthesis of R3v: 7- [2- (dimethylamino) ethyl] -3 - ({4-hydroxy- 1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with Synthesis compound R2v as reagent, Synthesis compound R3v was obtained as the HCl salt. MCBP: calculated for C ₂₈ H ₃₈ N ₆ O ₃ : 506.3005, found: 254.1581 [(M + 2H) ²⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 10.48 (brs, 1H), 9.27 / 8.8 (brs + brm, 2H), 8.16 / 8.11 (s / s, 1H), 7.377.16 (m, 5H), 7.25 (d, 1H), 6.57 / 6.54 (d / d, 1H), 4.9 (vbrs, 1H), 4.53 (m, 2H), 4.13-0.55 (m, 16H), 3.51 (m, 2H), 3.48 / 3.43 (brm / brm, 1H), 3.22 (m , 1H), 2.8 / 2.79 (d / d, 6H). ¹³ C-NMR (125 MHz, MSM-d ₆ ) δ ppm. 148.1, 124.4, 103, 55.9, 42.9, 42.6 / 42.4, 41 / 40.6, 39.6.

Synthesis of R3w: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperigin-4-carbonyl] piperidin-4-yl} methyl) -7 (2-hydroxyethyl) -3H, 4H, 7H- pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from Synthesis compound R2w as a reagent, Synthesis compound R3w was prepared.

1H NMR (400 MHz, MSM-d6) δ ppm. 8.05 / 7.99 (s / s, 1H), 7.27-7.02 (m, 5H), 7.16 / 7.14 (d / d, 1H), 6.47 / 6.45 (d / d, 1H), 4.94 / 4.93 (t / t, 1H), 4.83 / 4.8 (s / s, 1H), 4.15 (m, 2H), 4.06-0.72 (m, 16H), 3.71 (m, 2H), 3.2 / 3.15 (m / m, 1H), 2.86 ( m, 1H). ¹³ C-NMR (100 MHz, MSM-d6) δ ppm. 147.4, 125.1, 101.8 / 101.7, 60.6, 47.3, 46.5 / 46.4, 43.4.

Synthesis of R3x: 7 - [(4-chlorophenyl) methyl] -3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperigin-4-carbonyl] piperidin-4-yl} methyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with Synthesis compound R2x as reagent, Synthesis compound R3x was obtained as the HCl salt. MCBP: calculated for C ₃ iH _{34 ClN 5} O ₃ : 559.2350, found: 560.2418 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.04 / 8.63 (brd + brq, 2H), 8.07 / 8.02 (s, 1H), 7.44-7.07 (m, 9H), 7.26 / 7.24 (d, 1H), 6.54 / 6.5 (d, 1H), 5.34 / 5.33 (s, 2H), 4.81 (brs, 1H), 4.04-2.61 (m, 12H), 1.92-0.61 (m, 6H).

Synthesis of R3y: 7 - [(3-chlorophenyl) methyl] -3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperigin-4-carbonyl] piperidin-4-yl} methyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with Synthesis compound R2y as reagent, Synthesis compound R3y was obtained as the HCl salt. MCBP: calculated for C ₃₁ H ₃₄ ClN ₅ O ₃ : 559.2350, found: 560.2432 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6) δ ppm. 9.1 / 8.67 (brd + brq, 2H), 8.09 / 8.03 (s, 1H), 7.4-7.08 (m, 9H), 7.29 / 7.27 (d, 1H), 6.55 / 6.52 (d, 1H), 5.35 / 5.34 (s, 2H), 4.83 (brs, 1H), 4.05-2.62 (m, 12H), 1.91-0.61 (m, 6H).

Synthesis of R3z: 7-benzyl-3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperigin-4-carbonyl] piperigin-4-yl} methyl) -3H, 4H, 7H-pyrrolo [2 , 3-d] pyrimidin-4-one.

Using General Procedure 5, starting with the Synthesis compound R2z as a reagent, the Synthesis compound R3z was obtained as the HCl salt. MCBP calculated for C ₃₁ H ₃₅ N ₅ O ₃ : 525.2740, found: 526.2822 [(M + H) form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.31 / 8.82 (brd + brq, 2H), 8.1 / 8.05 (s, 1H), 7.36-7.09 (m, 10H), 7.25 / 7.22 (d, 1H), 6.53 / 6.5 (d, 1H), 5.34 / 5.33 (s, 2H), 4.05-2.63 (m, 12H), 1.92-0.62 (m, 6H).

Synthesis of R3aa: 7 - [(2-chlorophenyl) methyl] -3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidin-4-carbonyl] piperidin-4-yl} methyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with the Synthesis compound R2aa as a reagent, the Synthesis compound R3aa was obtained as the HCl salt. MCBP: calculated for C ₃₁ H ₃₄ ClN ₅ O ₃ : 559.2350, found: 560.2429 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6) δ ppm. 9.12 / 8.68 (brd + brq, 2H), 8.07 / 8.01 (s, 1H), 7.54-6.76 (m, 9H), 7.2 / 7.18 (d, 1H), 6.56 / 6.55 (d, 1H), 5.44 / 5.43 (s, 2H), 4.86 / 4.85 (s, 1H), 4.06-2.61 (m, 12H), 1.91-0.62 (m, 6H).

Synthesis of R3ac: 3 - ({4-hydroxy- 1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -7 (3,4,5-trimethoxyphenyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with the Synthesis compound R2ac as a reagent, the Synthesis compound R3ac was prepared as the HCl salt. MCBP: calculated for C ₃₃ H ₃₉ N ₅ O ₆ : 601.2900, found: 602.2960 [(M + H) + form].

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Ή NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.55 / 9.01 (brq + brd, 2H), 8.16 / 8.12 (s, 1H), 7.54 / 7.51 (d, 1H), 7.367.14 (m, 5H), 7.01 / 6.99 (s, 2H), 6.7 / 6.67 (d, 1H), 4.95 (brs, 1H), 4.1-2.61 (m, 12H), 3.83 (s, 6H), 3.7 (s, 3H),

1.98-0.62 (m, 6H).

Synthesis of R3ad: 7- (3,5-dichlorophenyl) -3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -3H, 4H , 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with the Synthesis compound R2ad as a reagent, the Synthesis compound R3ad was prepared as the HCl salt. MCBP: calculated for C ₃₀ H ₃₁ N5O ₃ Cl2: 579.1804, found: 580.1891 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6) δ ppm. 9.06 / 8.65 (brd + brq, 2H), 8.18 / 8.14 (s, 1H), 7.98 / 7.97 (d, 2H), 7.71 / 7.68 (d, 1H), 7.67 (t, 1H), 7.34-7.14 (m , 5H), 6.77 / 6.73 (d, 1H), 4.88 (brs, 1H), 4.12-2.62 (m, 12H), 1.960.62 (m, 6H).

Synthesis of R3ae: 7- (3-chloro-5-methoxyphenyl) -3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -3H , 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from the Synthesis compound R2ae as a reagent, the Synthesis compound R3ae was obtained as the HCl salt. MCBP: calculated for C ₃₁ H ₃₄ ClN ₅ O ₄ : 575.2299, found: 576.2382 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 8.83 (brs, 2H), 8.15 / 8.1 (s, 1H), 7.64 / 7.62 (d, 1H), 7.51 / 7.5 (t, 1H), 7.36 / 7.34 (t, 1H), 7.36-7.12 (m, 5H ), 7.09 (t, 1H), 6.74 / 6.7 (d, 1H), 4.87 (s, 1H), 4.11-2.62 (m, 12H), 3.85 (s, 3H), 1.94-0.62 (m, 6H).

Synthesis of R3af: 7- (3,5-dimethoxyphenyl) -3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -3H, 4H , 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with the Synthesis compound R2af as a reagent, the Synthesis compound R3af was obtained as the HCl salt. MCBP calculated for C ₃₂ H ₃₇ N ₅ O ₅ : 571.2795, found: 572.2881 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.11 / 8.68 (brq + brd, 2H), 8.12 / 8.07 (s, 1H), 7.57 / 7.55 (d, 1H), 7.347.13 (m, 5H), 6.93 / 6.91 (d, 2H), 6.71 / 6.67 (d, 1H), 6.56 / 6.55 (t, 1H), 4.86 (brs, 1H), 4.09-2.62 (m, 12H), 3.81 (s, 6H), 1.94-0.64 (m, 6H).

Synthesis of R3ag: 7- (3,4-dichlorophenyl) -3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -3H, 4H , 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with the Synthesis compound R2ag as a reagent, the Synthesis compound R3ag was prepared as the HCl salt. MCBP: calculated for C ₃₀ H ₃ iCl ₂ N ₅ O ₃ : 579.18042, found: 580.1870 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6) δ ppm. 9.16 / 8.71 (brq + brd, 2H), 8.2-7.79 (m, 3H), 8.17 / 8.13 (s, 1H), 7.65 / 7.63 (d, 1H), 7.35-7.12 (m, 5H), 6.76 / 6.72 (d, 1H), 4.85 (brs, 1H), 4.11-2.61 (m, 12H), 1.95-0.6 (m, 6H).

Synthesis of R3ah: 7- (4-chloro-3-fluorophenyl) -3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -3H , 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with the Synthesis compound R2ah as a reagent, the Synthesis compound R3ah was prepared as the HCl salt. MCBP: calculated for C ₃₀ H ₃₁ N ₅ O ₃ FCl: 563.2100, found: 564.2181 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.08 / 8.66 (brm / brm, 2H), 8.16 / 8.12 (s, 1H), 7.98 / 7.97 (dd, 1H), 7.827.72 (m, 1H), 7.78 (m, 1H), 7.65 / 7.63 (d , 1H), 7.33-7.26 (m, 2H), 7.26-7.2 (m, 2H), 7.17 (brt, 1H), 6.77 / 6.73 (d, 1H), 4.86 (vbrs, 1H), 4.12-0.58 (, 16H), 4.05 / 3.94 / 3.67 (d / s, 2H). 13C-NMR (125 MHz, MSM-d ₆ ) δ ppm. 158.3, 157.7, 148.7 / 148.6, 146.7 / 146.6, 131.6, 129 / 128.9, 128.3 / 128.1, 127.7, 124.1, 121, 112.7, 109.3 / 109.2, 104.5, 69.4, 53.6 / 53.3.

Synthesis of R3ai: 7- (4-chloro-3-methoxyphenyl) -3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -3H , 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from the Synthesis compound R2ai as a reagent, the Synthesis compound R3ai was obtained as the HCl salt. MCBP: calculated for C ₃₁ H ₃₄ ClN ₅ O ₄ : 575.2230, found: 576.2382 [(M + H) ⁺ form].

1H NMR (400 MHz, MSM-d6) δ ppm. 8.89 (brs, 2H), 8.14 / 8.06 (s, 1H), 7.62 / 7.6 (d, 1H), 7.6 (d, 1H), 7.51 / 7.5 (d, 1H), 7.38 / 7.36 (dd, 1H), 7.35-7.13 (m, 5H), 6.75 / 6.71 (d, 1H), 4.87 (s, 1H), 4.11-2.6 (m, 12H), 3.93 (s, 3H), 1.95-0.6 (m, 6H).

Synthesis of R3aj: 7- (4-fluoro-3-methoxyphenyl) -3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -3H , 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with the Synthesis compound R2aj as the reagent, the Synthesis compound R3aj was obtained as the HCl salt. MCBP calculated for C ₃₁ H ₃₄ FN ₅ O ₄ : 559.2595, found: 560.2638 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.13 / 8.7 (brd + brq, 1 + 1H), 8.12 / 8.07 (s / s, 1 H), 7.55 / 7.53 (d / d, 1H), 7.49 (m, 2H), 7.39 (m, 2H), 7.35-7.14 (m, 5H), 7.28 (m, 2 H), 6.73 / 6.69 (d / d, 1H), 4.65-0.6 (m, 16H), 3.91 (s, 3H), 3.48 / 3.42 (m / m, 1H), 3.22 (m, 1H). ¹³ C-NMR (125 MHz, MSM-d ₆ ) δ ppm. 148.4 / 148.3, 124.8 / 124.7, 116.8, 116.6, 110.8, 103.7, 56.8, 42.6 / 42.5, 41 / 40.6.

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Synthesis of R3ak: 7- (3,4-dimethoxyphenyl) -3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidin-4-carbonyl] piperidin-4-yl} methyl) -3H, 4H , 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from the Synthesis compound R2ak as a reagent, the compound

The synthesis of R3ak was obtained as the HCl salt. MCBP: calculated for C ₃₂ H ₃₇ N ₅ O ₅ : 571.2795, found: 572.2892

[(M + H) + form].

1H NMR (500 MHz, MSM-de) δ ppm. 9.11 / 8.69 (brd + brq, 2H), 8.09 / 8.04 (s, 1H), 7.48 / 7.46 (d, 1H), 7.357.06 (m, 8H), 6.69 / 6.68 (d, 1H), 4.86 (brs , 1H), 4.11-2.6 (m, 12H), 3.81 (s, 6H), 1.96-0.62 (m, 6H).

Synthesis of R3am: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -7 (4-methylphenyl) -3H, 4H, 7H- pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with Synthesis compound R2am as reagent, Synthesis compound R3am was prepared as the HCl salt. MCBP calculated for C3iH ₃₅ N ₅ O ₃ : 525.2734, found: 526.2816 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.31 / 8.82 (brd + brq, 2H), 8.11 / 8.06 (s, 1H), 7.6 / 7.58 (m, 2H), 7.49 / 7.46 (d, 1H), 7.35 / 7.34 (m, 2H), 7.32-7.11 (m, 5H), 6.71 / 6.67 (d, 1H), 4.81 (brs, 1H), 4.11-2.61 (m, 12H), 2.37 (s, 3H), 1.94-0.61 (m, 6H).

Synthesis of R3an: 4- [3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidin-4-carbonyl] piperidin-4-yl} methyl) 4-oxo-3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-7-yl] benzonitrile.

Using General Procedure 5, starting from the Synthesis compound R2an as a reagent, the Synthesis compound R3an was obtained as the HCl salt. MCBP calculated for C ₃₁ H ₃₂ N ₆ O ₃ : 536.2536, found: 537.2599 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6) δ ppm. 9.19 / 8.73 (brd + brq, 2H), 8.18 / 8.14 (s / s, 1H), 8.12-8 (m, 4H), 7.71 / 7.69 (d / d, 1H), 7.35-7.13 (m, 5H) , 6.8 / 6.76 (d / d, 1H), 4.85 (vbrs, 1H), 4.15-0.6 (m, 16H), 3.48 / 3.42 (m / m, 1H), 3.22 (m, 1H).

Synthesis of R3ao: 3 - ({4-hydroxy- 1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -7 [4- (trifluoromethyl) phenyl] -3H, 4H , 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from the Synthesis compound R2ao as a reagent, the Synthesis compound R3ao was obtained as the HCl salt. MCBP: calculated for C ₃₁ H3 ₂ N ₅ O3F3: 579.2457, found: 580.2529 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.13 / 8.7 (brs + brs, 2H), 8.17 / 8.12 (s / s, 1H), 8.05 / 8.04 (d / d, 2H), 7.94 / 7.93 (d / d, 2H), 7.68 / 7.66 (d / d, 1H), 7.35-7.12 (m, 5H), 6.79 / 6.75 (d / d, 1H), 4.88 (s, 1H), 4.2-0.59 (m, 16H), 3.48 / 3.42 (m / m, 1H ), 3.22 (m, 1H).

Synthesis of R3ap: 7- [4- (difluoromethyl) phenyl] -3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with the Synthesis compound R2ap as a reagent, the Synthesis compound R3ap was prepared as the HCl salt. MCBP: calculated for C ₃₁ H33F ₂ N ₅ O3: 561.2551, found: 562.2636 [(M + H) form].

1H NMR (500 MHz, MSM-d6) δ ppm. 9.11 / 8.68 (brd + brq, 2H), 8.14 / 8.09 (s, 1H), 7.93 / 7.91 (m, 2H), 7.76 / 7.75 (m, 2H), 7.62 / 7.6 (d, 1H), 7.34-7.12 (m, 5H), 7.13 (t, 1H), 6.77 / 6.73 (d, 1H), 4.87 (s, 1H), 4.11-2.61 (m, 12H), 1.93-0.64 (m, 6H).

Synthesis of R3aq: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -7 [4- (hydroxymethyl) phenyl] -3H, 4H , 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with Synthesis compound R2aq as reagent, Synthesis compound R3aq was prepared as the HCl salt. MCBP: calculated for C ₃₁ H ₃₅ N ₅ O ₄ : 541.2689, found: 542.2787 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6) δ ppm. 9.2 / 8.74 (brd + brq, 1 + 1H), 8.11 / 8.06 (s / s, 1H), 7.67 / 7.65 (dm / dm, 2H), 7.51 / 7.48 (d / d, 1H), 7.47 (m, 2H), 7.34-7.1 (m, 5H), 6.72 / 6.68 (d / d, 1H), 4.56 (s, 2H), 4.08-0.61 (m, 16H), 3.48 / 3.43 (m / m, 1H), 3.21 (m, 1H). 13C-NMR (125 MHz, MSM-d6) δ ppm. 148.3 / 148.2, 127.8, 124.4, 124.2, 103.8, 62.8, 42.6 / 42.5, 41 / 40.6.

Synthesis of R3ar: 7- (4-chlorophenyl) -3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -3H, 4H, 7H -pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with the Synthesis compound R2ar as a reagent, the Synthesis compound R3ar was obtained as the HCl salt. MCBP: calculated for C ₃₀ H ₃₂ ClN ₅ O ₃ : 545.2194, found: 546.2288 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.38 / 8.87 (brs, 2H), 8.24-6.62 (m, 12H), 4.13-0.58 (m, 18H).

Synthesis of R3as: 7- (4-fluorophenyl) -3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -3H, 4H, 7H -pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with the Synthesis compound R2as as a reagent, the Synthesis compound R3as was prepared as the HCl salt. MCBP: calculated for C ₃₀ H ₃₂ N ₅ O ₃ F: 529.2489, found: 530.2563 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.05 / 8.64 (brd + brq, 2H), 8.11 / 8.06 (s, 1H), 7.76 / 7.75 (m, 2H), 7.52 / 7.5 (d, 1H), 7.41 / 7.4 (m, 2H), 7.34-7.13 (m, 5H), 6.73 / 6.69 (d, 1H), 4.84 (brs, 1H), 4.1-2.65 (m, 12H), 1.95-58 037563

0.63 (m, 6H).

Synthesis of R3at: 7- [4- (dimethylamino) phenyl] -3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with the Synthesis compound R2at as a reagent, the Synthesis compound R3at was prepared as the HCl salt. MCBP: calculated for C ₃₂ H ₃₈ N ₆ O ₃ : 554.3005, found: 555.3076 [(M + H) + form].

1H NMR (500 MHz, MSM-d6) δ ppm. 9.15 / 8.71 (brd + brq, 2H), 8.07 / 8.02 (s, 1H), 7.52 (brm, 2H), 7.41 / 7.38 (d, 1H), 7.33-7.11 (m, 5H), 6.99 (brs, 2H ), 6.68 / 6.64 (d, 1H), 4.07-2.62 (m, 12H), 2.99 (s, 6H), 1.93-0.64 (m, 6H).

Synthesis of R3ax: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -7 (4-methoxyphenyl) -3H, 4H, 7H- pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with Synthesis compound R2ax as reagent, Synthesis compound R3ax was prepared as the HCl salt. MCBP: calculated for C ₃ iH ₃₅ N ₅ O ₄ : 541.2689, found: 542.2782 [(M + H) ⁺ form].

Ή NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.2 / 8.74 (brd + brq, 2H), 8.09 / 8.04 (s, 1H), 7.63-7.55 (m, 2H), 7.44 / 7.42 (d, 1H), 7.33-7.12 (m, 5H), 7.12-7.06 (m, 2H), 6.69 / 6.65 (d, 1H), 4.85 (brs, 1H), 4.07-2.63 (m, 12H), 3.82 / 3.75 (s, 3H), 1.95-0.61 (m, 6H).

Synthesis of R3ay: 3 - ({4-hydroxy- 1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -7 [4- (trifluoromethoxy) phenyl] -3H, 4H , 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with Synthesis compound R2ay as reagent, Synthesis compound R3ay was prepared as the HCl salt. MCBP: calculated for C ₃₁ H ₃₂ N ₅ O ₄ F ₃ : 595.2407, found: 596.2494 [(M + H) ⁺ form].

1H NMR (400 MHz, MSM-d6) δ ppm. 9.08 / 8.66 (brs, 2H), 8.13 / 8.08 (s, 1H), 7.93-7.53 (m, 4H), 7.59 / 7.57 (d, 1H), 7.36-7.12 (m, 5H), 6.75 / 6.72 (d , 1H), 4.86 (s, 1H), 4.14-2.59 (m, 12H), 1.95-0.63 (m, 6H).

Synthesis of R3az: 7- [4- (benzyloxy) phenyl] -3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidin-4-carbonyl] piperidin-4-yl} methyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with the Synthesis compound R2az as a reagent, the Synthesis compound R3az was prepared as the HCl salt. MCBP: calculated for C ₃₇ H ₃ 9N ₅ O ₄ : 617.3002, found: 618.3083 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.12 / 8.68 (brs + brs, 2H), 8.08 / 8.03 (s, 1H), 7.6 / 7.58 (m, 2H), 7.517.11 (m, 10H), 7.45 / 7.42 (d, 1H), 7.17 (m , 2H), 6.69 / 6.65 (d, 1H), 5.18 (s, 2H), 4.85 (s, 1H), 4.1-2.6 (m, 12H), 1.95-0.61 (m, 6H).

Synthesis of R3ba: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -7 (5-methylthiophen-2-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from the Synthesis compound R2ba as a reagent, the Synthesis compound R3ba was obtained as the HCl salt. MCBP calculated for C ₂₉ H ₃₃ N ₅ O ₃ S: 531.2304, found: 532.2361 [(M + H) form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.05 / 8.68 (brs + brs, 2H), 8.14 / 8.1 (s, 1H), 7.53 / 7.51 (d, 1H), 7.33-7.11 (m, 5H), 7.16 / 7.15 (d, 1H), 6.77 / 6.76 (m, 1H), 6.71 / 6.67 (d, 1H), 4.88 / 4.87 (s, 1H), 4.09-2.62 (m, 12H), 2.46 (d, 3H), 1.92-0.62 (m, 6H).

Synthesis of R3bb: 7- (5-chlorothiophen-2-yl) -3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -3H , 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with the Synthesis compound R2bb as a reagent, the Synthesis compound R3bb was prepared as the HCl salt. MCBP: calculated for C ₂₈ H ₃₀ ClN ₅ O ₃ S: 551.1758, found: 552.1844 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6) δ ppm. 9.06 / 8.76 (brs + brs, 2H), 8.21 / 8.16 (s / s, 1H), 7.71 / 7.68 (d / d, 1H), 7.32 / 7.31 (d / d, 1H), 7.32-7.12 (m, 5H), 7.15 / 7.14 (d / d, 1H), 6.76 / 6.73 (d / d, 1H), 4.1-0.58 (m, 16H), 3.47 / 3.41 (m / m, 1H), 3.21 (m, 1H ). 13C-NMR (125 MHz, MSM-d6) δ ppm. 149.2 / 149.1, 125.6, 123.6, 117.6 / 117.5, 104.9, 42.6 / 42.5, 41 / 40.6.

Synthesis of R3bc: 7- (2,3-dihydro-1,4-benzodioxin-6-yl) -3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine4-carbonyl] piperidine-4- yl} methyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from the Synthesis compound R2bc as a reagent, the Synthesis compound R3bc was obtained as the HCl salt. MCBP calculated for C ₃₂ H ₃₅ N ₅ O ₅ : 569.2638, found: 570.2709 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.42 / 8.89 (brd + brq, 2H), 8.11 / 8.06 (s, 1H), 7.44 / 7.41 (d, 1H), 7.337.11 (m, 5H), 7.23 / 7.22 (d, 1H), 7.15 / 7.13 (dd, 1H), 7 / 6.99 (d, 1H), 6.67 / 6.63 (d, 1H), 4.35-4.26 (m, 4H), 4.092.62 (m, 12H), 1.94-0.61 (m, 6H) ...

Synthesis of R3bd: 7- (2H-1,3-benzodioxol-5-yl) -3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidin-4-carbonyl] piperidin-4-yl} methyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from the Synthesis compound R2bd as a reagent, the Synthesis compound R3bd was obtained as the HCl salt. MCBP: calculated for C ₃₁ H ₃₃ N ₅ O ₅ : 555.2482, found: 570.2709

- 59 037563

[(M + H) + form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.21 / 8.78 (brs + brs, 2H), 8.1 / 8.05 (s, 1H), 7.44 / 7.42 (d, 1H), 7.35-7.11 (m, 5H), 7.3 / 7.28 (d, 1H), 7.14 / 7.13 (dd, 1H), 7.07 / 7.06 (d, 1H), 6.68 / 6.64 (d, 1H), 6.12 (s, 2H), 4.87 (s, 1H), 4.09-2.62 (m, 12H), 1.95-0.62 (m, 6H).

Synthesis of R3be: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -7 (naphthalen-2-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with the Synthesis compound R2be as a reagent, the Synthesis compound R3be was prepared as the HCl salt. MCBP calculated for C34H35N5O3: 561.2740, found: 562.2831 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6) δ ppm. 9.16 / 8.72 (brd + brq, 2H), 8.3-7.54 (m, 7 H), 8.16 / 8.11 (s, 1H), 7.67 / 7.65 (d, 1H), 7.35-7.13 (m, 5H), 6.79 / 6.75 (d, 1H), 4.89 (brs, 1H), 4.12-2.65 (m, 12H), 1.96-0.65 (m, 6H).

Synthesis of R3bf: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidin-4-carbonyl] piperidin-4-yl} methyl) -7 (3-methylphenyl) -3H, 4H, 7H- pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from Synthesis compound R2bf as a reagent, Synthesis compound R3bf was obtained. MCBP calculated for C ₃ iH ₃₅ N ₅ O ₃ : 525.2740, found: 526.2825 [(M + H) + form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.13 / 8.69 (brq + brd, 2H), 8.11 / 8.06 (s, 1H), 7.57-7.11 (m, 10H), 6.71 / 6.67 (d, 1H), 4.2-2.62 (m, 12H), 1.94-0.59 (m, 6H).

Synthesis of R3bg: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -7 [3 - (trifluoromethyl) phenyl] -3H, 4H , 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from the Synthesis compound R2bg as a reagent, the Synthesis compound R3bg was obtained as the HCl salt. MCBP: calculated for C ₃₁ H ₃₂ F ₃ N5O ₃ : 579.2457, found: 580.2509 [(M + H) ⁺ form].

1H NMR (400 MHz, MSM-d6) δ ppm. 9.2 / 8.74 (brd + brq, 2H), 8.19 / 8.17 (m, 1H), 8.17 / 8.13 (s, 1H), 8.09 / 8.07 (dm, 1H), 7.86-7.74 (m, 2H), 7.7 / 7.67 (d, 1H), 7.35-7.11 (m, 5H), 6.78 / 6.74 (d, 1H), 4.78 (brs, 1H), 4.11-2.6 (m, 12H), 1.94-0.62 (m, 6H).

Synthesis of R3bh: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -7 {3 - [(4-methylpiperazin-1-yl ) methyl] phenyl} -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with the Synthesis compound R2bh as a reagent, the Synthesis compound R3bh was obtained as the HCl salt. MCBP: calculated for C36H45N7O3: 623.3584, found: 624.3656 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6) δ ppm. 12.37 / 11.6 (brs, 2H), 9.33 / 8.83 (brd + brq, 2H), 8.18 / 8.12 (s, 1H), 8.04-7.5 (m, 5H), 7.35-7.13 (m, 5H), 6.75 / 6.72 (d, 1H), 4.6-2.6 (m, 22H), 2.79 (s, 3H), 1.98-0.66 (m, 6H).

Synthesis of R3bi: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -7 [3- (hydroxymethyl) phenyl] -3H, 4H , 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with the Synthesis compound R2bi as a reagent, the Synthesis compound R3bi was prepared as the HCl salt. MCBP: calculated for C ₃₁ H ₃ 5N5O ₄ : 541.2689, found: 542.2769 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6) δ ppm. 8.98 / 8.72 (brs + brs, 2H), 8.1 / 8.05 (s / s, 1H), 7.69-7.33 (m, 4H), 7.51 / 7.48 (d / d, 1H), 7.33-7.11 (m, 5H) , 6.73 / 6.69 (d / d, 1H), 5.36 (t, 1H), 4.59 (d, 2H), 4.15-0.61 (m, 16H), 3.48 / 3.42 (m / m, 1H), 3.22 (m, 1H).

Synthesis of R3bj: 7- (3-chlorophenyl) -3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -3H, 4H, 7H -pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from the Synthesis compound R2bj as a reagent, the Synthesis compound R3bj was obtained as the HCl salt. MCBP: calculated for C ₃₀ H ₃₂ N ₅ O ₃ Cl: 545.2194, found: 546.2277 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6) δ ppm. 9.17 / 8.72 (brd + brq, 2H), 8.15 / 8.11 (s, 1H), 7.94-7.45 (m, 4H), 7.63 / 7.6 (d, 1H), 7.34-7.12 (m, 5H), 6.75 / 6.71 (d, 1H), 4.88 (brs, 1H), 4.13-2.62 (m, 12H), 1.95-0.62 (m, 6H).

Synthesis of R3bk: 7- (3-fluorophenyl) -3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidin-4-carbonyl] piperidin-4-yl} methyl) -3H, 4H, 7H -pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from the Synthesis compound R2bk as a reagent, the Synthesis compound R3bk was obtained. MCBP: calculated for C ₃₀ H ₃₂ FN5O ₃ : 529.2489, found: 530.2571 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9 / 8.61 (brd + brq, 1 + 1H), 8.14 / 8.09 (s / s, 1H), 7.76-7.23 (m, 4H), 7.62 / 7.6 (d / d, 1H), 7.34-7.13 (m, 5H), 6.75 / 6.71 (d / d, 1H), 4.14-0.6 (m, 16H), 3.47 / 3.42 (m / m, 1H), 3.2 (m, 1H).

13C-NMR (125 MHz, MSM-d ₆ ) δ ppm. 148.6 / 148.5, 124.2, 104.3 / 104.2, 42.6 / 42.5, 41 / 40.6.

Synthesis of R3bl: 7- [3 - (dimethylamino) phenyl] -3 - ({4-hydroxy- 1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from the Synthesis compound R2bl as a reagent, the Synthesis compound R3bl was obtained as the HCl salt. MCBP: calculated for C ₃₂ H ₃₈ N ₆ O ₃ : 554.3005, found: 555.3086 [(M + H) ⁺ form].

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Ή NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.23 / 8.76 (brd + brq, 1 + 1H), 8.1 / 8.05 (s / s, 1H), 7.51 / 7.49 (d / d, 1H),

7.37 (brt, 1H), 7.33-7.13 (m, 5H), 7.18-6.76 (brd, 3H), 6.7 / 6.66 (d / d, 1H), 4.09-0.61 (m, 16H), 3.47 / 3.43 (m / m,

1H), 3.22 (m, 1H), 2.98 (s, 6H). ¹³ C-NMR (125 MHz, MSM-d6) δ ppm. 148.2 / 148.1, 130.2, 124.7, 103.6 / 103.5,

42.6 / 42.5, 41.1, 41 / 40.6.

Synthesis of R3bm: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -7 [3 - (morpholin-4-yl) phenyl] -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from the Synthesis compound R2bm as a reagent, the Synthesis compound R3bm was obtained as the HCl salt. MCBP calculated for C ₃₄ H ₄₀ N ₆ O ₄ : 596.3111, found: 597.3187 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6) δ ppm. 9.22 / 8.75 (brd + brq, 1 + 1H), 8.1 / 8.06 (s / s, 1H), 7.52 / 7.49 (d / d, 1H), 7.38 / 7.37 (t / t, 1H), 7.33-7.13 ( m, 5H), 7.23 / 7.21 (brs / brs, 1H), 7.14 / 7.12 (d / d, 1H), 7 (brd., 1H), 6.7 / 6.66 (d / d, 1H), 4.09-0.62 ( m, 16H), 3.76 (m, 4H), 3.47 / 3.42 (m / m, 1H), 3.22 (m, 1H), 3.19 (m, 4H). ¹³ C-NMR (125 MHz, MSM-d6) δ ppm. 148.2 / 148.1, 130.1, 124.7 / 124.6, 115.3, 114.2, 111.3 / 111.2, 103.6 / 103.5, 66.5, 48.7, 42.6, 41 / 40.5.

Synthesis of R3bo: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -7 (3-methoxyphenyl) -3H, 4H, 7H- pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with Synthesis compound R2bo as reagent, Synthesis compound R3bo was prepared as the HCl salt. MCBP: calculated for C ₃ iH ₃₅ N ₅ O ₄ : 541.2689, found: 542.2762 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.21 / 8.75 (brd + brq, 2H), 8.12 / 8.01 (s, 1H), 7.56 / 7.54 (d, 1H), 7.496.96 (m, 9H), 6.72 / 6.68 (d, 1H), 4.84 (brs , 1H), 4.16-2.62 (m, 12H), 1.95-0.63 (m, 6H).

Synthesis of R3bp: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidin-4-carbonyl] piperidin-4-yl} methyl) -7 [3 - (trifluoromethoxy) phenyl] -3H, 4H , 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from the Synthesis compound R2bp as a reagent, the Synthesis compound R3bp was obtained as the HCl salt. MCBP: calculated for C ₃₁ H ₃₂ N ₅ O ₄ F ₃ : 595.2407, found: 596.2491 [(M + H) ⁺ form].

1H NMR (400 MHz, MSM-d6) δ ppm. 8.87 (brs, 2H), 8.16 / 8.11 (s, 1H), 7.9 / 7.88 (brs, 1H), 7.85 / 7.84 (dm, 1H), 1.111.69 (t, 1H), 7.66 / 7.63 (d, 1H ), 7.43 (dm, 1H), 7.34-7.11 (m, 5H), 6.77 / 6.73 (d, 1H), 4.87 / 4.86 (s, 1H), 4.12-2.62 (m, 12H), 1.97-0.61 (m , 6H).

Synthesis of R3bq: 7- [3- (benzyloxy) phenyl] -3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidin-4-carbonyl] piperidin-4-yl} methyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from the Synthesis compound R2bq as a reagent, the Synthesis compound R3bq was obtained as the HCl salt. MCBP: calculated for C ₃₇ H ₃ 9N ₅ O ₄ : 617.3002, found: 618.3051 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6) δ ppm. 9.24 / 8.77 (brd + brq, 2H), 8.12 / 8.08 (s, 1H), 7.56 / 7.53 (d, 1H), 7.517.03 (m, 14H), 6.72 / 6.68 (d, 1H), 5.18 (s , 2H), 4.09-2.63 (m, 12H), 1.94-0.62 (m, 6H).

Synthesis of R3br: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -7 (6-methylpyridin-2-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with Synthesis compound R2br as reagent, Synthesis compound R3br was prepared as the HCl salt. MCBP calculated for C ₃₀ H ₃₄ N ₆ O ₃ : 526.2692, found: 527.2764 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6) δ ppm. 9.43 / 8.91 (brq + brd, 2H), 8.26 / 8.25 (dm, 1H), 8.25 / 8.2 (s, 1H), 7.92 / 7.9 (d, 1H), 7.92 (m, 1H), 7.34-7.11 (m , 5H), 7.26 (m, 1H), 6.73 / 6.69 (d, 1H), 4.12-2.63 (m, 12H), 2.53 / 2.52 (s, 3H), 1.95-0.64 (m, 6H).

Synthesis of R3bs: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -7 (6-methoxypyridin-2-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with the Synthesis compound R2bs as a reagent, the Synthesis compound R3bs was prepared as the HCl salt. MCBP: calculated for C ₃₀ H ₃₄ N ₆ O ₄ : 542.2642, found: 543.2698 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6) δ ppm. 8.95 (brs, 2H), 8.8 / 6.81 (dd, 1H), 8.23 / 8.18 (s, 1H), 8.08 / 8.07 (dd, 1H), 8 / 7.98 (d, 1H), 7.93 / 7.92 (t, 1H ), 7.35-7.1 (m, 5H), 6.75 / 6.72 (d, 1H), 4.14-2.62 (m, 12H), 3.95 / 3.94 (s, 3H), 1.96-0.62 (m, 6H).

Synthesis of R3bt: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -7 (naphthalen-1-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from the Synthesis compound R2bt as a reagent, the Synthesis compound R3bt was obtained as the HCl salt. MCBP: calculated for C ₃₄ H ₃₅ N ₅ O ₃ : 561.2740, found: 562.2827 [(M + H) form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.28 / 8.8 (brq + brd, 2H), 8.17-6.74 (m, 15H), 4.82 (brs, 1H), 4.26-0.57 (m, 18H).

Synthesis of R3bu: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -7phenyl-3H, 4H, 7H-pyrrolo [2,3 -d] pyrimidin-4-one.

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Using General Procedure 5, starting from the Synthesis compound R2bu as a reagent, the compound

The synthesis of R3bu was obtained as the HCl salt. MCBP: calculated for C ₃₀ H ₃₃ N ₅ O ₃ : 511.2583, found: 512.2675

[(M + H) shape].

Ή NMR (500 MHz, MSM-de) δ ppm 9.1 / 8.67 (brd + brd, 2H), 8.11 / 8.06 (s / s, 1H), 7.75-7.38 (m, 5H), 7.54 / 7.52 (d / d, 1H), 7.34-7.12 (m, 5H) , 6.73 / 6.69 (d / d, 1H), 4.86 (s, 1H), 4.13-0.62 (m, 16H), 3.47 / 3.42 (m / m, 1H), 3.22 (m, 1H). 13C-NMR (125 MHz, MSM-d6) δ ppm. 148.3 / 148.2, 124.5 / 124.4, 103.9 / 103.8, 42.6 / 42.5, 41 / 40.6.

Synthesis of R3ca: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -7 (pyridin-2-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from the Synthesis compound R2ca as a reagent, the Synthesis compound R3ca was obtained as the HCl salt. MCBP: calculated for C ₂₉ H ₃₂ N ₆ O ₃ : 512.2536, found: 513.2612 [(M + H) form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.07 / 8.65 (brd + brq, 2H), 8.56 / 8.55 (dm, 1H), 8.48 / 8.46 (dm, 1H), 8.22 / 8.17 (s, 1H), 8.05 (m, 1H), 7.94 / 7.92 (d , 1H), 7.41 (m, 1H), 7.33-7.12 (m, 5H), 6.75 / 6.71 (d, 1H), 4.9 (s, 1H), 4.15-2.63 (m, 12H), 1.92-0.65 (m , 6H).

Synthesis of R3cb: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidin-4-carbonyl] piperidin-4-yl} methyl) -7 (pyridin-3-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from the Synthesis compound R2cb as a reagent, the Synthesis compound R3cb was obtained. MCBP: calculated for C ₂₉ H ₃₂ N ₆ O ₃ : 512.2536, found: 513.261 [(M + H) form].

¹ H NMR (500 MHz, MSM-d6) δ ppm. 9.35 / 8.85 (brd + brq, 1 + 1H), 9.1 / 9.09 (d / d, 1H), 8.68 (dd, 1H), 8.39 (m, 1H), 8.2 / 8.15 (s / s, 1H), 7.75 (dd, 1H), 7.69 / 7.67 (d / d, 1H), 7.34-7.16 (m, 5H), 6.81 / 6.77 (d / d, 1H), 4.1-0.6 (m, 16H), 3.49 / 3.43 ( m / m, 1H), 3.23 (m, 1H). 13C-NMR (500 MHz, MSM-d6) δ ppm. 148.9 / 148.8, 146.5, 143.4, 133.6 / 133.5, 125.4, 124, 104.8 / 104.7, 42.6 / 42.4, 41 / 40.6.

Synthesis of R3cc: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -7 (thiophen-2-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from the Synthesis compound R2cc as a reagent, the Synthesis compound R3cc was obtained as the HCl salt. MCBP calculated for C ₂₈ H ₃₁ N ₅ O ₃ S: 517.2148, found: 518.2231 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.15 / 8.7 (brd + brq, 1 + 1H), 8.18 / 8.13 (s / s, 1H), 7.62 / 7.59 (d / d, 1H), 7.45 / 7.44 (dd, 1H), 7.4 / 7.39 (d / d, 1H), 7.32-7.11 (m, 5H), 7.09 / 7.08 (dd, 1H), 6.74 / 6.7 (d / d, 1H), 4.89 (brs, 1H), 4.1-0.6 (m, 16H), 3.47 / 3.42 (m / m, 1H), 3.21 (m, 1H). 13C-NMR (125 MHz, MSM-d ₆ ) δ ppm. 148.9 / 148.8, 126.1, 124.6, 122.9, 119.3 / 119.2, 104.5 / 104.4, 42.6 / 42.5, 41 / 40.6.

Synthesis of R3cd: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -7 (pyridin-4-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from Synthesis compound R2cd as a reagent, Synthesis compound R3cd was prepared. MCBP: calculated for C ₂₉ H ₃₂ N ₆ O ₃ : 512.2536, found: 513.2609 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6) δ ppm. 9.46 / 8.94 (brs + brq, 1 + 1H), 9 (dm, 2H), 8.74 (m, 2H), 8.4 / 8.36 (s / s, 1H), 8.05 / 8.03 (d / d, 1H), 7.38 -7.17 (m, 5H), 6.95 / 6.92 (d / d, 1H), 4.16-0.56 (m, 16H), 3.5 / 3.44 (m / m, 1H), 3.24 (m, 1H). 13C-NMR (500 MHz, MSM-d6) δ ppm. 149.8, 144.4, 123.2 / 123.1, 117.8, 107.4 / 107.3, 42.6 / 42.4, 41.1 / 40.6

Synthesis of R3cf: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidin-4-carbonyl] piperidin-4-yl} methyl) -7 (thiophen-3-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from the Synthesis compound R2cf as a reagent, the Synthesis compound R3cf was obtained as the HCl salt. MCBP calculated for C ₂₈ H ₃₁ N ₅ O ₃ S: 517.2148, found: 518.2233 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.29 / 8.8 (brd + brq, 2H), 8.17 / 8.12 (s, 1H), 7.97-7.66 (m, 3H), 7.62 / 7.6 (d, 1H), 7.33-7.11 (m, 5H), 6.71 / 6.67 (d, 1H), 4.91 (brs, 1H), 4.12-2.63 (m, 12H), 1.94-0.63 (m, 6H).

Synthesis of R3cg: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidin-4-carbonyl] piperidin-4-yl} methyl) -7 (1-methyl-1H-imidazol-4-yl ) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with the Synthesis compound R2cg as a reagent, the Synthesis compound R3cg was obtained as the HCl salt. MCBP: calculated for C ₂₈ H ₃₃ N ₇ O ₃ : 515.2645, found: 516.2728 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6) δ ppm. 9.3 / 8.81 (brq + brd), 8.19 / 8.14 (s, 1H), 7.85 (brs, 1H), 7.68 (brs, 1H), 7.6 / 7.57 (d, 1H), 7.33-7.11 (m, 5H), 6.68 / 6.64 (brs, 1H), 4.14-2.63 (brs, 12H), 3.77 (s, 3H), 1.95-0.63 (m, 6H).

Synthesis of R3ch: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidin-4-carbonyl] piperidin-4-yl} methyl) -7 (1-methyl-1H-pyrazol-4-yl ) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from the Synthesis compound R2ch as a reagent, the Synthesis compound R3ch was obtained as the HCl salt. MCBP calculated for C ₂₈ H ₃₃ N ₇ O ₃ : 515.2645, found: 516.2716 [(M + H) ⁺ form].

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Ή NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.25 / 8.78 (brd + brq., 2H), 8.3 / 8.29 (s / s, 1H), 8.15 / 8.1 (s / s, 1H),

7.94 / 7.92 (d / d, 1H), 7.47 / 7.44 (d / d, 1H), 7.33-7.11 (m, 5H), 6.68 / 6.64 (d / d, 1H), 4.15-0.6 (m, 16H) , 3.9 (s, 3H),

3.48 / 3.42 (m / m, 1H), 3.22 (m, 1H).

Synthesis of R3ci: 7- [1- (difluoromethyl) -1H-pyrazol-4-yl] -3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4carbonyl] piperidin-4-yl} methyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from the Synthesis compound R2ci as a reagent, the Synthesis compound R3ci was prepared. MCBP: calculated for C ₂₈ H ₃₁ F ₂ N ₇ O ₃ : 551.2457, found: 552.254 [(M + H) + form].

1H NMR (500 MHz, MSM-d6) δ ppm. 9.2 / 8.78 (brs + brs, 2H), 8.87 / 8.85 (d, 1H), 8.43 / 8.41 (d, 1H), 8.2 / 8.15 (s, 1H), 7.92 (t, 1H), 7.61 / 7.59 (d , 1H), 7.34-7.13 (m, 5H), 6.74 / 6.7 (d, 1H), 4.91 (s, 1H), 4.1-2.63 (m, 12H), 1.92-0.63 (m, 6H).

Synthesis of R3cj: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidin-4-carbonyl] piperidin-4-yl} methyl) -7 (pyrimidin-2-yl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from the Synthesis compound R2cj as a reagent, the Synthesis compound R3cj was obtained as the HCl salt. MCBP: calculated for C ₂₈ H ₃ iN ₇ O ₃ : 513.2488, found: 257.6326 [(M + 2H) ²⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.24 / 8.77 (brd + brq, 2H), 8.96 / 8.95 (brd, 1H), 8.18 / 8.13 (brs, 1H), 7.87 / 7.79 (d, 1H), 7.55 (t, 1H), 7.34-7.13 (m , 5H), 6.76 / 6.72 (d, 1H), 4.87 (brs, 1H), 4.13-2.61 (m, 12H), 1.930.63 (m, 6H).

Synthesis of R3ck: 3 - ({4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] piperidin-4-yl} methyl) -7 (1,3-thiazol-2-yl) - 3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with the Synthesis compound R2ck as a reagent, the Synthesis compound R3ck was prepared as the HCl salt. MCBP: calculated for C ₂₇ H ₃₀ N ₆ O ₃ S: 518.2100, found: 519.2181 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.3 / 8.81 (brd / brq, 2H), 8.35 / 8.31 (s, 1H), 7.91 / 7.89 (d, 1H), 7.7 / 7.69 (d, 1H), 7.65 / 7.64 (d, 1H), 7.33-7.12 (m, 5H), 6.81 / 6.77 (d, 1H), 4.14-2.61 (m, 12H), 1.95-0.6 (m, 6H).

Synthesis of R3cn: 3 - [[4-hydroxy-1 - [(3S, 4S) -3-phenylpiperidin-4-carbonyl] -4-piperidyl] methyl] pyrido [3,2-d] pyrimidin-4-one.

Using General Procedure 5, starting from 3H-pyrido [3,2-d] pyrimidin-4-one and tert-butyl (3S, 4S) -4 (1-oxa-6-azaspiro [2.5] oct-6-ylcarbonyl) Β-3-phenylpiperidine-1-carboxylate (in place of the Synthesis compound R1f) as reagents, the Synthesis compound R3cn was obtained as the HCl salt. MCBP: calculated for C ₂₅ H ₂₉ N ₅ O ₃ : 447.227, found: 448.2365 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6) δ ppm. 9.34 / 8.83 (brs / brd, 2H), 8.83 (brm, 1H), 8.34 / 8.30 (s / s, 1H), 8.14 / 8.12 (d / d, 1H), 7.40-7.09 (m, 5H), aliphatic protons: 4.13-0.52 (8xCH ₂ ), 3.49 / 3.42 (m, 1H), 3.21 (m, 1H). ¹³ C-NMR (500 MHz, MSM-d ₆ ) δ ppm. 150.3 / 150.2, 149.8, 136.1, 129.3, 42.6 / 42.4, 41.0 / 40.5.

Synthesis of R3co: 3 - [[4-hydroxy-1 - [(3R, 4R) -3-phenylpiperugin-4-carbonyl] -4-piperidyl] methyl] pyrido [3,2-d] pyrimidin-4-one.

Using General Procedure 5, starting with 3H-purido [3,2-d] pyrimidin-4-one as reagent, Synthesis compound R3co was prepared as the HCl salt. MCBP: calculated for C ₂₅ H ₂₉ N ₅ O ₃ : 447.227, found: 448.2365 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.34, 8.83 (brs + brs, 2H), 8.83 (brs, 1H), 8.34 / 8.30 (s / s, 1H), 8.14 / 8.12 (d / d, 1H), 7.40-7.09 (m, 5H), aliphatic protons: 4.13-0.52 (8xCH ₂ ), 3.49 / 3.42 (m, 1H), 3.21 (m, 1H). ¹³ C-NMR (500 MHz, MSM-d ₆ ) δ ppm. 150.3 / 150.2, 149.8, 136.1, 129.3, 42.6 / 42.4, 41.0 / 40.5.

Synthesis of R3cp: 3 - [[4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] thieno [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting with 3H-thieno [2,3-d] pyrimidin-4-one as a reagent, the Synthesis compound R3cp was prepared as the HCl salt. MCBP calculated for C ₂₄ H ₂₈ N ₄ O ₃ S: 452.1882, found: 453.1933 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.23 / 8.76 (brs / brm, 2H), 8.83 (brs, 1H), 8.26 / 8.21 (s / s, 1H), 7.61 / 7.59 (d / d, 1H), 7.43 / 7.39 (d / d, 1H) 7.34-7.15 (m, 5H) 4.93 / 4.92 (s / s, 1H) 4.04, 3.93 / 3.75 (d + d / s, 2H) 4.00-2.60 (m, 4H) 3.48 / 3.42 (m / m, 1H) 3.41-2.98 (m, 2H) 3.33-3.00 (m, 2H) 3.21 (m, 1H) 1.94-1.80 (m, 2H) 1.51-0.57 (m, 4H). ¹³ C-NMR (500 MHz, MSM-d6) δ ppm. 124.8, 122.5 / 122.4, 47.7 / 47.2, 42.7, 42.6 / 42.5, 41.1 / 40.4, 26.6 / 26.4.

Synthesis of R3cq: 6-chloro-3 - [[4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] pyrido [3,2-d] pyrimidine-4 -is he.

Using General Procedure 5, starting with 6-chloro-3H-pyrido [3,2-d] pyrimidin-4-one as reagent, the Synthesis compound R3cq was prepared as the HCl salt. MCBP: calculated for C ₂₅ H ₂₈ ClN ₅ O ₃ : 481.1881, found: 482.1949 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6) δ ppm. 9.13, 8.69 (brs + brm, 2H), 8.33 / 8.28 (s / s, 1H), 8.18 / 8.17 (d / d, 1H), 7.93 / 7.91 (d / d, 1H), 7.38-7.19 (m, 5H), 4.09 (brm, 1H), 4.05, 3.97 / 3.75 (d + d / s, 2H), 4.00-2.61 (m, 4H), 3.402.99 (brm, 4H), 3.48 / 3.40 (m / m , 1H), 3.22 (m, 1H) 1.95-1.80 (m, 2H), 1.52-0.52 (m, 4H). ¹³ C-NMR (125 MHz, MSM-d ₆ ) δ ppm. 150.8 / 150.7, 139.9, 130.4, 42.6 / 42.5, 41.1 / 40.5.

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Synthesis of R3cr: 3 - [[4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidin-4-carbonyl] -4-piperidyl] methyl] -6methoxypyrido [3,2D] pyrimidin-4-one and

Synthesis of R3cs: 3 - [[4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -5Hpyrido [3,2-d] pyrimidine-4,6- dion.

Using General Procedure 5, starting with 6-methoxy-3H-pyrido [3,2-d] pyrimidin-4-one as reagent, Synthesis compound R3cr and Synthesis compound R3cs (by-product) were obtained as the HCl salt and separated with using chromatography.

Synthesis of R3cr: MCBP: calculated for C ₂₆ H ₃ iN ₅ O ₄ : 477.2376, found: 478.2458 [(M + H) + form].

Ή NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.17, 8.72 (brs + brm, 2H) 8.22 / 8.17 (s / s, 1H) 8.02 / 8.00 (d / d, 1H), 7.35-7.15 (m, 5H), 7.31 / 7.29 (d / d, 1H) , 4.06, 3.93 / 3.77, 3.74 (d + d / d + d, 2H), 4.00-2.60 (m, 4H), 3.99 / 3.96 (s / s, 3H), 3.48 / 3.42 (m, 1H), 3.34 -2.98 (m, 4H), 3.21 (m, 1H), 1.94-1.80 (m, 2H), 1.52-0.57 (m, 4H). ¹³ C-NMR (125 MHz, MSM-d ₆ ) δ ppm. 148.2 / 148.1, 139.5, 119.1, 54.2, 42.6 / 42.4, 41.1 / 40.5.

Synthesis of R3cs: MCBP: calculated for C25H29N5O4: 463.222, found: 464.2312 [(M + H) ⁺ form].

¹ H NMR (500 MHz, MSM-d6) δ ppm. 11.67 (vbrs, 1H), 9.11, 8.68 (brs + brs, 2H), 8.08 / 8.04 (s / s, 1H), 7.75 / 7.73 (d / d, 1H), 6.83 / 6.81 (d / d, 1H) , 7.36-7.18 (m, 5H), 4.89 (vbrs, 1H), 4.00-2-60 (m, 4H), 3.99, 3.93 / 3.74, 3.70 (d + d / d + d, 2H), 3.48 / 3.41 (m, 1H), 3.34-3.01 (m, 4H), 3.20 (m, 1H), 1.92-1.80 (m, 2H), 1.51-0.48 (m, 4H). ¹³ C-NMR (125 MHz, MSM-d6) δ ppm. 146.2 / 146.1, 140.3, 129.4, 42.6 / 42.5, 41.0 / 40.6.

Synthesis of R3ct: 6- (benzylamino) -3 - [[4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] pyrido [3,2-d] pyrimidine -4 -on.

Using General Procedure 5, starting from 6-chloro-3H-pyrido [3,2-d] pyrimidin-4-one as reagent without deprotection step, the resulting crude Boc-protected compound (0.76 mmol) and K2CO3 (1.51 mmol) was stirred in benzylamine (5 ml) at 120 ° C for 17 h. The reaction mixture was purified using preparative LC (on a C-18 Gemini-NX 5 μm column, 5 mM aqueous NH4HCO3-MeCN, gradient).

The resulting crude product (187 mg, 0.283 mmol) was stirred in an aqueous solution of HCl (1N, 3 ml, 3 mmol) and PDO (3 ml) at 70 ° C for 2 h. The reaction mixture was purified using preparative LC ( on a C-18 Gemini-NX column 5 μm, 5 mM aqueous NH4HCO ₃ -MeCN, gradient) to obtain the Synthesis compound R3ct in the form of an HCl salt. MCBP: calculated for C ₃₂ H ₃ 5N ₆ O ₃ : 552.2849, found: 277.1497 [(M + 2H) ²⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.37 / 8.86 (m / m, 2H), 8.31-7.12 (m, aromatic protons, 13 H), 4.78-0.49 (m, aliphatic protons, 20 H).

Synthesis of R3cu: 3 - [[4-hydroxy-1 - [(3R, 4R) -3-phenylπiperidine-4-carbonyl] -4-πiperidyl] methyl] -6 - [(4methoxyphenyl) methylamino] pyrido [3,2- d] pyrimidin-4-one.

Using General Procedure 5, starting from 6-chloro-3H-pyrido [3,2-d] pyrimidin-4-one as reagent without deprotection step, the resulting crude Boc-protected compound (0.76 mmol) and K2CO3 (1.51 mmol) was stirred in benzylamine (5 ml) at 120 ° C for 17 h. The reaction mixture was purified using preparative LC (on a C-18 Gemini-NX 5 μm column, 5 mM aqueous NH4HCO ₃ -MeCN, gradient).

The resulting crude product (187 mg, 0.283 mmol) was stirred in an aqueous solution of HCl (1N, 3 ml, 3 mmol) and PDO (3 ml) at 70 ° C for 2 h. The reaction mixture was purified using preparative LC ( on a C-18 Gemini-NX column 5 μm, 5 mM aqueous NH4HCO ₃ -MeCN, gradient) to obtain the Synthesis compound R3cu in the form of an HCl salt. MCBP: calculated for C ₃₃ H ₃₈ N ₆ O ₄ : 582.2955, found: 292.1552 [(M + 2H) ²⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.33 / 8.83 (brt / brd, 2H), 8.23 / 8.18 (s / s, 1H), 7.91 (vbrs, 1H), 7.35-7.15 (m, 5H), 7.34 (d / d, 2H), 7.27 (brm , 1H), 6.92 / 6.91 (d / d, 2H), 4.62 / 4.59 (s / s, 2H), 4.08-0.54 (m, aliphatic protons, 8H), 3.73 (s, 3H), 3.48 / 3.42 (m / m, 1H), 3.21 (m, 1H).

Synthesis of R3cv: 6 - [[4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidin-4-carbonyl] -4-piperidyl] methyl] -3phenyltriazolo [4,5-d] pyrimidin-7-one.

Using General Procedure 5, starting with 3-phenyl-6H-triazolo [4,5-d] pyrimidin-7-one as reagent, the Synthesis compound R3cv was prepared as the HCl salt. MCBP calculated for C ₂₈ H ₃₁ N7O ₃ : 513.2488, found: 514.2576 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6) δ ppm. 9.28 / 8.79 (brd + brq, 2H), 8.5 / 8.47 (s, 1H), 8.06-7.54 (m, 5H), 7.4-7.19 (m, 5H), 4.98 / 4.96 (brs, 1H), 4.17-2.6 (m, 12H), 1.96-0.53 (m, 6H).

Synthesis of R3cw: 1 - [[4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidin-4-carbonyl] -4-piperidyl] methyl] -9phenylpurin-6-one.

Using General Procedure 5, starting with 9-phenyl-1H-nurin-6-one as a reagent, the Synthesis compound R3cw was prepared as the HCl salt. MCBP: calculated for C ₂₉ H ₃₂ N ₆ O ₃ : 512.2536, found: 513.2616 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.25 / 8.77 (brd + brq, 2H), 8.52 / 8.5 (s, 1H), 8.28 / 8.23 (s, 1H), 7.82-7.46 (m, 5H), 7.37-7.18 (s, 5H), 4.91 (brs , 1H), 4.14-2.63 (m, 12H), 1.96-0.58 (m, 6H).

Synthesis of R3cx: 5 - [[4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -1- 64 037563 phenylpyrazolo [3,4-d] nupuMuguH- 4-OH.

Using General Procedure 5, starting with 1-phenyl-5H-pyrazolo [3,4-d] pyrimidin-4-one as reagent, the Synthesis compound R3cx was prepared as the HCl salt. MCBP: calculated for C ₂₉ H ₃₂ N ₆ O ₃ :

512.2536, found: 513.2627 [(M + H) + form].

Ή NMR (500 MHz, MSM-d6) δ ppm 9.22 / 8.76 (brs + brs, 2H), 8.39 / 8.36 (s, 1H), 8.34 / 8.3 (s, 1H), 8.09-7.38 (m, 5H), 7.36-7.16 (m, 5H), 4.94 / 4.93 (s, 1H), 4.12-2.59 (m, 12H), 1.95-0.58 (m, 6H).

Synthesis of R3cy: 7-bromo-3 - [[4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] pyrrolo [2,1-f] [1, 2,4] triazin-4-one.

Using General Procedure 5, starting with 7-bromo-3H-pyrrolo [2,1-f] [1,2,4] triazin-4-one as reagent, the Synthesis compound R3cy was prepared as the HCl salt. MCBP: calculated for C ₂₄ H ₂₈ BrN ₅ O ₃ : 513.1376, found: 514.1462 [(M + H) ⁺ form].

¹ H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.25 / 8.77 (brs + brs, 2H), 8.03 / 8 (s, 1H), 7.33-7.1 (m, 5H), 7.03 / 6.99 / 6.77 / 6.75 (d, 2H), 4.93 / 4.91 (s, 1H) , 4.02-2.61 (m, 12H), 1.94-0.5 (m, 6H). 13C-NMR (125 MHz, MSM-d ₆ ) δ ppm. 154, 120.9, 102.9.

Synthesis of R3cz: 6 - [[4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -3phenylisothiazolo [4,5-d] pyrimidin-7-one.

Using General Procedure 5, starting with 3-phenyl-6H-isothiazolo [4,5-d] pyrimidin-7-one as reagent, the Synthesis compound R3cz was prepared as the HCl salt. MCBP calculated for C ₂₉ H ₃₁ N ₅ O ₃ S: 529.2148, found: 530.2223 [(M + H) ⁺ form].

1H NMR (400 MHz, MSM-d6) δ ppm. 9.37 / 8.86 (brs + brs, 2H), 8.49 / 8.46 (s, 1H), 8.43 (m, 2H), 7.62-7.5 (m, 3H), 7.39-7.13 (m, 5H), 5.06 / 5.03 (s , 1H), 4.2-2.6 (m, 12H), 1.98-0.52 (m, 6H).

Synthesis of R3da: 3 - [[4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7phenylthieno [3,4-d] pyrimidin-4-one.

Using General Procedure 5, starting with 7-chloro-3H-thieno [3,4-d] pyrimidin-4-one as reagent without deprotection step, the resulting Boc-protected compound was reacted with phenylboronic acid using General Procedure 9. The resulting phenylated crude product was deprotected according to Step 2 of General Procedure 5 to give the Synthesis compound R3da as an HCl salt. MCBP calculated for C ₃₀ H ₃₂ N ₄ O ₃ S: 528.2195, found: 529.2265 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.14 / 8.7 (brq + brd, 2H), 8.51 / 8.47 (s, 1H), 8.05 / 8.04 (m, 2H), 8.03 / 7.98 (s, 1H), 7.52-7.33 (m, 3H), 7.32-7.1 (m, 5H), 4.9 / 4.88 (s, 1H), 4.02-2.61 (m, 12H), 1.93-0.58 (m, 6H). 13C-NMR (125 MHz, MSM-d ₆ ) δ ppm. 158, 143.5, 134, 127.4.

Synthesis of R3db: 3 - [[4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7phenyl-5H-pyrrolo [3,2-d] pyrimidine- 4th.

Using General Procedure 5, starting with 7-phenyl-3,5-dihydropyrrolo [3,2-d] pyrimidin-4-one as reagent, the Synthesis compound R3db was prepared as the HCl salt. MCBP: calculated for C ₃₀ H ₃₃ N ₅ O ₃ : 511.2583, found: 512.2647 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6) δ ppm. 12.35 / 12.3 (d, 1H), 9.26 / 8.79 (brs + brs, 2H), 8.1 / 8.05 (s, 1H), 8.1 / 8.08 (m, 2H), 7.92 / 7.9 (d, 1H), 7.43-7.08 (m, 8H), 4.92 / 4.91 (s, 1H), 4.07-2.62 (m, 12H), 1.97-0.63 (m, 6H).

Synthesis of R3dc: 7-chloro-3 - [[4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] thieno [3,4-d] pyrimidine-4 -is he.

Using General Procedure 5, starting with 7-chloro-3H-thieno [3,4-d] pyrimidin-4-one as reagent, the Synthesis compound R3dc was prepared as the HCl salt. MCBP: calculated for C ₂₄ H ₂₇ ClN ₄ O ₃ S: 486.1492, found: 487.1544 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.16 / 8.71 (brd + brq, 2H), 8.44 / 8.4 (s, 1H), 8.01 / 7.96 (s, 1H), 7.34-7.15 (m, 5H), 4.87 / 4.85 (s, 1H), 4-2.59 (m, 12H), 1.93-0.52 (m, 6H).

Synthesis of R3dd: 6 - [[4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidin-4-carbonyl] -4-piperidyl] methyl] -3phenylisoxazolo [4,5-d] pyrimidin-7-one.

Using General Procedure 5, starting with 3-phenyl-6H-isoxazolo [4,5-d] pyrimidin-7-one as a reagent, the Synthesis compound R3dd was prepared as the HCl salt. MCBP calculated for C ₂₉ H ₃₁ N ₅ O ₄ : 513.2376, found: 514.2451 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6) δ ppm. 9.13 / 8.76 (brs + brs, 2H), 8.44 / 8.4 (s, 1H), 8.33-8.26 (m, 2H), 7.677.59 (m, 3H), 7.39-7.18 (m, 5H), 4.99 / 4.97 (s, 1H), 4.19-2.62 (m, 12H), 1.95-0.52 (m, 6H).

Synthesis of R3de: 5 - [[4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -1- (4methoxyphenyl) pyrazolo [3,4-d] pyrimidine -4-he.

Using General Procedure 5, starting with 1- (4-methoxyphenyl) -5H-pyrazolo [3,4-d] pyrimidin-4-one as reagent, Synthesis compound R3de was prepared as the HCl salt. MCBP: calculated for C ₃ oH ₃ 4N604: 542.2642, found: 543.2711 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ): δ ppm. 9.11 / 8.69 (brs + brm, 2H), 8.34 / 8.3 (s / s, 1H), 8.29 / 8.25 (s / s, 1H), 7.9 / 7.86 (dm / dm, 2H), 7.37-7.16 (m, 5H), 7.13 / 7.12 (m / m, 2H), 4.91 (brs, 1H), 4.13-0.53 (m, 16H), 3.81 (s, 3H), 3.48 / 3.42 (m / m, 1H), 3.22 ( m, 1H). 13C-NMR (125 MHz, MSM-d ₆ ) δ ppm. 152.6 / 152.5, 136.3 / 136.2, 123.8,

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114.9 / 114.8, 55.9, 42.6 / 42.5, 41.1 / 40.5.

Synthesis of R3df: 1- (2,3-dihydro-1,4-benzodioxin-6-yl) -5 - [[4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine4-carbonyl] -4-piperidyl ] methyl] pyrazolo [3,4-d] pyrimidin-4-one.

Using General Procedure 5, starting from 1- (2,3-dihydro-1,4-benzodioxin-6-yl) -5H-pyrazolo [3,4d] nupuMuguH-4-OHa as reagent, Synthesis compound R3df was obtained as HCl salt. MCBP calculated for C ₃₁ H ₃₄ N ₆ O ₅ : 570.2591, found: 571.2663 [(M + H) + form].

Ή NMR (500 MHz, MSM-d6): δ ppm 9.16 / 8.74 (brs + brs, 2H), 8.3 / 8.26 (s, 1H), 8.29 / 8.23 (s, 1H), 7.53 / 7.52 (d, 1H), 7.48 / 7.47 (dd, 1H), 7.36-7.15 (m, 5H), 7.04 (d, 1H), 4.92 / 4.9 (s, 1H), 4.35-4.26 (m, 4H), 4.1-2.6 (m, 12H), 1.94-0.58 (m, 6H).

Synthesis of R3dg: 6-chloro-7- (4-chloro-3-fluorophenyl) -3 - [[4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4carbonyl] -4-piperidyl] methyl] pyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from the Synthesis compound R2ah as a reagent, the Synthesis compound R3dg was obtained as the HCl salt. MCBP: calculated for C ₃₀ H ₃₀ N ₅ O ₃ FC _l2 : 597.171, found: 598.1772 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ): δ ppm. 8.07 / 8.03 (s, 1H), 7.85 (t, 1H), 7.75 (dd, 1H), 7.41 (dd, 1H), 7.3-7.09 (m, 5H), 6.87 / 6.84 (s, 1H), 4.81 / 4.79 (s, 1H), 4.06-2.51 (m, 12H), 1.68-0.74 (m, 6H).

Synthesis of R3dh: 3 - [[4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -6methyl-7-phenylpyrrolo [2,3 -d] pyrimidine- 4th.

Using General Procedure 5, starting from the Synthesis compound R2de as a reagent, the Synthesis compound R3dh was obtained as the HCl salt. MCBP: calculated for C ₃₁ H ₃₅ N ₅ O ₃ : 525.274, found: 526.2827 [(M + H) ⁺ form].

Ή NMR (500 MHz, MSM-d6): δ ppm 9.14 / 8.69 (brs + brs, 2H), 7.95 / 7.9 (s, 1H), 7.61-7.37 (m, 5H), 7.367.15 (m, 5H), 6.45 / 6.42 (q, 1H), 4.84 / 4.83 (s, 1H), 4.06-2.61 (m, 12H), 2.19 / 2.17 (d, 3H), 1.95-0.6 (m, 6H).

Synthesis of R3di: 3 - [[4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidin-4-carbonyl] -4-piperidyl] methyl] -9methylpyrimido [4,5-b] indol-4-one.

Using General Procedure 5, starting with Synthesis compound R2df as reagent, Synthesis compound R3di was prepared as the HCl salt. MCBP calculated for C ₂₉ H ₃₃ N ₅ O ₃ : 499.2583, found: 500.2677 [(M + H) ⁺ form].

Ή NMR (500 MHz, MSM-d ₆ ): δ ppm 9.19 / 8.74 (brq + brd, 2H), 8.38 / 8.33 (s, 1H), 8.07 / 8.02 (dm, 1H), 7.66 / 7.65 (dm, 1H), 7.43 / 7.42 (m, 1H), 7.37-7.12 (m, 5H), 7.32 (m, 1H), 4.9 (brs, 1H), 4.21-2.62 (m, 12H), 3.87 / 3.86 (s, 3H), 1.95-0.64 (m, 6H). 13C-NMR (125 MHz, MSM-d ₆ ) δ ppm. 158, 152.7, 137.2, 122, 99.

Synthesis of R3dj: 3 - [(4-hydroxy-1- {[(3R, 4R) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -6,8-dimethylpyrimido [5,4- b] indolizin-4 (3H) -one.

Using General Procedure 5, starting from the Synthesis compound R2dg as a reagent, the Synthesis compound R3dj was obtained as the HCl salt. MCBP calculated for C ₂₉ H ₃₄ N ₆ O ₃ : 514.2692, found: 515.2757 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6): δ ppm. 9.25 / 8.77 (brq + brd, 2H), 8.18 / 8.13 (s, 1H), 7.34-7.1 (m, 5H), 6.94 / 6.9 (s, 1H), 6.71 / 6.7 (q, 1H), 4.9 (brs , 1H), 4.13-2.6 (m, 12H), 2.47 / 2.45 (d, 3H), 2.45 / 2.44 (s, 3H), 1.950.62 (m, 6H). 13C-NMR (125 MHz, MSM-d6) δ ppm. 159.3, 152.6, 140.4, 139, 127.9, 115.4, 108.8, 91.4.

Synthesis of R3dk: 6-chloro-3 - [[4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7-phenylpyrrolo [2,3-d] pyrimidin-4-one.

Using General Procedure 5, starting from the Synthesis compound R2dh as a reagent, the Synthesis compound R3dk was obtained as the HCl salt. MCBP: calculated for C ₃₀ H ₃₂ ClN ₅ O ₃ : 545.2194, found: 546.2277 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d ₆ ) δ ppm. 9.15 / 8.71 (brd + brq, 2H), 8.05 / 8 (s, 1H), 7.64-7.41 (m, 5H), 7.37-7.18 (m, 5H), 6.83 / 6.8 (s, 1H), 4.85 (s , 1H), 4.07-2.61 (m, 12H), 1.94-0.61 (m, 6H).

Synthesis of R3dl: 3 - [[4-hydroxy-1 - [(3R, 4R) -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -6-iodo7-methylpyrrolo [2,3-d] pyrimidine- 4th.

Using General Procedure 5, starting with the Synthesis compound R2di as a reagent, the Synthesis compound R3dl was obtained as the HCl salt. MCBP calculated for C ₂₅ H ₃₀ IN ₅ O ₃ : 575.1393, found: 576.1455 [(M + H) ⁺ form].

1H NMR (500 MHz, MSM-d6) δ ppm. 8.02 / 7.97 (s / s, 1H), 7.28-7.02 (m, 5H), 6.84 / 6.83 (s / s, 1H), 4.16-0.65 (m, 16H), 3.65 / 3.64 (s / s, 3H) , 3.21 / 3.16 (m / m, 1H), 2.88 (m, 1H).

13C-NMR (125 MHz, MSM-d ₆ ) δ ppm. 147.9 / 147.8, 111.7 / 111.6, 80.7 / 80.6, 46.2, 43.2 / 42.8, 33.1.

Synthesis of R3dm: 3 - [[3,3-difluoro-4-hydroxy-1- [trans-3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7-phenylpyrrolo [2,3-d] pyrimidine- 4th.

Trimethylsulfoxonium iodide (1.11 g, 5 mmol) was dissolved in abs. MSM (10 ml), then a dispersion of sodium hydride (60% in mineral oil, 200 mg, 5 mmol) was added sequentially and stirred for 20 min at RT. To the mixture was added a solution of tert-butyl 3,3-difluoro-4-oxopiperidine-1-carboxylate (783 mg, 3.33 mmol) in MSM (5 ml, abs.) And stirred for 15 h at rt. The reaction mixture was poured into ice-water (40 ml) and was extracted with DEE (4x15 ml). The combined organic layer was washed with water, brine, then dried over MgSO ₄ and evaporated.

The crude epoxy product was reacted with the Synthesis compound R2bu according to General Procedure 5.

The resulting crude HCl salt was reacted with trans-1-tert-butoxycarbonyl-3-phenylpiperidine-4-carboxylic acid using General Procedure 7.

The crude product was deprotected according to Step 2 of General Procedure 5 to give Synthesis compound R3dm. MCBP: calculated for C ₃₀ H ₃₁ F ₂ N ₅ O ₃ : 547.2394, found: 548.2454 and 548.2490 (two diastereomers) [(M + H) + form].

1H NMR (500 MHz, MSM-d ₆ ): δ ppm. 9.24 / 8.82 (m + m, 2H), 8.19-8.09 (4 * s, 1H), 7.71 (m, 2H), 7.6-7.5 (4 * d, 1H), 7.56 (m, 2H), 7.42 (m , 1H), 7.34-7.16 (m, 5H), 6.79-6.67 (4 * d, 1H), 6.08 (brs, 1H), 4.74-2.35 (m, 12H), 2.06-1.1 (m, 4H).

Synthesis of R3dn: 3 - [[3,3-difluoro-4-hydroxy-1- [trans-3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7- (4-methoxyphenyl) pyrrolo [2,3 -d] pyrimidin-4-one.

Trimethylsulfoxonium iodide (1.11 g, 5 mmol) was dissolved in abs. MSM (10 ml), then a dispersion of sodium hydride (60% in mineral oil, 200 mg, 5 mmol) was added sequentially and stirred for 20 min at RT. To the mixture was added a solution of tert-butyl 3,3-difluoro-4-oxopiperidine-1-carboxylate (783 mg, 3.33 mmol) in MSM (5 ml, abs.) And stirred for 15 h at rt. The reaction mixture was poured into ice-water (40 ml) and was extracted with DEE (4x15 ml). The combined organic layer was washed with water, brine, then dried over MgSO ₄ and evaporated.

The crude epoxy product was reacted with Synthesis compound R2ax according to General Procedure 5.

The resulting crude HCl salt was reacted with trans-1-tert-butoxycarbonyl-3-phenylpiperidine-4-carboxylic acid according to General Procedure 7.

The crude product was deprotected according to Step 2 of General Procedure 5 to give the Synthesis compound R3dn. MCBP: calculated for C ₃ iH ₃₃ F ₂ N ₅ O ₄ : 577.2501, found: 578.2547 and 578.2572 (two diastereomers) [(M + H) ⁺ form].

Ή NMR (500 MHz, MSM-d ₆ ): δ ppm 9.13 / 8.74 (m + m, 2H), 8.16-8.05 (4 * s, 1H), 7.63-7.54 (m, 2H), 7.487.41 (4 * d, 1H), 7.36-7.16 (m, 5H) , 7.14-7.06 (m, 2H), 6.74-6.63 (4 * d, 1H), 6.17-5.95 (brs, 1H), 4.69-2.77 (m, 12H), 3.82 / 3.81 (s, 3H), 2.05- 1.15 (m, 4H).

Examples of

The following Examples illustrate the invention, but do not limit it in any way.

3 - [(1 - {[(3S, 4S) -1-benzyl-3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -3,7 dihydro-4H-pyrrolo [2 , 3-d] pyrimidin-4-one (Example 1).

Using General Procedure 6, starting from 3 - [(4-hydroxy-1 - {[(3S, 4S) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro- 4H-pyrrolo [2,3-d] pyrimidin-4-one (which was prepared according to General Procedure 5 using tert-butyl (3S, 4S) -4- (2-oxa-6-azaspiro [2.5] octane6- carbonyl) -3-phenylpiperidine-1-carboxylate and 3R, 4R, 7R-pyrrolo [2,3-d] pyrimidin-4-one) and benzyl bromide as reagents obtained Example 1. MCBP: calculated for C ₃ iH ₃₅ N ₅ O ₃ : 525.2739, found: 526.2815 [(M + H) ⁺ form].

7- (2-Chlorobenzyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5- yl] methyl} 3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 2).

Using General Procedure 6, starting from the Synthesis compound R3aa and the Synthesis compound R1c as reagents, Example 2. MCBP: calculated for C ₄₁ H ₄₂ ClN ₇ O ₃ S: 747.2758, found: 374.6457 [(M + 2H) ²⁺ form ].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3,4,5-trimethoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 3).

Using General Procedure 6, starting from the Synthesis compound R3ac and the Synthesis compound R1c as reagents, Example 3. MCBP: calculated for C ₄₃ H ₄₇ N ₇ O ₆ S: 789.3309, found: 395.6734 [(M + 2H) ²⁺ form ].

3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3,4,5-trimethoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one ( Example 4).

Using General Procedure 6, starting from the Synthesis compound R3ac and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 4. MCBP: Calculated for C ₄₃ H ₄₇ N ₇ O ₇ S: 805.3257 found: 403.6694 [(M + 2H) ²⁺ form].

7- (3,5-Dichlorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazole- 5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 5 ).

Using General Procedure 6, starting from the Synthesis compound R3ad and the Synthesis compound R1c as reagents, Example 5. MCBP: calculated for C ₄₀ H ₃₉ N ₇ O ₃ SCl ₂ : 767.2212, found:

768.2251 [(M + H) + form].

7- (3,5-Dichlorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyrudin-3-yl) -1,3-thiazole- 5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 6 ).

Using General Procedure 6, starting from the Synthesis compound R3ad and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 6. MCBP: Calculated for C ₄₀ H ₃₉ N ₇ O ₄ SCl ₂ : 783.2161, found: 784.2235 [(M + H) ⁺ form].

7- (3-Chloro-5-methoxyphenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3- thiazol-5 yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3d] pyrimidin-4-one (Example 7) ...

Using General Procedure 6, starting from the Synthesis compound R3ae and the Synthesis compound R1c as reagents, Example 7. MCBP: calculated for C ₄ iH _{42 ClN 7} O ₄ S: 763.2708, found: 764.2766 [(M + H) ⁺ form] ...

7- (3-Chloro-5-methoxyphenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3- thiazol5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 8 ).

Using General Procedure 6, starting from the Synthesis compound R3ae and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 8. MCBP: Calculated for C ₄₁ H ₄₂ ClN ₇ O ₅ S: 779.2657 found: 780.2734 [(M + H) + form].

7- (3,5-Dimethoxyphenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazole- 5 -yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 9 ).

Using General Procedure 6, starting from the Synthesis compound R3af and the Synthesis compound R1c as reagents, Example 9. MCBP: calculated for C ₄₂ H ₄₅ N ₇ O ₅ S: 759.3203, found: 760.3244 [(M + H) + form] ...

7- (3,5-Dimethoxyphenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypuridin-3-yl) -1,3-thiazole- 5yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 10).

Using General Procedure 6, starting from the Synthesis compound R3af and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 10. MCBP: Calculated for C ₄₂ H ₄₅ N ₇ O ₆ S: 775.3152 found: 776.32 [(M + H) + form].

7- (4-Chloro-3-fluorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1- {[2- (6-methylpyridin-3-yl) -1,3- thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one ( Example 11).

Using General Procedure 6, starting from the Synthesis compound R3ah and the Synthesis compound R1c as reagents, Example 11. MCBP: calculated for C ₄₀ H ₃₉ ClFN ₇ O ₃ S: 751.2508, found: 752.2564 [(M + H) + form] ...

7- (4-Chloro-3-fluorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1- {[2- (6-methoxypyridin-3-yl) -1,3- thiazol-5yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 12 ).

Using General Procedure 6, starting from the Synthesis compound R3ah and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 12. MCBP: Calculated for C ₄₀ H ₃₉ ClFN ₇ O ₄ S: 767.2457 found: 768.2552 [(M + H) + form].

7- (4-Chloro-3-methoxyphenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3- thiazol-5 yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 13).

Using General Procedure 6, starting from the Synthesis compound R3ai and the Synthesis compound R1c as reagents, Example 13. MCBP: calculated for C ₄₁ H ₄₂ ClN ₇ O ₄ S: 763.2708, found: 764.2792 [(M + H) + form] ...

7- (4-Chloro-3-methoxyphenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3- thiazol5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3d] pyrimidin-4-one (Example 14).

Using General Procedure 6, starting from the Synthesis compound R3ai and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 14. MCBP: Calculated for C ₄₁ H ₄₂ ClN ₇ O ₅ S: 779.2657 found: 780.2729 [(M + H) + form].

7- (4-Fluoro-3-methoxyphenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3- thiazol-5yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 15 ).

Using General Procedure 6, starting from the Synthesis compound R3aj and the Synthesis compound R1c as reagents, Example 15. MCBP: calculated for C ₄₁ H ₄₂ FN ₇ O ₄ S: 747.3003, found: 748.3047 [(M + H) ⁺ form] ...

- 68 037563

7- (4-Fluoro-3-methoxyphenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3- thiazol5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 16 ).

Using General Procedure 6, starting from the Synthesis compound R3aj and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 16. MCBP: Calculated for C ₄₁ H ₄₂ FN ₇ O ₅ S: 763.2952 found: 764.3029 [(M + H) + form].

7- (3,4-dimethoxyphenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazole- 5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 17 ).

Using General Procedure 6, starting from the Synthesis compound R3ak and the Synthesis compound R1c as reagents, Example 17 MCBP: calculated for C ₄₂ H ₄₅ N ₇ O ₅ S: 759.3203, found: 380.6691 [(M + 2H) ²⁺ form ].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methylphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 18).

Using General Procedure 6, starting from the Synthesis compound R3am and 5- (chloromethyl) -2- (6-methoxy3-pyridyl) thiazole as reagents, Example 18. MCBP: Calculated for C ₄₁ H ₄₃ N ₇ O ₄ S: 729.3096 found: 730.3162 [(M + H) ⁺ form].

4- {3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} - 3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -4-oxo-3,4-dihydro-7H-pyrrolo [2,3-d] pyrimidin-7yl} benzonitrile (Example 19).

Using General Procedure 6, starting from the Synthesis compound R3an and the Synthesis compound R1c as reagents, Example 19. MCBP: calculated for C ₄ iH ₄₀ N ₈ O ₃ S: 724.2944, found: 725.3009 [(M + H) + form] ...

4- {3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} - 3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -4-oxo-3,4-dihydro-7H-pyrrolo [2,3-d] pyrimidin-7-yl} benzonitrile (Example 20) ...

Using General Procedure 6, starting from the Synthesis compound R3an and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 20. MCBP: Calculated for C ₄ iH ₄₀ N ₈ O ₄ S: 740.2893 found: 741.2984 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- [4- (trifluoromethyl) phenyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one ( Example 21).

Using General Procedure 6, starting with Synthesis compound R3ao and Synthesis compound R1c as reagents, Example 21 was prepared. MCBP: Calculated for C ₄ iH ₄₀ N ₇ O ₃ F ₃ S: 767.2866, Found: 768.2899 [(M + H) + the form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- [4- (trifluoromethyl) phenyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 22).

Using General Procedure 6, starting from the Synthesis compound R3ao and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 22 was prepared. MCBP: Calculated for C ₄₁ H ₄₀ F ₃ N ₇ O ₄ S : 783.2814, found: 784.2887 [(M + H) + form].

7- [4- (Difluoromethyl) phenyl] -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazole -5yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 23) ...

Using General Procedure 6, starting from Synthesis compound R3ap and Synthesis compound R1c as reagents, Example 23 was prepared. MCBP: Calculated for C ₄ iH ₄ iF ₂ N ₇ O ₃ S: 749.2959, Found: 750.3017 [(M + H) + the form].

7- [4- (Difluoromethyl) phenyl] -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazole -5yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 24) ...

Using General Procedure 6, starting from the Synthesis compound R3ap and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 24 was prepared. MCBP: Calculated for C ₄₁ H ₄₁ F ₂ N ₇ O ₄ S : 765.2909, found: 766.297 [(M + H) + form].

7- [4- (Hydroxymethyl) phenyl] -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazole -5yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 25) ...

Using General Procedure 6, starting with Synthesis compound R3aq and Synthesis compound R1c as reagents, Example 25 was prepared. MCBP: calculated for C ₄ iH ₄₃ N ₇ O ₄ S: 729.3097, found: 730.3137 [(M + H) + form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- [4- (hydroxymethyl) phenyl] -3,7-dihydro-4H-pyrrolo [2,3-d]

- 69 037563 pyrimidin-4-one (Example 26).

Using General Procedure 6, starting from the Synthesis compound R3aq and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 26 was prepared. MCBP: Calculated for C ₄₁ H ₄₃ N ₇ O ₅ S:

745.3046, found: 746.3142 [(M + H) + form].

7- (4-Chlorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5- yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 27).

Using General Procedure 6, starting from the Synthesis compound R3ar and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 27 was prepared. MCBP: Calculated for C ₄₀ H ₄₀ ClN ₇ O ₄ S: 749.2551 found: 750.2639 [(M + H) ⁺ form].

3 - {[1 - ({(3R, 4R) -1 - [(2-BpoM- 1,3-thiazol-5-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidine- 4-yl] methyl} -7- (4-chlorophenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 28).

Using General Procedure 6, starting from the compound Synthesis of R3ar and 2-bromo-5- (bromomethyl) thiazole as reagents, Example 28 was prepared. MCBP: calculated for C ₃₄ H3 ₄ BrClN ₆ O ₃ S: 720.1285, found: 721.1355 [( M + H) ⁺ form].

7- (4-Fluorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1- {[2- (6-methylpyridin-3-yl) -1,3-thiazole-5 - yl] methyl} 3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 29).

Using General Procedure 6, starting from Synthesis compound R3as and Synthesis compound R1c as reagents, Example 29 was prepared. MCBP: calculated for C ₄₀ H ₄₀ N ₇ O ₃ FS: 717.2897, found: 718.2982 [(M + H) ⁺ form] ...

7- (4-Fluorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5- yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 30).

Using General Procedure 6, starting from the Synthesis compound R3as and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 30 was prepared. MCBP: Calculated for C ₄₀ H ₄₀ FN ₇ O ₄ S: 733.2847 found: 734.2907 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(2-Bromo-1,3-thiazol-5-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidine- 4-yl] methyl} -7- (4-fluorophenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 31).

Using General Procedure 6, starting from the compound Synthesis of R3as and 2-bromo-5- (bromomethyl) thiazole as reagents, Example 31 was prepared. MCBP: calculated for C ₃₄ H ₃₄ BrFN ₆ O ₃ S: 704.1580, found: 705.1642 [( M + H) + form].

7- [4- (Dimethylamino) phenyl] -3 - [(4-hydroxy-1- {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazole -5 yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 32 ).

Using General Procedure 6, starting with the Synthesis compound R3at and the Synthesis compound R1c as reagents, Example 32 was prepared. MCBP: calculated for C ₄₂ H ₄₆ N ₈ O ₃ S: 742.3414, found: 743.3467 [(M + H) + form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 33).

Using General Procedure 6, starting from the Synthesis compound R3ax and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 33 was prepared. MCBP: Calculated for C ₄ iH ₄ 3N ₇ O ₅ S: 745.3047 found: 746.3124 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(2-Bpom- 1,3-thiazol-5-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidine- 4-yl] methyl} -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 34).

Using General Procedure 6, starting from the compound Synthesis of R3ax and 2-bromo-5- (bromomethyl) thiazole as reagents, Example 34 was prepared. MCBP: calculated for C ₃₅ H37BrN ₆ O ₄ S: 716.1780396, found: 717.1836 [(M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(1-methyl-1H-pyrazol-4-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) piperidin-4 -yl] methyl} -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 35).

Using General Procedure 6, starting from the compound Synthesis of R3ax and 4- (chloromethyl) -1-methylpyrazole as reagents, Example 35 was prepared. MCBP: calculated for C ₃₆ H ₄ iN ₇ O ₄ : 635.3220, found: 636.3291 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - (pyrazin-2-ylmethyl) piperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7- ( 4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 36).

Using General Procedure 6 starting from the Synthesis compound R3ax and 2 (chloromethyl) pyrazine hydrochloride as reagents, Example 36 was prepared. MCBP: calculated for C ₃₆ H ₃ 9N ₇ O ₄ : 633.3063, found: 634.3114 [(M + H) ⁺ the form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(5-methyl-1,3-thiazol-2-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl)

- 70 037563 piperidin-4-yl] methyl} -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example

37).

Using General Procedure 6, starting from the compound Synthesis of R3ax and 2- (chloromethyl) -5-methylthiazole as reagents, Example 37 was prepared. MCBP: Calculated for C ₃₆ H ₄₀ N ₆ O ₄ S: 652.2832031, Found: 653.2891 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(5-Bromopyridin-3-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidin-4-yl] methyl} -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 38).

Using General Procedure 6, starting from the compound Synthesis of R3ax and 3-bromo-5- (chloromethyl) pyridine as reagents, Example 38 was prepared. MCBP: calculated for C ₃₇ H ₃₉ BrN ₆ O ₄ : 710.2216, found: 711.2297 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - (pyridin-3-ylmethyl) piperidin-4-yl] carbonyl} piperidin4-yl) methyl] -7 - ( 4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 3-9).

Using General Procedure 6 starting from the Synthesis compound R3ax and 3 (chloromethyl) pyridine hydrochloride as reagents, Example 39 was prepared. MCBP: calculated for C ₃₇ H ₄₀ N ₆ O ₄ : 632.3111, found: 633.3167 [(M + H) ⁺ the form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - (1,3-thiazol-5-ylmethyl) piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 40).

Using General Procedure 6, starting from the compound Synthesis of R3ax and 5- (chloromethyl) thiazole as reagents, Example 40 was prepared. MCBP: Calculated for C ₃₅ H ₃₈ N ₆ O ₄ S: 638.2675, Found: 639.2738 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - (1,3-thiazol-2-ylmethyl) piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 41).

Using General Procedure 6, starting from the compound Synthesis of R3ax and 2- (chloromethyl) thiazole as reagents, Example 41 was prepared. MCBP: Calculated for C ₃₅ H ₃₈ N ₆ O ₄ S: 638.2675, Found: 639.2758 [(M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(4-methyl-1,3-thiazol-2-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 42).

Using General Procedure 6, starting from the compound Synthesis of R3ax and 2- (chloromethyl) -4-methylthiazole as reagents, Example 42 was prepared. MCBP: Calculated for C ₃₆ H ₄₀ N ₆ O ₄ S: 652.2832, Found: 653.2885 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(4,5-Dimethyl-1,3-thiazol-2-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) -4hydroxypiperidine- 4-yl] methyl} -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 43).

Using General Procedure 6, starting from the compound Synthesis of R3ax and 2- (chloromethyl) -4,5dimethylthiazole as reagents, Example 43 was prepared. MCBP: Calculated for C ₃₇ H ₄₂ N ₆ O ₄ S: 666.2988, Found: 667.3059 [(M + H) ⁺ form].

3 - {[1 - ({(3R, 4R) -1 - [(2,4-Dimethyl-1,3-thiazol-5-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) -4hydroxypiperidine- 4-yl] methyl} -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 44).

Using General Procedure 6, starting from the compound Synthesis of R3ax and 5- (chloromethyl) -2,4dimethylthiazole as reagents, Example 44 was prepared. MCBP: calculated for C37H42N6O4S: 666.2988, found: 667.3047 [(M + H) ⁺ form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(1-methyl-1H-pyrazol-5-yl) methyl] -3-phenylpiperidin-4yl} carbonyl) piperidin-4-yl ] methyl} -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 45).

Using General Procedure 6, starting with the Synthesis compound R3ax and 5- (chloromethyl) -1methylpyrazole as reagents, Example 45 was prepared. MCBP: Calculated for C ₃₆ H ₄₁ N ₇ O ₄ : 635.3220, Found: 636.3288 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(1,3-Dimethyl-1H-pyrazol-5-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) -4hydroxypiperidin-4- yl] methyl} -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 46).

Using General Procedure 6, starting from the compound Synthesis of R3ax and 5- (chloromethyl) -1,3dimethylpyrazole as reagents, Example 46 was prepared. MCBP: calculated for C37H43N7O4: 649.3376, found: 650.3455 [(M + H) + form].

4 - ({(3R, 4R) -4 - [(4-Hydroxy-4 - {[7- (4-methoxyphenyl) -4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidin-3-yl] methyl} piperidin-1-yl) carbonyl] -3-phenylpiperidin-1-yl} methyl) pyridine-2-carbonitrile (Example 47).

Using General Procedure 6, starting from the compound Synthesis of R3ax and 4- (chloromethyl) pyridine-2carbonitrile as reagents, Example 47 was prepared. MCBP: Calculated for C ₃₈ H ₃₉ N ₇ O ₄ : 657.3063, Found: 658.3133 [(M + H ) + form].

- 71 037563

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(6-methylpyridin-3-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) piperidin-4-yl] methyl } -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example

48).

Using General Procedure 6, starting from the Synthesis compound R3ax and 5- (bromomethyl) 2-methylpyridine hydrobromide as reagents, Example 48 was prepared. MCBP: Calculated for C ₃₈ H ₄₂ N ₆ O ₄ : 646.3267, Found: 647.3343 [(M + H) + form].

5 - ({(3R, 4R) -4 - [(4-Hygroxy-4 - {[7- (4-methoxyphenyl) -4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidin-3-yl] methyl} piperidin-1-yl) carbonyl] -3-phenylpiperidin-1-yl} methyl) pyridine-2-carbonitrile (Example 49).

Using General Procedure 6, starting from the compound Synthesis of R3ax and 5- (bromomethyl) pyridine-2carbonitrile as reagents, Example 49 was prepared. MCBP: Calculated for C ₃₈ H ₃₉ N ₇ O ₄ : 657.3063, Found: 658.3138 [(M + H ) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - (1,3-oxazol-4-ylmethyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl ] -7- (4-methoxyphenyl) -3,7-dihydro-4H-nurrolo [2,3-d] pyrimigin-4-one (Example 50).

Using General Procedure 6, starting with the compound Synthesis of R3ax and 4- (chloromethyl) oxazole as reagents, Example 50 was prepared. MCBP: Calculated for C ₃₅ H ₃₈ N ₆ O ₅ : 622.2903, Found: 623.2975 [(M + H) + the form].

3 - {[1 - ({(3R, 4R) -1 - [(1,5-Dimethyl-1H-pyrazol-3-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) -4hydroxyniperidin-4- yl] methyl} -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 51).

Using General Procedure 6, starting from the compound Synthesis of R3ax and 3- (chloromethyl) -1,5dimethylpyrazole as reagents, Example 51 was prepared. MCBP: calculated for C ₃₇ H ₄₃ N ₇ O ₄ : 649.3376, found: 650.3431 [(M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(5-methyl-1,3-oxazol-2-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 52).

Using General Procedure 6, starting with the compound Synthesis of R3ax and 2- (chloromethyl) -5methyloxazole as reagents, Example 52 was prepared. MCBP: Calculated for C ₃₆ H ₄₀ N ₆ O ₅ : 636.3060, Found: 637.3141 [(M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(2-methyl-1,3-thiazol-4-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 53).

Using General Procedure 6, starting from the compound Synthesis of R3ax and 4- (chloromethyl) -2-methylthiazole as reagents, Example 53 was prepared. MCBP: Calculated for C ₃₆ H ₄₀ N ₆ O ₄ S: 652.2832, Found: 653.2896 [(M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(5-methyl-1,2-oxazol-3-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 54)

Using General Procedure 6, starting from the compound Synthesis of R3ax and 3- (chloromethyl) -5-methylisoxazole as reagents, Example 54 was prepared. MCBP: Calculated for C ₃₆ H ₄₀ N ₆ O ₅ : 636.3060, Found: 637.3118 [(M + H) + form].

3 - [(4-Hygroxy-1 - {[(3R, 4R) -1- (1,2-oxazol-3-ylmethyl) -3-phenylpiperigin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 55).

Using General Procedure 6, starting with the Synthesis compound R3ax and 3- (chloromethyl) isoxazole as reagents, Example 55 was prepared. MCBP: Calculated for C ₃₅ H ₃₈ N ₆ O ₅ : 622.2903, Found: 623.2961 [(M + H) + the form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(3-methyl-1,2-oxazol-5-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 56).

Using General Procedure 6, starting from the compound Synthesis of R3ax and 5- (chloromethyl) -3-methylisoxazole as reagents, Example 56 was prepared. MCBP: Calculated for C ₃₆ H ₄₀ N ₆ O ₅ : 636.3060, Found: 637.3119 [(M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(5-methyl-1,2-oxazol-4-yl) methyl] -3-phenylpiperidin-4yl} carbonyl) piperidine-4 -yl] methyl} -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 57).

Using General Procedure 6, starting from the compound Synthesis of R3ax and 4- (chloromethyl) -5-methylisoxazole as reagents, Example 57 was prepared. MCBP: Calculated for C ₃₆ H ₄₀ N ₆ O ₅ : 636.3060, Found: 637.3139 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[6- (trifluoromethyl) pyridin-3-yl] methyl} piperidin-4-yl] carbonyl} piperidine- 4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 58).

Using General Procedure 6, starting from the Synthesis compound R3ax and 5- (bromomethyl) -2-72 037563 (trifluoromethyl) pyridine as reactants, Example 58 was prepared. MCBP: Calculated for

C38H39F3N6O4 700.2985, found: 701.3082 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- [4- (trifluoromethoxy) phenyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 59).

Using General Procedure 6, starting from Synthesis compound R3ay and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 59 was prepared. MCBP: Calculated for C ₄₁ H ₄₀ F ₃ N ₇ O ₅ S : 799.2764, found: 800.2855 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- [4- (trifluoromethoxy) phenyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one ( Example 60).

Using General Procedure 6, starting with Synthesis compound R3ay and Synthesis compound R1c as reagents, Example 60 was prepared. MCBP: Calculated for C ₄ iH ₄₀ F ₃ N ₇ O ₄ S: 783.2814, Found: 784.2904 [(M + H) ⁺ the form].

7- [4- (Benzyloxy) phenyl] -3 - [(4-hydroxy-1 - {[(3R, 4R) -1- {[2- (6-methylpyridin-3-yl) -1,3-thiazole -5 -yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 61).

Using General Procedure 6, starting with the Synthesis compound R3az and the Synthesis compound R1c as reagents, Example 61 was prepared. MCBP: calculated for C ₄₇ H ₄₇ N ₇ O ₄ S: 805.3410, found: 403.6767 [(M + 2H) 2+ form ].

7- [4- (Benzyloxy) phenyl] -3 - [(4-hydroxy-1 - {[(3R, 4R) -1- {[2- (6-methoxypyridin-3-yl) -1,3-thiazole -5yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 62) ...

Using General Procedure 5, starting from the Synthesis compound R3az and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 62 was prepared. MCBP: Calculated for C ₄₇ H ₄₇ N ₇ O5S: 821.3359 Found : 822.3433 [(M + H) + form].

3 - [(1 - {[(3S, 4S) -1-Benzyl-3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 methyl-3,7-dihydro-4H -pyrrolo [2,3-d] pyrimidin-4-one (Example 63).

Using General Procedure 6, starting from 3 - ({4-hydroxy-1 - [(3S, 4S) -3-phenylpiperidin-4-carbonyl] piperidin-4-yl} methyl) -7-methyl-3H, 4H, 7H -pyrrolo [2,3-d] pyrimidin-4-one (which was prepared according to General Procedure 5 using tert-butyl (3S, 4S) -4- (2-oxa-6-azaspiro [2.5] octane-6carbonyl ) -3-phenylpiperidine-1-carboxylate and Synthesis compound R2b) and benzyl bromide as reagents obtained Example 63. MCBP: calculated for C ₃₂ H ₃₇ N ₅ O ₃ : 539.2896, found: 540.2984 [(M + H) + form ].

3 - [(1- {[(3R, 4R) -1-Benzyl-3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 methyl-3,7-dihydro-4H -pyrrolo [2,3-d] pyrimidin-4-one (Example 64).

Using General Procedure 6, starting from the Synthesis of R3b compound and benzyl bromide as reagents, Example 64 was prepared. MCBP: calculated for C ₃₂ H ₃₇ N ₅ O ₃ : 539.2896, found: 540.2977 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - (2-Fluorobenzyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3, 7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 65).

Using General Procedure 6, starting from the compound Synthesis of R3b and 1- (bromomethyl) -2-fluorobenzene as reagents, Example 65 was prepared. MCBP: calculated for C ₃₂ H ₃₆ FN ₅ O ₃ : 557.2802, found: 558.2879 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - (3-Fluorobenzyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3, 7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 66).

Using General Procedure 6, starting from the compound Synthesis of R3b and 1- (bromomethyl) -3-fluorobenzene as reagents, Example 66 was prepared. MCBP: calculated for C ₃₂ H ₃₆ FN ₅ O ₃ : 557.2802, found: 558.2902 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - (2-methylbenzyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl- 3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 67).

Using General Procedure 6, starting from the compound Synthesis of R3b and 1- (bromomethyl) -2-methylbenzene as reagents, Example 67 was prepared. MCBP: Calculated for C ₃₃ H ₃₉ N ₅ O ₃ : 553.3053, Found: 554.3138 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - (3-methylbenzyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl- 3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 68).

Using General Procedure 6, starting from the compound Synthesis of R3b and 1- (bromomethyl) -3-methylbenzene as reagents, Example 68 was prepared. MCBP: Calculated for C ₃₃ H ₃₉ N ₅ O ₃ : 553.3052, Found: 554.3090 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - (3-Bromobenzyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 -methyl-3, 7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 69).

Using General Procedure 6, starting from the compound Synthesis of R3b and 1-bromo-3- (bromomethyl) benzene in

- 73 037563 as reagents, received Example 69. MCBP: calculated for C ₃₂ H ₃₆ BrN ₅ O ₃ : 617.2001, found:

618.2094 [(M + H) + form].

6 - {[(3R, 4R) -4 - ({4-Hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine-3- yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] methyl} -1-methyl-3,4-dihydroquinolin-2 (1H) -one (Example 70).

Using General Procedure 6, starting from Synthesis compound R3b and 6- (chloromethyl) -1-methyl-3,4-dihydroquinolin-2-one as reactants, Example 70 was prepared. MCBP: Calculated for C ₃₆ H ₄₂ N ₆ O ₄ : 622.3268 found: 623.3354 [(M + H) ⁺ form].

3 - [(1- {[(3R, 4R) -1 - (3-Acetylbenzyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 -methyl-3, 7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 71).

Using General Procedure 6, starting from the Synthesis compound R3b and 1- [3- (chloromethyl) phenyl] ethanone as reagents, Example 71 was prepared. MCBP: Calculated for C ₃₄ H ₃₉ N ₅ O ₄ : 581.3002, Found: 582.3054 [( M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (5-methylthiophen-2-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 72).

Using General Procedure 6, starting from the Synthesis compound R3ba and the Synthesis compound R1c as reagents, Example 72 was prepared. MCBP: calculated for C ₃₉ H ₄₁ N ₇ O ₃ S ₂ : 719.2712, found: 720.2762 [(M + H) + form ].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (5-methylthiophen-2-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one ( Example 73).

Using General Procedure 6, starting from the Synthesis compound of R3ba and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 73 was prepared. MCBP: Calculated for C ₃₉ H ₄ iN ₇ O ₄ S ₂ : 735.2661, found: 736.2727 [(M + H) + form].

7- (5-Chlorothiophen-2-yl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypuridin-3-yl) -1,3- thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one ( Example 74).

Using General Procedure 6, starting from the Synthesis compound R3bb and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 74 was prepared. MCBP: Calculated for C ₃₈ H ₃₈ ClN ₇ O ₄ S ₂ : 755.2115, found: 756.219 [(M + H) + form].

7- (5-Chlorothiophen-2-yl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3- thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one ( Example 75).

Using General Procedure 6, starting with Synthesis compound R3bb and Synthesis compound R1c as reagents, Example 75 was prepared. MCBP: Calculated for C ₃₈ H ₃₈ N ₇ O ₃ S ₂ Cl: 739.2166, Found: 740.2222 [(M + H) + the form].

7- (2,3-Dihydro-1,4-benzodioxin-6-yl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3 -yl) 1,3-thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidine -4-one (Ex. 76).

Using General Procedure 6, starting with Synthesis compound R3bc and Synthesis compound R1c as reagents, Example 76 was prepared. MCBP: calculated for C ₄₂ H ₄₃ N ₇ O ₅ S: 757.3046, found: 758.3125 [(M + H) + form] ...

7- (2,3-Dihydro-1,4-benzodioxin-6-yl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridine-3 -yl) 1,3-thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidine -4-one (Example 77).

Using General Procedure 6, starting from the Synthesis compound R3bc and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 77 was prepared. MCBP: Calculated for C42H43N7O6S: 773.2996, Found: 774.3038 [(M + H) + form].

7- (1,3-Benzodioxol-5-yl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1, 3-thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine-4- he (Ex. 78).

Using General Procedure 6, starting with Synthesis compound R3bd and Synthesis compound R1c as reagents, Example 78 was prepared. MCBP: calculated for C ₄₁ H ₄₁ N ₇ O ₅ S: 743.2890, found: 372.6517 [(M + 2H) ²⁺ form ].

7- (1,3-Benzodioxol-5-yl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypuridin-3-yl) -1, 3-thiazol-5yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one ( Example 79).

Using General Procedure 6, starting from the Synthesis compound R3bd and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 79 was prepared. MCBP: Calculated for C ₄ iH ₄ iN ₇ O ₆ S: 759.2838 found: 380.6487 [(M + 2H) ²⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpi - 74 037563 peridin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3-methylphenyl) -3,7-dihydro-4H-pyrrolo [2,3 ^] pyrimidin-4-one (Example 80).

Using General Procedure 6, starting from the Synthesis compound R3bf and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 80 was prepared. MCBP: Calculated for C ₄₁ H ₄₃ N ₇ O ₄ S:

729.3097, found: 730.3189 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- [3 - (trifluoromethyl) phenyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one ( Example 81).

Using General Procedure 6, starting with Synthesis compound R3bg and Synthesis compound R1c as reagents, Example 81 was prepared. MCBP: Calculated for C ₄₁ H ₄₀ F ₃ N ₇ O ₃ S: 767.2865, Found: 768.2943 [(M + H) ⁺ the form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- [3 - (trifluoromethyl) phenyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 82).

Using General Procedure 6, starting from the Synthesis compound R3bg and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 82 was prepared. MCBP: Calculated for C ₄₁ H ₄₀ F ₃ N ₇ O ₄ S : 783.2814, found: 784.2897 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- {3 - [(4-methylpiperazin-1-yl) methyl] phenyl} -3,7-dihydro4H-pyrrolo [2,3-d ] pyrimidin-4-one (Example 83).

Using General Procedure 6, starting with Synthesis compound R3bh and Synthesis compound R1c as reagents, Example 83 was prepared. MCBP: calculated for C ₄₆ H ₅₃ N ₉ O ₃ S: 811.3992, found: 406.7081 [(M + 2H) 2+ form ].

7- [3- (Hydroxymethyl) phenyl] -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazole -5yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 84) ...

Using General Procedure 6, starting with Synthesis compound R3bi and Synthesis compound R1c as reagents, Example 84 was prepared. MCBP: calculated for C ₄₁ H ₄₃ N ₇ O ₄ S: 729.3098, found: 730.3153 [(M + H) + form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- [3 - (hydroxymethyl) phenyl] -3,7-dihydro-4H-pyrrolo [2,3d] pyrimidin-4-one (Example 85) ...

Using General Procedure 6, starting from the Synthesis compound R3bi and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 85 was prepared. MCBP: Calculated for C41H4 ₃ N ₇ O5S: 745.3046, Found: 746.313 [(M + H) + form].

7- (3-Chlorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5- yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 86).

Using General Procedure 6, starting from Synthesis compound R3bj and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 86 was prepared. MCBP: Calculated for C ₄₀ H ₄₀ N ₇ O ₄ SCl: 749.2551 found: 750.2624 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(2-Bromo-1,3-thiazol-5-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidine- 4-yl] methyl} -7- (3-chlorophenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 87).

Using General Procedure 6, starting from the compound Synthesis of R3bj and 2-bromo-5- (bromomethyl) thiazole as reagents, Example 87 was prepared. MCBP: calculated for C ₃₄ H ₃₄ BrClN ₆ O ₃ S: 720.1284, found: 721.1336 [( M + H) + form].

7- (3-Fluorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1- {[2- (6-methylpyridin-3-yl) -1,3-thiazole-5 - yl] methyl} 3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 88).

Using General Procedure 6, starting from the Synthesis compound R3bk and the Synthesis compound R1c as reagents, Example 88 was prepared. MCBP: calculated for C ₄₀ H ₄₀ FN ₇ O ₃ S: 717.2897, found: 359.6513 [(M + 2H) ²⁺ form ].

7- (3-Fluorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5- yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 89).

Using General Procedure 6, starting from the Synthesis compound R3bk and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 89 was prepared. MCBP: Calculated for C ₄₀ H ₄₀ FN ₇ O ₄ S: 733.2847 found: 734.2893 [(M + H) + form].

7- [3- (Dimethylamino) phenyl] -3 - [(4-hydroxy-1- {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazole -5 yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 90 ).

Using General Procedure 6, starting with Synthesis compound R3bl and Synthesis compound R1c as reagents, Example 90 was prepared. MCBP: calculated for C ₄₂ H ₄₆ N8O ₃ S: 742.3413, found: 372.1784

[(M + 2H) 2+ form].

7- [3- (Dumethylamino) phenyl] -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazole5 -yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3d] pyrimidin-4-one (Example 91).

Using General Procedure 6, starting from Synthesis compound R3bl and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 91 was prepared. MCBP: Calculated for C ₄₂ H ₄₆ N ₈ O ₄ S: 758.3362 found: 380.1752 [(M + 2H) ²⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- [3- (morpholin-4-yl) phenyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one (Example 92).

Using General Procedure 6, starting with Synthesis compound R3bm and Synthesis compound R1c as reagents, Example 92 was prepared. MCBP: calculated for C ₄₄ H ₄₈ N ₈ O ₄ S: 784.3519, found: 785.3594 [(M + H) ⁺ form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3phenylpiperidin-4 -yl] carbonyl} piperidin-4-yl) methyl] -7- [3- (morpholin-4-yl) phenyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one (Example 93).

Using General Procedure 6, starting from the Synthesis compound R3bm and 5- (chloromethyl) -2- (6-methoxy3-pyridyl) thiazole as reagents, Example 93 was prepared. MCBP: Calculated for C ₄₄ H ₄₈ N ₈ O ₅ S: 800.3468 found: 801.3546 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3phenylpiperidin-4 -yl] carbonyl} piperidin-4-yl) methyl] -7- (3-methoxyphenyl) -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one (Example 94).

Using General Procedure 6, starting from the Synthesis compound R3bo and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 94 was prepared. MCBP: Calculated for C ₄ iH ₄₃ N ₇ O ₅ S: 745.3046 found: 746.3117 [(M + H) ⁺ form].

3 - {[1 - ({(3R, 4R) -1 - [(2-Bromo-1,3-thiazol-5-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidine- 4-yl] methyl} -7- (3-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 95).

Using General Procedure 6, starting from the compound Synthesis of R3bo and 2-bromo-5- (bromomethyl) thiazole as reagents, Example 95 was prepared. MCBP: calculated for C ₃₅ H ₃₇ BrN ₆ O ₄ S: 716.1780, found: 717.1825 [( M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- [3 - (trifluoromethoxy) phenyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one ( Example 96).

Using General Procedure 6, starting with Synthesis compound R3bp and Synthesis compound R1c as reagents, Example 96 was prepared. MCBP: Calculated for C ₄ iH ₄₀ F ₃ N ₇ O ₄ S: 783.2814, Found: 784.2878 [(M + H) ⁺ the form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- [3 - (trifluoromethoxy) phenyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 97).

Using General Procedure 6 starting from the Synthesis compound R3bp and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 97 was prepared. MCBP: Calculated for C ₄ iH ₄₀ F ₃ N ₇ O ₅ S : 799.2764, found: 800.2856 [(M + H) ⁺ form].

7- [3- (Benzyloxy) phenyl] -3 - [(4-hydroxy-1 - {[(3R, 4R) -1- {[2- (6-methoxypyridin-3-yl) -1,3-thiazole -5yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 98) ...

Using General Procedure 6, starting from the Synthesis compound R3bq and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 98 was prepared. MCBP: Calculated for C ₄₇ H ₄₇ N ₇ O ₅ S: 821.3359 found: 822.343 [(M + H) ⁺ form].

7- [3- (Benzyloxy) phenyl] -3 - [(4-hydroxy-1 - {[(3R, 4R) -1- {[2- (6-methylpyridin-3-yl) -1,3-thiazole -5 -yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 99).

Using General Procedure 6, starting from Synthesis compound R3bq and Synthesis compound R1c as reagents, Example 99 was prepared. MCBP: calculated for C ₄₇ H ₄₇ N ₇ O ₄ S: 805.3410, found: 806.3484 (M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (6-methoxypyridin-2-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 100).

Using General Procedure 6, starting from Synthesis compound R3bs and Synthesis compound R1c as reagents, Example 100 was prepared. MCBP: calculated for C ₄₀ H ₄₂ N ₈ O ₄ S: 730.3049, found: 731.3128 [(M + H) + form] ...

- 76 037563

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (6-methoxypyridin-2-yl) -3,7-dihydro-4H-pyrrolo [2,3d] nupuMuguH-4-OH (Example 101 ).

Using General Procedure 6, starting from the Synthesis compound R3bs and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 101 was prepared. MCBP: Calculated for C ₄₀ H ₄₂ N8O ₅ S: 746.2998 Found : 747.308 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1-Benzyl-3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 phenyl-3,7-dihydro-4H -pyrrolo [2,3-d] pyrimidin-4-one (Example 102).

Using General Procedure 6, starting from the Synthesis compound of R3bu and benzyl bromide as reagents, Example 102 was prepared. MCBP: calculated for CvH39N ₅ O3: 601.3053, found: 602.3155 [(M + H) + form].

- {[1 - ({(3R, 4R) -1 - [(2-Bpom- 1,3-thiazol-5-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidin-4 -yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 103).

Using General Procedure 6, starting from the compound Synthesis of R3bu and 2-bromo-5- (bromomethyl) thiazole as reagents, Example 103 was prepared. MCBP: calculated for C ₃₄ H3 ₅ N ₆ O ₃ SBr: 686.1675, found: 687.1743 [( M + H) ⁺ form].

3 - {[1 - ({(3R, 4R) -1 - [(5-Bromopyridin-3-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidin-4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 104).

Using General Procedure 6, starting from the compound Synthesis of R3bu and 3-bromo-5- (chloromethyl) pyridine as reagents, Example 104 was prepared. MCBP: calculated for C ₃₆ H ₃₇ BrN ₆ O ₃ : 680.2111, found: 681.2179 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - (pyridin-4-ylmethyl) piperidin-4-yl] carbonyl} piperidin4-yl) methyl] -7-phenyl -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 105).

Using General Procedure 6, starting from the compound Synthesis of R3bu and 4- (chloromethyl) pyridine as reagents, Example 105 was prepared. MCBP: Calculated for C ₃₆ H ₃₈ N ₆ O ₃ : 602.3005, Found: 603.3085 [(M + H) + the form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - (pyridin-3-ylmethyl) piperidin-4-yl] carbonyl} piperidin4-yl) methyl] -7-phenyl -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 106).

Using General Procedure 6, starting from the compound of the Synthesis of R3bu and hydrobromide 3 (bromomethyl) pyridine as reagents, Example 106 was prepared. MCBP: calculated for C ₃₆ H ₃₈ N ₆ O ₃ : 602.3005, found: 603.3062 [(M + H) ⁺ the form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(1-methyl-1H-pyrazol-4-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) piperidin-4 -yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 107).

Using General Procedure 6, starting from the compound Synthesis of R3bu and 4- (chloromethyl) -1-methylpyrazole as reagents, Example 107 was prepared. MCBP: calculated for C ₃₅ H ₃₉ N ₇ O ₃ : 605.3115, found: 606.3188 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - (pyrazin-2-ylmethyl) piperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7-phenyl -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 108).

Using General Procedure 6 starting from the Synthesis compound R3bu and 2 (chloromethyl) pyrazine hydrochloride as reagents, Example 108 was prepared. MCBP: Calculated for C ₃₅ H ₃₇ N ₇ O ₃ : 603.2958, Found: 604.3021 [(M + H) ⁺ the form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - (1,3-thiazol-5-ylmethyl) piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 109).

Using General Procedure 9, starting from Example 103 and methyl 5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine-2-carboxylate as reactants, Example 109 was prepared by dehalogenation in Suzuki's combination time. MCBP calculated for C ₃₄ H ₃₆ N ₆ O ₃ S: 608.2567, found: 609.265 [(M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(5-methyl-1,3-oxazol-2-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 110).

Using General Procedure 6, starting from the compound Synthesis of R3bu and 2- (chloromethyl) -5-methyloxazole as reagents, Example 110 was prepared. MCBP: Calculated for C ₃₅ H ₃₈ N ₆ O ₄ : 606.2955, Found: 607.3016 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - (1,3-thiazol-2-ylmethyl) piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 111).

Using General Procedure 6, starting from the compound Synthesis of R3bu and 2- (chloromethyl) thiazole as reagents, Example 111 was prepared. MCBP: calculated for C ₃₄ H ₃₆ N ₆ O ₃ S: 608.2567, found: 609.2651 [(M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(5-methyl-1,3-thiazol-2-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 112).

Using General Procedure 6, starting from the compound Synthesis of R3bu and 2- (chloromethyl) -5-methylthiazole as reagents, Example 112 was prepared. MCBP: Calculated for C ₃₅ H ₃₈ N ₆ O ₃ S: 622.2726, Found: 623.2783 [(M + H) + form].

- 77 037563

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - (1,2-oxazol-3-ylmethyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl ] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 113).

Using General Procedure 6, starting from the Synthesis compound of R3bu and 3- (chloromethyl) isoxazole as reagents, Example 113 was prepared. MCBP: Calculated for C ₃₄ H ₃₆ N ₆ O ₄ : 592.2798 Found:

593.2864 [(M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(3-methyl-1,2-oxazol-5-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 114).

Using General Procedure 6, starting from the compound Synthesis of R3bu and 5- (chloromethyl) -3-methylisoxazole as reagents, Example 114 was prepared. MCBP: calculated for C ₃₅ H ₃₈ N ₆ O ₄ : 606.2955, found: 607.3046 [(M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(4-methyl-1,3-thiazol-2-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 115).

Using General Procedure 6, starting from the compound Synthesis of R3bu and 2- (chloromethyl) -4-methylthiazole as reagents, Example 115 was prepared. MCBP: Calculated for C ₃₅ H ₃₈ N ₆ O ₃ S: 622.2726, Found: 623.2782 [(M + H) ⁺ form].

3 - {[1 - ({(3R, 4R) -1 - [(2,4-Dimethyl-1,3-thiazol-5-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) -4- hydroxypiperidin-4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 116).

Using General Procedure 6, starting from the compound Synthesis of R3bu and 5- (chloromethyl) -2,4-dimethylthiazole as reagents, Example 116 was prepared. MCBP: Calculated for C ₃₆ H ₄₀ N ₆ O ₃ S: 636.2883, Found: 637.2942 [ (M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(4,5-Dimethyl-1,3-thiazol-2-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) -4- hydroxypiperidin-4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 117).

Using General Procedure 6, starting from the compound Synthesis of R3bu and 2- (chloromethyl) -4,5dimethylthiazole as reagents, Example 117 was prepared. MCBP: Calculated for C ₃₆ H ₄₀ N ₆ O ₃ S: 636.2883, Found: 637.2965 [(M + H) ⁺ form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(5-methyl-1,2-oxazol-4-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 118).

Using General Procedure 6, starting from the compound Synthesis of R3bu and 4- (chloromethyl) -5methylisoxazole as reagents, Example 118 was prepared. MCBP: Calculated for C ₃₅ H ₃₈ N ₆ O ₄ : 606.2955, Found: 607.3009 [(M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(1-methyl-1H-pyrazol-5-yl) methyl] -3-phenylpiperidin-4yl} carbonyl) piperidin-4-yl ] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 119).

Using General Procedure 6, starting from the Synthesis compound of R3bu and 5- (chloromethyl) -1methylpyrazole as reagents, Example 119 was prepared. MCBP: Calculated for C ₃₅ H ₃₉ N ₇ O ₃ : 605.3115, Found: 606.3186 [(M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(5-methyl-1,2-oxazol-3-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 120).

Using General Procedure 6, starting from the compound Synthesis of R3bu and 3- (chloromethyl) -5methylisoxazole as reagents, Example 120 was prepared. MCBP: Calculated for C ₃₅ H ₃₈ N ₆ O ₄ : 606.2955, Found: 607.3011 [(M + H) ⁺ form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(2-methyl-1,3-thiazol-4-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 121).

Using General Procedure 6, starting from the compound Synthesis of R3bu and 4- (chloromethyl) -2-methylthiazole as reagents, Example 121 was prepared. MCBP: Calculated for C ₃₅ H ₃₈ N ₆ O ₃ S: 622.2726, Found: 623.2799 [(M + H) + form].

4 - {[(3R, 4R) -4 - ({4-Hydroxy-4 - [(4-oxo-7-phenyl-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine-3- yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] methyl} pyridine-2-carbonitrile (Example 122).

Using General Procedure 6, starting from the compound Synthesis of R3bu and 4- (chloromethyl) pyridine-2carbonitrile as reagents, Example 122 was prepared. MCBP: Calculated for C ₃₇ H ₃₇ N ₇ O ₃ : 627.2958, Found: 628.3026 [(M + H ) + form].

5 - {[(3R, 4R) -4 - ({4-Hydroxy-4 - [(4-oxo-7-phenyl-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine-3- yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] methyl} pyridine-2-carbonitrile (Example 123).

Using General Procedure 6, starting from the compound Synthesis of R3bu and 5- (bromomethyl) pyridine-2carbonitrile as reagents, Example 123 was prepared. MCBP: Calculated for C ₃₇ H ₃₇ N ₇ O ₃ : 627.2958, Found: 628.3025 [(M + H ) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - (1,3-oxazol-4-ylmethyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl ] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 124).

Using General Procedure 6, starting from the compound Synthesis of R3bu and 4- (chloromethyl) oxazole as reagents, Example 124 was prepared. MCBP: Calculated for C ₃₄ H ₃₆ N ₆ O ₄ : 592.2797852, Found: 593.2876 [(M + H) ⁺ the form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(6-methylpyridin-3-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl)

- 78 037563 piperidin-4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 125).

Using General Procedure 6, starting from the Synthesis compound R3bu and 5- (bromomethyl) 2-methylpyridine hydrobromide as reactants, Example 125 was prepared. MCBP: Calculated for C ₃₇ H ₄₀ N ₆ O ₃ :

616.3162, found: 617.3241 [(M + H) + form].

3 - [(1 - {[(3S, 4S) -1-Benzyl-3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 ethyl-3,7-dihydro-4H -pyrrolo [2,3-d] pyrimidin-4-one (Example 126).

Using General Procedure 6, starting from 7-ethyl-3 - ({4-hydroxy-1 - [(3S, 4S) -3-phenylpiperidin-4carbonyl] piperidin-4-yl} methyl) -3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one (which was prepared according to General Procedure 5 using tert-butyl (3S, 4S) -4- (2-oxa-6-azaspiro [2.5] octane-6carbonyl) - 3-phenylpiperidine-1-carboxylate and Synthesis compound R2c) and benzyl bromide as reactants prepared Example 126. MCBP: calculated for C ₃₃ H ₃₉ N ₅ O ₃ : 553.3053, found: 554.312 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1-Benzyl-3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 ethyl-3,7-dihydro-4H -pyrrolo [2,3-d] pyrimidin-4-one (Example 127).

Using General Procedure 6, starting from the compound Synthesis of R3c and benzyl bromide as reagents, Example 127 was prepared. MCBP: calculated for C ₃₃ H ₃₉ N ₅ O ₃ : 553.3053, found: 554.3122 [(M + H) + form].

7-Ethyl-3 - [(1 - {[(3R, 4R) -1- (2-fluorobenzyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin4-yl) methyl] -3,7- dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 128).

Using General Procedure 6, starting from the Synthesis compound R3c and 1- (bromomethyl) -2-fluorobenzene as reagents, Example 128 was prepared. MCBP: Calculated for C ₃₃ H ₃₈ FN ₅ O ₃ : 571.2959, Found: 572.3022 [(M + H) + form].

7-Ethyl-3 - [(1 - {[(3R, 4R) -1- (3-fluorobenzyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin4-yl) methyl] -3,7- dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 129).

Using General Procedure 6, starting from the compound Synthesis of R3c and 1- (bromomethyl) -3-fluorobenzene as reagents, Example 129 was prepared. MCBP: calculated for C ₃₃ H ₃₈ FN ₅ O ₃ : 571.2959, found: 572.3037 [(M + H) + form].

7-Ethyl-3 - [(4-hydroxy-1 - {[(3R, 4R) -1- (2-methylbenzyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3 , 7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 130).

Using General Procedure 6, starting from the Synthesis compound R3c and 1- (bromomethyl) -2-methylbenzene as reagents, Example 130 was prepared. MCBP: Calculated for C ₃₄ H ₄₁ N ₅ O ₃ : 567.3209, Found: 568.327 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (thiophen-2-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin4-one (Example 131) ...

Using General Procedure 6, starting from the Synthesis compound R3cc and the Synthesis compound R1c as reagents, Example 131 was prepared. MCBP: calculated for C ₃₈ H ₃₉ N ₇ O ₃ S ₂ : 705.2556, found: 706.262 [(M + H) + form ].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (thiophen-2-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin4-one (Example 132).

Using General Procedure 6, starting from the Synthesis compound R3cc and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 132 was prepared. MCBP: Calculated for C ₃₈ H ₃₉ N ₇ O ₄ S ₂ : 721.2505, found: 722.2596 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (thiophen-3-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin4-one (Example 133).

Using General Procedure 6, starting from the Synthesis compound R3cf and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 133 was prepared. MCBP: Calculated for C ₃₈ H ₃₉ N ₇ O ₄ S ₂ : 721.2505 found: 722.2570 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (1-methyl-1H-imidazol-4-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine -4-one (Example 134).

Using General Procedure 6, starting with the Synthesis compound R3cg and the Synthesis compound R1c as reagents, Example 134 was prepared. MCBP: calculated for C ₃₈ H ₄ iN ₉ O ₃ S: 703.3053, found: 352.6599 [(M + 2H) ²⁺ form ].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3phenylpiperidin-4 -yl] carbonyl} piperidin-4-yl) methyl] -7- (1-methyl-1H-imidazol-4-yl) -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one ( Example 135).

Using General Procedure 6, starting from the Synthesis compound R3cg and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 135 was prepared. MCBP: Calculated for C ₃₈ H ₄₁ N ₉ O ₄ S: 719.3002 found: 360.6580 [(M + 2H) ²⁺ form].

- 79 037563

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (1-methyl-1H-pyrazol-4-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine -4-one (Example 136).

Using General Procedure 6, starting with Synthesis compound R3ch and Synthesis compound R1c as reagents, Example 136 was prepared. MCBP: calculated for C ₃₈ H ₄₁ N ₉ O ₃ S: 703.3053, found: 704.3095 [(M + H) + form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3phenylpiperidin-4 -yl] carbonyl} piperidin-4-yl) methyl] -7- (1-methyl-1H-pyrazol-4-yl) -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one ( Example 137).

Using General Procedure 6, starting from the Synthesis compound R3ch and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 137 was prepared. MCBP: Calculated for C ₃₈ H ₄ iN ₉ O ₄ S: 719.3002 found: 720.3059 [(M + H) ⁺ form].

7- [1- (Difluoromethyl) -1H-pyrazol-4-yl] -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl ) -1,3thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine- 4-one (Example 138).

Using General Procedure 6, starting with Synthesis compound R3ci and Synthesis compound R1c as reagents, Example 138 was prepared. MCBP: Calculated for C ₃₈ H ₃₉ F ₂ N ₉ O ₃ S: 739.2864, Found: 740.2936 [(M + H) + the form].

7- [1 - (Difluoromethyl) -1H-pyrazol-4-yl] -3 - [(4-hydroxy-1- {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl ) 1,3-thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidine-4 -on (Example 139).

Using General Procedure 6, starting from the Synthesis compound R3ci and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 139 was prepared. MCBP: Calculated for C ₃₈ H ₃₉ F ₂ N ₉ O ₄ S : 755.2814, found: 756.287 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (1,3-thiazol-2-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine-4 -on (Example 140).

Using General Procedure 6, starting from Synthesis compound R3ck and Synthesis compound R1c as reagents, Example 140 was prepared. MCBP: calculated for C ₃ 7H ₃₈ N ₈ O ₃ S ₂ : 706.2509, found: 707.257 [(M + H) + form ].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (1,3-thiazol-2-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine-4- he (Ex. 141).

Using General Procedure 6, starting from the Synthesis compound R3ck and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 141 was prepared. MCBP: Calculated for C ₃₇ H ₃₈ N ₈ O ₄ S ₂ : 722.2457, found: 723.2535 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (prop-2-yn-1-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine-4 -on (Example 142).

Using General Procedure 6, starting from Synthesis compound R3m and Synthesis compound R1c as reagents, Example 142 was prepared. MCBP: calculated for C ₃₇ H ₃₉ N ₇ O ₃ S: 661.2835, found: 662.2896 [(M + H) ⁺ form] ...

3 - {[1 - ({(3R, 4R) -1 - [(2-Bpom- 1,3-thiazol-5-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidine- 4-yl] methyl} -7- (2,2,2-trifluoroethyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 143).

Using General Procedure 6, starting with the compound Synthesis of R3o and 2-bromo-5- (bromomethyl) thiazole as reagents, Example 143 was prepared. MCBP: Calculated for C ₃₀ H ₃₂ BrF ₃ N ₆ O ₃ S: 692.1392, Found: 693.1452 [(M + H) ⁺ form].

7- (Buta-2,3-diene-1-yl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) - 1,3-thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine- 4-one (Example 144).

Using General Procedure 6, starting with the Synthesis compound R3s and the Synthesis compound R1c as reagents, Example 144 was prepared. MCBP: calculated for C ₃₈ H ₄₁ N ₇ O ₃ S: 675.2991, found: 676.3089 [(M + H) ⁺ form] ...

7- (4-Chlorobenzyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5- yl] methyl} 3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 145).

Using General Procedure 6, starting with Synthesis compound R3x and Synthesis compound R1c as reagents, Example 145 was prepared. MCBP: calculated for C ₄ iH ₄₂ C1N ₇ O ₃ S: 747.2758, found: 374.6462 [(M + 2H) ²⁺ form ].

7- (3-Chlorobenzyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5- yl] methyl} 3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4- 80 037563 one (Example 146) ...

Using General Procedure 6, starting from Synthesis compound R3y and Synthesis compound R1c as reagents, Example 146 was prepared. MCBP: Calculated for C ₄₁ H ₄₂ ClN ₇ O ₃ S: 747.2758 Found:

374.645 [(M + 2H) 2+ form].

7-Benzyl-3 - [(1 - {[1-benzyl-3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] 3,7-dihydro-4H-pyrrolo [2,3 -d] pyrimidin-4-one (Example 147).

Using General Procedure 6, starting from racemic 7-benzyl-3 - ({4-hydroxy-1- [3-phenylpiperidin-4-carbonyl] piperidin-4-yl} methyl) -3H, 4H, 7H-pyrrolo [2, 3-d] pyrimidin-4-one (which was prepared according to General Procedure 5 using racemic tert-butyl 4- (2-oxa-6azaspiro [2.5] octane-6-carbonyl) -3-phenylpiperidin-1-carboxylate and 7-benzyl-3H, 4H, 7H-pyrrolo [2,3d] pyrimidin-4-one) and benzyl bromide as reagents prepared Example 147. MCBP: calculated for C38H41N5O3: 615.3209, found: 616.3308 [(M + H) ⁺ the form].

7-Benzyl-3 - [(4-hydroxy-1- {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 148).

Using General Procedure 6, starting with Synthesis compound R3z and Synthesis compound R1c as reagents, Example 148 was prepared. MCBP: calculated for C ₄₁ H ₄₃ N ₇ O ₃ S: 713.3148, found: 357.6653 [(M + 2H) ²⁺ form ].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3,4,5-trimethoxyphenyl) -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one ( Example 149).

Using General Procedure 7, starting with Synthesis compound R3ac and Synthesis compound R1d as reagents, Example 149 was prepared. MCBP: calculated for C ₄₄ H ₄₇ N ₇ O ₇ S: 817.3257, found: 818.3322 [(M + H) + form] ...

7- (3,5-Dichlorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1), 3-thiazol5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3d] pyrimidin-4-one (Example 150 ).

Using General Procedure 7, starting from the Synthesis compound R3ad and the Synthesis compound R1d as reagents, Example 150 was prepared. MCBP: calculated for C ₄₁ H ₃₉ N ₇ O ₄ SCl ₂ : 795.2161, found: 796.225 [(M + H) + form ].

7- (3-Chlor-5-methoxyphenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) - 1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one ( Example 151).

Using General Procedure 7, starting from the Synthesis compound R3ae and the Synthesis compound R1d as reagents, Example 151. MCBP: calculated for C ₄₂ H ₄₂ N ₇ O ₅ SCl: 791.2657, found: 792.2736 [(M + H) + form] ...

7- (3,5-Dimethoxyphenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1), 3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one (Example 152 ).

Using General Procedure 7, starting with Synthesis compound R3af and Synthesis compound R1d as reagents, Example 152 was prepared. MCBP: calculated for C ₄₃ H ₄₅ N ₇ O ₆ S: 787.3152, found: 788.3224 [(M + H) + form] ...

7- (3,4-dichlorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1), 3-thiazol-5yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one ( Example 153).

Using General Procedure 7, starting with Synthesis compound R3ag and Synthesis compound R1d as reagents, Example 153 was prepared. MCBP: Calculated for C ₄ iH ₃₉ Cl ₂ N ₇ O ₄ S: 795.2161, Found: 796.2221 [(M + H) + the form].

7- (4-chloro-3-fluorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) - 1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one ( Example 154).

Using General Procedure 7, starting from the Synthesis compound R3ah and the Synthesis compound R1d as reagents, Example 154 was prepared. MCBP: calculated for C ₄₁ H ₃₉ ClFN ₇ O ₄ S: 779.2457, found: 780.2528 [(M + H) + form] ...

7- (4-chloro-3-methoxyphenyl) -3 - [(4-hydroxy-1- {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) - 1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one ( Example 155).

Using General Procedure 7, starting from the Synthesis compound R3ai and the Synthesis compound R1d as reagents, Example 155 was prepared. MCBP: calculated for C ₄₂ H ₄₂ ClN ₇ O ₅ S: 791.2657, found: 792.2735 [(M + H) + form] ...

7- (4-Fluoro-3-methoxyphenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1- {[4-methyl-2- (6-methylpyridin-3-yl) - 1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H- 81 037563 pyrrolo [2,3-d] pyrimidine- 4-one (Example 156).

Using General Procedure 7, starting from Synthesis compound R3aj and Synthesis compound R1d as reagents, Example 156 was prepared. MCBP: Calculated for C ₄₂ H ₄₂ FN ₇ O ₅ S: 775.2952 Found:

776.3023 [(M + H) + form].

7- (3,4-Dimethoxyphenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1), 3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one (Example 157 ).

Using General Procedure 7, starting with Synthesis compound R3ak and Synthesis compound R1d as reagents, Example 157 was prepared. MCBP: calculated for C ₄₃ H ₄₅ N ₇ O ₆ S: 787.3152, found: 394.6638 [(M + 2H) ²⁺ form ].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- [4- (trifluoromethyl) phenyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one (Example 158).

Using General Procedure 7, starting with Synthesis compound R3ao and Synthesis compound R1d as reagents, Example 158 was prepared. MCBP: Calculated for C ₄₂ H ₄₀ F ₃ N ₇ O ₄ S: 795.2814, Found: 796.2886 [(M + H) + the form].

7- [4- (Difluoromethyl) phenyl] -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1 , 3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one (Example 159).

Using General Procedure 7, starting with Synthesis compound R3ap and Synthesis compound R1d as reagents, Example 159 was prepared. MCBP: Calculated for C ₄₂ H ₄ iF ₂ N ₇ O ₄ S: 777.2909, Found: 778.2984 [(M + H) + the form].

7- [4- (Benzyloxy) phenyl] -3 - [(4-hydroxy-1 - {[(3R, 4R) -1- {[4-methyl-2- (6-methylpyridin-3-yl) -1 , 3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one (Example 160).

Using General Procedure 7, starting from the Synthesis compound R3az and the Synthesis compound R1d as reagents, Example 160 was prepared. MCBP: calculated for C ₄₈ H ₄₇ N ₇ O ₅ S: 833.3359, found: 834.3447 [(M + H) + form] ...

3 - {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(4-methyl-2-phenyl-1,3-thiazol-5-yl) carbonyl] -3-phenylpiperidin-4yl} carbonyl ) piperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-o n (Example 161)

Using General Procedure 7, starting from the compound Synthesis of R3b and 4-methyl-2-phenylthiazole-5carboxylic acid as reagents, Example 161 was prepared. MCBP: calculated for C ₃₆ H ₃₈ N ₆ O ₄ S: 650.2675, found: 651.2754 [( M + H) + form].

3 - {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(3-methyl-1,2-thiazol-4-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 162).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-methylisothiazole-4carboxylic acid as reagents, Example 162 was prepared. MCBP: Calculated for C ₃₀ H ₃₄ N ₆ O ₄ S: 574.2362, Found: 575.2434 [(M + H) ⁺ form].

3 - {[4-Hydroxy-1 - ({(3R, 4R) -3-phenyl-1 - [(2-phenyl-1,3-thiazol-5-yl) carbonyl] piperidine-4yl} carbonyl) piperidine- 4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-o n (Example 163).

Using General Procedure 7, starting from the Synthesis of R3b compound and 2-phenylthiazole-5-carboxylic acid as reactants, Example 163 was prepared.

MCBP calculated for C ₃₅ H ₃₆ N ₆ O ₄ S: 636.2519, found: 637.2593 [(M + H) + form].

3 - {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(4-methyl-1,3-thiazol-5-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 164).

Using General Procedure 7, starting from the compound Synthesis of R3b and 4-methylthiazole-5-carboxylic acid as reagents, Example 164 was prepared. MCBP: Calculated for C ₃₀ H ₃₄ N ₆ O ₄ S: 574.2362, Found: 575.2437 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(2-Benzyl-4-methyl-1,3-thiazol-5-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) - 4-hydroxypiperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 165).

Using General Procedure 7, starting from the compound Synthesis of R3b and 2-benzyl-4-methylthiazole-5carboxylic acid as reagents, Example 165 was prepared. MCBP: calculated for C ₃₇ H ₄₀ N ₆ O ₄ S: 664.2832, found: 665.2897 [( M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - (2-methylbenzoyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7 -methyl-3, 7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 166).

Using General Procedure 7, starting from the compound Synthesis of R3b and 2-methylbenzoic acid as reagents, Example 166 was prepared. MCBP: calculated for C ₃₃ H ₃₇ N ₅ O ₄ : 567.2846, found: 568.2904 [(M + H) + form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - (3-methylbenzoyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl)

82 037563 methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 167).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-methylbenzoic acid as reagents, Example 167 was prepared. MCBP: calculated for C ₃₃ H ₃₇ N5O ₄ : 567.2846, found:

668.2916 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - (4-methylbenzoyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7 -methyl- 3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 168).

Using General Procedure 7, starting from the compound Synthesis of R3b and 4-methylbenzoic acid as reagents, Example 168 was prepared. MCBP: calculated for C ₃₃ H ₃ 7N ₅ O ₄ : 567.2846, found: 568.2919 [(M + H) ⁺ form] ...

3 - [(1- {[(3R, 4R) -1 - (2-Fluorobenzoyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3, 7-dihydro-4H-pyrrolo [2,3-d] purimudin-4-one (Example 169).

Using General Procedure 7, starting from the compound Synthesis of R3b and 2-fluorobenzoic acid as reagents, Example 169 was prepared. MCBP: calculated for C ₃₂ H ₃₄ FN ₅ O ₄ : 571.2595, found: 572.266 [(M + H) ⁺ form] ...

3 - [(1- {[(3R, 4R) -1 - (3-Fluorobenzoyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3, 7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 170).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-fluorobenzoic acid as reagents, Example 170 was prepared. MCBP: calculated for C ₃₂ H ₃₄ FN ₅ O ₄ : 571.2595, found: 572.265 [(M + H) ⁺ form] ...

3 - [(1- {[(3R, 4R) -1 - (4-Fluorobenzoyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4yl) methyl] -7 -methyl-3,7- dihydro-4H-pyrrolo [2,3-d] pyrimigin-4-one (Example 171).

Using General Procedure 7, starting from the compound Synthesis of R3b and 4-fluorobenzoic acid as reagents, Example 171 was prepared. MCBP: calculated for C ₃₂ H ₃₄ FN ₅ O ₄ : 571.2595, found: 572.267 [(M + H) ⁺ form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (puridin-4-yl) -1,3-thiazol-5-yl] carbonyl} -3 -phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 172).

Using General Procedure 7, starting from the Synthesis compound of R3b and 4-methyl-2- (4-pyridyl) thiazole 5-carboxylic acid as reactants, Example 172 was prepared. MCBP: Calculated for C ₃ 5H ₃₇ N ₇ O ₄ S: 651.2628, found: 652.27 [(M + H) + form].

3 - [(4-Gugroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[2- (purugin-4-yl) -1,3-thiazol-5-yl] carbonyl} piperugin- 4yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 173).

Using General Procedure 7, starting from the compound Synthesis of R3b and 2- (4-pyridyl) thiazole-5carboxylic acid as reagents, Example 173 was prepared. MCBP: Calculated for C ₃₄ H ₃ 5N ₇ O ₄ S: 637.2471, Found: 638.254 [ (M + H) ⁺ form].

3 - [(1 - {[(3R, 4R) -1 - {[2- (2-Fluorophenyl) -4-methyl-1,3-thiazol-5-yl] carbonyl} -3-phenylpiperugin-4-yl ] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 174).

Using General Procedure 7, starting from the Synthesis compound R3b and 2- (2-fluorophenyl) -4methylthiazole-5-carboxylic acid as reagents, Example 174 was prepared. MCBP: Calculated for C ₃₆ H ₃₇ FN ₆ O ₄ S: 668.2581, found : 669.2668 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (2-methylphenyl) -1,3-thiazol-5-yl] carbonyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimigin-4-one (Example 175).

Using General Procedure 7, starting from the Synthesis compound of R3b and 4-methyl-2- (o-tolyl) thiazole-5carboxylic acid as reactants, Example 175 was prepared. MCBP: Calculated for C ₃₇ H ₄₀ N ₆ O ₄ S: 664.2832, found: 665.2917 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(5-Bromothiophen-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperudin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 176).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromothiophene-2-carboxylic acid as reagents, Example 176 was prepared. MCBP: Calculated for C ₃₀ H ₃₂ BrN ₅ O ₄ S: 637.1358, Found: 638.1430 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(1-Benzyl-1H-pyrrol-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4gugroxuniperugin-4-yl] methyl} -7-methyl-3,7-digugro-4H-purrolo [2,3-d] purimugin-4-one (Example 177).

Using General Procedure 7, starting from the compound Synthesis of R3b and 1-benzylpyrrole-2-carboxylic acid as reagents, Example 177 was prepared. MCBP: Calculated for C ₃₇ H ₄₀ N ₆ O ₄ : 632.3111, Found: 633.3184 [(M + H ) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(1-methyl-5-phenyl-1H-pyrrol-2-yl) carbonyl] -3-phenylpiperidin-4yl} carbonyl) piperidine -4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-o n (Example 178).

Using General Procedure 7, starting from the Synthesis compound R3b and 1-methyl-5-phenylpyrrole-2-83 037563 carboxylic acid as reactants, Example 178 was prepared. MCBP: Calculated for C ₃₇ H ₄₀ N ₆ O ₄ :

632.3111, found: 633.3183 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1- (1H-pyrrol-2-ylcarbonyl) piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] - 7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 179).

Using General Procedure 7, starting from the compound Synthesis of R3b and 1H-pyrrole-2-carboxylic acid as reagents, Example 179 was prepared. MCBP: Calculated for C ₃₀ H ₃₄ N ₆ O ₄ : 542.2642, Found: 543.2711 [(M + H ) ⁺ form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(1-methyl-1H-pyrrol-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) piperidin-4 -yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 180).

Using General Procedure 7, starting from the compound Synthesis of R3b and 1-methylpyrrole-2-carboxylic acid as reactants, Example 180 was prepared. MCBP: Calculated for C ₃ iH ₃₆ N ₆ O ₄ : 556.2798, Found: 557.2862 [(M + H ) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[1 - (pyridin-3-ylmethyl) -1H-pyrrol-2-yl] carbonyl} piperidine-4 -yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 181).

Using General Procedure 7, starting from the compound Synthesis of R3b and 1- (3-pyridylmethyl) pyrrole-2carboxylic acid as reactants, Example 181. MCBP: Calculated for C ₃₆ H ₃₉ N ₇ O ₄ : 633.3064, Found: 317.6602 [( M + 2H) 2+ form].

3 - [(1- {[(3R, 4R) -1 - {[5- (2-Aminopyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} -4 -hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 182).

Using General Procedure 7, starting from the Synthesis compound of R3b and 5- (2-amino-4-pyridyl) thiophene 2-carboxylic acid as reactants, Example 182 was prepared. MCBP: Calculated for C ₃₅ H ₃₇ N ₇ O ₄ S: 651.2628, found 326.638 [(M + 2H) ²⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-5- (pyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4 -yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 183).

Using General Procedure 7, starting from the Synthesis compound of R3b and 4-methyl-5- (4-pyridyl) thiophene 2-carboxylic acid as reactants, Example 183 was prepared. MCBP: Calculated for C ₃₆ H ₃₈ N ₆ O ₄ S: 650.2676, found: 651.2752 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3S, 4S) -3-phenyl-1 - {[5- (pyridin-4-yl) thiophen-2-yl] carbonyl} piperidin-4-yl] carbonyl } piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 184).

Using General Procedure 7, starting from 3 - ({4-hydroxy-1 - [(3S, 4S) -3-phenylpiperidin-4-carbonyl] piperidin-4-yl} methyl) -7-methyl-3H, 4H, 7H -pyrrolo [2,3-d] pyrimidin-4-one (which was prepared according to General Procedure 5 using tert-butyl (3S, 4S) -4- (2-oxa-6-azaspiro [2.5] octan-6carbonyl ) -3-phenylpiperidine-1-carboxylate and Synthesis compound R2b) and 5- (4-pyridyl) thiophene-2carboxylic acid as reagents obtained Example 184. MCBP: calculated for C35H36N6O4S: 636.2519, found: 637.2591 [(M + H ) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-nitro-5- (pyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4 -yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 185).

Using General Procedure 7, starting from Synthesis compound R3b and Synthesis compound R1p as reagents, Example 185 was prepared. MCBP: calculated for C ₃₅ H ₃₅ N ₇ O ₆ S: 681.2369, found: 682.2432 [(M + H) + form] ...

3 - {[1 - ({(3R, 4R) -1 - [(1-Etenyl-1H-pyrrol-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4hydroxypiperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 186).

Using General Procedure 7, starting from the compound Synthesis of R3b and 1-vinylpyrrole-2-carboxylic acid as reactants, Example 186 was prepared. MCBP: Calculated for C ₃₂ H ₃₆ N ₆ O ₄ : 568.2798, Found: 569.2884 [(M + H ) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[1 - (prop-2-en-1-yl) -1H-pyrrol-2-yl] carbonyl } piperidin4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 187).

Using General Procedure 7, starting from the compound Synthesis of R3b and 1-allylpyrrole-2-carboxylic acid as reagents, Example 187 was prepared. MCBP: calculated for C ₃₃ H ₃₈ N ₆ O ₄ : 582.2955, found: 583.3039 [(M + H ) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(1-methyl-1H-indol-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) piperidin-4 -yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 188).

Using General Procedure 7, starting from the compound Synthesis of R3b and 1-methylindole-2-carboxylic acid as reagents, Example 188 was prepared. MCBP: Calculated for C ₃₅ H ₃₈ N ₆ O ₄ : 606.2955, Found: 607.3033 [(M + H ) + form].

3 - {[1 - ({(3R, 4R) -1 - [(4-Bromo-1-methyl-1H-pyrrol-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) 4-hydroxypiperidine -4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example

- 84 037563

189).

Using General Procedure 7, starting from the compound Synthesis of R3b and 4-bromo-1-methylpyrrole-2carboxylic acid as reagents, Example 189 was prepared. MCBP: Calculated for C ₃₁ H ₃₅ BrN ₆ O ₄ : 634.1903, Found: 635.1981 [(M + H) + form].

4- hydroxypiperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 190).

Using General Procedure 7, starting from the compound Synthesis of R3b and 2,2-difluoro-1,3-benzodioxole 5-carboxylic acid as reactants, Example 190 was prepared. MCBP: Calculated for C ₃₃ H ₃₃ F ₂ N ₅ O ₆ : 633.2399, found: 634.2475 [(M + H) ⁺ form].

3 - [(4-Hygroxy-1 - {[(3R, 4R) -1- (1H-indol-5-ylcarbonyl) -3-phenylpiperigin-4-yl] carbonyl} piperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 191).

Using General Procedure 7, starting from the compound Synthesis of R3b and 1H-indole-5-carboxylic acid as reagents, Example 191. MCBP: Calculated for C ₃₄ H ₃₆ N ₆ O ₄ : 592.2798, Found: 593.2881 [(M + H ) + form].

tert-Butyl 6 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine -3-yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} -3,4-dihydroisoquinoline-2 (1H) -carboxylate (Example 192).

Using General Procedure 7, starting from the Synthesis compound R3b and 2-tert-butoxycarbonyl-3,4-dihydro-1H-isoquinoline-6-carboxylic acid as reactants, Example 192 was prepared. MCBP: Calculated for C ₄₀ H ₄₈ N ₆ O ₆ : 708.3635, found: 709.3717 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(1-Acetyl-1,2,3,4-tetrahydroquinolin-6-yl) carbonyl] -3-phenylpiperidin-4yl} carbonyl) -4- hydroxypiperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 193).

Using General Procedure 7, starting from the Synthesis compound R3b and 1-acetyl-3,4-dihydro-2Hquinoline-6-carboxylic acid as reactants, Example 193 was prepared. MCBP: Calculated for C ₃₇ H ₄₂ N ₆ O ₅ : 650.3217, found: 651.3306 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(4-Bromopyridin-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 194).

Using General Procedure 7, starting from the compound Synthesis of R3b and 4-bromopyridine-2-carboxylic acid as reagents, Example 194 was prepared. MCBP: Calculated for C ₃₁ H ₃₃ BrN ₆ O ₄ : 632.1747, Found: 633.1821 [(M + H ) + form].

3 - {[1 - ({(3R, 4R) -1 - [(2-Bromopyridin-4-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 195).

Using General Procedure 7, starting from the compound Synthesis of R3b and 2-bromopyridine-4-carboxylic acid as reactants, Example 195 was prepared. MCBP: calculated for C ₃ iH _{33 BrN 6} O ₄ : 632.1747, found: 633.1824 [(M + H ) + form].

3 - {[1 - ({(3R, 4R) -1 - [(5-Bromopyridin-3-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 196).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromopyridine-3-carboxylic acid as reactants, Example 196 was prepared. MCBP: Calculated for C ₃₁ H ₃₃ BrN ₆ O ₄ : 632.1747, Found: 633.1827 [(M + H ) + form].

3 - {[1 - ({(3R, 4R) -1 - [(5-Bromo-3-fluorothiophen-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4hydroxyniperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 197).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromo-3-fluorothiophene-2-carboxylic acid as reactants, Example 197 was prepared. MCBP: calculated for C ₃₀ H ₃₁ BrFN ₅ O ₄ S: 655.1264, found: 656.1341 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(6-Bromopyridin-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 198).

Using General Procedure 7, starting from the compound Synthesis of R3b and 6-bromopyridine-2-carboxylic acid as reagents, Example 198 was prepared. MCBP: calculated for C ₃₁ H ₃₃ BrN ₆ O ₄ 632.1747, found: 633.1822 [(M + H) + form].

3 - [(1 - {[(3R, 4R) -1- (1H-Benzotriazol-5-ylcarbonyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 - methyl 3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 199).

Using General Procedure 7, starting from the compound Synthesis of R3b and 1H-benzotriazole-5-carboxylic acid as reagents, Example 199 was prepared. MCBP: calculated for C ₃₂ H ₃₄ N ₈ O ₄ : 594.2703, found: 595.2782 [(M + H ) ⁺ form].

3 - [(4-Hygroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[trans-2-phenylcyclopropyl] carbonyl} piperigin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one, diastereoisomer 1 (Example 200).

Using General Procedure 7, starting from the compound Synthesis of R3b and trans-2-phenyl-1cyclopropanecarboxylic acid as reagents, Example 200 was obtained as a pure diastereoisomer 85 037563 after purification by preparative LC (C-18 Gemini-NX 5 μm column , 5 mM aqueous

NH4HCO3-MCN, isocratic mode: 37%). MCBP: calculated for C ₃₅ H ₃₉ N ₅ O ₄ : 593.3002, found:

594.3082 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - (3-Bromobenzoyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4yl) methyl] -7 -methyl-3,7- dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 201).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-bromobenzoic acid as reagents, Example 201 was prepared. MCBP: calculated for C ₃₂ H ₃₄ BrN ₅ O ₄ : 631.1794, found: 632.1873 [(M + H) + form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[trans-2-phenylcyclopropyl] carbonyl} piperidin-4yl] carbonyl} piperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one, diastereoisomer 2 (Example 202).

Using General Procedure 7, starting from the Synthesis of R3b compound and trans-2-phenylcyclopropanecarboxylic acid as reagents, Example 202 was obtained as a pure diastereoisomer after purification by preparative LC (C-18 Gemini-NX column 5 μm, 5 mM aqueous NH4HCO3MCN, isocratic mode: 37%). MCBP calculated for C ₃₅ H ₃₉ N ₅ O ₄ : 593.3002, found: 594.3084 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - (3-nitrobenzoyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7 -methyl-3, 7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 203).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-nitrobenzoic acid as reagents, Example 203 was prepared. MCBP: calculated for C ₃₂ H ₃₄ N ₆ O ₆ : 598.2539, found: 599.2625 [(M + H) + form] ...

3 - [(1- {[(3R, 4R) -1-Benzoyl-3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 methyl-3,7-dihydro-4H -pyrrolo [2,3-d] pyrimidin-4-one (Example 204).

Using General Procedure 7, starting from the compound Synthesis of R3b and benzoic acid as reagents, Example 204 was prepared. MCBP: Calculated for C ₃₂ H ₃₅ N ₅ O ₄ : 553.2689, found: 554.2782 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - (3-Ethynylbenzoyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4yl) methyl] -7 -methyl-3,7- dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 205).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-ethynylbenzoic acid as reagents, Example 205 was prepared. MCBP: calculated for C ₃₄ H ₃₅ N ₅ O ₄ : 577.2689, found: 578.2776 [(M + H) ⁺ form] ...

Methyl 3 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine-3yl ) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} benzoate (Example 206).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-methoxycarbonylbenzoic acid as reagents, Example 206 was prepared. MCBP: calculated for C ₃₄ H ₃₇ N ₅ O ₆ : 611.2744, found: 612.2837 [(M + H) + form] ...

- {[4-Hydroxy-1 - ({(3R, 4R) -3-phenyl-1- [3 - (trifluoromethyl) benzoyl] piperidin-4-yl} carbonyl) piperidin-4-yl] methyl} -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 207).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3- (trifluoromethyl) benzoic acid as reagents, Example 207 was prepared. MCBP: Calculated for C ₃₃ H ₃₄ F ₃ N ₅ O ₄ : 621.2563, Found: 622.265 [(M + H) + form].

3 - {[(3R, 4R) -4 - ({4-Hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine-3- yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} benzonitrile (Example 208).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-cyanobenzoic acid as reagents, Example 208 was prepared. MCBP: calculated for C ₃₃ H ₃₄ N ₆ O ₄ : 578.2642, found: 579.272 [(M + H) + form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - (3-methoxybenzoyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7 -methyl-3, 7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 209).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-methoxybenzoic acid as reagents, Example 209 was prepared. MCBP: calculated for C ₃₃ H ₃₇ N ₅ O ₅ : 583.2795, found: 584.2889 [(M + H) + form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1- (3-phenoxybenzoyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7 -methyl-3,7 -dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 210).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-phenoxybenzoic acid as reagents, Example 210 was prepared. MCBP: calculated for C ₃₈ H ₃₉ N ₅ O ₅ : 645.2951, found: 646.3025 [(M + H) + form] ...

3 - [(1- {[(3R, 4R) -1 - (3-tert-Butylbenzoyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin4-yl) methyl] -7-methyl-3, 7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 211).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-tert-butylbenzoic acid as reagents, Example 211. MCBP: calculated for C ₃₆ H ₄₃ N ₅ O ₄ : 609.3315, found: 610.3382 [(M + H) + the form].

5-Bromo-2 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidin-3- 86 037563 yl) methyl] piperidin-1 -yl} carbonyl) -3-phenylpiperidin-1 -yl] carbonyl} thiophene-3-carbonitrile (Example

212).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromo-3-cyanothiophene-2carboxylic acid as reagents, Example 212 was prepared. MCBP: calculated for C ₃₁ H ₃₁ BrN ₆ O ₄ S: 662.1311, found: 663.1384 [( M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - (quinolin-6-ylcarbonyl) piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 213).

Using General Procedure 7, starting from the compound Synthesis of R3b and quinoline-6-carboxylic acid as reagents, Example 213 was prepared. MCBP: Calculated for C ₃₅ H ₃₆ N ₆ O ₄ : 604.2798, Found: 605.2872 [(M + H) ⁺ the form].

3 - [(1- {[(3R, 4R) -1 - (2,3-Dihydro-1,4-benzodioxin-6-ylcarbonyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4 -yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 214).

Using General Procedure 7, starting from the compound Synthesis of R3b and 2,3-dihydro-1,4-benzodioxin6-carboxylic acid as reactants, Example 214 was prepared. MCBP: Calculated for C ₃₄ H ₃₇ N ₅ O ₆ : 611.2744 Found: 612.2822 [(M + H) ⁺ form].

3 - [(1 - {[(3R, 4R) -1- (5,6-Dihydro-4H-cyclopenta [b] thiophen-2-ylcarbonyl) -3-phenylpiperidin-4yl] carbonyl} -4-hydroxypiperidine-4 -yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 215).

Using General Procedure 7, starting from the Synthesis compound R3b and 5,6-dihydro-4H-cyclopenta [b] thiophene-2-carboxylic acid as reactants, Example 215 was prepared. MCBP: Calculated for C ₃₃ H ₃₇ N5O4S: 599.2567 Found : 600.2645 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - (4,5,6,7-tetrahydro-1-benzothiophen-2-ylcarbonyl) piperidin4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 216).

Using General Procedure 7, starting from the Synthesis compound R3b and 4,5,6,7-tetrahydrobenzothiophene-2-carboxylic acid as reactants, Example 216 was prepared. MCBP: Calculated for C ₃₄ H ₃₉ N ₅ O ₄ S: 613.2723 Found : 614.2805 [(M + H) ⁺ form].

3 - {[1 - ({(3R, 4R) -1 - [(5-Bromo-1-methyl-1H-pyrrol-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) 4-hydroxypiperidine -4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 217).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromo-1-methylpyrrole-2carboxylic acid as reagents, Example 217 was prepared. MCBP: Calculated for C ₃₁ H ₃₅ N ₆ O4Br: 634.1903, Found: 637.1959 [(M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -3-phenyl-1 - [(3-phenylcyclobutyl) carbonyl] piperidin-4-yl} carbonyl) piperidin-4-yl] methyl} -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 218).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-phenylcyclobutanecarboxylic acid as reagents, Example 218 was prepared. MCBP: calculated for C ₃₆ H ₄₁ N ₅ O ₄ : 607.3159, found: 608.3236 [(M + H) + form] ...

3 - [(1- {[(3R, 4R) -1 - (3-Ethoxybenzoyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4yl) methyl] -7 -methyl-3,7- dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 219).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-ethoxybenzoic acid as reagents, Example 219 was prepared. MCBP: calculated for C ₃₄ H ₃₉ N ₅ O ₅ : 597.2951, found: 598.3032 [(M + H) + form] ...

- {[4-Hydroxy-1 - ({(3R, 4R) -1- [3 - (4-methylpiperazin-1-yl) benzoyl] -3-phenylpiperidin-4-yl} carbonyl) piperidin-4-yl ] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 220).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3- (4-methylpiperazin-1-yl) benzoic acid as reagents, Example 220 was prepared. MCBP: calculated for C37H45N7O4: 651.3533, found: 652.3604 [(M + H) + the form].

- {[4-Hydroxy-1 - ({(3R, 4R) -3-phenyl-1- [3 - (propan-2-yl) benzoyl] piperidin-4-yl} carbonyl) piperidin-4-yl] methyl} -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 221).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-isopropylbenzoic acid as reagents, Example 221. MCBP: calculated for C ₃₅ H ₄₁ N ₅ O ₄ : 595.3159, found: 596.3251 [(M + H) + form] ...

- {[4-Hydroxy-1 - ({(3R, 4R) -3-phenyl-1- [3 - (pyrrolidin-1-ylmethyl) benzoyl] piperidin-4-yl} carbonyl) piperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 222).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3- (pyrrolidin-1-ylmethyl) benzoic acid as reactants, Example 222 was prepared. MCBP: Calculated for C37H44N6O4: 636.3424 Found: 637.3504 [(M + H) + Form] ...

3 - {[1 - ({(3R, 4R) -1- [3 - (Dimethylamino) benzoyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidin-4-yl] methyl} -7 -methyl -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 223).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3- (dimethylamino) benzoic

- 87 037563 acids as reagents prepared Example 223. MCBP: calculated for C ₃₄ H ₄₀ N ₆ O ₄ : 596.3111, found: 597.3194 [(M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1- [3 - (morpholin-4-yl) benzoyl] -3-phenylpiperidin-4yl} carbonyl) piperidin-4-yl] methyl} - 7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-o n (Example

224).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-morpholinobenzoic acid as reagents, Example 224 was prepared. MCBP: calculated for C ₃₆ H ₄₂ N ₆ O ₅ : 638.3217, found: 639.3282 [(M + H) ⁺ form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[1 - (methylsulfonyl) -1,2,3,4-tetrahydroquinolin-6-yl] carbonyl} -3 phenylpiperidin-4 -yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 225).

Using General Procedure 7, starting from the Synthesis compound R3b and 1-methylsulfonyl-3,4-dihydro-2H-quinoline-6-carboxylic acid as reactants, Example 225 was prepared. MCBP: Calculated for C ₃₆ H ₄₂ N ₆ O ₆ S: 686.2886 found: 687.2962 [(M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -3-phenyl-1- [3 - (piperidin-1-yl) benzoyl] piperidin-4-yl} carbonyl) piperidin-4-yl] methyl } -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 226).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3- (1-piperidyl) benzoic acid as reagents, Example 226 was prepared. MCBP: Calculated for C ₃₇ H ₄₄ N ₆ O ₄ : 636.3424, Found: 637.3483 [(M + H) + form].

6 - {[(3R, 4R) -4 - ({4-Hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine-3- yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} -1-methyl-3,4-dihydroquinolin-2 (1H) one (Example 227).

Using General Procedure 7, starting from the Synthesis compound R3b and 1-methyl-2-oxo-3,4-dihydroquinoline-6-carboxylic acid as reactants, Example 227 was prepared. MCBP: Calculated for C36H40N6O5: 636.3060, Found: 637.3162 [(M + H) + form].

3 - [(1 - {[(3R, 4R) -1- {3 - [(Dimethylamino) methyl] benzoyl} -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] - 7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 228).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3- (dimethylaminomethyl) benzoic acid as reagents, Example 228 was prepared. MCBP: Calculated for C ₃₅ H ₄₂ N ₆ O ₄ : 610.3268, Found: 611.335 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(1-Etenyl-1H-indol-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4hydroxypiperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 229).

Using General Procedure 7, starting from Synthesis compound R3b and Synthesis compound R1t as reagents, Example 229 was prepared. MCBP: calculated for C ₃₆ H ₃₈ N ₆ O ₄ : 618.2955, found: 619.3002 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(5-Bromo-1-ethenyl-1H-pyrrol-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4- hydroxypiperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 230).

Using General Procedure 7, starting from the Synthesis compound R3b and the Synthesis compound Rlu as reagents, Example 230 was prepared. MCBP: calculated for C ₃₂ H ₃₅ BrN ₆ O ₄ : 646.1903, found: 647.1989 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - (2-Acetylbenzoyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4yl) methyl] -7-methyl-3,7- dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 231)

Using General Procedure 7, starting from the compound Synthesis of R3b and 2-acetylbenzoic acid as reagents, Example 231 was prepared. MCBP: Calculated for C ₃₄ H ₃₇ N ₅ O ₅ : 595.2795, Found: 596.2861 [(M + H) + form] ...

3 - {[1 - ({(3R, 4R) -1 - [(3 -Fluoro-4,5-diiodothiophen-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4hydroxypiperidin-4- yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 232).

Using General Procedure 7, starting with Synthesis compound R3b and Synthesis compound R1h as reagents, Example 232 was prepared. MCBP: Calculated for C ₃₀ H ₃₀ FI ₂ N ₅ O ₄ S: 829.0092, Found: 830.0159 [(M + H) + the form].

Methyl 2 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine-3yl ) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} benzoate (Example 233).

Using General Procedure 7, starting from the compound Synthesis of R3b and 2-methoxycarbonylbenzoic acid as reagents, Example 233 was prepared. MCBP: calculated for C ₃₄ H ₃₇ N ₅ O ₆ : 611.2744, found: 612.2823 [(M + H) + form] ...

3 - {[1 - ({(3R, 4R) -1 - [(3-Fluoro-4-iodo-5-methylthiophen-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4- hydroxypiperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 234).

Using General Procedure 7, starting from the Synthesis compound R3b and the Synthesis compound R1i as reagents, Example 234 was prepared. MCBP: calculated for C ₃ iH ₃₃ FIN ₅ O ₄ S: 717.1282, found: 718.1352 [(M + H) + form] ...

- 88 037563

3 - {[1 - ({(3R, 4R) -1 - [(4-Bromo-1-ethenyl-1H-pyrrol-2-yl) carbonyl] -3-phenylnineridin-4-yl} carbonyl) -4- hydroxypiperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 235).

Using General Procedure 7, starting from Synthesis compound R3b and Synthesis compound R1v as reagents, Example 235 was prepared. MCBP: calculated for C ₃₂ H ₃₅ BrN ₆ O ₄ : 646.1903, found: 647.198 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(3-Chloro-4-methylthiophen-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4hydroxypiperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 236).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-chloro-4-methylthiophene-2carboxylic acid as reagents, Example 236 was prepared. MCBP: calculated for C ₃₁ H ₃₄ ClN ₅ O ₄ S: 607.2020, found: 608.2107 [( M + H) ⁺ form].

3 - [(1- {[(3R, 4R) -1 - {[3-Amino-4- (methylsulfonyl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidine -4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 237).

Using General Procedure 7, starting from the Synthesis compound of R3b and 3-amino-4-methylsulfonylthiophene-2-carboxylic acid as reactants, Example 237 was prepared. MCBP: Calculated for C ₃₁ H ₃₆ N ₆ O ₆ S ₂ : 652.2137 Found: 653.2224 [(M + H) ⁺ form].

3 - {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(3-iodo-4-methylthiophen-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) piperidin-4 -yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 238).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-iodo-4-methylthiophene-2carboxylic acid as reagents, Example 238 was prepared. MCBP: calculated for C ₃₁ H ₃₄ IN ₅ O ₄ S: 699.1376, found: 700.145 [( M + H) ⁺ form].

3 - {[1 - ({(3R, 4R) -1 - [(5-Bromo-3-chloro-4-methylthiophen-2-yl) kαcarbonyl] -3-phenylpineridin-4-yl} kαrbonyl) -4- hydroxypiperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 239).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromo-3-chloro-4-methylthiophene 2-carboxylic acid as reactants, Example 239 was prepared. MCBP: Calculated for C ₃₁ H ₃₃ BrClN ₅ O ₄ S: 685.1125 Found : 686.1217 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - ({1 - [(methylsulfanyl) methyl] -1H-pyrrol-2-yl} carbonyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 240).

Using General Procedure 7, starting from the compound Synthesis of R3b and 1- (methylsulfanylmethyl) pyrrole-2-carboxylic acid as reagents, Example 240 was prepared. MCBP: Calculated for C ₃₂ H ₃₈ N ₆ O ₄ S: 602.2675, Found: 603.2756 [ (M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - (quinoxalin-6-ylcarbonyl) piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 241).

Using General Procedure 7, starting from the compound Synthesis of R3b and quinoxaline-6-carboxylic acid as reagents, Example 241. MCBP: Calculated for C ₃₄ H ₃₅ N ₇ O ₄ : 605.2750, Found: 606.2831 [(M + H) + the form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(1-methyl-1H-indol-6-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) piperidin-4 -yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 242).

Using General Procedure 7, starting from the compound Synthesis of R3b and 1-methylindole-6-carboxylic acid as reagents, Example 242 was prepared. MCBP: Calculated for C ₃₅ H ₃₈ N ₆ O ₄ : 606.2955, Found: 607.3035 [(M + H ) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(5-okco-1-phenylpyrrolidin-3-yl) carbonyl] -3-phenylpiperidin-4yl} carbonyl) piperidin-4-yl ] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-o n (Example 243).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-oxo-1-phenylpyrrolidine-3carboxylic acid as reagents, Example 243 was prepared. MCBP: Calculated for C ₃₆ H ₄₀ N ₆ O ₅ : 636.3060, Found: 637.3129 [(M + H) + form].

tert-Butyl 7 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine -3-yl) methyl] piperidin-1 -yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} -3,4-dihydroquino xaline-1 (2H) -carboxylate (Example 244).

Using General Procedure 7, starting from the Synthesis compound R3b and 4-tert-butoxycarbonyl-2,3-dihydro-1H-quinoxaline-6-carboxylic acid as reactants, Example 244 was prepared. MCBP: Calculated for C ₃₉ H ₄₇ N ₇ O ₆ : 709.3588, found: 710.3667 [(M + H) + form].

tert-Butyl 7 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine -3-yl) methyl] piperidin-1 -yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} -3,4-dihydroquinoline 1 (2H) -carboxylate (Example 245).

Using General Procedure 7, starting from the Synthesis compound R3b and 1-tert-butoxycarbonyl-3,4-dihydro-2H-quinoline-7-carboxylic acid as reactants, Example 245 was prepared. MCBP: Calculated for C ₄₀ H ₄₈ N ₆ O ₆ : 708.3635, found: 709.3715 [(M + H) + form].

- 89 037563

- {[4-Г ugpoKCu-1 - ({(3R, 4R) -1- [3 - (hydroxyacetyl) benzoyl] -3-phenylpiperidin-4-yl} carbonyl) piperidin-4 -yl] methyl} -7- methyl 3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 246).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3- (2-chloroacetyl) benzoic acid as reagents, Example 246 was prepared. MCBP: Calculated for C ₃₄ H ₃₇ N ₅ O ₆ : 611.2744, Found: 612.2817 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(3-Bromomuophen-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 247).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-bromothiophene-2-carboxylic acid as reagents, Example 247 was prepared. MCBP: Calculated for C30H3 ₂ BrN ₅ O ₄ S: 637.1359, Found: 638.1428 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(4-Bromo-1,3-thiazol-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidine- 4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 248).

Using General Procedure 7, starting from the compound Synthesis of R3b and 4-bromothiazole-2-carboxylic acid as reagents, Example 248 was prepared. MCBP: Calculated for C ₂₉ H ₃ iBrN ₆ O ₄ S: 638.1311, Found: 639.1389 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(5-Brommuophen-3-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 249).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromothiophene-3-carboxylic acid as reactants, Example 249 was prepared. MCBP: Calculated for C ₃₀ H ₃₂ BrN ₅ O ₄ S: 637.1359, Found: 638.1438 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(2-Brommuophen-3-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 250).

Using General Procedure 7, starting from the compound Synthesis of R3b and 2-bromothiophene-3-carboxylic acid as reagents, Example 250 was prepared. MCBP: calculated for C ₃₀ H ₃₂ BrN ₅ O ₄ S: 637.1359, found: 638.1443 [(M + H) + form].

3-Ethoxy-N- (4 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3 -d] pyrimidin-3-yl) methyl] piperidin-1 -yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} benzyl) propanamide (Example 251).

Using General Procedure 7, starting from the compound Synthesis of R3b and 4 - [(3-ethoxypropanoylamino) methyl] benzoic acid as reactants, Example 251. MCBP: Calculated for C ₃₈ H ₄₆ N ₆ O ₆ : 682.3479 Found: 683.3559 [ (M + H) ⁺ form].

tert-Butyl (4 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidin-3-yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} benzyl) carbamate (Example 252).

Using General Procedure 7, starting from the compound Synthesis of R3b and 4 - [(tert-butoxycarbonylamino) methyl] benzoic acid as reagents, Example 252 was prepared. MCBP: calculated for C38H46N6O6: 682.3479, found: 683.3567 [(M + H) ⁺ form ].

3 - {[1 - ({(3R, 4R) -1 - [(3-Chloro-5-iodothiophen-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidin-4- yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 253).

Using General Procedure 7, starting with Synthesis compound R3b and Synthesis compound R1j as reagents, Example 253 was prepared. MCBP: calculated for C ₃₀ H ₃₁ ClIN ₅ O ₄ S: 719.0830, found: 720.0905 [(M + H) ⁺ form] ...

3 - [(1- {[(3R, 4R) -1 - (3-Acetylbenzoyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4yl) methyl] -7 -methyl-3,7- dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 254).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-acetylbenzoic acid as reagents, Example 254 was prepared. MCBP: calculated for C34H3-N5O5: 595.2795, found: 596.2875 [(M + H) + form].

3 - {[(3R, 4R) -4 - ({4-Hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine-3- yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} benzaldehyde (Example 255).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-formylbenzoic acid as reagents, Example 255 was prepared. MCBP: calculated for C33H35N5O5: 581.2638, found: 582.271 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - (3-Etenylbenzoyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4yl) methyl] -7 -methyl-3,7- dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 256).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-vinylbenzoic acid as reagents, Example 256 was prepared. MCBP: calculated for C ₃₄ H ₃₇ N ₅ O ₄ : 579.2845, found: 580.2931 [(M + H) ⁺ form] ...

3 - [(1- {[(3R, 4R) -1 - (3-Ethylbenzoyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3, 7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 257).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-ethylbenzoic acid as reagents, Example 257 was prepared. MCBP: calculated for C ₃₄ H ₃₉ N ₅ O ₄ : 581.3002, found: 582.3077 [(M + H) + form] ...

- 90 037563

- {[4-Г ugpoKCu-1 - ({(3R, 4R) -1- [3 - (methylsulfonyl) benzoyl] -3-phenylpiperidin-4-yl} carbonyl) piperidin-4-yl] methyl} -7- methyl 3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 258).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-methylsulfonylbenzoic acid as reagents, Example 258 was prepared. MCBP: calculated for C ₃₃ H ₃₇ N ₅ O ₆ S: 631.2465, found: 632.2549 [(M + H) + form ].

3 - {[1 - ({(3R, 4R) -1 - [(4,5-Dichloro-3-fluorothiophen-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4hydroxypiperidin-4- yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 259).

Using General Procedure 7, starting with Synthesis compound R3b and Synthesis compound R1w as reagents, Example 259 was prepared. MCBP: Calculated for C ₃₀ H ₃₀ Cl ₂ FN ₅ O ₄ S: 645.1379, Found: 646.1449 [(M + H) ⁺ the form].

tert-Butyl 3 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine -3-yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} benzoate (Example 260).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-tert-butoxycarbonylbenzoic acid as reagents, Example 260 was prepared. MCBP: calculated for C37H43N5O6: 653.3214, found: 654.3298 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(5-Chloro-3-fluoro-4-methylthiophen-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4- hydroxypiperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 261).

Using General Procedure 7, starting from the Synthesis compound R3b and the Synthesis compound R1l as reagents, Example 261. MCBP: calculated for C ₃₁ H ₃₃ ClFN ₅ O ₄ S: 625.1926, found: 626.1997 [(M + H) ⁺ form] ...

3 - [(1 - {[(3R, 4R) -1 - {[2,4-bis (6-Metulpurigin-3-ul) -1,3-tuαzol-5-ul] carbonyl} -3-phenylpunerigin- 4yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 262).

Using General Procedure 7, starting from the Synthesis compound of R3b and 2,4-bis (6-methyl-3pyridyl) thiazole-5-carboxylic acid as reactants, Example 262 was prepared. MCBP: Calculated for C ₄₁ H ₄₂ N ₈ O ₄ S : 742.3049, found: 743.3126 [(M + H) ⁺ form].

3 - [(1- {[(3R, 4R) -1 - {[4-Chloro-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidine -4 -yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 263).

Using General Procedure 7, starting from the Synthesis compound R3b and 4-chloro-2- (6-methyl-3pyridyl) thiazole-5-carboxylic acid as reactants, Example 263 was prepared. MCBP: Calculated for C ₃ 5H ₃ 6ClN7O4S: 685.2238, found: 686.2299 [(M + H) ⁺ form].

3 - {[1 - ({(3R, 4R) -1 - [(4-Chloro-2-methoxy-1,3-thiazol-5-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) - 4-hydroxypiperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 264).

Using General Procedure 7, starting from the compound Synthesis of R3b and 4-chloro-2-methoxythiazole-5carboxylic acid as reagents, Example 264 was prepared. MCBP: calculated for C ₃₀ H ₃₃ ClN ₆ O ₅ S: 624.1921, found: 625.2 [(M + H) ⁺ form].

3 - {[1 - ({(3R, 4R) -1 - [(4-Bromo-2-methoxy-1,3-thiazol-5-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) - 4-hydroxypiperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 265).

Using General Procedure 7, starting from the compound Synthesis of R3b and 4-bromo-2-methoxythiazole-5carboxylic acid as reagents, Example 265 was prepared. MCBP: calculated for C ₃₀ H ₃₃ BrN ₆ O ₅ S: 668.1417, found: 669.1494 [( M + H) ⁺ form].

6 - {[(3R, 4R) -4 - ({4-Hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine-3- yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} quinazolin-4 (3H) -one (Example 266).

Using General Procedure 7, starting from the compound Synthesis of R3b and 4-oxo-3H-quinazoline-6carboxylic acid as reagents, Example 266 was prepared. MCBP: Calculated for C ₃₄ H ₃₅ N ₇ O ₅ : 621.2699, Found: 622.2775 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[5 - (pyridin-2-yl) thiophen-2-yl] carbonyl} piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 267).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5- (2-pyridyl) thiophene-2carboxylic acid as reagents, Example 267 was prepared. MCBP: Calculated for C ₃₅ H ₃₆ N ₆ O ₄ S: 636.2519, Found: 637.2603 [ (M + H) ⁺ form].

7 - {[(3R, 4R) -4 - ({4-Hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine-3- yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} -3,4-dihydroisoquinolin-1 (2H) -one (Example 268).

Using General Procedure 7, starting from the Synthesis compound R3b and 1-oxo-3,4-dihydro-2Hisoquinoline-7-carboxylic acid as reactants, Example 268 was prepared. MCBP: Calculated for C ₃₅ H ₃₈ N ₆ O ₅ : 622.2903, found: 623.2977 [(M + H) ⁺ form].

3 - {[1 - ({(3R, 4R) -1 - [(3 -Fluoro-5-iodothiophen-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4-91 037563 hydroxypiperidine- 4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 269).

Using General Procedure 7, starting with Synthesis compound R3b and Synthesis compound R1g as reagents, Example 269 was prepared. MCBP: Calculated for C ₃₀ H ₃₁ N ₅ O ₄ FSI: 703.1125 Found:

704.1203 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - {[4-Chloro-2- (2-oxopyridin-1 (2H) -yl) -1,3-thiazol-5-yl] carbonyl} - 3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 270 ).

Using General Procedure 7, starting from the Synthesis compound R3b and 4-chloro-2- (2-oxo-1-pyridyl) thiazole-5-carboxylic acid as reagents, Example 270 was prepared. MCBP: Calculated for C34H34ClN? O5S: 687.2031, found: 688.2081 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (pyridin-2-ylmethyl) -1,3-thiazol-5-yl] carbonyl} - 3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 271).

Using General Procedure 7, starting from the Synthesis compound of R3b and 4-methyl-2- (2-pyridylmethyl) thiazole-5-carboxylic acid as reactants, Example 271. MCBP: Calculated for C ₃₆ H39N ₇ O ₄ S: 665.2784 Found: 666.2862 [(M + H) + form].

5 - {[(3R, 4R) -4 - ({4-Hygroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimigin-3- yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} -1H-indole-2,3-dione (Example 272).

Using General Procedure 7, starting from the compound Synthesis of R3b and 2,3-dioxoindoline-5-carboxylic acid as reagents, Example 272 was prepared. MCBP: calculated for C ₃₄ H ₃₄ N ₆ O ₆ 622.2539, found: 623.2633 [(M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1- [3 - (hydroxymethyl) benzoyl] -3-phenylpiperidin-4-yl} carbonyl) piperigin-4-yl] methyl} -7- methyl 3,7-dihydro-4H-pyrrolo [2,3-d] pyrimigin-4-one (Example 273).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3- (hydroxymethyl) benzoic acid as reagents, Example 273 was obtained. MCBP: Calculated for C ₃₃ H ₃₇ N ₅ O ₅ : 583.2795, Found: 584.2875 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - (2-hydroxybenzoyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7 -methyl-3, 7-dihydro-4H-pyrrolo [2,3-d] pyrimigin-4-one (Example 274).

Using General Procedure 7, starting from the compound Synthesis of R3b and 2-hydroxybenzoic acid as reagents, Example 274 was prepared. MCBP: calculated for C ₃₂ H ₃₅ N ₅ O ₅ : 569.2638, found: 570.2727 [(M + H) + form] ...

3 - [(1- {[(3R, 4R) -1 - {[5-Chloro-4- (dimethylamino) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidine -4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 275).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-chloro-4- (dimethylamino) thiophene-2-carboxylic acid as reagents, Example 275 was prepared. MCBP: Calculated for C32H37CMO4S: 636.2286, Found: 637.2358 [(M + H ) + form].

3 - {[1 - ({(3R, 4R) -1 - [(5-Bromo-4-methoxythiophen-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4hydroxypiperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 276).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromo-4-methoxythiophene-2carboxylic acid as reagents, Example 276 was prepared. MCBP: calculated for C ₃₁ H ₃₄ BrN ₅ O ₅ S: 667.1464, found: 668.153 [( M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(4,5-dibromothiophen-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 277).

Using General Procedure 7, starting from the compound Synthesis of R3b and 4,5-dibromothiophene-2carboxylic acid as reagents, Example 277 was prepared. MCBP: calculated for C ₃₀ H ₃ iBr ₂ N ₅ O ₄ S: 715.0463, found: 716.053 [( M + H) ⁺ form].

3 - {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(3-oxo-2,3-dihydro-1H-inden-5-yl) carbonyl] -3-phenylpiperidin-4yl} carbonyl ) piperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-o n (Example 278).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-oxoindane-5-carboxylic acid as reactants, Example 278 was prepared. MCBP: Calculated for C ₃₅ H ₃₇ N ₅ O ₅ : 607.2795, Found: 608.2871 [(M + H ) + form].

3 - {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(3-oxo-2,3-dihydro-1H-isoindol-5-yl) carbonyl] -3-phenylpiperidin-4-yl } carbonyl) piperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 279).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-oxoisoindoline-5carboxylic acid as reagents, Example 279 was prepared. MCBP: calculated for C34H36N6O5: 608.2747, found: 609.2814 [(M + H) ⁺ form].

3 - [(1- {[(3R, 4R) -1 - {[4-Chloro-2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidine -4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 280).

- 92 037563

Using General Procedure 7, starting from the Synthesis compound R3b and 4-chloro-2- (6-methoxy-3pyridyl) thiazole-5-carboxylic acid as reactants, Example 280 was prepared. MCBP: Calculated for C ₃₅ H ₃₆ N ₇ O ₅ SCl: 701.2187, found: 702.2257 [(M + H) + form].

Methyl 5 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine-3yl ) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} pyridine-3-carboxylate (Example 281).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-methoxycarbonylpyridine-3carboxylic acid as reagents, Example 281. MCBP: Calculated for C ₃₃ H ₃₆ N ₆ O ₆ : 612.2697 Found: 613.2776 [(M + H) ⁺ the form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1- [3 - (2-hydroxyethyl) benzoyl] -3-phenylpiperidin-4-yl} carbonyl) piperidin-4-yl] methyl} - 7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 282).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3- (2-hydroxyethyl) benzoic acid as reagents, Example 282 was prepared. MCBP: Calculated for C ₃₄ H ₃₉ N ₅ O ₅ : 597.2951, Found: 598.3031 [(M + H) ⁺ form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1- [3 - (methylsulfanyl) benzoyl] -3-phenylpiperidin-4-yl} carbonyl) piperidin-4-yl] methyl} -7- methyl 3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 283).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-methylsulfanylbenzoic acid as reagents, Example 283 was prepared. MCBP: calculated for C ₃₃ H ₃₇ N ₅ O ₄ S: 599.2567, found: 600.2656 [(M + H) + form ].

4 - {[(3R, 4R) -4 - ({4-Hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine-3- yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} pyridine-2-carbonitrile (Example 284).

Using General Procedure 7, starting from the compound Synthesis of R3b and 2-cyanopyridine-4-carboxylic acid as reagents, Example 284 was prepared. MCBP: Calculated for C ₃₂ H ₃₃ N ₇ O ₄ : 579.2594, Found: 580.2682 [(M + H ) + form].

Methyl 3 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine-3yl ) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} -5-nitrobenzoate (Example 285).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-methoxycarbonyl-5-nitrobenzoic acid as reagents, Example 285 was prepared. MCBP: Calculated for C ₃₄ H ₃₆ N ₆ O ₈ : 656.2595, Found: 657.2679 [(M + H ) + form].

Dimethyl 5 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidin3-yl ) methyl] piperidin-1 -yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} benzene-1,3-dicarboxylate (Example 286).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3,5-bis (methoxycarbonyl) benzoic acid as reagents, Example 286 was prepared. MCBP: calculated for C36H39N5O8: 669.2798, found: 670.2847 [(M + H) + form].

Methyl 3-bromo-5 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d ] pyrimidin-3-yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} benzoate (Example 287).

Using General Procedure 7, starting from the compound Synthesis of R3b and 3-bromo-5methoxycarbonylbenzoic acid as reagents, Example 287 was prepared. MCBP: calculated for C ₃₄ H ₃₆ BrN ₅ O ₆ : 689.1849, found: 690.1936 [(M + H) + the form].

tert-Butylmethyl 5 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine -3-yl) methyl] piperidin-1 -yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} benzene 1,3-dicarboxylate (Example 288).

Using General Procedure 7, starting from the Synthesis of R3b compound and 3-tert-butoxycarbonyl-5methoxycarbonylbenzoic acid as reagents, Example 288 was prepared. MCBP: calculated for C ₃₉ H45N5O8: 711.3268, found: 712.3342 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[5 - (pyridin-4-yl) thiophen-2-yl] carbonyl} piperidin-4yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 289).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5- (4-pyridyl) thiophene-2-carboxylic acid as reactants, Example 289 was prepared. MCBP: Calculated for C ₃₅ H ₃₆ N ₆ O ₄ S: 636.2519 Found: 637.2597 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (5-methylthiophen-2-yl) -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one ( Example 290).

Using General Procedure 7, starting from the Synthesis compound R3ba and the Synthesis compound R1d as reagents, Example 290 was prepared. MCBP: calculated for C ₄₀ H ₄ iN ₇ O ₄ S ₂ : 747.2662, found: 748.2743 [(M + H) ⁺ form ].

7- (5-Chlorothiophen-2-yl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) - 1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine- 4-one (Example 291).

- 93 037563

Using General Procedure 7, starting from Synthesis compound R3bb and Synthesis compound R1d as reagents, Example 291. MCBP: calculated for C ₃₉ H ₃₈ ClN ₇ O ₄ S ₂ : 767.2115, found:

768.2171 [(M + H) + form].

7- (2,3-Dihydro-1,4-benzodioxin-6-yl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6 -methylpyridin3-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro4H-pyrrolo [2,3- d] pyrimidin-4-one (Example 292).

Using General Procedure 7, starting with Synthesis compound R3bc and Synthesis compound R1d as reagents, Example 292 was prepared. MCBP: calculated for C ₄₃ H ₄₃ N ₇ O ₆ S: 785.2996, found: 786.307 [(M + H) + form] ...

7- (1,3-Benzodioxol-5-yl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl ) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidine-4- he (Ex. 293).

Using General Procedure 7, starting with Synthesis compound R3bd and Synthesis compound R1d as reagents, Example 293 was prepared. MCBP: calculated for C ₄₂ H ₄ iN ₇ O ₆ S: 771.2839, found: 772.2895 [(M + H) + form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- [3 - (trifluoromethyl) phenyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one (Example 294).

Using General Procedure 7, starting with Synthesis compound R3bg and Synthesis compound R1d as reagents, Example 294 was prepared. MCBP: Calculated for C ₄₂ H ₄₀ F ₃ N ₇ O ₄ S: 795.2814, Found: 796.2883 [(M + H) + the form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- [3 - (hydroxymethyl) phenyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one (Example 295).

Using General Procedure 7, starting with Synthesis compound R3bi and Synthesis compound R1d as reagents, Example 295 was prepared. MCBP: calculated for C ₄₂ H ₄₃ N ₇ O ₅ S: 757.3046, found: 758.3124 [(M + H) + form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- [3 - (trifluoromethoxy) phenyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one (Example 296).

Using General Procedure 7, starting with Synthesis compound R3bp and Synthesis compound R1d as reagents, Example 296 was prepared. MCBP: Calculated for C ₄₂ H ₄₀ N ₇ O ₅ F ₃ S: 811.2764, Found: 812.2837 [(M + H) + the form].

7- [3- (Benzyloxy) phenyl] -3 - [(4-hydroxy-1 - {[(3R, 4R) -1- {[4-methyl-2- (6-methylpyridin-3-yl) -1 , 3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one (Example 297).

Using General Procedure 7, starting with Synthesis compound R3bq and Synthesis compound R1d as reagents, Example 297 was prepared. MCBP: calculated for C ₄₈ H ₄₇ N ₇ O ₅ S: 833.3359, found: 834.3436 [(M + H) + form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (6-methylpyridin-2-yl) -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one ( Example 298).

Using General Procedure 7, starting with Synthesis compound R3br and Synthesis compound R1d as reagents, Example 298 was prepared. MCBP: calculated for C ₄ iH ₄₂ N ₈ O ₄ S: 742.3049, found: 743.313 [(M + H) + form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (6-methoxypyridin-2-yl) -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one ( Example 299).

Using General Procedure 7, starting with Synthesis compound R3bs and Synthesis compound R1d as reagents, Example 299 was prepared. MCBP: calculated for C ₄₁ H ₄₂ N ₈ O ₅ S: 758.2998, found: 759.3062 [(M + H) + form] ...

3 - [(1 - {[(3R, 4R) -1 - {[4-chloro-2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidine -4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 300).

Using General Procedure 7, starting from the Synthesis compound R3bu and 4-chloro-2- (6-methoxy-3pyridyl) thiazole-5-carboxylic acid as reactants, Example 300 was prepared. MCBP: calculated for C4oH ₃ 8N ₇ 05SC1: 763.2344, found: 764.242 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3S, 4S) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 301).

Using General Procedure 7, starting from 3 - [(4-hydroxy-1 - {[(3S, 4S) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3, 7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (which was prepared according to General Procedure 5 using tert-butyl (3S, 4S) -4- (2-oxa- 6-azaspiro

[2.5] octane-6-carbonyl) -3-phenylpiperidine-1-carboxylate and Synthesis compounds R2bu) and compounds

Synthesis of R1d as reagents prepared Example 301. MCBP: calculated for C ₄₁ H ₄₁ N ₇ O ₄ S: 727.2941, found: 364.6536 [(M + 2H) ² + form].

3 - {[1 - ({(3R, 4R) -1 - [(2-Bromo-pyridin-4-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidin-4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 302).

Using General Procedure 7, starting from the compound Synthesis of R3bu and 2-bromopyridine-4-carboxylic acid as reagents, Example 302 was prepared. MCBP: Calculated for C ₃₆ H ₃₅ N ₆ O ₄ Br: 694.1903, Found: 695.1969 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(5-Bromopyridin-3-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidin-4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 303).

Using General Procedure 7, starting from the compound Synthesis of R3bu and 5-bromopyridine-3-carboxylic acid as reagents, Example 303 was prepared. MCBP: Calculated for C ₃₆ H ₃₅ N ₆ O4Br: 694.1903, Found: 695.1974 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - (1,3-thiazol-5-ylcarbonyl) piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 304).

Using General Procedure 7, starting from the compound Synthesis of R3bu and thiazole-5-carboxylic acid as reagents, Example 304 was prepared. MCBP: Calculated for C ₃₄ H ₃₄ N ₆ O ₄ S: 622.2362, Found: 623.2429 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - (1,3-thiazol-4-ylcarbonyl) piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 305).

Using General Procedure 7, starting from the compound Synthesis of R3bu and thiazole-4-carboxylic acid as reagents, Example 305 was prepared. MCBP: Calculated for C ₃₄ H ₃₄ N ₆ O ₄ S: 622.2362, Found: 623.2434 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (morpholin-4-yl) -1,3-thiazol-5-yl] carbonyl} -3 -phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 306).

Using General Procedure 7, starting from the compound Synthesis of R3bu and 4-methyl-2-morpholinothiazole 5-carboxylic acid as reagents, Example 306 was prepared. MCBP: calculated for C ₃₉ H ₄₃ N ₇ O ₅ S: 721.3046, found: 722.311 [( M + H) ⁺ form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(4-methyl-1,3-thiazol-5-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 307).

Using General Procedure 7, starting from the compound Synthesis of R3bu and 4-methylthiazole-5-carboxylic acid as reagents, Example 307 was prepared. MCBP: Calculated for C ₃₅ H ₃₆ N ₆ O ₄ S: 636.2519, Found: 637.2595 [(M + H) + form].

3 - {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(2-methyl-1,3-thiazol-5-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 308).

Using General Procedure 7, starting from the compound Synthesis of R3bu and 2-methylthiazole-5-carboxylic acid as reactants, Example 308 was prepared. MCBP: Calculated for C ₃₅ H ₃₆ N ₆ O ₄ S: 636.2519, Found: 637.2582 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(2-Chloro-1,3-tusol-5-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidine- 4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 309).

Using General Procedure 7, starting from the compound Synthesis of R3bu and 2-chlorothiazole-5-carboxylic acid as reagents, Example 309 was prepared. MCBP: calculated for C ₃₄ H ₃₃ ClN ₆ O ₄ S: 656.1973, found: 657.2041 [(M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(1-methyl-1H-indol-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) piperidin-4 -yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 310).

Using General Procedure 7, starting from the compound Synthesis of R3bu and 1-methylindole-2-carboxylic acid as reagents, Example 310 was prepared. MCBP: Calculated for C ₄₀ H ₄₀ N ₆ O ₄ : 668.3111, Found: 669.3183 [(M + H ) ⁺ form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(1-methyl-5-phenyl-1H-pyrrol-2-yl) carbonyl] -3-phenylpiperidin-4yl} carbonyl) piperidine -4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 311).

Using General Procedure 7, starting from the compound Synthesis of R3bu and 1-methyl-5-phenylpyrrole-2carboxylic acid as reagents, Example 311 was prepared. MCBP: Calculated for C ₄₂ H ₄₂ N ₆ O ₄ : 694.3268, Found: 695.3331 [(M + H) + form].

Methyl 3 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(4-oxo-7-phenyl-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine-3yl ) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} benzoate (Example 312).

Using General Procedure 7, starting from the compound Synthesis of R3bu and 3-methoxycarbonylbenzoic acid as reagents, Example 312 was prepared. MCBP: calculated for C ₃₉ H ₃₉ N ₅ O ₆ : 673.2900, found: 674.2969 [(M + H) + form] ...

Methyl 5 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(4-oxo-7-phenyl-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine-3 95 037563 yl) methyl] piperidin-1 -yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} pyridine-3 -carboxylate (Example 313).

Using General Procedure 7, starting from the compound Synthesis of R3bu and 5-methoxycarbonylpyridine3-carboxylic acid as reagents, Example 313 was prepared. MCBP: Calculated for C ₃₈ H ₃₈ N ₆ O ₆ : 674.2853, Found: 675.291 [(M + H) + the form].

Methyl 4 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(4-oxo-7-phenyl-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine-3yl ) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} pyridine-2-carboxylate (Example 314).

Using General Procedure 7, starting from the compound Synthesis of R3bu and 2-methoxycarbonylpyridine4-carboxylic acid as reagents, Example 314 was prepared. MCBP: Calculated for C ₃₈ H ₃₈ N ₆ O ₆ : 674.2853, Found: 675.2914 [(M + H) ⁺ the form].

7-Ethyl-3 - {[4-hydroxy-1 - ({(3R, 4R) -1 - [(4-methyl-2-phenyl-1,3-thiazol-5-yl) carbonyl] -3-phenylpiperidine -4-yl} carbonyl) piperidin-4-yl] methyl} -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 315).

Using General Procedure 7, starting from the compound Synthesis of R3c and 4-methyl-2-phenylthiazole-5carboxylic acid as reagents, Example 315 was prepared. MCBP: calculated for C ₃₇ H ₄₀ N ₆ O ₄ S: 664.2832, found: 665.2903 [( M + H) ⁺ form].

7-Ethyl-3 - {[4-hydroxy-1 - ({(3R, 4R) -1 - [(3-methyl-1,2-thiazol-4-yl) carbonyl] -3-phenylpiperidin-4-yl } carbonyl) piperidin-4-yl] methyl} -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 316).

Using General Procedure 7, starting from the compound Synthesis of R3c and 3-methylisothiazole-4carboxylic acid as reagents, Example 316 was prepared. MCBP: calculated for C ₃ iH ₃₆ N ₆ O4S: 588.2519, found: 589.2601 [(M + H) ⁺ form ].

7-Ethyl-3 - {[4-hydroxy-1 - ({(3R, 4R) -3-phenyl- 1 - [(2-phenyl- 1,3-thiazol-5-yl) carbonyl] piperidine-4- yl} carbonyl) piperidin-4-yl] methyl} -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 317).

Using General Procedure 7, starting from the compound Synthesis of R3c and 2-phenylthiazole-5-carboxylic acid as reagents, Example 317 was prepared. MCBP: Calculated for C ₃₆ H ₃₈ N ₆ O ₄ S: 650.2675, Found: 651.2749 [(M + H) + form].

7-Ethyl-3 - {[4-hydroxy-1 - ({(3R, 4R) -1 - [(4-methyl-1,3-thiazol-5-yl) carbonyl] -3-phenylpiperidin-4-yl } carbonyl) piperidin-4-yl] methyl} -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 318).

Using General Procedure 7, starting from the compound Synthesis of R3c and 4-methylthiazole-5-carboxylic acid as reagents, Example 318 was prepared. MCBP: Calculated for C ₃₁ H ₃₆ N ₆ O4S: 588.2519, Found: 589.259 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(2-Benzyl-4-methyl-1,3-thiazol-5-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) - 4-hydroxypiperidin-4-yl] methyl} -7-ethyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 319).

Using General Procedure 7, starting from the compound Synthesis of R3c and 2-benzyl-4-methylthiazole-5carboxylic acid as reagents, Example 319 was prepared. MCBP: calculated for C ₃₈ H ₄₂ N ₆ O ₄ S: 678.2988, found: 679.3065 [( M + H) + form].

7-Ethyl-3 - [(4-hydroxy-1- {[(3R, 4R) -1 - (2-methylbenzoyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3 , 7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 320).

Using General Procedure 6, starting from the compound Synthesis of R3c and 2-methylbenzoic acid as reagents, Example 320 was prepared. MCBP: calculated for C ₃₄ H ₃₉ N ₅ O ₄ : 581.3002, found: 582.3088 [(M + H) + form] ...

7-Ethyl-3 - [(4-hydroxy-1- {[(3R, 4R) -1 - (3-methylbenzoyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3 , 7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 321).

Using General Procedure 7, starting from the compound Synthesis of R3c and 3-methylbenzoic acid as reagents, Example 321 was prepared. MCBP: calculated for C ₃₄ H ₃₉ N ₅ O ₄ : 581.3002, found: 582.3075 [(M + H) + form] ...

7-Ethyl-3 - [(4-hydroxy-1- {[(3R, 4R) -1 - (4-methylbenzoyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3 , 7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 322).

Using General Procedure 7, starting from the compound Synthesis of R3c and 4-methylbenzoic acid as reagents, Example 322 was prepared. MCBP: calculated for C ₃₄ H ₃₉ N ₅ O ₄ : 581.3002, found: 582.3073 [(M + H) + form] ...

7-Ethyl-3 - [(1 - {[(3R, 4R) -1- (2-fluorobenzoyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -3, 7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 323).

Using General Procedure 7, starting from the compound Synthesis of R3c and 2-fluorobenzoic acid as reagents, Example 323 was prepared. MCBP: calculated for C ₃₃ H ₃₆ FN ₅ O ₄ : 585.2751, found: 586.282 [(M + H) + form] ...

7-Ethyl-3 - [(1 - {[(3R, 4R) -1- (3-fluorobenzoyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -3, 7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 324).

Using General Procedure 7, starting from the compound Synthesis of R3c and 3-fluorobenzoic acid as reagents, Example 324 was prepared. MCBP: calculated for C ₃₃ H ₃₆ FN ₅ O ₄ : 585.2751, found:

- 96 037563

586.2827 [(M + H) + form].

7-Ethyl-3 - [(1 - {[(3R, 4R) -1- (4-fluorobenzoyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -3, 7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 325).

Using General Procedure 7, starting from the compound Synthesis of R3c and 4-fluorobenzoic acid as reagents, Example 325 was prepared. MCBP: calculated for C ₃₃ H ₃₆ FN ₅ O ₄ : 585.2751, found: 586.2846 [(M + H) ⁺ form] ...

7-Ethyl-3 - [(1 - {[(3R, 4R) -1 - {[2- (2-fluorobenzyl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl ] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 326).

Using General Procedure 7, starting from the Synthesis compound of R3c and 2 - [(2-fluorophenyl) methyl] thiazole 5-carboxylic acid as reactants, Example 326 was prepared. MCBP: Calculated for C ₃ 7H ₃₉ FN ₆ O ₄ S: 682.2738 Found : 683.2804 [(M + H) ⁺ form].

7-Ethyl-3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (2-methylphenyl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 327).

Using General Procedure 7, starting from the Synthesis compound of R3c and 4-methyl-2- (o-tolyl) thiazole-5carboxylic acid as reactants, Example 327 was prepared. MCBP: Calculated for C ₃₈ H ₄₂ N ₆ O ₄ S: 678.2988, found: 679.3069 [(M + H) ⁺ form].

7-Ethyl-3 - [(4-hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[5- (pyridin-4-yl) thiophen-2-yl] carbonyl} piperidin-4 -yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 328).

Using General Procedure 7, starting from the compound Synthesis of R3c and 5- (4-pyridyl) thiophene-2carboxylic acid as reagents, Example 328 was prepared. MCBP: calculated for C ₃₆ H ₃₈ N ₆ O ₄ S: 650.2675, found: 651.2755 [ (M + H) ⁺ form].

7-Ethyl-3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (pyridin-4-yl) -1,3-thiazol-5-yl]] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 329).

Using General Procedure 7, starting from the Synthesis compound of R3c and 4-methyl-2- (4-pyridyl) thiazole 5-carboxylic acid as reactants, Example 329 was prepared. MCBP: Calculated for C ₃₆ H ₃₉ N ₇ O ₄ S: 665.2784, found: 666.2855 [(M + H) + form].

7-Ethyl-3 - [(4-hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[2- (pyridin-4-yl) -1,3-thiazol-5-yl]] carbonyl} piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 330).

Using General Procedure 7, starting from the compound Synthesis of R3c and 2- (4-pyridyl) thiazole-5carboxylic acid as reagents, Example 330 was prepared. MCBP: Calculated for C ₃ 5H ₃₇ N ₇ O ₄ S: 651.2628, Found: 652.269 [ (M + H) ⁺ form].

7-Ethyl-3 - [(1 - {[(3R, 4R) -1 - {[2- (2-fluorophenyl) -4-methyl-1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidine4 -yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 331).

Using General Procedure 7, starting from the Synthesis compound R3c and 2- (2-fluorophenyl) -4methylthiazole-5-carboxylic acid as reactants, Example 331 was prepared. MCBP: Calculated for C ₃₇ H ₃₉ FN ₆ O ₄ S: 682.2738 Found : 683.2823 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (pyridin-2-yl) -3,7-dihydro-4H-pyrrolo [2,3d] pyrimidin-4-one (Example 332 ).

Using General Procedure 7, starting with Synthesis compound R3ca and Synthesis compound R1d as reagents, Example 332 was prepared. MCBP: calculated for C ₄₀ H ₄₀ N ₈ O ₄ S: 728.2893, found: 729.2970 [(M + H) + form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (1-methyl-1H-imidazol-4-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine- 4-one (Example 333).

Using General Procedure 7, starting with Synthesis compound R3cg and Synthesis compound R1d as reagents, Example 333 was prepared. MCBP: Calculated for C ₃₉ H ₄₁ N ₉ O ₄ S: 731.3002, Found: 732.3086 [(M + H) + form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (1-methyl-1H-pyrazol-4-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine- 4-one (Example 334).

Using General Procedure 7, starting from Synthesis compound R3ch and Synthesis compound R1d as reagents, Example 334 was prepared. MCBP: calculated for C ₃₉ H ₄ iN ₉ O ₄ S: 731.3002, found: 732.3083 [(M + H) + form] ...

7- [1 - (Difluoromethyl) -1H-pyrazol-4-yl] -3 - [(4-hydroxy-1- {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridine3 -yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro- 97 037563

4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 335).

Using General Procedure 7, starting from Synthesis compound R3ci and Synthesis compound R1d as reagents, Example 335 was prepared. MCBP: calculated for C ₃₉ H ₃₉ F ₂ N ₉ O ₄ S: 767.2814, found:

768.2908 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (pyrimidin-2-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimigin-4-one ( Example 336).

Using General Procedure 7, starting with Synthesis compound R3cj and Synthesis compound R1d as reagents, Example 336 was prepared. MCBP: calculated for C ₃₉ H ₃₉ N ₉ O ₄ S: 729.2845, found: 730.2922 [(M + H) ⁺ form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7 - (1,3-thiazol-2-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine- 4-one (Example 337).

Using General Procedure 7, starting with Synthesis compound R3ck and Synthesis compound R1d as reagents, Example 337 was prepared. MCBP: calculated for C ₃₈ H ₃₈ N ₈ O ₄ S ₂ : 734.2457, found: 735.2523 [(M + H) ⁺ form ].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7 - (1-methylpiperidin-4-yl) -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one ( Example 338).

Using General Procedure 7, starting with Synthesis compound R3k and Synthesis compound R1d as reagents, Example 338 was prepared. MCBP: calculated for C ₄ iH ₄₈ N ₈ O ₄ S: 748.3519, found: 375.1823 [(M + 2H) ²⁺ form ].

3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (prop-2-yn-1-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine -4-one (Example 339)

Using General Procedure 7, starting with Synthesis compound R3m and Synthesis compound R1d as reagents, Example 339 was prepared. MCBP: calculated for C ₃₈ H ₃₉ N ₇ O ₄ S: 689.2784, found: 690.2847 [(M + H) + form] ...

3 - {[1 - ({(3R, 4R) -1 - [(3-fluoro-5-iodothiophen-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4hydroxypiperidin-4-yl] methyl} -7- (2,2,2-trifluoroethyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 340).

Using General Procedure 7, starting with Synthesis compound R3o and Synthesis compound R1g as reagents, Example 340 was prepared. MCBP: Calculated for C ₃ iH ₃₀ F ₄ IN ₅ O ₄ S: 771.0999, Found: 772.1074 [(M + H) + the form].

7- (Buta-2,3-diene-1-yl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3 -yl) -1,3-thiazol5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3d] pyrimidine- 4-one (Example 341).

Using General Procedure 7, starting from the Synthesis compound R3s and the Synthesis compound R1d as reagents, Example 341 was prepared. MCBP: Calculated for C ₃₉ H ₄₁ N ₇ O ₄ S: 703.2941, Found: 704.3008 [(M + H) + form] ...

3 - {[1 - ({(3R, 4R) -1 - [(5-Bromothiophen-2-yl) sulfonyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 342).

Using General Procedure 8, starting from the compound Synthesis of R3b and 5-bromothiophene-2-sulfonyl chloride as reagents, Example 342 was prepared. MCBP: Calculated for C ₂₉ H ₃₂ BrN ₅ O ₅ S ₂ : 673.1028, Found: 674.1114 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(3-Bromophenyl) sulfonyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidin-4-yl] methyl} -7-methyl -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 343).

Using General Procedure 8, starting from the compound Synthesis of R3b and 3-bromobenzenesulfonyl chloride as reagents, Example 343 was prepared. MCBP: calculated for C ₃₁ P ₃₄ BrN ₅ O ₅ S: 667.1464, found: 668.153 [(M + H) + form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - (phenylsulfonyl) piperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7-phenyl-3,7 -dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 344).

Using General Procedure 8, starting from the Synthesis compound of R3bu and benzenesulfonyl chloride as reagents, Example 344 was prepared. MCBP: calculated for C ₃₆ H ₃₇ N ₅ O ₅ S: 651.2515, found: 652.2577 [(M + H) + form].

7- (3,4-Dichlorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazole- 5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 345 ).

Using General Procedure 6, starting with Synthesis compound R3ag and Synthesis compound R1c as reagents, Example 345 was prepared. MCBP: Calculated for C ₄₀ H ₃₉ Cl ₂ N ₇ O ₃ S: 767.2212, Found: 768.2266 [(M + H) + the form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperi-98 037563 din-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methylphenyl) -3,7-dihydro-4H-pyrrolo [2,3 ^] pyrimidin-4-one ( Example 346).

Using General Procedure 6, starting with Synthesis compound R3am and Synthesis compound R1c as reagents, Example 346 was prepared. MCBP: Calculated for C ₄₁ H ₄₃ N ₇ O ₃ S: 713.3148 Found:

714.3224 [(M + H) + form].

7- (4-Chlorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyrigin-3-yl) -1,3- thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one ( Example 347).

Using General Procedure 7, starting from the Synthesis compound R3ar and the Synthesis compound R1d as reagents, Example 347 was prepared. MCBP: calculated for C ₄₁ H ₄₀ N ₇ O ₄ SCl: 761.2551, found: 762.2622 [(M + H) ⁺ form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 348 ).

Using General Procedure 7, starting with Synthesis compound R3ax and Synthesis compound R1d as reagents, Example 348 was prepared. MCBP: calculated for C ₄₂ H ₄₃ N ₇ O ₅ S: 757.3046, found: 758.3117 [(M + H) ⁺ form] ...

3 - {[1 - ({(3R, 4R) -1 - [(2-Bromo-4-methyl-1,3-thiazol-5-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) 4 -hydroxypiperigin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimigin-4-one (Example 349).

Using General Procedure 7, starting from the compound Synthesis of R3b and 2-bromo-4-methylthiazole-5carboxylic acid as reagents, Example 349 was prepared. MCBP: calculated for C ₃₀ H ₃₃ BrN ₆ O ₄ S: 652.1467, found: 653.1548 [( M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(4-methyl-2-phenyl-1,3-thiazol-5-yl) sulfonyl] -3-phenylpiperidin-4yl} carbonyl ) piperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-o n (Example 350).

Using General Procedure 8, starting from the Synthesis compound R3b and 2-bromo-4-methyl-1,3-thiazole 5-sulfonyl chloride as reactants, the resulting crude bromo compound was reacted with phenylboronic acid according to General Procedure 9 to give Example 350. MCBP: calculated for C ₃₅ H ₃₈ N ₆ O ₅ S ₂ : 686.2345, found: 687.2389 [(M + H) + form].

3 - [(4-Hydroxy-1- {[(3R, 4R) -1 - {[4-methyl-2- (pyridin-4-yl) -1,3-thiazol-5-yl] sulfonyl} -3 -phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 351).

Using General Procedure 8, starting from the Synthesis compound R3b and 2-bromo-4-methyl-1,3-thiazole 5-sulfonyl chloride as reactants, the resulting crude bromine compound was reacted with 4- (4,4,5,5 -tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine according to General Procedure 9 to give Example 351. MCBP: calculated for C ₃₄ H ₃₇ N ₇ O ₅ S ₂ : 687.2298, found: 344.6232 [(M + 2H) ²⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (pyrimidin-5-yl) -1,3-thiazol-5-yl] sulfonyl} - 3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 352).

Using General Procedure 8, starting from the Synthesis compound R3b and 2-bromo-4-methyl-1,3-thiazole-5sulfonyl chloride as reactants, the resulting crude bromine compound was reacted with pyrimidin-5-ylboronic acid according to General Procedure 9 to give Example 352. MCBP: calculated for C ₃₃ H ₃₆ N ₈ O ₅ S ₂ : 688.2250, found: 689.2304 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (1-methyl-1H-pyrazol-5-yl) -1,3-thiazole-5- yl] sulfonyl} 3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 353).

Using General Procedure 8, starting from the Synthesis compound R3b and 2-bromo-4-methyl-1,3-thiazole-5sulfonyl chloride as reagents, the resulting crude bromo compound was reacted with 1-methyl-5- (4,4, 5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyrazole according to General Procedure 9 to give Example 353. MCBP: calculated for C ₃₃ H ₃₈ N ₈ O ₅ S ₂ : 690.2407, found: 691.2481 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[5 - (pyrimidin-5-yl) -1,3-thiazol-2-yl] carbonyl} piperidine4 -yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 354).

Using General Procedure 7, starting from the Synthesis compound R3b and 5-bromothiazole-2-carboxylic acid as reactants, the resulting crude bromine compound was reacted with pyrimidin-5-ylboronic acid according to General Procedure 9 to give Example 354. mCbP: calculated for C ₃₃ H ₃₄ N ₈ O ₄ S: 638.2424, found: 639.25 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[5 - (pyridin-3-yl) -1,3-thiazol-2-yl] carbonyl} piperidine -4yl] carbonyl} piperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example

- 99 037563

355).

Using General Procedure 7, starting from the Synthesis of R3b compound and 5-bromothiazole-2-carboxylic acid as reactants, the resulting crude bromine compound was reacted with 3pyridylboronic acid according to General Procedure 9 to give Example 355. MCBP: Calculated for C ₃₄ H ₃₅ N ₇ O ₄ S: 637.2471, found: 638.254 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[5 - (pyridin-4-yl) -1,3-thiazol-2-yl] carbonyl} piperidine -4yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 356).

Using General Procedure 7, starting from the Synthesis compound of R3b and 5-bromothiazole-2-carboxylic acid as reactants, the resulting crude bromine compound was reacted with 4 (4,4,5,5-tetramethyl-1,3,2 -dioxaborolan-2-yl) pyridine according to General Procedure 9 to give Example 356. MCBP: calculated for C ₃₄ H ₃₅ N ₇ O ₄ S: 637.2471, found: 638.252 [(M + H) + form].

3 - [(4-Hygroxy-1 - {[(3R, 4R) -1 - {[5- (1-methyl-1H-pyrazol-5-yl) -1,3-thiazol-2-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 357).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromothiazole-2-carboxylic acid as reactants, the resulting crude bromine compound was reacted with 1methyl-5- (4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl) pyrazole according to General Procedure 9 to give Example 357. MCBP: calculated for C ₃₃ H ₃₆ N ₈ O ₄ S: 640.2580, found: 641.268 [(M + H) + form] ...

3 - [(4-Hydroxy-1- {[(3R, 4R) -3-phenyl-1 - {[5 - (pyridin-3-yl) thiophen-2-yl] methyl} piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 358).

Using General Procedure 6, starting from the Synthesis compound R3b and 2-bromo-5- (chloromethyl) thiophene as reactants, the resulting crude bromine compound was reacted with 3pyridylboronic acid according to General Procedure 9 to give Example 358. MCBP: calculated for C ₃₅ H ₃₈ N ₆ O ₃ S: 622.2726, found: 623.2807 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[5 - (pyridin-4-yl) thiophen-2-yl] methyl} piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 359).

Using General Procedure 6, starting from the Synthesis compound of R3b and 2-bromo-5- (chloromethyl) thiophene as reagents, the resulting crude bromo compound was reacted with 4 (4,4,5,5-tetramethyl-1,3 , 2-dioxaborolan-2-yl) pyridine according to General Procedure 9 to give Example 359. MCBP: calculated for C ₃₅ H ₃₈ N ₆ O ₃ S: 622.2726, found: 623.2807 [(M + H) + form].

3 - {[4-Hygroxy-1 - ({(3R, 4R) -3-phenyl-1 - [(5-phenylthiophen-2-yl) methyl] piperigin-4-yl} carbonyl) piperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 360).

Using General Procedure 6, starting from the Synthesis compound R3b and 2-bromo-5 (chloromethyl) thiophene as reactants, the resulting crude bromine compound was reacted with phenylboronic acid according to General Procedure 9 to give Example 360. MCBP: Calculated for C ₃₆ H ₃₉ N ₅ O ₃ S: 621.2773, found: 622.2859 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (1-methyl-1H-pyrazol-5-yl) thiophen-2-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-nurrolo [2,3-d] pyrimigin-4-one (Example 361).

Using General Procedure 6, starting from the compound Synthesis of R3b and 2-bromo-5- (chloromethyl) thiophene as reagents, the resulting crude bromo compound was reacted with 1methyl-5- (4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl) pyrazole according to General Procedure 9 to give Example 361. MCBP: calculated for C ₃₄ H ₃₆ N ₇ O ₃ S: 625.2835, found: 626.2919 [(M + H) + the form].

3 - {[4-Hygroxy-1 - ({(3R, 4R) -3-phenyl-1 - [(5-phenyl-1,3-thiazol-2-yl) carbonyl] piperidin-4-yl} carbonyl) piperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 362).

Using General Procedure 7, starting from the Synthesis compound of R3b and 5-bromothiazole-2-carboxylic acid as reactants, the resulting crude bromine compound was reacted with phenylboronic acid according to General Procedure 9 to give Example 362. MCBP: Calculated for C ₃₅ H ₃₆ N ₆ O ₄ S: 636.2519, found: 637.2592 [(M + H) + form].

3 - [(4-Hygroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[5- (pyrimidin-5-yl) thiophen-2-yl] methyl} piperigin-4-yl] carbonyl } piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 363).

Using General Procedure 6, starting from the Synthesis compound R3b and 2-bromo-5- (chloromethyl) thiophene as reactants, the resulting crude bromine compound was reacted with pyrimidin-5-ylboronic acid according to General Procedure 9 to give Example 363. MCBP: calculated for C ₃₄ H ₃₇ N ₇ O ₃ S: 623.2679, found: 624.2761 [(M + H) + form].

3 - [(4-Hygroxy-1 - {[(3R, 4R) -1 - {[4-methyl-5- (1-methyl-1H-pyrazol-5-yl) -1,3-thiazol-2- yl] carbonyl} -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 364 ).

Using General Procedure 7, starting from the Synthesis compound R3b and 5-bromo-4-methylthiazole-2-100 037563 carboxylic acid as reactants, the resulting crude bromine compound was reacted with 1-methyl-5- (4,4, 5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyrazole according to General Procedure 9 to give Example 364. MCBP: calculated for C ₃₄ H ₃₈ N8O ₄ S: 654.2737, found:

655.2814 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (1-methyl-1H-pyrαzol-5-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 365).

Using General Procedure 6, starting from the compound Synthesis of R3b and 2-bromo-5- (bromomethyl) thiazole as reagents, the resulting crude bromo compound was reacted with 1methyl-5- (4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl) pyrazole according to General Procedure 9 to give Example 365. MCBP: calculated for C ₃₃ H ₃₈ N ₈ O ₃ S: 626.2787, found: 627.2871 [(M + H) + the form].

3 - {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(4-methyl-5-phenyl-1,3-thiazol-2-yl) carbonyl] -3-phenylpiperidin-4yl} carbonyl ) piperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-o n (Example 366).

Using General Procedure 7, starting from the Synthesis compound of R3b and 5-bromo-4-methylthiazole-2carboxylic acid as reactants, the resulting crude bromine compound was reacted with phenylboronic acid according to General Procedure 9 to give Example 366. MCBP: calculated for C ₃₆ H ₃₈ N ₆ O ₄ S: 650.2675, found: 651.2756 [(M + H) + form].

3 - {[4-Hydroxy-1 - ({(3R, 4R) -3-phenyl-1 - [(2-phenyl-1,3-thiazol-5-yl) methyl] piperidin-4-yl} carbonyl) piperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 367).

Using General Procedure 6, starting from the Synthesis compound of R3b and 2-bromo-5- (bromomethyl) thiazole as reactants, the resulting crude bromine compound was reacted with phenylboronic acid according to General Procedure 9 to give Example 367. MCBP: calculated for C ₃₃ H ₃ 8N6O ₃ S: 622.2726, found: 623.2794 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-5- (pyridin-4-yl) -1,3-thiazol-2-yl] carbonyl} -3 -phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 368).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromo-4-methylthiazole-2carboxylic acid as reactants, the resulting crude bromo compound was reacted with 4- (4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl) pyridine according to General Procedure 9 to give Example 368. MCBP: calculated for C ₃₅ H ₃₇ N ₇ O ₄ S: 651.2628, found: 652.2727 [(M + H) + form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[2- (pyridin-4-yl) -1,3-thiazol-5-yl] methyl} piperidine- 4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 369).

Using General Procedure 6, starting from the Synthesis compound of R3b and 2-bromo-5- (bromomethyl) thiazole as reactants, the resulting crude bromo compound was reacted with 4 (4,4,5,5-tetramethyl-1,3 , 2-dioxaborolan-2-yl) pyridine according to General Procedure 9 to give Example 369. MCBP: calculated for C ₃₄ H ₃₇ N ₇ O ₃ S: 623.2679, found: 624.274 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-5- (pyrimidin-5-yl) -1,3-thiazol-2-yl] carbonyl} - 3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 370).

Using General Procedure 7, starting from the Synthesis compound of R3b and 5-bromo-4-methylthiazole-2carboxylic acid as reactants, the resulting crude bromine compound was reacted with pyrimidin-5-ylboronic acid according to General Procedure 9 to give Example 370. MCBP calculated for C ₃₄ H ₃₆ N ₈ O ₄ S: 652.2580, found: 653.2632 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[2- (pyrimidin-5-yl) -1,3-thiazol-5-yl] methyl} piperidine- 4yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 371).

Using General Procedure 6, starting from the Synthesis compound R3b and 2-bromo-5- (bromomethyl) thiazole as reactants, the resulting crude bromine compound was reacted with pyrimidin-5-ylboronic acid according to General Procedure 9 to give Example 371. MCBP calculated for C ₃₃ H ₃₆ N8O ₃ S: 624.2631, found: 625.2706 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-5- (pyridin-3-yl) -1,3-thiazol-2-yl] carbonyl} -3 -phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 372).

Using General Procedure 7, starting from the Synthesis of R3b compound and 5-bromo-4-methylthiazole-2carboxylic acid as reactants, the resulting crude bromine compound was reacted with 3-pyridylboronic acid according to General Procedure 9 to give Example 372. MCBP calculated for C ₃₅ H ₃₇ N ₇ O ₄ S: 651.2628, found: 652.2723 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[2- (pyridin-3-yl) -1,3-thiazol-5-yl] methyl} piperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 373).

- 101 037563

Using General Procedure 6, starting from the Synthesis compound of R3b and 2-bromo-5- (bromomethyl) thiazole as reactants, the resulting crude bromine compound was reacted with 3pyridylboronic acid according to General Procedure 9 to give Example 373. MCBP:

calculated for C ₃₄ H ₃₇ N ₇ O ₃ S: 623.2679, found: 624.2747 [(M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - {[5-Chloro-3-fluoro-4- (2-methylpyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidine- 4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 374).

Using General Procedure 7, starting from the Synthesis compound R3b and the Synthesis compound R1k as reagents, the resulting crude product was reacted with 2-methyl-4- (4,4,5,5 tetramethyl-1,3,2-dioxaborolane-2 -yl) pyridine according to General Procedure 9 to give Example 374. MCBP: calculated for C ₃₆ H ₃₆ ClFN ₆ O ₄ S: 702.2191, found: 703.2273 [(M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - {[3-Fluoro-5-methyl-4- (2-methylpyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidine- 4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 375).

Using General Procedure 7, starting from the Synthesis compound R3b and the Synthesis compound R1i as reagents, the resulting crude product was reacted with 2-methyl-4- (4,4,5,5 tetramethyl-1,3,2-dioxaborolane-2 -yl) pyridine according to General Procedure 9 to give Example 375. MCBP: calculated for C ₃₇ H ₃₉ FN ₆ O ₄ S: 682.2737, found: 683.28 [(M + H) + form].

3 - [(4-Hydroxy-1- {[(3R, 4R) -3-phenyl-1 - {[5 - (pyridin-3-yl) -1,3-thiazol-2-yl] methyl} piperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 376).

Using General Procedure 6, starting from the Synthesis compound of R3b and 5-bromo-2- (bromomethyl) thiazole as reactants, the resulting crude product was reacted with 3pyridylboronic acid according to General Procedure 9 to give Example 376. MCBP: Calculated for C ₃₄ H ₃₇ N ₇ O ₃ S: 623.2679, found: 624.2737 [(M + H) + form].

3 - [(4-Hygroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[5- (pyrimidin-5-yl) -1,3-thiazol-2-yl] methyl} piperigine- 4yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 377).

Using General Procedure 6, starting from the Synthesis compound R3b and 5-bromo-2- (bromomethyl) thiazole as reactants, the resulting crude product was reacted with pyrimidine-5ylboronic acid according to General Procedure 9 to give Example 377. MCBP: calculated for C ₃₃ H ₃₆ N8O ₃ S: 624.2631, found: 625.2697 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[5 - (pyridin-4-yl) -1,3-thiazol-2-yl] methyl} piperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 378).

Using General Procedure 6, starting from the compound Synthesis of R3b and 5-bromo-2- (bromomethyl) thiazole as reagents, the resulting crude product was reacted with 4- (4,4,5,5 tetramethyl-1,3,2- dioxaborolan-2-yl) pyridine according to General Procedure 9 to give Example 378. MCBP: calculated for C ₃₄ H ₃₇ N ₇ O ₃ S: 623.2679, found: 624.274 [(M + H) + form].

3 - {[4-Hygroxy-1 - ({(3R, 4R) -3-phenyl-1 - [(5-phenyl-1,3-thiazol-2-yl) methyl] piperidin-4-yl} carbonyl) piperigin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 379).

Using General Procedure 6, starting from the Synthesis compound of R3b and 5-bromo-2- (bromomethyl) thiazole as reactants, the resulting crude product was reacted with phenylboronic acid according to General Procedure 9 to give Example 379. MCBP: Calculated for C ₃₃ H ₃ 8N6O ₃ S: 622.2726, found: 623.2816 [(M + H) ⁺ form].

3 - [(4-Hygroxy-1 - {[(3R, 4R) -1 - {[5- (1-methyl-1H-pyrazol-5-yl) -1,3-thiazol-2-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 380).

Using General Procedure 6, starting from the compound Synthesis of R3b and 5-bromo-2- (bromomethyl) thiazole as reagents, the resulting crude product was reacted with 1-methyl-5 (4,4,5,5-tetramethyl-1 , 3,2-dioxaborolan-2-yl) pyrazole according to General Procedure 9 to give Example 380. MCBP: calculated for C ₃₃ H ₃₈ N ₈ O ₃ S: 626.2787, found: 627.2861 [(M + H) + form ].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (2-methylpyridin-4-yl) -1,3-thiazol-2-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 381).

Using General Procedure 6, starting from the compound Synthesis of R3b and 5-bromo-2- (bromomethyl) thiazole as reagents, the resulting crude product was reacted with 2-methyl-4 (4,4,5,5-tetramethyl-1 , 3,2-dioxaborolan-2-yl) pyridine according to General Procedure 9 to give Example 381. MCBP: calculated for C ₃₅ H ₃₉ N ₇ O ₃ S: 637.2835, found: 638.2912 [(M + H) + form ].

3 - [(4-Hygroxy-1 - {[(3R, 4R) -1 - {[2- (2-methoxy-6-methylpyrigin-4-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 382).

Using General Procedure 6, starting from the compound Synthesis of R3b and 2-bromo-5- (bromomethyl) thiazole as reagents, the resulting crude product was reacted with 2-methoxy-6-102 037563 methyl-4- (4.4, 5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine according to General Procedure 9 to give Example 382. MCBP: calculated for C ₃₆ H ₄₁ N ₇ O ₄ S: 667.2940, found: 668.3009 [ (M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[3-methyl-5- (2-methylpyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidine- 4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 383).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromo-3-methylthiophene-2carboxylic acid as reactants, the resulting crude product was reacted with 2-methyl-4- (4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl) pyridine according to General Procedure 9 to give Example 383. MCBP: calculated for C ₃₇ H ₄₀ N ₆ O ₄ S: 664.2832, found: 665.291 [(M + H) + the form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (2-methoxypyridin-4-yl) -3-methylthiophen-2-yl] carbonyl} -3-phenylpiperidin-4 -yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 384).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromo-3-methylthiophene-2carboxylic acid as reactants, the resulting crude product was reacted with (2-methoxy-4-pyridyl) boronic acid according to General Procedure 9 to give Example 384. MCBP: calculated for C ₃₇ H ₄₀ N ₆ O ₅ S: 680.2781, found: 681.2864 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (3-methoxypyridin-4-yl) -3-methylthiophen-2-yl] carbonyl} -3-phenylpiperidin-4 -yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 385).

Using General Procedure 7, starting from the Synthesis compound of R3b and 5-bromo-3-methylthiophene-2carboxylic acid as reactants, the resulting crude product was reacted with (3-methoxy-4-pyridyl) boronic acid according to General Procedure 9 to give Example 385. MCBP: calculated for C ₃₇ H ₄₀ N ₆ O ₅ S: 680.2781, found: 681.286 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[3-methyl-5- (pyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4 -yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 386).

Using General Procedure 7, starting from the Synthesis compound of R3b and 5-bromo-3-methylthiophene-2carboxylic acid as reactants, the resulting crude product was reacted with 3-pyridylboronic acid according to General Procedure 9 to give Example 386. MCBP: calculated for C ₃₆ H ₃₈ N ₆ O ₄ S: 650.2675, found: 651.2762 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (2-methylpyridin-4-yl) thiophen-2-yl] methyl} -3-phenylpiperidin-4yl] carbonyl } piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 387).

Using General Procedure 6, starting from the compound Synthesis of R3b and 2-bromo-5- (chloromethyl) thiophene as reagents, the resulting crude product was reacted with 2-methyl-4 (4,4,5,5-tetramethyl-1 , 3,2-dioxaborolan-2-yl) pyridine according to General Procedure 9 to give Example 387. MCBP: calculated for C ₃₆ H ₄₀ N ₆ O ₃ S: 636.2883, found: 637.2976 [(M + H) + form ].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (2-methoxypyridin-4-yl) thiophen-2-yl] methyl} -3-phenylpiperidin4-yl] carbonyl } piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 388).

Using General Procedure 6, starting from the Synthesis compound R3b and 2-bromo-5- (chloromethyl) thiophene as reagents, the resulting crude product was reacted with (2-methoxy-4pyridyl) boronic acid according to General Procedure 9 to give Example 388. MCBP: calculated for C ₃₆ H ₄₀ N ₆ O ₄ S: 652.2832, found: 327.1501 [(M + 2H) ²⁺ form].

3 - [(1- {[(3R, 4R) -1 - (2,3'-Bithiophen-5-ylmethyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 389).

Using General Procedure 6, starting from the compound Synthesis of R3b and 2-bromo-5- (chloromethyl) thiophene as reagents, the resulting crude product was reacted with 4,4,5,5 tetramethyl-2- (3-thienyl) -1 , 3,2-dioxaborolane according to General Procedure 9 to give Example 389. MCBP: calculated for C ₃₄ H37N ₅ O3S ₂ : 627.2338, found: 628.2426 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (6-methylpyridin-3-yl) thiophen-2-yl] methyl} -3-phenylpiperidin-4yl] carbonyl } piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 390).

Using General Procedure 6, starting from the Synthesis compound R3b and 2-bromo-5- (chloromethyl) thiophene as reactants, the resulting crude product was reacted with (6-methyl-3pyridyl) boronic acid according to General Procedure 9 to give Example 390. MCBP: calculated for C ₃₆ H ₄₀ N ₆ O ₃ S: 636.2883, found: 637.2964 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (3-methoxypyridin-4-yl) thiophen-2-yl] methyl} -3-phenylpiperidin4-yl] carbonyl } piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 391).

- 103 037563

Using General Procedure 6, starting from the Synthesis compound R3b and 2-bromo-5- (chloromethyl) thiophene as reactants, the resulting crude product was reacted with (3-methoxy-4pyridyl) boronic acid according to General Procedure 9 to give Example 391. MCBP:

calculated for C ₃₆ H ₄₀ N ₆ O ₄ S: 652.2832, found: 653.2935 [(M + H) + form].

tert-Butyl [4- (5 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3 -d] pyrimidin-3-yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] methyl} thiophen-2-yl) pyridin-2yl] carbamate (Example 392).

Using General Procedure 6, starting from the compound Synthesis of R3b and 2-bromo-5- (chloromethyl) thiophene as reagents, the resulting crude product was reacted with tert-butyl N [4- (4,4,5,5-tetramethyl -1,3,2-dioxaborolan-2-yl) -2-pyridyl] carbamate according to General Procedure 9 to give Example 392. MCBP: calculated for C ₄₀ H ₄₇ N ₇ O ₅ S: 737.3359, found: 738.3434 [ (M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - {[5- (6-Aminopyridin-3-yl) thiophen-2-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} -4 -hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 393).

Using General Procedure 6, starting from the compound of the Synthesis of R3b and 2-bromo-5- (chloromethyl) thiophene as reagents, the resulting crude product was reacted 5- (4,4,5,5 tetramethyl-1,3,2-dioxaborolane -2-yl) pyridin-2-amine according to General Procedure 9 to give Example 393. MCBP: calculated for C ₃₅ H ₃₉ N ₇ O ₃ S: 637.2835, found: 638.2918 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (2-methoxy-6-methylpyridin-4-yl) thiophen-2-yl] methyl} -3-phenylpiperidine- 4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 394).

Using General Procedure 6, starting from the compound Synthesis of R3b and 2-bromo-5- (chloromethyl) thiophene as reagents, the resulting crude product was reacted 2-methoxy-6methyl-4- (4,4,5,5-tetramethyl -1,3,2-dioxaborolan-2-yl) pyridine according to General Procedure 9 to give Example 394. MCBP: calculated for C ₃₇ H ₄₂ N ₆ O ₄ S: 666.2988, found: 667.3071 [(M + H) + form].

3 - [(4-Hydroxy-1- {[(3R, 4R) -1 - {[5- (6-methoxypyridin-3-yl) thiophen-2-yl] methyl} -3-phenylpiperidin4-yl] carbonyl } piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 395).

Using General Procedure 6, starting from the Synthesis compound of R3b and 2-bromo-5- (chloromethyl) thiophene as reagents, the resulting crude product was reacted with (6-methoxy-3pyridyl) boronic acid according to General Procedure 9 to give Example 395. MCBP: calculated for C ₃₆ H ₄₀ N ₆ O ₄ S: 652.2832, found: 653.2910 [(M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(4-methyl-2,3'-bithiophen-5-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) piperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 396).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromo-3-methylthiophene-2carboxylic acid as reactants, the resulting crude product was reacted with 4,4,5,5-tetramethyl-2- (3-thienyl) -1,3,2-dioxaborolane according to General Procedure 9 to obtain Example 396. MCBP: calculated for C ₃₅ H ₃₇ N ₅ O ₄ S ₂ : 655.2287, found: 656.2362 [(M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(3-methyl-5-phenylthiophen-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) piperidin-4 -yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 397).

Using General Procedure 7, starting from the Synthesis compound of R3b and 5-bromo-3-methylthiophene-2carboxylic acid as reactants, the resulting crude product was reacted with phenylboronic acid according to General Procedure 9 to give Example 397. MCBP: Calculated for C ₃₇ H ₃₉ N ₅ O ₄ S: 649.2723, found: 650.2806 [(M + H) + form].

tert-Butyl [4- (5 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3 -d] pyrimidin-3-yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} -3-methylthiophen-2yl) pyridin-2-yl] carbamate (Example 398).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromo-4-methylthiophene-2carboxylic acid as reactants, the resulting crude product was reacted with tert-butyl N- [4- (4,4,5,5- tetramethyl-1,3,2-dioxaborolαn-2-yl) -2-pyridyl] carbamate according to General Procedure 9 to give Example 398. MCBP: calculated for C ₄₁ H ₄₇ N ₇ O ₆ S: 765.3309, found: 766.3374 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-5- (6-methylpyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 399).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromo-4-methylthiophene-2carboxylic acid as reactants, the resulting crude product was reacted with (6-methyl-3-pyridyl) boronic acid according to General Procedure 9 to give Example 399. MCBP: calculated for C ₃₇ H ₄₀ N ₆ O ₄ S: 664.2832, found: 665.2922 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (6-methoxypyridin-3-yl) -4-methylthiophen-2-yl] carbonyl} -3- 104 037563 phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 400).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromo-4-methylthiophene-2carboxylic acid as reactants, the resulting crude product was reacted with (6-methoxy-3-pyridyl) boronic acid according to General Procedure 9 to give Example 400. MCBP: calculated for C ₃₇ H ₄₀ N ₆ O ₅ S: 680.2781, found: 681.2854 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - {[5- (6-Aminopyridin-3-yl) -4-methylthiophen-2-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} - 4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 401).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromo-4-methylthiophene-2carboxylic acid as reactants, the resulting crude product was reacted with 5- (4,4,5,5-tetramethyl-1,3, 2-dioxaborolan-2-yl) pyridine-2-amine according to General Procedure 9 to give Example 401. MCBP: calculated for C ₃₆ H ₃₉ N ₇ O ₄ S: 665.2784, found: 333.6475 [(M + 2H) ^{2 +} form].

tert-Butyl [4- (5 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3 -d] pyrimidin-3-yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} -4-methylthiophen-2yl) pyridin-2-yl] carbamate (Example 402).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromo-3-methylthiophene-2carboxylic acid as reactants, the resulting crude product was reacted with tert-butyl N- [4- (4,4,5,5- tetramethyl-1,3,2-dioxaborolan-2-yl) -2-pyrigyl] carbamate according to General Procedure 9 to give Example 402. MCBP: calculated for C ₄ iH ₄₇ N ₇ O ₆ S: 765.3309, found: 766.3381 [(M + H) ⁺ form].

3 - [(4-Hygroxy-1 - {[(3R, 4R) -1 - {[5- (2-methoxypyrigin-4-yl) -1,3-thiazol-2-yl] carbonyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 403).

Using General Procedure 7, starting from the Synthesis compound of R3b and 5-bromothiazole-2-carboxylic acid as reactants, the resulting crude product was reacted with (2-methoxy4-pyridyl) boronic acid according to General Procedure 9 to give Example 403 MSBP calculated for C ₃₅ H ₃₇ N ₇ O ₅ S: 667.2577, found: 668.2654 [(M + H) + form].

3 - [(4-Hygroxy-1 - {[(3R, 4R) -1 - {[5- (3-methoxypyrigin-4-yl) -1,3-thiazol-2-yl] carbonyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimigin-4-one (Example 404).

Using General Procedure 7, starting from the Synthesis compound of R3b and 5-bromothiazole-2-carboxylic acid as reactants, the resulting crude product was reacted with (3-methoxy4-pyridyl) boronic acid according to General Procedure 9 to give Example 404 MSBP calculated for C ₃₅ H ₃₇ N ₇ O ₅ S: 667.2577, found: 668.2651 [(M + H) + form].

3 - [(4-Hygroxy-1 - {[(3R, 4R) -1 - {[5- (6-methoxypyrigin-3-yl) -1,3-thiazol-2-yl] carbonyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 405).

Using General Procedure 7, starting from the Synthesis compound of R3b and 5-bromothiazole-2-carboxylic acid as reactants, the resulting crude product was reacted with (6-methoxy3-pyridyl) boronic acid according to General Procedure 9 to give Example 405 MCBP calculated for C ₃₅ H ₃₇ N ₇ O ₅ S: 667.2577, found: 668.2649 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (6-methylpyridin-3-yl) -1,3-thiazol-2-yl] carbonyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 406).

Using General Procedure 7, starting from the Synthesis compound of R3b and 5-bromothiazole-2-carboxylic acid as reactants, the resulting crude product was reacted with (6-methyl-3pyridyl) boronic acid according to General Procedure 9 to give Example 406 MCBP: calculated for C ₃₅ H ₃₇ N ₇ O ₄ S: 651.2628, found: 652.2702 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(3-Fluoro-5-phenylthiophen-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4hydroxypiperigin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimigin-4-one (Example 407).

Using General Procedure 7, starting from Synthesis compound R3b and Synthesis compound R1g as reagents, the resulting crude product was reacted with phenylboronic acid according to General Procedure 9 to give Example 407. MCBP: Calculated for C ₃ 6H ₃ 6FN5O4S: 653.2472 found: 654.2545 [(M + H) ⁺ form].

3 - [(4-Hygroxy-1 - {[(3R, 4R) -1 - ({3-methyl-5- [2- (trifluoromethyl) pyrigin-4-yl] thiophen-2-yl} carbonyl) 3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 408).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromo-3-methylthiophene-2carboxylic acid as reactants, the resulting crude product was reacted with 4- (4,4,5,5-tetramethyl-1,3, 2-dioxaborolan-2-yl) -2- (trifluoromethyl) pyridine in accordance with the General

105 037563 by Procedure 9 to give Example 408. MCBP Calculated for C ₃₇ H ₃₇ F ₃ N ₆ O ₄ S: 718.2549 Found:

719.2627 [(M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(4-methyl-5-phenylthiophen-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) piperidin-4 -yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 409).

Using General Procedure 7, starting from the Synthesis compound of R3b and 5-bromo-4-methylthiophene-2carboxylic acid as reactants, the resulting crude product was reacted with phenylboronic acid according to General Procedure 9 to give Example 409. MCBP: Calculated for C ₃₇ H ₃₉ N ₅ O ₄ S: 649.2723, found: 650.2803 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[5 - (thiophen-3-yl) -1,3-thiazol-2-yl] carbonyl} piperidine -4yl] carbonyl} piperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 410).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromothiazole-2-carboxylic acid as reactants, the resulting crude product was reacted with 4,4,5,5 tetramethyl-2- (3-thienyl) -1,3 , 2-dioxaborolane according to General Procedure 9 to give Example 410. MCBP: calculated for C ₃₃ H ₃₄ N ₆ O ₄ S ₂ : 642.2083, found: 643.2166 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - ({5- [2- (trifluoromethyl) pyridin-4-yl] -1,3-thiazol-2-yl } carbonyl) piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 411).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromothiazole-2-carboxylic acid as reactants, the resulting crude product was reacted with 4- (4,4,5,5 tetramethyl-1,3,2-dioxaborolane- 2-yl) -2- (trifluoromethyl) pyridine according to General Procedure 9 to give Example 411. MCBP: calculated for C ₃₅ H ₃₄ N ₇ O4F ₃ S: 705.2345, found: 706.2421 [(M + H) + form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - ({4-methyl-5- [2- (trifluoromethyl) pyridin-4-yl] thiophen-2-yl} carbonyl) 3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 412).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromo-4-methylthiophene-2carboxylic acid as reactants, the resulting crude product was reacted with 4- (4,4,5,5-tetramethyl-1,3, 2-dioxaborolan-2-yl) -2- (trifluoromethyl) pyridine according to General Procedure 9 to give Example 412. MCBP: calculated for C ₃₇ H ₃₇ N ₆ O ₄ F ₃ S: 718.2549, found: 719.2622 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - ({5- [2- (trifluoromethyl) pyridin-4-yl] thiophen-2-yl} methyl) piperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 413).

Using General Procedure 6, starting from the compound Synthesis of R3b and 2-bromo-5- (chloromethyl) thiophene as reactants, the resulting crude product was reacted with 4- (4,4,5,5 tetramethyl-1,3,2- dioxaborolan-2-yl) -2- (trifluoromethyl) pyridine according to General Procedure 9 to give Example 413. MCBP: calculated for C ₃₆ H ₃₇ F ₃ N ₆ O ₃ S: 690.2600, found: 691.2681 [(M + H ) + form].

3 - [(4-Hydroxy-1- {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 414).

Using General Procedure 6, starting from the Synthesis compound of R3b and 2-bromo-5- (bromomethyl) thiazole as reactants, the resulting crude product was reacted with (6-methyl-3pyridyl) boronic acid according to General Procedure 9 to give Example 414. MCBP: calculated for C ₃₅ H ₃₉ N ₇ O ₃ S: 637.2835, found: 638.2893 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - ({2- [6- (trifluoromethyl) pyridin-3 -yl] - 1,3-thiazole-5- yl} methyl) piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 415).

Using General Procedure 6, starting from the compound Synthesis of R3b and 2-bromo-5- (bromomethyl) thiazole as reactants, the resulting crude product was reacted with [2- (trifluoromethyl) -4-pyridyl] boronic acid according to General Procedure 9 to give Example 415. MCBP Calculated for C ₃₅ H ₃₆ F ₃ N ₇ O ₃ S: 691.2552, Found: 692.2610 [(M + H) + Form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (2-methylpyridin-4-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 416).

Using General Procedure 6, starting from the compound Synthesis of R3b and 2-bromo-5- (bromomethyl) thiazole as reagents, the resulting crude product was reacted with 2-methyl-4 (4,4,5,5-tetramethyl-1 , 3,2-dioxaborolan-2-yl) pyridine according to General Procedure 9 to give Example 416. MCBP: calculated for C ₃₅ H ₃₉ N ₇ O ₃ S: 637.2835, found: 638.2889 [(M + H) + form ].

3 - [(1- {[(3R, 4R) -1 - {[3-Fluoro-4,5-bis (6-methylpyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4 -yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyri- 106 037563 midin-4-one (Example 417) and

3 - [(1- {[(3R, 4R) -1 - {[5-chloro-3-fluoro-4- (6-methylpyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidine- 4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 418).

Using General Procedure 7, starting from Synthesis compound R3b and Synthesis compound R1k as reagents, the resulting crude product was reacted with (6-methyl-3pyridyl) boronic acid according to General Procedure 9 to give Example 417 and Example 418, which separated using chromatography.

Example 417 MCBP calculated for C ₄₂ H ₄₂ FN ₇ O ₄ S: 759.3003, found: 760.3079 [(M + H) + form].

Example 418 MCBP calculated for C ₃₆ H ₃₆ ClFN ₆ O ₄ S: 702.2191, found: 703.227 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - {[3-Fluoro-4,5-di (pyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl ] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 419) and

3 - [(1 - {[(3R, 4R) -1 - {[5-chloro-3-fluoro-4- (pyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 420).

Using General Procedure 7, starting from Synthesis compound R3b and Synthesis compound R1k as reagents, the resulting crude product was reacted with 3-pyridylboronic acid according to General Procedure 9 to give Example 419 and Example 420, which were separated by chromatography.

Example 419 MCBP calculated for C ₄₀ H ₃₈ FN ₇ O ₄ S: 731.2690, found: 732.275 [(M + H) + form].

Example 420: MCBP: calculated for C ₃₅ H ₃₄ ClFN ₆ O ₄ S: 688.2035, found: 689.212 [(M + H) + form].

3 - [(4-Hydroxy-1- {[(3R, 4R) -3-phenyl-1 - {[4- (pyridin-4-yl) thiophen-2-yl] carbonyl} piperidin-4yl] carbonyl} piperidine -4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 421).

Using General Procedure 7, starting from the compound Synthesis of R3b and 4-bromothiophene-2-carboxylic acid as reactants, the resulting crude product was reacted with 4- (4,4,5,5 tetramethyl-1,3,2-dioxaborolane- 2-yl) pyridine according to General Procedure 9 to give Example 421. MCBP: calculated for C ₃₅ H ₃₆ N ₆ O ₄ S: 636.2519, found: 637.2608 (M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4- (6-methylpyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl ] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 422).

Using General Procedure 7, starting from the Synthesis compound of R3b and 4-bromothiophene-2-carboxylic acid as reactants, the resulting crude product was reacted with (6-methyl-3pyridyl) boronic acid according to General Procedure 9 to give Example 422 MCBP calculated for C ₃₆ H ₃₈ N ₆ O ₄ S: 650.2675, found: 651.2778 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[4- (pyridin-3-yl) thiophen-2-yl] carbonyl} piperidin-4-yl] carbonyl} niperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 423).

Using General Procedure 7, starting from the Synthesis compound of R3b and 4-bromothiophene-2-carboxylic acid as reactants, the resulting crude product was reacted with 3pyridylboronic acid according to General Procedure 9 to give Example 423. MCBP: Calculated for C ₃₅ H ₃₆ N ₆ O ₄ S: 636.2519, found: 637.2606 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4- (2-methylpyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl ] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 424).

Using General Procedure 7, starting from the compound Synthesis of R3b and 4-bromothiophene-2-carboxylic acid as reactants, the resulting crude product was reacted with 2-methyl-4 (4,4,5,5-tetramethyl-1,3 , 2-dioxaborolan-2-yl) pyridine according to General Procedure 9 to give Example 424. MCBP: calculated for C ₃₆ H ₃₈ N ₆ O ₄ S: 650.2675, found: 651.2763 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[7- (6-methylpyridin-3-yl) -2,3-dihydrothieno [3,4-b] [1,4 ] dioxin-5yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one (Example 425).

Using General Procedure 7, starting from the Synthesis compound R3b and 5-bromo-2,3-dihydrothieno [3,4-d] [1,4] dioxin-7-carboxylic acid as reactants, the resulting crude product was reacted with (6-methyl-3-pyridyl) boronic acid according to General Procedure 9 to give Example 425. MCBP: calculated for C ₃₈ H ₄₀ N ₆ O ₆ S: 708.2730, found: 709.2799 [(M + H) + form] ...

5- (5 - {[(3R, 4R) -4 - ({4-Hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine -3-yl) methyl] piperidin-1 -yl} carbonyl) -3-phenylpiperidin-1-yl] methyl} -1,3-thiazol-2-yl) pyridin-2-carbonitrile (Example 426).

Using General Procedure 6, starting from the compound Synthesis of R3b and 2-bromo-5- (chloromethyl) thiazole as reagents, the resulting crude product was reacted with 5- (4,4,5,5-107 037563 tetramethyl-1, 3,2-dioxaborolan-2-yl) pyridine-2-carbonitrile according to General Procedure 9 to give Example 426. MCBP: calculated for C ₃₅ H ₃₆ N ₈ O ₃ S: 648.2631, found: 649.2731 [(M + H ) + form].

3 - [(1 - {[(3R, 4R) -1 - ({2- [6- (Cyclopropylmethoxy) pyrigin-3-yl] -1,3-thiazol-5-yl} methyl) -3-phenylpiperidine- 4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 427).

Using General Procedure 6, starting from the compound Synthesis of R3b and 2-bromo-5- (chloromethyl) thiazole as reagents, the resulting crude product was reacted with 2 (cyclopropylmethoxy) -5- (4,4,5,5-tetramethyl -1,3,2-dioxaborolan-2-yl) pyridine according to General Procedure 9 to give Example 427. MCBP: calculated for C ₃₈ H ₄₃ N ₇ O ₄ S: 693.3098, found: 347.6613 [(M + 2H) ²⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4- (methoxymethyl) -5- (6-methoxypuridin-3-yl) thiophen-2-yl] carbonyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 428).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromo-4- (methoxymethyl) thiophene-2-carboxylic acid as reactants, the resulting crude product was reacted with (6-methoxy-3-pyridyl) boronic acid in following General Procedure 9 to give Example 428. MCBP: Calculated for C ₃₈ H ₄₂ N ₆ O ₆ S: 710.2886, Found: 711.2966 [(M + H) + Form].

3 - [(1 - {[(3R, 4R) -1 - {[5- (6-Eminopuridin-3-yl) -4- (methoxymethyl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4- yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 429).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromo-4- (methoxymethyl) thiophene-2-carboxylic acid as reactants, the resulting crude product was reacted with 5- (4,4,5,5-tetramethyl -1,3,2-dioxaborolan-2-yl) pyridine-2-amine according to General Procedure 9 to give Example 429. MCBP: calculated for C ₃₇ H ₄ iN ₇ O ₅ S: 695.2890, found: 696.2961 [M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4- (methylamino) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4- yl) methyl] -7-methyl-3,7-dihydro-4H-purrolo [2,3-d] purimudin-4-one (Example 430) and

3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4- (methylamino) -5- (6-methylpyridin-3-yl) thiophen-2-yl] carbonyl} -3 phenylpiperuidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-purrolo [2,3-d] pyrimidin-4-one (Example 431).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-chloro-3- (methylamino) thiophene-2-carboxylic acid as reactants, the resulting crude product was reacted with (6-methyl-3-pyridyl) boronic acid in following General Procedure 9 to give Example 430 (dehalogenated by-product) and Example 431, which were separated by chromatography.

Example 430 MCBP calculated for C ₃₁ H ₃₆ N ₆ O ₄ S: 588.2519, found: 589.2593 [(M + H) + form].

Example 431: MCBP calculated for C ₃₇ H ₄₁ N ₇ O ₄ S: 679.2941, found: 680.3015 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - ({2- [6- (Dimethylamino) pyridin-3-yl] - 1,3-thiazol-5-yl} methyl) -3-phenylpiperidin4- yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-purrolo [2,3-d] pyrimidin-4one (Example 432).

Using General Procedure 6, starting from the compound of the Synthesis of R3b and 2-bromo-5 (chloromethyl) thiazole as reagents, the resulting crude product was reacted with 6- (dimethylamino) -3-pyridyl] boronic acid according to General Procedure 9 to give Example 432.

MCBP: calculated for C ₃₆ H ₄₂ N ₈ O ₃ S: 666.3101, found: 667.3171 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[3- (6-methylpyridin-3-yl) -4,5,6,7-tetrahydro-2-benzothiophene-1yl]] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4Hpyrrolo [2,3-d] purimidin-4-one (Example 433).

Using General Procedure 7, starting from the Synthesis compound R3b and 3-iodo-4,5,6,7-tetrahydro-2benzothiophene-1-carboxylic acid as reactants, the resulting crude product was reacted with (6-methyl-3- pyridyl) boronic acid according to General Procedure 9 to give Example 433. MCBP: calculated for C ₄₀ H ₄₄ N ₆ O ₄ S: 704.3145, found: 705.3219 [(M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - {[4-Amino-5- (2-methylpuridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperudin-4yl] carbonyl} -4-hydroxyiperudin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-purrolo [2,3-d] pyrimidin-4one (Example 434).

4-amino-5-bromo-2-thiophenecarboxylic acid (500 mg, 2.25 mmol) was dissolved in PDO (2 ml) and water (2 ml), then sodium hydroxide (194 mg, 4.86 mmol ) and then Boc ₂ O (1768 mg, 8.1 mmol) was added. The reaction mixture was stirred for 116 h while warming the reaction mixture to rt. An aqueous solution of HCl (1N, 4 ml) was added to the mixture, the precipitate was filtered off, washed with water and dried.

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The resulting 4- (tert-butoxycarbonylamino) -5-methylthiophene-2-carboxylic acid (316 mg, 0.93 mmol) and Synthesis compound R3b (488 mg, 0.93 mmol, as bis-HCl salt) were combined using General Procedure 7 ...

The resulting product (320 mg, 0.42 mmol) was stirred in PDO (3 mL) and aqueous HCl solution (12.2 M, 103 μL, 1.26 mmol) at 50 ° C for 20 h. The reaction mixture was purified using preparative LC (on column C-18 Gemini-NX 5 μm, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient).

Using General Procedure 9, starting with the resulting amino compound and 2-methyl-4 (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine as reagents, Example 434 was prepared. MCBP : calculated for C ₃₆ H ₃₉ N ₇ O ₄ S: 665.2784, found: 333.648 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (naphthalen-2-yl) -3,7-dihydro-4H-pyrrolo [2,3d] pyrimidin-4-one (Example 435 ).

Using General Procedure 7, starting from the compound Synthesis of R3be and 2-bromo-4-methylthiazole-5carboxylic acid as reactants, the resulting crude product was reacted with (6-methyl-3-pyridyl) boronic acid according to General Procedure 9 to give Example 435. MCBP: calculated for C ₄₅ H ₄₃ N ₇ O ₄ S: 777.3098, found: 778.3185 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7 - (3-methylphenyl) -3,7-dihydro-4H-pyrrolo [2,3d] pyrimidin-4-one (Example 436).

Using General Procedure 6, starting from the Synthesis compound of R3bf and 2-bromo-5- (bromomethyl) thiazole as reactants, the resulting crude product was reacted with (6-methyl-3pyridyl) boronic acid according to General Procedure 9 to give Example 436. MCBP: calculated for C ₄ iH ₄₃ N ₇ O ₃ S: 713.3148, found: 714.3205 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (naphthalen-1-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine-4- he (Ex. 437).

Using General Procedure 7, starting from the Synthesis compound of R3bt and 2-bromo-4-methylthiazole-5carboxylic acid as reactants, the resulting crude product was reacted with (6-methyl-3-pyridyl) boronic acid according to General Procedure 9 to give Example 437. MCBP: calculated for C ₄₅ H ₄₃ N ₇ O ₄ S: 777.3098, found: 778.3177 [(M + H) + form].

7-Ethyl-3 - [(1 - {[(3R, 4R) -1 - {[3-fluoro-5- (pyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 438).

Using General Procedure 7, starting with Synthesis compound R3c and Synthesis compound R1g as reagents, the resulting crude product was reacted with 3-pyridylboronic acid according to General Procedure 9 to give Example 438. MCBP: Calculated for C ₃ 6H ₃₇ FN6O4S : 668.2581, found: 669.2654 [(M + H) ⁺ form].

7-Ethyl-3 - [(1 - {[(3R, 4R) -1 - {[3-fluoro-5- (pyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 439).

Using General Procedure 7, starting from the Synthesis compound R3c and the Synthesis compound R1g as reagents, the resulting crude product was reacted with 4- (4,4,5,5-tetramethyl1,3,2-dioxaborolan-2-yl) pyridine according to General Procedure 9 to obtain Example 439. MCBP: calculated for C ₃₆ H ₃₇ FN ₆ O ₄ S: 668.2581, found: 669.2661 [(M + H) + form].

7-Ethyl-3 - [(1 - {[(3R, 4R) -1 - {[3-fluoro-5- (2-methylpyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidine- 4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 440).

Using General Procedure 7, starting from the Synthesis compound R3c and the Synthesis compound R1g as reagents, the resulting crude product was reacted with 2-methyl-4- (4,4,5,5 tetramethyl-1,3,2-dioxaborolane-2 -yl) pyridine according to General Procedure 9 to give Example 440. MCBP: calculated for C ₃₇ H ₃₉ FN ₆ O ₄ S: 682.2737, found: 683.2819 [(M + H) + form].

7-ethyl-3 - {[1 - ({(3R, 4R) -1 - [(4-fluoro-2,3'-bithiophen-5-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidin-4-yl] methyl} -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 441).

Using General Procedure 7, starting from the Synthesis compound R3c and the Synthesis compound R1g as reagents, the resulting crude product was reacted with 4,4,5,5-tetramethyl-2 (3-thienyl) -1,3,2-dioxaborolane according to General Procedure 9 to obtain Example 441. MCBP: calculated for C ₃₅ H ₃₆ FN ₅ O ₄ S ₂ : 673.2193, found: 674.2272 [(M + H) + form].

7-Ethyl-3 - {[1 - ({(3R, 4R) -1 - [(3-fluoro-5-phenylthiophen-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4- hydroxypiperidin-4-yl] methyl} -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 442).

Using General Procedure 7, starting from Synthesis compound R3c and Synthesis compound R1g as reagents, the resulting crude product was reacted with phenylboronic acid according to General Procedure 9 to give Example 442. MCBP: Calculated for

- 109 037563

C37H38FN5O4S: 667.2629, found: 668.2702 [(M + H) + form].

7-Ethyl-3 - [(1 - {[(3R, 4R) -1 - ({3-fluoro-5- [2- (trifluoromethyl) pyridin-4-yl] thiophen-2-yl} carbonyl) -3phenylpiperidine -4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 443).

Using General Procedure 7, starting from the Synthesis compound R3c and the Synthesis compound R1g as reagents, the resulting crude product was reacted with 4- (4,4,5,5-tetramethyl1,3,2-dioxaborolan-2-yl) - 2- (trifluoromethyl) pyridine according to General Procedure 9 to give Example 443. MCBP: calculated for C ₃₇ H ₃₆ F ₄ N ₆ O ₄ S: 736.2455, found: 737.2524 (M + H) + form].

7-ethyl-3 - [(1 - {[(3R, 4R) -1 - {[3-fluoro-5- (2-methoxy-6-methylpyridin-4-yl) thiophen-2-yl] carbonyl} - 3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 444).

Using General Procedure 7, starting from the Synthesis compound R3c and the Synthesis compound R1g as reagents, the resulting crude product was reacted with 2-methoxy-6-methyl-4 (4,4,5,5-tetramethyl-1,3, 2-dioxaborolan-2-yl) pyridine according to General Procedure 9 to give Example 444. MCBP: calculated for C ₃₈ H ₄₁ FN ₆ O ₅ S: 712.2843, found: 713.2916 (M + H) + form].

3 - [(4-Hydroxy-1- {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (pyridin-2-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin4-one (Example 445) ...

Using General Procedure 6, starting from the Synthesis compound of R3ca and 2-bromo-5- (bromomethyl) thiazole as reactants, the resulting crude product was reacted with (6-methyl-3pyridyl) boronic acid according to General Procedure 9 to give Example 445. MCBP: calculated for C ₃₉ H ₄₀ N ₈ O ₃ S: 700.2944, found: 701.2986 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (pyridin-3-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine-4- he (Ex. 446).

Using General Procedure 7, starting from the Synthesis compound of R3cb and 2-bromo-4-methylthiazole-5carboxylic acid as reactants, the resulting crude product was reacted with (6-methyl-3-pyridyl) boronic acid according to General Procedure 9 to give Example 446. MCBP: calculated for C ₄₀ H ₄₀ N ₈ O ₄ S: 728.2893, found: 729.2968 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (pyridin-3-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin4-one (Example 447) ...

Using General Procedure 6, starting from the Synthesis compound of R3cb and 2-bromo-5- (bromomethyl) thiazole as reactants, the resulting crude product was reacted with (6-methyl-3pyridyl) boronic acid according to General Procedure 9 to give Example 447. MCBP: calculated for C ₃₉ H ₄₀ N ₈ O ₃ S: 700.2944, found: 701.2985 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (thiophen-3-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine-4- he (Ex. 448).

Using General Procedure 7, starting from the Synthesis compound of R3cf and 2-bromo-4-methylthiazole-5carboxylic acid as reactants, the resulting crude product was reacted with (6-methyl-3-pyridyl) boronic acid according to General Procedure 9 to give Example 448. MCBP: calculated for C ₃₉ H ₃₉ N ₇ O ₄ S ₂ : 733.2505, found: 734.2596 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (thiophen-3-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin4-one (Example 449) ...

Using General Procedure 6, starting from the Synthesis compound of R3cf and 2-bromo-5- (bromomethyl) thiazole as reagents, the resulting crude product was reacted with (6-methyl-3pyridyl) boronic acid according to General Procedure 9 to give Example 449. MCBP: calculated for C ₃₈ H ₃₉ N ₇ O ₃ S ₂ : 705.2556, found: 706.2666 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - {[3-Fluoro-5- (6-methylpyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7- (propan-2-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 450).

Using General Procedure 7, starting with Synthesis compound R3d and Synthesis compound R1g as reagents, the resulting crude product was reacted with (6-methyl-3pyridyl) boronic acid according to General Procedure 9 to give Example 450. MCBP: Calculated for C ₃₈ H ₄ iFN ₆ O ₄ S: 696.2894, found: 697.2968 [(M + H) + form].

3 - [(4-Hydroxy-1- {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (propan-2-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin4-one (Example 451) ...

Using General Procedure 6, starting from the compound of the Synthesis of R3d and 2-bromo-5- (bromomethyl) thiazole as reagents, the resulting crude product was reacted with (6-methyl-3-110 037563 pyridyl) boronic acid according to General Procedure 9 to obtain Example 451. MCBP:

calculated for C ₃₇ H ₄₃ N ₇ O ₃ S: 665.3148, found: 333.6636 [(M + 2H) 2+ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7 - (propan-2-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one ( Example 452).

Using General Procedure 7, starting from the compound Synthesis of R3d and 2-bromo-4-methylthiazole-5carboxylic acid as reactants, the resulting crude product was reacted with (6-methyl-3-pyridyl) boronic acid according to General Procedure 9 to give Example 452. MCBP: calculated for C ₃₈ H ₄₃ N ₇ O ₄ S: 693.3098, found: 694.3173 [(M + H) + form].

7-Cyclopropyl-3 - {[1 - ({(3R, 4R) -1 - [(3-fluoro-5-phenylthiophen-2-yl) carbonyl] -3-phenylpiperidin-4yl} carbonyl) -4-hydroxypiperidine- 4-yl] methyl} -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 453).

Using General Procedure 7, starting from Synthesis compound R3g and Synthesis compound R1g as reagents, the resulting crude product was reacted with phenylboronic acid according to General Procedure 9 to give Example 453. MCBP: Calculated for C ₃₈ H ₃₈ FN ₅ O ₄ S: 679.2629, found: 680.2696 [(M + H) ⁺ form].

7-Cyclopropyl-3 - [(1 - {[(3R, 4R) -1 - {[3-fluoro-5- (2-methylpyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidine- 4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 454).

Using General Procedure 7, starting from the Synthesis compound R3g and the Synthesis compound R1g as reagents, the resulting crude product was reacted with 2-methyl-4- (4,4,5,5 tetramethyl-1,3,2-dioxaborolane-2 -yl) pyridine according to General Procedure 9 to give Example 454. MCBP: calculated for C ₃₈ H ₃₉ FN ₆ O ₄ S: 694.2737, found: 695.2808 [(M + H) + form].

7-Cyclopropyl-3 - [(1 - {[(3R, 4R) -1 - {[3-fluoro-5- (pyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4- yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 455).

Using General Procedure 7, starting from the Synthesis compound R3g and the Synthesis compound R1g as reagents, the resulting crude product was reacted with 4- (4,4,5,5-tetramethyl1,3,2-dioxaborolan-2-yl) pyridine according to General Procedure 9 to obtain Example 455. MCBP: calculated for C ₃₇ H ₃₇ FN ₆ O ₄ S: 680.2581, found: 681.2645 [(M + H) + form].

7-Cyclopropyl-3 - [(1 - {[(3R, 4R) -1 - {[3-fluoro-5- (pyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4- yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin4-one (Example 456).

Using General Procedure 7, starting from Synthesis compound R3g and Synthesis compound R1g as reagents, the resulting crude product was reacted with 3-pyridylboronic acid according to General Procedure 9 to give Example 456. MCBP: Calculated for C ₃₇ H ₃₇ FN6O4S : 680.2581, found: 681.2648 [(M + H) + form].

7-Cyclopropyl-3 - {[1 - ({(3R, 4R) -1 - [(4-fluoro-2,3'-bithiophen-5-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidin-4-yl] methyl} -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 457).

Using General Procedure 7, starting from the Synthesis compound R3g and the Synthesis compound R1g as reagents, the resulting crude product was reacted with 4,4,5,5-tetramethyl-2 (3-thienyl) -1,3,2-dioxaborolane according to General Procedure 9 to obtain Example 457. MCBP: calculated for C ₃₆ H ₃₆ FN ₅ O ₄ S ₂ : 685.2193, found: 686.2269 [(M + H) + form].

7-Cyclopropyl-3 - [(1 - {[(3R, 4R) -1 - {[3-fluoro-5- (6-methylpyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidine- 4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 458).

Using General Procedure 7, starting from Synthesis compound R3g and Synthesis compound R1g as reagents, the resulting crude product was reacted with (6-methyl-3-pyridyl) boronic acid according to General Procedure 9 to give Example 458. MCBP: calculated for C ₃₈ H ₃₉ FN ₆ O ₄ S: 694.2737, found: 695.2812 [(M + H) + form].

7-Cyclopropyl-3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazole-5 - yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 459).

Using General Procedure 7, starting from the Synthesis compound of R3g and 2-bromo-4-methylthiazole-5carboxylic acid as reactants, the resulting crude product was reacted with (6-methyl-3-pyridyl) boronic acid according to General Procedure 9 to give Example 459. MCBP: calculated for C ₃₈ H ₄ iN ₇ O ₄ S: 691.2941, found: 692.3024 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (1-methylpiperidin-4-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 460).

Using General Procedure 6, starting from the Synthesis compound R3k and 2-bromo-5- (bromomethyl) thia-111 037563 ash as reagents, the resulting crude product was reacted with (6-methyl-3pyridyl) boronic acid according to General Procedure 9 to obtain Example 460. MCBP:

calculated for C ₄₀ H ₄₈ N8O ₃ S: 720.3570, found: 361.1855 [(M + 2H) ² + form].

3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (2-methylpropyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 461).

Using General Procedure 6, starting from the Synthesis compound of R3n and 2-bromo-5- (bromomethyl) thiazole as reactants, the resulting crude product was reacted with (6-methyl-3pyridyl) boronic acid according to General Procedure 9 to give Example 461. MCBP: calculated for C ₃₈ H ₄₅ N ₇ O ₃ S: 679.3304, found: 340.6733 [(M + 2H) ²⁺ form].

7- (2,2-Difluoroethyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazole- 5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 462 ).

Using General Procedure 6, starting from the Synthesis compound R3p and 2-bromo-5- (bromomethyl) thiazole as reactants, the resulting crude product was reacted with (6-methyl-3pyridyl) boronic acid according to General Procedure 9 to give Example 462. MCBP: calculated for C ₃₆ H ₃₉ F ₂ N ₇ O ₃ S: 687.2803, found: 344.6487 [(M + 2H) ²⁺ form].

7- (2,2-Difluoroethyl) -3 - [(1 - {[(3R, 4R) -1 - {[3-fluoro-5- (6-methylpyridin-3-yl) thiophen-2-yl] carbonyl } -3phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 463).

Using General Procedure 7, starting from Synthesis compound R3p and Synthesis compound R1g as reagents, the resulting crude product was reacted with (6-methyl-3pyridyl) boronic acid according to General Procedure 9 to give Example 463. MCBP: Calculated for C ₃₇ H ₃₇ N ₆ O ₄ F ₃ S: 718.2549, found: 719.2625 [(M + H) + form].

7- (Cyclonropylmethyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylnyridin-3-yl) -1,3-thiazol-5-yl]] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 464).

Using General Procedure 6, starting from the Synthesis compound R3q and 2-bromo-5- (bromomethyl) thiazole as reactants, the resulting crude product was reacted with (6-methyl-3pyridyl) boronic acid according to General Procedure 9 to give Example 464. MCBP: calculated for C ₃₈ H ₄₃ N ₇ O ₃ S: 677.3149, found: 339.6648 [(M + 2H) ²⁺ form].

7- (Cyclonropylmethyl) -3 - [(1 - {[(3R, 4R) -1 - {[3-fluoro-5- (6-methylpyridin-3-yl) thiophen-2-yl] carbonyl} 3-phenylpiperidine -4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 465).

Using General Procedure 7, starting with Synthesis compound R3q and Synthesis compound R1g as reagents, the resulting crude product was reacted with (6-methyl-3pyridyl) boronic acid according to General Procedure 9 to give Example 465. MCBP: Calculated for C ₃₉ H ₄₁ N ₆ O ₄ FS: 708.2894, found: 709.2973 [(M + H) + form].

7- (cyclobutylmethyl) -3 - [(4-hydroxy-1- {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol5- yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3d] pyrimidin-4-one (Example 466).

Using General Procedure 7, starting from the Synthesis of R3r compound and 2-bromo-4-methylthiazole-5carboxylic acid as reactants, the resulting crude product was reacted with (6-methyl-3-pyridyl) boronic acid according to General Procedure 9 to give Example 466. MCBP: calculated for C ₄₀ H ₄₅ N7O ₄ S: 719.3254, found: 720.3333 [(M + H) + form].

7- (Cyclobutylmethyl) -3 - [(1- {[(3R, 4R) -1- {[3-fluoro-5- (6-methylpyridin-3-yl) thiophen-2-yl] carbonyl} 3-phenylpiperidine -4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 467).

Using General Procedure 7, starting with Synthesis compound R3r and Synthesis compound R1g as reagents, the resulting crude product was reacted with (6-methyl-3pyridyl) boronic acid according to General Procedure 9 to give Example 467. MCBP: Calculated for C ₄₀ H ₄₃ FN ₆ O ₄ S: 722.3051, found: 723.3125 [(M + H) + form].

7- (cyclobutylmethyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl]] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 468).

Using General Procedure 6, starting from the Synthesis compound of R3r and 2-bromo-5- (bromomethyl) thiazole as reactants, the resulting crude product was reacted with (6-methyl-3pyridyl) boronic acid according to General Procedure 9 to give Example 468. MCBP: calculated for C ₃ 9H ₄₅ N ₇ O ₃ S: 691.3304, found: 692.3396 [(M + H) + form].

7- (2-Fluoroethyl) -3 - [(4-hydroxy-1- {[(3R, 4R) -1- {[2- (6-methylpyridin-3-yl) -1,3-thiazole-5 - yl] methyl} -3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 469).

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Using General Procedure 6, starting from the Synthesis compound of R3u and 2-bromo-5- (bromomethyl) thiazole as reactants, the resulting crude product was reacted with (6-methyl-3pyridyl) boronic acid according to General Procedure 9 to give Example 469. MCBP:

calculated for C ₃₆ H ₄₀ FN ₇ O ₃ S: 669.2897, found: 335.6529 [(M + 2H) 2+ form].

7- (2-Fluoroethyl) -3 - [(1 - {[(3R, 4R) -1 - {[3-fluoro-5- (6-methylpyrigin-3-yl) thiophen-2-yl] carbonyl} - 3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 470).

Using General Procedure 7, starting from Synthesis compound R3u and Synthesis compound R1g as reagents, the resulting crude product was reacted with (6-methyl-3pyridyl) boronic acid according to General Procedure 9 to give Example 470. MCBP: Calculated for C ₃₇ H ₃₈ N ₆ O ₄ F ₂ S: 700.2643, found: 701.2725 [(M + H) + form].

7- (2-Hygroxyethyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyrigin-3-yl) -1,3-thiazol-5- yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 471).

Using General Procedure 6, starting from the Synthesis compound R3w and 2-bromo-5- (bromomethyl) thiazole as reactants, the resulting crude product was reacted with (6-methyl-3pyridyl) boronic acid according to General Procedure 9 to give Example 471. MCBP: calculated for C ₃₆ H ₄₁ N ₇ O ₄ S: 667.2941, found: 334.6543 [(M + 2H) ²⁺ form].

3 - [(1- {[(3R, 4R) -1 - {[3-Fluoro-5- (6-methylpyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7- (2-hydroxyethyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 472)

Using General Procedure 7, starting from Synthesis compound R3w and Synthesis compound R1g as reagents, the resulting crude product was reacted with (6-methyl-3pyridyl) boronic acid according to General Procedure 9 to give Example 472. MCBP: Calculated for C ₃₇ H ₃₉ N ₆ O ₅ FS: 698.2687, found: 699.2757 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - (3-Fluorobenzyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -3,7-dihydro- 4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 473).

Using General Procedure 6, starting from the compound Synthesis of R1n and 1- (bromomethyl) -3-fluorobenzene as reagents, the resulting crude product (35 mg, 0.052 mmol) was reacted with TBAF (1 M in THF, 0.16 mL, 0.156 mmol) in THF (2 ml) at 75 ° C for 4 days. The reaction mixture was purified using preparative LC (on a C-18 Gemini-NX column 5 μm, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient) to give Example 473. MCBP: calculated for C ₃ iH ₃₄ FN ₅ O ₃ : 543.2646 found: 544.272 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - (2-Fluorobenzyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -3,7-dihydro- 4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 474).

Using General Procedure 6, starting from the compound Synthesis of R1n and 1- (bromomethyl) -2-fluorobenzene as reagents, the resulting crude product (80 mg, 0.12 mmol) was reacted with TBAF (1 M in THF, 0.24 mL, 0.24 mmol) in THF (3 ml) at 75 ° C for 1 day. The reaction mixture was purified by preparative LC (5 μm C-18 Gemini-NX column, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient) followed by flash chromatography (MeOH-DCM, gradient) to give Example 474. MCBP: calculated for C ₃₁ H ₃₄ FN ₅ O ₃ : 543.2646, found: 544.274 [(M + H) + form].

3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - (3-methylbenzyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4yl) methyl] -3,7-dihydro-4H -pyrrolo [2,3-d] pyrimidin-4-one (Example 475).

Using General Procedure 6, starting from the compound Synthesis of R1n and 1- (bromomethyl) -3-methylbenzene as reagents, the resulting crude product (74 mg, 0.11 mmol) was reacted with TBAF (1 M in THF, 0.22 mL, 0.22 mmol) in THF (3 ml) at 75 ° C for 1 day. The reaction mixture was purified by preparative LC (5 μm C-18 Gemini-NX column, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient) followed by flash chromatography (MeOH-DCM, gradient) to give Example 475. MCBP: calculated for C ₃₂ H ₃₇ N ₅ O ₃ : 539.2896, found: 540.2940 [(M + H) + form].

3 - [(4-Hydroxy-1- {[(3R, 4R) -1 - (2-methylbenzyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7- dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 476).

Using General Procedure 6, starting from the compound Synthesis of R1n and 1- (bromomethyl) -2methylbenzene as reagents, the resulting crude product (88 mg, 0.13 mmol) was reacted with TBAF (1 M in THF, 0.26 mL, 0.26 mmol) in THF (3 ml) at 75 ° C for 1 day. The reaction mixture was purified by preparative LC (on a Gemini-NX C-18 column 5 μm, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient) followed by flash chromatography (MeOH-DCM, gradient) to give Example 476. MCBP calculated for C ₃₂ H ₃₇ N ₅ O ₃ : 539.2896, found: 540.295 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - (1-Benzofuran-2-ylmethyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -3, 7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 477).

Using General Procedure 6, starting from the compound Synthesis of R1n and 2- (chloromethyl) benzofuran as reagents, the resulting crude product (32 mg, 0.046 mmol) was reacted with TBAF (1 M in THF, 0.09 mL, 0.09 mmol) in THF (3 ml) at 75 ° C for 1 day. The reaction mixture was purified by preparative LC (on a C-18 Gemini-NX 5 μm column, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient), then by flash chromatography (MeOH-DCM, gradient) with obtaining Example 477.

MCBP calculated for C ₃₃ H ₃₅ N ₅ O ₄ : 565.2689, found: 566.2772 [(M + H) + form].

3 - {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(4-methyl-1,3-thiazol-5-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 478).

Using General Procedure 7, starting from the compound Synthesis of R1n and 4-methylthiazole-5-carboxylic acid as reagents, the resulting crude product (87 mg, 0.126 mmol) was reacted with TBAF (1 M in THF, 0.315 mL, 0.315 mmol ) in THF (3 ml) at 75 ° C for 1 day. The reaction mixture was purified by preparative LC (5 μm C-18 Gemini-NX column, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient) followed by flash chromatography (MeOH-DCM, gradient) to give Example 478. MCBP: calculated for C ₂₉ H ₃₂ N ₆ O ₄ S: 560.2206, found: 561.228 [(M + H) + form].

3 - {[4-Hydroxy-1 - ({(3R, 4R) -3-phenyl-1 - [(2-phenyl-1,3-thiazol-5-yl) carbonyl] piperidin-4-yl} carbonyl) piperidin-4-yl] methyl} -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 479).

Using General Procedure 7, starting from the compound Synthesis of R1n and 2-phenylthiazole-5-carboxylic acid as reagents, the resulting crude product (86 mg, 0.11 mmol) was reacted with TBAF (1 M in THF, 0.285 mL, 0.285 mmol ) in THF (3 ml) at 75 ° C for 1 day. The reaction mixture was purified by preparative LC (5 μm Gemini-NX C-18 column, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient) followed by flash chromatography (MeOH-DCM, gradient) to give Example 479. MCBP: calculated for C ₃₄ H ₃₄ N ₆ O ₄ S: 622.2362, found: 623.2442 [(M + H) + form].

3 - {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(4-methyl-2-phenyl-1,3-thiazol-5-yl) carbonyl] -3-phenylpiperidin-4yl} carbonyl ) piperidin-4-yl] methyl} -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 480).

Using General Procedure 7, starting from the compound Synthesis of R1n and 4-methyl-2-phenylthiazole-5carboxylic acid as reagents, the resulting crude product (90 mg, 0.117 mmol) was reacted with TBAF (1 M in THF, 0.293 mL, 0.293 mmol) in THF (3 ml) at 75 ° C for 1 day. The reaction mixture was purified by preparative LC (on a Gemini-NX C-18 column 5 μm, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient) followed by flash chromatography (MeOH-DCM, gradient) to give Example 480. MCBP calculated for C ₃₅ H ₃₆ N ₆ O ₄ S: 636.2519, found: 637.2601 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7 - (2-oxopyrrolidin-1-yl) -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one ( Example 481).

Using General Procedure 11, starting from Synthesis compound R2ab and Synthesis compound R1m as reagents, Example 481 was prepared. MCBP: calculated for C ₃₉ H ₄₂ N ₈ O ₅ S: 734.2999, found: 735.3045 [(M + H) ⁺ form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7 - (4-methylphenyl) -3,7-dihydro-4H-pyrrolo [2,3d] pyrimidin-4-one (Example 482).

Using General Procedure 11, starting from Synthesis compound R2am and Synthesis compound R1m as reagents, Example 482 was prepared. MCBP: calculated for C ₄₂ H ₄₃ N ₇ O ₄ S: 741.3098, found: 742.3167 [(M + H) ⁺ form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- [4- (hydroxymethyl) phenyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one (Example 483).

Using General Procedure 11, starting from Synthesis compound R2aq and Synthesis compound R1m as reagents, Example 483 was prepared. MCBP: calculated for C ₄₂ H ₄₃ N ₇ O ₅ S: 757.3046, found: 758.3122 [(M + H) ⁺ form] ...

7- (4-fluorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3- thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one ( Example 484).

Using General Procedure 11, starting from Synthesis compound R2as and Synthesis compound R1m as reagents, Example 484 was prepared. MCBP: calculated for C ₄₁ H ₄₀ FN ₇ O ₄ S: 745.2847, found: 373.6485 [(M + 2H) ²⁺ form ].

7- [4- (Dimethylamino) phenyl] -3 - [(4-hydroxy-1- {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1 , 3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one (Example 485).

Using General Procedure 11, starting from Synthesis compound R2at and Synthesis compound R1m as reagents, Example 485 was prepared. MCBP: calculated for C ₄₃ H ₄₆ N ₈ O ₄ S: 770.3362, found: 771.3439 [(M + H) ⁺ form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- [4- (4-methylpiperazin-1-yl) phenyl] -3,7 dihydro-4H-pyrrolo [2,3-d] pyrimidine -4-one (Ex. 486).

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Using General Procedure 11, starting from Synthesis compound R2au and Synthesis compound R1m as reagents, Example 486 was prepared. MCBP: calculated for C ₄₆ H5iN ₉ O ₄ S: 825.3785, found:

413.6974 [(M + 2H) 2+ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- [4- (morpholin-4-yl) phenyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidine -4-one (Example 487).

Using General Procedure 11, starting from Synthesis compound R2av and Synthesis compound R1m as reagents, Example 487 was prepared. MCBP: calculated for C ₄₅ H ₄₈ N ₈ O ₅ S: 812.3469, found: 813.3555 [(M + H) ⁺ form] ...

3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[5- (2-methylpyrimidin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl]] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 488).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) thiophene-2-carboxylic acid as reactants, the resulting crude boronic acid reacted with 4-bromo-2-methylpyrimidine as the halogen compound according to General Procedure 9 to give Example 488. MCBP: Calculated for C ₃₅ H ₃₇ N ₇ O ₄ S: 651.2628, Found: 652.2698 [(M + H) ⁺ the form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (5-methylpyrazin-2-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl ] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 489).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) thiophene-2-carboxylic acid as reactants, the resulting crude boronic acid reacted with 2-bromo-5-methylpyrazine as the halogen compound according to General Procedure 9 to give Example 489. MCBP: Calculated for C ₃₅ H ₃₇ N ₇ O ₄ S: 651.2628, Found: 652.2703 [(M + H ) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[5 - (pyrazin-2-yl) thiophen-2-yl] carbonyl} piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 490).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) thiophene-2-carboxylic acid as reactants, the resulting crude boronic acid reacted with 2-chloropyrazine as the halogen compound according to General Procedure 9 to give Example 490. MCBP: calculated for C ₃₄ H ₃₅ N ₇ O ₄ S: 637.2471, found: 638.2547 [(M + H) ⁺ form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (6-methylpyridazin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl ] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 491).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) thiophene-2-carboxylic acid as reactants, the resulting crude boronic acid reacted with 3-chloro-6-methylpyridazine as the halogen compound according to General Procedure 9 to give Example 491. MCBP: Calculated for C ₃₅ H ₃₇ N ₇ O ₄ S: 651.2628, Found: 652.2709 [(M + H) ⁺ the form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (6-methylpyrazin-2-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl ] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 492).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) thiophene-2-carboxylic acid as reactants, the resulting crude boronic acid reacted with 2-chloro-6-methylpyrazine as the halogen compound according to General Procedure 9 to give Example 492. MCBP: Calculated for C ₃₅ H ₃₇ N ₇ O ₄ S: 651.2628, Found: 652.2699 [(M + H ) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3-methylphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one ( Example 493).

Using General Procedure 11, starting with Synthesis compound R2bf and Synthesis compound R1m as reagents, Example 493 was prepared. MCBP: calculated for C ₄₂ H ₄₃ N ₇ O ₄ S: 741.3098, found: 742.3171 [(M + H) + form] ...

7- (3-Chlorophenyl) -3 - [(4-hydroxy-1- {[(3R, 4R) -1- {[4-methyl-2- (6-methylpyridin-3-yl) -1,3- thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one ( Example 494).

Using General Procedure 11, starting from Synthesis compound R3bj and Synthesis compound R1m as reagents, Example 494 was prepared. MCBP: calculated for C ₄₁ H ₄₀ N ₇ O ₄ SCl: 761.2551, found: 762.2622 [(M + H) + form] ...

7- (3-fluorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3- thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d]

- 115 037563 pyrimidin-4-one (Example 495).

Using General Procedure 11, starting from Synthesis compound R2bk and Synthesis compound R1m as reagents, Example 495 was prepared. MCBP: calculated for C ₄₁ H ₄₀ FN ₇ O ₄ S: 745.2847, found:

373.6504 [(M + 2H) 2+ form].

7- [3- (Dimethylamino) phenyl] -3 - [(4-hydroxy-1- {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1 , 3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one (Example 496).

Using General Procedure 11, starting from Synthesis compound R2bl and Synthesis compound R1m as reagents, Example 496 was prepared. MCBP: calculated for C ₄₃ H ₄₆ N ₈ O ₄ S: 770.3362, found: 771.3436 [(M + H) ⁺ form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- [3- (morpholin-4-yl) phenyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidine-4 -on (Example 497).

Using General Procedure 11, starting from Synthesis compound R2bm and Synthesis compound R1m as reagents, Example 497 was prepared. MCBP: calculated for C ₄₅ H ₄₈ N ₈ O ₅ S: 812.3469, found: 813.3544 [(M + H) ⁺ form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3-hydroxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 498 ).

Using General Procedure 10 starting from Example 297 and boron tribromide as reagents, Example 498 was prepared. MCBP: calculated for C ₄ iH ₄ iN ₇ O ₅ S: 743.2890, found: 744.2956 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 499 ).

Using General Procedure 11, starting from Synthesis compound R2bo and Synthesis compound R1m as reagents, Example 499 was prepared. MCBP: calculated for C ₄₂ H ₄₃ N ₇ O ₅ S: 757.3046, found: 379.6582 [(M + 2H) ²⁺ form ].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (2-methylphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one ( Example 500).

Using General Procedure 11, starting from Synthesis compound R2bv and Synthesis compound R1m as reagents, Example 500 was prepared. MCBP: calculated for C ₄₂ H ₄₃ N ₇ O ₄ S: 741.3098, found: 742.3169 [(M + H) + form] ...

7- (2-Chlorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3- thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one ( Example 501).

Using General Procedure 11, starting from Synthesis compound R2bw and Synthesis compound R1m as reagents, Example 501 was prepared. MCBP: calculated for C ₄₁ H ₄₀ ClN ₇ O ₄ S: 761.2551, found: 762.2633 [(M + H) + form] ...

7- (2-Fluorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1- {[4-methyl-2- (6-methylpyridin-3-yl) -1,3- thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one ( Example 502).

Using General Procedure 11, starting from Synthesis compound R2bx and Synthesis compound R1m as reagents, Example 502 was prepared. MCBP: calculated for C ₄ iH ₄₀ N ₇ O ₄ FS: 745.2847, found: 746.2924 [(M + H) + form] ...

7- [2- (Dimethylamino) phenyl] -3 - [(4-hydroxy-1- {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1 , 3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one (Example 503).

Using General Procedure 11, starting from Synthesis compound R2by and Synthesis compound R1m as reagents, Example 503 was prepared. MCBP: calculated for C ₄₃ H ₄₆ N ₈ O ₄ S: 770.3362, found: 771.3447 [(M + H) + form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (2-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3d] pyrimidin-4-one (Example 504 ).

Using General Procedure 11, starting from Synthesis compound R2bz and Synthesis compound R1m as reagents, Example 504 was prepared. MCBP: calculated for C ₄₂ H ₄₃ N ₇ O ₅ S: 757.3046, found: 758.3114 [(M + H) + form] ...

3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7 - (thiophen-2-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 505).

Using General Procedure 11, starting from Synthesis compound R2cc and Synthesis compound R1m as reagents, Example 505 was prepared. MCBP: calculated for C ₃₉ H ₃₉ N ₇ O ₄ S ₂ : 733.2505, found:

- 116 037563

734.2591 [(M + H) + form].

7- (Furan-3-yl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1), 3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3H] pyrimidin-4-one ( Example 506).

Using General Procedure 11, starting from Synthesis compound R2ce and Synthesis compound R1m as reagents, Example 506 was prepared. MCBP: calculated for C ₃₉ H ₃₉ N ₇ O ₅ S: 717.2733, found: 718.2818 [(M + H) ⁺ form] ...

3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7 - (1H-indol-1-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine-4 -on (Example 507).

Using General Procedure 11, starting from Synthesis compound R2cl and Synthesis compound R1m as reagents, Example 507 was prepared. MCBP: calculated for C ₄₃ H ₄₂ N ₈ O ₄ S: 766.3050, found: 767.312 [(M + H) ⁺ form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (1H-pyrrol-1-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine-4- he (Example 508).

Using General Procedure 11, starting with Synthesis compound R2cm and Synthesis compound R1m as reagents, Example 508 was prepared. MCBP: calculated for C ₃₉ H ₄₀ N ₈ O ₄ S: 716.2893, found: 717.2976 [(M + H) ⁺ form] ...

7-Cyclopentyl-3 - [(4-hydroxy-1- {[(3R, 4R) -1- {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazole-5 - yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 509).

Using General Procedure 11, starting from Synthesis compound R2i and Synthesis compound R1m as reagents, Example 509 was prepared. MCBP: calculated for C ₄₀ H ₄₅ N ₇ O ₄ S: 719.3254, found: 718.3195 [(M-H) ^- form] ...

7-Cyclohexyl-3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5- yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 510).

Using General Procedure 11, starting from Synthesis compound R2j and Synthesis compound R1m as reagents, Example 510 was prepared. MCBP: calculated for C ₄₁ H ₄₇ N ₇ O ₄ S: 733.3410, found: 732.3356 [(M + H) + form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (tetraugro-2H-pyran-4-yl) -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidine- 4-one (Example 511).

Using General Procedure 11, starting from Synthesis compound R21 and Synthesis compound R1m as reagents, Example 511 was prepared. MCBP: calculated for C ₄₀ H ₄₅ N ₇ O ₅ S: 735.3203, found: 734.3166 [(M-H) ^- form] ...

3 - [(1- {[(3R, 4R) -1 - (3-Aminobenzoyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4yl) methyl] -7-methyl-3,7- dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 512).

Using General Procedure 12 starting from Example 203 as a starting material, Example 512 was prepared. MCBP: Calculated for C ₃₂ H ₃₆ N ₆ O ₄ : 568.2798, Found: 569.2855 [(M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1- [3 - (methylamino) benzoyl] -3-phenylpiperidin-4-yl} carbonyl) piperidin-4-yl] methyl} -7- methyl 3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 513).

Using General Procedure 13, starting from Example 512 as the amino reagent, Example 513 was prepared. MCBP: calculated for C ₃₃ H ₃₈ N ₆ O ₄ : 582.2955, found: 583.3036 [(M + H) + form].

tert-Butyl 4-acetyl-7 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3 -d] pyrimidin-3-yl) methyl] piperidin-1 -yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} -3,4-dihydroquino xaline-1 (2H) -carboxylate (Example 514).

Using General Procedure 7, starting with Example 244 and acetic acid as reagents, Example 514 was prepared. MCBP: calculated for C ₄₁ H ₄₉ N ₇ O ₇ : 751.3693, found: 752.3755 [(M + H) + form].

7- {4- [6- (Dimethylamino) pyridin-3-yl] phenyl} -3 - [(1 - {[(3R, 4R) -1 - ({2- [6- (dimethylamino) pyridin-3yl] - 1,3-thiazol-5-yl} methyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -3,7 dihydro-4H-pyrrolo [2,3-d ] pyrimidin-4-one (Example 515) and

7- (4-chlorophenyl) -3 - [(1 - {[(3R, 4R) -1 - ({2- [6- (dimethylamino) pyridin-3-yl] -1,3-thiazol-5-yl } methyl) -3phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 516).

Using General Procedure 9, starting from Example 28 and [6- (dimethylamino) -3-pyridyl] boronic acid as reagents, Example 515 and Example 516 were prepared and separated by chromatography.

Example 515 MCBP calculated for C ₄₈ H ₅₂ Ni ₀ O ₃ S: 848.3945, found: 425.2060 [M + 2H) ²⁺ form].

Example 516 MCBP calculated for C ₄₁ H ₄₃ ClN ₈ O ₃ S: 762.2867, found: 382.1494 [M + 2H) ²⁺ form].

5- [5 - ({(3R, 4R) -4 - [(4 - {[7- (4-Chlorophenyl) -4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine -3-yl] me- 117 037563 thyl} -4-hydroxypiperidin-1 -yl) carbonyl] -3-phenylpiperidin-1 -yl} methyl) -1,3-thiazol-2-yl] pyridine-2 carbonitrile (Example 517).

Using General Procedure 9, starting from Example 28 and 5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl) pyridine-2-carbonitrile as reagents, Example 517 was prepared. MCBP: Calculated for

C ₄₀ H ₃₇ ClN ₈ O ₃ S: 744.2398, found: 745.2471 [M + H) ⁺ form].

7- (4-Chlorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazole-5- yl] methyl} 3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 518).

Using General Procedure 9, starting from Example 28 and (6-methyl-3-pyridyl) boronic acid as reactants, Example 518 was prepared. MCBP: Calculated for C ₄₀ H ₄₀ ClN ₇ O ₃ S: 733.2602, Found: 367.6385 [( M + 2H) ²⁺ form].

5- [5 - ({(3R, 4R) -4 - [(4 - {[7- (4-Fluorophenyl) -4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine -3-yl] methyl} -4-hydroxypiperidin-1-yl) carbonyl] -3-phenylpiperidin-1 -yl} methyl) -1,3-thiazol-2-yl] pyridine-2 carbonitrile (Example 519).

Using General Procedure 9, starting from Example 31 and 5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl) pyridine-2-carbonitrile as reagents, Example 519 was prepared. MCBP: Calculated for C ₄₀ H ₃₇ FN ₈ O ₃ S: 728.2693, found: 729.2757 (M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[2- (thiophen-2-yl) -1,3-thiazol-5-yl] methyl} piperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 520).

Using General Procedure 9, starting from Example 34 and 2-thienylboronic acid as reagents, Example 520 was prepared. MCBP: calculated for C ₃₉ H ₄₀ N ₆ O ₄ S ₂ : 720.2552, found: 721.2612 [(M + H) + form ].

3 - [(1 - {[(3R, 4R) -1 - ({2- [6- (Dimethylamino) pyridin-3-yl] -1,3-thiazol-5-yl} methyl) -3-phenylpiperidin4- yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 521).

Using General Procedure 9, starting from Example 34 and [6- (dimethylamino) -3-pyridyl] boronic acid as reactants, Example 521 was prepared. MCBP: Calculated for C ₄₂ H ₄₆ N ₈ O ₄ S: 758.3362 Found: 380.1763 [M + 2H) ²⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - ({2- [6- (trifluoromethyl) pyridin-3 -yl] - 1,3-thiazole-5- yl} methyl) piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 522).

Using General Procedure 9, starting from Example 34 and [6- (trifluoromethyl) -3-pyridyl] boronic acid as reactants, Example 522 was prepared. MCBP: Calculated for C ₄ iH ₄₀ F ₃ N ₇ O ₄ S: 783.2814 Found : 784.2893 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[2- (pyrimidin-5-yl) -1,3-thiazol-5-yl] methyl} piperidine- 4yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 523).

Using General Procedure 9, starting from Example 34 and pyrimidin-5-ylboronic acid as reagents, Example 523 was prepared. MCBP: Calculated for C ₃₉ H ₄₀ N ₈ O ₄ S: 716.2893, Found: 717.2999 [(M + H) + the form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (1-methyl-1H-pyrαzol-5-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one ( Example 524).

Using General Procedure 9, starting from Example 34 and 1-methyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyrazole as reagents, Example 524 was prepared. MCBP: Calculated for C39H42N8O4S: 718.3050, found: 719.3108 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (1-methyl-1H-pyrazol-4-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one ( Example 525).

Using General Procedure 9, starting from Example 34 and 1-methyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyrazole as reagents, Example 525 was prepared. MCBP: Calculated for C ₃₉ H ₄₂ N ₈ O ₄ S: 718.3050, found: 719.3131 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (1-methyl-1H-pyrrol-3-yl) -1,3-thiazol-5-yl] methyl } -3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one (Example 526 ).

Using General Procedure 9 starting from Example 34 and 1-methyl-3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyrrole as reagents, Example 526 was prepared. MCBP: calculated for C40H43N7O4S: 717.3098, found: 718.3145 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[2- (thiophen-3-yl) -1,3-thiazol-5-yl] methyl} piperidine -4yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 527).

- 118 037563

Using General Procedure 9, starting from Example 34 and 4,4,5,5-tetramethyl-2- (3-thienyl) -1,3,2-dioxaborolane as reagents, Example 527 was prepared. MCBP: Calculated for C ₃₉ H ₄₀ N ₆ O ₄ S ₂ :

720.2552, found: 721.2649 [(M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - {[2- (Furαn-3-yl) -1,3-miazol-5-ul] methyl} -3-phenylpuneridin-4-yl] kαrbonyl } -4hydroxypiperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 528).

Using General Procedure 9, starting from Example 34 and 2- (3-furyl) -4,4,5,5-tetramethyl-1,3,2-dioxaborolane as reagents, Example 528 was prepared. MCBP: Calculated for C ₃₉ H ₄₀ N ₆ O ₅ S: 704.2781, found: 705.2852 [(M + H) ⁺ form].

3 - [(1 - {[(3R, 4R) -1 - {[2- (Furan-2-yl) -1,3-miazol-5-ul] methyl} -3-phenylpiperidin-4-yl] kαrbonyl } -4hydroxypiperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 529).

Using General Procedure 9, starting from Example 34 and 2-furylboronic acid as reagents, Example 529 was prepared. MCBP: Calculated for C ₃₉ H ₄₀ N ₆ O ₅ S: 704.2781 Found: 705.2837 [(M + H) + Form] ...

5- [5 - ({(3R, 4R) -4 - [(4-Hydroxy-4 - {[7- (4-methoxyphenyl) -4-oxo-4,7-dihydro-3H-pyrrolo [2,3 -d] pyrimidin-3-yl] methyl} piperidin-1 -yl) carbonyl] -3-phenylpiperidin-1 -yl} methyl) -1,3-thiazol-2-yl] pyridine 2-carbonitrile (Example 530).

Using General Procedure 9, starting from Example 34 and 5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl) pyridine-2-carbonitrile as reagents, Example 530 was prepared. MCBP: Calculated for C41H40N8O4S: 740.2893, found: 741.2956 [M + H) + form].

3 - [(4-Hydroxy-1- {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 531) ...

Using General Procedure 9, starting from Example 34 and (6-methyl-3-pyridyl) boronic acid as reactants, Example 531 was prepared. MCBP: Calculated for C ₄₁ H ₄₃ N ₇ O ₄ S: 729.3098, Found: 365.6619 [( M + 2H) ²⁺ form].

3 - [(1 - {[(3R, 4R) -1 - {[5- (Furan-2-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} -4hydroxypiperidin-4 -yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 532).

Using General Procedure 9, starting from Example 176 and 2-furylboronic acid as reagents, Example 532 was prepared. MCBP: calculated for C ₃₄ H ₃₅ N ₅ O ₅ S: 625.2359, found: 626.2436 [(M + H) + form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (1-methyl-1H-pyrazol-5-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidine- 4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 533).

Using General Procedure 9, starting from Example 176 and 1-methyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyrazole as reagents, Example 533 was prepared. MCBP: Calculated for C ₃₄ H ₃₇ N ₇ O ₄ S: 639.2628, found: 640.2696 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[5 - (pyridin-3-yl) thiophen-2-yl] carbonyl} piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 534).

Using General Procedure 9, starting from Example 176 and 3-pyridylboronic acid as reagents, Example 534 was prepared. MCBP: Calculated for C ₃₅ H ₃₆ N ₆ O ₄ S: 636.2519, Found: 637.2582 [(M + H) + Form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (1-methyl-1H-pyrrol-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 535).

Using General Procedure 9 starting from Example 176 and 1-methyl-3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyrrole as reagents, Example 535 was prepared. MCBP: calculated for C ₃₅ H ₃₈ N ₆ O ₄ S: 638.2675, found: 639.2750 [M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - {[5- (4-Fluorophenyl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} -4hydroxypiperidin-4-yl ) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 536).

Using General Procedure 9, starting from Example 176 and (4-fluorophenyl) boronic acid as reactants, Example 536 was prepared. MCBP: Calculated for C ₃₆ H ₃₆ FN ₅ O ₄ S: 653.2472, Found: 654.254 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - {[5- (3-Fluorophenyl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} -4hydroxypiperidin-4-yl ) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 537).

Using General Procedure 9, starting from Example 176 and (3-fluorophenyl) boronic acid as reagents, Example 537 was prepared. MCBP: Calculated for C ₃₆ H ₃₆ FN ₅ O ₄ S: 653.2472, Found: 654.2552 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (3-methylphenyl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidine -4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 538).

Using General Procedure 9, starting with Example 176 and m-tolylboronic acid as re-119 037563 gents, Example 538 was prepared. MCBP: Calculated for C ₃₇ H ₃₉ N ₅ O ₄ S: 649.2723, Found: 650.2793 [(M + H ) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (2-methylphenyl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidine- 4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 539).

Using General Procedure 9, starting from Example 176 and o-tolylboronic acid as reagents, Example 539 was prepared. MCBP: calculated for C ₃₇ H ₃₉ N ₅ O ₄ S: 649.2723, found: 650.2793 [(M + H) + form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (4-methylphenyl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidine- 4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 540).

Using General Procedure 9, starting from Example 176 and p-tolylboronic acid as reagents, Example 540 was prepared. MCBP: Calculated for C ₃₇ H ₃₉ N ₅ O ₄ S: 649.2723, Found: 650.2792 [(M + H) + Form] ...

3 - [(1 - {[(3R, 4R) -1 - {[5- (Furan-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} -4hydroxypiperidin-4 -yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 541).

Using General Procedure 9, starting from Example 176 and 2- (3-furyl) -4,4,5,5-tetramethyl-1,3,2-dioxaborolane as reagents, Example 541 was prepared. MCBP calculated for C ₃₄ H ₃₅ N ₅ O ₅ S 626.2425: 625.2359, found: [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[5 - (pyrimidin-5-yl) thiophen-2-yl] carbonyl} piperidin-4yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 542).

Using General Procedure 9, starting from Example 176 and pyrimidin-5-ylboronic acid as reactants, Example 542 was prepared. MCBP: Calculated for C ₃₄ H ₃₅ N ₇ O ₄ S: 637.2471, Found: 638.2544 [(M + H) ⁺ the form].

3 - [(1 - {[(3R, 4R) -1 - {[2- (Furan-2-yl) -4-methyl-1,3-thiazol-5-ul] kαcarbonyl} -3-phenylpuneridin-4 -yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 543).

Using General Procedure 9, starting from Example 349 and 2-furylboronic acid as reagents, Example 543 was prepared. MCBP: calculated for C ₃₄ H ₃₆ N ₆ O ₅ S: 640.2468, found: 641.2544 [(M + H) + form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (pyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3 -phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 544).

Using General Procedure 9, starting from Example 349 and 3-pyridylboronic acid as reagents, Example 544 was prepared. MCBP: Calculated for C ₃₅ H ₃₇ N ₇ O ₄ S: 651.2628, Found: 652.2697 [(M + H) + Form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (1-methyl-1H-pyrazol-5-yl) -1,3-thiazole-5- yl] carbonyl} -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 545 ).

Using General Procedure 9 starting from Example 349 and 1-methyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyrazole as reagents, Example 545 was prepared. MCBP: Calculated for C ₃₄ H ₃₈ N ₈ O ₄ S: 654.2737, found: 655.2823 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (1-methyl-1H-pyrrol-3-yl) -1,3-thiazole-5- yl] carbonyl} -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 546 ).

Using General Procedure 9, starting from Example 349 and 1-methyl-3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyrrole as reagents, Example 546 was prepared. MCBP: Calculated for C ₃ 5H ₃₉ N ₇ O4S: 653.2784, found: 654.2848 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (1-methyl-1H-pyrazol-4-yl) -1,3-thiazole-5- yl] carbonyl} -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 547 ).

Using General Procedure 9, starting from Example 349 and 1-methyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyrazole as reagents, Example 547 was prepared. MCBP: Calculated for C ₃₄ H ₃₈ N ₈ O ₄ S: 654.2737, found: 655.2817 [(M + H) ⁺ form].

3 - [(1 - {[(3R, 4R) -1 - {[2- (Furan-3-yl) -4-methyl-1,3-miazol-5-ul] kαarbonyl} -3-phenylpuneridin-4 -yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 548).

Using General Procedure 9, starting from Example 349 and 2-furylboronic acid as reagents, Example 548 was prepared. MCBP: calculated for C ₃₄ H ₃₆ N ₆ O ₅ S: 640.2468, found: 641.2541 [(M + H) + form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (pyrimidin-5-yl) -1,3-thiazol-5-yl] carbonyl} -3 -phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 549).

- 120 037563

Using General Procedure 9, starting from Example 349 and pyrimidin-5-ylboronic acid as reactants, Example 549 was prepared. MCBP: Calculated for C ₃₄ H ₃₆ N8O ₄ S: 652.2580 Found:

653.2656 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (3-methylphenyl) -1,3-thiazol-5-yl] carbonyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 550).

Using General Procedure 9, starting from Example 349 and m-tolylboronic acid as reagents, Example 550 was prepared. MCBP: Calculated for C ₃₇ H ₄₀ N ₆ O ₄ S: 664.2832, Found: 665.2893 [(M + H) + Form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (thiophen-2-yl) -1,3-thiazol-5-yl] carbonyl} -3 -phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 551).

Using General Procedure 9, starting from Example 349 and 2-thienylboronic acid as reagents, Example 551 was prepared. MCBP: Calculated for C ₃₄ H ₃₆ N ₆ O ₄ S ₂ : 656.2239, Found: 657.2318 [(M + H) + form ].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (4-methylphenyl) -1,3-thiazol-5-yl] carbonyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 552).

Using General Procedure 9, starting from Example 349 and p-tolylboronic acid as reagents, Example 552 was prepared. MCBP: Calculated for C ₃₇ H ₄₀ N ₆ O ₄ S: 664.2832, Found: 665.2908 [(M + H) + Form] ...

3 - [(1- {[(3R, 4R) -1 - {[2- (4-fluorophenyl) -4-methyl-1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl ] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 553).

Using General Procedure 9, starting from Example 349 and (4-fluorophenyl) boronic acid as reactants, Example 553 was prepared. MCBP: Calculated for C ₃₆ H ₃₇ FN ₆ O ₄ S: 668.2581, Found: 669.2656 [(M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - {[2- (3-Fluorophenyl) -4-methyl-1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl ] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 554).

Using General Procedure 9, starting from Example 349 and (3-fluorophenyl) boronic acid as reactants, Example 554 was prepared. MCBP: Calculated for C ₃₆ H ₃₇ FN ₆ O ₄ S: 668.2581, Found: 669.2659 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (thiophen-3-yl) -1,3-thiazol-5-yl] carbonyl} - 3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 555).

Using General Procedure 9 starting from Example 349 and 4,4,5,5-tetramethyl-2- (3-thienyl) -1,3,2-dioxaborolane as reagents, Example 555 was prepared. MCBP: Calculated for C ₃₄ H ₃₆ N ₆ O ₄ S ₂ : 656.2239, found: 657.2300 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - {[5- (3-Fluoropyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} -4 -hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 556).

Using General Procedure 9, starting from Example 176 and (3-fluoro-4-pyridyl) boronic acid as reagents, Example 556 was prepared. MCBP: Calculated for C ₃₅ H ₃₅ FN ₆ O ₄ S: 654.2425, Found: 655.2499 [( M + H) + form].

3 - [(1- {[(3R, 4R) -1 - (2,2'-Bithiophen-5-ylcarbonyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 557).

Using General Procedure 9, starting from Example 176 and 2-thienylboronic acid as reagents, Example 557 was prepared. MCBP: Calculated for C ₃₄ H ₃₅ N ₅ O ₄ S ₂ : 641.2130, Found: 642.2219 [(M + H) + form ].

3 - [(1 - {[(3R, 4R) -1- (2,3'-Bithiophen-5-ylcarbonyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 558).

Using General Procedure 9, starting from Example 176 and 4,4,5,5-tetramethyl-2- (3-thienyl) -1,3,2-dioxaborolane as reagents, Example 558 was prepared. MCBP: Calculated for C ₃₄ H ₃₅ N ₅ O ₄ S ₂ : 641.2131, found: (642.2210 [(M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - {[5- (2-Fluorophenyl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} -4hydroxypiperidin-4-yl ) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 559).

Using General Procedure 9, starting from Example 176 and (2-fluorophenyl) boronic acid as reactants, Example 559 was prepared. MCBP: Calculated for C ₃₆ H ₃₆ FN ₅ O ₄ S: 653.2472, Found: 654.2541 [(M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -3-phenyl-1 - [(5-phenylthiophen-2-yl) carbonyl] piperidin-4-yl} carbonyl) piperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 560).

- 121 037563

Using General Procedure 9 starting from Example 176 and phenylboronic acid as reagents, Example 560 was prepared. MCBP: calculated for C ₃₆ H ₃₇ N ₅ O ₄ S: 635.2566, found: 636.264 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (1-methyl-1H-pyrazol-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidine- 4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 561).

Using General Procedure 9, starting from Example 176 and 1-methyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyrazole as reagents, Example 561. MCBP: calculated for C34H37N7O4S: 639.2628, found: 640.2695 [(M + H) ⁺ form].

3 - [(1- {[(3R, 4R) -1 - {[5- (2-Chloropyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} -4 -hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 562).

Using General Procedure 9, starting from Example 176 and (2-chloro-4-pyridyl) boronic acid as reactants, Example 562 was prepared. MCBP: Calculated for C ₃₅ H ₃₅ ClN ₆ O ₄ S: 670.2129, Found: 671.2194 [( M + H) + form].

3 - [(1- {[(3R, 4R) -1 - {[5- (3-Chloropyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} -4 -hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 563).

Using General Procedure 9, starting from Example 176 and (3-chloro-4-pyridyl) boronic acid as reagents, Example 563 was prepared. MCBP: calculated for C35H35C1N6O4S: 670.2129, found: 671.2188 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (3-methylpyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl ] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 564).

Using General Procedure 9, starting from Example 176 and (3-methyl-4-pyridyl) boronic acid as reactants, Example 564 was prepared. MCBP: Calculated for C ₃₆ H ₃₈ N ₆ O ₄ S: 650.2675, Found: 651.2742 [( M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (2-methylpyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl ] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 565).

Using General Procedure 9, starting from Example 176 and (2-methyl-4-pyridyl) boronic acid as reactants, Example 565 was prepared. MCBP: Calculated for C ₃₆ H ₃₈ N ₆ O ₄ S: 650.2675, Found: 651.2724 [( M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - {[5- (5-Chloro-2-fluoropyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 566).

Using General Procedure 9, starting from Example 176 and (5-chloro-2-fluoro-4-pyridyl) boronic acid as reagents, Example 566 was prepared. MCBP: Calculated for C ₃₅ H ₃₄ ClFN ₆ O ₄ S: 688.2035 Found : 689.2135 [(M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - {[5- (2,5-Dichloropyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 567).

Using General Procedure 9 starting from Example 176 and 2,5-dichloro-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine as reagents, Example 567 was prepared. MCBP: calculated for C35H34N6O4SCI2: 704.1740, found: 705.1819 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - {[5- (2-Fluoropyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} -4 -hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 568).

Using General Procedure 9, starting from Example 176 and (2-fluoro-4-pyridyl) boronic acid as reactants, Example 568 was prepared. MCBP: Calculated for C3 ₅ H ₃₅ N ₆ O ₄ S: 654.2425, Found: 655.251 [( M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -3-phenyl-1 - [(5-phenylthiophen-2-yl) sulfonyl] piperidin-4-yl} carbonyl) piperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 569).

Using General Procedure 9, starting from Example 342 and phenylboronic acid as reagents, Example 569 was prepared. MCBP: Calculated for C35H ₃₇ N5O ₅ S ₂ : 671.2236, Found: 672.2297 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[5- (pyridin-4-yl) thiophen-2-yl] sulfonyl} piperidine-4yl] carbonyl} piperidine -4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 570).

Using General Procedure 9 starting from Example 342 and 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl) pyridine as reagents, Example 570 was prepared. MCBP: Calculated for C ₃₄ H ₃₆ N ₆ O ₅ S ₂ : 672.2189, found: 337.1169 [(M + 2H) ²⁺ form].

- 122 037563

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[5 - (pyrimidin-5-yl) thiophen-2-yl] sulfonyl} piperidin-4yl] carbonyl} piperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] nupuMuguH-4-OH (Example

571).

Using General Procedure 9, starting from Example 342 and pyrimidin-5-ylboronic acid as reactants, Example 571 was prepared. MCBP: Calculated for C ₃₃ H ₃₅ N ₇ O ₅ S ₂ : 673.2141, Found: 674.221 [(M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1- [3 - (1-methyl-1H-pyrazol-5-yl) benzoyl] -3-phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 572)

Using General Procedure 9 starting from Example 201 and 1-methyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyrazole as reagents, Example 572 was prepared. MCBP: calculated for C ₃ 6H ₃₉ N ₇ O4: 633.3063, found: 634.3140 [(M + H) ⁺ form].

- {[4-Hydroxy-1 - ({(3R, 4R) -3-phenyl-1- [3 - (pyrimidin-5-yl) benzoyl] piperidin-4-yl} carbonyl) piperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 573).

Using General Procedure 9, starting from Example 201 and pyrimidin-5-ylboronic acid as reagents, Example 573 was prepared. MCBP: Calculated for C ₃₆ H ₃₇ N ₇ O ₄ : 631.2907 Found: 632.2982 [(M + H) + form ].

- {[4-Hydroxy-1 - ({(3R, 4R) -3-phenyl-1- [3 - (pyridin-4-yl) benzoyl] piperidin-4-yl} carbonyl) piperidin-4-yl] methyl} -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 574).

Using General Procedure 9, starting from Example 201 and 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl) pyridine as reagents, Example 574 was prepared. MCBP: Calculated for C ₃₇ H ₃₈ N ₆ O ₄ : 630.2955, found: 316.1552 [(M + 2H) ²⁺ form].

- {[4-Hydroxy-1 - ({(3R, 4R) -3-phenyl-1- [3 - (pyridin-3-yl) benzoyl] piperidin-4-yl} carbonyl) piperidin-4-yl] methyl} -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 575).

Using General Procedure 9, starting from Example 201 and 3-pyridylboronic acid as reagents, Example 575 was prepared. MCBP: calculated for C ₃₇ H ₃₈ N ₆ O ₄ : 630.2955, found: 631.3037 [(M + H) + form].

3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4- (1-methyl-1H-pyrazol-5-yl) pyridin-2-yl] carbonyl} -3 phenylpiperidin-4 -yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3d] pyrimidin-4-one (Example 576).

Using General Procedure 9, starting from Example 194 and 1-methyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyrazole as reagents, Example 576 was prepared. MCBP: Calculated for C ₃₃ H ₃ 8N8O4: 634.3016, found: 635.3092 [(M + H) ⁺ form].

3 - [(1 - {[(3R, 4R) -1- (4,4'-Bipyridin-2-ylcarbonyl) -3-phenylpineridin-4-yl] carbonyl} -4-hydroxupiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 577).

Using General Procedure 9 starting from Example 194 and 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl) pyridine as reagents, Example 577 was prepared. MCBP: Calculated for C ₃₆ H ₃₇ N ₇ O ₄ : 631.2907, found: 632.2978 [(M + H) + form].

3 - [(4-Hydroxy-1- {[(3R, 4R) -1 - {[5- (1-methyl-1H-pyrαzol-5-yl) thiophen-2-yl] sulfonyl} -3-phenylpiperidine- 4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 578).

Using General Procedure 9, starting from Example 342 and 1-methyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyrazole as reagents, Example 578 was prepared. MCBP: Calculated for C ₃₃ H ₃₇ N ₇ O5S2: 675.2297, found: 676.2372 [(M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -3-phenyl-1- [3 - (pyrimidin-5-yl) benzyl] piperidin-4-yl} carbonyl) piperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 579).

Using General Procedure 9, starting from Example 69 and pyrimidin-5-ylboronic acid as reactants, Example 579 was prepared. MCBP: calculated for C ₃₆ H ₃₉ N ₇ O ₃ : 617.3115, found: 618.3169 [(M + H) + form ].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[3 - (pyrimidin-5-yl) phenyl] sulfonyl} piperidin-4-yl] carbonyl} piperidine- 4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 580).

Using General Procedure 9, starting from Example 343 and pyrimidin-5-ylboronic acid as reactants, Example 580 was prepared. MCBP: Calculated for C ₃₅ H ₃₇ N ₇ O ₅ S: 667.2577, Found: 668.2657 [(M + H) + the form].

3 - [(1- {[(3R, 4R) -1 - (Biphenyl-3-ylmethyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin4-yl) methyl] -7 -methyl-3, 7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 581).

Using General Procedure 9, starting from Example 69 and phenylboronic acid as reagents, Example 581 was prepared. MCBP: calculated for C ₃₈ H ₄ iN ₅ O ₃ : 615.3209, found: 616.3306 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - (Biphenyl-3 -ylsulfonyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl- 3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 582).

Using General Procedure 9, starting with Example 343 and phenylboronic acid as reagents, Example 582 was prepared. MCBP: Calculated for C ₃₇ H ₃₉ N ₅ O ₅ S: 665.2672 Found: 666.2747 [(M + H) +

- 123 037563 form].

- {[4-Hydroxy-1 - ({(3R, 4R) -3-phenyl-1- [3 - (pyridin-4-yl) benzyl] piperidin-4-yl} carbonyl) piperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-o n (Example 583).

Using General Procedure 9, starting from Example 69 and 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl) pyridine as reagents, Example 583 was prepared. MCBP: Calculated for C ₃₇ H ₄₀ N ₆ O ₃ : 616.3162, found: 309.1648 [(M + 2H) ² + form].

3 - [(1 - {[(3R, 4R) -1 - {[3-Fluoro-5- (pyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 584).

Using General Procedure 9, starting from Example 197 and 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl) pyridine as reagents, Example 584 was prepared. MCBP: Calculated for C ₃₅ H ₃₅ FN ₆ O ₄ S: 654.2425, found: (655.2508 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (1-methyl-1H-pyrazol-5-yl) pyridin-4-yl] carbonyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 585).

Using General Procedure 9, starting from Example 195 and 1-methyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyrazole as reagents, Example 585 was prepared. MCBP: calculated for C ₃₅ H ₃₈ N ₈ O ₄ : 634.3016, found: 635.3109 [(M + H) ⁺ form].

3 - [(1- {[(3R, 4R) -1 - (2,4'-Bipyridin-4-ylcarbonyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 586).

Using General Procedure 9, starting from Example 195 and 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl) pyridine as reagents, Example 586 was prepared. MCBP: Calculated for C ₃₆ H ₃₇ N ₇ O ₄ : 631.2907, found: 632.2999 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (1-methyl-1H-pyrazol-5-yl) pyridin-3-yl] carbonyl} -3-phenylpiperidine- 4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 587).

Using General Procedure 9, starting from Example 196 and 1-methyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyrazole as reagents, Example 587 was prepared. MCBP: calculated for C ₃₅ H ₃₈ N ₈ O ₄ : 634.3016, found: 635.3091 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - (3,4'-Bipyridin-5-ylcarbonyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 588).

Using General Procedure 9, starting from Example 196 and 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl) pyridine as reagents, Example 588 was prepared. MCBP: Calculated for C ₃₆ H ₃₇ N ₇ O ₄ : 631.2907, found: 632.2985 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[6- (1-methyl-1H-pyrazol-5-yl) pyridin-2-yl] carbonyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 589).

Using General Procedure 9, starting from Example 198 and 1-methyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyrazole as reagents, Example 589 was prepared. MCBP: Calculated for C ₃₅ H ₃₈ N ₈ O ₄ : 634.3016, found: 635.3110 [(M + H) + form].

3 - [(1 - {[(3R, 4R) -1- (2,4'-Bipyridin-6-ylcarbonyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 590).

Using General Procedure 9, starting from Example 198 and 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl) pyridine as reagents, Example 590 was prepared. MCBP: Calculated for C ₃₆ H ₃₇ N ₇ O ₄ : 631.2907, found: 632.2996 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[3 - (pyridin-4-yl) phenyl] sulfonyl} piperidin-4-yl] carbonyl} piperidine- 4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 591).

Using General Procedure 9 starting from Example 343 and 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl) pyridine as reagents, Example 591 was prepared. MCBP: Calculated for C ₃₆ H ₃₈ N ₆ O ₅ S: 666.2625, found: 667.2711 [(M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(1-methyl-4-phenyl-1H-pyrrol-2-yl) carbonyl] -3-phenylpiperidin-4yl} carbonyl) piperidine -4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-o n (Example 592).

Using General Procedure 9, starting from Example 189 and phenylboronic acid as reagents, Example 592 was prepared. MCBP: calculated for C ₃₇ H ₄₀ N ₆ O ₄ : 632.3111, found: 633.3178 [(M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1- [3 - (1-methyl-1H-pyrazol-5-yl) benzyl] -3-phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 593).

Using General Procedure 9, starting from Example 69 and 1-methyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyrazole as reagents, Example 593 was prepared. MCBP: Calculated for C ₃₆ H ₄₁ N ₇ O ₃ : 619.3271, found: 620.3359 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[3 - (1-methyl-1H-pyrazol-5-yl) phenyl] sulfonyl} -3-phenylpiperidine-124 037563

4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example

594).

Using General Procedure 9, starting from Example 343 and 1-methyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyrazole as reagents, Example 594 was prepared. MCBP: Calculated for C ₃₅ H ₃₉ N ₇ O ₅ S: 669.2733, found: 670.2827 [(M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - {[5- (2,3-Dichloropyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 595).

Using General Procedure 9 starting from Example 176 and 2,3-dichloro-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine as reagents, Example 595 was prepared. MCBP: calculated for C35H34N6O4SQ2: 704.1740, found: 705.1807 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (2-methoxypyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl ] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 596).

Using General Procedure 9, starting from Example 176 and (2-methoxy-4-pyridyl) boronic acid as reagents, Example 596 was prepared. MCBP: Calculated for C ₃₆ H ₃₈ N ₆ O ₄ S: 666.2625, Found: 667.2699 [( M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (3-methoxypyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl ] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 597).

Using General Procedure 9, starting from Example 176 and (3-methoxy-4-pyridyl) boronic acid as reagents, Example 597 was prepared. MCBP: Calculated for C ₃₆ H3 ₈ N ₆ O ₅ S: 666.2625, Found: 667.2702 [( M + H) + form].

2 - {[(3R, 4R) -4 - ({4-Hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine-3- yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} -5- (pyridin-4-yl) thiophene-3carbonitrile (Example 598).

Using General Procedure 9, starting from Example 212 and 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl) pyridine as reagents, Example 598 was prepared. MCBP: Calculated for C ₃₆ H ₃₅ N ₇ O ₄ S: 661.2471, found: 662.2543 [(M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - {[3-Fluoro-5- (2-methylpyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 599).

Using General Procedure 9, starting from Example 197 and (2-methyl-4-pyridyl) boronic acid as reactants, Example 599 was prepared. MCBP: Calculated for C3 ₆ H ₃₇ N ₆ O ₄ FS: 668.2581, Found: 669.2662 [( M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (4-methylpyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl ] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 600).

Using General Procedure 9, starting from Example 176 and (4-methyl-3-pyridyl) boronic acid as reactants, Example 600 was prepared. MCBP: Calculated for C ₃₆ H ₃₈ N ₆ O ₄ S: 650.2675, Found: 651.2756 [( M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (5-methylpyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl ] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 601).

Using General Procedure 9, starting from Example 176 and (5-methyl-3-pyridyl) boronic acid as reactants, Example 601 was prepared. MCBP: Calculated for C ₃₆ H ₃₈ N ₆ O ₄ S: 650.2675, Found: 651.2774 [( M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (6-methylpyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl ] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 602).

Using General Procedure 9, starting from Example 176 and (6-methyl-3-pyridyl) boronic acid as reactants, Example 602 was prepared. MCBP: Calculated for C ₃₆ H ₃₈ N ₆ O ₄ S: 650.2675, Found: 651.2757 [( M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (2-methylpyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl ] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 603).

Using General Procedure 9, starting from Example 176 and 2-methyl-3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine as reagents, Example 603 was prepared. MCBP: Calculated for C36H38N6O4S: 650.2675, found: 651.2768 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - {[5- (6-Aminopyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} -4 -hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 604).

- 125 037563

Using General Procedure 9, starting from Example 176 and 5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl) pyridin-2-amine as reagents, Example 604 was prepared. MCBP: Calculated for C ₃₅ H ₃₇ N ₇ O ₄ S:

651.2628, found: 651.2710 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (6-methoxypyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl ] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 605).

Using General Procedure 9, starting from Example 176 and (6-methoxy-3-pyridyl) boronic acid as reagents, Example 605 was prepared. MCBP: Calculated for C ₃₆ H ₃₈ N ₆ O ₅ S: 666.2625, Found: 667.2700 [( M + H) + form].

3 - [(1- {[(3R, 4R) -1 - {[5- (4-Chloropyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} -4 -hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 606).

Using General Procedure 9 starting from Example 176 and 4-chloro-3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine as reagents, Example 606 was prepared. MCBP: Calculated for C ₃₅ H ₃₅ ClN ₆ O ₄ S: 670.2129, found: 671.2207 (M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (4-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 607).

Using General Procedure 9, starting from Example 349 and (4-methyl-3-pyridyl) boronic acid as reagents, Example 607 was prepared. MCBP: Calculated for C ₃₆ H ₃₉ N ₇ O ₄ S: 665.2784, Found: 666.2838 [( M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (5-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl } -3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 608).

Using General Procedure 9, starting from Example 349 and (5-methyl-3-pyridyl) boronic acid as reactants, Example 608 was prepared. MCBP: Calculated for C ₃₆ H ₃₉ N ₇ O ₄ S: 665.2784, Found: 666.2845 [( M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 609).

Using General Procedure 9, starting from Example 349 and (6-methyl-3-pyridyl) boronic acid as reagents, Example 609 was prepared. MCBP: Calculated for C ₃₆ H ₃₉ N ₇ O ₄ S: 665.2784 Found: 666.2829 [( M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (2-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 610).

Using General Procedure 9, starting from Example 349 and 2-methyl-3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine as reagents, Example 610 was prepared. MCBP: Calculated for C ₃₆ H ₃₉ N ₇ O ₄ S: 665.2784, found: 666.2825 (M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - {[2- (6-Aminopyridin-3-yl) -4-methyl-1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidine -4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 611).

Using General Procedure 9 starting from Example 349 and 5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl) pyridin-2-amine as reagents, Example 611 was prepared. MCBP: Calculated for C ₃₅ H ₃₈ N ₈ O ₄ S: 666.2737, found: 667.2802 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -4-methyl-1,3-thiazol-5-yl] carbonyl} -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 612).

Using General Procedure 9, starting from Example 349 and (6-methoxy-3-pyridyl) boronic acid as reagents, Example 612 was prepared. MCBP: Calculated for C ₃₆ H ₃₉ N ₇ O ₅ S: 681.2733, Found: 682.2797 [( M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[1-methyl-5- (2-methylpyridin-4-yl) -1H-pyrrol-2-yl] carbonyl} - 3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 613).

Using General Procedure 9, starting from Example 217 and (2-methyl-4-pyridyl) boronic acid as reactants, Example 613 was prepared. MCBP: Calculated for C ₃₇ H ₄ iN ₇ O ₄ : 647.3220, Found: 648.3316 [(M + H) + form].

3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[1 -methyl-5- (pyridin-3-yl) -1H-pyrrol-2-yl] carbonyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 614).

Using General Procedure 9, starting from Example 217 and 3-pyridylboronic acid as reagents, Example 614 was prepared. MCBP: Calculated for C ₃₆ H ₃₉ N ₇ O ₄ : 633.3063, Found: 634.3138

- 126 037563

[(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[1-methyl-5- (pyrimidin-5-yl) -1H-pyrrol-2-yl] carbonyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin4-one (Example 615).

Using General Procedure 9, starting from Example 217 and pyrimidin-5-ylboronic acid as reactants, Example 615 was prepared. MCBP: Calculated for C ₃₅ H ₃₈ N ₈ O ₄ : 634.3016, Found: 635.3092 [(M + H) + form ].

3 - [(1- {[(3R, 4R) -1 - {[2- (5-Chloropyridin-3-yl) -4-methyl-1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidine -4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 616).

Using General Procedure 9 starting from Example 349 and 3-chloro-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine as reagents, Example 616 was prepared. MCBP: Calculated for C ₃ 5H ₃ 6ClN7O4S: 685.2238, found: 686.2306 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[1-methyl-5- (1-methyl-1H-pyrazol-5-yl) -1H-pyrrol-2-yl]] carbonyl} -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 617).

Using General Procedure 9, starting from Example 217 and 1-methyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyrazole as reagents, Example 617 was prepared. MCBP: Calculated for C ₃₅ H ₄₀ N ₈ O ₄ : 636.3173, found: 637.3251 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[1-methyl-5- (pyridin-4-yl) -1H-pyrrol-2-yl] carbonyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 618).

Using General Procedure 9 starting from Example 217 and 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl) pyridine as reagents, Example 618 was prepared. MCBP: Calculated for C ₃₆ H ₃₉ N ₇ O ₄ : 633.3063, found: 634.3128 [(M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - {[3-fluoro-5- (2-Methoxypyrigin-4-yl) tyophen-2-yl] carbonyl} -3-phenylpinerigin4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine-4one (Example 619).

Using General Procedure 9, starting from Example 197 and (2-methoxy-4-pyridyl) boronic acid as reagents, Example 619 was prepared. MCBP: Calculated for C ₃₆ H ₃₇ FN ₆ O ₅ S: 684.2530, Found: 685.2594 [( M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (3-methoxypyridin-4-yl) -4-methyl-1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3d] pyrimidin-4-one (Example 620).

Using General Procedure 9, starting from Example 349 and (3-methoxy-4-pyridyl) boronic acid as reagents, Example 620 was prepared. MCBP: Calculated for C ₃₆ H ₃₉ N ₇ O ₅ S: 681.2733, Found: 682.2827 [( M + H) + form].

3 - [(1- {[(3R, 4R) -1 - {[5- (5-Chloropyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} -4 -hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 621).

Using General Procedure 9, starting from Example 176 and 3-chloro-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine as reagents, Example 621 was prepared. MCBP: Calculated for C ₃ 5H ₃ 5ClN6O4S: 670.2129, found: 671.2200 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-5- (2-methylpyridin-4-yl) -1,3-thiazol-2-yl] carbonyl } -3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 622).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromo-4-methylthiazole-2carboxylic acid as reactants, the resulting crude product was reacted with (2-methyl-4-pyridyl) boronic acid according to General Procedure 9 to give Example 622. MCBP: calculated for C ₃₆ H ₃₉ N ₇ O ₄ S: 665.2784, found: 666.2863 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (2-methoxypyridin-4-yl) -4-methyl-1,3-thiazol-5-yl] carbonyl} -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 623).

Using General Procedure 9, starting from Example 349 and (2-methoxy-4-pyridyl) boronic acid as reagents, Example 623 was prepared. MCBP: Calculated for C ₃₆ H ₃₉ N ₇ O ₅ S: 681.2733, Found: 682.2807 [( M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - {[3-Fluoro-5- (2-methoxy-6-methylpyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidine- 4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 624).

Using General Procedure 9, starting from Example 269 and 2-methoxy-6-methyl-4- (4,4,5,5-tetramethyl1,3,2-dioxaborolan-2-yl) pyridine as reagents, Example 624 was prepared. MCBP: calculated for C ₃₇ H ₃₉ FN ₆ O ₅ S: 698.2687, found: 699.2764 [(M + H) + form].

- 127 037563

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (2-methylpyridin-4-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 625).

Using General Procedure 9, starting from Example 349 and (2-methyl-4-pyridyl) boronic acid as reactants, Example 625 was prepared. MCBP: Calculated for C ₃₆ H ₃₉ N ₇ O ₄ S: 665.2784, Found: 666.287 [( M + H) + form].

3 - [(1- {[(3R, 4R) -1 - {[3-Fluoro-5- (pyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} -4 -hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 626).

Using General Procedure 9, starting from Example 269 and 3-pyridylboronic acid as reagents, Example 626 was prepared. MCBP: calculated for C ₃₅ H ₃₅ FN ₆ O ₄ S: 654.2424, found: 655.2505 [(M + H) + form] ...

3 - [(1- {[(3R, 4R) -1 - {[3 -Fluoro-5- (3-methoxypyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine-4one (Example 627).

Using General Procedure 9, starting from Example 269 and (3-methoxy-4-pyridyl) boronic acid as reagents, Example 627 was prepared. MCBP: Calculated for C ₃₆ H ₃₇ FN ₆ O ₅ S: 684.2530, Found: 685.2598 [( M + H) + form].

tert-Butyl [4- (4-fluoro-5 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3d] pyrimidin-3-yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} thiophen-2yl) pyridin-2-yl] carbamate (Example 628).

Using General Procedure 9, starting from Example 269 and tert-butyl N- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -2-pyridyl] carbamate as reagents, Example 628 MCBP calculated for C ₄₀ H ₄₄ FN ₇ O ₆ S: 769.3058, found: 770.3118 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[3-methyl-5- (pyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4 -yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 629).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromo-3-methylthiophene-2carboxylic acid as reactants, the resulting crude product was reacted with 4- (4,4,5,5-tetramethyl-1,3, 2-dioxaborolan-2-yl) pyridine according to General Procedure 9 to give Example 629. MCBP: calculated for C ₃₆ H ₃₈ N ₆ O ₄ S: found: 651.2752 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - {[3-Fluoro-5- (6-methoxypyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine-4one (Example 630).

Using General Procedure 9, starting from Example 269 and (6-methoxy-3-pyridyl) boronic acid as reagents, Example 630 was prepared. MCBP: Calculated for C ₃₆ H ₃₇ FN ₆ O ₅ S: 684.253, Found: 685.2619 [( M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (6-methoxypyridin-3-yl) -3-methylthiophen-2-yl] carbonyl} -3-phenylpiperidin-4 -yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 631).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromo-3-methylthiophene-2carboxylic acid as reactants, the resulting crude product was reacted with (6-methoxy-3-pyridyl) boronic acid according to General Procedure 9 to give Example 631. MCBP: calculated for C ₃₇ H ₄₀ N ₆ O ₅ S: 680.2781, found: 681.2868 [(M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - {[5- (6-Aminopyridin-3-yl) -3-fluorothiophen-2-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} - 4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 632).

Using General Procedure 9 starting from Example 269 and 5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl) pyridin-2-amine as reagents, Example 632 was prepared. MCBP: Calculated for C ₃₅ H ₃₆ FN ₇ O ₄ S: 669.2534, found: 335.6352 (M + 2H) ²⁺ form].

3 - [(1- {[(3R, 4R) -1 - {[5- (6-Aminopyridin-3-yl) -3-methylthiophen-2-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} - 4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 633)

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromo-3-methylthiophene-2carboxylic acid as reactants, the resulting crude product was reacted with 5- (4,4,5,5-tetramethyl-1,3, 2-dioxaborolan-2-yl) pyridine-2-amine according to General Procedure 9 to give Example 633. MCBP: calculated for C ₃₆ H ₃₉ N ₇ O ₄ S: 665.2784, found: 333.647 [(M + 2H) ^{2 +} form].

3 - [(4-Hydroxy-1- {[(3R, 4R) -1 - {[3-methyl-5- (6-methylpyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 634).

Using General Procedure 7, starting from the Synthesis compound R3b and 5-bromo-3-methylthiophene-2-128 037563 carboxylic acid as reactants, the resulting crude product was reacted with (6-methyl-3-pyridyl) boronic acid according to with General Procedure 9 to obtain Example

634. MCBP calculated for C ₃₇ H ₄₀ N ₆ O ₄ S: 664.2832, found: 665.2914 [(M + H) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(3-methyl-2,3'-thiophen-5-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) piperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 635).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromo-4-methylthiophene-2carboxylic acid as reactants, the resulting crude product was reacted with 4,4,5,5-tetramethyl-2- (3-thienyl) -1,3,2-dioxaborolane according to General Procedure 9 to give Example 635. MCBP: calculated for C ₃₅ H ₃₇ N ₅ O ₄ S ₂ : 655.2287, found: 656.2362 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-5- (2-methylpyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 636).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromo-4-methylthiophene-2carboxylic acid as reactants, the resulting crude product was reacted with (2-methyl-4-pyridyl) boronic acid according to General Procedure 9 to give Example 636. MCBP: calculated for C ₃₇ H ₄₀ N ₆ O ₄ S: 664.2832, found: 665.2913 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (2-methoxypyridin-4-yl) -4-methylthiophen-2-yl] carbonyl} -3-phenylpiperidin-4 -yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 637).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromo-4-methylthiophene-2carboxylic acid as reactants, the resulting crude product was reacted with (2-methoxy-4-pyridyl) boronic acid according to General Procedure 9 to give Example 637. MCBP: calculated for C ₃₇ H ₄₀ N ₆ O ₅ S: 680.2781, found: [(681.2854 (M + H) + form].

3 - [(4-Hydroxy-1- {[(3R, 4R) -1 - {[4-methyl-5- (pyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4 -yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 638).

Using General Procedure 7, starting from the Synthesis compound of R3b and 5-bromo-4-methylthiophene-2carboxylic acid as reactants, the resulting crude product was reacted with 3-pyridylboronic acid according to General Procedure 9 to give Example 638. MCBP: calculated for C ₃₆ H ₃₈ N ₆ O ₄ S: 650.2675, found: 651.2737 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (3-methoxypyridin-4-yl) -4-methylthiophen-2-yl] carbonyl} -3phenylpiperidin-4-yl ] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 639).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromo-4-methylthiophene-2carboxylic acid as reactants, the resulting crude product was reacted with (3-methoxy-4-pyridyl) boronic acid according to General Procedure 9 to give Example 639. MCBP: calculated for C ₃₇ H ₄₀ N ₆ O ₅ S: 680.2781, found: 681.2859 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - ({4-methyl-2- [2- (trifluoromethyl) pyridin-4-yl]] -1,3-thiazol-5-yl } carbonyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 640).

Using General Procedure 9, starting from Example 349 and 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl) -2- (trifluoromethyl) pyridine as reagents, Example 640 was prepared. MCBP: calculated for C ₃ 6H ₃ 6F3N? O4S: 719.2502, found: 720.2566 [(M + H) ⁺ form].

3 - [(1 - {[(3R, 4R) -1 - ({3-Fluoro-5- [2- (trifluoromethyl) pyridin-4-yl] thiophen-2-yl} carbonyl) -3-phenylpiperidin-4 -yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 641).

Using General Procedure 9, starting from Example 269 and 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl) -2- (trifluoromethyl) pyridine as reagents, Example 641. MCBP: calculated for C ₃₆ H ₃₄ F ₄ N ₆ O ₄ S: 722.2299, found: 723.2378 [(M + H) ⁺ form].

3 - {[1 - ({(3R, 4R) -1 - [(4-Fluoro-2,3'-bithiophen-5-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidin-4 -yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 642).

Using General Procedure 9 starting from Example 269 and 4,4,5,5-tetramethyl-2- (3-thienyl) -1,3,2-dioxaborolane as reagents, Example 642 was prepared. MCBP: Calculated for C ₃₄ H ₃₄ FN ₅ O ₄ S ₂ : 659.2036, found: 660.2108 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (2-methylpyridin-4-yl) -1,3-thiazol-2-yl] carbonyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 643).

Using General Procedure 7, starting from the Synthesis compound of R3b and 5-bromothiazole-2-carboxylic acid as reactants, the resulting crude product was reacted with (2-methyl-4pyridyl) boronic acid according to General Procedure 9 to give Example 643 MCBP calculated for C ₃₅ H ₃₇ N ₇ O ₄ S: 651.26276, found: 652.2709 [(M + H) + form].

tert-Butyl [4- (2 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3 -d] pyri- 129 037563 midin-3-yl) methyl] piperidin-1 -yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} -1,3-thiazol-5 yl) pyridin-2-yl] carbamate (Example 644).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromothiazole-2-carboxylic acid as reactants, the resulting crude product was reacted with tert-butyl N- [4- (4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl) -2-pyridyl] carbamate according to General Procedure 9 to give Example 644. MCBP: calculated for C ₃₉ H ₄₄ N ₈ O ₆ S: 752.3104, found: 753.318 [( M + H) + form].

tert-Butyl [4- (5 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3 -d] pyrimidin-3-yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} -4-methyl-1,3-thiazol-2yl) pyridin-2-yl] carbamate (Example 645).

Using General Procedure 9, starting from Example 349 and tert-butyl N- [4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -2-pyridyl] carbamate as reagents, Example 645 MCBP calculated for C ₄₀ H ₄₆ N ₈ O ₆ S: 766.3261, found: 767.3336 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-3,5-bis (2-methylpyridin-4-yl) thiophen-2-yl] carbonyl} - 3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 646) and

3 - [(1- {[(3R, 4R) -1 - {[3-chloro-4-methyl-5- (2-methylpyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidine- 4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 647).

Using General Procedure 9, starting from Example 239 and (2-methyl-4-pyridyl) boronic acid as reagents, Example 646 and Example 647 were prepared and separated by chromatography.

Example 646: MCBP calculated for C ₄₃ H ₄₅ N ₇ O ₄ S: 755.3254, found: 756.3331 [(M + H) + form].

Example 647: MCBP calculated for C ₃₇ H ₃₉ ClN ₆ O ₄ S: 698.2442, found: 699.253 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(3-chloro-4-methyl-5-phenylthiophen-2-yl) carbonyl] -3-phenylpiperidin-4yl} carbonyl) -4-hydroxypiperidine- 4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 648).

Using General Procedure 9 starting from Example 239 and phenylboronic acid as reagents, Example 648 was prepared. MCbP: calculated for C ₃₇ H ₃₈ ClN ₅ O ₄ S: 683.2333, found: 684.241 [(M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - {[3-Chloro-4-methyl-5- (pyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine-4one (Example 649).

Using General Procedure 9 starting from Example 239 and 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl) pyridine as reagents, Example 649 was prepared. MCBP: Calculated for C36H37ClN6O4S: 684.2286, found: 685.2365 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - ({4-methyl-2- [6- (trifluoromethyl) pyridin-3-yl] -1,3-thiazol-5-yl } carbonyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 650).

Using General Procedure 9, starting from Example 349 and [6- (trifluoromethyl) -3-pyridyl] boronic acid as reactants, Example 650 was prepared. MCBP: Calculated for C ₃₆ H ₃₆ F ₃ N ₇ O ₄ S: 719.2502 Found : 720.2575 [(M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - {[2- (2,6-Difluoropyridin-3-yl) -4-methyl-1,3-thiazol-5-yl] carbonyl} -3 -phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 651) ...

Using General Procedure 9, starting from Example 349 and (2,6-difluoro-3-pyridyl) boronic acid as reagents, Example 651 was prepared. MCBP: Calculated for C ₃₅ H ₃₅ F ₂ N ₇ O ₄ S: 687.2440 Found : 688.2516 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - {[2- (6-Fluoropyridin-3-yl) -4-methyl-1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidine -4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 652).

Using General Procedure 9, starting from Example 349 and (6-fluoro-3-pyridyl) boronic acid as reactants, Example 652 was prepared.

MCBP: calculated for C ₃₅ H ₃₆ FN ₇ O ₄ S: 669.25336, found: 670.2603 [(M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - {[3-Fluoro-4- (pyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 653) and

3 - [(1 - {[(3R, 4R) -1 - {[3-fluoro-4,5-di (pyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl } -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 654).

Using General Procedure 9, starting from Example 232 and 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl) pyridine as reactants, Example 653 (dehalogenated by-product) and Example 654 were prepared and separated them using chromatography.

- 130 037563

Example 653: MCBP calculated for C ₃₅ H ₃₅ FN ₆ O ₄ S: 654.2424, found: 655.2502 [(M + H) + form].

Example 654 MCBP calculated for C ₄₀ H ₃₈ FN ₇ O ₄ S: 731.2690, found: 732.2764 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - {[3-Chloro-4-methyl-5- (6-methylpyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidine- 4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 655).

Using General Procedure 9, starting from Example 239 and (6-methyl-3-pyridyl) boronic acid as reactants, Example 655 was prepared. MCBP: Calculated for C ₃₇ H ₃₉ ClN ₆ O ₄ S: 698.2442, Found: 699.2514 [( M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - ({3-Chloro-4-methyl-5- [2- (trifluoromethyl) pyridin-4-yl] thiophen-2-yl} carbonyl) -3phenylpiperidine -4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 656).

Using General Procedure 9, starting from Example 239 and 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl) -2- (trifluoromethyl) pyridine as reagents, Example 656 was prepared. MCBP: calculated for C ₃₇ H ₃ 6ClF ₃ N6O4S: 752.2159, found: 753.2258 [(M + H) ⁺ form].

tert-Butyl [4- (5 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3 -d] pyrimidin-3-yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} -1,3-thiazol-2-yl) pyridin-2-yl] carbamate (Example 657).

Using General Procedure 7, starting from the compound Synthesis of R3b and 2-bromothiazole-5-carboxylic acid as reagents, the resulting crude product was reacted with tert-butyl N- [4- (4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl) -2-pyridyl] carbamate according to General Procedure 9 to give Example 657. MCBP: calculated for C ₃₉ H ₄₄ N ₈ O ₆ S: 752.3104, found: 753.3187 [( M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[3 - (2-methylpyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl ] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 658).

Using General Procedure 9, starting from Example 247 and (2-methyl-4-pyridyl) boronic acid as reactants, Example 658 was prepared. MCBP: Calculated for C ₃₆ H ₃₈ N ₆ O ₄ S: 650.2675, Found: 651.2767 [( M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[3 - (pyridin-4-yl) thiophen-2-yl] carbonyl} piperidin-4-yl]] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 659).

Using General Procedure 9 starting from Example 247 and 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl) pyridine as reagents, Example 659 was prepared. MCBP: Calculated for C35H36N6O4S: 636.2519, found: 637.2606 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[3 - (6-methylpyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl ] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 660).

Using General Procedure 9, starting from Example 247 and (6-methyl-3-pyridyl) boronic acid as reactants, Example 660 was prepared. MCBP: Calculated for C ₃₆ H ₃₈ N ₆ O ₄ S: 650.2675, Found: 651.2762 [( M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[3 - (pyridin-3-yl) thiophen-2-yl] carbonyl} piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 661).

Using General Procedure 9, starting from Example 247 and 3-pyridylboronic acid as reagents, Example 661. MCBP: Calculated for C ₃₅ H ₃₆ N ₆ O ₄ S: 636.2519, Found: 637.2617 [(M + H) + Form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[4- (pyridin-4-yl) - 1,3-thiazol-2-yl] carbonyl} piperidine -4yl] carbonyl} piperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 662).

Using General Procedure 9, starting from Example 248 and 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl) pyridine as reagents, Example 662 was prepared. MCBP: Calculated for C ₃₄ H ₃₅ N ₇ O ₄ S: 637.2471, found: 638.2564 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4- (6-methylpyridin-3-yl) -1,3-thiazol-2-yl] carbonyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 663).

Using General Procedure 9, starting from Example 248 and (6-methyl-3-pyridyl) boronic acid as reactants, Example 663 was prepared. MCBP: Calculated for C ₃₅ H ₃₇ N ₇ O ₄ S: 651.26276, Found: 652.272 [( M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[4- (pyridin-3-yl) -1,3-thiazol-2-yl] carbonyl} piperidine -4yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 664).

Using General Procedure 9, starting from Example 248 and 3-pyridylboronic acid as reagents, Example 664 was prepared. MCBP: calculated for C ₃₄ H ₃₅ N ₇ O ₄ S: 637.2471, found: 638.256 [(M + H) + form] ...

- 131 037563

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4- (2-methylpyridin-4-yl) -1,3-thiazol-2-yl] carbonyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 665).

Using General Procedure 9, starting from Example 248 and (2-methyl-4-pyridyl) boronic acid as reactants, Example 665 was prepared. MCBP: Calculated for C ₃ 5H ₃₇ N ₇ O ₄ S: 651.2628, Found: 652.2727 [( M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[5 - (pyridin-4-yl) thiophen-3-yl] carbonyl} piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 666).

Using General Procedure 9, starting from Example 249 and 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl) pyridine as reagents, Example 666 was prepared. MCBP: Calculated for C ₃₅ H ₃₆ N ₆ O ₄ S: 636.2519, found: 637.2601 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[5- (6-methylpyridin-3-yl) thiophen-3-yl] carbonyl} -3-phenylpiperidin-4-yl ] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 667).

Using General Procedure 9, starting from Example 249 and (6-methyl-3-pyridyl) boronic acid as reactants, Example 667 was prepared. MCBP: Calculated for C ₃₆ H ₃₈ N ₆ O ₄ S: 650.2675, Found: 651.2766 [( M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[5 - (pyridin-3-yl) thiophen-3-yl] carbonyl} piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 668).

Using General Procedure 9, starting from Example 249 and 3-pyridylboronic acid as reagents, Example 668 was prepared. MCBP: Calculated for C ₃₅ H ₃₆ N ₆ O ₄ S: 636.2519, Found: 637.26 [(M + H) + Form] ...

3 - [(4-Hydroxy-1- {[(3R, 4R) -1 - {[5- (2-methylpyridin-4-yl) thiophen-3-yl] carbonyl} -3-phenylpiperidin-4-yl ] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 669).

Using General Procedure 9, starting from Example 249 and (2-methyl-4-pyridyl) boronic acid as reactants, Example 669 was prepared. MCBP: Calculated for C ₃₆ H ₃₈ N ₆ O ₄ S: 650.2675, Found: 651.2756 [( M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[2- (pyridin-4-yl) thiophen-3-yl] carbonyl} piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 670).

Using General Procedure 9, starting from Example 250 and 4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl) pyridine as reagents, Example 670 was prepared. MCBP: Calculated for C ₃₅ H ₃₆ N ₆ O ₄ S: 636.2519, found: 637.2615 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[2- (pyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} piperidine -4yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 671).

Using General Procedure 7, starting from the Synthesis compound of R3b and 2-bromothiazole-5-carboxylic acid as reactants, the resulting crude product was reacted with 3pyridylboronic acid according to General Procedure 9 to give Example 671. MCBP: Calculated for C ₃₄ H ₃ 5N ₇ O ₄ S: 637.2471, found: 638.2542 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (2-methylpyridin-4-yl) -1,3-thiazol-5-yl] carbonyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 672).

Using General Procedure 7, starting from the Synthesis compound of R3b and 2-bromothiazole-5-carboxylic acid as reactants, the resulting crude product was reacted with (2-methyl-4pyridyl) boronic acid according to General Procedure 9 to give Example 672 MSBP calculated for C ₃ 5H ₃₇ N ₇ O ₄ S: 651.2628, found: 652.2702 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 673).

Using General Procedure 7, starting from the Synthesis compound of R3b and 2-bromothiazole-5-carboxylic acid as reactants, the resulting crude product was reacted with (6-methoxy3-pyridyl) boronic acid according to General Procedure 9 to give Example 673 MCBP calculated for C ₃ 5H ₃₇ N ₇ O5S: 667.2577, found: 668.2648 [(M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - {[2- (6-Aminopyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl ] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 674).

Using General Procedure 7, starting from the compound Synthesis of R3b and 2-bromothiazole-5-carboxylic acid as reagents, the resulting crude product was reacted with 5- (4,4,5,5 tetramethyl-1,3,2-dioxaborolane- 2-yl) pyridine-2-amine according to General Procedure 9 to give Example 674. MCBP: calculated for C ₃₄ H ₃₆ N ₈ O ₄ S: 652.2580, found: 327.1370 [(M + 2H) ²⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - ({2- [2- (trifluoromethyl) pyridin-4-yl] -1,3-thiazol-5-yl } car-132 037563 bonyl) piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3D] pyrimidin-4-one (Example 675 ).

Using General Procedure 7, starting from the compound Synthesis of R3b and 2-bromothiazole-5-carboxylic acid as reagents, the resulting crude product was reacted with 4- (4,4,5,5 tetramethyl-1,3,2-dioxaborolane- 2-yl) -2- (trifluoromethyl) pyridine according to General Procedure 9 to give Example 675. MCBP: calculated for C ₃₅ H ₃₄ F ₃ N ₇ O ₄ S: 705.2345, found: 706.2403 [(M + H) + the form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (3-methoxypyridin-4-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 676).

Using General Procedure 7, starting from the Synthesis compound R3b and 2-bromothiazole-5-carboxylic acid as reactants, the resulting crude product was reacted with (3-methoxy4-pyridyl) boronic acid according to General Procedure 9 to give Example 676 MCBP calculated for C ₃₅ H ₃₇ N ₇ O ₅ S: 667.2577, found: 668.2638 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[2- (thiophen-3-yl) -1,3-thiazol-5-yl] carbonyl} piperidine- 4yl] carbonyl} piperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example

677).

Using General Procedure 7, starting from the compound Synthesis of R3b and 2-bromothiazole-5-carboxylic acid as reactants, the resulting crude product was reacted with 4,4,5,5 tetramethyl-2- (3-thienyl) -1,3 , 2-dioxaborolane according to General Procedure 9 to give Example 677. MCBP: calculated for C ₃₃ H ₃₄ N ₆ O ₄ S ₂ : 642.2083, found: 643.2151 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 678).

Using General Procedure 7, starting from the Synthesis compound of R3b and 2-bromothiazole-5-carboxylic acid as reactants, the resulting crude product was reacted with (6-methyl-3pyridyl) boronic acid according to General Procedure 9 to give Example 678 MSBP calculated for C ₃₅ H ₃₇ N ₇ O ₄ S: 651.2628, found: 652.2696 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) thiophen-3-yl] carbonyl} -3-phenylpiperidin-4-yl ] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 679).

Using General Procedure 9, starting from Example 250 and (6-methyl-3-pyridyl) boronic acid as reactants, Example 679 was prepared. MCBP: Calculated for C ₃₆ H ₃₈ N ₆ O ₄ S: 650.2675, Found: 651.277 [( M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[2- (pyridin-3-yl) thiophen-3-yl] carbonyl} piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 680).

Using General Procedure 9, starting from Example 250 and 3-pyridylboronic acid as reagents, Example 680 was prepared. MCBP: Calculated for C ₃₅ H ₃₆ N ₆ O ₄ S: 636.2519, Found: 637.2603 [(M + H) + Form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (2-methylpyridin-4-yl) thiophen-3-yl] carbonyl} -3-phenylpiperidin-4-yl ] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 681).

Using General Procedure 9, starting from Example 250 and (2-methyl-4-pyridyl) boronic acid as reactants, Example 681. MCBP: Calculated for C ₃₆ H ₃₈ N ₆ O ₄ S: 650.2675, Found: 651.2761 [( M + H) + form].

3 - [(1- {[(3R, 4R) -1 - {[3-Chloro-5 - (pyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 682).

Using General Procedure 9, starting from Example 253 and 3-pyridylboronic acid as reagents, Example 682 was prepared. MCBP: calculated for C ₃₅ H ₃₅ ClN ₆ O ₄ S: 670.2129, found: 671.2205 [(M + H) + form] ...

3 - [(1- {[(3R, 4R) -1 - {[3-Chloro-5 - (6-methylpyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 683).

Using General Procedure 9, starting from Example 253 and (6-methyl-3-pyridyl) boronic acid as reagents, Example 683 was prepared. MCBP: Calculated for C ₃₆ H ₃₇ ClN ₆ O ₄ S: 684.2286, Found: 685.2368 [( M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - ({3-Chloro-5- [6- (trifluoromethyl) pyridin-3-yl] thiophen-2-yl} carbonyl) -3-phenylpiperidin-4 -yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 684).

Using General Procedure 9, starting from Example 253 and [6- (trifluoromethyl) -3-pyridyl] boronic acid as reactants, Example 684 was prepared. MCBP: Calculated for C ₃₆ H ₃₄ ClF ₃ N ₆ O ₄ S: 738.2003,

- 133,037563 found: 739.2071 [(M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - ({5- [6- (Dimethylamino) pyridin-3-yl] -3-fluorothiophen-2-yl} carbonyl) -3-phenylpiperidin-4- yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 685).

Using General Procedure 9, starting from Example 269 and [6- (dimethylamino) -3-pyridyl] boronic acid as reactants, Example 685 was prepared. MCBP: Calculated for C ₃₇ H ₄₀ FN ₇ O ₄ S: 697.2847, Found: 349.6491 [(M + 2H) 2+ form].

3 - {[1 - ({(3R, 4R) -1 - [(4-Chloro-3-fluorothiophen-2-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4hydroxypiperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 686).

Using General Procedure 9, starting from Example 259 and (6-methyl-3-pyridyl) boronic acid as reactants, Example 686 was obtained as a dehalogenated by-product. MCBP: calculated for C ₃₀ H ₃ iClFN ₅ O ₄ S: 611.1769, found: 612.1852 [(M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - ({5- [6- (Cyclopropylmethoxy) pyridin-3-yl] -3-fluorothiophen-2-yl} carbonyl) -3-phenylpiperidin-4- yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3d] pyrimidin-4-one (Example 687).

Using General Procedure 9, starting from Example 269 and 2- (cyclopropylmethoxy) -5- (4,4,5,5tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine as reagents, Example 687 was prepared. MCBP: calculated for C ₃₉ H ₄₁ FN ₆ O ₅ S: 724.2843, found: 363.1484 [(M + 2H) 2+ form].

3 - [(1 - {[(3R, 4R) -1 - {[5- (6-Ethoxypyridin-3-yl) -3-fluorothiophen-2-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} - 4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 688).

Using General Procedure 9, starting from Example 269 and (6-ethoxy-3-pyridyl) boronic acid as reagents, Example 688 was prepared. MCBP: Calculated for C ₃₇ H ₃₉ FN ₆ O ₅ S: 698.2687, Found: 350.1408 [( M + 2H) ²⁺ form].

3 - [(1- {[(3R, 4R) -1 - {[4-Chloro-3-fluoro-5- (6-methylpyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidine- 4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 689).

Using General Procedure 9, starting from Example 259 and (6-methyl-3-pyridyl) boronic acid as reactants, Example 689 was prepared. MCBP: Calculated for C ₃₆ H ₃₆ ClFN ₆ O ₄ S: 702.2191, Found: 703.2265 [( M + H) ⁺ form].

5- (4-Fluoro-5 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3 -d] pyrimidin-3-yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} thiophen-2-yl) pyridine-2carbonitrile (Example 690).

Using General Procedure 9, starting from Example 269 and (6-cyano-3-pyridyl) boronic acid as reagents, Example 690 was prepared. MCBP: calculated for C ₃₆ H ₃₄ FN ₇ O ₄ S: 679.2377, found: 680.2461 [( M + H) + form].

3 - [(1- {[(3R, 4R) -1 - {[3-Chloro-5 - (2-methylpyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 691).

Using General Procedure 9, starting from Example 253 and (2-methyl-4-pyridyl) boronic acid as reactants, Example 691. MCBP: calculated for C ₃₆ H ₃₇ ClN ₆ O ₄ S: 684.2286, found: 685.2357 [( M + H) + form].

3 - [(1- {[(3R, 4R) -1 - {[3 -Fluoro-4-methyl-5- (6-methylpyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidine- 4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 692).

Using General Procedure 9, starting from Example 261 and (6-methyl-3-pyridyl) boronic acid as reagents, Example 692 was prepared. MCBP: calculated for C ₃₇ H ₃₉ FN ₆ O ₄ S: 682.2737, found: 683.2826 [( M + H) + form].

3 - [(1- {[(3R, 4R) -1 - {[3-Fluoro-4-methyl-5- (2-methylpyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidine- 4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 693).

Using General Procedure 9, starting from Example 261 and (2-methyl-4-pyridyl) boronic acid as reactants, Example 693 was prepared. MCBP: Calculated for C ₃₇ H ₃₉ FN ₆ O ₄ S: 682.2737, Found: 683.2816 [( M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - {[4-Cyclopropyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidine -4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 694).

Using General Procedure 9, starting from Example 263 and cyclopropylboronic acid as reagents, Example 694 was prepared. MCBP: Calculated for C ₃₈ H ₄₁ N ₇ O ₄ S: 691.2941, found: 692.3038 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - {[3-Fluoro-5- (6-methoxypyridin-3-yl) -4-methylthiophen-2-yl] carbonyl} -3-phenylpiperidin-4 -yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d]

- 134 037563 pyrimidin-4-one (Example 695).

Using General Procedure 9, starting from Example 261 and (6-methoxy-3-pyridyl) boronic acid as reactants, Example 695 was prepared. MCBP: Calculated for C ₃₇ H ₃₉ FN ₆ O ₅ S: 698.2687 Found:

350.1423 [(M + 2H) 2+ form].

3 - [(1 - {[(3R, 4R) -1 - ({3-Fluoro-4-methyl-5- [6- (trifluoromethyl) pyridin-3-yl] thiophen-2-yl} carbonyl) -3phenylpiperidine -4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 696).

Using General Procedure 9, starting from Example 261 and [6- (trifluoromethyl) -3-pyridyl] boronic acid as reactants, Example 696 was prepared. MCBP: Calculated for C ₃₇ H ₃₆ F ₄ N ₆ O ₄ S: 736.2455 Found : 737.2549 [(M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - {[3-Fmor-5- (umudazo [1,2-a] pyrudin-7-ul) muofen-2-ul] kαrbonyl} -3- fenilliperudin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 697).

Using General Procedure 9, starting from Example 269 and imidazo [1,2-a] pyridin-7-ylboronic acid as reagents, Example 697 was prepared. MCBP: Calculated for C ₃₇ H ₃₆ FN ₇ O ₄ S: 693.2534 Found: 694.2616 [(M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - ({2- [6- (Dumethylamino) pyrugin-3-ul] -4-methyl-1,3-thiazol-5-ul} kαrbonyl) - 3phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 698).

Using General Procedure 9, starting from Example 349 and [6- (dimethylamino) -3-pyridyl] boronic acid as reactants, Example 698 was prepared. MCBP: Calculated for C ₃₇ H ₄₂ N ₈ O ₄ S: 694.3050, Found: 695.3133 [(M + H) ⁺ form].

3 - [(1 - {[(3R, 4R) -1 - ({3-Fluoro-5- [6- (piperazin-1-yl) pyridin-3-yl] thiophen-2-yl} carbonyl) -3 -phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 699) ...

Using General Procedure 9, starting from Example 269 and 1- [5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -2-pyridyl] piperazine as reagents, Example 699. MCBP: calculated for C ₃₉ H ₄₃ FN ₈ O ₄ S: 738.3112, found: 739.3183 [(M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - ({2- [6- (Cyclopropylmethoxy) pyridin-3-yl] -4-methyl-1,3-thiazol-5-yl} carbonyl) 3 -phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 700) ...

Using General Procedure 9, starting from Example 349 and 2- (cyclopropylmethoxy) -5- (4,4,5,5tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine as reagents, Example 700 was prepared. MCBP: calculated for C ₃₉ H ₄₃ N ₇ O ₅ S: 721.3046, found: 722.3118 [(M + H) + form].

5- (5 - {[(3R, 4R) -4 - ({4-Hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine -3-yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} -4-methyl-1,3-thiazol-2-yl) pyridine 2-carbonitrile (Example 701).

Using General Procedure 9, starting from Example 349 and (6-cyano-3-pyridyl) boronic acid as reagents, Example 701 was prepared. MCBP: Calculated for C ₃₆ H ₃₆ N ₈ O ₄ S: 676.2580, Found: 677.2649 [( M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4- (methoxymethyl) -5- (6-methylpyridin-3-yl) thiophen-2-yl] carbonyl} 3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 702).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromo-4- (methoxymethyl) thiophene-2-carboxylic acid as reactants, the resulting crude product was reacted with (6-methyl-3-pyridyl) boronic acid in according to General Procedure 9 to obtain Example 702. MCBP: calculated for C ₃₈ H ₄₂ N ₆ O ₅ S: 694.2938, found: 695.302 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4- (methoxymethyl) -5- (2-methylnyridin-4-yl) thiophen-2-yl] carbonyl} 3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 703).

Using General Procedure 7, starting from the compound Synthesis of R3b and 5-bromo-4- (methoxymethyl) thiophene-2-carboxylic acid as reagents. The resulting crude product was reacted with (2-methyl-4-pyridyl) boronic acid according to General Procedure 9 to give Example 703. MCBP: Calculated for C ₃₈ H ₄₂ N ₆ O ₅ S: 694.2938, Found: 695.3030 [ (M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - ({3-Fluoro-5- [6- (2,2,2-trifluoroethoxy) pyridin-3-yl] thiophen-2-yl} carbonyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3d] pyrimidin-4-one (Example 704) ...

Using General Procedure 9, starting from Example 269 and [6- (2,2,2-trifluoroethoxy) -3pyridyl] boronic acid as reactants, Example 704 was prepared. MCBP: Calculated for C ₃₇ H ₃ 6F4N6O5S: 752.2404, Found: 753.2476 [(M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - {[3-Fluoro-5- (3-methyl-3H-imidazo [4,5-b] pyridin-6-yl) thiophen-2-yl ] carbonyl} -3phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo

- 135 037563

[2,3-d] nupuMuguH-4-OH (Example 705).

Using General Procedure 9, starting from Example 269 and 3-methyl-6- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) imidazo [4,5-b] pyridine as reagents, obtained Example 705. MCBP: calculated for C ₃₇ H ₃₇ FN ₈ O ₄ S: 708.2642, found: 709.2708 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - {[4-Ethyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidine4 -yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 706).

Using General Procedure 9, starting from Example 263 and potassium ethyl trifluoroborate as reagents, Example 706 was prepared. MCBP: Calculated for C ₃₇ H ₄₁ N ₇ O ₄ S: 679.2941, found: 680.3022 [(M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - {[4- (Dimethylamino) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} 4-hydroxypiperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 707) and

3 - [(1 - {[(3R, 4R) -1 - {[4- (Dimethylαmino) -5- (6-methylpyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4- yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 708).

Using General Procedure 9, starting from Example 275 and (6-methyl-3-pyridyl) boronic acid as reagents, Example 707 (dehalogenated by-product) and Example 708 were prepared and separated by chromatography.

Example 707 MCBP calculated for C ₃₂ H ₃₈ N ₆ O ₄ S: 602.2675, found: 603.2751 [(M + H) + form].

Example 708: MCBP calculated for C3 ₈ H ₄₃ N ₇ O ₄ S: 693.3098, found: 694.3175 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methoxy-5- (6-methylpyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 709).

Using General Procedure 9, starting from Example 276 and (6-methyl-3-pyridyl) boronic acid as reagents, Example 709 was prepared. MCBP: Calculated for C ₃₇ H ₄₀ N ₆ O ₅ S: 680.2781, Found: 681.2860 [( M + H) + form].

3 - [(1- {[(3R, 4R) -1 - {[4-Bromo-5- (6-methylpyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 710) and

3 - [(1 - {[(3R, 4R) -1 - {[4,5-bis (6-Methylpyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} - 4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 711).

Using General Procedure 9, starting from Example 277 and (6-methyl-3-pyridyl) boronic acid as reagents, Example 710 and Example 711 were prepared and separated by chromatography.

Example 710 MCBP calculated for C ₃₆ H3 ₇ N ₆ O ₄ SBr: 728.1780, found: 729.1856 [(M + H) + form].

Example 711 MCBP calculated for C ₄₂ H ₄₃ N ₇ O ₄ S: 741.3098, found: 742.3166 [(M + H) + form].

Methyl 3 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine-3yl ) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} -5- (6-methylpyridin-3-yl) benzoate (Example 712).

Using General Procedure 9, starting from Example 287 and (6-methyl-3-pyridyl) boronic acid as reagents, Example 712 was prepared. MCBP: Calculated for C ₄₀ H ₄₂ N ₆ O ₆ : 702.3166, Found: 703.323 [(M + H) ⁺ form].

3 - [(1- {[(3R, 4R) -1 - {[3-Fluoro-5- (6-methylpyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 713).

Using General Procedure 9, starting from Example 269 and (6-methyl-3-pyridyl) boronic acid as reactants, Example 713 was prepared. MCBP: calculated for C3 ₆ H ₃₇ FN ₆ O ₄ S: 668.2581, found: 669.2661 [( M + H) + form].

5- [5 - ({(3R, 4R) -4 - [(4 - {[7- (3-chlorophenyl) -4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine -3-yl] methyl} -4-hydroxypiperidin-1-yl) carbonyl] -3-phenylpiperidin-1 -yl} methyl) -1,3-thiazol-2-yl] pyridine-2 carbonitrile (Example 714).

Using General Procedure 9, starting from Example 87 and (6-cyano-3-pyridyl) boronic acid as reagents, Example 714 was prepared. MCBP: Calculated for C ₄₀ H ₃₇ ClN ₈ O ₃ S: 744.2398, Found: 745.2479 [( M + H) ⁺ form].

7- (3-Chlorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazole-5- yl] methyl} 3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 715).

Using General Procedure 9, starting from Example 87 and (6-methyl-3-pyridyl) boronic acid as reactants, Example 715 was prepared. MCBP: Calculated for C ₄₀ H ₄₀ ClN ₇ O ₃ S: 733.2602, Found: 734.2693 [( M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[2- (thiophen-2-yl) -1,3-thiazol-5-yl] methyl} piperidine -4-yl]

136 037563 carbonyl} piperidin-4-yl) methyl] -7- (3-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 716).

Using General Procedure 9, starting from Example 95 and 2-thienylboronic acid as reagents, Example 716 was prepared. MCBP: Calculated for C ₃₉ H ₄₀ N ₆ O ₄ S ₂ : 720.2552, Found: 721.2616 [(M + H) + form ].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[2- (pyrimidin-5-yl) -1,3-thiazol-5-yl] methyl} piperidine- 4yl] carbonyl} piperidin-4-yl) methyl] -7 - (3-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 717).

Using General Procedure 9, starting from Example 95 and pyrimidin-5-ylboronic acid as reagents, Example 717 was prepared. MCBP: Calculated for C ₃₉ H ₄₀ N8O ₄ S: 716.2893, Found: 717.2989 [(M + H) + Form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (1-methyl-1H-pyrazol-5-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one ( Example 718).

Using General Procedure 9, starting from Example 95 and 1-methyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyrazole as reagents, Example 718 was prepared. MCBP: Calculated for C ₃₉ H ₄₂ N ₈ O ₄ S: 718.3050, found: 719.3109 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (1-methyl-1H-pyrazol-4-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one ( Example 719).

Using General Procedure 9, starting from Example 95 and 1-methyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyrazole as reagents, Example 719 was prepared. MCBP: Calculated for C39H42N8O4S: 718.3050, found: 719.3087 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (1-methyl-1H-pyrrol-3-yl) -1,3-thiazol-5-yl] methyl } -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 720).

Using General Procedure 9, starting from Example 95 and 1-methyl-3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyrrole as reagents, Example 720 was prepared. MCBP: calculated for C ₄₀ H ₄₃ N ₇ O ₄ S: 717.3098, found: 718.3169 [(M + H) ⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[2- (thiophen-3-yl) -1,3-thiazol-5-yl] methyl} piperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 721).

Using General Procedure 9, starting from Example 95 and 4,4,5,5-tetramethyl-2- (3-thienyl) -1,3,2-dioxaborolane as reagents, Example 721 was prepared. MCBP: Calculated for C39H40N6O4S2: 720.2552, found : 721.2639 [(M + H) ⁺ form].

3 - [(1 - {[(3R, 4R) -1 - {[2- (furαn-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpinerigin-4-yl] carbonyl } -4hydroxypiperidin-4-yl) methyl] -7- (3-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 722).

Using General Procedure 9, starting from Example 95 and 2- (3-furyl) -4,4,5,5-tetramethyl-1,3,2-dioxaborolane as reagents, Example 722 was prepared. MCBP: Calculated for C ₃₉ H ₄₀ N ₆ O ₅ S: 704.2781, found: 705.2823 [(M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - {[2- (Furαn-2-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpinerigin-4-yl] carbonyl } -4hydroxypiperidin-4-yl) methyl] -7- (3-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 723).

Using General Procedure 9, starting from Example 95 and 2-furylboronic acid as reagents, Example 723 was prepared. MCBP: calculated for C ₃₉ H ₄₀ N ₆ O ₅ S: 704.2781, found: 705.2846 [(M + H) + form] ...

5- [5 - ({(3R, 4R) -4 - [(4-Hydroxy-4 - {[7- (3-methoxyphenyl) -4-oxo-4,7-dihydro-3H-pyrrolo [2,3 -d] pyrimidin-3-yl] methyl} piperidin-1 -yl) carbonyl] -3-phenylpiperidin-1 -yl} methyl) -1,3-thiazol-2-yl] pyridine 2-carbonitrile (Example 724).

Using General Procedure 9, starting from Example 95 and (6-cyano-3-pyridyl) boronic acid as reagents, Example 724 was prepared. MCBP: Calculated for C ₄ iH ₄₀ N ₈ O ₄ S: 740.2893, Found: 741.2958 [( M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 725) ...

Using General Procedure 9, starting from Example 95 and (6-methyl-3-pyridyl) boronic acid as reactants, Example 725 was prepared. MCBP: Calculated for C ₄ iH ₄₃ N ₇ O ₄ S: 729.3098, Found: 365.6635 [( M + 2H) ²⁺ form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(6'-methyl-3,3'-bipyridin-5-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl ) piperidin-4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 726).

Using General Procedure 9, starting from Example 303 and (6-methyl-3-pyridyl) boronic acid in

- 137 037563 as reagents, received Example 726. MCBP: calculated for C ₄₂ H ₄₁ N ₇ O ₄ : 707.3220, found:

708.329 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - {[3-Fluoro-5- (6-methylpyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 727).

Using General Procedure 7, starting from Synthesis compound R3bu and Synthesis compound R1g as reagents, the resulting crude product was reacted with (6-methyl-3pyridyl) boronic acid according to General Procedure 9 to give Example 727. MCBP: Calculated for C ₄₁ H ₃₉ FN ₆ O ₄ S: 730.2737, found: 731.2812 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(2-Bromo-4-methyl-1,3-thiazol-5-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) 4 -hydroxypiperidin-4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 728).

Using General Procedure 7, starting from the compound Synthesis of R3bu and 2-bromo-4-methylthiazole-5carboxylic acid as reagents, Example 728 was prepared. MCBP: calculated for C ₃₅ H ₃₅ N ₆ O ₄ SBr: 714.1624, found: 715.1701 [( M + H) ⁺ form].

5- (5 - {[(3R, 4R) -4 - ({4-Hydroxy-4 - [(4-oxo-7-phenyl-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine -3-yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} -4-methyl-1,3-thiazol-2-yl) pyridine 2-carbonitrile (Example 729).

Using General Procedure 9, starting from Example 728 and (6-cyano-3-pyridyl) boronic acid as reagents, Example 729 was prepared. MCBP: Calculated for C ₄₁ H ₃₈ N ₈ O ₄ S: 738.2737, Found: 739.2816 [( M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - ({2- [6- (Dimethylamino) pyridin-3-yl] -4-methyl-1,3-thiazol-5-yl} carbonyl) - 3phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 730).

Using General Procedure 9, starting from Example 728 and [6- (dimethylamino) -3-pyridyl] boronic acid as reactants, Example 730 was prepared. MCBP: Calculated for C ₄₂ H ₄₄ N ₈ O ₄ S: 756.3206 Found: 757.3285 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - ({4-methyl-2- [6- (trifluoromethyl) pyridin-3-yl] -1,3-thiazol-5-yl } carbonyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 731).

Using General Procedure 9, starting from Example 728 and [6- (trifluoromethyl) -3-pyridyl] boronic acid as reagents, Example 731 was prepared. MCBP: Calculated for C ₄₁ H ₃₈ F ₃ N ₇ O ₄ S: 781.2658 Found : 782.2735 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - ({2- [6- (Dimethylamino) pyridin-3-yl] - 1,3-thiazol-5-yl} methyl) -3-phenylpiperidin4- yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 732).

Using General Procedure 9, starting from Example 103 and [6- (dimethylamino) -3-pyridyl] boronic acid as reactants, Example 732 was prepared. MCBP: Calculated for C ₄₁ H ₄₄ N ₈ O ₃ S: 728.3257 Found: 365.1688 [(M + 2H) ²⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 733).

Using General Procedure 9, starting from Example 103 and (6-methoxy-3-pyridyl) boronic acid as reagents, Example 733 was prepared. MCBP: Calculated for C ₄₀ H ₄₁ N ₇ O ₄ S: 715.2941, Found: 358.6536 [( M + 2H) ²⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -4-methyl-1,3-thiazol-5-yl] carbonyl} -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 734).

Using General Procedure 9, starting from Example 728 and (6-methoxy-3-pyridyl) boronic acid as reagents, Example 734 was prepared. MCBP: Calculated for C ₄₁ H ₄₁ N ₇ O ₅ S: 743.2890, Found: 744.2969 [( M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - ({2- [6- (morpholin-4-yl) pyridin-3-yl] -1,3-thiazol-5-yl } methyl) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 735) ...

Using General Procedure 9, starting from Example 103 and (6-morpholino-3-pyridyl) boronic acid as reagents, Example 735 was prepared. MCBP: Calculated for C ₄₃ H ₄₆ N ₈ O ₄ S: 770.3362, Found: 386.1758 [( M + 2H) ²⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - ({2- [6- (trifluoromethyl) pyridin-3 -yl] - 1,3-thiazole-5- yl} methyl) piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 736).

Using General Procedure 9, starting from Example 103 and [6- (trifluoromethyl) -3-pyridyl] boronic acid as reactants, Example 736 was prepared. MCBP: Calculated for C ₄₀ H ₃₈ F ₃ N ₇ O ₃ S: 753.2709,

- 138,037563 found: 754.2786 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - ({2- [6- (piperαzin-1-yl) pyridin-3-yl] -1,3-thiazole -5-yl} methyl) piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3H] pyrimidin-4-one (Example 737 ).

Using General Procedure 9, starting from Example 103 and 1- [5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -2-pyridyl] piperazine as reagents, Example 737. MCBP calculated for C ₄₃ H ₄₇ N ₉ O ₃ S: 769.3522, found: 770.3601 [(M + H) ⁺ form].

5- (5 - {[(3R, 4R) -4 - ({4-Hydroxy-4 - [(4-oxo-7-phenyl-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine -3-yl) methyl] piperidin-1 -yl} carbonyl) -3-phenylpiperidin-1-yl] methyl} -1,3-thiazol-2-yl) pyridin-2-carbonitrile (Example 738).

Using General Procedure 9, starting from Example 103 and (6-cyano-3-pyridyl) boronic acid as reagents, Example 738 was prepared. MCBP: Calculated for C ₄₀ H ₃₈ N ₈ O ₃ S: 710.2787, Found: 711.2881 [( M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - ({2- [6- (hydroxymethyl) pyridin-3-yl] -1,3-thiazol-5-yl} methyl) - 3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 739).

Using General Procedure 9, starting from Example 103 and [6- (hydroxymethyl) -3-pyridyl] boronic acid as reagents, Example 739 was prepared. MCBP: Calculated for C ₄₀ H ₄₁ N ₇ O ₄ S: 715.2941, Found: 716.3019 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (3-methyl-3H-imidazo [4,5-b] pyridin-6-yl) -1,3- thiazol-5yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one ( Example 740).

Using General Procedure 9, starting from Example 103 and 3-methyl-6- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) imidazo [4,5-b] pyridine as reagents, obtained Example 740. MCBP: calculated for C ₄ iH ₄ iN ₉ O ₃ S: 739.3053, found: 370.6594 [(M + 2H) 2+ form].

3 - [(1- {[(3R, 4R) -1 - {[2- (5-fluoro-6-hydroxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine4 -yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 741).

Using General Procedure 9, starting from Example 103 and (5-fluoro-6-hydroxy-3-pyridyl) boronic acid as reactants, Example 741 was prepared. MCBP: Calculated for C ₃₉ H ₃₈ FN ₇ O ₄ S: 719.2690 Found : 720.2742 [(M + H) + form].

5- (5 - {[(3R, 4R) -4 - ({4-Hydroxy-4 - [(4-oxo-7-phenyl-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine -3-yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] methyl} -1,3-thiazol-2-yl) pyridine-3-carboxamide (Example 742)

Using General Procedure 9, starting from Example 103 and 5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan2-yl) pyridine-3-carboxamide as reagents, Example 742 was prepared. MCBP: Calculated for C40H40N8O4S: 728.2893, found: 729.296 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - ({2- [5- (hydroxymethyl) pyridin-3-yl] -1,3-thiazol-5-yl} methyl) - 3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 743).

Using General Procedure 9, starting from Example 103 and [5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -3-pyridyl] methanol as reagents, Example 743 was prepared. MCBP calculated for C4oH4iN ₇ 04S: 715.2941, found: 358.6526 [(M + 2H) ²⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - ({2- [6- (tetrahydro-2H-pyran-4-yloxy) pyridin-3-yl] - 1,3thiazol-5-yl} methyl) piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine-4 -on (Example 744).

Using General Procedure 9, starting from Example 103 and 2-tetrahydropyran-4-yloxy-5- (4,4,5,5tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine as reagents, Example 744 was prepared. MCBP: calculated for C ₄₄ H ₄₇ N ₇ O ₅ S: 785.3359, found: 393.6745 [(M + 2H) ²⁺ form].

3 - [(1 - {[(3R, 4R) -1 - {[2- (5-Amino-6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 745).

Using General Procedure 9, starting from Example 103 and 2-methoxy-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridin-3-amine as reagents, Example 745 was prepared. MCBP: calculated for C40H42N8O4S: 730.3050, found: 366.1585 [(M + 2H) ²⁺ form].

Methyl 5- (5 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(4-oxo-7-phenyl-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidin3-yl) methyl] piperidin-1 -yl} carbonyl) -3-phenylpiperidin-1 -yl] methyl} -1,3-thiazol-2-yl) pyridine-2carboxylate (Example 746).

Using General Procedure 9, starting from Example 103 and methyl 5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine-2-carboxylate as reagents, Example 746 was prepared. MCBP: Calculated for C ₄₁ H ₄₁ N ₇ O ₅ S: 743.2890, found: 744.2954 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - ({2- [6- (2-methoxyethoxy) pyridin-3-yl] -1,3-thiazol-5-yl}) methyl) -3 - 139 037563 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one ( Example 747).

Using General Procedure 9, starting from Example 103 and 2- (2-methoxyethoxy) -5- (4,4,5,5-tetramethyl1,3,2-dioxaborolan-2-yl) pyridine as reagents, Example 747 was prepared. MCBP: calculated for

C ₄₂ H ₄₅ N ₇ O ₅ S: 759.3203, found: 760.3268 [(M + H) + form].

3 - {[4-Hydroxy-1 - ({(3K, 4K) -1 - [(2- {6 - [(2-methoxyethyl) amino] pyridin-3-yl} -1,3-thiazol-5- yl) methyl] 3-phenylpiperidin-4-yl} carbonyl) piperidin-4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3d] pyrimidin-4-one (Example 748) ...

Using General Procedure 9, starting from Example 103 and N- (2-methoxyethyl) -5- (4,4,5,5-tetramethyl1,3,2-dioxaborolan-2-yl) pyridin-2-amine as reagents, obtained Example 748. MCBP: calculated for C ₄₂ H ₄₆ N ₈ O ₄ S: 758.3362, found: 380.1717 [(M + 2H) ²⁺ form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1 - [(6'-methyl-2,3'-bipuridin-4-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl ) piperidin-4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] purimidin-4-one (Example 749).

Using General Procedure 9, starting from Example 302 and (6-methyl-3-pyridyl) boronic acid as reagents, Example 749 was prepared. MCBP: Calculated for C ₄₂ H ₄₁ N ₇ O ₄ : 707.3220, Found: 708.3294 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperudin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 750).

Using General Procedure 9, starting from Example 728 and (6-methyl-3-pyridyl) boronic acid as reactants, Example 750 was prepared. MCBP: calculated for C ₄ iH ₄ iN ₇ O ₄ S: 727.2941, found: 728.3013 [( M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 751).

Using General Procedure 9, starting from Example 103 and (6-methyl-3-pyridyl) boronic acid as reagents, Example 751. MCBP: calculated for C ₄₀ H ₄₁ N ₇ O ₃ S: 699.2991, found: 350.6573 [( M + 2H) ²⁺ form].

7-Ethyl-3 - [(4-hydroxy-1- {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazole-5yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3d] purimidin-4-one (Example 752).

Using General Procedure 7, starting from the Synthesis compound of R3c and 2-bromo-4-methylthiazole-5carboxylic acid as reactants, the resulting crude product was reacted with (6-methyl-3-pyridyl) boronic acid according to General Procedure 9 to give Example 752. MCBP: calculated for C ₃₇ H ₄ iN ₇ O ₄ S: 679.2941, found: 680.3014 [(M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - {[2- (6-Aminopyridin-3-yl) -4-methyl-1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidine -4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-ethyl-3,7-dihydro-4H-purrolo [2,3-d] pyrimidin-4-one (Example 753).

Using General Procedure 7, starting from the compound Synthesis of R3c and 2-bromo-4-methylthiazole-5carboxylic acid as reactants, the resulting crude product was reacted with 5- (4,4,5,5-tetramethyl-1,3, 2-dioxaborolan-2-yl) pyridine-2-amine according to General Procedure 9 to give Example 753. MCBP: calculated for C ₃₆ H ₄₀ N ₈ O ₄ S: 680.2893, found: 341.1534 [(M + 2H) ^{2 +} form].

7-Ethyl-3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - ({4-methyl-2- [6- (Ίfluoromethyl) pyridin-3-yl]] -1,3-thiazole -5yl} carbonyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 754) ...

Using General Procedure 7, starting from the compound Synthesis of R3c and 2-bromo-4-methylthiazole-5carboxylic acid as reactants, the resulting crude product was reacted with [6- (trifluoromethyl) -3-pyridyl] boronic acid according to General Procedure 9 to give Example 754. MCBP Calculated for C ₃₇ H ₃₈ N ₇ O ₄ F ₃ S: 733.2658, Found: 734.2738 [(M + H) + Form].

7-Ethyl-3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -4-methyl-1,3-thiazole-5- yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 755).

Using General Procedure 7, starting from the Synthesis compound of R3c and 2-bromo-4-methylthiazole-5carboxylic acid as reagents, the resulting crude product was reacted with (6-methoxy-3-pyridyl) boronic acid according to General Procedure 9 to give Example 755. MCBP: calculated for C ₃₇ H ₄ iN ₇ O ₅ S: 695.2890, found: 696.2959 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (pyridin-4-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine-4- he (Ex. 756).

Using General Procedure 7, starting from the compound Synthesis of R3cd and 2-bromo-4-methylthiazole-5carboxylic acid as reactants, the resulting crude product was reacted with

- 140 037563 (6-methyl-3-pyridyl) boronic acid according to General Procedure 9 to give Example

756. MCBP: calculated for C ₄₀ H ₄₀ N8O ₄ S: 728.2893, found: 729.2971 [(M + H) + form].

7-Cyclopropyl-3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 757).

Using General Procedure 6, starting from the Synthesis compound R3g and 2-bromo-5- (bromomethyl) thiazole as reactants, the resulting crude product was reacted with (6-methyl-3pyridyl) boronic acid according to General Procedure 9 to give Example 757. MCBP: calculated for C37H ₄ iN ₇ O ₃ S: 663.2991, found: 332.6581 [(M + 2H) 2+ form].

7-Cyclonropyl-3 - [(1 - {[(3R, 4R) -1 - ({3-fluoro-5- [6- (2,2,2-trifluoroethoxy) pyridin-3-yl] thiophen-2yl} carbonyl) -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one (Example 758).

Using General Procedure 7, starting from Synthesis compound R3g and Synthesis compound R1g as reagents, the resulting crude product was reacted with [6- (2,2,2-trifluoroethoxy) -3-pyridyl] boronic acid according to General Procedure 9 to give Example 758. MCBP calculated for C ₃ 9H ₃₈ F ₄ N ₆ O ₅ S: 778.256, found: 779.2595 [(M + H) + form].

-Cyclobutyl-3 - [(4-hydroxy-1- {[(3R, 4R) -1- {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl ] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 759).

Using General Procedure 7, starting from Synthesis compound R3h and Synthesis compound R1g as reagents, the resulting crude product was reacted with (6-methyl-Zpyridyl) boronic acid according to General Procedure 9 to give Example 759. MCBP: Calculated for C39H43N7O4S: 705.3098, found: 706.3173 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (2-methylpropyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 760 ).

Using General Procedure 6, starting from the Synthesis compound of R3n and 2-bromo-5- (bromomethyl) thiazole as reactants, the resulting crude product was reacted with (6-methyl-Zpyridyl) boronic acid according to General Procedure 9 to give Example 760. MCBP: calculated for C ₃₉ H ₄ 5N ₇ O ₄ S: 707.3254, found: 708.3342 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - {[3-fluoro-5- (6-methylpyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 - (2-methylpropyl) -3,7-dihydro-4H-pyrrolo [2,3d] pyrimidin-4-one (Example 761).

Using General Procedure 7, starting from Synthesis compound R3n and Synthesis compound R1g as reagents, the resulting crude product was reacted with (6-methyl-Zpyridyl) boronic acid according to General Procedure 9 to give Example 761. MCBP: Calculated for C ₃₉ H ₄₃ FN ₆ O ₄ S: 710.3051, found: 711.3123 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(2-bromo-4-methyl-1,3-thiazol-5-yl) carbonyl] -3-phenylniperidin-4-yl} carbonyl) 4 -hydroxyniperidin-4-yl] methyl} -7- (2,2,2-trifluoroethyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 762).

Using General Procedure 7, starting from the Synthesis of R3o compound and 2-bromo-4-methylthiazole-5carboxylic acid as reagents, Example 762 was prepared. MCBP: calculated for C31H32BrF3N6O4S: 720.1341, found: 721.1421 [(M + H) ⁺ form].

3 - [(1- {[(3R, 4R) -1 - {[3-Fluoro-5- (6-methylpyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7- (2,2,2-trifluoroethyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 763).

Using General Procedure 9, starting from Example 340 and (6-methyl-3-pyridyl) boronic acid as reactants, Example 763 was prepared. MCBP: calculated for C37H36F4N6O4S: 736.2455, found: 737.253 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (2,2,2-trifluoroethyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine- 4-one (Example 764).

Using General Procedure 9, starting from Example 762 and (6-methyl-3-pyridyl) boronic acid as reagents, Example 764 was prepared. MCBP: calculated for C37H38F3N7O4S: 733.2658, found: 734.274 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (2,2,2-trifluoroethyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 765).

Using General Procedure 9, starting from Example 143 and (6-methyl-3-pyridyl) boronic acid as reagents, Example 765 was prepared. MCBP: calculated for C36H38N7O3F3S: 705.2709, found: 706.2759 [(M + H) + form].

7- (2,2-Difluoroethyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1), 3-thiazol-5- 141 037563 yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine- 4-one (Example 766).

Using General Procedure 7, starting from the Synthesis compound of R3p and 2-bromo-4-methylthiazole-5carboxylic acid as reactants, the resulting crude product was reacted with (6-methyl-3-pyridyl) boronic acid according to General Procedure 9 to give Example 766. MCBP: calculated for C3 ₇ H ₃₉ F ₂ N7O ₄ S: 715.2752, found: 716.2836 [(M + H) + form].

7- (Cyclopropylmethyl) -3 - [(4-hydroxy-1- {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazole- 5-yl] carbonyl} -3-phenylpiperigin-4-yl] carbonyl} piperigin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 767 ).

Using General Procedure 7, starting from the Synthesis compound R3q and 2-bromo-4-methylthiazole-5carboxylic acid as reactants, the resulting crude product was reacted with (6-methyl-3-pyridyl) boronic acid according to General Procedure 9 to give Example 767. MCBP: calculated for C ₃₉ H ₄₃ N ₇ O ₄ S: 705.3098, found: 353.6637 [(M + 2H) ²⁺ form].

7- [3- (Dimethylamino) npropyl] -3 - [(1 - {[(3R, 4R) -1 - {[3-fluoro-5- (6-methylpyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperigin-4-yl] carbonyl} -4-hydroxypiperigin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 768) ...

Using General Procedure 7, starting from Synthesis compound R3t and Synthesis compound R1g as reagents, the resulting crude product was reacted with (6-methyl-3pyridyl) boronic acid according to General Procedure 9 to give Example 768. MCBP: Calculated for C ₄₀ H ₄₆ FN ₇ O ₄ S: 739.3316, found: 370.6742 [(M + 2H) ²⁺ form].

7- (2-Fluoroethyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyrigin-3-yl) -1,3- thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one ( Example 769).

Using General Procedure 7, starting from the Synthesis of R3u compound and 2-bromo-4-methylthiazole-5carboxylic acid as reactants, the resulting crude product was reacted with (6-methyl-3-pyridyl) boronic acid according to General Procedure 9 to give Example 769.

MCBP calculated for C ₃₇ H ₄₀ FN ₇ O ₄ S: 697.2847, found: 698.2920 [(M + H) + form].

7- [2- (Dimethylamino) ethyl] -3 - [(4-hydroxy-1 - {[(3R, 4R) -1- {[4-methyl-2- (6-methylpyridin-3-yl) -1 , 3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one (Example 770).

Using General Procedure 7, starting from the Synthesis compound of R3v and 2-bromo-4-methylthiazole-5carboxylic acid as reactants, the resulting crude product was reacted with (6-methyl-3-pyridyl) boronic acid according to General Procedure 9 to give Example 770. MCBP: calculated for C ₃₉ H ₄₆ N ₈ O ₄ S: 722.3362, found: 362.1756 [(M + 2H) ²⁺ form].

7- [2- (Dimethylamino) ethyl] -3 - [(1 - {[(3R, 4R) -1 - {[3-fluoro-5- (6-methylpyrigin-3-yl) thiophen-2-yl]] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 771) ...

Using General Procedure 7, starting with Synthesis compound R3v and Synthesis compound R1g as reactants, the resulting crude product was reacted with (6-methyl-3pyridyl) boronic acid according to General Procedure 9 to give Example 771. MCBP: Calculated for C ₃₉ H ₄₄ FN ₇ O ₄ S: 725.3160, found: 363.6647 [(M + 2H) ²⁺ form].

7- [2- (Dimethylamino) ethyl] -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazole -5yl] methyl} -3-phenylpiperigin-4-yl] carbonyl} piperigin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 772) ...

Using General Procedure 6, starting from the Synthesis compound R3v and 2-bromo-5- (bromomethyl) thiazole as reactants, the resulting crude product was reacted with (6-methyl-3pyridyl) boronic acid according to General Procedure 9 to give Example 772. MCBP: calculated for C ₃₈ H ₄₆ N ₈ O ₃ S: 694.3414, found: 348.1773 [(M + 2H) ²⁺ form].

7- (2-Hygroxyethyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylnirigin-3-yl) -1,3- thiazol-5yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 773 ).

Using General Procedure 7, starting from the Synthesis compound R3w and 2-bromo-4-methylthiazole-5carboxylic acid as reactants, the resulting crude product was reacted with (6-methyl-3-pyridyl) boronic acid according to General Procedure 9 to obtain Example 773. MCBP: calculated for C ₃₇ H ₄ iN ₇ O ₅ S: 695.2890, found: 696.2960 [(M + H) + form].

3 - [(4-Hygroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyrigin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-hydroxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 774 ).

Using General Procedure 10 starting from Example 160 and boron tribromide as reagents, Example 774 was prepared. MCBP: Calculated for C ₄₁ H ₄₁ N ₇ O ₅ S: 743.289ο, found: 744.2970 [(M + H) + form].

3 - [(4-Hydroxy-1- {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperi-142 037563 din-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-hydroxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 775).

Using General Procedure 10 starting from Example 61 and boron tribromide as reagents, Example 775 was prepared. MCBP: calculated for C ₄₀ H ₄₁ N ₇ O ₄ S: 715.2941, found: 358.6539 [(M + 2H) ² + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-hydroxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-hydroxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 776) and

3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-hydroxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 777).

Using General Procedure 10, starting from Example 62 and boron tribromide as reagents, Example 776 and Example 777 were prepared and separated by chromatography.

Example 776: MCBP calculated for C ₃₉ H ₃₉ N ₇ O ₅ S: 717.2733, found: 718.2818 [(M + H) + form].

Example 777 MCBP calculated for C ₄₀ H ₄ iN ₇ O ₅ S: 731.2890, found: 732.2963 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - {[5- (2-Aminopyridin-4-yl) -3 -methylthiophen-2-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} - 4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 778).

Using General Procedure 14 starting from Example 402 as reactant, Example 778 was prepared. MCBP: calculated for C ₃₆ H ₃₉ N ₇ O ₄ S: 665.2784, found: 333.6468 [(M + 2H) ²⁺ form].

3 - [(1- {[(3R, 4R) -1 - {[4-Amino-5- (pyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 779).

Using General Procedure 12 starting from Example 185 as reactant, Example 779 was prepared. MCBP: calculated for C ₃₅ H ₃₇ N ₇ O ₄ S: 651.2628, found: 326.6382 [(M + 2H) ²⁺ form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1- (1,2,3,4-tetrahydroisoquinolin-6-ylcarbonyl) piperidin-4yl] carbonyl} piperidin-4-yl ) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example

780).

Using General Procedure 14 starting from Example 192 as reactant, Example 780 was prepared. MCBP: calculated for C ₃₅ H ₄₀ N ₆ O ₄ : 608.3111, found: 305.1639 [(M + 2H) ²⁺ form].

N- (3 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine -3yl) methyl] piperidin-1 -yl} carbonyl) -3-phenylpiperidin-1 -yl] carbonyl} phenyl) acetamide (Example 781).

Using General Procedure 7, starting from Example 512 and acetic acid as reagents, Example 781 was prepared. MCBP: calculated for C ₃₄ H3 ₈ N ₆ O ₅ : 610.2903, found: 611.2989 [(M + H) + form].

N- (3 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine -3-yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} phenyl) benzamide (Example 782).

Using General Procedure 7, starting from Example 512 and benzoic acid as reagents, Example 782 was prepared. MCBP: Calculated for C ₃₉ H ₄₀ N ₆ O ₅ : 672.30603, Found: 673.3148 [(M + H) + form].

tert-Butyl (2-bromo-5 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2, 3-d] pyrimidin-3-yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} thiophene-3-yl) carbamate (Example 783).

Using General Procedure 7, starting with Synthesis compound R3b and Synthesis compound R1o as reagents, Example 783 was prepared. MCBP: calculated for C ₃₅ H ₄₁ BrN ₆ O ₆ S: 752.1992, found: 753.2074 [(M + H) ⁺ form] ...

2-Chloro-N- (3 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3 -d] pyrimidin-3-yl) methyl] piperidin-1 -yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} phenyl) acetamide (Example 784).

Example 512 (100 mg, 0.176 mmol) and chloroacetyl chloride (17 μl, 24 mg, 0.21 mmol) and potassium carbonate (73 mg, 0.527 mmol) were stirred in DMF (2 ml) at RT. for 3 h. The reaction mixture was purified using preparative LC (on a C-18 Gemini-NX 5 μm column, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient) to give Example 784. MCBP: calculated for C ₃₄ H ₃₇ ClN ₆ O ₅ : 644.2514, found: 645.2606 [(M + H) + form].

N- (3 - {[(3R, 4R) -4 - ({4-Hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine -3-yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} phenyl) prop-2-enamide (Example

785).

Using General Procedure 7, starting from Example 512 and acrylic acid as reagents, Example 785 was prepared. MCBP: calculated for C ₃₅ H ₃₈ N ₆ O ₅ : 622.2903, found: 623.2988 [(M + H) + form].

3 - [(1 - {[(3R, 4R) -1 - {[5- (2-Aminopyridin-4-yl) -3-fluorothiophen-2-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} - 4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 786).

Using General Procedure 14 starting from Example 628 as reactant, Example 786 was prepared. MCBP: calculated for C ₃₅ H ₃₆ FN ₇ O ₄ S: 669.2534, found: 335.6337 [(M + 2H) ²⁺ form].

3 - [(1 - {[(3R, 4R) -1 - {[5- (2-Aaminopyridin-4-yl) thiophen-2-yl] methyl} -3-phenylpiperidin-4-yl] carbo-143 037563 nyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] nupuMuguH-4-OH (Example 787).

Using General Procedure 14 starting from Example 392 as reactant, Example 787 was prepared. MCBP: calculated for C ₃₅ H3 ₉ N ₇ O ₃ S: 637.2835, found: 319.6503 [(M + 2H) ² + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - (1,2,3,4-tetrahydroquinolin-7-ylcarbonyl) piperidin-4-yl] carbonyl} piperidine- 4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 788).

Using General Procedure 14 starting from Example 245 as reactant, Example 788 was prepared. MCBP: calculated for C ₃₅ H ₄₀ N ₆ O ₄ : 608.3111, found: 609.3200 [(M + H) + form].

3 - [(1- {[(3R, 4R) -1 - {[5- (2-aminopyridin-4-yl) -1,3-thiazol-2-yl] carbonyl} -3-phenylpiperidin-4-yl ] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 789).

Using General Procedure 14 starting from Example 644 as reactant, Example 789 was prepared. MCBP: calculated for C ₃₄ H ₃₆ N ₈ O ₄ S: 652.2580, found: 327.137 [(M + 2H) ²⁺ form].

3 - [(1 - {[(3R, 4R) -1 - {[2- (2-Aminopyridin-4-yl) -4-methyl-1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidine -4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 790).

Using General Procedure 14 starting from Example 645 as reactant, Example 790 was prepared. MCBP: calculated for C ₃₅ H ₃₈ N ₈ O ₄ S: 666.2737, found: 334.1454 [(M + 2H) ²⁺ form].

3 - [(1 - {[(3R, 4R) -1 - {[5- (2-Aminopyridin-4-yl) -4-methylthiophen-2-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} - 4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 791).

Using General Procedure 14 starting from Example 398 as reactant, Example 791 was prepared. MCBP: calculated for C ₃₆ H ₃₉ N ₇ O ₄ S: 665.2784, found: 333.6473 [(M + 2H) ²⁺ form].

3 - [(1 - {[(3R, 4R) -1 - {[2- (2-Aminopyridin-4-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl ] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7 -methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 792).

Using General Procedure 14 starting from Example 657 as reactant, Example 792 was prepared. MCBP: calculated for C ₃₄ H ₃₆ N ₈ O ₄ S: 652.2580, found: 653.2646 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1- [4- (Aminomethyl) benzoyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidin-4-yl] methyl} -7-methyl -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-o n (Example 793).

Using General Procedure 14 starting from Example 252 as reactant, Example 793 was prepared. MCBP: calculated for C ₃₃ H ₃₈ N ₆ O ₄ : 582.2955, found: 292.1560 [(M + 2H) ²⁺ form].

N- (4 - {[(3R, 4R) -4 - ({4-Hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine -3-yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} benzyl) prop-2-enamide (Example

794).

Using General Procedure 7, starting from Example 793 and acrylic acid as reagents, Example 794 was prepared. MCBP: calculated for C ₃₆ H ₄₀ N ₆ O ₅ : 636.3060, found: 637.3134 [(M + H) + form].

3 - {[1 - ({(3R, 4R) -1 - [(1-Acryloyl-1,2,3,4-meterαhydroquinolun-7-yl) kαrbonyl] -3-phenylpuperidin-4yl} carbonyl) -4- hydroxypiperidin-4-yl] methyl} -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one (Example 795).

Using General Procedure 7, starting from Example 788 and acrylic acid as reagents, Example 795 was prepared. MCBP: Calculated for C ₃₈ H ₄₂ N ₆ O ₅ : 662.3217, Found: 663.3297 [(M + H) + form].

3 - {[(3R, 4R) -4 - ({4-Hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine-3- yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} benzamide (Example 796).

A mixture of Example 208 (0.23 mmol), acetaldoxime (141 μL, 137 mg, 2.3 mmol, 10 eq.) And a molecular sieve treated with copper (II) chloride (4A, 50 mg) was stirred in MeOH (2 mL) for 5 h at 60 ° C. The reaction mixture was filtered, the filtrate was purified using preparative LC (on a C-18 Gemini-NX column 5 μm, 5 mM aqueous NH4HCO ₃ -MeCN, gradient) to give Example 796. MCBP: calculated for C ₃₃ H ₃₆ N ₆ O ₅ : 596.2747, found: 597.283 [(M + H) + form].

3 - {[(3R, 4R) -4 - ({4-Hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine-3- yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} benzoic acid (Example 797).

A mixture of Example 260 (0.66 mmol) and hydrochloric acid (aq. 1N, 1.33 ml, 2 eq.) In MeCN (2 ml) was stirred at 80 ° C for 4 h. The reaction mixture was introduced onto preparative LC (on a C- 18 Gemini-NX 5 μm, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient) to give Example 797. MCBP: calculated for C ₃₃ H ₃₅ N ₅ O ₆ 597.2587, found: 598.2659 [(M + H) + form] ...

3 - {[(3R, 4R) -4 - ({4-Hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine-3- yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} -N-methylbenzamide (Example 798).

Using General Procedure 7, starting from Example 797 as a carboxylic acid reactant and methylamine hydrochloride as an amine reactant, Example 798 was prepared. MCBP: calculated for C ₃ 4H ₃ 8N6O5: 610.2903, found: 611.2978 [(M + H) + form ].

3 - {[(3R, 4R) -4 - ({4-Hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine-3- yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} -N, N-dimethylbenzamide (Example 799).

- 144 037563

Using General Procedure 7, starting from Example 797 as a carboxylic acid reactant and methylamine dihydrochloride as an amine reactant, Example 799 was prepared. MCBP: Calculated for C ₃₅ H ₄₀ N ₆ O ₅ : 624.3060, Found: 625.3139 [(M + H ) + form].

- {[4-Hydroxy-1 - ({(3R, 4R) -1- [3 - (morpholin-4-ylcarbonyl) benzoyl] -3-phenylpiperidin-4-yl} carbonyl) piperidin-4-yl] methyl } -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 800).

Using General Procedure 7, starting from Example 797 as a carboxylic acid reactant and morpholine as an amine reactant, Example 800 was prepared. MCBP: calculated for C ₃₇ H ₄₂ N ₆ O ₆ : 666.3166, found: 334.1668 [(M + 2H) ²⁺ form].

5 - {[(3R, 4R) -4 - ({4-Hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine-3- yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} -2- (6-methylpyridin-3-yl) -1,3-thiazole 4-carbonitrile (Example 801).

A mixture of Example 263 (0.15 mmol) and copper (I) cyanide (156 mg, 1.74 mmol, 12 eq.) In NMP (5 ml) was subjected to microwave irradiation for 4 h at 200 ° C. The reaction mixture was purified using preparative LC (on a C-18 Gemini-NX column 5 μm, 5 mM aqueous formic acid-MeCN, then 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient) to give Example 801. MCBP: calculated for C ₃₆ H ₃₆ N ₈ O ₄ S: 676.2580, found: 677.266 [(M + H) + form].

(3 - {[(3R, 4R) -4 - ({4-Hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine-3 -yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} phenyl) (methyl) sulfoniumolate (Example 802).

A mixture of Example 283 (0.267 mmol) and oxone® (164 mg, 0.267 mmol, 1 eq) in MeOH (5 ml), water (5 ml) and MeCN (5 ml) was stirred at rt. over 10 hours. Water (30 ml) and MSM (3 ml) were added to the reaction mixture and evaporated. To the residue was added brine (30 ml) and extracted with DCM (4x50 ml), the combined organic layers were dried over MgSO ₄ and evaporated. The residue was purified by preparative LC (on a C-18 Gemini-NX column 5 μm, 5 mM aqueous NH4HCO3-MeCN, gradient) to give Example 802. MCBP: calculated for C ₃₃ H ₃₇ N ₅ O ₅ S: 615.2515, found: 616.2622 [(M + H) + form].

methyl 3-amino-5 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d ] pyrimidin-3-yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} benzoate (Example 803).

Using General Procedure 12 starting from Example 285 as reactant, Example 803 was prepared. MCBP: calculated for C ₃₄ H ₃₈ N ₆ O ₆ : 626.2853, found: 627.295 [(M + H) + form].

3 - {[(3R, 4R) -4 - ({4-Hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine-3- yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} -N-methoxy-N-methylbenzamide (Example 804).

Using General Procedure 7, starting from Example 797 as a carboxylic acid reactant and N, O-dimethylhydroxylamine hydrochloride as an amine reactant, Example 804 was prepared. MCBP: calculated for C ₃₅ H ₄₀ N ₆ O ₆ : 640.3009, found: 641.3089 [ (M + H) + form].

Methyl 3- (acetylαmino) -5 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3 -d] pyrimidin-3-yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} benzoate (Example 805).

Using General Procedure 7 starting from Example 803 and acetic acid as reactants, Example 805 was prepared. MCBP: calculated for C ₃₆ H ₄₀ N ₆ O ₇ : 668.2958, found: 669.3036 [(M + H) + form].

methyl 3- (Benzoylαmino) -5 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(7-methyl-4-oxo-4,7-dihydro-3H-pyrrolo [2,3 -d] pyrimidin-3-yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} benzoate (Example 806).

Using General Procedure 7, starting from Example 803 and benzoic acid as reagents, Example 806 was prepared. MCBP: calculated for C ₄ iH ₄₂ N ₆ O ₇ : 730.3115, found: 731.3194 [(M + H) + form].

7- (3-Chlorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-hydroxypyridin-3-yl) -1,3-thiazol-5- yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 807).

Using General Procedure 10, starting from Example 86 as reactant, Example 807 was prepared. MCBP: calculated for C ₃₉ H ₃₈ N ₇ O ₄ SCl: 735.2394, found: 736.2464 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3-hydroxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 808) ...

Using General Procedure 10 starting from Example 99 as reactant, Example 808 was prepared. MCBP: calculated for C ₄₀ H ₄ iN ₇ O ₄ S: 715.2941, found: 716.3012 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-hydroxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3-hydroxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 809) ...

Using General Procedure 10, starting from Example 94 as reactant, Example 809 was prepared. MCBP: calculated for C ₃₉ H ₃₉ N ₇ O ₅ S: 717.2733, found: 718.2805 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-oxo-1,6-dihydropyridin-3-yl) -1,3-thiazol-5-yl]] methyl} -3- 145 037563 phenylpiperudin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (6-methoxypuridin-2-yl) -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one (Example 810).

Using General Procedure 15, starting from Example 101 as reactant, Example

810. MCBP calculated for C ₃₉ H ₄₀ N ₈ O ₅ S: 732.2842, found: 733.2893 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methyl-1-oxidopyridin-3-yl) -1,3-thiazole-5 -yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 811).

A mixture of Example 750 (0.137 mmol), mCPBA (24 mg, 0.137 mmol, 1 eq.) In DCM (1 ml) was stirred at rt. for 25 h. The reaction mixture was evaporated and purified by preparative LC (on a C-18 Gemini-NX column 5 μm, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient) to give Example 811. MCBP: calculated for C ₄ iH ₄ iN ₇ O ₅ S: 743.2890, found: 744.2959 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-hydroxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperudin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 812).

Using General Procedure 10 starting from Example 733 as reactant, Example 812 was prepared. MCBP: calculated for C ₃₉ H ₃₉ N ₇ O ₄ S: 701.2784, found: 702.2841 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (4-methylpiperazin-1-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 813).

A mixture of Example 103 (0.391 mmol) and N-methylpiperazine (96 μl, 87 mg, 0.872 mmol, 3 eq.), And PDO (5 ml) was subjected to microwave irradiation for a total of 9 h at 150 ° C. The reaction mixture was purified using preparative LC (on a C-18 Gemini-NX column 5 μm, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient) to give Example 813. MCBP: calculated for C ₃₉ H ₄₆ N ₈ O ₃ S: 706.3414, found: 707.3487 [(M + H) + form].

5- (5 - {[(3R, 4R) -4 - ({4-Hydroxy-4 - [(4-oxo-7-phenyl-4,7-dihydro-3H-purrolo [2,3-d] purimudine -3-yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] methyl} -1,3-thiazol-2-yl) pyridine-2-carboxylic acid (Example 814).

Using General Procedure 9, starting from Example 103 and methyl 5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine-2-carboxylate as reagents, the crude product was dissolved in MeOH (5 ml) and water (5 ml), lithium hydroxide monohydrate (74 mg, 1.76 mmol) was added and the mixture was stirred for 2 h at rt. The reaction mixture was evaporated to water, neutralized with HCl solution (aq, 1N), purified by preparative LC (on a C-18 Gemini-NX column 5 μm, 5 mM aqueous NH4HCO3MeCN, gradient) to give Example 814. MCBP: calculated for C ₄₀ H ₃₉ N ₇ O ₅ S: 729.2733, found: 730.278 [(M + H) + form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-oxo-1,6-dihydropuridin-3-yl) -1,3-thiazol-5-yl]] methyl} -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (6-oxo-1,6-dihydropyridin-2-yl) -3,7duhydro-4H-purrolo [2,3- d] purimudin-4-one (Example 815).

Using General Procedure 15 starting from Example 101 as reactant, Example 815 was prepared. MCBP: calculated for C ₃₈ H ₃₈ N ₈ O ₅ S: 718.2686, found: 719.2756 [(M + H) + form].

3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (6-oxo-1,6-dihydropuridin-2-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one (Example 816).

Using General Procedure 15 starting from Example 100 as reactant, Example 816 was prepared. MCBP: Calculated for C ₃₉ H ₄₀ N ₈ O ₄ S: 716.2893, Found: 717.2966 [(M + H) + Form].

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3 - phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (1-methyl-6-oxo-1,6-dihydropyridin-2-yl) -3,7-dihydro4H-pyrrolo [2,3 -d] pyrimidin-4-one (Example 817).

Using General Procedure 13, starting from Example 816 as reactant and iodomethane as reactant, Example 817 was prepared. MCBP: calculated for C ₄₀ H ₄₂ N ₈ O ₄ S: 730.3050, found: 731.3121 [(M + H) + form] ...

3 - [[1 - [(3S, 4S) -1-Benzyl-3-phenylpiperidine-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] thieno [2,3d] purimudin-4-one (Example 818 ).

Using General Procedure 6, starting from 3 - [[4-hydroxy-1 - [(3S, 4S) -3-phenylpiperidine-4-carbonyl] 4-piperidyl] methyl] thieno [2,3-d] pyrimidin-4- she (which was prepared according to General Procedure 5 using tert-butyl (3S, 4S) -4- (2-oxa-6-azaspuro [2.5] octane-6-carbonyl) -3-phenylpiperudine-1carboxylate and 3H-thieno [2,3-d] pyramidin-4-one) and benzyl bromide as reagents prepared Example 818. MCBP: calculated for C ₃ iH ₃₄ N ₄ O ₃ S: 542.2352, found: 543.2419 [(M + H) + form ].

3 - [[1 - [(3R, 4R) -1-Benzyl-3-phenylpiperidin-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] thieno [2,3d] purimudin-4-one (Example 819 ).

Using General Procedure 6, starting from the compound Synthesis of R3cp and benzyl bromide as reagents, Example 819 was prepared. MCBP: calculated for C ₃ iH ₃₄ N ₄ O ₃ S: 543.2352, found: 543.2401 [(M + H) + form].

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3 - [[1 - [(3S, 4S) -1-Benzyl-3-phenylpiperidin-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] pyrido [3,2d] pyrimidin-4-one (Example 820 ).

Using General Procedure 6, starting from the compound Synthesis of R3cn and benzyl bromide as reagents, Example 820 was prepared. MCBP: calculated for C ₃₂ H ₃₅ N ₅ O ₃ : 537.274, found: 538.2837 [(M + H) + form].

3 - [[1 - [(3R, 4R) -1-Benzyl-3-phenylpiperidin-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] pyrido [3,2-d] pyrimidin-4-one ( Example 821).

Using General Procedure 6, starting from the Synthesis of R3co compound and benzyl bromide as reagents, Example 821 was prepared. MCBP: calculated for C ₃₂ H ₃₅ N ₅ O ₄ : 537.2740, found: 538.2809 [(M + H) + form].

3 - [[1 - [(3R, 4S) -1-Benzyl-3- (2-myienyl) pynerigin-4-kαrbonyl] -4-hydroxy-4-pynerigyl] methyl] pyrigo [3,2-d] pyrimidine -4-one (Ex. 822).

Using General Procedure 5, starting from 3H-pyrido [3,2-d] pyrimidin-4-one and Synthesis compound R1e as reactants, the resulting crude piperidine product was reacted with Synthesis compound R1q- (3R, 4S) according to with General Procedure 7 to obtain Example 822. MCBP: calculated for C ₃₀ H33N ₅ O ₃ S: 544.2304, found: 544.2381 [(M + H) + form].

3 - [[1 - [(3 S, 4R) -1-Benzyl-3 - (2-thienyl) piperidine-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] pyrido [3,2-d] pyrimidin-4-one (Example 823).

Using General Procedure 5, starting from 3H-pyrido [3,2-d] pyrimidin-4-one and Synthesis compound R1e as reactants, the resulting crude piperidine product was reacted with Synthesis compound R1q- (3S, 4R) according to with General Procedure 7 to obtain Example 823. MCBP: calculated for C ₃₀ H33N ₅ O3S: 544.2304, found: 544.2394 [(M + H) + form].

3 - [[1 - [(3R, 4R) -1 - [(2-Fluorophenyl) methyl] -3-phenylpiperidine-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] thieno [2,3-d ] pyrimidin-4-one (Example 824).

Using General Procedure 6, starting from the compound Synthesis of R3cp and 1- (bromomethyl) -2-fluorobenzene as reagents, Example 824 was prepared. MCBP: Calculated for C ₃₁ H33FN ₄ O ₃ S: 560.2257, Found: 561.2301 [(M + H ) ⁺ form].

3 - [[1 - [(3R, 4R) -1 - [(3-Fluorophenyl) methyl] -3-phenylpiperidine-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] thieno [2,3-d ] pyrimidin-4-one (Example 825).

Using General Procedure 6, starting from the compound Synthesis of R3cp and 1- (bromomethyl) -3-fluorobenzene as reagents, Example 825 was prepared. MCBP: Calculated for C ₃₁ H33FN ₄ O ₃ S: 560.2257, Found: 561.2331 [(M + H ) ⁺ form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- (o-tolylmethyl) -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] thieno [2,3-d] pyrimidine- 4-one (Example 826).

Using General Procedure 6, starting from the compound Synthesis of R3cp and 1- (bromomethyl) -2-methylbenzene as reagents, Example 826 was prepared. MCBP: Calculated for C3 ₂ H ₃₆ N ₄ O ₃ S: 556.2508, Found: 557.2565 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- (m-tolylmethyl) -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] thieno [2,3-d] pyrimidine- 4-one (Example 827).

Using General Procedure 6, starting from the compound Synthesis of R3cp and 1- (bromomethyl) -3methylbenzene as reagents, Example 827 was prepared. MCBP: Calculated for C ₃₂ H ₃₆ N ₄ O ₃ S: 556.2508, Found: 557.2597 [(M + H ) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- (4-methyl-2-phenylthiazole-5-carbonyl) -3-phenylpiperidine-4-carbonyl] 4-piperidyl] methyl] pyrido [ 3,2-d] pyrimidin-4-one (Example 828).

Using General Procedure 7, starting from the Synthesis of R3co compound and 4-methyl-2-phenylthiazole-5carboxylic acid as reagents, Example 828 was prepared. MCBP: Calculated for C36H36N6O4S: 648.2519, found: 649.2583 [(M + H) ⁺ form].

3 - [[4-Hydroxy- 1 - [(3R, 4R) -3-phenyl-1 - (2-phenylthiazole-5-carbonyl) piperidine-4-carbonyl] -4-piperidyl] methyl] pyrido [3, 2-d] pyrimidin-4-one (Example 829).

Using General Procedure 7, starting from the compound Synthesis of R3co and 2-phenylthiazole-5-carboxylic acid as reagents, Example 829 was prepared. MCBP: Calculated for C ₃₅ H ₃₄ N ₆ O ₄ S: 634.2362, Found: 635.2429 [(M + H) + form].

3 - [[1 - [(3R, 4R) -1-Benzyl-3-phenylpiperidine-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] -6-chloropyrido [3,2-d] pyrimidine-4 -on (Example 830).

Using General Procedure 6, starting from the Synthesis compound R3cq and benzyl bromide as reagents, Example 830 was prepared. MCBP: calculated for C ₃₂ H ₃ 4ClN ₃ O ₃ : 571.235, found: 572.2416 [(M + H) + form].

3 - [[1 - [(3R, 4R) -1-Benzyl-3-phenylpiperidine-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] -6-methoxypyrido [3,2-d] pyrimidine-4 -on (Example 831).

Using General Procedure 6, starting from the compound Synthesis of R3cr and benzyl bromide as reagents, Example 831 was prepared. MCBP: calculated for C ₃₃ H ₃₇ N ₅ O ₄ : 567.2846, found: 568.2902 [(M + H) + form].

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3 - [[1 - [(3R, 4R) -1-Benzyl-3-phenylpiperidine-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] -5Hnupugo [3,2-d] nupuMuguH-4,6 -guoH (Example 832).

Using General Procedure 6, starting from the compound Synthesis of R3cs and benzyl bromide as reagents, Example 832 was prepared. MCBP: calculated for C ₃₂ H ₃₅ N ₅ O ₄ : 553.2689, found: 554.2762 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- (3-methylisothiazole-4-carbonyl) -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] pyrido [3,2-d] pyrimidin-4-one (Example 833).

Using General Procedure 7, starting from the compound Synthesis of R3co and 3-methylisothiazole-4carboxylic acid as reagents, Example 833 was prepared. MCBP: Calculated for C ₃₀ H ₃₂ N ₆ O ₄ S: 572.2206, Found: 573.2285 [(M + H) ⁺ form].

3 - [[1 - [(3R, 4R) -1 - [(2-Fluorophenyl) methyl] -3-phenylpiperidine-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] pyrido [3,2-d ] pyrimidin-4-one (Example 834).

Using General Procedure 6, starting from the compound Synthesis of R3co and 1- (bromomethyl) -2-fluorobenzene as reagents, Example 834 was prepared. MCBP: calculated for C ₃₂ H ₃₄ FN ₅ O ₃ : 555.2646, found: 556.2701 [(M + H) ⁺ form].

3 - [[1 - [(3R, 4R) -1 - [(3-Fluorophenyl) methyl] -3-phenylpiperidine-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] pyrido [3,2-d ] pyrimidin-4-one (Example 835).

Using General Procedure 6, starting from the compound Synthesis of R3co and 1- (bromomethyl) -3-fluorobenzene as reagents, Example 835 was prepared. MCBP: Calculated for C ₃₂ H ₃₄ FN ₅ O ₄ : 555.2647, Found: 556.2702 [(M + H) ⁺ form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- (o-tolylmethyl) -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] pyrido [3,2-d] pyrimidine- 4-one (Example 836).

Using General Procedure 6, starting from the Synthesis compound of R3co and 1- (bromomethyl) -2-methylbenzene as reagents, Example 836 was prepared. MCBP: Calculated for C ₃₃ H ₃₇ N ₅ O ₃ : 551.2896, Found: 552.2943 [(M + H) ⁺ form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- (m-tolylmethyl) -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] pyrido [3,2-d] pyrimidine- 4-one (Example 837).

Using General Procedure 6 starting from the Synthesis compound of R3co and 1- (bromomethyl) -3-methylbenzene as reagents, Example 837 was prepared. MCBP: Calculated for C ₃₃ H ₃₇ N ₅ O ₄ : 551.2897, Found: 552.2990 [(M + H) ⁺ form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- (4-methyl-2-phenylthiazole-5-carbonyl) -3-phenylpiperidine-4-carbonyl] 4-piperidyl] methyl] thieno [ 2,3-d] pyrimidin-4-one (Example 838).

Using General Procedure 7, starting from the compound Synthesis of R3cp and 4-methyl-2-phenylthiazole-5carboxylic acid as reagents, Example 838 was prepared. MCBP: calculated for C ₃₅ H ₃₅ N ₅ O ₄ S ₂ : 653.2130, found: 654.2212 [ (M + H) ⁺ form].

3 - [[1 - [(3R, 4R) -1 - (2-Benzyl-4-methylthiazole-5-carbonyl) -3-phenylpiperidine-4-carbonyl] -4-hydroxy4-piperidyl] methyl] thieno [2, 3-d] pyrimidin-4-one (Example 839).

Using General Procedure 7, starting from the compound Synthesis of R3cp and 2-benzyl-4-methylthiazole-5carboxylic acid as reagents, Example 839 was prepared. MCBP: Calculated for C ₃₆ H ₃₇ N ₅ O ₄ S ₂ : 667.2287, Found: 668.2371 [ (M + H) + form].

3 - [[4-Hydroxy- 1 - [(3R, 4R) -1- (3-methylisothiazole-4-carbonyl) -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] thieno [2,3-d ] pyrimidin-4-one (Example 840).

Using General Procedure 7, starting from the compound Synthesis of R3cp and 3-methylisothiazole-4carboxylic acid as reagents, Example 840 was prepared. MCBP: Calculated for C ₂₉ H ₃ iN ₅ O ₄ S ₂ : 577.1817, Found: 578.1901 [(M + H ) ⁺ form].

3 - [[1 - [(3R, 4R) -1 - (Benzofuran-2-ylmethyl) -3-phenylpiperidin-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] thieno [2,3-d] pyrimidin-4-one (Example 841).

Using General Procedure 6, starting with the compound Synthesis of R3cp and 2- (chloromethyl) benzofuran as reagents, Example 841 was prepared. MCBP: Calculated for C ₃₃ H ₃₄ N ₄ O ₄ S: 582.2301, Found: 583.2376 [(M + H) + form].

3 - [(3R, 4R) -4- [4-Hydroxy-4 - [(4-oxothieno [2,3-d] pyrimidin-3-yl) methyl] piperidine-1-carbonyl] -3phenylpiperidine-1-carbonyl ] -1H-indazole-5-carbonitrile (Example 842).

Using General Procedure 7, starting from the compound Synthesis of R3cp and 5-cyano-1H-indazole-3carboxylic acid as reagents, Example 842 was prepared. MCBP: calculated for C ₃₃ H ₃₁ N ₇ O ₄ S: 621.2158, found: 622.2229 [( M + H) + form].

3 - [[1 - [(3R, 4R) -1 - (2-Benzyl-4-methylthiazole-5-carbonyl) -3-phenylpiperidine-4-carbonyl] -4-hydroxy4-piperidyl] methyl] pyrido [3, 2-d] pyrimidin-4-one (Example 843).

Using General Procedure 7, starting from the compound Synthesis of R3co and 2-benzyl-4-methylthiazole-5carboxylic acid as reagents, Example 843 was prepared. MCBP: calculated for C ₃₇ H ₃₈ N ₆ O ₄ S: 662.2675, found: 663.2743 [( M + H) + form].

3 - [[1 - [(3R, 4R) -1- [2- (2-Fluorophenyl) -4-methylthiazole-5-carbonyl] -3-phenylpiperidine-4-carbonyl] -4hydroxy-4-piperidyl] methyl] pyrido [3,2-d] pyrimidin-4-one (Example 844).

- 148 037563

Using General Procedure 7, starting from the Synthesis compound of R3co and 2- (2-fluorophenyl) -4methylthiazole-5-carboxylic acid as reactants, Example 844 was prepared. MCBP: Calculated for

C ₃₆ H ₃₅ FN ₆ O ₄ S: 666.2425, found: 667.2498 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (o-tolyl) thiazole-5-carbonyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl ] methyl] pyrido [3,2-d] pyrimidin-4-one (Example 845).

Using General Procedure 7, starting from the Synthesis compound of R3co and 4-methyl-2- (o-tolyl) thiazole-5carboxylic acid as reactants, Example 845 was prepared. MCBP: Calculated for C ₃₇ H ₃₈ N ₆ O ₄ S: 662.2675, found: 663.2751 [(M + H) ⁺ form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -3-phenyl-1- [2- (4-pyridyl) thiazole-5-carbonyl] piperidine-4-carbonyl] -4-piperidyl] methyl] pyrido [ 3,2-d] pyrimidin-4-one (Example 846).

Using General Procedure 7, starting from the Synthesis of R3co compound and 2- (4-pyridyl) thiazole-5carboxylic acid as reagents, Example 846 was prepared. MCBP: Calculated for C34H33N7O4S: 635.2314, Found: 636.2401 [(M + H) ⁺ Form] ...

3 - [[4-Hydroxy-1 - [(3S, 4S) -3-phenyl-1- [2- (4-pyridyl) thiazole-5-carbonyl] piperidine-4-carbonyl] -4-piperidyl] methyl] pyrido [ 3,2-d] pyrimidin-4-one (Example 847).

Using General Procedure 7, starting from the compound Synthesis of R3cn and 2- (4-pyridyl) thiazole-5carboxylic acid as reagents, Example 847 was prepared. MCBP: Calculated for C ₃₄ H ₃₃ N ₇ O ₄ S: 635.2315, Found: 318.6241 [ (M + 2H) ²⁺ form].

3 - [[1 - [(3R, 4R) -1- [2 - [(2-Fluorophenyl) methyl] thiazole-5-carbonyl] -3-phenylpiperidine-4-carbonyl] -4hydroxy-4-piperidyl] methyl] pyrido [3,2-d] pyrimidin-4-one (Example 848).

Using General Procedure 7, starting from the Synthesis compound of R3co and 2 - [(2-fluorophenyl) methyl] thiazole-5-carboxylic acid as reactants, Example 848 was prepared. MCBP: Calculated for C ₃ 6H ₃₃ FN6O4S: 666.2425, Found: 667.2498 [(M + H) ⁺ form].

6- (Benzylamino) -3 - [[1 - [(3R, 4R) -1-benzyl-3-phenylpiperidine-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] pyrido [3,2-d] pyrimidin-4-one (Example 849).

Using General Procedure 6, starting from the Synthesis of R3ct compound and benzyl bromide as reagents, Example 849 was prepared. MCBP: Calculated for C ₃₉ H ₄₂ N ₆ O ₃ : 642.3318, found: 322.1727 [(M + 2H) ²⁺ form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -3-phenyl-1- [5- (4-pyridyl) thiophene-2-carbonyl] piperidine-4-carbonyl] -4piperidyl] methyl] pyrido [ 3,2-d] pyrimidin-4-one (Example 850).

Using General Procedure 7, starting from the Synthesis of R3co compound and 5- (4-pyridyl) thiophene-2carboxylic acid as reactants, Example 850 was prepared. MCBP: Calculated for C35H34N6O4S: 634.2362, Found: 635.2439 [(M + H) ⁺ form] ...

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (4-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4carbonyl] -4-piperidyl] methyl ] pyrido [3,2-d] pyrimidin-4-one (Example 851).

Using General Procedure 7, starting from the Synthesis compound of R3co and 4-methyl-2- (4-pyridyl) thiazole 5-carboxylic acid as reactants, Example 851 was prepared. MCBP: Calculated for C ₃₅ H ₃₅ N ₇ O ₄ S: 649.2471, found: 650.2547 [(M + H) + form].

3 - [[1 - [(3R, 4R) -1 - [(2-Fluorophenyl) methyl] -3-phenylpiperidine-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] -6 - [(4- methoxyphenyl) methylamino] pyrido [3,2-d] pyrimidin-4-one (Example 852).

Using General Procedure 6, starting from the compound Synthesis of R3cu and 1- (bromomethyl) -2-fluorobenzene as reagents, Example 852 was prepared. MCBP: calculated for C ₄₀ H ₄₃ FN ₆ O ₄ : 690.333, found: 346.1732 [(M + 2H) ²⁺ form].

6-Chloro-3 - [[4-hydroxy-1 - [(3R, 4R) -1- (4-methyl-2-phenylthiazole-5-carbonyl) -3-phenylpiperidine-4carbonyl] -4-piperidyl] methyl] pyrido [3,2-d] pyrimidin-4-one (Example 853).

Using General Procedure 5, Step 1, starting with 6-chloro-3H-pyrido [3,2-d] pyrimidin-4-one and Synthesis compound R1s as the epoxy compound, Example 853 was prepared. MCBP: Calculated for C ₃ 6H ₃ 5ClN6O4S: 682.2129, found: 683.2201 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -3-phenyl-1- (5-pyrimidin-5-ylthiophen-2-carbonyl) piperidine-4-carbonyl] -4-piperidyl] methyl] thieno [2,3-d] pyrimidin-4-one (Example 854).

Using General Procedure 7, starting from the Synthesis compound of R3cp and 5-bromothiophene-2carboxylic acid as reactants, the resulting crude bromine compound was reacted according to General Procedure 9 with pyrimidin-5-ylboronic acid to give Example 854. MCBP: calculated for C ₃₃ H ₃₂ N ₆ O ₄ S ₂ : 640.1926, found: 641.1995 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- (4-methyl-2-pyrimidin-5-ylthiazole-5-carbonyl) -3-phenylpiperidine-4carbonyl] -4-piperidyl] methyl] thieno [2,3-d] pyrimidin-4-one (Example 855).

Using General Procedure 7, starting from the Synthesis compound of R3cp and 2-bromo-4-methylthiazole-5carboxylic acid as reactants, the resulting crude bromine compound was reacted according to General Procedure 9 with pyrimidin-5-ylboronic acid to give Example 855. MCBP: calculated for C ₃₃ H ₃₃ N ₇ O ₄ S ₂ : 655.2035, found: 656.2132 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -3-phenyl-1- (5-pyrimidin-5-ylthiophen-2-carbonyl) piperidine-4-carbonyl] -4-piperidyl] methyl] pyrido [3,2-d] pyrimidin-4-one (Example 856).

- 149 037563

Using General Procedure 7, starting from the Synthesis compound of R3co and 5-bromothiophene-2-carboxylic acid as reactants, the resulting crude bromine compound was reacted according to General Procedure 9 with pyrimidin-5-ylboronic acid to give Example

856. MCBP: calculated for C ₃₄ H ₃₃ N ₇ O ₄ S: 635.2315, found: 636.2387 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- [5- (2-methylpyrazol-3-yl) thiophene-2-carbonyl] -3-phenylpiperidine-4carbonyl] -4-piperidyl] methyl ] thieno [2,3-d] pyrimidin-4-one (Example 857).

Using General Procedure 7, starting from the Synthesis compound of R3cp and 5-bromothiophene-2-carboxylic acid as reagents, the resulting crude bromine compound was reacted according to General Procedure 9 with 1-methyl-5- (4,4, 5,5-tetramethyl-1,3,2-dioxaborolane-2yl) pyrazole to give Example 857. MCBP: calculated for C ₃₃ H ₃₄ N ₆ O ₄ S ₂ : 642.2083, found: 643.2163 [(M + H) ⁺ form ].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (2-methylpyrαzol-3-yl) thiazole-5-carbonyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] thieno [2,3-d] pyrimidin-4-one (Example 858).

Using General Procedure 7, starting from the Synthesis compound of R3cp and 2-bromo-4-methylthiazole-5carboxylic acid as reagents, the resulting crude bromine compound was reacted according to General Procedure 9 with 1-methyl-5- (4, 4,5,5-tetramethyl-1,3,2-dioxaborolane-2yl) pyrazole to give Example 858. MCBP: calculated for C ₃₃ H ₃₅ N ₇ O ₄ S ₂ : 657.2192, found: 658.2279 [(M + H) ⁺ form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- [5- (2-methylpyrazol-3-yl) thiophene-2-carbonyl] -3-phenylpiperidine-4carbonyl] -4-piperidyl] methyl ] pyrido [3,2-d] pyrimidin-4-one (Example 859).

Using General Procedure 7, starting from the Synthesis of R3co compound and 5-bromothiophene-2carboxylic acid as reactants, the resulting crude bromine compound was reacted according to General Procedure 9 with 1-methyl-5- (4,4,5, 5-tetramethyl-1,3,2-dioxaborolane-2yl) pyrazole to give Example 859. MCBP: calculated for C ₃₄ H ₃₅ N ₇ O ₄ S: 637.2471, found: 638.2525 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- [2- (6-methoxy-3-pyridyl) -4-methylthiazole-5-carbonyl] -3-phenylpiperidine-4-carbonyl] - 4-piperidyl] methyl] thieno [2,3-d] pyrimidin-4-one (Example 860).

Using General Procedure 7, starting from the Synthesis of R3cp compound and 2-bromo-4-methylthiazole-5carboxylic acid as reactants, the resulting crude bromine compound was reacted according to General Procedure 9 c (6-methoxy-3-pyridyl) boronic acid to give Example 860. MCBP: calculated for C ₃₅ H ₃₆ N ₆ O ₅ S ₂ : 684.2189, found: 685.2269 [(M + H) + form].

3 - [[1 - [(3R, 4R) -1- [2- (6-Amino-3-pyridyl) -4-methylthiazole-5-carbonyl] -3-phenylpiperidine-4carbonyl] -4-hydroxy-4- piperidyl] methyl] thieno [2,3-d] pyrimidin-4-one (Example 861).

Using General Procedure 7, starting from the Synthesis compound of R3cp and 2-bromo-4-methylthiazole-5carboxylic acid as reactants, the resulting crude bromine compound was reacted according to General Procedure 9 with 5- (4,4,5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine 2-amine to give Example 861. MCBP: calculated for C ₃₄ H ₃₅ N ₇ O ₄ S ₂ : 669.2192, found: 670.2245 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] thieno [2,3-d] pyrimidin-4-one (Example 862).

Using General Procedure 7, starting from the Synthesis of R3cp compound and 2-bromo-4-methylthiazole-5carboxylic acid as reactants, the resulting crude bromine compound was reacted according to General Procedure 9 c (6-methyl-3-pyridyl) boronic acid to give Example 862. MCBP: calculated for C ₃₅ H ₃₆ N ₆ O ₄ S ₂ : 668.2239, found: 669.2306 [(M + H) + form].

3 - [[1 - [(3R, 4R) -1- [3-Fluoro-5- (6-methyl-3-pyridyl) thiophene-2-carbonyl] -3-phenylpiperidine-4carbonyl] -4-hydroxy-4 -piperidyl] methyl] thieno [2,3-d] pyrimidin-4-one (Example 863).

Using General Procedure 7, starting from Synthesis compound R3cp and Synthesis compound R1g as reagents, the resulting crude iodine compound was reacted according to General Procedure 9 with (6-methyl-3-pyridyl) boronic acid to give Example 863. MCBP calculated for C ₃₅ H ₃₄ FN ₅ O ₄ S ₂ : 671.2036, found: 336.6092 [(M + 2H) ²⁺ form].

3 - [[1 - [(3R, 4R) -1- [5- (6-Amino-3-pyridyl) -3-fluorothiophene-2-carbonyl] -3-phenylpiperidine-4-carbonyl] -4-hydroxy- 4-piperidyl] methyl] thieno [2,3-d] pyrimidin-4-one (Example 864).

Using General Procedure 7, starting from Synthesis compound R3cp and Synthesis compound R1g as reagents, the resulting crude iodine compound was reacted according to General Procedure 9 with 5- (4,4,5,5-tetramethyl-1,3 , 2-dioxaborolan-2-yl) pyridine-2-amine to give Example 864. MCBP: calculated for C ₃₄ H ₃₃ FN ₆ O ₄ S ₂ : 672.1989, found: 671.1926 [(MH) ^- form].

3 - [[1 - [(3R, 4R) -1- [3-Fluoro-5- (6-piperazine-1 -yl-3-pyridyl) thiophene-2-carbonyl] -3-phenylpiperidine-4carbonyl] -4 -hydroxy-4-piperidyl] methyl] thieno [2,3-d] pyrimidin-4-one (Example 865).

Using General Procedure 7, starting from Synthesis compound R3cp and Synthesis compound R1g as reagents, the resulting crude iodine compound was reacted according to General Procedure 9 with 1- [5- (4,4,5,5-tetramethyl- 1,3,2-dioxaborolan-2-yl) -2-pyridyl] piperazine to give Example 865. MCBP: calculated for C ₃₈ H ₄₀ FN ₇ O ₄ S ₂ : 741.2567, found: 740.2504 [(MH) ^- for- 150 037563 ma].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [[2- (6-methyl-3-pyridyl) thiazol-5-yl] methyl] -3-phenylpiperidine-4-carbonyl] - 4-piperidyl] methyl] thieno [2,3-d] pyrimidin-4-one (Example 866).

Using General Procedure 6, starting with Synthesis compound R3cp and Synthesis compound R1c as reagents, Example 866 was prepared. MCBP: Calculated for C ₃₄ H ₃₆ N ₆ O ₃ S ₂ : 640.2290, Found: 641.2336 [(M + H) + form ].

3 - [[4-Hygroxy-1 - [(3R, 4R) -1 - [[2- (6-methoxy-3-pyridyl) thiazol-5-yl] methyl] -3-phenylpiperidine-4carbonyl] -4- piperidyl] methyl] thieno [2,3-d] pyrimidin-4-one (Example 867).

Using General Procedure 6, starting from the Synthesis compound R3cp and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 867 was prepared. MCBP: Calculated for C34H36N6O4S2: 656.2239, Found: 657.2343 [(M + H) ⁺ form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -3-phenyl-1 - [[2- (6-piperazin-1-yl-3-pyridyl) thiazol-5-yl] methyl] piperidine- 4-carbonyl] -4-piperidyl] methyl] thieno [2,3-d] pyrimidin-4-one (Example 868).

Using General Procedure 6, starting from the Synthesis compound of R3cp and 2-bromo-5- (bromomethyl) thiazole as reagents, the resulting crude bromine compound was reacted according to General Procedure 9 with 1- [5- (4.4 , 5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -2-pyridyl] piperazine to give Example 868. MCBP: calculated for C ₃₇ H ₄₂ N ₈ O ₃ S ₂ : 710.2821, found: 356.1477 [(M + 2H) ²⁺ form].

3 - [[1 - [(3R, 4R) -1 - [[2- (6-Amino-3-pyridyl) thiazol-5-yl] methyl] -3-phenylpiperidine-4-carbonyl] -4hygroxy-4- piperigyl] methyl] thieno [2,3-d] pyrimigin-4-one (Example 869).

Using General Procedure 6, starting from the Synthesis compound of R3cp and 2-bromo-5- (bromomethyl) thiazole as reagents, the resulting crude bromine compound was reacted according to General Procedure 9 with 5- (4,4,5, 5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyridine-2-amine to give Example 869. MCBP: calculated for C ₃₃ H ₃₅ N ₇ O ₃ S ₂ : 641.2243, found: 642.2342 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [[2- (3-methylimidazo [4,5-b] pyridin-6-yl) thiazol-5-yl] methyl] -3 -phenylpiperidin-4-carbonyl] -4-piperidyl] methyl] thieno [2,3-d] pyrimidin-4-o n (Example 870).

Using General Procedure 6, starting from the Synthesis compound of R3cp and 2-bromo-5- (bromomethyl) thiazole as reagents, the resulting crude bromine compound was reacted according to General Procedure 9 with 3-methyl-6- (4, 4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) imidazo [4,5b] pyridine to give Example 870. MCBP: calculated for C ₃₅ H ₃₆ N ₈ O ₃ S ₂ : 680.2352, found : 341.1257 [(M + 2H) ²⁺ form].

3 - [[4-Hydroxy- 1 - [(3R, 4R) -1 - [(2-imidazo [1,2-a] nyridin-7-ylthiazol-5-yl) methyl] -3-phenylpiperidine4-carbonyl ] -4-piperidyl] methyl] thieno [2,3-d] pyrimidin-4-one (Example 871).

Using General Procedure 6, starting from the Synthesis of R3cp compound and 2-bromo-5- (bromomethyl) thiazole as reagents, the resulting crude bromine compound was reacted according to General Procedure 9 with imigazo [1,2-a] pyrigine -7-ylboronic acid to give Example 871. MCBP: calculated for C ₃₅ H ₃₅ N ₇ O ₃ S ₂ : 665.2243, found: 333.6191 [(M + 2H) ²⁺ form].

6 - [[4-Hygroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-nirigyl) thiazole-5-carbonyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -3-phenyltriazolo [4,5-d] pyrimidin-7-one (Example 872).

Using General Procedure 7, starting from Synthesis compound R3cv and Synthesis compound R1d as reagents, Example 872 was prepared. MCBP: calculated for C ₃₉ H ₃₉ N ₉ O ₄ S: 729.2845, found: 730.2937 [(M + H) + form] ...

1 - [[4-Hygroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-nirigyl) thiazole-5-carbonyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -9-phenylpurin-6-one (Example 873).

Using General Procedure 7, starting with Synthesis compound R3cw and Synthesis compound R1d as reagents, Example 873 was prepared. MCBP: calculated for C ₄₀ H ₄₀ N ₈ O ₄ S: 728.2893, found: 727.2866 [(M + H) + form] ...

5 - [[4-Hygroxy-1 - [(3R, 4R) -1 - [[2- (6-methyl-3-pyrigyl) thiazol-5-yl] methyl] -3-phenylpiperidine-4-carbonyl] - 4-piperidyl] methyl] -1-phenylpyrazolo [3,4-d] pyrimidin-4-one (Example 874).

Using General Procedure 6, starting with Synthesis compound R3cx and Synthesis compound R1c as reagents, Example 874 was prepared. MCBP: calculated for C ₃₉ H ₄₀ N ₈ O ₃ S: 700.2944, found: 701.3000 [(M + H) + form] ...

1 - [[4-Hygroxy-1 - [(3R, 4R) -1 - [[2- (6-methyl-3-pyrigyl) thiazol-5-yl] methyl] -3-phenylpiperidine-4-carbonyl] - 4-piperidyl] methyl] -9-phenylpurin-6-one (Example 875).

Using General Procedure 6, starting with Synthesis compound R3cw and Synthesis compound R1c as reagents, Example 875 was prepared. MCBP: calculated for C ₃₉ H ₄₀ N ₈ O ₃ S: 700.2944, found: 351.1551 [(M + 2H) ²⁺ form ].

1 - [[4-Hygroxy-1 - [(3R, 4R) -1 - [[2- (6-methoxy-3-pyridyl) thiazol-5-yl] methyl] -3-phenylpiperidine-4carbonyl] -4- piperidyl] methyl] -9-phenylpurin-6-one (Example 876).

Using General Procedure 6, starting from the Synthesis compound R3cw and 5- (chloromethyl) -2- (6-methoxy3-pyridyl) thiazole as reagents, Example 876 was prepared. MCBP: Calculated for C ₃₉ H ₄₀ N ₈ O ₄ S:

- 151 037563

716.2893, found: 359.1535 [(M + 2H) ² + form].

5 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [[2- (6-methoxy-3-puridyl) thiazol-5-yl] methyl] -3-phenylpiperidine-4carbonyl] -4- piperidyl] methyl] -1-phenylpyrazolo [3,4-d] pyrimidin-4-one (Example 877).

Using General Procedure 6, starting from Synthesis compound R3cx and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 877 was prepared. MCBP: Calculated for C ₃ 9H ₄₀ N ₈ O ₄ S: 716.2893 found: 717.2979 [(M + H) ⁺ form].

5 - [[4-Hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -1-phenylpyrazolo [3,4-d] pyrimidin-4-one (Example 878).

Using General Procedure 7, starting from Synthesis compound R3cx and Synthesis compound R1d as reagents, Example 878 was prepared. MCBP: calculated for C ₄₀ H ₄₀ N ₈ O ₄ S: 728.2893, found: 729.2961 [(M + H) ⁺ form] ...

7-Bromo-3 - [[4-hydroxy-1 - [(3R, 4R) -1 - [[2- (6-methyl-3-pyridyl) thiazol-5-yl] methyl] -3-phenylpiperidine4-carbonyl ] -4-piperidyl] methyl] pyrrolo [2,1-f] [1,2,4] triazin-4-one (Example 879).

Using General Procedure 6, starting with the Synthesis compound R3cy and the Synthesis compound R1c as reagents, Example 879 was prepared. MCBP: calculated for C ₃₄ H ₃₆ BrN ₇ O ₃ S: 701.1783, found: 702.1856 [(M + H) ⁺ form] ...

6 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [[2- (6-methyl-3-pyridyl) thiazol-5-yl] methyl] -3-phenylpiperidine-4carbonyl] -4- piperidyl] methyl] -3-phenylisothiazolo [4,5-d] pyrimidin-7-one (Example 880).

Using General Procedure 6, starting with the Synthesis compound R3cz and the Synthesis compound R1c as reagents, Example 880 was prepared. MCBP: calculated for C ₃₉ H ₃₉ N ₇ O ₃ S ₂ : 717.2556, found: 718.2602 [(M + H) ⁺ form ].

6 - [[4-Hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -3-phenylisothiazolo [4,5-d] pyrimidin-7-one (Example 881).

Using General Procedure 7, starting with Synthesis compound R3cz and Synthesis compound R1d as reagents, Example 881 was prepared. MCBP: Calculated for C ₄₀ H ₃₉ N ₇ O ₄ S ₂ : 745.2505, Found: 746.2575 [(M + H) + form ].

7-Bromo-3 - [[4-hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine- 4-carbonyl] -4-piperidyl] methyl] pyrrolo [2.1-1] [1,2,4] triazin-4-one (Example 882).

Using General Procedure 7, starting with Synthesis compound R3cy and Synthesis compound R1d as reagents, Example 882 was prepared. MCBP: calculated for C ₃₅ H ₃₆ BrN ₇ O ₄ S: 729.1733, found: 730.1797 [(M + H) + form] ...

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7-phenylthieno [3,4-d] pyrimidin-4-one (Example 883).

Using General Procedure 7, starting from the Synthesis compound R3da and the Synthesis compound R1d as reagents, Example 883 was prepared. MCBP: calculated for C ₄ iH ₄₀ N ₆ O ₄ S ₂ : 744.2552, found: 745.2617 [(M + H) + form ].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [[2- (6-methyl-3-pyridyl) thiazol-5-yl] methyl] -3-phenylpiperidine-4-carbonyl] - 4-piperidyl] methyl] -7-phenylthieno [3,4-d] pyrimidin-4-one (Example 884).

Using General Procedure 6, starting from the Synthesis compound R3da and the Synthesis compound R1c as reagents, Example 884 was prepared. MCBP: calculated for C ₄₀ H ₄₀ N ₆ O ₃ S ₂ : 716.2603, found: 717.2680 [(M + H) + form ].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [[2- (6-methoxy-3-puridyl) thiazol-5-yl] methyl] -3-phenylpiperidine-4carbonyl] -4- piperidyl] methyl] -7-phenylthieno [3,4-d] pyrimidin-4-one (Example 885).

Using General Procedure 6, starting from the Synthesis compound R3da and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 885 was prepared. MCBP: Calculated for C40H40N6O4S2: 732.2552, Found: 733.2628 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7-phenyl-5H-pyrrolo [3,2-d] pyrimidin-4-one (Example 886).

Using General Procedure 7, starting with Synthesis compound R3db and Synthesis compound R1d as reagents, Example 886 was prepared. MCBP: calculated for C ₄₁ H ₄₁ N ₇ O ₄ S: 727.2941, found: 728.3012 [(M + H) + form] ...

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [[2- (6-methyl-3-pyridyl) thiazol-5-yl] methyl] -3-phenylpiperidine-4carbonyl] -4- piperidyl] methyl] -7-phenyl-5H-pyrrolo [3,2-d] pyrimidin-4-one (Example 887).

Using General Procedure 6, starting with Synthesis compound R3db and Synthesis compound R1c as reagents, Example 887 was prepared. MCBP: calculated for C ₄₀ H ₄ iN ₇ O ₃ S: 699.2991, found: 700.3065 [(M + H) ⁺ form] ...

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [[2- (6-methoxy-3-puridyl) thiazol-5-yl] methyl] -3-phenylpiperidine-4carbonyl] -4- piperidyl] methyl] -7-phenyl-5H-pyrrolo [3,2-d] pyrimidin-4-one (Example 888).

Using General Procedure 6, starting from the Synthesis compound R3db and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 888 was prepared. MCBP: Calculated for C ₄₀ H ₄ iN ₇ O ₄ S: 715.2941 found: 716.3013 [(M + H) + form].

7-Chloro-3 - [[4-hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenyl- 152 037563 piperidin-4-carbonyl] -4-piperidyl] methyl] thieno [3,4-d] pyrimidin-4-o n (Example 889).

Using General Procedure 7, starting from Synthesis compound R3dc and Synthesis compound R1d as reagents, Example 889 was prepared. MCBP: calculated for C ₃₅ H ₃₅ N ₆ O ₄ S2Cl: 702.185, found:

703.1921 [(M + H) + form].

7-Chloro-3 - [[4-hydroxy-1 - [(3R, 4R) -1 - [[2- (6-methyl-3-pyridyl) thiazol-5-yl] methyl] -3-phenylpiperidine 4-carbonyl ] -4-piperidyl] methyl] thieno [3,4-d] pyrimidin-4-one (Example 890).

Using General Procedure 6, starting with Synthesis compound R3dc and Synthesis compound R1c as reagents, Example 890 was prepared. MCBP: calculated for C ₃₄ H ₃₅ ClN ₆ O ₃ S ₂ : 674.1901, found: 675.1992 [(M + H) ⁺ form ].

6 - [[4-Hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4 -carbonyl] -4-piperidyl] methyl] -3-phenylisoxazolo [4,5-d] pyrimidin-7-one (Example 891).

Using General Procedure 7, starting from the Synthesis compound R3dd and the Synthesis compound R1d as reagents, Example 891 was prepared. MCBP: Calculated for C ₄₀ H ₃₉ N ₇ O ₅ S: 729.2733, Found: 730.2806 [(M + H) ⁺ Form] ...

6 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [[2- (6-methyl-3-pyridyl) thiazol-5-yl] methyl] -3-phenylpiperidine-4-carbonyl] - 4-piperidyl] methyl] -3-phenylisoxazolo [4,5-d] pyrimidin-7-one (Example 892).

Using General Procedure 6, starting with Synthesis compound R3dd and Synthesis compound R1c as reagents, Example 892 was prepared. MCBP: calculated for C ₃₉ H ₃₉ N ₇ O ₄ S: 701.2784, found: 702.2878 [(M + H) ⁺ form] ...

5 - [[1 - [(3R, 4R) -1 - [(2-Bromothiazol-5-yl) methyl] -3-phenylpiperidine-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] -1- (4-methoxyphenyl) pyrazolo [3,4-d] pyrimidin-4-one (Example 893).

Using General Procedure 6, starting from the compound Synthesis of R3de and 2-bromo-5- (bromomethyl) thiazole as reagents, Example 893 was prepared. MCBP: calculated for C ₃₄ H ₃₆ BrN ₇ O ₄ S: 717.1733, found: 718.1792 [( M + H) + form].

5 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [[2- (6-methyl-3-pyridyl) thiazol-5-yl] methyl] -3-phenylpiperidine-4carbonyl] -4- piperidyl] methyl] -1 - (4-methoxyphenyl) pyrazolo [3,4-d] pyrimidin-4-one (Example 894).

Using General Procedure 6, starting from the Synthesis compound R3de and the Synthesis compound R1c as reagents, Example 894 was prepared. MCBP: calculated for C ₄₀ H ₄₂ N ₈ O ₄ S: 730.305, found: 731.3146 [(M + H) + form] ...

5 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [[2- (6-methoxy-3-pyridyl) thiazol-5-yl] methyl] -3-phenylpiperidin-4carbonyl] -4- piperidyl] methyl] -1- (4-methoxyphenyl) pyrazolo [3,4-d] pyrimidin-4-one (Example 895).

Using General Procedure 6, starting from the Synthesis compound R3de and 5- (chloromethyl) -2- (6-methoxy-3pyridyl) thiazole as reagents, Example 895 was prepared. MCBP: Calculated for C40H42N8O5S: 746.2999, Found: 747.3071 [(M + H) + form].

5 - [[4-Hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -1- (4-methoxyphenyl) pyrazolo [3,4-d] pyrimidin-4-one (Example 896).

Using General Procedure 7, starting from the Synthesis compound R3de and the Synthesis compound R1d as reagents, Example 896 was prepared. MCBP: calculated for C ₄₁ H ₄₂ N ₈ O ₅ S: 758.2999, found: 759.3064 [(M + H) + form] ...

1- (2,3-Dihydro-1,4-benzodioxin-6-yl) -5 - [[4-hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl -3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] pyrazolo [3,4-d] pyrimidin-4-one (Example 897).

Using General Procedure 7, starting from Synthesis compound R3df and Synthesis compound R1d as reagents, Example 897 was prepared. MCBP: calculated for C ₄₂ H ₄₂ N ₈ O ₆ S: 786.2948, found: 787.3016 [(M + H) + form] ...

1- (2,3-Dihydro-1,4-benzodioxin-6-yl) -5 - [[4-hydroxy-1 - [(3R, 4R) -1 - [[2- (6-methyl-3- pyridyl) thiazol5-yl] methyl] -3-phenylpiperidin-4-carbonyl] -4-piperidyl] methyl] pyrazolo [3,4-d] pyrimidin-4-one (Example 898).

Using General Procedure 6, starting from Synthesis compound R3df and Synthesis compound R1c as reagents, Example 898 was prepared. MCBP: calculated for C ₄₁ H ₄₂ N ₈ O ₅ S: 758.2999, found: 759.3077 [(M + H) + form] ...

6-amino-3 - [[1 - [(3R, 4R) -1-benzyl-3-phenylpiperidine-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] pyrido [3,2-d] pyrimidine- 4-one (Example 899).

Example 830 (8 mg, 0.013 mmol), benzophenone imine (18 mg, 0.1 mmol), cesium carbonate (11.1 mg, 0.033 mmol), 4,5-bis (diphenylphosphino) -9,9-dimethylxanthene (1.3 mg, 0.002 mmol ), tris (dibenzylideneacetone) dipalladium (0) (1.1 mg, 0.001 mmol) was stirred in abs. toluene (3 ml) at 110 ° C for 5 h. The reaction mixture was evaporated, an aqueous solution of HCl (1N, 2 ml) and PDO (1 ml) were added to the residue, and the mixture was stirred at rt. for 3 h. The reaction mixture was purified using preparative LC (on a C-18 Gemini-NX column 5 μm, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient) to obtain Example 899. MCBP: calculated for C ₃₂ H ₃₆ N ₆ O ₃ : 552.2849, found: 551.2818 [(M + H) + form].

6-amino-3 - [[1 - [(3R, 4R) -1 - [(2-fluorophenyl) methyl] -3-phenylpiperidine-4-carbonyl] -4-hydroxy-4piperidyl] methyl] pyrido [3,2 -d] pyrimidin-4-one (Example 900).

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A solution of Example 852 (110 mg, 0.159 mmol) in TFA (3 ml) was stirred at 70 ° C for 90 min, then evaporated. The residue was purified by preparative LC (on a C-18 Gemini-NX column 5 μm, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient) to give Example 900. MCBP: calculated for C ₃₂ H ₃₅ FN ₆ O ₃ :

570.2755, found 286.1457 [(M + 2H) 2+ form].

N- [3 - [[1 - [(3R, 4R) -1 - [(2-Fluorophenyl) methyl] -3-phenylpiperudine-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] -4-oxopyrido [3,2-d] pyrimidin-6-yl] -2- (2-oxoindolin-6-yl) acetamide (Example 901).

Using General Procedure 7, starting from Example 900 as the amine component and 2- (2oxoindolin-6-yl) acetic acid as the carboxylic acid reactant, Example 901 was prepared. MCBP: Calculated for C ₄₂ H ₄₂ FN ₇ O ₅ : 743.3231 found: 372.6692 [(M + 2H) ²⁺ form].

N- [3 - [[1 - [(3R, 4R) -1 - [(2-Fluorophenyl) methyl] -3-phenylpiperidine-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] -4-oxopyrido [3,2-d] pyrimidin-6-yl] -2- (3-hydroxyphenyl) acetamide (Example 902).

Using General Procedure 7, starting from Example 900 as the amine component and 3hydroxyphenylacetic acid as the carboxylic acid reactant, Example 902 was prepared. MCBP: calculated for C ₄₀ H ₄ iFN ₆ O ₅ : 704.3122, found: 353.1636 [(M + 2H ) ²⁺ form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- (4-methyl-2-phenylthiazole-5-carbonyl) -3-phenylpiperidine-4-carbonyl] 4-piperidyl] methyl] -6 - [(4-methoxyphenyl) methylamino] pyrido [3,2-d] pyrimidin-4-one (Example 903).

Example 853 (320 mg, 0.468 mmol) was stirred in 4-methoxybenzylamine (7 ml) at 100 ° C for 4 h.The reaction mixture was purified using preparative LC (on a C-18 Gemini-NX 5 μm column, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient) to give Example 903. MCBP: calculated for C ₄₄ H ₄₅ N ₇ O ₅ S: 783.3203, found: 784.326 [(M + H) ⁺ form].

6-amino-3 - [[4-hydroxy-1 - [(3R, 4R) -1- (4-methyl-2-phenylthiazole-5-carbonyl) -3-phenylpiperidine-4carbonyl] -4-piperidyl] methyl] pyrido [3,2-d] pyrimidin-4-one (Example 904).

A solution of Example 903 (159 mg, 0.203 mmol) in TFA (3 ml) was stirred at 70 ° C for 120 min, then evaporated. The residue was purified by preparative LC (on a C-18 Gemini-NX column 5 μm, 5 mM aqueous NH4HCO3-MeCN, gradient) to give Example 904. MCBP: calculated for C ₃₆ H ₃₇ N ₇ O ₄ S: 663.2628, found: 332.6401 [(M + 2H) ²⁺ form].

N- [3 - [[4-Hydroxy-1 - [(3R, 4R) -1- (4-methyl-2-phenylthiazole-5-carbonyl) -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl ] -4-oxopyrido [3,2-d] pyrimidin-6-yl] -2- (2-oxoindolin-6-yl) acetamide (Example 905).

Using General Procedure 7, starting from Example 904 as the amine component and 2- (2oxoindolin-6-yl) acetic acid as the carboxylic acid reactant, Example 905 was prepared. MCBP: Calculated for C ₄₆ H ₄₄ N ₈ O ₆ S: 836.3105, found: 837.3173 [(M + H) + form].

N- [3 - [[4-Hydroxy-1 - [(3R, 4R) -1- (4-methyl-2-phenylthiazole-5-carbonyl) -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl ] -4-oxopyrido [3,2-d] pyrimidin-6-yl] -2- (3-hydroxyphenyl) acetamide (Example 906).

Using General Procedure 7, starting from Example 904 as the amine component and 3-hydroxyphenylacetic acid as the carboxylic acid reactant, Example 906 was prepared. MCBP: Calculated for C ₄₄ H ₄₃ N ₇ O ₆ S: 797.2996, Found: 798.3073 [(M + H) + form].

N- [3 - [[4-Hydroxy-1 - [(3R, 4R) -1- (4-methyl-2-phenylthiazole-5-carbonyl) -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl ] -4-oxopyrido [3,2-d] pyrimidin-6-yl] -2-phenylαcetamide (Example 907).

Using General Procedure 7, starting from Example 904 as the amine component and phenylacetic acid as the α-carboxylic acid reactant, Example 907 was prepared. MCBP: calculated for C4zH4 ₃ N ₇ O5S: 781.3046, found: 782.3136 [(M + H) + form ].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [[2- (6-methyl-3-pyridyl) thiazol-5-yl] methyl] -3-phenylpiperidine-4carbonyl] -4- piperidyl] methyl] -7-phenylpyrrolo [2,1-f] [1,2,4] triαzin-4-one (Example 908).

Using General Procedure 9, starting from Example 879 as reactant and phenylboronic acid as reactant, Example 908 was prepared. MCBP: calculated for C ₄₀ H ₄ iN ₇ O ₃ S: 699.2991, found: 700.3034 [(M + H) + form ].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-puridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7-phenylpyrrolo [2,1-G | [1,2,4] triazin-4-one (Example 909).

Using General Procedure 9, starting from Example 882 as reactant and phenylboronic acid as reagent, Example 909 was prepared. MCBP: calculated for C ₄₁ H ₄₁ N ₇ O ₄ S: 727.2941, found: 728.3013 [(M + H) + form ].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-puridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -5-methyl-7-phenylpyrrolo [3,2-d] pyrimidin-4-one (Example 910).

A suspension of Example 886 (0.052 mmol), iodomethane (6.5 μl, 0.104 mmol) and K ₂ CO ₃ (14.4 mg, 0.104 mmol) in DMF (1 ml) was stirred at rt. during the night. The reaction mixture was filtered through a syringe filter and purified by preparative LC (on a C-18 Gemini-NX column 5 μm, 5 mM aqueous NH4HCO3-MeCN, gradient) to give Example 910. MCBP: calculated for C42H43N7O4S: 741.3098, found: 742.3171 [ (M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [[2- (6-methyl-3-pyridyl) thiazol-5-yl] methyl] -3-phenylpiperidine-4carbonyl] -4- piperidyl] methyl] -7- (1-methylpyrrol-3-yl) thieno [3,4-d] pyrimidin-4-one (Example 911).

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Using General Procedure 9, starting from Example 890 and 1-methyl-3- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyrrole as reagents, Example 911 was prepared. MCBP: calculated for

C ₃₉ H ₄₁ N ₇ O ₃ S ₂ : 719.2712, found: 718.2672 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [[2- (6-methyl-3-pyridyl) thiazol-5-yl] methyl] -3-phenylpiperidine-4carbonyl] -4- piperidyl] methyl] -7- (1-methylpyrazol-4-yl) thieno [3,4-d] pyrimidin-4-one (Example 912).

Using General Procedure 9, starting from Example 890 and 1-methyl-4- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) pyrazole as reagents, Example 912 was prepared. MCBP: Calculated for C ₃₈ H ₄₀ N ₈ O ₃ S ₂ : 720.2665, found: 721.2703 [(M + H) ⁺ form].

7- (3-Furyl) -3 - [[4-hydroxy-1 - [(3R, 4R) -1 - [[2- (6-methyl-3-pyridyl) thiazol-5-yl] methyl] -3 -phenylpiperidin-4-carbonyl] -4-piperidyl] methyl] thieno [3,4-d] pyrimidin-4-o n (Example 913).

Using General Procedure 9, starting from Example 890 and 2- (3-furyl) -4,4,5,5-tetramethyl-1,3,2-dioxaborolane as reagents, Example 913 was prepared. MCBP: Calculated for C ₃₈ H ₃₈ N ₆ O ₄ S ₂ : 706.2396, found: 707.2448 [(M + H) ⁺ form].

7- [4- (Hydroxymethyl) phenyl] -3 - [[4-hydroxy-1 - [(3R, 4R) -1 - [[2- (6-methyl-3-pyridyl) thiazol-5-yl] methyl ] -3-phenylpiperidin-4-carbonyl] -4-piperidyl] methyl] thieno [3,4-d] pyrimidin-4-one (Example 914).

Using General Procedure 9, starting from Example 890 and [4- (hydroxymethyl) phenyl] boronic acid as reactants, Example 914 was prepared. MCBP: calculated for C ₄ iH ₄₂ N ₆ O ₄ S ₂ : 746.2709, found: 747.2782 [( M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [[2- (6-methyl-3-pyridyl) thiazol-5-yl] methyl] -3-phenylpiperidine-4carbonyl] -4- piperidyl] methyl] -7- (1-methylpyrrol-3-yl) pyrrolo [2,1-f] [1,2,4] triazin-4-one (Example 915).

Using General Procedure 9, starting from Example 879 as reactant and 1-methyl-3- (4,4,5,5tetramethyl-1,3,2-dioxaborolan-2-yl) pyrrole as reagent, Example 915 was prepared. MCBP : calculated for C ₃₉ H ₄₂ N ₈ O ₃ S: 702.3101, found: 703.3187 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [[2- (6-methyl-3-pyridyl) thiazol-5-yl] methyl] -3-phenylpiperidine-4carbonyl] -4- piperidyl] methyl] -7- (1-methylpyrazol-4-yl) pyrrolo [2,1-f] [1,2,4] triazin-4-one (Example 916).

Using General Procedure 9, starting from Example 879 as reactant and 1-methyl-4- (4,4,5,5tetramethyl-1,3,2-dioxaborolan-2-yl) pyrazole as boronic acid reactant, Example 916. MCBP calculated for C ₃₈ H ₄₁ N ₉ O ₃ S: 703.3053, found: 704.3159 [(M + H) + form].

7- (3-Furyl) -3 - [[4-hydroxy-1 - [(3R, 4R) -1 - [[2- (6-methyl-3-pyridyl) thiazol-5-yl] methyl] -3 -phenylpiperidin-4-carbonyl] -4-piperidyl] methyl] pyrrolo [2,1-f | [1,2,4] triazin-4-one (Example 917).

Using General Procedure 9, starting from Example 879 as reactant and 2- (3-furyl) -4,4,5,5tetramethyl-1,3,2-dioxaborolane as boronic acid reagent, Example 917 was prepared. MCBP: Calculated for C ₃₈ H ₃₉ N ₇ O ₄ S: 689.2784, found: 690.2875 [(M + H) + form].

7- (2-Furyl) -3 - [[4-hydroxy-1 - [(3R, 4R) -1 - [[2- (6-methyl-3-pyridyl) thiazol-5-yl] methyl] -3 -phenylpiperidin-4-carbonyl] -4-piperidyl] methyl] pyrrolo [2,1-f] [1,2,4] triazin-4-one (Example 918).

Using General Procedure 9, starting from Example 879 as reactant and 2-furylboronic acid as boronic acid reactant, Example 918 was prepared. MCBP: Calculated for C ₃₈ H ₃₉ N ₇ O ₄ S: 689.2784, Found: 690.2865 [(M + H) + form].

7- [4- (Hydroxymethyl) phenyl] -3 - [[4-hydroxy-1 - [(3R, 4R) -1 - [[2- (6-methyl-3-pyridyl) thiazol-5-yl] methyl ] -3-phenylpiperidin-4-carbonyl] -4-piperidyl] methyl] pyrrolo [2,1-f] [1,2,4] triazin-4-one (Example 919).

Using General Procedure 9, starting from Example 879 as reactant and [4- (hydroxymethyl) phenyl] boronic acid as α-boronic acid reactant, Example 919 was prepared. MCBP: Calculated for C ₄ iH ₄₃ N ₇ O ₄ S: 729.3098, found: 730.3161 [(M + H) + form].

6-Chloro-7- (4-chloro-3-fluorophenyl) -3 - [[4-hydroxy-1 - [(3R, 4R) -1 - [[2- (6-methyl-3-pyridyl) thiazole- 5-yl] methyl] -3-phenylpiperidin-4-kαcarbonyl] -4-piperidyl] methyl] purrolo [2,3-d] purimidin-4-one (Example 920).

Using General Procedure 6, starting with Synthesis compound R3dg and Synthesis compound R1c as reagents, Example 920 was prepared. MCBP: Calculated for C ₄₀ H ₃₈ Cl ₂ FN ₇ O ₃ S: 785.2118, Found: 786.2163 [(M + H) + the form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [[2- (6-methyl-3-pyridyl) thiazol-5-yl] methyl] -3-phenylpiperidine-4carbonyl] -4- piperidyl] methyl] -6-methyl-7-phenylpyrrolo [2,3-d] pyrimidin-4-one (Example 921).

Using General Procedure 6, starting with Synthesis compound R3dh and Synthesis compound R1c as reagents, Example 921 was prepared. MCBP: calculated for C ₄₁ H ₄₃ N ₇ O ₃ S: 713.3148, found: 714.3208 [(M + H) + form] ...

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -9-methylpyrimido [4,5-b] indol-4-one (Example 922).

Using General Procedure 7, starting from the Synthesis compound R3di and the Synthesis compound R1d as reagents, Example 922 was prepared. MCBP: calculated for C ₄₀ H ₄ iN ₇ O ₄ S: 715.2941, found: 716.3047 [(M + H) + form] ...

3 - [(4-Hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -6,8-dimethylpyrimido [5 ', 4': 4,5] pyrrolo [1,2b] pyridazin-4 (3H) -one (Example 923).

Using General Procedure 7, starting with Synthesis compound R3dj and Synthesis compound R1d as reagents 155 037563, Example 923 was prepared. MCBP: Calculated for C ₄₀ H ₄₂ N ₈ O ₄ S: 730.305, Found: 731.3134

[(M + H) + form].

3 - [[4-hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-pyrigyl) thiazole-5-carbonyl] -3-phenylpiperidine4-carbonyl] -4 -piperidyl] methyl] -6-methyl-7-phenylpyrrolo [2,3-d] pyrimidin-4-one (Example 924).

Using General Procedure 7, starting with Synthesis compound R3dh and Synthesis compound R1d as reagents, Example 924 was prepared. MCBP: calculated for C ₄₂ H ₄₃ N ₇ O ₄ S: 741.3098, found: 742.3179 [(M + H) ⁺ form] ...

6-chloro-3 - [[4-hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine- 4-carbonyl] -4-piperidyl] methyl] -7-phenylpyrrolo [2,3-d] pyrimidin-4-o n (Example 925).

Using General Procedure 7, starting with Synthesis compound R3dk and Synthesis compound R1d as reagents, Example 925 was prepared. MCBP: calculated for C ₄ iH _{40 ClN 7} O ₄ S: 761.2551, found: 762.2633 [(M + H) ⁺ form] ...

3 - [[1 - [(3R, 4R) -1- [3-Fluoro-5- (2-methyl-4-pyridyl) thiophene-2-carbonyl] -3-phenylpiperidine-4-carbonyl] -4-hydroxy -4-piperidyl] methyl] -7-methyl-6- (2-thienyl) pyrrolo [2,3-d] pyrimidin-4-one (Example 926).

Using General Procedure 9, starting from the Synthesis compound R3dl as a halogenated reactant and 2-thienylboronic acid as a reagent - boronic acid, 3 - [(4hydroxy-1 - {[(3R, 4R) -3-phenylpiperidin-4-yl ] carbonyl} piperidin-4-yl) methyl] -7-methyl-6- (thiophen-2yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one. This intermediate was reacted with the Synthesis compound R1g according to General Procedure 7, and the crude iodine compound was reacted according to General Procedure 9 with (2-methyl-4-pyridyl) boronic acid to give Example 926. MCBP: calculated for C ₄₀ H ₃₉ FN ₆ O ₄ S ₂ : 750.2458, found: 751.2537 [(M + H) + form].

N - [[3 - [[1 - [(3R, 4R) -1 - [(3-Fluorophenyl) methyl] -3-phenylpiperidine-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] -4- oxo-7H-pyrrolo [2,3-d] pyrimidin-6-yl] methyl] acetamide (Example 927).

2 - [(4-Chloropyrrolo [2,3-d] pyrimidin-7-yl) methoxy] ethyltrimethylsilane (3.5 g, 12.3 mmol) was dissolved in abs. THF (55 ml) and cooled to -78 ° C, then LDA (2.0 M, 6.8 ml, 13.6 mmol) was added to the mixture and stirred at -78 ° C for 40 min, then iodine (3.13 g, 12.3 mmol) and stirring was continued at -78 ° C for 3 h. Water (25 ml) was added to the reaction mixture and extracted with EEO (2 x 30 ml). The combined organic layers were evaporated, loaded onto celite and purified by flash chromatography (heptane-EEO, gradient).

Part of the crude product (2.38 g, 5.81 mmol) and lithium hydroxide hydrate (2.44 g, 58.1 mmol) were dissolved in a mixture of PDO and water (30 ml, v / v = 1: 1) and stirred at 100 ° C for 70 h. The reaction mixture was acidified with 1N. aqueous HCl solution. The resulting solid compound was filtered off, washed with water and dried.

The pyrimidone product was reacted using General Procedure 5 with the Synthesis compound R1e as the epoxy component.

Crude product (3.5 g, 5.79 mmol), copper (I) cyanide (2.18 g, 24.32 mmol), tetraethylammonium cyanide (950 mg, 6.08 mmol), tris (dibenzylideneacetone) dipalladium (0) (531 mg, 0.58 mmol), and 1,1'-bis (diphenylphosphino) ferrocene (1.29 g, 2.32 mmol) was dissolved in abs. PDO (45 ml) and the mixture was stirred at 110 ° C for 2.3 h. The reaction mixture was filtered, the filtrate was evaporated, the residue was diluted with MeOH (15 ml) and then filtered again. The filtrate was evaporated, loaded onto celite and purified by flash chromatography (DCM-MeOH, gradient).

The resulting Boc-protected cyanoproduct (2.42 g, 4.81 mmol) was deprotected by stirring in a mixture of TFA (1.11 mL, 14.47 mmol), formic acid (6.29 mL, 166.6 mmol), and DCM (60 mL) at RT. _{over 52 h. K 2} CO ₃ (25 g) and DCM (180 ml) were added to the reaction mixture and extracted with water (2x 160 ml). The organic layer was evaporated.

The crude piperidine product was reacted with (3R, 4R) -1-tert-butoxycarbonyl-3-phenylpiperidine-4-carboxylic acid using General Procedure 7.

The resulting Boc-protected product (798 mg, 1.16 mmol) was deprotected by stirring in a mixture of TFA (266 μl, 3.48 mmol), formic acid (503 μl, 13.3 mmol) and DCM (15 ml) at RT. over 164 h. K ₂ CO ₃ (2.8 g) was added to the reaction mixture and extracted with water (2x75 ml). The organic layer was evaporated.

The crude piperidine product was reacted with 3-fluorobenzyl chloride according to General Procedure 6.

The resulting crude product (534 mg, 0.76 mmol) and Raney nickel (240 mg) were stirred in a solution of ammonia in methanol (7 M, 15 ml) under a hydrogen atmosphere (2 bar) for 68 h. The reaction mixture was filtered, the filtrate was evaporated ...

The crude aminomethyl product was reacted with acetic acid according to General Procedure 7.

The resulting product (85.7 mg, 0.115 mmol) was stirred in a solution of TBAF (1 M in THF, 223 μL, 0.223 mmol) and THF (0.5 mL) at 75 ° C for 65 h. The reaction mixture was purified using preparative LC (on column C-18 Gemini-NX 10 μm, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient 156 037563 ents) to obtain Example 927. MCBP: calculated for C ₃₄ H ₃₉ FN ₆ O ₄ : 614.3017, found: 615.3082

[(M + H) + form].

3 - [[4-Hydroxy- 1 - [(3R, 4R) -3-phenyl-1 - (p-tolylmethyl) piperidine-4-carbonyl] -4-piperidyl] methyl] -6 (2-thienyl) - 7H-pyrrolo [2,3-d] pyrimidin-4-one (Example 928).

2 - [(4-Chloropyrrolo [2,3-d] pyrimidin-7-yl) methoxy] ethyltrimethylsilane (3.5 g, 12.3 mmol) was dissolved in THF (abs, 55 ml) and cooled to -78 ° C, then to the mixture LDA (2.0 M, 6.8 mL, 13.6 mmol) was added and stirred at -78 ° C for 40 min, then iodine (3.13 g, 12.3 mmol) was added to the mixture and stirring was continued at -78 ° C for 3 h. the reaction mixture was added water (25 ml) and was extracted with EEO (2x30 ml). The combined organic layers were evaporated, loaded onto celite and purified by flash chromatography (heptane-EEO, gradient).

Part of the crude product (2.0 g, 4.88 mmol) and lithium hydroxide hydrate (2.05 g, 48.8 mmol) were dissolved in a mixture of PDO and water (30 ml, v / v = 1: 1) and stirred at 100 ° C for 65 h. The reaction mixture was acidified with 1N. aqueous HCl solution. The resulting solid compound was filtered off, washed with water and dried.

The pyrimidone product was reacted using General Procedure 5 with the Synthesis compound R1e as the epoxy component.

The resulting Boc-protected product (930 mg, 1.54 mmol) was deprotected by stirring in a mixture of TFA (363 μL, 4.74 mmol), formic acid (2.06 mL, 54.6 mmol), and DCM (18.6 mL) at RT. over 46 h. K2CO3 (6.5 g) was added to the reaction mixture and extracted with water (2 x 80 ml). The organic layers were evaporated and the residue was triturated with water (5 ml) to give a solid compound, which was filtered off and dried.

The crude piperidine product was reacted with (3R, 4R) -1-tert-butoxycarbonyl-3-phenylpiperidine-4-carboxylic acid using General Procedure 7.

The crude Boc-protected product (647 mg, 0.82 mmol) was deprotected by stirring in a mixture of TFA (188 μL, 2.46 mmol), formic acid (356 μL, 9.43 mmol) and DCM (13 mL) at RT. over 214 h. K2CO3 (1.99 g) was added to the reaction mixture. The solution was extracted with water (2x70 ml) and the organic layer was evaporated.

The crude product was N-alkylated with 4-methylbenzyl chloride according to General Procedure 6.

Crude alkylated compound (165 mg, 0.21 mmol), 2-thienylboronic acid (41 mg, 0.32 mmol), lithium chloride (27 mg, 0.63 mmol) and [1,1'-bis (diphenylphosphino) ferrocene] dichloropalladium (I) ( 15 mg, 0.021 mmol) was dissolved in an aqueous solution of Na ₂ CO ₃ (2 M, 265 μL, 0.53 mmol), toluene (4 mL), and EtOH (4 mL) and stirred at 80 ° C for 23 h. The insoluble part was filtered off , the filtrate was evaporated and the residue was purified using preparative LC (on a C-18 Gemini-NX 10 μm column, 25 mM aqueous NH ₄ HCO ₃ -MeCN, gradient).

The resulting product (72 mg, 0.096 mmol) was stirred in a solution of TBAF (1 M in THF, 144 μL, 0.144 mmol) and THF (0.5 mL) at 75 ° C for 65 h. The reaction mixture was purified using preparative LC ( on a column C-18 Gemini-NX 10 μm, 5 mM aqueous NH4HCO3-MeCN, gradient) to obtain Example 928. MCBP: calculated for C ₃₆ H ₃₉ N ₅ O ₃ S: 621.2773, found: 622.2846 [(M + H) + form].

3 - [[4-Hydroxy- 1 - [(3R, 4R) -3-phenyl-1 - (p-tolylmethyl) piperidine-4-carbonyl] -4-piperidyl] methyl] -6 (3-thienyl) - 7H-pyrrolo [2,3-d] pyrimidin-4-one (Example 929).

2 - [(4-Chloropyrrolo [2,3-d] pyrimidin-7-yl) methoxy] ethyltrimethylsilane (3.5 g, 12.3 mmol) was dissolved in THF (abs, 55 ml) and cooled to -78 ° C, then to the mixture LDA (2.0 M, 6.8 mL, 13.6 mmol) was added and stirred at -78 ° C for 40 min, then iodine (3.13 g, 12.3 mmol) was added to the mixture and stirring was continued at -78 ° C for 3 h. the reaction mixture was added water (25 ml) and was extracted with EEO (2 x 30 ml). The combined organic layers were evaporated, loaded onto celite and purified by flash chromatography (heptane-EEO, gradient).

Part of the crude product (2.0 g, 4.88 mmol) and lithium hydroxide hydrate (2.05 g, 48.8 mmol) were dissolved in a mixture of PDO and water (30 ml, v / v = 1: 1) and stirred at 100 ° C for 65 h. The reaction mixture was acidified with 1N. aqueous HCl solution. The resulting solid compound was filtered off, washed with water and dried.

The pyrimidone product was reacted using General Procedure 5 with the Synthesis compound R1e as the epoxy component.

The resulting Boc-protected product (930 mg, 1.54 mmol) was deprotected by stirring in a mixture of TFA (363 μL, 4.74 mmol), formic acid (2.06 mL, 54.6 mmol), and DCM (18.6 mL) at RT. over 46 h. K2CO3 (6.5 g) was added to the reaction mixture and extracted with water (2 x 80 ml). The organic layers were evaporated and the residue was triturated with water (5 ml) to give a solid compound, which was filtered off and dried.

The crude piperidine product was reacted with (3R, 4R) -1-tert-butoxycarbonyl-3-phenylpiperidine-4-carboxylic acid using General Procedure 7.

The crude Boc-protected product (647 mg, 0.82 mmol) was deprotected by stirring in

- 157 037563 mixture of TFA (188 μl, 2.46 mmol), formic acid (356 μl, 9.43 mmol) and DCM (13 ml) at rt. over 214 h. K ₂ CO ₃ (1.99 g) was added to the reaction mixture. The solution was extracted with water (2 x 70 ml) and the organic layer was evaporated.

The crude product was N-alkylated with 4-methylbenzyl chloride according to General Procedure 6.

Crude alkylated compound (170 mg, 0.21 mmol), 4,4,5,5-tetramethyl-2- (3-thienyl) -1,3,2 dioxaborolane (67 mg, 0.32 mmol), lithium chloride (27 mg, 0.63 mmol ) and [1,1'-bis (diphenylphosphino) ferrocene] dichloropalladium (P) (15 mg, 0.021 mmol) were dissolved in an aqueous solution of Na ₂ CO ₃ (2 M, 265 μL, 0.53 mmol), toluene (4 ml) and EtOH (4 ml) and stirred at 80 ° C for 23 h. The insoluble part was filtered off, the filtrate was evaporated, and the residue was purified using preparative LC (on a C-18 Gemini-NX column 5 μm, 5 mM aqueous NH ₄ HCO ₃ -MeCN , gradient).

The resulting product (72 mg, 0.096 mmol) was stirred in a solution of TBAF (1 M in THF, 144 μL, 0.144 mmol) and THF (0.5 mL) at 75 ° C for 60 h. The reaction mixture was purified using preparative LC ( on the C-18 Gemini-NX column 10 μm, 5 mM aqueous NH4HCO ₃ -MeCN, gradient) to obtain Example 929. MCBP: calculated for C3 ₆ H39N ₅ O ₃ S: 621.2773, found: 622.2834 [(M + H) + the form].

6- (2-Fluorophenyl) -3 - [[4-hydroxy-1 - [(3R, 4R) -3-phenyl-1- (p-tolylmethyl) piperidine-4-carbonyl] -4piperidyl] methyl] -7H- pyrrolo [2,3-d] pyrimidin-4-one (Example 930).

2 - [(4-Chloropyrrolo [2,3-d] pyrimidin-7-yl) methoxy] ethyltrimethylsilane (3.5 g, 12.3 mmol) was dissolved in THF (abs, 55 ml) and cooled to -78 ° C, then to the mixture LDA (2.0 M, 6.8 mL, 13.6 mmol) was added and stirred at -78 ° C for 40 min, then iodine (3.13 g, 12.3 mmol) was added to the mixture and stirring was continued at -78 ° C for 3 h. the reaction mixture was added water (25 ml) and was extracted with EEO (2x30 ml). The combined organic layers were evaporated, loaded onto celite and purified by flash chromatography (heptane-EEO, gradient).

Part of the crude product (2.0 g, 4.88 mmol) and lithium hydroxide hydrate (2.05 g, 48.8 mmol) were dissolved in a mixture of PDO and water (30 ml, v / v = 1: 1) and stirred at 100 ° C for 65 h. The reaction mixture was acidified with 1N. aqueous HCl solution. The resulting solid compound was filtered off, washed with water and dried.

The pyrimidone product was reacted using General Procedure 5 with the Synthesis compound R1e as the epoxy component.

The resulting Boc-protected product (930 mg, 1.54 mmol) was deprotected by stirring in a mixture of TFA (363 μL, 4.74 mmol), formic acid (2.06 mL, 54.6 mmol), and DCM (18.6 mL) at RT. over 46 h. K ₂ CO ₃ (6.5 g) was added to the reaction mixture and extracted with water (2 x 80 ml). The organic layers were evaporated and the residue was triturated with water (5 ml) to give a solid compound, which was filtered off and dried.

The crude piperidine product was reacted with (3R, 4R) -1-tert-butoxycarbonyl-3-phenylpiperidine-4-carboxylic acid using General Procedure 7.

The crude Boc-protected product (647 mg, 0.82 mmol) was deprotected by stirring in a mixture of TFA (188 μL, 2.46 mmol), formic acid (356 μL, 9.43 mmol) and DCM (13 mL) at RT. over 214 h. K ₂ CO ₃ (1.99 g) was added to the reaction mixture. The solution was extracted with water (2x70 ml) and the organic layer was evaporated.

The crude product was N-alkylated with 4-methylbenzyl chloride according to General Procedure 6.

Crude alkylated compound (170 mg, 0.21 mmol), 2-fluorophenylboronic acid (44 mg, 0.32 mmol), lithium chloride (27 mg, 0.63 mmol) and [1,1'-bis (diphenylphosphino) ferrocene] dichloropalladium (II) ( 15 mg, 0.021 mmol) was dissolved in an aqueous solution of Na ₂ CO ₃ (2 M, 265 μL, 0.53 mmol), toluene (4 mL), and EtOH (4 mL) and stirred at 80 ° C for 22 h. The insoluble part was filtered off , the filtrate was evaporated and the residue was purified using preparative LC (on a C-18 GeminiNX 5 μm column, 5 mM aqueous NH ₄ HCO ₃ -MeCN, gradient).

The resulting product (70 mg, 0.09 mmol) was stirred in a solution of TBAF (1 M in THF, 138 μL, 0.138 mmol) and THF (0.5 mL) at 75 ° C for 60 h. The reaction mixture was purified using preparative LC ( on a C-18 Gemini-NX column 10 μm, 5 mM aqueous NH4HCO3-MeCN, gradient) to give Example 930. MCBP: calculated for C3 ₈ H ₄₀ FN ₅ O ₃ : 633.3115, found: 634.3194 [(M + H) + the form].

5-Fluoro-3 - [[4-hydroxy- 1 - [(3R, 4R) -1 - (4-methyl-2-phenylthiazole-5-carbonyl) -3-phenylpiperidine-4carbonyl] -4-piperidyl] methyl] -7-methylpyrrolo [2,3-d] pyrimidin-4-one (Example 931).

Using General Procedure 11, starting from the compound Synthesis of R2dj and (4-methyl-2-phenyl-1,3-thiazol5-yl) [(3R, 4R) -4- (1-oxa-6-azaspuro [2.5] oct- 6-ylcarbonyl) -3-phenylpiperidin-1-yl] methanone as reagents prepared Example 931. MCBP: calculated for C ₃₆ H ₃₇ FN ₆ O ₄ S: 668.2581, found: 669.2649 [(M + H) + form] ...

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-nyridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7,8-dihydro-6H-pyrimido [5,4-b] pyrrolizin-4-one (Example 932).

Using General Procedure 11, starting from the Synthesis compound R2dk and the Synthesis compound R1m in

- 158 037563 as reagents, received Example 932. MCBP: calculated for C ₃₈ H ₄₁ N ₇ O ₄ S: 691.2941, found:

346.6539 [M + 2H) ²⁺ form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -6,7,8,9-tetrahydropyrimido [5,4-b] indolizin-4-one (Example 933).

Using General Procedure 11, starting from Synthesis compound R2dl and Synthesis compound R1m as reagents, Example 933 was prepared. MCBP: calculated for C ₃₉ H ₄₃ N ₇ O ₄ S: 705.3098, found: 706.3172 [(M + H) ⁺ form] ...

3 - [[1 - [(3R, 4S) -1-Benzyl-3- (2-mienyl) piperigin-4-kαarbonyl] -4-hydroxy-4-piperigyl] methyl] -7Hpyrrolo [2,3-d] pyrimidin-4-one (Example 934).

Using General Procedure 5, starting from 3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one and Synthesis compound R1e as the epoxy component, the crude product was reacted with Synthesis compound R1q- (3R, 4S) in following General Procedure 7 to give Example 934. MCBP: calculated for C ₂₉ H ₃₃ N ₅ O ₃ S: 531.2304, found: 532.2388 [(M + H) + form].

3 - [[1 - [(3 S, 4R) -1-Benzyl-3 - (2-thienyl) piperidine-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] -7Hpyrrolo [2,3-d ] pyrimidin-4-one (Example 935)

Using General Procedure 5, starting from 3H, 4H, 7H-pyrrolo [2,3-d] pyrimidin-4-one and Synthesis compound R1e as the epoxy component, the crude product was reacted with Synthesis compound R1q- (3S, 4R) in following General Procedure 7 to give Example 935. MCBP: calculated for C ₂₉ H ₃₃ N ₅ O ₃ S: 531.2304, found: 532.2388 [(M + H) ⁺ form].

3 - [[1 - [(3R, 4S) -1-Benzyl-3- (2-thienyl) piperidine-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] -6methyl-7H-pyrrolo [2, 3-d] pyrimidin-4-one (Example 936).

2 - [(4-Chloropyrrolo [2,3-d] pyrimidin-7-yl) methoxy] ethyltrimethylsilane (600 mg, 2.11 mmol) was dissolved in abs. THF (12 ml) and cooled to -78 ° C, then a LDA solution (2.0 M, 1.2 ml, 2.4 mmol) was added to the mixture and stirred at -78 ° C for 1 h, then iodomethane (158 μl, 2.53 mmol), and stirring was continued at -78 ° C for 3 h. Water (10 ml) was added to the reaction mixture and extracted with EEO (2x20 ml). The combined organic layers were evaporated and purified by preparative LC (on a C-18 Gemini-NX 5 μm column, 5 mM aqueous NH4HCO ₃ -MeCN, gradient).

Part of the crude product (300 mg, 1.01 mmol) and lithium hydroxide hydrate (423 mg, 10.1 mmol) were dissolved in a mixture of PDO and water (4 ml, v / v = 1: 1) and stirred at 100 ° C for 142 h. The reaction mixture was acidified with an aqueous solution of HCl (1N, 9.5 ml). The resulting solid compound was filtered off, washed with water and dried.

Using General Procedure 5, starting with the crude product and the Synthesis compound R1e as the epoxy component, the resulting product (140 mg, 0.28 mmol) was then stirred in a TBAF solution (1 M in THF, 1.4 mL, 1.4 mmol) at 90 ° C. over 24 h. Water (5 ml) was added to the reaction mixture and extracted with EEO (2x10 ml). The combined organic layers were extracted with water (2x10 ml), dried over MgSO ₄ and evaporated. The residue was purified by preparative LC (on a C-18 Gemini-NX 10 μm column, 25 mM aqueous NH ₄ HCO ₃ -MeCN, ISO39).

The resulting desilylated product (23.5 mg, 0.065 mmol) was stirred in a mixture of an aqueous solution of HCl (0.65 ml) and PDO (0.5 ml) at 60 ° C for 4 h. The reaction mixture was evaporated.

The crude product was reacted with the Synthesis compound R1q- (3R, 4S) according to General Procedure 7 to give Example 936. MCBP: calculated for C ₃₀ H ₃₅ N ₅ O ₃ S: 545.2460, found: 546.2546 [(M + H) + form].

3 - [[1 - [(3 S, 4R) -1-Benzyl-3 - (2-thienyl) piperidine-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] -6methyl-7H-pyrrolo [2 , 3-d] pyrimidin-4-one (Example 937).

2 - [(4-Chloropyrrolo [2,3-d] pyrimidin-7-yl) methoxy] ethyltrimethylsilane (600 mg, 2.11 mmol) was dissolved in abs. THF (12 ml) and cooled to -78 ° C, then LDA (2.0 M, 1.2 ml, 2.4 mmol) was added to the mixture and stirred at -78 ° C for 1 h, then iodomethane (158 μL, 2.53 mmol) and stirring was continued at -78 ° C for 3 h. Water (10 ml) was added to the reaction mixture and extracted with EEO (2x20 ml).

The combined organic layers were evaporated and purified by preparative LC (C-18 Gemini-NX 5 μm column, 5 mM aqueous NH4HCO3-MeCN, gradient).

Part of the crude product (300 mg, 1.01 mmol) and lithium hydroxide hydrate (423 mg, 10.1 mmol) were dissolved in a mixture of PDO and water (4 ml, v / v = 1: 1) and stirred at 100 ° C for 142 h. The reaction mixture was acidified with an aqueous solution of HCl (1N, 9.5 ml) The resulting solid compound was filtered off, washed with water and dried.

Using General Procedure 5, starting with the crude product and the Synthesis compound R1e as the epoxy component, the resulting product (140 mg, 0.28 mmol) was then stirred in a TBAF solution (1 M in THF, 1.4 mL, 1.4 mmol) at 90 ° C. over 24 h. Water (5 ml) was added to the reaction mixture and extracted with EEO (2x10 ml). The combined organic layers were extracted with 159 037563 water (2x10 ml), dried over MgSO ₄ and evaporated. The residue was purified by preparative LC (on a C-18 Gemini-NX 10 μm column, 25 mM aqueous NH ₄ HCO ₃ -MeCN, ISO39).

The resulting desilylated product (23.5 mg, 0.065 mmol) was stirred in a mixture of an aqueous solution of HCl (0.65 ml) and PDO (0.5 ml) at 60 ° C for 4 h. The reaction mixture was evaporated.

The crude product was reacted with the Synthesis compound R1q- (3S, 4R) according to General Procedure 7 to give Example 937. MCBP: calculated for C ₃₀ H ₃₅ N ₅ O ₃ S: 545.246, found: 546.2527 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7- (1-methylpyrazol-4-yl) pyrrolo [2,1-f] [1,2,4] triazin-4-one (Example 938).

Using General Procedure 7, starting from the Synthesis compound R3cy and the Synthesis compound R1d as reagents, the resulting crude product was reacted with 1-methyl-4- (4,4,5,5 tetramethyl-1,3,2-dioxaborolane-2 -yl) pyrazole according to General Procedure 9 to give Example 938. MCBP: calculated for C ₃₉ H ₄ iN ₉ O ₄ S: 731.3002, found: 732.3057 [(M + H) + form].

7- (3-Furyl) -3 - [[4-hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] - 3phenylpiperidin-4-carbonyl] -4-piperidyl] methyl] pyrrolo [2,1-f] [1,2,4] triazin-4-one (Example 939).

Using General Procedure 7, starting from the Synthesis compound R3cy and the Synthesis compound R1d as reagents, the resulting crude product was reacted with 2- (3-furyl) -4,4,5,5 tetramethyl-1,3,2-dioxaborolane in following General Procedure 9 to give Example 939. MCBP: calculated for C ₃₉ H ₃₉ N ₇ O ₅ S: 717.2734, found: 718.2804 [(M + H) + form].

7- (3-Furyl) -3 - [[4-hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] - 3phenylpiperidin-4-carbonyl] -4-piperidyl] methyl] thieno [3,4-d] pyrimidin-4-one (Example 940).

Using General Procedure 7, starting from the Synthesis compound R3dc and the Synthesis compound R1d as reagents, the resulting crude product was reacted with 2- (3-furyl) -4,4,5,5 tetramethyl-1,3,2-dioxaborolane in following General Procedure 9 to give Example 940. MCBP: calculated for C ₃₉ H ₃₈ N ₆ O ₅ S ₂ : 734.2345, found: 735.2417 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4carbonyl] -4 -piperzdyl] methyl] -7- (1-methylpyrazol-4-yl) thieno [3,4-d] pyrimzdin-4-one (Example 941).

Using General Procedure 7, starting from the Synthesis compound R3dc and the Synthesis compound R1d as reagents, the resulting crude product was reacted with 1-methyl-4- (4,4,5,5 tetramethyl-1,3,2-dioxaborolane-2 -yl) pyrazole according to General Procedure 9 to give Example 941. MCBP: calculated for C ₃₉ H ₄₀ N ₈ O ₄ S ₂ : 748.2614, found: 749.2704 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7- [4- (hydroxymethyl) phenyl] pyrrolo [2,1-G] [1,2,4] triazin-4-one (Example 942).

Using General Procedure 7, starting with Synthesis compound R3cy and Synthesis compound R1d as reagents, the resulting crude product was reacted with [4- (hydroxymethyl) phenyl] boronic acid according to General Procedure 9 to give Example 942. MCBP: Calculated for C ₄₂ H ₄₃ N ₇ O ₅ S: 757.3046, found: 758.3135 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7- [4- (hydroxymethyl) phenyl] thieno [3,4-d] pyrimidin-4-one (Example 943).

Using General Procedure 7, starting from Synthesis compound R3dc and Synthesis compound R1d as reagents, the resulting crude product was reacted with [4- (hydroxymethyl) phenyl] boronic acid according to General Procedure 9 to give Example 943. MCBP: Calculated for C ₄₂ H ₄₂ N ₆ O ₅ S ₂ : 774.2658, found: 775.2733 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- [2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl ] methyl] -7-phenylpyrrolo [2,3-d] pyrimidin-4-one (Example 944).

Using General Procedure 7, starting with Synthesis compound R3bu and Synthesis compound R1x as reagents, Example 944 was prepared. MCBP: calculated for C ₄₀ H ₃₉ N ₇ O ₄ S: 713.2784, found: 714.2859 [(M + H) ⁺ form] ...

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7- (1-methylpyrrol-3-yl) pyrrolo [2,1-f] [1,2,4] triazin-4-one (Example 945).

Using General Procedure 7, starting with Synthesis compound R3cy and Synthesis compound R1d as reagents, the resulting crude product was reacted with 1-methyl-3- (4,4,5,5 tetramethyl-1,3,2-dioxaborolane-2 -yl) pyrrole according to General Procedure 9 to give Example 945. MCBP: calculated for C ₄₀ H ₄₂ N ₈ O ₄ S: 730.3050, found: 731.3113 [(M + H) + form].

7- (3-Chlorophenyl) -3 - [[4-hydroxy-1 - [(3R, 4R) -1- [2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine- 4-carbonyl] -4-piperidyl] methyl] pyrrolo [2,3-d] pyrimidin-4-one (Example 946).

Using General Procedure 7, starting with the Synthesis compound R3ar and the Synthesis compound R1x as reagents, Example 946 was prepared. MCBP: calculated for C ₄₀ H ₃₈ N ₇ O ₄ SCl: 747.2395, found:

748.2461 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- [2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl ] methyl] -7- (3-methoxyphenyl) pyrrolo [2,3-d] pyrimidin-4-one (Example 947).

Using General Procedure 7, starting with Synthesis compound R3bo and Synthesis compound R1x as reagents, Example 947 was prepared. MCBP: calculated for C ₄₁ H ₄₁ N ₇ O ₅ S: 743.2890, found: 744.2968 [(M + H) ⁺ form] ...

7- (4-Phtorphenyl) -3 - [[4-hydroxy-1 - [(3R, 4R) -1- [2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine- 4-carbonyl] -4-piperidyl] methyl] pyrrolo [2,3-d] pyrimidin-4-one (Example 948).

Using General Procedure 7, starting from the Synthesis compound R3as and the Synthesis compound Rlx as reagents, Example 948 was prepared. MCBP: calculated for C ₄₀ H ₃₈ N ₇ O ₄ FS: 731.2690, found: 732.2765 [(M + H) ⁺ form] ...

3 - [[4-hydroxy-1 - [(3R, 4R) -1- [2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4carbonyl] -4-piperidyl] methyl ] -7- (4-methoxyphenyl) pyrrolo [2,3-d] pyrimidin-4-one (Example 949).

Using General Procedure 7, starting with Synthesis compound R3ax and Synthesis compound R1x as reagents, Example 949 was prepared. MCBP: calculated for C ₄₁ H ₄₁ N ₇ O ₅ S: 743.2890, found: 744.2951 [(M + H) ⁺ form] ...

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- [2- (6-methoxy-3-puridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4carbonyl] -4-piperidyl] methyl ] -7- (4-methoxyphenyl) pyrrolo [2,3-d] pyrimidin-4-one (Example 950).

Ethyl 2- (6-methoxy-3-pyridyl) thiazole-5-carboxylate (0.75 mmol) was stirred with lithium hydroxide hydrate (3 mmol) in a mixture of water (2 ml) and methanol (2 ml) at 40 ° C for 4 including the Reaction mixture was neutralized 1N. aqueous HCl solution (3 ml), then evaporated. The resulting crude 2 (6-methoxy-3-pyridyl) thiazole-5-carboxylic acid was reacted with Synthesis compound R3ax according to General Procedure 7 to give Example 950. MCBP: Calculated for C ₄₁ H ₄₁ N ₇ O ₆ S : 759.2839, found: 760.2908 [(M + H) + form].

7- (2-Furyl) -3 - [[4-hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] - 3phenylpiperidin-4-carbonyl] -4-piperidyl] methyl] pyrrolo [2,1-f] [1,2,4] triazin-4-one (Example 951).

Using General Procedure 7, starting with Synthesis compound R3cy and Synthesis compound R1d as reagents, the resulting crude product was reacted with 2-furylboronic acid according to General Procedure 9 to give Example 951. MCBP: Calculated for C ₃₉ H ₃₉ N ₇ O ₅ S: 717.2734, found: 718.2801 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7- (1-methylpyrrol-3-yl) thieno [3,4-d] pyrimidin-4-one (Example 952).

Using General Procedure 7, starting from the Synthesis compound R3dc and the Synthesis compound R1d as reagents, the resulting crude product was reacted with 1-methyl-3- (4,4,5,5 tetramethyl-1,3,2-dioxaborolane-2 -yl) pyrrole according to General Procedure 9 to give Example 952. MCBP: calculated for C ₄₀ H ₄ iN ₇ O ₄ S ₂ : 747.2661, found: 748.2722 [(M + H) + form].

3 - [[3,3-Difluoro-4-hydroxy-1- [trans-1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4- carbonyl] -4-piperidyl] methyl] -7-phenylpyrrolo [2,3-d] pyrimidin-4-one, enantiomer 1 (Example 953) and

3 - [[3,3-difluoro-4-hydroxy-1- [trans-1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4- carbonyl] -4-piperidyl] methyl] -7-phenylpyrrolo [2,3-d] pyrimidin-4-one, enantiomer 2 (Example 954).

Using General Procedure 7, starting from Synthesis compound R3dm and Synthesis compound R1d as reagents, Example 953 and Example 954 were prepared and separated by liquid chromatography.

Example 953: MCBP calculated for C ₄ iH ₃₉ N ₇ O ₄ F ₂ S: 763.2752, found: 382.6463 [(M + 2H) ²⁺ form].

Example 954: MCBP calculated for C ₄ iH ₃₉ N ₇ O ₄ F ₂ S: 763.2752, found: 382.6463 [(M + 2H) ²⁺ form].

3 - [[3,3-Difluoro-4-hydroxy-1- [trans-1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4- carbonyl] -4-piperidyl] methyl] -7- (4-methoxyphenyl) pyrrolo [2,3-d] pyrimidin-4-one, enantiomer 1 (Example 955) and

3 - [[3,3-difluoro-4-hydroxy-1- [trans-1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4- carbonyl] -4-piperidyl] methyl] -7- (4-methoxyphenyl) pyrrolo [2,3-d] pyrimidin-4-one, enantiomer 2 (Example 956).

Using General Procedure 7, starting from the Synthesis compound R3dn and the Synthesis compound R1d as reagents, Example 955 and Example 956 were prepared and separated by liquid chromatography.

Example 955: MCBP calculated for C ₄₂ H ₄ iN ₇ O ₅ F ₂ S: 793.2858, found: 794.2910 [(M + H) + form].

Example 956: MCBP calculated for C ₄₂ H ₄ iN ₇ O ₅ F ₂ S: 793.2858, found: 794.2960 [(M + H) + form].

3 - [[4-hydroxy-1 - [(3R, 4R) -1 - [[4-methyl-2- (6-methyl-3-pyridyl) thiazol-5-yl] methyl] -3-phenylpiperidine-4 -carbonyl] -4-piperidyl] methyl] -7-phenylpyrrolo [2,3-d] pyrimidin-4-one (Example 957).

Using General Procedure 6 starting from the Synthesis compound R3bu and 5- (chloromethyl) -4-methyl-2- (6-161 037563 methyl-3-pyridyl) thiazole as reagents, Example 957 was prepared. MCBP: Calculated for

C41H43N7O3S: 713.3148, found: 714.3215 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [[4-methyl-2- (6-methyl-3-pyridyl) thiazol-5-yl] methyl] -3-phenylpiperidine-4 -carbonyl] -4-piperidyl] methyl] -7- (4-methoxyphenyl) pyrrolo [2,3-d] pyrimidin-4-one (Example 958).

Using General Procedure 6, starting from the Synthesis compound R3ax and 5- (chloromethyl) -4-methyl-2- (6methyl-3-pyridyl) thiazole as reagents, Example 958 was prepared. MCBP: Calculated for C ₄₂ H ₄₅ N ₇ O ₄ S: 743.3254, found: 744.3323 [(M + H) ⁺ form].

7- (3,5-Dimethoxyphenyl) -3 - [[4-hydroxy-1 - [(3S, 4S) -1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl ] -3-phenylpiperidin-4-carbonyl] -4-piperidyl] methyl] pyrrolo [2,3-d] pyrimidin-4-one (Example 959).

Using General Procedure 7, starting with Synthesis compound R3af and Synthesis compound R1d as reagents, Example 959 was prepared. MCBP: calculated for C ₄₃ H ₄₅ N ₇ O ₆ S: 787.3152, found: 788.3226 [(M + H) ⁺ form] ...

3 - [[4-Hydroxy- 1 - [(3R, 4R) -3-phenyl-1 - (pyrimidin-4-ylmethyl) piperidine-4-carbonyl] -4-piperidyl] methyl] -7-phenylpyrrolo [2 , 3-d] pyrimidin-4-one (Example 960)

Using General Procedure 6, starting from the compound Synthesis of R3bu and 4 (chloromethyl) pyrimidine as reagents, Example 960 was prepared. MCBP: calculated for C ₃₅ H ₃₇ N ₇ O ₃ : 603.2958, found: 604.2303 [(M + H) ⁺ form ].

3 - [[4-Hydroxy- 1 - [(3R, 4R) -3-phenyl-1 - (pyrimidin-4-ylmethyl) piperidine-4-carbonyl] -4-piperidyl] methyl] -7- (4- methoxyphenyl) pyrrolo [2,3-d] pyrimidin-4-one (Example 961).

Using General Procedure 6, starting with the Synthesis compound R3ax and 4- (chloromethyl) pyrimidine as reagents, Example 961 was prepared. MCBP: Calculated for C ₃₆ H ₃₉ N ₇ O ₄ : 633.3064, Found: 634.3140 [(M + H) + the form].

3 - [[4-Hydroxy- 1 - [(3R, 4R) -1 - [(2-methoxypyrimidin-4-yl) methyl] -3-phenylpiperidin-4-carbonyl] -4-piperidyl] methyl] -7-phenylpyrrolo [2,3-d] pyrimidin-4-one (Example 962)

Using General Procedure 6, starting from the compound Synthesis of R3bu and 4- (chloromethyl) -2methoxypyrimidine as reagents, Example 962 was obtained. MCBP: calculated for C ₃₆ H ₃₉ N ₇ O ₄ : 633.3064, found: 634.3126 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [(2-methoxypyrimidin-4-yl) methyl] -3-phenylpiperidine-4-carbonyl] -4piperidyl] methyl] -7- ( 4-methoxyphenyl) pyrrolo [2,3-d] pyrimidin-4-one (Example 963).

Using General Procedure 6, starting from the compound Synthesis of R3ax and 4- (chloromethyl) -2methoxypyrimidine as reagents, Example 963 was prepared. MCBP: calculated for C ₃₇ H ₄₁ N ₇ O ₅ : 663.3169, found: 664.3251 [(M + H) + form].

3 - [[1 - [(3R, 4R) -1 - (3-Fluorophenyl) sulfonyl-3-phenylpiperidine-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] -7-phenyl pyrrolo [2,3 -d] pyrimidin-4-one (Example 964).

Using General Procedure 8, starting from the compound Synthesis of R3bu and 3-fluorobenzenesulfonyl chloride as reagents, Example 964 was prepared. MCBP: calculated for C ₃₆ H ₃₆ N ₅ O ₅ FS: 669.2421, found: 670.2489 [(M + H) ⁺ form] ...

3 - [[1 - [(3R, 4R) -1 - (3-Fluorophenyl) sulfonyl-3-phenylpiperidine-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] -7- (4-methoxyphenyl) purrolo [2,3-d] pyrimidin-4-one (Example 965).

Using General Procedure 8, starting with the Synthesis compound R3ax and 3-fluorobenzenesulfonyl chloride as reagents, Example 965 was prepared. MCBP: calculated for C ₃₇ H ₃₈ N ₅ O ₆ FS: 699.2527, found: 700.2596 [(M + H) ⁺ form] ...

3 - [[1 - [(3R, 4R) -1 - (2-Fluorophenyl) sulfonyl-3-phenylpiperidine-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] -7-phenylpyrrolo [2,3- d] pyrimidin-4-one (Example 966).

Using General Procedure 8, starting from the compound Synthesis of R3bu and 2-fluorobenzenesulfonyl chloride as reagents, Example 966 was prepared. MCBP: calculated for C ₃₆ H ₃₆ N ₅ O ₅ FS: 669.2421, found: 670.2492 [(M + H) + form] ...

3 - [[1 - [(3R, 4R) -1 - (2-Fluorophenyl) sulfonyl-3-phenylpiperidine-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] -7- (4-methoxyphenyl) purrolo [2,3-d] pyrimidin-4-one (Example 967).

Using General Procedure 8, starting from the Synthesis compound R3ax and 2-fluorobenzenesulfonyl chloride as reagents, Example 967 was prepared. MCBP: calculated for C ₃₇ H ₃₈ N ₅ O ₆ FS: 699.2527, found: 700.2598 [(M + H) + form] ...

3 - [[1 - [(3R, 4R) -1 - (4-Fluorophenyl) sulfonyl-3-phenylpiperidine-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] -7-phenylpyrrolo [2,3- d] pyrimidin-4-one (Example 968).

Using General Procedure 8, starting from the compound Synthesis of R3bu and 4-fluorobenzenesulfonyl chloride as reagents, Example 968 was prepared. MCBP: calculated for C ₃₆ H ₃₆ N ₅ O ₅ FS: 669.2421, found: 670.2494 [(M + H) + form] ...

3 - [[1 - [(3R, 4R) -1 - (4-Fluorophenyl) sulfonyl-3-phenylpiperidine-4-carbonyl] -4-hydroxy-4-piperidyl] methyl] -7- (4-methoxyphenyl) purrolo [2,3-d] pyrimidin-4-one (Example 969).

Using General Procedure 8, starting with the Synthesis compound R3ax and 4-fluorobenzenesulfonyl chloride as reagents, Example 969 was prepared. MCBP: calculated for C ₃₇ H ₃₈ N ₅ O ₆ FS: 699.2527, found: 700.2598 [(M + H) + form] ...

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7-Bromo-3 - [[4-hydroxy-1 - [(3R, 4R) -3-phenyl-1- (pyrazin-2-ylmethyl) piperidine-4-carbonyl] -4-piperidyl] methyl] pyrrolo [2 , 1-f] [1,2,4] triazin-4-one (Example 970).

Using General Procedure 6, starting from the Synthesis compound of R3cy and 2- (chloromethyl) pyrazine as reagents, Example 970 was prepared. MCBP: Calculated for C ₂₉ H ₃₂ N ₇ O ₃ Br: 605.1750 Found:

606.1826 [(M + H) + form].

7-Chloro-3 - [[4-hydroxy-1 - [(3R, 4R) -3-phenyl-1- (pyrazin-2-ylmethyl) piperidine-4-carbonyl] -4-piperidyl] methyl] thieno [3 , 4-d] pyrimidin-4-one (Example 971).

Using General Procedure 6, starting from the compound Synthesis of R3dc and 2- (chloromethyl) pyrazine as reagents, Example 971 was prepared. MCBP: calculated for C ₂₉ H ₃ iN ₆ O ₃ SCl: 578.1867, found: 579.1947 [(M + H) ⁺ form].

3 - [[4-Hydroxy- 1 - [(3R, 4R) -3-phenyl-1 - (pyrazine-2-carbonyl) piperidine-4-carbonyl] -4-piperidyl] methyl] -7-phenylpyrrolo [2 , 3-d] pyrimidin-4-one (Example 972).

Using General Procedure 7, starting from the compound Synthesis of R3bu and pyrazine-2-carboxylic acid as reagents, Example 972 was prepared. MCBP: Calculated for C ₃₅ H ₃₅ N ₇ O ₄ : 617.2751, Found: 618.2826 [(M + H) ⁺ the form].

3 - [[4-Hydroxy- 1 - [(3R, 4R) -3-phenyl-1 - (pyrazine-2-carbonyl) piperidine-4-carbonyl] -4-piperidyl] methyl] -7- (4- methoxyphenyl) pyrrolo [2,3-d] pyrimidin-4-one (Example 973).

Using General Procedure 7, starting from the compound Synthesis of R3ax and pyrazine-2-carboxylic acid as reagents, Example 973 was prepared. MCBP: Calculated for C ₃₆ H ₃₇ N ₇ O ₅ : 647.2856, Found: 648.2931 [(M + H) ⁺ the form].

3 - [[4-Hydroxy- 1 - [(3R, 4R) -1 - [(6-methylpyrazin-2-yl) methyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7-phenylpyrrolo [2,3-d] pyrimidin-4-one (Example 974).

Using General Procedure 6, starting from the compound Synthesis of R3bu and 2- (chloromethyl) -6-methylpyrazine as reagents, Example 974 was prepared. MCBP: Calculated for C ₃₆ H ₃₉ N ₇ O ₃ : 617.3114, Found: 618.3178 [(M + H) + form].

3 - [[4-Hydroxy- 1 - [(3R, 4R) -1 - [(6-methylpyrazin-2-yl) methyl] -3-phenylpiperidine-4-carbonyl] -4piperudyl] methyl] -7- ( 4-methoxyphenyl) purrolo [2,3-d] purimudin-4-one (Example 975).

Using General Procedure 6 starting from the Synthesis compound R3ax and 2- (chloromethyl) -6-methylpyrazine as reagents, Example 975 was prepared. MCBP: Calculated for C ₃₇ H ₄₁ N ₇ O ₄ : 647.3220, Found: 648.3285 [(M + H) + form].

3 - [[1 - [(3R, 4R) -1 - [(4,6-Dimethylpyrimigin-2-yl) methyl] -3-phenylpiperidine-4-carbonyl] -4-hydroxy4-piperidyl] methyl] -7- phenylpyrrolo [2,3-d] pyrimidin-4-one (Example 976).

Using General Procedure 6, starting from the Synthesis compound of R3bu and 2- (chloromethyl) -4,6dimethylpyrimidine as reagents, Example 976 was prepared. MCBP: Calculated for C ₃₇ H ₄₁ N ₇ O ₃ : 631.3271, Found: 632.3338 [(M + H) ⁺ form].

3 - [[1 - [(3R, 4R) -1 - [(4,6-Dimethylpyrimigin-2-yl) methyl] -3-phenylpiperidine-4-carbonyl] -4-hydroxy4-piperidyl] methyl] -7- (4-methoxyphenyl) pyrrolo [2,3-d] pyrimidin-4-one (Example 977).

Using General Procedure 6, starting from the compound Synthesis of R3ax and 2- (chloromethyl) -4,6-dimethylpyrimidine as reagents, Example 977 was prepared. MCBP: calculated for C ₃₈ H ₄₃ N ₇ O ₄ : 661.3377, found: 662.3424 [( M + H) + form].

3 - [[4-Hydroxy- 1 - [(3R, 4R) -3-phenyl-1 - (pyrazin-2-ylmethyl) piperidine-4-carbonyl] -4-piperidyl] methyl] -7-phenylpyrrolo [2 , 1-f] [1,2,4] triazin-4-one (Example 978).

Using General Procedure 9, starting from Example 970 and phenylboronic acid as reagents, Example 978 was prepared. MCBP: Calculated for C ₃₅ H ₃₇ N ₇ O ₃ : 603.2958, Found: 604.3022 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -3-phenyl-1- (pyrazin-2-ylmethyl) piperidine-4-carbonyl] -4-piperidyl] methyl] -7- (4-methoxyphenyl ) pyrrolo [2,1-1 '] [1,2,4] triazin-4-one (Example 979).

Using General Procedure 9, starting from Example 970 and (4-methoxyphenyl) boronic acid as reactants, Example 979 was prepared. MCBP: Calculated for C ₃₆ H ₃₉ N ₇ O ₄ : 633.3064, Found: 634.3127 [(M + H) + the form].

3 - [[4-Hydroxy- 1 - [(3R, 4R) -3-phenyl-1 - (pyrazin-2-ylmethyl) piperidine-4-carbonyl] -4-piperidyl] methyl] -7-phenylthieno [3 , 4-d] pyrimidin-4-one (Example 980).

Using General Procedure 9, starting from Example 971 and phenylboronic acid as reagents, Example 980 was prepared. MCBP: Calculated for C ₃₅ H ₃₆ N ₆ O ₃ S: 620.2570, Found: 621.2627 [(M + H) + form].

3 - [[4-Hygroxy-1 - [(3R, 4R) -3-phenyl-1- (pyrazin-2-ylmethyl) piperidine-4-carbonyl] -4-piperidyl] methyl] -7- (4-methoxyphenyl ) thieno [3,4-d] pyrimidin-4-one (Example 981).

Using General Procedure 9, starting from Example 971 and (4-methoxyphenyl) boronic acid as reactants, Example 981 was prepared. MCBP: Calculated for C ₃₆ H ₃₈ N ₆ O ₄ S: 650.2676, Found: 651.2745 [(M + H) + form].

3 - [[4-Hydroxy- 1 - [(3R, 4R) -3-phenyl-1 - (pyridazin-3-ylmethyl) piperidine-4-carbonyl] -4-piperidyl] methyl] -7-phenylpyrrolo [2 , 3-d] pyrimidin-4-one (Example 982).

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Using General Procedure 6, starting from the Synthesis compound of R3bu and 3- (bromomethyl) pyridazine as reagents, Example 982 was prepared. MCBP: Calculated for C ₃₅ H ₃₇ N ₇ O ₃ : 603.2958 Found:

604.3017 [(M + H) + form].

3 - [[4-Hydroxy- 1 - [(3R, 4R) -3-phenyl-1 - (pyridazin-3-ylmethyl) piperidine-4-carbonyl] -4-piperidyl] methyl] -7- (4- methoxyphenyl) pyrrolo [2,3-d] pyrimidin-4-one (Example 983).

Using General Procedure 6, starting from the compound Synthesis R3ax and 3- (bromomethyl) pyridazine as reagents, Example 983 was prepared. MCBP: calculated for C ₃₆ H ₃₉ N ₇ O ₄ : 633.3064, found: 634.3139 [(M + H) ⁺ the form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [(5-methylpyrazin-2-yl) methyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7- phenylpyrrolo [2,3-d] pyrimidin-4-one (Example 984).

Using General Procedure 6, starting from the Synthesis compound of R3bu and 2- (chloromethyl) -5-methylpyrazine as reagents, Example 984 was prepared. MCBP: Calculated for C ₃₆ H ₃₉ N ₇ O ₃ : 617.3114, Found: 618.3172 [(M + H) ⁺ form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [(5-methylpyrazin-2-yl) methyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7- (4-methoxyphenyl) pyrrolo [2,3-d] pyrimidin-4-one (Example 985).

Using General Procedure 6, starting with the Synthesis compound R3ax and 2- (chloromethyl) -5methylpyrazine as reagents, Example 985 was prepared. MCBP: Calculated for C ₃₇ H ₄₁ N ₇ O ₄ : 647.3220, Found: 648.3314 [(M + H) + form].

3 - [[4-Hydroxy- 1 - [(3R, 4R) -3-phenyl-1 - (pyrimidin-2-ylmethyl) piperidine-4-carbonyl] -4-piperidyl] methyl] -7-phenylpyrrolo [2 , 3-d] pyrimidin-4-one (Example 986).

Using General Procedure 6, starting from the compound Synthesis of R3bu and 2- (chloromethyl) pyrimidine as reagents, Example 986 was prepared. MCBP: Calculated for C ₃₅ H ₃₇ N ₇ O ₃ : 603.2958, Found: 604.3022 [(M + H) + the form].

3 - [[4-Hydroxy- 1 - [(3R, 4R) -3-phenyl-1 - (pyrimidin-2-ylmethyl) piperidine-4-carbonyl] -4-piperidyl] methyl] -7- (4- methoxyphenyl) pyrrolo [2,3-d] pyrimidin-4-one (Example 987).

Using General Procedure 6, starting with the Synthesis compound R3ax and 2- (chloromethyl) pyrimidine as reagents, Example 987 was prepared. MCBP: Calculated for C ₃₆ H ₃₉ N ₇ O ₄ : 633.3064, Found: 634.3128 [(M + H) + the form].

3 - [[4-Hydroxy- 1 - [(3R, 4R) -1 - [(4-methylpyrimidin-2-yl) methyl] -3-phenylpiperidin-4-carbonyl] -4piperidyl] methyl] -7-phenylpyrrolo [2,3-d] pyrimidin-4-one (Example 988).

Using General Procedure 6, starting from the compound Synthesis of R3bu and 2- (chloromethyl) -4-methylpyrimidine as reagents, Example 988 was prepared. MCBP: Calculated for C ₃₆ H ₃₉ N ₇ O ₃ : 617.3114, Found: 618.3158 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [(4-methylpyrimidin-2-yl) methyl] -3-phenylpiperidine-4-carbonyl] -4piperidyl] methyl] -7- ( 4-methoxyphenyl) pyrrolo [2,3-d] pyrimidin-4-one (Example 989).

Using General Procedure 6, starting from the Synthesis compound R3ax and 2- (chloromethyl) -4-methylpyrimidine as reagents, Example 989 was prepared. MCBP: Calculated for C ₃₇ H ₄ iN ₇ O ₄ : 647.3220, Found: 648.3298 [(M + H) + form].

3 - [[4-Hydroxy- 1 - [(3R, 4R) -1 - [(2-methylpyrimidin-4-yl) methyl] -3-phenylpiperidin-4-carbonyl] -4piperidyl] methyl] -7-phenylpyrrolo [2,3-d] pyrimidin-4-one (Example 990).

Using General Procedure 6, starting from the compound Synthesis of R3bu and 4- (chloromethyl) -2-methylpyrimidine as reagents, Example 990 was prepared. MCBP: Calculated for C ₃₆ H ₃₉ N ₇ O ₃ : 617.3114, Found: 618.3179 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [(2-methylpyrimidin-4-yl) methyl] -3-phenylpiperidine-4-carbonyl] -4piperidyl] methyl] -7- ( 4-methoxyphenyl) pyrrolo [2,3-d] pyrimidin-4-o n (Example 991).

Using General Procedure 6, starting from the compound Synthesis of R3ax and 4- (chloromethyl) -2-methylpyrimidine as reagents, Example 991 was prepared. MCBP: Calculated for C ₃₇ H ₄ iN ₇ O ₄ : 647.3220, Found: 648.3282 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [(6-methoxypyridazin-3-yl) methyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7-phenylpyrrolo [2,3-d] pyrimidin-4-one (Example 992).

Using General Procedure 6, starting from the compound Synthesis of R3bu and 3- (chloromethyl) -6-methoxypyridazine as reagents, Example 992 was prepared. MCBP: calculated for C ₃₆ H ₃₉ N ₇ O ₄ : 633.3064, found: 634.3129 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [(6-methoxypyridazin-3-yl) methyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7- ( 4-methoxyphenyl) pyrrolo [2,3-d] pyrimidin-4-one (Example 993).

Using General Procedure 6, starting from the compound Synthesis of R3ax and 3- (chloromethyl) -6-methoxypyridazine as reagents, Example 993 was prepared. MCBP: calculated for C ₃₇ H ₄ iN ₇ O ₅ : 663.3169, found: 664.3223 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [(3-methoxypyrazin-2-yl) methyl] -3-phenylpiperidin-4-carbonyl] -4-piperidyl] methyl] -7-phenylpyrrolo [2,3-d] pyrimidin-4-one (Example 994).

Using General Procedure 6, starting from the compound Synthesis of R3bu and 2- (chloromethyl) -3-methoxypyrazine as reagents, Example 994 was prepared. MCBP: calculated for C ₃₆ H ₃₉ N ₇ O ₄ : 633.3064, found 164 037563 deno: 634.3142 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [(3-methylpyrazin-2-yl) methyl] -3-phenylpiperidin-4-carbonyl] -4-piperidyl] methyl] -7-phenylpyrrolo [2,3-d] pyrimidin-4-one (Example 995).

Using General Procedure 6, starting from the compound Synthesis of R3bu and 2- (chloromethyl) -3-methylpyrazine as reagents, Example 995 was prepared. MCBP: calculated for C36H39N-O3: 617.3114, found: 618.3214 [(M + H) ⁺ form] ...

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [(3-methylpyrazin-2-yl) methyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7 - (4-methoxyphenyl) pyrrolo [2,3-d] pyrimidin-4-one (Example 996).

Using General Procedure 6 starting from the Synthesis compound R3ax and 2- (chloromethyl) -3-methylpyrazine as reagents, Example 996 was prepared. MCBP: Calculated for C ₃₇ H ₄ iN ₇ O ₄ : 647.3220, Found: 648.3265 [(M + H) ⁺ form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [(3-methoxypyrazin-2-yl) methyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7- ( 4-methoxyphenyl) pyrrolo [2,3-d] pyrimidin-4-one (Example 997).

Using General Procedure 6, starting from the Synthesis compound R3ax and 2- (chloromethyl) -3-methoxypyrazine as reagents, Example 997 was prepared. MCBP: Calculated for C ₃₇ H ₄₁ N ₇ O ₅ : 663.3169, Found: 664.3211 [(M + H) + form].

4 - [[(3R, 4R) -4- [4-Hydroxy-4 - [[4-oxo-7- (2-pyridyl) pyrrolo [2,3-d] pyrimidin-3-yl] methyl] piperidine- 1-carbonyl] -3-phenyl-1-piperidyl] methyl] pyridine-2-carbonitrile (Example 998).

Using General Procedure 6, starting from the Synthesis compound of R3ca and 4- (chloromethyl) pyridine-2carbonitrile as reagents, Example 998 was prepared. MCBP: Calculated for C ₃₆ H ₃₆ N ₈ O ₅ : 628.2910, Found: 629.2987 [(M + H ) + form].

5 - [[(3R, 4R) -4- [4-Hydroxy-4 - [[7- (1-methylpyrazol-4-yl) -4-oxonirrolo [2,3-d] pyrimidin-3-yl] methyl ] piperidine-1-carbonyl] -3-phenyl-1-piperidyl] methyl] pyridine-2-carbonitrile (Example 999).

Using General Procedure 6, starting from the compound Synthesis of R3ch and 4- (bromomethyl) pyridine-2carbonitrile as reagents, Example 999 was prepared. MCBP: Calculated for C ₃₅ H ₃₇ N ₉ O ₃ : 631.3019, Found: 632.3066 [(M + H ) + form].

5 - [[(3R, 4R) -4- [4-Hydroxy-4 - [[4-oxo-7- (2-pyridyl) pyrrolo [2,3-d] pyrimidin-3-yl] methyl] piperidine- 1 -carbonyl] -3-phenyl-1-piperidyl] methyl] pyridine-2-carbonitrile (Example 1000).

Using General Procedure 6, starting from the compound Synthesis of R3ca and 4- (bromomethyl) pyridine-2carbonitrile as reagents, Example 1000 was prepared. MCBP: Calculated for C ₃₆ H ₃₆ N8O ₃ : 628.2910, Found: 629.2976 [(M + H) + the form].

5 - [[(3R, 4R) -4- [4-Hydroxy-4 - [[7- (1-methylpyrazol-4-yl) -4-oxonirrolo [2,1-f] [1,2,4] triazin-3-yl] methyl] piperidine-1-carbonyl] -3-phenyl-1-piperidyl] methyl] pyridine-2-carbonitrile (Example 1001).

Using General Procedure 6, starting from the compound Synthesis of R3cy and 5- (bromomethyl) pyridine-2carbonitrile as reagents, the resulting crude product was reacted with 1methyl-4- (4,4,5,5-tetramethyl-1,3, 2-dioxaborolan-2-yl) pyrazole according to General Procedure 9 to give Example 1001. MCBP: calculated for C ₃₅ H ₃₇ N ₉ O ₃ : 631.3019, found: 632.3068 [(M + H) + form].

4 - [[(3R, 4R) -4- [4-Hydroxy-4 - [[7- (1-methylpyrazol-4-yl) -4-oxopyrrolo [2,1-f] [1,2,4] triazin-3-yl] methyl] piperidine-1-carbonyl] -3-phenyl-1-piperidyl] methyl] pyridine-2-carbonitrile (Example 1002).

Using General Procedure 6, starting from the Synthesis of R3cy compound and 4- (chloromethyl) pyridine-2carbonitrile as reagents, the resulting crude product was reacted with 1methyl-4- (4,4,5,5-tetramethyl-1,3, 2-dioxaborolan-2-yl) pyrazole according to General Procedure 9 to give Example 1002. MCBP: calculated for C ₃₅ H ₃₇ N ₉ O ₃ : 631.3019, found: 632.3071 [(M + H) + form].

4 - [[(3R, 4R) -4- [4-Hydroxy-4 - [[7- (1-methylpyrazol-4-yl) -4-oxothieno [3,4-d] nyrimidin-3-yl] methyl ] piperidine-1-carbonyl] -3-phenyl-1-piperidyl] methyl] pyridine-2-carbonitrile (Example 1003).

Using General Procedure 6, starting from the compound Synthesis of R3dc and 4- (chloromethyl) pyridine-2carbonitrile as reagents, the resulting crude product was reacted with 1methyl-4- (4,4,5,5-tetramethyl-1,3, 2-dioxaborolan-2-yl) pyrazole according to General Procedure 9 to give Example 1003. MCBP: calculated for C ₃₅ H ₃₆ N ₈ O ₃ S: 648.2631, found: 649.2693 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [(5-methylnyrazin-2-yl) methyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7- phenylthieno [3,4-d] pyrimidin-4-one (Example 1004).

Using General Procedure 6, starting from the compound Synthesis of R3da and 2- (chloromethyl) -5-methylpyrazine as reagents, Example 1004 was prepared. MCBP: Calculated for C ₃₆ H ₃₈ N ₆ O ₃ S: 634.2726, Found: 635.2793 [(M + H) + form].

3 - [[4-Hydroxy- 1 - [(3R, 4R) -3-phenyl-1 - (pyrimidin-2-ylmethyl) piperidine-4-carbonyl] -4-piperidyl] methyl] -7-phenylthieno [3 , 4-d] pyrimidin-4-one (Example 1005).

Using General Procedure 6, starting from the compound Synthesis of R3da and 2- (chloromethyl) pyrimidine as reagents, Example 1005 was prepared. MCBP: Calculated for C ₃₅ H ₃₆ N ₆ O ₃ S: 620.2570, Found: 621.2619 [(M + H) + form].

- 165 037563

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [(4-methylpyrimidin-2-yl) methyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7-phenylthieno [3,4-d] nupuMuguH-4-OH (Example 1006).

Using General Procedure 6, starting from the compound Synthesis of R3da and 2- (chloromethyl) -4-methylpyrimidine as reagents, Example 1006 was prepared. MCBP: Calculated for C ₃₆ H ₃₈ N ₆ O ₃ S: 634.2726, Found: 635.2791 [(M + H) + form].

3 - [[4-Hydroxy- 1 - [(3R, 4R) -3-phenyl-1 - (pyrimidin-4-ylmethyl) piperidine-4-carbonyl] -4-piperidyl] methyl] -7-phenylthieno [3 , 4-d] pyrimidin-4-one (Example 1007).

Using General Procedure 6, starting from the compound Synthesis of R3da and 4- (chloromethyl) pyrimidine as reagents, Example 1007 was prepared. MCBP: Calculated for C ₃₅ H ₃₆ N ₆ O ₃ S: 620.2570, Found: 621.2656 [(M + H) ⁺ form].

3 - [[1 - [(3R, 4R) -1 - [(4,6-Dimethylpyrimidin-2-yl) methyl] -3-phenylpiperidine-4-carbonyl] -4-hydroxy4-piperidyl] methyl] -7- phenylthieno [3,4-d] pyrimidin-4-one (Example 1008).

Using General Procedure 6, starting from the compound Synthesis of R3da and 2- (chloromethyl) -4,6-dimethylpyrimidine as reagents, Example 1008 was prepared. MCBP: Calculated for C ₃₇ H ₄₀ N ₆ O ₃ S: 648.2883, Found: 649.2952 [ (M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [(2-methoxypyrimidin-4-yl) methyl] -3-phenylpiperidin-4-carbonyl] -4-piperidyl] methyl] -7-phenylthieno [3,4-d] pyrimidin-4-one (Example 1009).

Using General Procedure 6, starting from the compound Synthesis of R3da and 4- (chloromethyl) -2-methoxypyrimidine as reagents, Example 1009 was prepared. MCBP: Calculated for C ₃₆ H ₃₈ N ₆ O ₄ S: 650.2675, Found: 651.2744 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [(2-methylpyrimidin-4-yl) methyl] -3-phenylpiperidin-4-carbonyl] -4-piperidyl] methyl] -7-phenylthieno [3,4-d] pyrimidin-4-one (Example 1010).

Using General Procedure 6, starting from the compound Synthesis of R3da and 4- (chloromethyl) -2-methylpyrimidine as reagents, Example 1010 was prepared. MCBP: calculated for C36H38N6O3S: 634.2726, found: 635.2805 [(M + H) + form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [(6-methylpyrazin-2-yl) methyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7 -phenylthieno [3,4-d] pyrimidin-4-one (Example 1011).

Using General Procedure 6, starting from the compound Synthesis of R3da and 2- (chloromethyl) -6-methylpyrazine as reagents, Example 1011 was prepared. MCBP: Calculated for C ₃₆ H ₃₈ N ₆ O ₃ S: 634.2726, Found: 635.2792 [(M + H) + form].

3 - [[4-Hydroxy- 1 - [(3R, 4R) -1 - [(3-methylpyrazin-2-yl) methyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7-phenylthieno [3,4-d] pyrimidin-4-one (Example 1012).

Using General Procedure 6, starting from the compound Synthesis of R3da and 2- (chloromethyl) -3-methylpyrazine as reagents, Example 1012 was prepared. MCBP: calculated for C36H38N6O3S: 634.2726, found: 635.2782 [(M + H) ⁺ form].

3 - [[4-Hydroxy-1 - [(3R, 4R) -1 - [(3-methoxypyrazin-2-yl) methyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7-phenylthieno [3,4-d] pyrimidin-4-one (Example 1013).

Using General Procedure 6, starting from the compound Synthesis of R3da and 2- (chloromethyl) -3-methoxypyrazine as reagents, Example 1013 was prepared. MCBP: Calculated for C ₃₆ H ₃₈ N ₆ O ₄ S: 650.2675, Found: 651.2764 [(M + H) + form].

Pharmacological research

Example A Evaluation of USP7 Inhibition by Reading Fluorescence Intensity Data (FLINT).

The activity of USP7 was measured using rhodamine-110-labeled c-terminus ubiquitin as a substrate (Viva Biosciences). Incubation with USP7 resulted in the release of rhodamine-110, which in turn resulted in increased fluorescence that can be used to continuously measure USP7 activity.

USP7 reactions were performed in a 50 μl volume, 384 well low binding black solid plates (Corning # 3575). The reaction buffer consisted of 100 mM Bicine pH 8.0, 0.01% Triton100, 1 mM TCEP, and 10% DMSO.

0.25 nM His-His-USP7 (aa208-560, [C315A]) was incubated with compound (final DMSO concentration 10%) for 60 min at 30 ° C. The reaction was then initiated by the addition of 500 nM ubiquitin-rhodamine-110 substrate and the plates were read every 3 minutes for 21 minutes to measure rhodamine-110 release. Reading of fluorescence intensity data (FLINT) was performed using a Biomek Neo plate reader (Exc. 485 nm, Emit. 535 nm).

Inhibition by increasing doses of the compound was expressed as a percentage decrease in kinetic rate versus kinetic rates established between the 'DMSO only' and 'complete inhibition' controls (no USP7). Inhibitory concentrations that resulted in a 50% decrease in kinetic rate (IC50) were determined from 11-point dose-response curves in XL-Fit using a 4-parameter logistic model (sigmoidal dose response model).

The results are presented in table. 1 below, show that the compounds of the invention inhibit

- 166 037563 interaction between the USP7 protein and the fluorescent peptide described above.

Example B. In vitro cytotoxicity.

Cytotoxicity studies were performed using MTT assay using MM1S multiple myeloma or Z138 mantle lymphoma tumor cell lines. Cells were plated onto microplates and exposed to test compounds for 96 hours. Cell viability was then quantified using the Microculture Tetrazolium Assay colorimetric assay (Carmichael et al., Cancer Res. 1987, 47, 936-942). The results are expressed in IC ₅₀ (concentration of the compound that inhibits cell viability by 50%) and are presented in table. 1 below.

The results show that the compounds of the invention are cytotoxic.

Table 1. IC _{50 of} USP7 inhibition and cytotoxicity for MM1S or Z138 cells. Note: IC ₅₀ cytotoxicity for the Z138 tumor cell line is underlined.

Example 1C ₅₀ (M) USP7 FLINT 1S ₅₀ (M) MTT Example 1C ₅₀ (M) USP7 FLINT IC ₅₀ (Μ) MTT one 1.4Е-07 2.8E-06 nineteen 1.2E-08 2.4E-09 2 7.9E-08 NT twenty 9.3E-09 NT 3 4.9Е-09 3.ZE-09 21 5.1E-08 1.9Е-08 four 3.ZE-09 3.4E-09 22 7.3E-08 NT five 5.2E-08 2.1E-08 23 7.5E-09 4.8E-09 6 1.2E-07 NT 24 2.3E-08 7.4E-09 7 2.8E-08 5.0E-09 25 6.8E-09 1.1E-09 eight 7.3E-08 NT 26 1.5E-08 2.7Е-09 nine 1.2E-08 4.3E-09 27 1.5E-08 9.1E-09 10 1.5E-08 1.1E-08 28 1.6E-08 1.1E-08 eleven 1.6E-08 7.6E-09 29 1.2E-08 2.8Е-09 12 3.2E-08 1.6E-08 thirty LIE-08 6.5Е-09 13 5.9E-09 6.1E-09 31 1.4Е-08 1.7E-08 fourteen 1.6E-08 1.5E-08 32 9.4E-09 1.5E-08 fifteen 6.2E-09 2.4E-09 33 9.1E-09 2.4E-09 sixteen 1.ZE-08 7.1E-09 34 7.7E-09 9.1E-09 17 2.7E-08 5.9E-09 35 2.5E-08 7.6E-09 eighteen 2.9E-08 4.6E-09 36 1.6E-08 2.6E-09 37 2.2E-08 7.7E-09 69 3.6E-08 2.1E-07 38 1.7E-08 5.1E-09 70 1.3E-07 NT 39 1.8E-08 NT 71 9.1E-08 nt 40 9.9Е-09 4.23E-09 72 1.6E-08 4.0E-09 41 2.5E-08 NT 73 2.0E-08 7.6E-09 42 3.2E-08 nt 74 3.4E-08 1.7E-08 43 6.6E-08 nt 75 1.2E-08 6.4Е-09 44 4.3E-08 5.2E-09 76 7.0Е-09 2.8Е-09 45 1.0E-07 NT 77 LIE-08 4.1E-09 46 2.2E-08 nt 78 4.3E-09 2.4E-09 47 1.1E-08 2.56E-09 79 1.2E-08 5.0E-09 48 2.0E-08 NT 80 2.0E-08 8.3E-09 49 2.2E-08 nt 81 2.0E-08 9.5E-09 fifty 2.9E-08 7.3E-09 82 3.8E-08 1.6E-08 51 3.ZE-08 1.0E-08 83 1.7E-09 4.7E-08 52 2.2E-08 9.7E-09 84 4.6E-09 2.5E-09 53 2.3E-08 NT 85 8.2E-09 9.6E-09 54 2.7E-08 5.48E-09 86 1.7E-08 2.1E-08 55 3.ZE-08 1.0E-08 87 2.4E-08 3.8E-08 56 1.7E-08 NT 88 1.2E-08 6.1E-09 57 2.3E-08 7.84E-09 89 6.7E-09 1.9Е-08

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58 7.0E-08 E42E-08 90 8.3E-09 6.6E-09 59 5.9E-08 HT 91 1.1E-08 2.0E-08 60 4.ZE-08 HT 92 5.0E-09 5.3E-09 61 9.3E-09 HT 93 3.8E-09 7.0E-09 62 3.7E-08 HT 94 9.4E-09 6.3E-09 63 8.4E-05 HT 95 1.5E-08 3.2E-08 64 1.0E-07 7.7E-07 96 3.2E-08 1.5E-08 65 7.0E-08 HT 97 7.3E-08 HT 66 1.4E-07 HT 98 7.9E-08 HT 67 1.1E-07 HT 99 3.4E-08 1.7E-08 68 1.1E-07 HT 100 4.7E-08 1.7E-08 101 1.0E-07 2.4E-08 133 1.6E-08 6.9E-09 102 5.8E-08 1.2E-08 134 1.7E-08 4.1E-08 103 1.1E-08 6.2E-09 135 1.9E-08 4.8E-08 104 7.9E-09 7.2E-09 136 1.1E-08 4.9E-09 105 1.7E-08 3.6E-09 137 6.7E-09 4.8E-09 106 9.9E-09 9.2E-09 138 1.2E-08 8.3E-09 107 2.5E-08 2.1E-08 139 1.2E-08 1.2E-08 108 2.5E-08 4.3E-09 140 1.7E-08 9.9E-08 109 1.9E-08 7.4E-09 141 4.6E-08 HT 110 3.9E-08 1.3E-08 142 2.4E-08 4.5E-08 111 1.2E-08 1.6E-08 143 8.1E-07 HT 112 2.0E-08 9.0E-09 144 3.2E-08 5.3E-08 113 3.9E-08 1.7E-08 145 8.9E-08 HT 114 5.8E-08 9.3E-09 146 1.0E-07 HT 115 3.6E-08 1.4E-08 147 4.2E-07 3.5E-06 116 3.2E-08 1.0E-08 148 6.2E-08 2.9E-07 117 2.9E-08 1.3E-08 149 4.4E-09 2.4E-09 118 4.2E-08 2.6E-08 150 2.2E-08 1.4E-08 119 3.4E-08 3.8E-08 151 1.7E-08 3.1E-09 120 5.8E-08 1.1E-08 152 9.1E-09 2.3E-09 121 4.8E-08 1.8E-08 153 4.7E-08 8.8E-09 122 5.1E-09 7.67E-09 154 2.0E-08 3.7E-09 123 2.5E-08 5.2E-09 155 1.4E-08 5.5E-09 124 6.3E-08 HT 156 6.7E-09 2.0E-09 125 5.2E-08 1.17E-08 / E93E-08 157 2.1E-08 5.2E-09 126 5.5E-05 HT 158 5.2E-08 1.4E-08 127 1.1E-07 HT 159 6.4E-09 3.3E-09 128 6.4E-08 HT 160 1.6E-08 HT 129 1.3E-07 HT 161 1.5E-08 7.1E-08 130 1.5E-07 HT 162 7.4E-08 HT 131 1.0E-08 8.2E-09 163 3.2E-08 HT 132 1.2E-08 8.7E-09 164 6.1E-08 HT 165 3.6E-08 HT 197 1.9E-08 1.3E-07

- 168 037563

166 9.3E-08 HT 198 1.4E-07 HT 167 3.7E-08 3.2E-07 199 1.1E-07 HT 168 9.1E-08 HT 200 2.4E-07 HT 169 2.4E-07 HT 201 2.8E-08 HT 170 5.7E-08 HT 202 7.5E-07 HT 171 9.7E-08 HT 203 2.6E-08 6.9E-08 172 1.6E-08 3.9E-08 204 1.5E-07 HT 173 2.5E-08 6.4E-08 205 7.2E-08 1.2E-07 174 2.3E-08 HT 206 4.1E-08 4.4E-08 175 4.1E-08 HT 207 1.5E-07 HT 176 8.4E-08 HT 208 6.5E-08 HT 177 5.8E-07 HT 209 1.2E-07 HT 178 2.7E-08 1.2E-07 210 1.3E-07 HT 179 3.8E-07 HT 211 4.7E-07 HT 180 9.9E-08 HT 212 4.5E-08 HT 181 5.9E-07 HT 213 2.7E-08 1.1E-07 182 1.1E-08 5.3E-08 214 4.1E-08 1.7E-07 183 1.0E-08 3.6E-08 215 8.3E-08 HT 184 1.5E-05 1.3E-05 216 1.2E-07 HT 185 1.6E-08 5.7E-08 217 2.7E-08 1.4E-07 186 9.0E-08 HT 218 1.4E-07 HT 187 1.8E-07 HT 219 5.2E-08 1.6E-07 188 2.3E-08 HT 220 4.5E-08 3.8E-07 189 1.7E-08 1.2E-07 221 6.8E-08 HT 190 1.9E-08 1.7E-07 222 1.9E-07 HT 191 6.4E-08 HT 223 1.4E-07 HT 192 9.5E-08 HT 224 1.5E-07 HT 193 1.1E-07 6.2E-07 225 6.0E-08 HT 194 1.7E-07 HT 226 3.1E-07 HT 195 7.3E-08 HT 227 4.7E-08 HT 196 4.6E-08 HT 228 9.7E-08 HT 229 3.4E-07 1.6E-07 261 3.6E-08 1.3E-07 230 3.4E-07 HT 262 1.0E-07 HT 231 9.3E-07 HT 263 2.1E-08 2.8E-08 232 2.2E-07 HT 264 9.6E-08 HT 233 1.2E-06 HT 265 1.3E-07 HT 234 6.3E-08 HT 266 3.0E-08 3.8E-07 235 3.5E-08 4.1E-08 267 4.7E-08 6.5E-08 236 9.3E-08 HT 268 7.4E-08 HT 237 1.1E-07 HT 269 4.4E-08 1.7E-07 238 1.6E-07 HT 270 4.4E-08 4.5E-08 239 4.2E-08 1.0E-07 271 1.5E-07 HT 240 1.1E-06 HT 272 2.6E-08 3.8E-07 241 8.4E-08 HT 273 1.0E-07 HT 242 1.8E-07 HT 274 8.2E-07 HT

- 169 037563

243 1.4E-06 HT 275 3.3E-07 HT 244 2.8E-07 HT 276 8.7E-08 HT 245 2.2E-07 HT 277 8.6E-08 HT 246 1.8E-08 4.6E-08 278 5.4E-08 HT 247 8.2E-08 HT 279 1.2E-07 HT 248 3.4E-07 HT 280 5.5E-08 HT 249 1.2E-07 HT 281 2.6E-08 1.8E-07 250 1.8E-07 HT 282 1.2E-07 HT 251 4.3E-07 HT 283 1.0E-07 HT 252 1.6E-07 HT 284 4.1E-08 HT 253 4.6E-08 1.5E-07 285 1.6E-08 HT 254 2.3E-08 1.2E-07 286 1.5E-08 HT 255 2.9E-08 1.8E-07 287 2.5E-08 HT 256 5.5E-08 1.0E-07 288 6.0E-09 2.3E-08 257 8.0E-08 HT 289 1.2E-08 5.4E-08 258 9.7E-08 HT 290 7.4E-09 2.0E-09 259 3.1E-08 1.7E-07 291 8.4E-09 2.5E-09 260 2.2E-08 7.4E-08 292 5.8E-09 2.0E-09 293 4.0E-09 2.2E-09 325 8.6E-08 HT 294 9.8E-09 5.6E-09 326 7.9E-08 HT 295 8.0E-09 5.3E-09 327 3.9E-08 9.8E-08 296 2.3E-08 1.1E-08 328 2.0E-08 HT 297 1.4E-08 HT 329 1.8E-08 5.0E-08 298 1.4E-08 1.1E-08 330 2.0E-08 7.6E-08 299 3.9E-08 1.3E-08 331 4.4E-08 HT 300 2.5E-08 HT 332 3.2E-08 8.3E-09 301 1.ZE-06 5.5E-07 333 1.9E-08 3.3E-08 302 1.6E-08 7.1E-09 334 7.1E-09 5.1E-09 303 1.5E-08 4.0E-09 335 1.1E-08 8.9E-09 304 5.7E-09 1.5E-08 336 2.4E-08 7.2E-08 305 1.8E-08 3.4E-08 337 2.1E-08 1.1E-07 306 1.1E-08 7.3E-09 338 1.4E-08 1.2E-06 307 1.4Е-08 5.4E-09 339 2.5E-08 2.1E-08 308 1.2E-08 5.4E-09 340 5.0E-07 HT 309 1.1E-08 9.1E-09 341 2.6E-08 6.4E-08 310 3.6E-08 1.5E-08 342 2.3E-07 HT 311 1.2E-08 1.4E-08 343 3.3E-08 HT 312 5.5E-09 9.6E-09 344 9.6E-09 1.1E-08 313 8.2E-09 8.2E-09 345 1.1E-07 HT 314 2.1E-08 3.4E-08 346 2.1E-08 2.2E-09 315 4.9E-08 HT 347 1.5E-08 1.6E-09 316 1.2E-07 HT 348 1.2E-08 1.6E-09 317 5.ZE-08 HT 349 7.6E-08 HT 318 8.7E-08 HT 350 3.5E-07 HT 319 6.4E-08 HT 351 5.7E-07 HT

- 170 037563

320 1.6E-07 HT 352 3.9E-07 HT 321 1.0E-07 HT 353 1.2E-07 HT 322 1.4E-07 HT 354 3.9E-08 2.7E-07 323 2.3E-07 HT 355 4.1E-08 HT 324 7.2E-08 HT 356 1.4E-08 3.3E-08 357 6.4E-08 HT 389 1.7E-07 HT 358 4.5E-08 HT 390 3.9E-08 HT 359 4.1E-08 HT 391 6.0E-08 6.9E-08 360 1.1E-07 HT 392 8.0E-08 HT 361 7.2E-08 HT 393 6.2E-08 HT 362 2.9E-08 1.9E-07 394 6.0E-08 HT 363 2.8E-08 7.0E-08 395 6.6E-08 HT 364 3.5E-08 2.8E-07 396 1.7E-08 4.5E-08 365 4.2E-08 1.2E-07 397 2.8E-08 9.4E-08 366 3.8E-08 2.3E-07 398 3.3E-08 6.0E-08 367 2.0E-08 1.4E-07 399 3.6E-08 2.5E-08 368 2.7E-08 1.2E-07 400 4.8E-08 HT 369 2.6E-08 3.8E-08 401 2.9E-08 9.3E-08 370 1.0E-07 HT 402 2.7E-08 3.7E-08 371 5.4E-08 HT 403 1.4E-08 8.8E-08 372 9.4E-08 HT 404 1.9E-08 1.2E-07 373 3.4E-08 4.9E-08 405 3.5E-08 HT 374 2.8E-08 4.5E-08 406 2.3E-08 9.8E-08 375 4.4E-08 4.0E-08 407 2.4E-08 9.0E-08 376 3.1E-08 5.2E-08 408 2.1E-08 4.5E-08 377 3.7E-08 8.6E-08 409 5.2E-08 HT 378 3.1E-08 5.6E-08 410 4.0E-08 1.5E-07 379 9.2E-08 HT 411 4.8E-08 HT 380 9.8E-08 HT 412 2.4E-08 1.1E-07 381 4.3E-08 HT 413 3.5E-08 HT 382 2.1E-08 3.2E-08 414 1.3E-08 HT 383 1.9E-08 1.6E-08 415 2.0E-08 3.0E-08 384 1.6E-08 2.5E-08 416 1.9E-08 2.6E-08 385 2.5E-08 2.8E-08 417 2.5E-08 5.7E-08 386 2.1E-08 2.2E-08 418 3.0E-08 4.7E-08 387 1.5E-08 2.4E-08 419 2.3E-08 1.2E-07 388 5.4E-08 4.3E-08 420 2.3E-08 6.9E-08 421 2.6E-08 1.0E-07 453 2.7E-08 6.4E-08 422 2.8E-08 9.2E-08 454 1.1E-08 1.5E-08 423 2.8E-08 8.3E-08 455 1.1E-08 8.4E-09 424 3.1E-08 1.4E-07 456 8.6E-09 1.3E-08 425 8.0E-09 4.5E-08 457 1.7E-08 2.8E-08 426 1.9E-08 1.1E-07 458 1.5E-08 1.2E-08 427 1.9E-08 6.4E-08 459 8.7E-09 1.8E-08 428 4.2E-08 2.5E-07 460 6.1E-09 HT

- 171 037563

429 7.3E-08 HT 461 1.9E-07 HT 430 4.2E-07 HT 462 9.9E-08 HT 431 1.1E-07 HT 463 7.6E-08 HT 432 3.8E-08 2.9E-08 464 4.0E-08 4.3E-08 433 1.5E-08 2.0E-08 465 2.1E-08 3.3E-08 434 6.5E-08 2.5E-07 466 3.9E-08 3.7E-08 435 1.6E-08 5.7E-09 467 7.0E-08 HT 436 1.4E-08 2.7E-09 468 9.8E-08 HT 437 6.7E-08 1.3E-08 469 5.0E-08 HT 438 1.ZE-08 1.5E-08 470 2.6E-08 2.4E-08 439 2.3E-08 1.5E-08 471 2.7E-08 2.5E-07 440 1.0E-08 1.7E-08 472 2.5E-08 1.3E-07 441 4.1E-08 HT 473 1.2E-07 HT 442 3.6E-08 7.9E-08 474 4.7E-08 HT 443 4.2E-08 HT 475 1.1E-07 HT 444 1.0E-07 HT 476 7.8E-08 HT 445 1.7E-08 1.1E-08 477 8.0E-08 HT 446 1.6E-08 4.0E-09 478 6.1E-08 HT 447 7.1E-09 4.9E-09 479 2.8E-08 HT 448 9.4E-09 1.7E-09 480 1.9E-08 7.6E-08 449 1.8E-08 3.4E-09 481 8.2E-08 HT 450 1.5E-08 1.8E-08 482 1.1E-08 E9E-09 451 3.7E-08 5.0E-08 483 1.5E-08 5.6E-09 452 2.5E-08 2.2E-08 484 1.5E-08 2.0E-09 485 4.6E-08 2.6E-09 517 9.9E-09 6.2E-09 486 5.5E-09 7.1E-09 518 2.6E-08 3.5E-09 487 6.1E-09 8.4E-09 519 4.9E-09 4.0E-09 488 8.2E-08 HT 520 9.7E-09 5.6E-09 489 2.6E-08 6.0E-08 521 3.4E-08 3.1E-09 490 3.1E-08 5.4E-08 522 4.3E-08 9.8E-09 491 4.8E-08 7.0E-08 523 4.7E-09 E9E-09 492 7.1E-08 HT 524 5.5E-09 2.8E-09 493 1.4E-08 2.6E-09 525 8.8E-09 3.5E-09 494 1.9E-08 4.2E-09 526 1.8E-08 8.6E-09 495 1.3E-08 2.7E-09 527 1.6E-08 9.8E-09 496 5.0E-08 2.6E-09 528 6.6E-09 3.5E-09 497 1.8E-08 2.7E-09 529 6.7E-09 3.0E-09 498 4.3E-09 6.0E-09 530 2.2E-08 3.1E-09 499 1.2E-08 2.0E-09 531 5.5E-09 2.1E-09 500 1.5E-07 HT 532 2.7E-08 1.1E-07 501 7.2E-08 8.8E-09 533 1.3E-08 8.1E-08 502 5.1E-08 7.2E-09 534 2.1E-08 5.0E-08 503 4.3E-07 HT 535 9.0E-08 HT 504 2.0E-07 1.4E-08 536 2.9E-08 HT 505 5.9E-09 2.9E-09 537 4.0E-08 HT

- 172 037563

506 5.6E-09 2.1E-09 538 5.3E-08 HT 507 1.2E-07 HT 539 4.5E-08 HT 508 1.9E-08 6.9E-09 540 2.0E-08 HT 509 3.1E-08 1.5E-08 541 2.0E-08 1.0E-07 510 3.ZE-08 2.0E-08 542 1.4E-08 7.9E-08 511 4.6E-08 7.8E-08 543 1.6E-08 6.2E-08 512 2.0E-07 HT 544 1.4E-08 4.9E-08 513 1.5E-07 HT 545 1.4E-08 1.3E-07 514 1.1E-07 HT 546 3.5E-08 8.9E-08 515 1.5E-07 HT 547 1.7E-08 1.4E-07 516 4.9Е-08 6.5E-09 548 1.2E-08 9.4E-08 549 1.9Е-08 6.5E-08 581 4.5E-08 HT 550 2.9E-08 HT 582 4.1E-08 HT 551 1.7E-08 4.2E-08 583 2.4E-08 HT 552 1.8E-08 HT 584 1.2E-08 1.4E-08 553 1.ZE-08 8.1E-08 585 1.2E-07 HT 554 1.9Е-08 4.5E-08 586 5.4E-08 HT 555 3.2E-08 4.2E-08 587 8.0E-08 HT 556 1.1E-08 2.0E-07 588 5.4E-08 HT 557 2.4E-08 HT 589 3.6E-07 HT 558 1.8E-08 6.7E-08 590 2.0E-07 HT 559 2.5E-08 HT 591 1.1E-07 HT 560 2.4E-08 1.4E-07 592 9.0E-08 HT 561 2.4E-08 HT 593 8.9E-08 HT 562 9.6E-09 5.6E-08 594 1.8E-07 HT 563 1.1E-08 8.6E-08 595 1.7E-08 1.1E-07 564 1.1E-08 7.1E-08 596 1.6E-08 4.9E-08 565 9.6E-09 4.5E-08 597 1.8E-08 5.6E-08 566 3.3E-08 HT 598 2.5E-08 8.5E-08 567 2.3E-08 HT 599 6.7E-09 4.0E-08 568 1.4E-08 5.4E-08 600 3.3E-08 7.3E-08 569 3.4E-07 HT 601 3.1E-08 4.8E-08 570 5.0E-07 HT 602 7.7E-09 4.0E-08 571 4.3E-07 HT 603 3.6E-08 7.6E-08 572 2.9E-08 2.8E-07 604 2.0E-08 4.2E-08 573 2.1E-08 2.1E-07 605 2.4E-08 4.7E-08 574 4.8E-08 1.5E-07 606 4.1E-08 9.6E-08 575 6.1E-08 1.2E-07 607 4.4E-08 HT 576 2.2E-07 HT 608 3.1E-08 3.6E-08 577 1.2E-07 HT 609 1.4E-08 2.7E-08 578 1.3E-07 HT 610 3.8E-08 8.6E-08 579 5.2E-08 HT 611 2.1E-08 5.5E-08 580 1.3E-07 HT 612 6.0E-08 3.6E-08 613 3.2E-08 6.4E-08 645 2.2E-08 HT 614 5.6E-08 HT 646 7.0E-08 HT

- 173 037563

615 6.9E-08 NT 647 3.2E-08 2.6E-08 616 6.1E-08 6.2E-08 648 6.9E-08 NT 617 3.5E-08 8.9E-08 649 1.5E-08 2.7E-08 618 2.0E-08 3.4E-08 650 1.9Е-08 3.8E-08 619 3.8E-08 3.0E-08 651 2.8E-08 8.9E-08 620 3.0E-08 5.0E-08 652 1.4Е-08 8.2E-08 621 4.1E-08 NT 653 2.4E-08 1.1E-07 622 5.7E-08 nt 654 1.9Е-08 8.9E-08 623 2.7E-08 3.5E-08 655 2.7E-08 4.7E-08 624 6.2E-08 NT 656 2.7E-08 8.6E-08 625 3.1E-08 4.0E-08 657 6.2E-08 NT 626 1.2E-08 1.2E-08 658 6.2E-07 NT 627 2.0E-08 1.8E-08 659 5.7E-07 nt 628 4.1E-08 NT 660 7.7E-07 nt 629 1.2E-08 9.2E-09 661 3.8E-07 nt 630 2.5E-08 2.6E-08 662 2.6E-07 nt 631 3.1E-08 3.4E-08 663 1.6E-07 nt 632 1.0E-08 9.4E-09 664 2.2E-07 nt 633 1.9Е-08 1.4Е-08 665 2.3E-07 nt 634 1.7E-08 1.4Е-08 666 3.4E-08 9.7E-08 635 4.0E-08 8.ZE-08 667 3.2E-08 8.7E-08 636 2.7E-08 2.8E-08 668 3.1E-08 1.1E-07 637 3.ZE-08 5.4E-08 669 2.7E-08 1.1E-07 638 3.8E-08 7.9E-08 670 6.7E-07 NT 639 9.0E-08 NT 671 3.0E-08 5.9E-08 640 3.0E-08 5.4E-08 672 2.8E-08 6.3E-08 641 2.5E-08 5.0E-08 673 1.6E-08 2.8E-08 642 2.0E-08 5.4E-08 674 2.6E-08 1.2E-07 643 3.2E-08 5.4E-08 675 2.7E-08 6.3E-08 644 6.2E-08 NT 676 2.9E-08 5.6E-08 677 4.2E-08 NT 709 1.6E-08 2.0E-08 678 1.9Е-08 4.1E-08 710 2.9E-08 4.3E-08 679 5.8E-07 NT 711 3.6E-08 NT 680 5.8E-07 nt 712 2.2E-08 nt 681 5.9E-07 nt 713 7.9Е-09 1.7E-08 682 1.ZE-08 1.5E-08 714 1.1E-08 1.6E-08 683 1.8E-08 1.4Е-08 715 1.0E-08 4.1E-09 684 1.2E-08 4.7E-08 716 1.ZE-08 5.8E-09 685 7.8E-09 2.1E-08 717 7.1E-09 3.1E-09 686 2.3E-07 NT 718 7.3E-09 2.8Е-09 687 1.6E-08 3.ZE-08 719 9.4E-09 1.5E-09 688 1.5E-08 3.2E-08 720 8.6E-09 5.0E-09 689 1.7E-08 2.2E-08 721 1.8E-08 7.8E-09 690 1.0E-08 1.6E-08 722 2.2E-08 2.4E-09 691 1.2E-08 1.9Е-08 723 1.2E-08 6.5Е-09

- 174 037563

692 2.0E-08 2.0E-08 724 5.1E-09 3.6E-09 693 3.2E-08 2.6E-08 725 4.4E-08 4.7E-09 694 1.9E-08 4.1E-08 726 3.4E-09 3.9E-09 695 2.0E-08 4.9E-08 727 1.7E-08 1.4E-09 696 2.1E-08 4.5E-08 728 4.0E-08 6.4E-09 697 1.4E-08 1.4E-08 729 2.6E-08 2.7E-09 698 2.0E-08 1.9E-08 730 5.0E-08 2.4E-09 699 8.0E-09 1.2E-08 731 6.9E-08 4.0E-09 700 2.4E-08 3.9E-08 732 1.7E-08 4.3E-09 701 2.2E-08 3.4E-08 733 2.3E-08 5.7E-09 702 2.4E-08 1.8E-07 734 1.5E-08 3.1E-09 703 2.6E-08 1.6E-07 735 1.6E-08 2.3E-09 704 2.9E-08 5.6E-08 736 1.5E-08 1.2E-08 705 7.7E-09 1.1E-08 737 2.0E-09 3.3E-09 706 1.1E-07 HT 738 2.1E-08 2.8E-09 707 2.9E-07 HT 739 6.5E-09 1.7E-09 708 9.9E-08 HT 740 4.3E-09 1.5E-09 741 4.5E-09 7.1E-09 773 4.8E-08 HT 742 2.9E-09 6.8E-09 774 1.5E-09 4.1E-09 743 4.9E-09 4.2E-09 775 4.8E-09 4.0E-09 744 1.0E-08 2.9E-09 776 1.8E-09 2.3E-09 745 9.2E-09 3.0E-09 777 5.3E-09 1.1E-08 746 5.1E-09 1.5E-08 778 1.0E-08 1.7E-08 747 5.2E-09 3.7E-09 779 5.5E-08 HT 748 4.8E-09 5.8E-09 780 1.2E-07 HT 749 1.3E-08 7.04E-09 781 2.0E-07 HT 750 7.7E-09 2.3E-09 782 6.5E-08 HT 751 1.3E-08 1.6E-09 783 1.7E-07 HT 752 2.3E-08 4.2E-08 784 7.5E-08 HT 753 2.6E-08 1.0E-07 785 1.7E-07 HT 754 2.4E-08 4.4E-08 786 1.2E-08 4.0E-08 755 2.8E-08 3.8E-08 787 3.9E-08 4.6E-08 756 1.1E-08 1.4E-08 788 1.4E-07 HT 757 1.9E-08 3.5E-08 789 2.4E-08 1.0E-07 758 1.8E-08 6.9E-08 790 2.0E-08 2.3E-07 759 2.3E-08 HT 791 1.5E-08 9.5E-08 760 8.3E-08 HT 792 2.2E-08 9.9E-08 761 5.1E-08 HT 793 1.2E-07 HT 762 5.3E-07 HT 794 2.6E-07 HT 763 2.6E-08 3.0E-07 795 1.4E-07 HT 764 5.4E-08 HT 796 7.2E-08 HT 765 7.6E-08 HT 797 5.7E-07 HT 766 8.5E-08 HT 798 9.8E-08 HT 767 3.5E-08 2.4E-08 799 2.0E-07 HT 768 5.1E-09 6.6E-08 800 5.1E-07 HT

- 175 037563

769 2.1E-08 5.2E-08 801 4.9Е-08 NT 770 1.1E-08 3.8E-07 802 1.ZE-07 NT 771 8.5E-09 1.6E-07 803 3.6E-08 NT 772 3.0E-08 3.8E-07 804 1.5E-07 NT 805 3.1E-08 8.9E-06 836 2.6E-07 NT 806 1.8E-08 1.4Е-07 837 3.6E-07 NT 807 1.ZE-08 6.7E-09 838 7.9E-08 NT 808 9.6E-09 2.5E-09 839 1.2E-07 NT 809 3.ZE-09 5.6E-09 840 4.7E-07 NT 810 1.6E-08 1.1E-08 841 3.2E-07 NT 811 7.1E-09 4.2E-09 842 5.6E-07 NT 812 4.9Е-09 4.1E-09 843 7.4E-08 nt 813 1.0E-08 5.2E-09 844 3.7E-08 2.8E-07 814 1.4Е-08 NT 845 6.5E-08 NT 815 3.6E-08 1.6E-07 846 1.9Е-08 1.ZE-06 816 3.6E-08 2.3E-08 847 8.ZE-06 NT 817 3.0E-08 1.6E-08 848 1.5E-07 nt 818 48.2% @ 400 μM 52.4% @ 400 μM NT 849 2.9E-07 nt 819 2.2E-07 NT 850 2.1E-08 nt 820 58.5% @ 400 μM 60.9% @ 400 μM NT 851 2.4E-08 nt 821 1.8E-07 NT 852 1.0E-07 nt 822 68.6% @ 400 μM 66.3% @ 400 μM NT 853 1.ZE-07 nt 823 1.1E-07 NT 854 7.5E-08 nt 824 1.8E-07 NT 855 8.5E-08 nt 825 1.2E-07 NT 856 3.9E-08 3.8E-07 826 4.3E-07 NT 857 8.6E-08 NT 827 2.4E-07 nt 858 1.1E-07 nt 828 4.2E-08 4.3E-07 859 6.5E-08 nt 829 5.7E-08 NT 860 8.2E-08 nt 830 3.4E-07 nt 861 5.6E-08 4.1E-07 831 3.1E-06 nt 862 7.3E-08 1.6E-07 832 1.7E-06 nt 863 2.9E-08 1.1E-07 833 3.2E-07 nt 864 3.1E-08 1.0E-07 834 8.6E-08 nt 865 1.5E-08 6.4Е-08 835 1.7E-07 nt 866 8.8E-08 NT 867 1.5E-07 nt 899 5.ZE-07 nt 868 2.5E-08 1.6E-07 900 1.4Е-07 nt 869 7.3E-08 NT 901 1.5E-08 nt 870 4.5E-08 nt 902 2.9E-08 nt 871 5.8E-08 nt 903 1.4Е-07 nt 872 3.1E-08 3.1E-08 904 5.5E-08 nt 873 8.6E-09 3.2E-08 905 1.2E-08 nt

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874 1.5E-08 6.4E-09 906 2.2E-08 HT 875 2.2E-08 1.8E-08 907 3.8E-08 HT 876 2.7E-08 2.3E-08 908 3.7E-08 5.8E-09 877 1.7E-08 1.5E-08 909 2.4E-08 2.8E-09 878 5.2E-09 4.4E-09 910 4.1E-07 HT 879 1.6E-08 HT 911 2.3E-08 HT 880 3.9E-08 5.5E-08 912 1.1E-08 1.06E-08 / 2.01E-08 881 3.9E-08 6.6E-08 913 2.2E-08 2.94E-08 882 4.6E-09 8.2E-09 914 7.9E-09 6.4 IE-09 883 5.3E-09 3.7E-09 915 3.5E-08 1.69Е-08 / 2.29E-08 884 9.8E-09 3.1E-09 916 2.5E-08 T79E-Q8 885 3.6E-08 1.2E-08 917 2.8E-08 9.48E-Q8 886 9.1E-09 1.6E-09 918 1.2E-07 HT 887 9.8E-09 2.8E-09 919 3.3E-08 2.86E-09 888 1.1E-08 5.6E-09 920 2.7E-08 2.1E-08 889 3.0E-09 1.3E-08 921 9.7E-09 4.2E-Q9 890 2.6E-08 HT 922 8.1E-07 HT 891 1.6E-08 3.77E-08 923 2.6E-08 7.5E-09 892 2.6E-08 7.7E-08 924 1.2E-08 2.1 IE-09 893 8.6E-09 2.3E-08 925 5.6E-09 4.6E-09 894 4.8E-09 6.4E-09 926 1.4E-08 5.3E-08 895 6.3E-09 4.7E-09 927 2.8E-07 HT 896 4.1E-09 3.1E-09 928 6.4E-08 HT 897 3.2E-09 2.0E-09 929 1.5E-07 HT 898 6.4E-09 2.2E-09 930 4.1E-07 HT 931 1.2E-07 HT 963 3.78E-08 1.49E-09 932 1.7E-08 5.7E-08 964 8.61E-08 HT 933 1.1E-08 4.1E-08 965 9.40E-08 HT 934 2.3E-05 HT 966 4.73E-08 4.11E-09 935 1.7E-07 7.9E-07 967 4.23E-08 2.21E-09 936 2.0E-05 HT 968 1.74E-07 HT 937 2.6E-07 HT 969 1.53E-07 HT 938 2.58E-08 1.78E-08 970 3.07E-08 9.92E-08 939 2.91E-08 3.25E-08 971 3.35E-08 2.86E-07 940 1.25E-08 7.48E-09 972 6.09E-08 HT 941 1.43E-08 3.99E-09 973 5.19E-08 9.67E-09 942 1.02E-08 1.56E-09 974 2.79E-08 3.66E-09 943 6.62E-09 1.48E-09 975 2.44E-08 2.92E-09 944 1.01E-08 3.19E-09 976 5.76E-08 6.67E-09 945 5.28E-08 6.32E-09 977 4.70E-08 3.95E-09 946 1.80E-08 6.08E-09 978 5.93E-08 1.20E-08 947 1.44E-08 1.96E-09 979 4.58E-08 7.15E-09 948 8.13E-09 2.73E-09 980 4.44E-08 9.71E-09

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949 7.34E-09 2.01E-09 981 4.79E-08 8.68E-09 950 1.22E-08 3.36E-09 982 6.77E-08 1.23E-08 951 3.19E-08 4.66E-08 983 7.25E-08 2.92E-09 952 1.73E-07 NT 984 3.11E-08 1.34E-09 953 2.14E-08 1.51E-09 985 3.25E-08 1.35E-09 954 1.92E-07 NT 986 4.56E-08 2.08E-09 955 1.31E-08 1.18E-09 987 5.15E-08 1.92Е-09 956 1.36E-07 NT 988 6.09E-08 6.05E-09 957 1.52E-08 2.75E-09 989 7.86E-08 3.50E-09 958 1.74E-08 2.40E-09 990 4.69E-08 1.99Е-09 959 1.19E-06 1.24E-06 991 4.60E-08 8.32E-10 960 5.19E-08 2.81E-09 992 6.29E-08 3.03E-09 961 3.58E-08 2.10E-09 993 6.43E-08 1.52E-09 962 3.78E-08 1.90Е-09 994 6.35E-08 9.57E-09 995 8.82E-08 7.82E-09 1005 4.52E-08 8.38E-09 996 5.29E-08 2.81E-09 1006 5.27E-08 1.16E-08 997 3.16E-08 4.21E-09 1007 2.43E-08 1.32E-08 998 6.01E-08 4.48E-08 1008 4.65E-08 1.21E-08 999 3.40E-08 1.62E-08 1009 2.40E-08 7.61E-09 1000 7.97E-08 4.13E-08 1010 2.84E-08 6.27E-09 1001 1.09E-07 NT 1011 2.71E-08 1.09E-08 1002 8.61E-08 1.25E-07 1012 2.75E-08 1.92E-08 1003 3.90E-08 4.07E-08 1013 4.76E-08 2.14E-08 1004 1.81E-08 6.77E-09

NT: not tested.

For partial inhibitors, the percent fluorescence intensity is indicated for the given concentration of the test compound. Accordingly, 48.2% @ 400 μM means that 48.2% fluorescence intensity is observed for a test compound concentration of 400 μM.

Example C. Antitumor activity in vivo.

The antitumor activity of the compounds of the invention was evaluated in a xenograft model using multiple myeloma and / or acute lymphoblastic leukemia cells.

Human tumor cells were transplanted subcutaneously into immunosuppressive mice.

When the tumor volume (TV) reached approximately 200 mm ³ , the mice were orally administered the various compounds once a day for 3 weeks on a 5-day-administration / 2-day-off schedule. Tumor mass was determined twice a week from the very beginning of treatment.

The compounds of the invention exhibited antitumor activity, represented by a TGI (tumor growth inhibition) value at the end of the treatment period, in the range of 40 to 133.4%. The TGI was determined as follows:

/ Median (DTV in Dx in the treatment group) \ TGI = (1 - -----------------------------— I х 100, \ Median (DTV in Dx in the counter, group) / where DTV (delta tumor volume) in Dx = (TV in Dx) - (TV at randomization in the case of each animal).

Example D. Pharmaceutical composition: tablets.

The compound selected from Examples 1-1013, based on 1000 tablets containing it in a dosage of 5 mg 5 g

Wheat starch 20 g Maize starch 20 g Lactose 30 g Magnesium stearate 2 g Silica gel 1 g Hydroxypropyl cellulose 2 g

- 178 -

Claims (35)

CLAIM 1. Compound of formula (I) O R _t where R ₁ represents an aryl group or a heteroaryl group, R ₂ represents a hydrogen atom or a halogen atom, n represents an integer equal to 0, 1 or 2, J represents -C (O) -group, -CH (R ₃ ) -group or -SO ₂ -group, R3 represents a hydrogen atom or a linear or branched _(C1-C6) alkyl group, K represents a bond or -Cy ₁ -group, L represents -Cy ₂ -group or -CH ₂ -Cy ₂ -group, W represents a group o where A is a heteroaryl ring, X represents a carbon atom or a nitrogen atom, R4 represents a hydrogen atom, a halogen atom, a linear or branched _(C1-C6) alkyl group, a linear or branched (C ₂ -C ₆₎ alkenyl group, a linear or branched (C ₂ -C ₆₎ alkynyl group, -Y ₁ -NR ₆ R ₇ group, -Y1-OR6 group, a straight or branched halo _(C1-C6) alkyl group, an oxo group, -Y1-Cy ₃ group, -Cy ₃ -R ₇ group, -Cy ₃ -OR ₇ group , or -Y1-NR6C (O) -R7 group, R5 represents a hydrogen atom, a halogen atom, or a linear or branched (C1-C6) alkyl group, R6 represents a hydrogen atom or a linear or branched _(C1-C6) alkyl group, R ₇ represents a hydrogen atom, a linear or branched _(C1-C6) alkyl group, or -Y ₂ -Cy ₄ group, Y1 and Y ₂ independently represent a bond or a linear or branched (C1S ₄₎ alkylene group, Cy1 represents a cycloalkyl group, a heterocycloalkyl group, an aryl group, or a heteroaryl group that is attached to the J group and to the L group, Cy ₂ , Cy ₃ and Cy ₄ independently represent a cycloalkyl group, a heterocycloalkyl group, an aryl group, or a heteroaryl group, where aryl means a phenyl, naphthyl or indanyl group, heteroaryl means any mono- or fused bicyclic group consisting of 5- 10 ring members containing at least one aromatic moiety and containing from 1 to 3 heteroatoms selected from oxygen, sulfur and nitrogen, cycloalkyl means any mono- or fused bicyclic non-aromatic carbocyclic group containing from 3 to 7 ring members, heterocycloalkyl means any a non-aromatic mono- or fused bicyclic group containing from 3 to 10 ring members and containing from 1 to 3 heteroatoms selected from oxygen, sulfur and nitrogen, wherein the aryl, heteroaryl, cycloalkyl and heterocycloalkyl groups thus defined may be substituted with 1 - 4 groups selected from line or branch nnogo _(C1-C6) alkyl, linear or branched (C ₂ -C ₆₎ alkenyl, linear or branched (C ₂ -C ₆₎ alkynyl, linear or branched halo _(C1-C6) alkyl, -Y1-OR ' , -Y1-NR'R, -Y1-S (O) m-R ', oxo (or N-oxide, as appropriate), nitro, cyano, -C (O) -R', -C (O) -OR ', -OC (O) -R', -C (O) -NR'R, -Y1-NR'-C (O) -R, -Y1-NR'-C (O) -OR, halogen , cyclopropyl and pyridinyl, which may be substituted by linear or branched _(C1-C6) alkyl group, wherein R 'and R independently represent a hydrogen atom, a linear or branched _(C1-C6) alkyl group, a linear or branched (C ₂ -C ₆ ) alkenyl group, linear or branched (C1-C ₆ ) alkoxy group, linear or branched halogen (C1-C ₆ ) alkyl group, linear or branched hydroxy (C1-C ₆ ) alkyl group, linear or branched (C1S _C6) alkoxy _(C1-C6) alkyl group, a phenyl group, a cyclopropylmethyl group, a tetrahydropyranyl group or substituent pairs (R ', R) in place with the nitrogen atom carrying them, form a non-aromatic ring consisting of 5-7 ring members, which may contain, in addition to the nitrogen atom, a second - 179 037563 heteroatom selected from oxygen and nitrogen, where the second nitrogen in question may be substituted by 1 -2 groups representing a hydrogen atom or a linear or branched (C ₁ -C ₆ ) alkyl group, and where m is an integer equal to 0 , 1 or 2, its enantiomers, diastereoisomers and their addition salts with a pharmaceutically acceptable acid or base. 2. Compounds according to claim 1, where W is a group o Λ bm / \ Ν k (A I where R4, R5 and A are as defined in item 1. 3. Compounds according to claim 1, wherein W is a group where R4, R5 and A are as defined in claim 1. 4. Compounds according to claim 1, wherein R ₁ is a phenyl group or a thienyl group. 5. Compounds according to claim 1, wherein R ₂ represents a hydrogen atom and a fluorine atom. 6. Compounds according to claim 1, wherein R ₃ is a hydrogen atom or a methyl group. 7. Compounds according to claim 1, wherein J is a —C (O) - group or —CH ₂ - group. 8. Compounds according to claim 1, wherein K is a bond or a -Cy ₁ -group selected from a phenyl group, a pyrrolyl group, a thienyl group, a thiazolyl group, a pyridinyl group, a tetrahydrobenzothienyl group, a dihydrothienodioxynyl group, a cyclopropyl group, a cyclobutyl group or a pyrrolidinyl groups. 9. A compound according to claim 1, wherein L is a —Cy ₂ group. 10. A compound according to claim 1, wherein Cy ₂ represents a cycloalkyl group, a heterocycloalkyl group, an aryl group or a heteroaryl group which is substituted by 1 or 2 groups selected from linear or branched _(C1-C6) alkyl, linear or branched halo ( _{C1-C6) alkyl, -Y1-OR ', -Y r} NR'R, N- oxide, cyano, -C (O) -OR', -C (O) -NR'R, halogen, wherein R ' and R each independently represent a hydrogen atom, a linear or branched _(C1-C6) alkyl group, a linear or branched _(C1-C6) alkoxy group, or a tetrahydropyranyl group or substituent pairs (R ', R) together with the atom nitrogen carrying them form a non-aromatic ring consisting of 5-7 ring members, which may contain, in addition to the nitrogen atom, a second heteroatom selected from oxygen and nitrogen, where the second considered nitrogen may be substituted by linear or branched (C1- _C6 ) an alkyl group. 11. A compound according to claim 1, wherein K is a thienyl group, a thiazolyl group, or a pyridinyl group, and L is a pyrrolyl group, a furyl group, a thienyl group, a pyrazolyl group, a pyridinyl group, a pyrimidinyl group, or an imidazopyridinyl group, each said heteroaryl group may be substituted with 1 or 2 groups selected from linear or branched _(C1-C6) alkyl, linear or branched halo _{(C1-C6) alkyl, -Y1-oR ', -Y r} NR'R, N- oxide , cyano, -C (O) -NR'R, halogen, wherein R 'and R independently represent a hydrogen atom, a linear or branched _(C1-C6) alkyl group, a linear or branched (C1-C ₆₎ alkoxy, linear or branched _(C1-C6) alkoxy _(C1-C6) alkyl group, or a tetrahydropyranyl group or substituent pairs (R ', R) together with the nitrogen atom carrying them, form a non-aromatic ring consisting of 5- 7 ring members, which can contain in addition to nitrogen atom, a second heteroatom selected from oxygen and nitrogen. 12. Compounds according to claim 1, wherein K is a bond and L is a phenyl group, a thiazolyl group, an oxazolyl group, an isoxazolyl group, a pyrazolyl group, a pyridinyl group, a pyrazinyl group, a pyridazinyl group or a pyrimidinyl group, and each said heteroaryl group may be substituted with 1 or 2 groups selected from linear or branched _{(C1-C6) alkyl, -Y1-oR ', -Y r} NR'R, cyano, -C (O) -OR', halogen, wherein R 'and R independently of each other represent a hydrogen atom, a linear or branched (C _r C ₆ ) alkyl group, or substituents of the pair (R ', R) together with the nitrogen atom carrying them form a non-aromatic ring consisting of 5-7 ring members which may contain, in addition to the nitrogen atom, a second heteroatom selected from oxygen and nitrogen, wherein the second considered nitrogen may be substituted by 1-2 groups representing a hydrogen atom or a linear or branched (C _r C ₆ ) alkyl group. 13. Compounds according to claim 1, where R4 represents a halogen atom, linear or branched (C _r - 180 037563 C ₆ ) an alkyl group or —Y ₁ -Cy ₃ group. 14. Compounds according to claim 1, wherein Cy ₃ is a cycloalkyl group, a heterocycloalkyl group, an aryl group or a heteroaryl group which are substituted by 1-3 groups selected from linear or branched (C ₁ -C ₆ ) alkyl, linear or branched halogen (C ₁ -C ₆ ) alkyl, -Y1OR ', -Yj-NR'R, cyano, halogen, where R' and R independently of each other represent a hydrogen atom or a linear or branched (C ₁ -C ₆ ) alkyl group , or the substituents of the pair (R ', R), together with the nitrogen atom carrying them, form a non-aromatic ring consisting of 5-7 ring members, which may contain, in addition to the nitrogen atom, a second heteroatom selected from oxygen and nitrogen. 15. Compounds according to claim 1, wherein R ₅ represents a hydrogen atom or a methyl group. 16. Compounds according to claim 1, wherein R ₆ is a hydrogen atom or a methyl group. 17. Compounds according to claim 1, wherein R ₇ is a hydrogen atom, a methyl group or a —CH ₂ —Cy ₄ group. 18. Compounds according to claim 1, which are 3 - [(4-hydroxy-1- {[(3R, 4R) -1 - {[3-methyl-5- (pyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4- yl] carbonyl} piperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(1 - {[(3R, 4R) -1 - {[5- (6-aminopyridin-3-yl) -3-fluorothiophen-2-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} - 4-hydroxypiperidin-4-yl) methyl] -7-methyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine-4one; 7-cyclopropyl-3 - [(1- {[(3R, 4R) -1- {[3-fluoro-5- (pyridin-4-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidine-4- yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(1 - {[(3R, 4R) -1 - {[3-fluoro-5- (6-methylpyridin-3-yl) thiophen-2-yl] carbonyl} -3-phenylpiperidin-4yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine-4one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (pyridin-3-yl) -3,7-dihydro-4H-pyrrolo [2,3d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (thiophen-3-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine-4- is he; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (naphthalen-2-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine-4- is he; 7- (4-chlorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3- thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3-methylphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methylphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 7- (3-chlorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3- thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 7- (furan-3-yl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1), 3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine-4- is he; 7- (2-fluorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3- thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 7- (2-chlorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3- thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; - 181 037563 7- [4- (dimethylamino) phenyl] -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1 , 3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] nupuMuguH-4-OH; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- [4- (4-methylpiperazin-1-yl) phenyl] -3,7 dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 7- [3- (dimethylamino) phenyl] -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1 , 3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (1H-pyrrol-1-yl) -3,7-dihydro-4H-pyrrolo [2,3 -d] pyrimidine-4 -is he; 3 - {[1 - ({(3R, 4R) -1 - [(2-bromo-4-methyl-1,3-thiazol-5-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) 4 -hydroxypiperidin-4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 5- (5 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(4-oxo-7-phenyl-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine -3-yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} -4-methyl-1,3-thiazol-2-yl) pyridine 2-carbonitrile; 3 - [(1 - {[(3R, 4R) -1 - ({2- [6- (dumemulamino) nyridin-3-yl] -4-methyl-1,3-thiazol-5-yl} kαrbonyl) - 3-phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - ({4-methyl-2- [6- (trifluoromethyl) pyridin-3-yl]] -1,3-thiazol-5-yl } carbonyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-III-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -4-methyl-1,3-thiazol-5-yl] carbonyl} -3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3d] pyrimidin-4-one; 7- (3-fluorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3- thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-III-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(1 - {[(3R, 4R) -1 - ({2- [6- (dumemulamino) nyridin-3-yl] -1,3-thiazol-5-yl} methyl) -3-phenylpinerigin4- yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-III-pyrrolo [2,3-d] pyrimidine-4one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 7- (4-fluorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3- thiazol-5 yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-III-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (thiophen-3-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - ({2- [6- (morpholin-4-yl) pyridin-3-yl] -1,3-thiazol-5-yl } methyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-III-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3-methylphenyl) -3,7-dihydro-III-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methylphenyl) -3,7-dihydro-III-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-III-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(1 - {[(3R, 4R) -1 - ({2- [6- (dimethylamino) pyridin-3-yl] -1,3-thiazol-5-yl} methyl) -3-phenylpiperidin4- yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-III-pyrrolo [2,3-d] pyrimidin-4-one; 7- (4-chlorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazole-5- yl] methyl} -3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine-4one; 7- (4-chlorophenyl) -3 - [(1 - {[(3R, 4R) -1 - ({2- [6- (dimethulamino) pyridin-3-yl] -1,3-miazol-5-yl } methyl) -3-182 037563 phenylpiperidin-4-yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -6,8-dimethylpyrimido [5 ', 4': 4,5] pyrrolo [1,2-b] pyridαzine-4 (3H) - is he; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- [3- (morpholin-4-yl) phenyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidine- 4th; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- [4- (morpholin-4-yl) phenyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidine- 4th; 7- (3-chlorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazole-5- yl] methyl} -3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine-4one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methyl-1-oxidopyridin-3-yl) -1,3-thiazole-5- yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-III-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - ({2- [6- (piperαzin-1-yl) pyridin-3-yl] -1,3-thiazole -5-yl} methyl) piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - ({2- [6- (trifluoromethyl) pyridin-3-yl] - 1,3-thiazol-5-yl } methyl) piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 7- (3,4-dichlorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1), 3-thiazol-5yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-III-pyrrolo [2,3-d] pyrimidin-4-one; 5- (5 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(4-oxo-7-phenyl-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine -3-yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] methyl} -1,3-thiazol-2-yl) pyridine-2-carbonitrile; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3-methoxyphenyl) -3,7-dihydro-III-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (pyridin-2-yl) -3,7-dihydro-III-pyrrolo [2,3-d] pyrimidine-4- is he; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- [4- (hydroxymethyl) phenyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (thiophen-2-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine-4- is he; 7- (3,4-dimethoxyphenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1), 3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one; 7- (3,4-dimethoxyphenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazole- 5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (pyridin-3-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin4-one; 5 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4 -yl] carbonyl} piperidin-4-yl) methyl] -1-phenyl-1,5-dihydro-4H-pyrazolo [3,4-d] pyrimidin-4-one; 7- (3,5-dimethoxyphenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1), 3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one; 7- (3,5-dimethoxyphenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazole- 5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 7- (4-fluorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazole-5- yl] methyl} 3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one; 4- {3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} - 3-phenylpiperi-183 037563 din-4-yl] carbonyl} piperidin-4-yl) methyl] -4-oxo-3,4-dihydro-7H-pyrrolo [2,3-d] pyrimidin-7-yl} benzonitrile ; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7 - (1-methyl-1H-pyrazol-4-yl) -3,7-dihydro-4H pyrrolo [2,3-d] nupuMuguH -4-OH; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (1-methyl-1H-pyrazol-4-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine- 4th; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- [3 - (hydroxymethyl) phenyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one; 7- [3- (hydroxymethyl) phenyl] -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazole -5yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 7- (4-chloro-3-fluorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) - 1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one; 5 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -1-phenyl-1,5-dihydro-4H-pyrazolo [3,4-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (1-methyl-1H-pyrazol-4-yl) -3,7-dihydro-4H-pyrrolo [2,3d] pyrimidine-4- is he; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- [3 - (hydroxymethyl) phenyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 7- (4-fluorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5- yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 7- (4-chloro-3-fluorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3- thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 7- (3-chloro-5-methoxyphenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) - 1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one; 7- (3-chloro-5-methoxyphenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3- thiazol-5 yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 7- (4-fluoro-3-methoxyphenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) - 1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one; 7- (4-fluoro-3-methoxyphenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3- thiazol-5yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 7- (4-fluoro-3-methoxyphenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3- thiazol5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 7- (4-chloro-3-methoxyphenyl) -3 - [(4-hydroxy-1- {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) - 1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one; 7- (4-chloro-3-methoxyphenyl) -3 - [(4-hydroxy-1- {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3- thiazol-5 yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 7- (4-chlorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5- yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 7- (5-chlorothiophen-2-yl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) - 1,3-thiazol5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3d] pyrimidin-4-one; 7- (5-chlorothiophen-2-yl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3- thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; - 184 037563 7-bromo-3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazole-5- yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] pyrrolo [2,1-f] [1,2,4] triazin-4 (3H) -one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (5-methylthiophen-2-yl) -3,7-dihydro-4Hpyrrolo [2,3-d] nupuMuguH-4-OH ; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (5-methylthiophen-2-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (5-methylthiophen-2-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 7- [4- (hydroxymethyl) phenyl] -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazole -5yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- [4- (hydroxymethyl) phenyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenylpyrrolo [2,1-f] [1,2,4] triazin-4 (3H) -one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenylpyrrolo [2,1-f] [1,2,4] triazin-4 (3H) -one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (thiophen-2-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (thiophen-2-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenylthieno [3,4-d] pyrimidin-4 (3H) -one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenylthieno [3,4-d] pyrimidin-4 (3H) -one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,5-dihydro-4H-pyrrolo [3,2-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,5-dihydro-4H-pyrrolo [3,2-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,5-dihydro-4H-pyrrolo [3,2-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3-methylphenyl) -3,7-dihydro-III-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methylphenyl) -3,7-dihydro-III-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (thiophen-3-yl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- [3 - (morpholin-4-yl) phenyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine-4 -is he; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- [3 - (morpholin-4-yl) phenyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine-4 -is he; 3 - {[1 - ({(3R, 4R) -1 - [(2-bromo-1,3-tuazol-5-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidine- 4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-hydroxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-hydroxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-hydroxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpipe - 185 037563 ridin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-hydroxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3D] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-hydroxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - ({2- [6- (hydroxymethyl) pyridin-3-yl] -1,3-thiazol-5-yl} methyl) - 3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- [3 - (trifluoromethyl) phenyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- [3 - (trifluoromethyl) phenyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 7- [4- (difluoromethyl) phenyl] -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1 , 3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one; 7- [4- (difluoromethyl) phenyl] -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazole -5yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 7- [4- (difluoromethyl) phenyl] -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazole) -5yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 7- [1- (difluoromethyl) -1H-pyrazol-4-yl] -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridine -3yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro4H-pyrrolo [2,3-d] pyrimidin-4-one; 7- [1- (difluoromethyl) -1H-pyrazol-4-yl] -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl ) -1,3thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3 -d] pyrimidine- 4-one; 3 - [(4-hugroxu-1 - {[(3R, 4R) -1 - {[2- (3-methyl-3H-imidazo [4,5-b] purigin-6-yl) -1,3- tuazol-5-yl] methyl} 3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-III-pyrrolo [2,3-d] pyrimidine-4 -is he; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 7- [3- (dimethylαmino) phenyl] -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazole -5yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 7- (3-fluorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazole-5- yl] methyl} 3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one; 3 - [(1- {[(3R, 4R) -1 - {[2- (5-fluoro-6-hydroxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine4 -yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-III-pyrrolo [2,3-d] pyrimidine-4one; 5- (5 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(4-oxo-7-phenyl-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine -3-yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] methyl} -1,3-thiazol-2-yl) pyridine-3-carboxamide; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - ({2- [5- (hydroxymethyl) pyridin-3-yl] -1,3-thiazol-5-yl} methyl) - 3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-III-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - ({2- [6- (tetrahydro-2H-pyran-4-yloxy) pyridin-3-yl] -1 , 3thiazol-5-yl} methyl) piperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one; 3 - [(1- {[(3R, 4R) -1 - {[2- (5-amino-6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine4 -yl] carbonyl} -4-hydroxypiperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-III-pyrrolo [2,3-d] pyrimidine-4one; 3 - {[1 - ({(3R, 4R) -1 - [(2-bromo-1,3-thiazol-5-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidine- 4-yl] methyl} -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[2- (thiophen-2-yl) -1,3-thiazol-5-yl] methyl} piperidine- 4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; - 186 037563 3 - [(4-hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[2- (pyrimidin-5-yl) -1,3-thiazol-5-yl] methyl} piperidine- 4yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (1-methyl-1H-pyrazol-5-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] nurimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (1-methyl-1H-pyrazol-4-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (1-methyl-1H-pyrrol-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[2- (thiophen-3-yl) -1,3-thiazol-5-yl] methyl} piperidine- 4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 7- (2,3-dihydro-1,4-benzodioxin-6-yl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6 -methylpyridin3-yl) -1,3-thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro4H-pyrrolo [2,3- d] pyrimidin-4-one; 7- (2,3-dihydro-1,4-benzodioxin-6-yl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3 -yl) 1,3-thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidine -4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3-hydroxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - {[1 - ({(3R, 4R) -1 - [(2-bromopyridin-4-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidin-4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - {[1 - ({(3R, 4R) -1 - [(5-bromopyridin-3-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidin-4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 7- (3-chlorophenyl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-hydroxypyridin-3-yl) -1,3-thiazole-5- yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(1 - {[(3R, 4R) -1 - {[2- (furan-3-yl) -1,3-tuαzol-5-yl] methyl} -3-phenylnineridin-4-ul] kαrbonyl } -4hydroxypiperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-III-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(1 - {[(3R, 4R) -1 - {[2- (furan-2-yl) -1,3-tuazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl } -4hydroxypiperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-III-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[2- (thiophen-2-yl) -1,3-thiazol-5-yl] methyl} piperidine- 4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[2- (pyrimidin-5-yl) -1,3-thiazol-5-yl] methyl} piperidine- 4yl] carbonyl} piperidin-4-yl) methyl] -7 - (3-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (1-methyl-1H-pyrazol-5-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (1-methyl-1H-pyrazol-4-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (1-methyl-1H-pyrrol-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - {[2- (thiophen-3-yl) -1,3-thiazol-5-yl] methyl} piperidine- 4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(1 - {[(3R, 4R) -1 - {[2- (furan-3-yl) -1,3-tuαzol-5-yl] methyl} -3-phenylnineridin-4-ul] kαrbonyl } -4hydroxypiperidin-4-yl) methyl] -7- (3-methoxyphenyl) -3,7-dihydro-III-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(1 - {[(3R, 4R) -1 - {[2- (furan-2-yl) -1,3-tuazol-5-yl] methyl} -3-phenylnineridin-4-ul] carbonyl } -4hydroxypiperidin-4-yl) methyl] -7- (3-methoxyphenyl) -3,7-dihydro-III-pyrrolo [2,3-d] pyrimidin-4-one; 7- (2,3-dihydro-1,4-benzodioxin-6-yl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridine-3 -yl) 1,3-thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidine -4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3,4,5-trimethoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3,4,5-trimethoxyphenyl) -3,7-dihydro-4H-pyrrolo - 187 037563 [2,3-d] pyrimidin-4-one; 7- (1,3-benzodioxol-5-yl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl ) -1,3thiazol-5-yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidine-4- is he; 7- (1,3-benzodioxol-5-yl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1, 3-thiazol-5yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 7- (1,3-benzodioxol-5-yl) -3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methoxypyridin-3-yl) -1, 3-thiazol-5yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - {[1 - ({(3R, 4R) -1 - [(5-bromopyridin-3-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidin-4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl}) -3phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3,4,5-trimethoxyphenyl) -3,7-dihydro-4Hpyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - (pyridin-3 -ylmethyl) piperidin-4-yl] carbonyl} piperidin4-yl) methyl] -7-phenyl- 3,7-dihydro-3-pyrrolo [2,3-d] pyrimidin-4-one; 3 - {[4-hydroxy-1 - ({(3R, 4R) -1 - [(6'-methyl-3,3'-bipyridin-5-yl) carbonyl] -3-phenylpiperidin-4yl} carbonyl) piperidine -4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3-hydroxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - (pyridin-4-ylmethyl) piperidin-4-yl] carbonyl} piperidin4-yl) methyl] -7-phenyl- 3,7-dihydro-3-pyrrolo [2,3-d] pyrimidin-4-one; 5- [5 - ({(3R, 4R) -4 - [(4-hydroxy-4 - {[7- (3-methoxyphenyl) -4-oxo-4,7-dihydro-3H-pyrrolo [2,3 -d] pyrimidin-3-yl] methyl} piperidin-1-yl) carbonyl] -3-phenylpiperidin-1 -yl} methyl) -1,3-thiazol-2-yl] pyridine 2-carbonitrile; 5- [5 - ({(3R, 4R) -4 - [(4 - {[7- (4-chlorophenyl) -4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine -3yl] methyl} -4-hydroxypiperidin-1-yl) carbonyl] -3-phenylpiperidin-1-yl} methyl) -1,3-thiazol-2yl] pyridine-2-carbonitrile; 5- [5 - ({(3R, 4R) -4 - [(4-hydroxy-4 - {[7- (4-methoxyphenyl) -4-oxo-4,7-dihydro-3H-pyrrolo [2,3 -d] pyrimidin-3-yl] methyl} piperidin-1-yl) carbonyl] -3-phenylpiperidin-1 -yl} methyl) -1,3-thiazol-2-yl] pyridine 2-carbonitrile; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (morpholin-4-yl) -1,3-thiazol-5-yl] carbonyl} -3 -phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidine-4one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - ({2- [6- (2-methoxyethoxy) pyridin-3-yl] -1,3-thiazol-5-yl} methyl ) -3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (4-methylpiperazin-1-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-hydroxypyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -7- (3-hydroxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - {[4-hydroxy-1 - ({(3R, 4R) -1 - [(4-methyl-1,3-thiazol-5-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7-phenyl-3,7-dihydro-III-pyrrolo [2,3-d] pyrimidin-4-one; 3 - {[4-hydroxy-1 - ({(3R, 4R) -1 - [(2-methyl-1,3-thiazol-5-yl) carbonyl] -3-phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7-phenyl-3,7-dihydro-III-pyrrolo [2,3-d] pyrimidin-4-one; 3 - {[1 - ({(3R, 4R) -1 - [(2-chloro-1,3-tuazol-5-yl) kαarbonyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidine- 4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - (pyrazin-2-ylmethyl) piperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7-phenyl- 3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - (1,3-thiazol-5-ylmethyl) piperidin-4-yl] carbonyl} piperidin4-yl) methyl] - 7-phenyl-3,7-dihydro-III-pyrrolo [2,3-d] pyrimidin-4-one; 5- [5 - ({(3R, 4R) -4 - [(4 - {[7- (4-fluorophenyl) -4-oxo-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine -3-yl] methyl} -4-hydroxypiperidin-1-yl) carbonyl] -3-phenylpiperidin-1 -yl} methyl) -1,3-thiazol-2-yl] pyridine-2 carbonitrile; methyl 3 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(4-oxo-7-phenyl-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine-3yl ) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} benzoate; 5 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -1 - (4-methoxyphenyl) -1,5-dihydro-4H-pyrazolo [3,4-d] pyrimidin-4-one; - 188 037563 5 - [(4-rugpoKCu-1 - {[(3R, 4R) -1 - {[2- (6-MeTOKCunupuguH-3-yl) -1,3-thiazol-5-yl] methyl} -3-phenylpiperidine -4-yl] carbonyl} piperidin-4-yl) methyl] -1 - (4-methoxyphenyl) -1,5-dihydro-4H-pyrazolo [3.4D] pyrimidin-4-one; 5 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6-methylpyridin-3-yl) -1,3-thiazol-5-yl] carbonyl} -3 phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -1- (4-methoxyphenyl) -1,5-dihydro-4H-pyrazolo [3,4-d] nupuMuguH-4-OH; 3 - {[4-hydroxy-1 - ({(3R, 4R) -1 - [(2- {6 - [(2-methoxyethyl) amino] pyridin-3-yl} -1,3-thiazol-5- yl) methyl] 3-phenylpiperidin-4-yl} carbonyl) piperidin-4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - {[4-hydroxy-1 - ({(3R, 4R) -1 - [(1-methyl-1H-pyrazol-4-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) piperidin-4 -yl] methyl} -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -3-phenyl-1 - (pyrazin-2-ylmethyl) piperidin-4-yl] carbonyl} piperidin-4yl) methyl] -7- (4 -methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] nupuMuguH-4-OH; 3 - {[4-hydroxy-1 - ({(3R, 4R) -1 - [(5-methyl-1,3-thiazol-2-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - {[1 - ({(3R, 4R) -1 - [(5-bromopyridin-3-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) -4-hydroxypiperidin-4-yl] methyl} -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; methyl 5 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(4-oxo-7-phenyl-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine-3yl ) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] carbonyl} pyridine-3-carboxylate; 1- (2,3-gigro-1,4-benzoguoxin-6-ul) -5 - [(4-gigroxy-1 - {[(3R, 4R) -1 - {[4-methyl-2- (6 -methylnirigin3-yl) -1,3-thiazol-5 -yl] carbonyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -1,5-dihydro4H-pyrazolo [3,4- d] pyrimidin-4-one; 1- (2,3-dihydro-1,4-benzodioxin-6-yl) -5 - [(4-hydroxy-1 - {[(3R, 4R) -1 - {[2- (6-methylpyridin-3 -yl) 1,3-thiazol-5-yl] methyl} -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -1,5-dihydro-4Hpyrazolo [3,4-d] pyrimidine -4-one; 3 - {[4-hydroxy-1 - ({(3R, 4R) -1 - [(5-methyl-1,3-thiazol-2-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - {[4-hydroxy-1 - ({(3R, 4R) -1 - [(3-methyl-1,2-oxazol-5-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7-phenyl-3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - {[1 - ({(3R, 4R) -1 - [(2,4-gimethyl-1,3-thiazol-5-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) -4hydroxypiperidine- 4-yl] methyl} -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - [(4-hydroxy-1 - {[(3R, 4R) -1 - (1,3-oxazol-4-ylmethyl) -3-phenylpiperidin-4-yl] carbonyl} piperidin-4-yl) methyl] -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 3 - {[4-hydroxy-1 - ({(3R, 4R) -1 - [(5-methyl-1,3-oxazol-2-yl) methyl] -3-phenylpiperidin-4-yl} carbonyl) piperidine -4-yl] methyl} -7- (4-methoxyphenyl) -3,7-dihydro-4H-pyrrolo [2,3-d] pyrimidin-4-one; 5 - {[(3R, 4R) -4 - ({4-hydroxy-4 - [(4-oxo-7-phenyl-4,7-dihydro-3H-pyrrolo [2,3-d] pyrimidine-3- yl) methyl] piperidin-1-yl} carbonyl) -3-phenylpiperidin-1-yl] methyl} pyridine-2-carbonitrile; 3 - [[4-hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine4-carbonyl] -4 -piperidyl] methyl] -7- [4- (hydroxymethyl) phenyl] pyrrolo [2,1-f] [1,2,4] triazin-4-one; 3 - [[4-hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine4-carbonyl] -4 -piperidyl] methyl] -7- [4- (hydroxymethyl) phenyl] thieno [3,4-d] pyrimidin-4-one; 3 - [[4-hydroxy-1 - [(3R, 4R) -1- [2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl ] methyl] -7- (3-methoxyphenyl) pyrrolo [2,3-d] pyrimidin-4-one; 3 - [[3,3-difluoro-4-hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3 - phenylpiperidin-4-carbonyl] -4-piperidyl] methyl] -7-phenylpyrrolo [2,3-d] pyrimidin-4-one; 3 - [[3,3-difluoro-4-hydroxy-1 - [(3R, 4R) -1- [4-methyl-2- (6-methyl-3-pyridyl) thiazole-5-carbonyl] -3phenylpiperidine- 4-carbonyl] -4-piperidyl] methyl] -7- (4-methoxyphenyl) pyrrolo [2,3-d] pyrimidin-4-one; 3 - [[4-hydroxy- 1 - [(3R, 4R) -1 - [(2-methoxypyrimidin-4-yl) methyl] -3-phenylpiperidin-4-carbonyl] -4-piperidyl] methyl] -7-phenylpyrrolo [ 2,3 -d] pyrimidin-4-one; 3 - [[4-hydroxy- 1 - [(3R, 4R) -1 - [(2-methoxypyrimidin-4-yl) methyl] -3-phenylpiperidin-4-carbonyl] -4piperidyl] methyl] -7- (4 -methoxyphenyl) pyrrolo [2,3-d] pyrimidin-4-one; 3 - [[4-hydroxy-1 - [(3R, 4R) -1 - [(5-methylpyrazin-2-yl) methyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7-phenylpyrrolo [ 2,3 -d] pyrimidin-4-one; 3 - [[4-hydroxy-1 - [(3R, 4R) -1 - [(5-methylpyrazin-2-yl) methyl] -3-phenylpiperidine-4-carbonyl] -4piperidyl] methyl] -7- (4 -methoxyphenyl) pyrrolo [2,3-d] pyrimidin-4-one; 3 - [[4-hydroxy- 1 - [(3R, 4R) -3-phenyl-1- (pyrimidin-2-ylmethyl) piperidine-4-carbonyl] -4-piperidyl] methyl] -7-phenylpyrrolo [2, 3-d] pyrimidin-4-one; 3 - [[4-hydroxy- 1 - [(3R, 4R) -3-phenyl-1- (pyrimidin-2-ylmethyl) piperidine-4-carbonyl] -4-piperidyl] methyl] -7- (4-methoxyphenyl ) pyrrolo [2,3-d] pyrimidin-4-one; 3 - [[4-hydroxy-1 - [(3R, 4R) -1 - [(2-methylpyrimidin-4-yl) methyl] -3-phenylpiperidin-4-carbonyl] -4-piperidyl] methyl] -7-phenylpyrrolo [ 2,3 -d] pyrimidin-4-one; 3 - [[4-hydroxy-1 - [(3R, 4R) -1 - [(2-methylpyrimidin-4-yl) methyl] -3-phenylpiperidine-4-carbonyl] -4-189 037563 piperidyl] methyl] - 7- (4-methoxyphenyl) pyrrolo [2,3-d] pyrimidin-4-one; 3 - [[4-hydroxy-1 - [(3 R, 4R) -1 - [(6-methoxypyridazin-3-yl) methyl] -3-phenylpiperidine-4-carbonyl] -4piperidyl] methyl] -7- ( 4-methoxyphenyl) pyrrolo [2,3-d] pyrimidin-4-one; 3 - [[4-hydroxy-1 - [(3 R, 4R) -1 - [(5-methylpyrazin-2-yl) methyl] -3-phenylpiperidine-4-carbonyl] -4-piperidyl] methyl] -7 -phenylthieno [3,4-d] pyrimidin-4-one; 3 - [[4-hydroxy-1 - [(3 R, 4R) -1 - [(2-methylpyrimidin-4-yl) methyl] -3-phenylpiperidine-4-carbonyl] -4piperidyl] methyl] -7-phenylthieno [3,4-d] pyrimidin-4-one. 19. A method of obtaining a compound of formula (I) according to claim 1, characterized in that the compound of formula (II) is used as the starting material where R ₂ and n are as defined for formula (I), which is coupled with a compound of formula (III) where R ₁ is as defined for formula (I) and PG is an amine protecting group to give a compound of formula (IV) where R _b R ₂ , n and PG are as defined above, the compound of formula (IV) is then converted to an epoxy compound of formula (V) where R _b R ₂ , n and PG are as defined above, the compound of formula (V) is then coupled with a compound of formula (VI) (VI), where W is as defined for formula (I), to give a compound formula (VII) where R _b R ₂ , n, W and PG are as defined above, the compound of formula (VII), after the reaction to remove the protecting group PG, is then coupled with the compound of formula (XI) where J, K and L are as defined for formula (I) and Y is a hydroxy group or a halogen atom to give a compound of formula (I). 20. A method of obtaining a compound of formula (Ia), a particular case of a compound of formula (I) according to claim 1, where the compound of formula (VII), after the reaction of deprotection of the protective group PG, is then coupled with a compound of formula (VIII) (VIII), where J is as defined for formula (I), K 'is —Cy ₁ —group, Y is hydroxy or a halogen atom, and Z is a halogen atom to give a compound of formula (IX) where R _b R ₂ , J, n, W and Z are as defined in clause 19, and K 'is as defined 190 037563 above, a compound of formula (IX) is then coupled with a compound of formula (X) where L is as defined for formula (I) and RB1 and R _B2 represent a hydrogen atom, a linear or branched (C _r C ₆ ) alkyl group, or R _B1 and R _{B2 are} joined by a linear or branched (C ₂ -C ₆ ) an alkylene group, to obtain a compound of formula (Ia), a particular case of compounds of formula (I) where R1, R ₂ , J, K ', L, n and W are as defined above. 21. A method of obtaining a compound of formula (I-a), a particular case of a compound of formula (I) according to claim 1, characterized in that the compound of formula (XII) where R1 is as defined for formula (I) and PG is a protecting group of the carboxylic acid function which is coupled with a compound of formula (VIII) y ^ H (VIII), where J is as defined for formula (I) , K 'is a -Cy ₁ -group, Y is a hydroxy group or a halogen atom and Z is a halogen atom, to give a compound of formula (XIII) where R1, J, K ', Z and PG are as defined above and the compound of formula (XIII) is then coupled with a compound of formula (X) where L is as defined for formula (I) and RB1 and R _B2 represent a hydrogen atom, a linear or branched (C1-C6) alkyl group, or RB1 and R _{B2 are} joined by a linear or branched (C ₂ -C ₆ ) an alkylene group to give a compound of formula (XIV) where R1, J, K ', L and PG are as defined above, the compound of formula (XIV), after the deprotection reaction PG, is coupled with a compound of formula (II) where R ₂ and n are as defined for formula (I) to give a compound of formula (XVI) wherein R1, R _2, J, K ', L and n are as defined above, the compound of formula (XVI) is then converted into an epoxy compound of formula (XVII) - 191 037563 where R1, R ₂ , J, K ', L and n are as defined above, the compound of formula (XVII) is then coupled with a compound of formula (VI) (VI), where W is as defined for formula (I-a), a particular case of compounds of formula (I) where R1, R ₂ , J, K ', L, n and W are as defined above. 22. A method of obtaining a compound of formula (I) according to claim 1, characterized in that the compound of formula (XII) where R1 is as defined for formula (I) and PG is a protecting group of the carboxylic acid function which is coupled with a compound of formula (XI) where J, K and L are as defined for formula (I) and Y is hydroxy or a halogen atom to give a compound of formula (XV) where R1, J, K, L and PG are as defined above, the compound of formula (XV) after the deprotection reaction PG is then coupled with a compound of formula (II) where R2 and n are as defined for formula (I) to give a compound of formula (XVIII) where R1, R ₂ , J, K, L and n are as defined above, the compound of formula (XVIII) is then converted to an epoxy compound of formula (XIX) where R1, R ₂ , J, K, L and n are as defined above, the compound of formula (XIX) is then coupled with a compound of formula (VI) 7 < ^νι > · where W is as defined for formula (I) to give a compound of formula (I). 23. A pharmaceutical composition containing a compound of formula (I) according to any one of claims 1 to 18 or an addition salt thereof with a pharmaceutically acceptable acid or base in combination with one or more pharmaceutically acceptable excipients. 24. The use of a pharmaceutical composition according to claim 23 as proapoptotic and / or antiproliferative agents. - 192 037563 25. Use of a pharmaceutical composition according to claim 24 for the treatment of malignant diseases and autoimmune diseases, and diseases of the immune system. 26. The use of the pharmaceutical composition according to claim 25 for the treatment of cancer of the bladder, brain, breast and uterus, chronic lymphoid leukemia, cancer of the colon, esophagus and liver, lymphoblastic leukemia, acute myeloid leukemia, lymphomas, melanomas, malignant blood diseases, myeloma, ovarian cancer, non-small cell lung cancer, prostate cancer, pancreatic cancer, and small cell lung cancer. 27. The use of a pharmaceutical composition according to claim 23 for the manufacture of medicaments as proapoptotic and / or antiproliferative agents. 28. The use of a pharmaceutical composition according to claim 23 for the manufacture of medicaments for the treatment of malignant diseases and autoimmune diseases, and diseases of the immune system. 29. The use of a pharmaceutical composition according to claim 23 for the manufacture of medicines for the treatment of cancer of the bladder, brain, breast and uterus, chronic lymphoid leukemia, cancer of the colon, esophagus and liver, lymphoblastic leukemia, acute myeloid leukemia, lymphoma, melanoma, malignant blood diseases, myelomas, ovarian cancer, non-small cell lung cancer, prostate cancer, pancreatic cancer and small cell lung cancer. 30. Use of a compound of formula (I) according to any one of claims 1 to 18 or an addition salt thereof with a pharmaceutically acceptable acid or base for the treatment of cancer of the bladder, brain, breast and uterus, chronic lymphoid leukemia, cancer of the colon, esophagus and liver, lymphoblastic leukemia, acute myeloid leukemia, lymphomas, melanomas, malignant blood diseases, myelomas, ovarian cancer, non-small cell lung cancer, prostate cancer, pancreatic cancer, and small cell lung cancer. 31. Use of a compound of formula (I) according to any one of claims 1 to 18 or an addition salt thereof with a pharmaceutically acceptable acid or base for the manufacture of medicaments for the treatment of cancer of the bladder, brain, breast and uterus, chronic lymphoid leukemia, cancer colon, esophagus and liver, lymphoblastic leukemia, acute myeloid leukemia, lymphomas, melanomas, malignant blood diseases, myelomas, ovarian cancer, non-small cell lung cancer, prostate cancer, pancreatic cancer and small cell lung cancer. 32. A pharmaceutical combination having the activity of a USP7 inhibitor, a compound of formula (I) according to any one of claims 1-18 with antineoplastic agents selected from genotoxic agents, mitotic poisons, antimetabolites, proteasome inhibitors, kinase inhibitors, protein-protein interaction inhibitors, immunomodulators , E3 ligase inhibitors, T cells with chimeric antigen receptors and antibodies. 33. A pharmaceutical composition comprising a combination according to claim 32 in combination with one or more pharmaceutically acceptable excipients. 34. Use of a combination according to claim 32 for the treatment of malignant diseases. 35. Use of a combination according to claim 32 for the manufacture of medicaments for the treatment of malignant diseases.