MX2008008521A - Protein kinase inhibitors - Google Patents

Abstract

Compounds of formula (I) that inhibit protein kinases, compositions containing the compounds and methods of treating diseases using the compounds are disclosed.

Description

INHIBITORS OF PROTEIN CINASA This application claims priority with respect to the SOUTHERN PROVISIONAL NORTEAM ERICANA LIC SERIES NUMBER OF SERI E 60 / 754,685, SUBMITTED ON DECEMBER 29, 2005. FIELD OF THE INVENTION The present invention relates to compounds that in h iben proteins. kinases, to compositions containing the compounds, and to methods for the treatment of diseases using the compounds. BACKGROUND OF THE INVENTION Numerous diseases in humans are characterized by increased and uncontrolled cell growth. This biology is managed, in many cases, by an increase in signaling of the growth factor. In addition, these pathologies often require an expanded blood supply and new growth of blood vessels. Protein kinases are key components of both cell proliferation and endothelial cell expansion. The kinases are, therefore, important targets for therapeutic intervention in pathologies characterized by uncontrolled cell growth. BRIEF DESCRIPTION OF THE INVENTION One embodiment of the present invention, therefore, relates to compounds that inhibit protein kinases and that have the formula I oo, and salts, prodrugs, salts of prodrugs and metabolites thereof, wherein one of X1 or X2 is C, and the other is C or N; X3 is C (H), C (alkyl of 1 to 4 carbon atoms), or N; X4 is N or C; X5 is C (H) or N; X6 is C (H) or N; A1 is R1 or R2; R1 is a phenyl radical, which is fused with benzene, heteroarene or heterocycloalkane, which is fused or not with benzene; R2 is a heteroaryl radical, which is fused with benzene or heteroarene; B1 is R3, R \ R5 or W1; R3 is phenyl which is fused or not with benzene, heteroarene or R3A; R3A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R 4 is a heteroaryl radical, which is or is not fused with benzene, heteroarene or R A; R 4A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R5 is a cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl radical, each of which is or not fused with benzene, heteroarene or R5A; R5A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; W1 is an alkyl, alkenyl or alkynyl radical, each of which is or is not substituted with one or two groups which are independently selected from W2, W3, W4, OH, OW5, SW5, S (O) W5, SO2W5, NH2, NHW5, N (W5) 2, C (O) NH2, C (O) NHW5, C (O) N (W5) 2, NHC (O) W5o NW5C (O) W5; W2 is a phenyl radical, which is or is not fused with benzene, heteroarene or W2A; W2A is a cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene radical; W3 is a heteroaryl radical, which is or is not fused with benzene, heteroarene OW3A; W3A is a cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene radical; W4 is a cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl radical, each of which is or is not fused with benzene, heteroarene or W5A; W5A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; W5 is an alkyl, alkenyl or alkynyl radical; Where the portions represented by A0 B \ W2, W3 and W4 are independently substituted or unsubstituted with one or two or three or four groups which are independently selected from R6, OR6, SR6, S (O) R6, SO2R6, NH2, NHR6, N (R6) 2, C (O) R6, C (O) OR6, C (O) NH2I C (O) NHR6, C (O) N (R6) 2, NHC (O) R6, NR6C (O R6, NHSO2R6, NR6SO2R6; NHC (O) OR6, NR6C (O) OR6, SO2NH2, SO2NHR6, SO2N (R6) 2, NHC (O) NH2, NHC (O) NHR6, NHC (O) N (R6) 2, NR6C (O) N ( R6) 2, C (N) NH2, C (N) NHR6, C (N) N (R6) 2, NHC (N) NH2, NHC (N) NHR6, NHC (N) N (R6) 2, OH, (O), C (O) H, C (O) OH, NO2, CN, CF3, OCF3, CF2CF3, F, Cl, Br or I; R6 is R7, R8, R9, or R10; R7 is a phenyl radical which is or is not fused with benzene, heteroarene, or R7A; R7A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R8 is a heteroaryl radical, which is or is not fused with benzene, heteroarene or R8A; R8A is a cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene radical; R9 is a cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl radical, each of which is or is not fused with benzene, heteroarene; or R9A; R9A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R10 is an alkyl, alkenyl or alkynyl radical, each of which is or is not substituted with or two groups that are independently selected from R11, OR1 \ SR1 \ S (O) R1 \ SO2R1 \ NH2, NHR11 N (R11) 2 , C (O) R11, C (O) NH2, C (O) NHR1C (O) N (R11) 2, NHC (O) R11 NR 1C (O) R11, NHSO2R11, NR11SO2R10 NHC (O) OR11 NR11 , C (O) OR11 SO2NH2, SO2NHR11, SO2N (R11) 2, NHC (O) NH2, NHC (O) NHR11 NHC (O) N (R11) 2, NR11C (O) N (R11) 2) OH, ( O), C (O) OH, CN, CF3, OCF3 CF2CF3, F, Cl, Br or I; R1 is alkyl, alkenyl, alkynyl R12, R13, R14 or T1; R12 is a phenyl radical, which is or is not fused with benzene, heteroarene or R12A; R12A is a cycloalkane, cycloalkene heterocycloalkane or heterocycloalkene radical; R13 is a heteroaryl radical which is or is not fused with benzene, heteroarene or R13A; R13A is a cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene radical; and R14 is a cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl radical, each of which is or is not fused with benzene, heteroarene; or R1 A; R14A is a cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene radical; T1 is an alkenyl or alkynyl alkyl radical, each of which is substituted with one or two groups which are independently selected from OH, OT2, ST2, S (O) T2, NH2, NHT2 or N (T2) 2; T2 is an alkyl, alkenyl or alkynyl radical; Wherein the portions represented by R7, R8, R9 and R11 are independently substituted or not with one or two or three or four groups that are independently selected from R15, OR15, SR15, S (O) R15, SO2R15, C (O) R15 , C (O) (O) R15, C (O) NH2, C (O) NHR15, C (O) N (R15) 2, OH, (O), C (O) OH, CN, CF3OCF3, CF2CF3 F , Cl, Br or I, wherein R15 is an alkyl, alkenyl, alkynyl radical, each of which is unsubstituted or substituted by phenyl, heteroaryl, cycloalkyl, heterocycloalkyl, OH, OR16, C (O) NH2, C (O ) NHR16, C (O) N (R16) 2; wherein R16 is an alkyl, alkenyl or alkynyl radical; and wherein the phenyl, heteroaryl, cycloalkyl and heterocycloalkyl radicals of R15 are unsubstituted or substituted with O (alkyl). Another embodiment refers to compounds that have the formula I, where One of X1 or X2 is C, and the other is C or N; X3 is C (H) or N; X4 is N or C; X5N; X6 is C (H); A1 is R1 or R2; R1 is a phenyl radical which is fused with benzene, heteroarene or heterocycloalkane, which is or is not fused with benzene; R2 is a heteroaryl radical, which is fused with benzene or heteroarene; B1 is R3, R4, R5 or W1; R3 is a phenyl radical, which is or is not fused with benzene or heteroarene; R 4 is a heteroaryl radical which is fused or not with benzene or heteroarene; R5 is a cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl radical, each of which is or is not fused with benzene or heteroarene; W1 is an alkyl, alkenyl, or alkynyl radical, each of which is or is not substituted with W2, W3, W4, OH, OW5, SW5, S (O) W5, SO2W5, NH2, NHW5, N (W5) 2 l C (O) NH2, C (O) N HW5, C (O) N (W5) 2, N HC (O) W5 or NW5C (O) W5; W2 is a phenyl radical, which is or is not fused with benzene or heteroarene; W3 is a heteroaryl radical, which is or is not fused with benzene or heteroarene; w4 is a cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl radical, each of which is or is not fused with benzene or heteroarene; W5 is an alkyl, alkenyl or alkynyl radical; wherein the portions represented by A \ B \ W2, W3 and W4 are independently substituted or unsubstituted with one or two or three or four groups which are independently selected from R6, OR6, SR6, S (O) R6, SO2R6, NH2 , NHR6, N (R6) 2, C (O) R6, C (O) OR6, C (O) NH2, C (O) NHR6, C (O) N (R6) 2, NHC (O) R6, NR6C (O) R6, NHSO2R6, NR6SO2R6, NHC (O) OR6, NR6C (O) OR6, SO2NH2, SO2NHR6, SO2N (R6) 2, OH, (O), C (O) H, C (O) OH, NO2 , CN, CF3, OCF3, CF2CF3, F, Cl, Br or I; R6 is R7, R8, R9, or R10; R7 is a phenyl radical, which is or is not fused with benzene or heteroarene; R8 is a heteroaryl radical, which is or is not fused with benzene or heteroarene; is a cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl radical, each of which is or is not fused with benzene or heteroarene, R 0 is an alkyl, alkenyl or alkynyl radical, each of which is or is not substituted with one or two groups which are independently selected from R1 \ OR \ SR10S (O) R1 \ SO2R1 \ NH2, NHR1 \ N (R1) 2, C (O) R1 \ C (O) NH2, C (O) NHR10 C (O) N (R11) 2, NHC (O) R1 \ NR11C (O) R1 \ NHSO2R1 \ NR11S2R11NHC (O) OR11 NR1C (O) OR1 \ SO2NH2, SO2NHR1 \ SO2N (R11) 2, OH, (O), C ( O) OH, CN, CF3) OCF3CF2CF3, F, Cl, Br or I; R 11 is an alkyl, alkenyl, alkynyl, R 12, R 3, R 14 or T r 12 radical is a phenyl radical, which is or is not fused with benzene or heteroarene; R 13 is a heteroaryl radical, which is or is not fused with benzene or heteroarene; R 4 is a cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl radical, each of which is or is not fused with benzene or heteroarene; T1 is an alkyl, alkenyl, or alkynyl radical, each of which is substituted with one or two groups which is independently selected from OH, OT2, ST2, S (O) T2, NH2, NHT2 or N (T2) 2; T2 is an alkyl, alkenyl or alkynyl radical; wherein the portions represented by R7, R8, R9 and R11 are independently substituted or not with one or two or three or four groups that are independently selected from R15, OR15, SR15, S (O) R15, SO2R15, C (O) R15, C (O) (O) R15, C (O) NH2, C (O) NHR15, C (O) N (R15) 2, OH, (O), C (O) OH, CN, CF3, OCF3 , CF2CF3, F, Cl, Br or I; wherein R15 is an alkyl, alkenyl, alkynyl radical, each of which is unsubstituted or substituted by phenyl, heteroaryl, cycloalkyl, heterocycloalkyl OH, OR16, C (O) NH2, C (O) NHR16, C (O) N (R16) 2; wherein R16 is an alkyl, alkenyl, or alkynyl radical; and where the phenyl, heteroaryl, cycloalkyl and heterocycloalkyl radicals of R15 are or are not substituted with O (alkyl). Yet another embodiment refers to compositions comprising an excipient and a therapeutically effective amount of a compound having the formula I. Still another embodiment refers to compositions comprising an excipient and therapeutically effective amounts of a compound having the formula I, and one or more additional therapeutic agents. Still another embodiment relates to methods for the treatment of a mammal suffering from a disease that involves the overexpression or deregulation of a protein kinase, which comprises administering thereto, a therapeutically effective amount of a compound having the formula I. Yet another embodiment relates to methods for the treatment of a mammal suffering from a disease that involves the overexpression or deregulation of a protein kinase, which comprises administering to it, radiotherapy and a therapeutically effective amount of a compound having the formula I . Yet another embodiment relates to methods for the treatment of a mammal suffering from cervical cancer, colon cancer, endometrial cancer, esophageal cancer, lung cancer which comprises administering to it, a therapeutically effective amount of a compound having the formula I. Still another modality refers to methods for the treatment of a mammal suffering from cervical cancer, colon cancer, endometrial cancer, esophageal cancer, lung cancer comprising administering to it, radiotherapy and a therapeutically effective amount of a compound having the formula I. Still another embodiment, relates to methods for the treatment of diseases involving the overexpression or deregulation of a protein kinase in a mammal, which comprises administering to it, therapeutically effective amounts of a compound having the formula I, and one or more additional therapeutic agents. Yet another embodiment comprises methods for the treatment of diseases involving the overexpression or deregulation of a protein kinase in a mammal, comprising administering to it, radiotherapy and therapeutically effective amounts of a compound having the Formula I and one or more of one of the additional therapeutic agents. Still another embodiment comprises methods for the treatment of cervical cancer, colon cancer, endometrial cancer, esophageal cancer, lung cancer in a mammal, which comprises administering thereto, a therapeutically effective amount of a compound having Formula I, and one or more of one of the additional therapeutic agents. Still another embodiment comprises methods for the treatment of cervical cancer, colon cancer, endometrial cancer, esophageal cancer, lung cancer in a mammal, comprising administering to the same, radiotherapy and a therapeutically effective amount of a compound having the Formula I, and one or more of one of the additional therapeutic agents. Still another embodiment comprises the compounds: c s-4- (4- (4-amino-3- (2-phenyl-1 H -benzimidazol-6-yl) -1 H -pyrazolo [3,4-d] pyrimidine- 1 -yl) -cyclohexyl) -1-methylpiperazin-2-one; c / s-4- (4- (4-amino-3- (2- (4-fluorophenyl) -1 H -benzimidazol-6-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1 - il) cyclohexyl) -1-methylpiperazin-2-one; c / s-4- (4- (4-amino-3- (2-cyclopropyl-1 H -benzimidazol-6-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) -1-methylpiperazin-2-one; c / s-4- (4- (4-amino-3- (2-pyridin-2-yl-1 H-benzimidazol-6-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1 - il) cyclohexyl) -1-methylpiperazin-2-one; trans- 1 - (4- (2-methoxyethoxy) cyclohexyl) -3- (2-phen i 1-1 H -benzimidazol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; c / 's-1 - (4- (4-methyl-piperazin-1-yl) -cyclohexyl) -3- (2-phenyl-1 H-benzimidazol-5-yl) -1 H-pyrazolo [3,4-d] ] pyrimidin-4-amine; frans- 1 - (4-morpholin-4-yl-cyclohexyl) -3- (2-phenyl-1 H -benzimidazol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; í? ans-3- (2- (4-methylphenyl) -1 H -benzimidazol-6-yl) -1 - (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; Irans-3- (2- (4-chlorophenyl) -1 H -benzimidazol-6-yl) -1 - (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidine- 4-amine; fra / 7S-3- (2- (4-methoxyphenyl) -1 H -benzimidazol-6-yl) -1 - (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; f -a 7S-3- (2- (3,4-dichlorophenyl) -1 H -benzimidazol-6-yl) -1 - (4- morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; r? aps-3- (2-benzyl-1 H -benzimidazol-6-yl) -1 - (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4- amine; frans- 1 - (4-morpholin-4-yl-cyclohexyl) -3- (2- (2-phenylethyl) -1 H -benzimidazol-6-yl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; frans- 1 - (4-morphol-4-yl-cyclohexy I) -3- (2- (thien-2-I -methyl) - 1 H-benzimidazol-6-yl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; Rrans-3- (2- (3-chlorobenzyl) -1 H -benzimidazol-6-yl) -1 - (4-morphol in -4-i I-cyclohexy I) - 1 H-pyrazolo [3,4- d] pyrimidin-4-amine; frans-3- (2- (4-chlorobenzyl) -1 H -benzimidazol-6-yl) -1 - (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidine- 4-amine; fra /?-1 - (4-morpholin-4-yl-cyclohexyl) -3- (2- (1-phenylethyl) -1 H -benzimidazol-6-yl) -1 H-pyrazolo [3,4-d] ] pyrimidin-4-amine; f? ans-3- (2- (2-chlorobenzyl) -1 H -benzimidazol-6-yl) -1 - (4-morfol i n-4-i I-cyclohexy I) -1 H-pyrazolo [3 , 4-d] pyrimidin-4-amine; fA-a / 7S-3- (2- (2-fluorobenzyl) -1 H -benzimidazole-6-M) -1 - (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4- d] pyrimidin-4-amine; γ -ans-3- (2- (2-methylbenzyl) -1 H -benzimidazol-6-yl) -1 - (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; frans-3- (2- (3-fluorobenzyl) -1 H -benzimidazol-6-yl) -1 - (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidine- 4-amine; fra / 7S-3- (2- (3-methylbenzyl) -1 H -benzimidazol-6-yl) -1 - (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; fra / 7s-3- (2- (4-fluorobenzyl) -1 H -benzimidazol-6-yl) -1 - (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4- d] pyrimidin-4-amine; frar? s-3- (2- (4-methylbenzyl) -1H-benzimidazol-6-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidine- 4-amine; Iris-3- (2- (3,4-dichlorobenzyl) -1H-benzimidazol-6-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidine- 4-amine; tVans-3- (2- (2,6-dichlorobenzyl) -1H-benzimidazol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3, 4-d] pyrimidin-4-amine; fra /? -3- (2- (2,3-dichlorobenzyl) -1H-benzimidazol-5-yl) -1- (4-morphol i n-4-i I-cyclohexy I) - 1 H-pyrazolo [3,4-d] pyrimidin-4-amine; fra? s-3- (2 - ((3-fluorophenyl) amino) -1H-benzimidazol-6-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4- d] pyrimidin-4-amine; irra-3- (2-benzyl-4-methyl-1 H-benzimidazol-6-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; rrans-3- (2-benzyl-1-methyl-1 H-benzimidazol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidine -4-amine; fra / 7S-1- (4- (4-amino-3- (2-benzyl-1 H-benzimidazol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) pyrrolidin-3-ol; c / s-1- (4- (4-amino-3- (2-benzyl-1 H-benzimidazol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl) -cyclohexyl pyrrolidin-3-ol; frans-3- (2-benzyl-1 H-benzimidazol-5-yl) -1- (4- (4- (ethylsulfonyl) piperazin-1-yl) cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidine -4-amine; c / s-3- (2-benzyl-1H-benzimidazol-5-yl) -1- (4- (4- (ethylsulfonyl) piperazin-1-yl) cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; rrans-3- (2-benzyl-1 H-benzimidazol-5-yl) -1- (4- (4- (2- methoxyethyl) piperazin-1-yl) cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; c / s-3- (2-benzyl-1H-benzimidazol-5-yl) -1- (4- (4- (2-methoxyethyl) piperazin-1-yl) cyclohexyl) -1 H-pyrazolo [3,4 -d] pyrimidin-4-amine; frar > s-3- (2-Benzyl-1H-benzimidazol-5-yl) -1- (4 - ((3R, 5S) -3,5-dimethylpiperazin-1-yl) cyclohexyl) -1H-pyrazolo [3,4 -d] pyrimidin-4-amine; c / 's-3- (2-benzyl-1H-benzimidazol-5-yl) -1- (4 - ((3R, 5S) -3,5-dimethylpiperazin-1-yl) cyclohexyl) -1H-pyrazolo [ 3,4-d] pyrimidin-4-amine; í? a7S-1- (4- (4-acetylpiperazin-1-yl) cyclohexyl) -3- (2-benzyl-1 H-benzimidazol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidine- 4-amine; cis- 1- (4- (4-acetylpiperazin-1-yl) cyclohexy l) -3- (2-benzyl-1 H -benzimidazol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidine- 4-amine; f? a /? s-3- (2-benzyl-1H-benzimidazol-5-yl) -1- (4- (3- (trifluoromethyl) -5,6-dihydro [1,2,4] triazolo [4 , 3-a] pyrazin-7 (8H) -yl) cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; c / s-3- (2-benzyl-1H-benzimidazol-5-yl) -1- (4- (3- (trifluoromethyl) -5,6-dihydro [1,2,4] triazolo [4.3-] a] pyrazin-7 (8H) -yl) cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; 2- (4- (4-amino-3- (2-benzyl-1H-benzimidazol-5-yl) -1H-pyrazolo [3,4-d] pyrimidin-1-yl) piperidin-1-yl) acetamide; rraps-1- (4- (4-amino-3- (2-benzyl-1 H-benzimidazol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) piperidin- 3-carboxamide; c / s-1- (4- (4-amino-3- (2-benzyl-1 H-benzimidazol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) piperidine-3-carboxamide; frans-1- (4- (4-amino-3- (2-benzyl-1 H-benzimidazol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) piperidin- 4-carboxamide; c / s-1- (4- (4-amino-3- (2-benzyl-1 H-benzimidazol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) piperidine-4-carboxamide; 3- (2-Benzyl-1H-benzimidazol-5-yl) -1- (4- (morpholin-4-yl-methyl) phenyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; frar / s-3- (2-benzyl-1 H-benzimidazol-5-yl) -1- (4- (4- (methylsulfonyl) piperazin-1-yl) cyclohexyl) -1 H-pyrazolo [3,4- d] pyrimidin-4-amine; c / s-3- (2-benzyl-1 H-benzimidazol-5-yl) -1- (4- (4- (methylsulfonyl) piperazin-1-yl) cyclohexyl) -1 H-pyrazolo [3,4- d] pyrimidin-4-amine; 3- (2-Benzyl-1H-benzimidazol-5-yl) -1- (1- (morpholin-4-yl-carbonyl) piperidin-4-yl) -1H-pyrazolo [3,4-d] pyrimidin-4 -amine; 2- (3- (4-amino-3- (2-benzyl-1H-benzimidazol-5-yl) -1H-pyrazolo [3,4-d] pyrimidin-1-yl) pyrrolidin-1-yl) acetamide; frans-2- (4- (4- (4-amino-3- (2-benzyl-1 H-benzimidazol-5-yl) -1H-pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) piperazin-1-yl) ethanol; c / s-2- (4- (4- (4-amino-3- (2-benzyl-1 H-benzimidazol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl ) cyclohexyl) piperazin-1-yl) ethanol; 4- (4-amino-3- (2-benzyl-1 H-benzimidazol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexanol; c / s-7- (4- (4-methyl-piperazin-1-yl) -cyclohexyl) -5- (2-phenyl-1 H-benzimidazol-5-yl) -7H-pyrrolo [2,3-d] pyrimidine- 4-amine; c / s-7- (4- (4-methyl-piperazin-1-yl) -cyclohexyl) -5- (2- (2-phenylethyl) - 1H-benzimidazol-5-yl) -7H-pyrrolo [2,3-d] pyrimidin-4-amine; c / s-3- (2-anilino-1,3-benzoxazol-6-yl) -1- (4- (4-methylpiperazin-1-yl) cyclohexyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; fraps-3- (2-anilino-1,3-benzoxazol-6-yl) -1- (4- (4-methylpiperazin-1-yl) cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4 -amine; f? ans-3- (2-anilino-1,3-benzoxazol-6-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4 -amine; Iris-3- (2-anilino-1,3-benzoxazol-6-yl) -1- (4- (2-methoxyethoxy) cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; r / "aris-3- (2- (2-chloro-6-fluorobenzyl) -1H-benzimidazol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3, 4-d] pyrimidin-4-amine; rra /? S-3- (1- (2-chlorobenzyl) -1H-indol-4-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; frar / s-3- (1- (2-chlorobenzyl) -1H-indol-6-yl) -1- (4-morpholin-4-yl) -cyclohexyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; f / -ar; s-3- (1- (2-chlorobenzyl) -1 H-indol-5-yl) -1 - (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; rra? S-3- (1- (3-chlorobenzyl) -1 H-indole- 5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; f? A /? S-3- (2-benzyl) 1,3-benzoxazol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; frans-3- (1- ( 2-chlorobenzyl) -1H-indazol-6-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; frans-3- ( 1- (3-chlorobenzyl) -1H-indazol-6-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine; frar? s-3- (2-benzyl-1, 3-benzoxazol-6-yl) -1 - (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4 -amine; trans-3- (1 - (3-f luorobenzyl) -1 H-indazol-6-yl) -1 - (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidine -4-amine; 3- (2-Benzyl-1 H-benzimidazol-5-yl) -1 - (1 - (methylsulfonyl) piperidin-4-yl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; (2S) -1 - (4-amino-3- (2-benzyl-1 H-benzimidazol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl) -3-morpholine- 4-yl-propan-2-ol; frans-3- (2- (2,6-difluorobenzyl) -1 H -benzimidazol-6-yl) -1 - (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4 -d] pyrimidin-4-amine; Ira / 7S-3- (2- (3-trifluorobenzyl) -1 H-benzimidazol-6-yl) -1 - (4-morphol i n-4-i I-cyclohexy I) - 1 H-pyrazolo [ 3,4-d] pyrimidin-4-amine; rraps-3- (3 - ((2,4-dimethylphenyl) amino) -1 H -indazol-6-yl) -1 - (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4 -d] pyrimidin-4-amine; Ipses-3- (3 - ((2-chlorophenyl) amino) -1 H -indazol-5-yl) -1 - (4-morpholin-4-yl-cyclohexyl) -1 H-priazolo [3,4-d] ] pyrimidin-4-amine; frans-3- (3 - ((3-chlorophenyl) amino) -1 H -indazol-5-yl) -1 - (4-morphol i n-4-i I-cyclohexy I) - 1 H-pyrazolo [ 3,4-d] pyrimidin-4-amine; í? aps-3- (3 - ((3-fluorophenyl) amino) -1 H -indazol-5-yl) -1 - (4-morphol n-4-yl-cyclohexyl) -1 H-pyrazolo [3 , 4-d] pyrimidin-4-amine; f / -ans-1 - (4-morpholin-4-yl-cyclohexyl) -3- (3 - ((3-nitrophenyl) amino) -1 H -indazol-5-yl) -1 H-pyrazolo [3, 4-d] pyrimidin-4-amine; frans-3- (3 - ((2-methoxyphenyl) amino) -1 H -ndazol-5-yl) -1 - (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4- d] pyrimidin-4-amine; trans- 1 - (4-morpholin-4-yl-cyclohexyl) -3- (3 - ((6- (trifluoromethyl) pyridin-3-yl) amino) -1 H -indazol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; frar / s-3- (3- (benzylamino) -1H-indazol-6-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidine-4- amine; frans- 1- (4-morpholin-4-yl-cyclohexyl) -3- (3 - ((4- (trifluoromethyl) phenyl) amino) -1H-indazol-5-yl) -1H-pyrazolo [3,4 -d] pyrimidin-4-amine; frans-3- (3 - ((4-ferf-butylphenyl) amino) -1H-indazol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4- d] pyrimidin-4-amine; frans-3 - ((5- (4-amino-1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-3-yl) -1 H- indazol-3-yl) amino) phenol; frans-3- (3 - ((2-fluoro-5-methylphenyl) amino) -1H-indazol-6-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1H-pyrazolo [3,4 -d] pyrimidin-4-amine; fraps-3- (3 - ((2,5-dimethylphenyl) amino) -1H-indazol-6-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1H-pyrazolo [3,4-d] ] pyrimidin-4-amine; ions? 3- (3 - ((2,5-difluorophenyl) amino) -1H-indazol-6-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3, 4-d] pyrimidin-4-amine; frar / s-3- (3 - [(4-fluoro-2-methylphenyl) amino] -1H-indazol-6-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H- pyrazolo [3,4-d] pyrimidin-4-amine; and frar / s-1- (4-morpholin-4-yl-cyclohexyl) -3- (2-phenoxy-1 H-benzimidazol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-4 -amine; 3- (2-Benzyl-1H-benzimidazol-5-yl) -1- (1- (methylsulfonyl) piperidin-4-yl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; (frans) -3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1- (4-morpholin-4-yl cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4 -amine; (frans) -3- (1 - (2-chlorobenzyl) -1 H -indazol-6-yl) -1 - (4-morpholin-4-i-cyclohexy I) -1 H-pyrazolo [3,4 -d] pyrimidin-4-amine; 3- (2-Benzyl-1 H-benzimidazol-6-yl) -1 - (2-morpholin-4-yl-ethyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; 3- (2-benzyl-1 H-benzimidazol-6-yl) -1 - (1-pyrimidin-2-yl-piperidin-4-yl) -1 H -pyrazolo [3,4-d] pyrimidin-4- amine; (frans) -3- (2- (2, 3-d if luorobenzyl) -1 H-benzimidazol-6-yl) -1 - (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3, 4-d] pyrimidin-4-amine; (frans) -3- (2- (3,4-difluorobenzyl) -1 H -benzimidazol-6-yl) -1 - (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4- d] pyrimidin-4-amine; (frans) -3- (2- (3,5-difluorobenzyl) -1 H -benzimidazol-6-yl) -1 - (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4- d] pyrimidin-4-amine; (frans) -3- (2-Benzyl-1 H-benzimidazol-5-yl) -1 - (4 - ((2- (methylsulfonyl) ethyl) amino) cyclohexyl) -1 H-pyrazolo [3,4-d ] pyrimidin-4-amine; (c / s) -3- (2-Benzyl-1 H-benzimidazol-5-yl) -1 - (4 - ((2- (methylsulfonyl) ethyl) amino) cyclohexyl) -1 H-pyrazolo [3,4 -d] pyrimidin-4-amine; 3- (2-Benzyl-1 H-benzimidazol-5-yl) -1 - (4- (1,1-dioxydothiomorpholin-4-yl) cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4 -amine; 3- (2-Benzyl-1 H-benzimidazol-5-yl) -1 - (4 - (((2- (methylsulfonyl) ethyl) amino) methyl) phenyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; (frans) -2- (4- (4- (4-amino-3- (2- (2-fluorobenzyl) -1 H -benzimidazol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidine -1 - il) cyclohexyl) piperazin-1-yl) ethanol; (c / 's) -2- (4- (4- (4-amino-3- (2- (2-fluorobenzyl) -1 H- benzimidazol-5-yl) -1 H-pyrazolo [3,4- d] pyrimidin-1-yl) cyclohexyl) piperazin-1-yl) ethanol; (frans) -3- (2- (2-Chloro-3-fluorophenyl) -1 H -benzimidazol-6-yl) -1 - (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3, 4-d] pyrimidin-4-amine; (frans) - 1 - (4-morpholine-4-yl-cyclohexyl) -3- (2- (3- (trifluoromethyl) benzyl) -1 H -benzimidazol-6-yl) -1 H-pyrazolo [3, 4- d] pyrimidin-4-amine; N- (4- (4-amino-3- (2-benzyl-1 H -benzimidazol-5-yl) -1 H-pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) methanesulfonamide; 4- (4-amino-3- (2-benzyl-1 H -benzimidazol-5-yl) -1 H- pyrazolo [3,4-d] pyrimidin-1-yl) -cyclohexylcarbamate in ethyl; 3- (2-Benzyl-1 H-benzimidazol-5-yl) -1 - (1 - (2- '(methylsulfonyl) ethyl) pyrrolidin-3-yl) -1 H -pyrazolo [3,4-d] pyrimidine -4-amine; 3- (2- (2-fluorobenzyl) -1 H -benzimidazol-5-yl) -1 - (1 - (2- (methylsulfonyl) ethyl) pyrrolidin-3-yl) -1 H-pyrazolo [3,4- d] pyrimidin-4-amine; (frans) -3- (2-benzyl-1 H-benzimidazol-5-yl) -1 - (4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl) -1 H-pyrazolo [3, 4-d] pyrimidin-4-amine; (c / s) -3- (2-Benzyl-1 H-benzimidazol-5-yl) -1 - (4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl) -1 H-pyrazolo [ 3,4-d] pyrimidin-4-amine; (frans) -3- (1-benzyl-1 H -indol-5-yl) -1- (4-morphol-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4 -amine; (frans) -3- (1- (2-methylbenzyl) -1H-indol-5-yl) -1- (4-morphol i n-4-i-cyclohexyl) -1 H-pyrazolo [3,4- d] pyrimidin-4-amine; (frans) -3- (1- (3-methylbenzyl) -1H-indol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidine -4-amine; (frans) -3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1- (4-morpholin-4-y1-cyclohexy I) -1 H-pyrazolo [3,4- d] pyrimidin-4-amine; (frans) -3- (1 - (3-f luorobenzyl) -1H-indol-5-i I) -1- (4-morfol i n-4-i I-cyclohexy I) -1 H-pyrazolo [ 3,4-d] pyrimidin-4-amine; (frans) -1- (4-morpholin-4-yl-cyclohexyl) -3- (1- (2- (trifluoromethyl) benzyl) -1H-indol-5-yl) -1 H-pyrazolo [3,4- d] pyrimidin-4-amine; (frans) -3- (1- (2-fluorobenzyl) -1H-indazol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidine- 4-amine; (frans) -3- (1- (2-chlorobenzyl) - 1H-indazol-5-yl) -1- (4-morphol-n-4-yl-cyclohexyl) -1 H-pyrazolo [3,4- d] pyrimidin-4-amine; (frans) -3- (1- (3-chlorobenzyl) -1H-indazol-5-yl) -1- (4-morphol-n-4-yl-cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine; (frans) -3- (1-Benzyl-1H-indazol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; 3- (2-Benzyl-1H-benzimidazol-5-yl) -1- (1- (2- (methylsulfonyl) ethyl) piperidin-4-yl) -1 H -pyrazolo [3,4-d] pyrimidine-4- amine; 3- (2- (2-fluorobenzyl) -1H-benzimidazol-5-yl) -1- (1- (2- (methylsulfonyl) ethyl) piperidin-4-yl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; (frans) -3- (1- (cyclohexylmethyl) -1H-indol-5-i I) -1- (4-morfol i n-4-i I-cyclohexy I) -1 H-pyrazolo [3,4 -d] pyrimidin-4-amine; (frans) -3- (1-cyclopentyl-1H-indol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine; (frans) -3- (1- (2,3-difluorobenzyl) -1H-indol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4-d] ] pyrimidin-4-amine; (frans) -3- (1- (2,5-difluorobenzyl) -1H-indol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4-d] ] pyrimidin-4-amine; (frans) -3- (1 - (2,6-difluorobenzyl) -1H-indol-5-yl) -1- (4-morphol i n-4-i I-cyclohexy I) -1 H-pyrazolo [ 3,4-d] pyrimidin-4-amine; (frans) -3- (1- (2,5-dichlorobenzyl) -1H-indol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; (frans) -3- (1- (2,6-dichlorobenzyl) -1H-indol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; (frans) - 1- (4-morpholin-4-yl-cyclohexyl) -3- (2- (phenylsulfonyl) -1 H -benzimidazol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidine- 4-amine; (frans) -2- (4- (4- (4-amino-3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidine- 1-yl) cyclohexyl) piperazin-1-yl) ethanol; (frans) -3- (1- (2-fluorobenzyl) -1H-indazol-6-yl) -1- (4-morphol-n-4-yl-cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine; 3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1- (4- (4- (2-ethoxyethyl) piperazin-1-yl) cyclohexyl) -1 H-pyrazolo [3, 4 -d] pyrimidin-4-a mine; (c / s) -2- (4- (4- (4-amino-3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1 H-pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) piperazin-1-yl) ethanol; 4- (4-amino-3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexanol; 3- (2-Benzyl-1H-benzimidazol-6-yl) -1- (3-pyridin-3-yl-propyl) - 1 H-pyrazolo [3,4-d] pyrimidin-4-amine; 3- (2-Benzyl-1H-benzimidazol-6-yl) -1- (1-benzylpiperidin-4-yl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; 3- (2-Benzyl-1 H-benzimidazol-6-yl) -1- (2- (4-methyl-1,3-thiazol-5-yl) ethyl) -1 H-pyrazolo [3,4-d] ] pyrimidin-4-amine; 3- (2-Benzyl-1H-benzimidazol-6-yl) -1- (1- (6-chloropyridazin-3-yl) piperidin-4-yl) -1 H -pyrazolo [3,4-d] pyrimidine- 4-amine; and 143c 3- (2-benzyl-1H-benzimidazol-6-yl) -1- (4-morpholin-4-yl-but-2-ynyl) -1 H -pyrazolo [3,4-d] pyrimidin-4- amine; 3- (2-Benzyl-1H-benzimidazol-6-yl) -1- (4- (4- (ethylsulfonyl) piperazin-1-yl) but-2-ynyl) -1 H -pyrazolo [3,4-d] ] pyrimidin-4-amine; (c / 's) -5- (2- (2-chlorobenzyl) -1H-benzimidazol-6-yl) -7- (4- (4-methylpiperazin-1-yl) cyclohexyl) -7H-pyrrolo [2, 3-d] pyrimidin-4-amine; (frans) -3- (4- (4- (4-amino-3- (2-benzyl-1 H-benzimidazol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl ) cyclohexyl) piperazin-1-yl) propan-1-ol; (c / s) -3- (4- (4- (4-amino-3- (2-benzyl-1 H-benzimidazol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1 -yl) cyclohexyl) piperazin-1-yl) propan-1-ol; (c / s) -3- (4- (4- (4-amino-3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1 H-pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) piperazin-1-yl) propan-1-ol; (frans) -3- (4- (4- (4-amino-3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidine- 1-yl) cyclohexyl) piperazin-1-yl) propan-1-ol; 2- (1- (4- (4-amino-3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl ) piperidin-4-yl) ethanol; (frans) -2- (1- (4- (4-amino-3- (1- (2-chlorobenzyl) -1H-indol-5-yl) - 1 H -pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) piperidin-4-yl) ethanol; (c / s) - (1- (4- (4-amino-3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] pyrimidin-1 -yl) cyclohexyl) piperidin-4-yl) methanol; (frans) - (1- (4- (4-amino-3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] pyrimidin-1-yl ) cyclohexyl) piperidin-4-yl) methanol; (c / s) -3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1- (4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; (frans) -3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1- (4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; 3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1- (4-pyrrolidin-1-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; 3- (4- (4- (4-amino-3- (1- (2-chlorobe'zyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] pyrimidin-1-yl cyclohexyl) piperazin-1-yl) propanenitrile; 3- (1- (2-fluorobenzyl) -1H-indol-5-M) -1- (4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl) -1 H-pyrazolo [3,4 -d] pyrimidin-4-amine; 1- (4- (4- (2-ethoxyethyl) piperazin-1-yl) cyclohexyl) -3- (1- (2-f luorobenzyl) -1 H-indol-5-yl) -1 H -pyrazolo [3, 4-d] pyrimidin-4-amine; (c / s) -2- (4- (4- (4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1 H-pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) piperazin-1-yl) ethanol; (frans) -2- (4- (4- (4-am ino-3- (1 - (2-f luorobenzyl) -1 H-indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) piperazin-1-yl) ethanol; (c / s) -3- (4- (4- (4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) - 1 H-pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) piperazin-1-yl) propan-1-ol; (frans) -3- (4- (4- (4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1 -yl) cyclohexyl) piperazin-1-yl) propan-1-ol; 3- (4- (4- (4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] pyrimidin-1-yl) - cyclohexyl) piperazin-1-yl) propanenitrile; 3- (2-Benzyl-1H-benzimidazol-6-yl) -1 - ((2-pyridin-3-yl-1,3-thiazol-4-yl) methyl) -1 H-pyrazolo [3,4- d] pyrimidin-4-amine; 3- (2-Benzyl-1H-benzimidazol-6-yl) -1 - ((4-benzylmorpholin-2-yl) methyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; 3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1- (3- (1,1-dioxidothiomorpholin-4-yl) propyl) -1H-pyrazolo [3,4-d] pyrimidine -4-amine; 1- (4- (4-acetylpiperazin-1-yl) but-2-ynyl) -3- (2-benzyl-1H-benzimidazol-6-yl) -1 H -pyrazolo [3,4-d] pyrimidine- 4-amine; 3- (2-Benzyl-1H-benzimidazol-6-yl) -1- (4- (4- (2-methoxyethyl) piperazin-1-yl) but-2-ynyl) -1 H -pyrazolo [3,4- d] pyrimidin-4-amine; 3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1- (4- (1,1-dioxidothiomorpholin-4-yl) but-2-ynyl) -1 H -pyrazolo [3,4 -d] pyrimidin-4-amine; 1- (4- (4-acetylpiperazin-1-yl) but-2-ynyl) -3- (1- (2-chlorobenzyl) -1 H -indol-5-yl) -1 H -pyrazolo [3,4- d] pyrimidin-4-amine; 3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1- (4- (4- (2-methoxyethyl) piperazin-1-yl) but-2-ynyl) -1 H -pyrazolo [ 3,4-d] pyrimidin-4-amine; 1 - ((4-benzylmorpholin-2-yl) methyl) -3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-4- amine; (frans) -3- (2- (2-chlorobenzyl) -1H-benzimidazol-6-yl) -1- (4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl) -1 H -pyrazolo [ 3,4-d] pyrimidin-4-amine; 3- (2-Benzyl-1H-benzimidazol-5-yl) -1- (1- (3-methoxypropyl) pyrrolidin-3-yl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine; (frans) -3- (2-Benzyl-1H-benzimidazol-5-yl) -1- (4- (4- (2- (1,3-dioxolan-2-yl) ethyl) piperazin-1-yl cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine; (c / s) -3- (2-Benzyl-1 H-benzimidazol-5-yl) -1- (4- (4- (2- (1,3-dioxolan-2-yl) ethyl) piperazin-1 -yl) cyclohexyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; (frans) - 1- (4-morphol-n-4-yl-cyclohexy I) -3- (1 - (tetrahydro-2H-pyran-2-yl-methyl) -1H-indol-5-yl ) -1H-pyrazolo [3,4-d] pyrimidin-4-amine; (frans) -1- (4-morpholin-4-yl-cyclohexyl) -3- (1- (pyridin-3-yl-methyl) -1H-indol-5-yl) -1 H -pyrazolo [3,4- d] pyrimidin-4-amine; (frans) - 1- (4-morfol i n-4-i I-cyclohexy l) -3- (1- (pyrid i n-2 -i l-meti I) -1H-indol-5-yl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; 3- (2-Benzyl-1H-benzimidazol-5-yl) -1-ferf-butyl-1H-pyrazolo [3,4-d] pyrimidin-4-amine; 5- (2-Benzyl-1H-benzimidazol-5-yl) -7-ferf-butyl-7H-pyrrolo [2,3-d] pyrimidin-4-amine; 5- (2-Benzyl-1 H-benzimidazol-5-yl) -7- (4- (4-methyl-piperazin-1-yl) -cyclohexyl) -7H-pyrrolo [2,3-d] pyrimidin-4-amine; (frans) -3- (1 -benz 1-1 H -benzi midazol-5-i I) -1- (4-morphol in -4-i-cyclohexyl) -1 H-pyrazolo [3,4-d ] pyrimidin-4-amine; (frans) -3- (1- (2-chlorobenzyl) -1H-benzimidazol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidine- 4-amine; (frans) -3- (1 - (2-f luorobenzyl) - 1 H -benzidazol-5-i I) - 1 - (4-morphol i n-4-i I-cyclohexy I) - 1 H-pyrazolo [3,4-d] pyrimidin-4-amine; 3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1-tetrahydro-2 H -pyran-4-yl-1 H -pyrazolo [3,4-d] pyrimidin-4-amine; 3- (2-Benzyl-1 H-benzimidazol-5-yl) -1- (3-methoxypropyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; 3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1- (3-methoxypropyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine; 3- (2-Benzyl-1H-benzimidazol-5-yl) -1-tetrahydro-2 H -pyran-4-yl-1 H -pyrazolo [3,4-d] pyrimidin-4-amine; 3- (2-Benzyl-1 H-benzimidazol-5-yl) -1- (1-methylpiperidin-4-yl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; 3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1- (1-methylpiperidin-4-yl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; 3- (2-Benzyl-1H-benzimidazol-5-yl) -1- (3- (dimethylamino) propyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; 3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1- (3- (dimethylamino) propyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine; (frans) -3- (2- (2-bromobenzyl) -1H-benzimidazol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidine- 4-amine; (frans) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidine -4-amine; (c / s) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-5-yl) -1- (4- (4- (3- methoxy propyl) pipe razin-1 -i l) cyclohexy l) -1 H-p i razo lo [3,4-d] pyrim id i n-4-amine; (frans) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-5-yl) -1- (4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; (frans) -3- (2- (2-bromobenzyl) -1H-benzimidazol-5-yl) -1- (4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; (c / s) -3- (2- (2-Bromobenzyl) -1H-benzimidazol-5-yl) -1- (4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; 3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1- (1, -methyl-1,4'-bipiperidin-4-yl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine; 3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1- (1'-ethyl-1,4'-bipiperidin-4-yl) -1 H-pyrazolo [3,4-d] ] pyrimidin-4-amine; 3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1- (1, -propyl-1,4, -bipiperidin-4-yl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine; 3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1- (r-isopropyl-1,4'-bipiperidin-4-yl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; 3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1- (1, -isobutyl-1,4'-bipiperidin-4-yl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine; (frans) -3- (2-Benzyl-1H-indol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine; (frans) -3- (2-Benzyl-1H-indol-6-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; 3 (1- (2-chlorobenzyl) -1H-indol-5-yl) -1- (4 - ((4- (3-methoxypropyl) piperazin-1-yl) methyl) phenyl) -1H-pyrazolo [3, 4-d] pyrimidin-4-amine; (frans) -3- (2- (2-chlorobenzyl) -1H-indol-6-yl) -1- (4-morpholin-4-yl-cyclohexy I) - 1 H-pyrazolo [3,4-d] ] pyrimidin-4-amine; (3 - ((4- (4-amino-3- (1- (2-fluorobenzyl) -1 H -indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) amino) phenyl) methanol; 4 - ((4- (4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) amino ) -3-methylphenol; 3 - ((4- (4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) amino )phenol; 4 - ((4- (4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) amino ethyl benzoate; Acid (frans) -3 - ((4- (4-amino-3- (1- (2-fluorobenzyl) -1 H -indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1 -yl) cyclohexyl) amino) benzoic acid; Acid (c / s) -3 - ((4- (4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1 H -pi razolo [3, 4-d] pirim id i n-1 -yl) cyclohexy I) amino) benzoic; (frans) -3- (2- (2-chlorobenzyl) -1H-indol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidine -4-amine; (frans) -3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidine -4-amine; 3 - ((4- (4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1 H-pi acid [3, 4-d] pirim id in-1- il) cyclohexyl) amino) -4-chlorobenzoic acid; (frans) -3- (2- (4-methylphenoxy) -1H-benzimidazol-6-yl) -1- (4-morphol i n-4-i I-cyclohexy I) - 1 H-pyrazolo [3, 4-d] pyrimidin-4-amine; (frans) -3- (2- (3-methylphenoxy) -1H-benzimidazol-6-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidine -4-amine; 3- (4- (4- (4-amino-3- (3- (2-fluorobenzyl) -1 H -indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl ) cyclohexyl) piperazin-1-yl) propan-1-ol; (c / 's) -3- (4- (4- (4-amino-3- (2- (2-fluorobenzyl) -1H-indol-5-yl) - 1 H -pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) piperazin-1-yl) propan-1-ol; (frans) -3- (4- (4- (4-amino-3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidine -1-yl) cyclohexyl) piperazin-1-yl) propan-1-ol; 3- (3- (2-fluorobenzyl) -1H-indol-5-yl) -1- (4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl) -1 Hp i razo lo [3, 4-d] pyrim-din-4-amine; 3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1- (4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl) -1 H -pi-reazole [3 , 4-d] pyrim id i n-4-amine; 2- (4- (4- (4-amino-3- (3- (2-fluorobenzyl) -1 H -indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl ) cyclohexyl) piperazin-1-yl) ethanol; (c / s) -2- (4- (4- (4-amino-3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1 H-pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) piperazin-1-yl) ethanol; (frans) -2- (4- (4- (4-amino-3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1 -yl) cyclohexyl) piperazin-1-yl) ethanol; (cs) -3- (4- (4- (4-amino-3- (2-benzyl-1 H -indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl ) cyclohexyl) piperazin-1-yl) propan-1-ol; (frans) -3- (4- (4- (4-amino-3- (2-benzyl-1 H -indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl ) cyclohexyl) piperazin-1-yl) propan-1-ol; 3- (2-benzyl-1H-indol-5-yl) -1- (4- (4- (3-methoxypropyl) piperazine- 1-yl) cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; (c / s) -2- (4- (4- (4-amino-3- (2-benzyl-1 H -indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1 -yl) cyclohexyl) piperazin-1-yl) ethanol; (frans) -2- (4- (4- (4-amino-3- (2-benzyl-1 H -indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl ) cyclohexyl) piperazin-1-yl) ethanol; (c / s) -4- (4- (4-amino-5- (1- (2-fluorobenzyl) -1H-indol-5-yl) -7H-pyrrolo [2,3-d] pyrimidin-7- il) cyclohexyl) -1-isopropylpiperazin-2-one; (c / s) -4- (4- (4-amino-5- (1- (2-chlorobenzyl) -1H-indol-5-yl) -7H-pyrrolo [2,3-d] pyrimidin-7- il) cyclohexyl) -1-isopropylpiperazin-2-one; (c / s) -4- (4- (4-amino-5- (1- (2-fluorobenzyl) -1H-indol-5-yl) -7H-pyrrolo [2,3-d] pyrimidin-7- il) cyclohexyl) -1-ethylpiperazin-2-one; (c / s) -4- (4- (4-amino-5- (1- (2-chlorobenzyl) -1H-indol-5-yl) -7H-pyrrolo [2,3-d] pyrimidin-7- il) cyclohexyl) -1-ethylpiperazin-2-one; 5- (1- (2-fluorobenzyl) -1H-indol-5-yl) -7- (4- (4-methylpiperazin-1-yl) cyclohexyl) -7H-pyrrolo [2,3-d] pyrimidin-4 -amine; 5- (1- (2-chlorobenzyl) -1H-indol-5-yl) -7- (4- (4-methylpiperazin-1-yl) cyclohexyl) -7H-pyrrolo [2,3-d] pyrimidin-4 -amine; 7-ferf-butyl-5- (1- (2-fluorobenzyl) -1H-indol-5-yl) -7H-pyrrolo [2,3-d] pyrimidin-4-amine; 7-ferf-butyl-5- (1- (2-chlorobenzyl) -1 H -indol-5-yl) -7H-pyrrolo [2,3-d] pyrimidin-4-amine; 3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1- (4- (morpholin-4-yl-methyl) phenyl) -1 H -pyrazolo [3,4-d] pyrimidin-4 -amine; Acid (frans) -4 - ((4- (4-amino-3- (1- (2-fluorobenzyl) -1 H-indol 5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1- il) cyclohexyl) amino) benzoic; Acid (c / s) -4 - ((4- (4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] pyrimidine- 1-yl) cyclohexyl) amino) benzoic acid; 3- (2- (2-chlorobenzyl) -1H-benzimidazol-5-yl) -1- (4- (morpholin-4-yl-methyl) phenyl) -1 H -pyrazolo [3,4-d] pyrimidin-4 -amine; 3- (2- (3-methylbenzyl) -1 H -benzimidazol-5-yl) -1- (4- (morpholin-4-yl-methyl) phenyl) -1 H -pyrazolo [3,4-d] pyrimidine- 4-amine; 3- (2- (2-bromobenzyl) -1H-benzimidazol-5-yl) -1- (4- (morpholin-4-yl-methyl) phenyl) -1H-pyrazolo [3,4-d] ] pyrimidin-4-amine; 3- (2- (2-methoxybenzyl) -1H-benzimidazol-5-yl) -1- (4- (morpholin-4-yl-methyl) phenyl) -1 H -pyrazolo [3,4-d] pyrimidine- 4-amine; (frans) -4- (4- (4- (4-amino-3- (2-benzyl-1 H-benzimidazol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) piperazin-1-yl) -2-methylbutan-2-ol; (cs) -4- (4- (4- (4-amino-3- (2-benzyl-1 H-benzimidazol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl ) cyclohexyl) piperazin-1-yl) -2-methylbutan-2-ol; (c / s) -3 - ((4- (4-amino-3- (1- (2-fluorobenzyl) -1 H -indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidine -1-yl) cyclohexyl) amino) propan-1-ol; (frans) -3 - ((4- (4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1- il) cyclohexyl) amino) propan-1-ol; 2 - ((4- (4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) amino )ethanol; 2- (2 - ((4- (4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) amino) ethoxy) ethanol; (c / s) - (2S) -3 - ((4- (4-amino-3- (1- (2-fluorobenzyl) -1H-indole-5- il) -1 H-pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) amino) propane-1,2-diol; (frans) - (2S) -3 - ((4- (4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1 H-pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) amino) propane-1,2-diol; 2,2 '- (4- (4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexylazanodiil ) diethanol; (c / s) -N- (4- (4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] pyrimidin-1- il) cyclohexyl) -beta-alanine; (frans) -N- (4- (4-amino-3- (1 - (2-f luorobenzyl) -1 H-indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1- il) cyclohexyl) -beta-alanine; (frans) -4- (4-amino-3- (2- (2-methoxybenzyl) -1 H -benzi m id azol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl cyclohexanol; N- (4- (4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-M) -1H-pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) -L -to the girl; (c / s) -N- (4- (4-amino-3- (1- (2-fluorobenzyl) -1 H -indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidine- 1-yl) cyclohexyl) -D-alanine; (frans) -N- (4- (4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl ) cyclohexyl) -D-alanine; N- (4- (4-amino-3- (1- (2-fluorobenzyl) -1 H -indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) -N-methylglycine; (frans) - 1- (4- (4- (3-methoxy propi I) pipe razin-1 -i I) cyclohexy I) -3- (2- (thien-2-yl-methyl) -1 H- benzimidazol-6-yl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine; 3- (2-Benzyl-1H-benzimidazol-6-yl) -1- (1 '- (3-methoxypropyl) -1,4'-bipiperidin-4-yl) -1 H-pyrazolo [3,4-d] ] pyrimidin-4-amine; (c / s) -2- (4- (4- (4-amino-3- (1- (2- (difluoromethoxy) benzyl) -1H-indol-5-yl) -1 H-pyrazolo [3, 4-d] pyrimidin-1-yl) cyclohexyl) piperazin-1-yl) ethanol; (frans) -2- (4- (4- (4-amino-3- (1- (2- (difluoromethoxy) benzyl) -1H-indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) piperazin-1-yl) ethanol; (c / s) -3- (4- (4- (4-amino-3- (1- (2- (difluoromethoxy) benzyl) -1 H -indol-5-yl) -1 H-pyrazolo [3, 4-d] pyrimidin-1-yl) cyclohexyl) piperazin-1-yl) propan-1-ol; (frans) -3- (4- (4- (4-amino-3- (1- (2- (difluoromethoxy) benzyl) -1H-indol-5-yl) -1 H-pyrazolo [3,4-d] ] pyrimidin-1-yl) cyclohexyl) piperazin-1-yl) propan-1-ol; 3- (2- (2,6-difluorobenzyl) -1H-benzimidazol-5-yl) -1- (4- (morpholin-4-yl-methyl) phenyl) -1H-pyrazolo [3,4-d] pyrimidine -4-amine; 2- (4- (4-amino-3- (2-benzyl-1H-benzimidazol-6-yl) -1H-pyrazolo [3,4-d] pyrimidin-1-yl) -1,4'-bipiperidin- 1'-il) ethanol; 3- (4- (4-amino-3- (2-benzyl-1H-benzimidazol-6-yl) -1H-pyrazolo [3,4-d] pyrimidin-1-yl) -1,4'-bipiperidin- 1'-il) propan-1-ol; 3- (2-Benzyl-1H-benzimidazol-6-yl) -1- (1, - (2-methoxyethyl) -1,4'-bipiperidin-4-yl) -1 H-pyrazolo [3,4-d] ] pyrimidin-4-amine; 2- (4- (4-amino-3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1H-pi RI (3, 4-d) pyrim id i n-1 -i I ) - 1,4'-bipiperidin-1'-yl) ethanol; 3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1- (1, - (2-methoxyethyl) -1,4, -bipiperidin-4-yl) -1H-pyrazolo [3, 4-d] pyrimidin-4-amine; 3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1- (4- (4-pyridin-2-yl- piperazin-1-yl) -cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine; (frans) -3- (2-Benzyl-1H-benzimidazol-5-yl) -1- (4- (4-pyridin-2-yl-piperazin-1-yl) cyclohexyl) -1 H -pyrazolo [3,4 -d] pyrimidin-4-amine; (c / s) -3- (2-Benzyl-1H-benzimidazol-5-yl) -1- (4- (4-pyridin-2-yl-piperazin-1-yl) cyclohexyl) -1 H -pyrazolo [3 , 4-d] pyrimidin-4-amine; (frans) -1- (4-morpholin-4-yl-cyclohexyl) -3- (2- (pyridin-2-yl-methyl) -1 H -benzimidazol-6-yl) -1 H -pyrazolo [3,4 -d] pyrimidin-4-amine; 3- (2-benzyl-1H-benzimidazol-6-yl) -1- (1'-isobutyl-1,4'-bipiperidin-4-yl) -1H-pyrazolo [3,4-d] pyrimidin-4- amine; (frans) -1 - (4-morpholin-4-yl-cyclohexyl) -3- (2- (pyrid-n-3-yl-methyl) -1H-benzimidazol-6-yl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine; (c / s) -1- (1- (2-chlorobenzyl) -1H-indol-5-yl) -3- (3- (4-methylpiperazin-1-yl) cyclobutyl) imidazo [1, 5-a] pyrazin-8-amine; (c / s) -1- (2-Benzyl-1H-indol-5-yl) -3- (3- (4-methylpiperazin-1-yl) cyclobutyl) imidazo [1,5-a] pyrazin-8- amine; (c / s) -1- (2-Benzyl-1H-benzimidazol-5-yl) -3- (3- (4-methylpiperazin-1-yl) cyclobutyl) imidazo [1,5-a] pyrazine- 8-amine; (f? ans) -1- (4-morpholin-4-yl-cyclohexyl) -3- (2- (thien-3-yl-methyl) -1H-benzimidazol-6-yl) -1H-pyrazolo [3, 4-d] pyrimidin-4-amine; (frans) -3- (2- (1, 3-benzodioxol-5-yl-methyl) -1 H -benzimidazol-6-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H- pyrazoloth3,4-d] pyrimidin-4-amine; (frans) -3- (2- (2-Fluorobenzyl) -1H-indol-5-yl) -1- (4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl) -1 H -pyrazolo [ 3,4-d] pyrimidin-4-amine; (c / s) -3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1- (4- (4- (3- methoxy propyl) piperazin-1-1) cyclohexy l) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; (frans) -4- (4-amino-3- (2- (2- (trifluoromethoxy) benzyl) -1 H -benzimidazol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1 - il) cyclohexanol; (frans) - 1 - (4- (4- (3-methoxyprop i I) pipe razin-1 -i I) cyclohexy l) -3- (2- (2- (trifluoromethoxy) benzyl) -1 H -benzimidazole -5-yl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; (c / 's) - 1 - (4- (4- (3-methoxypropi I) pipe razin-1 -yl) cyclohexyl) -3- (2- (2- (trifluoromethoxy) benzyl) -1 H- benzimidazol-5-yl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; (frans) - 1 - (4-morpholin-4-M-cyclohexyl) -3- (2- (2-naphthylmethyl) -1 H -benzimidazol-6-yl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; (frans) -3- (2- (2,6-difluorobenzyl) -1 H -benzimidazol-5-yl) -1 - (4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; (c / s) -3- (2- (2,6-difluorobenzyl) -1 H -benzimidazol-5-yl) -1 - (4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; (frans) -2 - ((6- (4-amino-1 - (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-3-yl) -1 H- benzimidazol-2-yl) methyl) phenol; 3- (2- (2-methoxybenzyl) -1 H -benzimidazol-5-yl) -1 - (4 - ((4- (3-methoxypropyl) piperazin-1-yl) methyl) phenyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; 1 - (4 - ((4- (2- (1, 3-dioxolan-2-yl) ethyl) piperazin-1-yl) methyl) phenyl) -3- (2- (2-methoxybenzyl) -1 H- benzimidazol-5-yl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; (frans) -3- (2 - ((2-methyl-1,3-thiazol-4-yl) methyl) -1H-benzimidazol-6-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; 3- (2- (2-methoxybenzyl) -1H-benzimidazol-5-yl) -1- (4 - ((4- (methylsulfonyl) piperazin-1-yl) methyl) phenyl) -1H-pyrazolo [3 , 4-d] pyrimidin-4-amine; 2- (4- (4-amino-3- (2- (2-fluorobenzyl) -1 H -indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl) -1 , 4'-bipiperidin-1'-yl) ethanol; 3- (4- (4-amino-3- (2- (2-fluorobenzyl) -1 H -indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl) -1 , 4'-bipiperidin-1'-yl) propan-1-ol; S - ^ - ^ - fluorobenzylMH-indol-d-i-l-O '- ^ - methoxyeti -' - bipiperidin-4-yl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine; 3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1- (1 '- (3-methoxypropyl) -1,4'-bipiperidin-4-yl) -1H-pyrazolo [3, 4-d] pyrimidin-4-amine; 3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1- (1, -isobutyl-1,4'-bipiperidin-4-yl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine; 2- (4- (4- (4-amino-3- (2- (2,5-difluorobenzyl) -1 H -indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1 -yl) cyclohexyl) piperazin-1-yl) ethanol; 3- (4- (4- (4-amino-3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl ) piperazin-1-yl) propan-1-ol; (c / s) -1- (4 - ((2- (2- (2-aminoethoxy) ethoxy) ethyl) amino) cyclohexyl) -3- (2- (2-f luorobenzyl) -1H-indole-5- il) -1 H-pyrazolo [3,4-d] pyrim id i n-4-amine; 1- (4 ^ ((2- (2- (2-aminoethoxy) ethoxy) ethyl) amino) cyclohexyl) -3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [ 3,4-d] pyrimidin-4-amine; (frans) -1- (4 - ((2- (2- (2- aminoethoxy) ethoxy) ethyl) amino) cyclohexyl) -3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine; 2- (2 - ((4- (4-amino-3- (2- (2-fluorobenzyl) -1 H -indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1- il) cyclohexyl) amino) ethoxy) ethanol; 2- (1- (4- (4-amino-3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pi RI (3, 4-d) pyrim id in-1- il) cyclohexyl) piperidin-4-yl) ethanol; (1- (4- (4-amino-3- (2- (2-fluorobenzyl) -1 H -indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl ) piperidin-4-yl) methanol; (frans) -3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1- (4- (4- (2- (2-methoxyethoxy) ethyl) piperazin-1-yl) cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine; (frans) -3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1- (4- (4- (2- (methoxymethoxy) ethyl) piperazin-1-yl) cyclohexyl) -1 H p i razo I or [3,4-d] pyrimidin-4-amine; 3- (4- (4- (4-amino-3- (2- (2,5-difluorobenzyl) -1 H -indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1 -yl) cyclohexyl) piperazin-1-yl) propan-1-ol; 2- (4- (4- (4-amino-3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl ) piperazin-1-yl) ethanol; (frans) -1- (4- (4- (2- (2-ethoxyethoxy) ethyl) piperazin-1-yl) cyclohexyl) -3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine; 1- (4- (4-amino-3- (2- (2-methoxybenzyl) -1 H -benzi m id azo l-5-yl) -1 H-pyrazolo [3,4-d] pyrimidin-1- il) cyclohexyl) piperidin-4-ol; (frans) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-5-yl) -1- (4- (4- (4-methoxyphenyl) piperazin-1-yl) cyclohexyl) -1 H -pyrazolo [ 3,4-d] pyrimidin-4-amine; (c / s) -3- (2- (2-methoxybenzyl) -1 H -benzimidazol-5-yl) -1 - (4- (4- (4-methoxyphenyl) piperazin-1-yl) cyclohexyl) -1 H-pyrazole or [3,4-d] pyrim id i n-4-amine; (frans) -4- (4- (4-amino-3- (2- (2-methoxybenzyl) -1 H -benzimidazol-5-yl) -1 H- pi razo lo [3,4-d] pyrim id i n-1 -yl) cyclohexyl) piperazin-2-one; (c / s) -4- (4- (4-amino-3- (2- (2-methoxybenzyl) -1 H -benzimidazol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidine- 1 -yl) cyclohexyl) piperazin-2-one; (frans) -5- (2- (2-methoxybenzyl) -1 H -benzimidazol-5-yl) -7- (4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl) -7H-pyrrolo [2,3-d] pyrimidin-4-amine; (c / s) -5- (2- (2-methoxybenzyl) -1 H -benzimidazol-5-yl) -7- (4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl) -7H -pyrrolo [2,3-d] pyrimidin-4-amine; (frans) -3- (2- (2-methoxybenzyl) -1 H -benzimidazol-5-yl) -1 - (4- (4- (tetrahydrofuran-2-yl-methyl) piperazin-1-yl) cyclohexyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; (c / s) -3- (2- (2-methoxybenzyl) -1 H -benzimidazol-5-yl) -1 - (4- (4- (tetrahydrofuran-2-yl-methyl) piperazin-1-yl) cyclohexyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; (frans) -3- (2- (2-methoxybenzyl) -1 H -benzimidazol-5-yl) -1 - (4- (4- (tetrahydrofuran-2-yl-carbonyl) piperazin-1-yl) cyclohexyl) -1 H-pyrazolo [3,4-d] pyrim id-n-4-amine; (c / 's) -3- (2- (2-methoxybenzyl) -1 H -benzimidazol-5-yl) -1 - (4- (4- (tetrahydrofuran-2-yl-carbonyl) piperazin-1-yl) ) cyclohexyl) -1 H- pyrazolo [3,4-d] pyrimidin-4-amine; (c / s) -2- (2 - ((4- (4-amino-3- (1 - (2-fluorobenzyl) -1 H -indol-5-yl) -1 H-pyrazolo [3,4- d] pyrimidin-1-yl) cyclohexyl) amino) ethoxy) ethanol; (frans) -2- (2 - ((4- (4-amino-3- (1 - (2-fluorobenzyl) -1 H -indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) amino) ethoxy) ethanol; (frans) -3- (4- (4- (4-amino-3- (2- (2-fluorobenzyl) -1 H -indol-6-yl) -1 H -pyrazolo [3,4-d] pyrimidine -1 -yl) cyclohexyl) -piperazin-1-yl) propan-1 -ol; (frans) -3- (2- (2-fluorobenzyl) -1 H -indol-6-yl) -1 - (4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl) -1 Hp i razólo [3, 4-d] pirim id i n-4-amine; (frans) -2- (4- (4- (4-amino-3- (2- (2-fluorobenzyl) -1 H -indole-6-M) -1 H -pyrazolo [3,4-d] pyrimidine -1 -yl) cyclohexyl) piperazin-1-yl) ethanol; (frans) -1 - (4- (4-amino-3- (2- (2-fluorobenzyl) -1 H -indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1 - il) cyclohexyl) piperidin-4-ol; (frans) -1 - (4- (4- (2- (1, 3-dioxolan-2-yl) ethyl) piperazin-1-yl) cyclohexyl) -3- (2- (2-methoxybenzyl) -1 H -benzimidazol-5-yl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine; (c / s) -1 - (4- (4- (2- (1, 3-dioxolan-2-yl) ethyl) piperazin-1-yl) cyclohexyl) -3- (2- (2-methoxybenzyl) - 1 H-benzimidazol-5-yl) -1 H-pyrazolo [3,4-d] pyrim id in-4-amine; (frans) -3- (2- (2-methoxybenzyl) -1 H -benzimidazol-6-yl) -1 - (4- (2- (trifluoromethyl) -5,6-dihydroimidazo [1, 2-a] pyrazin -7 (8H) -yl) cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; 4- (4-amino-3- (2- (2-methoxybenzyl) -1 H -benzimidazol-6-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexanone; (c / s) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-6-yl) -1- (4- (2- (trifluoromethyl) -5,6-dihydroimidazole [1,2-a] pyrazin-7 (8H) -yl) cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; (frans) -2- (4- (4- (4-amino-3- (2- (2-methoxy-benzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] pyrimidine -1-yl) cyclohexyl) piperazin-1-yl) ethanol; (frans) -3- (4- (4- (4-amino-3- (2- (2-methoxybenzyl) -1H-indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1 -yl) cyclohexyl) piperazin-1-yl) propan-1-ol; (frans) -3- (2- (2-methoxybenzyl) -1H-indol-5-yl) -1- (4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl) -1H-priazolo [ 3,4-d] pyrimidin-4-amine; (frans) -2- (4- (4- (4-amino-3- (2- (2-methoxybenzyl) -1H-indol-6-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1 -yl) cyclohexyl) piperazin-1-yl) ethanol; (frans) -3- (4- (4- (4-amino-3- (2- (2-methoxybenzyl) -1H-indol-6-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1 -yl) cyclohexyl) piperazin-1-yl) propan-1-ol; (frans) -3- (2- (2-methoxybenzyl) -1H-indol-6-yl) -1- (4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl) -1 H -pyrazolo [ 3,4-d] pyrimidin-4-amine; (frans) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-5-yl) -1- (4-piperazin-1-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidine- 4-amine; (frans) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-5-yl) -1- (4- (4-methylpiperazin-1-yl) cyclohexyl) -1 H-pyrazolo [3,4- d] pyrimidin-4-amine; (frans) - (5- (4-amino-1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrim idin-3-yl) -1-benzofuran-2- il) (phenyl) methanone; (frans) -3- (2-benzyl-1,3-benzothiazol-5-yl) -1 - (4-morpholin-4-M-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4 -amine; (rans) -3-di benzo (b, d) tie n-3-i 1-1 - (4-morfol i n-4-i I-cyclohexy I) -1 H-pyrazolo [3,4-d ] pyrimidin-4-amine; (frans) -1 - (4- (4-ethylpiperazin-1-yl) cyclohexyl) -3- (2- (2-methoxybenzyl) -1 H -benzimidazol-6-yl) -1 H-pyrazolo [3,4 -d] pyrimidin-4-amine; (c / s) -1 - (4- (4-ethylpiperazin-1-yl) cyclohexyl) -3- (2- (2-methoxybenzyl) -1 H -benzimidazol-6-yl) -1 H-pyrazolo [3 , 4-d] pyrim idin-4-amine; (frans) -5- (2- (2-methoxybenzyl) -1 H -benzimidazol-5-yl) -7- (4- (2-methoxyethoxy) cyclohexyl) -7H-pyrrolo [2,3-d] pyrimidine- 4-amine; (frans) -1 - (4- (4-acetylpiperazin-1-yl) cyclohexyl) -3- (2- (3-methoxybenzyl) -1 H -benzimidazol-6-yl) -1 H-pyrazolo [3,4 -d] pyrimidin-4-amine; (frans) -4- (4- (4- (4-amino-3- (2- (2-methoxy-benzyl) -1 H-benzimidazol-6-yl) -1 H-pyrazolo [3,4-d] ] pyrimidin-1-yl) cyclohexyl) piperazin-1-yl) -2-methylbutan-2-ol; (c / s) -4- (4- (4- (4-amino-3- (2- (3-methoxybenzyl) -1 H -benzimidazol-6-yl) -1 H-pyrazolo [3,4-d] ] pyrimidin-1-yl) cyclohexyl) piperazin-1-yl) -2-methylbutan-2-ol; (c / s) -3- (2- (2-methoxybenzyl) -1 H -benzimidazol-6-yl) -1 - (4- (4-pyrazin-2-yl-piperazin-1-yl) cyclohexyl) - 1 H-pyrazolo [3,4-d] pyrimidin-4-amine; (c / 's) -2- (4- (4- (4-amino-3- (2- (2-methoxybenzyl) -1 H- benzimidazol-6-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) piperazin-1-yl) ethanol; (frans) -2- (4- (4- (4-amino-3- (2- (2-methoxybenzyl) -1 H -benzimidazol-6-yl) -1 H -pyrazolo [3,4-d] pyrimidine -1 -yl) cyclohexyl) piperazin-1-yl) ethanol; (frans) -4- (4- (4-amino-3- (2- (2-methoxybenzyl) -1 H -benzimidazol-6-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1 - il) cyclohexyl) -N, Nd i met i I pi pe razin-1 -carboxamide; (c / s) -4- (4- (4-amino-3- (2- (2-methoxybenzyl) -1 H -benzimidazol-6-yl) -1 H -pyrazolo [3,4-d] pyrimidine- 1 -yl) cyclohexyl) -N, N-dimethylpiperazin-1 -carboxamide; 4- (4- (4-amino-3- (2- (2-methoxybenzyl) -1 H -benzoimidazol-6-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) piperazin-1-carboxylate (frans) -ethyl; 4- (4- (4-amino-3- (2- (2-methoxybenzyl) -1 H -benzimidazol-6-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) piperazin-1-carboxylate of (c / s) -ethyl; (c / s) -3- (7-Chloro-2- (2-methoxybenzyl) -1 H -benzimidazol-5-yl) -1 - (4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl) -1 H -pyrazole or [3,4-d] pyrimidin-4-amine; (frans) -1 - (4- (4- (ethylsulfonyl) piperazin-1-yl) cyclohexyl) -3- (2- (2-methoxybenzyl) -1 H -benzimidazol-6-yl) -1 H-pyrazolo [ 3,4-d] pyrim id in-4-amine; (c / s) -1 - (4- (4- (ethylsulfonyl) piperazin-1-yl) cyclohexyl) -3- (2- (2-methoxybenzyl) -1 H -benzimidazol-6-yl) -1 H- pyrazolo [3,4-d] pyrimidin-4- amine; (frans) -3- (7-Chloro-2- (2-methoxybenzyl) -1H-benzimidazol-5-yl) -1- (4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl) - 1 H-pyrazolo [3,4-d] pyrimidin-4-amine; (frans) -1- (4- (4- (2- (2- (2-aminoethoxy) ethoxy) ethyl) piperazin-1-yl) cyclohexyl) -3- (2- (2-methoxybenzyl) -1H-benzimidazole -6-yl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; (trans) - 1- (4- (4- (cyclopropyl methyl) pipe ratio i-1 -i I) cyclohexy I) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-6-yl ) -1H-pyrazolo [3,4-d] pyrimidin-4-amine; (c / 's) - 1- (4- (4- (cyclopropylmethyl) pipe-razin-1-yl) cyclohexyl) -3- (2- (2-methoxybenzyl) -1H-benzimidazole-6- il) -1H-pyrazolo [3,4-d] pyrimidin-4-amine; (frans) -4- (4- (4- (4-amino-3- (2- (2,6-difluorobenzyl) -1H-benzimidazol-5-yl) -1H-pyrazolo [3,4-d] pyrimidine -1-yl) cyclohexyl) piperazin-1-yl) -2-methylbutan-2-ol; (c / s) -4- (4- (4- (4-amino-3- (2- (2,6-difluorobenzyl) -1H-benzimidazol-5-yl) -1 H-pyrazolo [3,4- d] pyrimidin-1-yl) cyclohexyl) piperazin-1-yl) -2-methylbutan-2-ol; (frans) -2- (4- (4- (4-amino-3- (2- (2,6-difluorobenzyl) -1 H -benzimidazol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) piperazin-1-yl) ethanol; (c / s) -2- (4- (4- (4-amino-3- (2- (2,6-difluorobenzyl) -1H-benzimidazol-5-yl) -1H-pyrazolo [3,4-d] ] pyrimidin-1-yl) cyclohexyl) piperazin-1-yl) ethanol; (frans) -3- (2- (2,6-difluorobenzyl) -1H-benzimidazole-5-M) -1- (4- (4-ethylpiperazin-1-yl) cyclohexyl) -1H-pyrazolo [3,4 -d] pyrimidin-4-amine; (c / 's) -3- (2- (2,6-difluorobenzyl) -1H-benzimidazol-5-yl) -1- (4- (4-ethylpiperazin-1-yl) cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine; (frans) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-6-yl) -1- (4- (4- (2-methoxyethyl) piperazin-1-yl) cyclohexyl) -1 H- pyrazolo [3,4-d] pyrimidin-4-amine; (c / s) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-6-yl) -1- (4- (4- (2-methoxyethyl) piperazin-1-yl) cyclohexyl) -1H- pyrazolo [3,4-d] pyrimidin-4-amine; (frans) -1- (4- (4-isopropylpiperazin-1-yl) cyclohexyl) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-6-yl) -1 H -pyrazolo [3,4-d] ] pyrimidin-4-amine; (c / s) -1- (4- (4-isopropylpiperazin-1-yl) cyclohexyl) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-6-yl) -1 H-pyrazolo [3, 4-d] pyrimidin-4-amine; (frans) -3- (2- (cyclohexylmethyl) -1H-benzimidazol-6-yl) -1- (4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl) -1 H-pyrazolo [3 , 4-d] pyrimidin-4-amine; (frans) -3- (2- (cyclopentylmethyl) -1H-benzimidazol-6-yl) -1- (4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl) -1 H-pyrazolo [3 , 4-d] pyrimidin-4-amine; (frans) -3- (1- (3-fluorobenzyl) -1H-indazol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidine- 4-amine; (frans) -3- (1- (2-methylbenzyl) -1H-indazol-5-yl) -1- (4-morpholin-4-) il-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine; (frans) -3- (1- (3-methylbenzyl) -1H-indazol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidine -4-amine; (frans) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-6-yl) -1- (4- (4-phenylpiperazin-1-yl) cyclohexyl) -1 H -pyrazolo [3,4-d] ] pyrimidin-4-amine; (c / s) -3- (2- (2-methoxy-benzyl) -1 H -benzimidazol-6-yl) -1- (4- (4-phenylpiperazin-1-yl) cyclohexyl) -1 H-pyrazolo [3 , 4-d] pyrimidin-4-amine; (frans) -3- (2- (2-Chlorobenzyl) -1H-benzimidazol-6-yl) -1- (4- (4-ethylpiperazin-1-yl) cyclohexyl) -1 H -pyrazolo [3,4-d] ] pyrimidin-4-amine; (c / s) -3- (2- (2-Chlorobenzyl) -1H-benzimidazol-6-yl) -1- (4- (4-ethylpiperazin-1-yl) cyclohexyl) -1 H-pyrazolo [3, 4-d] pyrimidin-4-amine; (trans) -2- (4- (4- (4-amino-3- (2- (2-chlorobenzyl) -1H-benzimidazol-6-yl) -1 H- pyrazolo [3,4-d] pyrimidine- 1-yl) cyclohexyl) piperazin-1-yl) ethanol; (c / s) -2- (4- (4- (4-amino-3- (2- (2-chlorobenzyl) -1 H -benzimidazol-6-yl) -1 H -pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) piperazin-1-yl) ethanol; and the salts, esters, amides, prodrugs and salts of esters, amides and prodrugs thereof. DETAILED DESCRIPTION OF THE INVENTION The variable portions of the compounds of the present are represented by identifiers (uppercase letters with numerical and / or alphabetical superscripts) and can be specifically included in embodiments of the invention. It should be understood that the valences are maintained suitable for all portions and combinations thereof, that monovalent portions having more than one carbon atom are linked through their left ends. It should also be understood that a specific embodiment of a variable portion may be the same or different from another specific modality having the same identifier. The term "cyclic portion" as used herein, means a radical benzene, cycloalkane, cycloalkyl, cycloalkene, cycloalkenyl, heteroarene, heteroaryl, heterocycloalkane, heterocycloalkyl, heterocycloalkene, heterocycloalkenyl, phenyl, spiroalkyl, spiroalkenyl, spiroheteroalkyl, and spiroheteroalkenyl. The term "cycloalkane" as used herein means cycloalkane of 3 carbon atoms, cycloalkane of 4 carbon atoms, cycloalkane of 5 carbon atoms and cycloalkane of 6 carbon atoms. The term "cycloalkyl", as used herein, means a cycloalkyl group of 3 carbon atoms, cycloalkyl of 4 carbon atoms, cycloalkyl of 5 carbon atoms and cycloalkyl of 6 carbon atoms. The term "cycloalkene", as used herein, means a cycloalkene group of 4 carbon atoms, cycloalkene of 5 carbon atoms and cycloalkene of 6 carbon atoms. The term "cycloalkenyl", as used in the present, means cycloalkenyl of 4 carbon atoms, cycloalkenyl of 5 carbon atoms and cycloalkenyl of 6 carbon atoms. The term "heteroarene" as used herein, means a furan group, imidazole, isothiazole, isoxazole, 1,2,3-oxadiazole, 1, 2,5-oxadiazole, oxazole, pyrazine, pyrazolo, pyridazine, pyridine, pyrimidine, pyrrolo, thiazole, thiophene, triazine, and 1,2,3-triazole. The term "heteroaryl," as used herein, means a furanyl, imidazolyl, isothiazolyl, isoxazolyl, 1, 2,3-oxadiazolyl, 1, 2,5-oxadiazolyl, oxazolyl, pyrazinyl, pyrazolyl, pyridazinyl, pyridinyl radical. , pyrimidinyl, pyrrolyl, tetrazolyl, thiazolyl, thiophenyl, triazinyl and 1,2,3-triazolyl. The term "heterocycloalkane", as used herein, means a cycloalkane radical having one or two or three CH 2 portions replaced with, and independently selected from, O, S, S (O), SO 2 or NH, and one or two CH portions replaced or not with N, and also means a cycloalkane radical having one or two or three CH2 portions replaced or not with, and independently selected from O, S, S (O), SO2 or NH, and one or two CH portions replaced with N. The term "heterocycloalkyl", as used herein, means a cycloalkyl radical having one or two or three CH 2 portions replaced with, and independently selected from, O, S, S (O), SO 2 or NH, and one or two CH portions replaced or not with N, and also means a cycloalkyl radical having one or two or three CH2 portions replaced or not with, and independently selected from O, S, S (O), SO2 or N H, and one or two CH portions replaced with N. The term "heterocycloalkene", as used herein, means a cycloalkene radical having one or two or three CH2 portions, replaced with, and independently selected from, O, S, S (O), SO2 or NH, and a or two CH portions substituted or not with N, and also means a cycloalkene radical having one or two or three CH2 portions replaced or not with, and independently selected from O, S, S (O), SO2 or NH, and one or two CH portions replaced with N. The term "heterocycloalkenyl", as used herein, means a cycloalkenyl radical having one or two or three CH2 portions replaced with, and independently selected from, O, S, S (O), SO2 or NH, and a or two CH portions substituted or not with N, and also means a cycloalkenyl radical having one or two or three CH2 portions replaced or not, and independently selected from O, S, S (O); SO2 or N H, and one or two CH portions replaced with N. The term "alkenyl", as used herein, means an alkenyl radical of 2 carbon atoms, alkenyl of 3 carbon atoms, alkenyl of 4 carbon atoms, alkenyl of 5 carbon atoms, and alkenyl of 6 atoms of carbon. The term "alkyl", as used herein, means an alkyl radical of 1 carbon atom, alkyl of 2, carbon atoms, alkyl of 3 carbon atoms, alkyl of 4 carbon atoms, alkyl of 5 carbon atoms, and alkyl of 6 carbon atoms. The term "alkynyl", as used herein, means an alkynyl radical of 2 carbon atoms, alkynyl of 3 carbon atoms, alkynyl of 4 carbon atoms, alkynyl of 5 carbon atoms, and alkynyl of 6 atoms of carbon. The term "2-carbon alkenyl", as used herein, means ethenyl (vinyl). The term "C 3 -alkenyl", as used herein, means 1-propen-1-yl, 1-propen-2-yl. (isopropenyl) and 1-propen-3-yl (allyl). The term "C 4 -alkenyl", as used herein, means 1-buten-1-yl, 1-buten-2-yl, 1,3-butadien-1-yl, 1, 3- butadien-2-yl, 2-buten-1-yl, 2-buten-2-yl, 3-buten-1-yl, 3-buten-2-yl, 2-methyl-1-propen-1-yl and 2-methyl-2-propen-1-yl. The term "C5-alkenyl" as used herein means 2-methylene-3-buten-1-yl, 2-methylene-but-1 -l, 2-methyl-1-buten- 1-yl, 2-methyl-1,3-butadien-1-yl, 2-methyl-2-buten-1-yl, 2-methyl-3-buten-1-yl, 2-methyl-3-buten- 2-yl, 3-methyl-1-buten-1-yl, 3-methyl-1-buten-2-yl, 3-methyl-1,3-butadien-1-yl, 3-methyl-1,3- butadien-2-yl, 3-methyl-2-buten-1-yl, 3-methyl-2-buten-2-yl, 3-methyl-3-buten-1-yl, 3-methyl-3-buten- 2-yl, 1-penten-1-yl, 1-penten-2-yl, 1-penten-3-yl, 1,3-pentadien-1-yl, 1,3-pentadien-2-yl, 1, 3- or pentadien-3-yl, 1,4-pentadien-1-yl, 1,4-pentadien-2-yl, 1,4-pentadien-3-yl, 2-penten-1-yl, 2-penten-2- ilo, 2-penten-3-yl, 2,4-pentadien-1-yl, 2,4-pentadien-2-yl, 3-penten-1-yl, 3-penten-2-yl, 4-penten- 1-yl and 4-penten-2-yl. The term "C 6 -alkenyl", as used herein, means 2,2-dimethyl-3-buten-1-yl, 2,3-dimethyl-1-buten-1-yl, 2, 3-dimethyl-1-1, 3-butadien-1-yl, 2,3-dimethyl-2-buten-1-yl, 2,3-dimethyl-3-buten-1-yl, 2,3-dimethyl- 3-buten-2-yl, 3,3-dimethyl-1-buten-1-yl, 3,3-dimethyl-1-buten-2-yl, 2-ethenyl-1,3-butadien-1-yl, 2-ethenyl-2-buten-1-yl, 2-ethyl-1-buten-1-yl, 2-ethyl-1,3-butadien-1-yl, 2-ethyl-2-buten-1-yl, 2-ethyl-3-buten-1-yl, 1-hexen-1-yl, 1-hexen-2-yl, 1-hexen-3-yl, 1,3-hexadien-1-yl, 1, 3- hexadien-2-yl, 1,3-hexadien-3-yl, 1, 3,5-hexatrien-1-yl, 1, 3,5-hexatrien-2-yl, 1, 3,5-hexatrien-3- ilo, 1, 4-hexadien-1-yl, 1,4-hexadien-2-yl, 1,4-hexadien-3-yl, 1,5-hexadien-1-yl, 1,5-hexadien-2-yl, 1,5-hexadien-3-yl, 2-hexen-1-yl, 2 -hexen-2-yl, 2-hexen-3-yl, 2,4-hexadien-1-yl, 2,4-hexadien-2-yl, 2,4-hexadien-3-yl, 2,5-hexadien -1-yl, 2,5, -hexadien-2-yl, 2,5-hexadien-3-yl, 3-hexen-1-yl, 3-hexen-2-yl, 3-hexen-3-yl, 3,5-hexadien-1-yl, 3,5-hexadien-2-yl, 3,5-hexadien-3-yl, 4-hexen-1-yl, 4-hexen-2-yl, 4-hexen- 3-yl, 5-hexen-1-yl, 5-hexen-2-yl, 5-hexen-3-yl, 2-methylene-3-methyl-3-buten-1-yl, 2-methylene-3- methyl-but-1-yl, 2-methylene-3-penten-1-yl, 2-methylene-4-penten-1-yl, 2-methylene-pent-1-yl, 2-methylene-pent-3 ilo, 3-methylene-1-penten-1-yl, 3-methylene-1-penten-2-yl, 3-methylene-pent-1-yl, 3-methylene-1,4-pentadien-1-yl, 3-Methylene-1,4-pentadien-2-yl, 3-methylene-pent-2-yl, 2-methyl-1-penten-1-yl, 2-methyl-1- penten-3-yl, 2-methyl-1,3-pentadien-1-yl, 2-methyl-1,3-pentadien-3-yl, 2-methyl-1,4-pentadien-1-yl, 2- methyl-1, 4-pentadien-3-yl, 2-methyl-2-penten-1-yl, 2-methyl-2-penten-3-yl, 2-methyl-2,4-pentadien-1-yl, 2-methyl-2,4-pentadien-3-yl, 2-methyl-3-penten-1-yl, 2-methyl-3-penten-2-yl, 2-methyl-3-penten-3-yl, 2-methyl-4-penten-1-yl, 2-methyl-4-penten-2-yl, 2-methyl-4-penten-3-yl, 3-methyl-1-penten-1-yl, 3- methyl-1-penten-2-yl, 3-methyl-1,3-pentadien-1-yl, 3-methyl-1,3-pentadien-2-yl, 3-methyl-1,4-pentadien-1 - ilo, 3-methyl-1, 4-pentadien-2-yl, 3-methyl-2-penten-1-yl, 3-methyl-2-penten-2-yl, 3-methyl-2,4-pentadien- 1 -yl, 3-methyl-3-penten-1-yl, 3-methyl-3-penten-2-yl, 3-methyl-4-penten-1-yl, 3-methyl-4-penten-2- ilo, 3-methyl-4-penten-3-yl, 4-methyl-1-penten-1-yl, 4-methyl-1-penten-2-yl, 4-methyl-1-penten-3-yl, 4-methyl-1,3-pentadien-1-yl, 4-methyl-1,3-pentadien-2-yl, 4-methyl-1,3-pentadien-3-yl, 4-methyl-1, 4- pentadien-1-yl, 4-methyl-1,4-pentadien-2-yl, 4-methyl- 1, 4-pentadien-3-yl, 4-methylene-2-penten-3-yl, 4-methyl-2-penten-1-yl, 4-methyl-2-penten-2-yl, 4-methyl- 2-penten-3-yl, 4-methyl-2,4-pentadien-1-yl, 4-methyl-2,4-pentadien-2-yl, 4-methyl-3-penten-1-yl, 4- methyl-3-penten-2-yl, 4-methyl-3-penten-3-yl, 4-methyl-4-penten-1-yl and 4-methyl-4-penten-2-yl. The term "alkyl of 1 carbon atom", as used herein, means a methyl radical. The term "2-carbon-alkyl", as used herein, means an ethyl radical. The term "3-carbon-alkyl", as used herein, means a prop-1-yl and prop-2-yl (isopropyl) radical.

The term "C 4 -alkyl", as used herein, means a but-1-yl, but-2-yl, 2-methylprop-1-yl and 2-methylprop-2-yl radical ( tert-butyl). The term "C 5 -alkyl", as used herein, means 2,2-dimethylprop-1 -yl (neopentyl), 2-methylbut-1-yl, 2-methylbut-2-yl, 3 -methylbut-1-yl, 3-methylbut-2-yl, pent-1-yl, pent-2-yl and pent-3-yl. The term "C 6 -alkyl", as used herein, means a 2, 2-dimethylbut-1-yl, 2,3-dimethylbut-1-yl, 2,3-dimethylbut-2 radical. -yl, 3,3-dimethylbut-1-yl, 3,3-dimethylbut-2-yl, 2-ethylbut-1-yl, hex-1-yl, hex-2-yl, hex-3-yl, 2 -methylpent-1-yl, 2-methylpent-2-yl, 2-methylpent-3-yl, 3-methylpent-1-yl, 3-methylpent-2-yl, 3-methylpent-3-yl, 4-methylpent -1 -yl and 4-methylpent-2-i. The term "2-carbon alkynyl", as used herein, means an ethynyl (acetylenyl) radical. The term "3-carbon alkynyl", as used herein, means a 1-propin-1-yl radical and 2-propin-1-yl (propargyl). The term "C4-alkynyl", as used herein, means a radical 1-butyne-1-yl, 1,3-butadiin-1-yl, 2-butyne-1-yl, 3- butin-1-yl and 3-butin-2-yl. The term "C5-alkynyl", as used herein, means a radical 2-methyl-3-butin-1-yl, 2-methyl-3-butin-2-yl, 3-methyl- 1-butin-1-yl, 1,3-pentadiin-1-yl, 1, 4- pentadiin-1-yl, 1,4-pentadiin-3-yl, 2,4-pentadiin-1-yl, 1 -pentin-1-yl, 1-pentin-3-yl, 2-pentin-1-yl, 3-pentin-1-yl, 3-pentin-2-yl, 4-pentin-1-yl and 4-pentin-2-yl. The term "C 6 -alkinyl", as used herein, means a 2,2-dimethyl-3-butin-1-yl radical, 3,3-dimethyl-1-butin-1-yl, 2-ethyl-3-butin-1-yl, 2-ethynyl-3-butin-1-yl, 1-hexin-1-yl, 1-hexin- 3-yl, 1,3-hexadin-1-yl, 1, 3,5-hexatriin-1-yl, 1,4-hexadin-1-yl, 1,4-hexadin-3-yl, 1,5- hexadin-1-yl, 1,5-hexadin-3-yl, 2-hexin-1-yl, 2,5-hexadin-1-yl, 3-hexin-1-yl, 3-hexin-2-yl, 3,5-hexadiin-2-yl, 4-hexin-1-yl, 4-hexin-2-yl, 4-hexin-3-yl, 5-hexin-1-yl, -Hexy-2-yl, 5-Hexy-3-yl, 2-methyl-3-pentin-1-yl, 2-methyl-3-pentin-2-yl, 2-methyl-4-pentin-1- ilo, 2-methyl-4-pentin-2-yl, 2-methyl-4-pentyne-3-yl, 3-methyl-1-pentyne-1-yl, 3-methyl-4-pentyne-1-yl, 3-methyl-4-pentyne-2-yl, 3 -methyl-1,4-pentadiin-1-yl, 3-methyl-1,4-pentadiin-3-yl, 3-methyl-4-pentin-1-yl, 3-methyl-4-pentin-3-yl , 4-methyl-1-pentin-1-yl and 4-methyl-2-pentin-1-yl. The term "cycloalkane of 4 carbon atoms" as used herein means a cyclobutane radical. The term "cycloalkane of 5 carbon atoms" as used herein means a cyclopentane radical. The term "cycloalkane of 6 carbon atoms" as used herein means a cydohexane radical. The term "4-carbon-cycloalkene" as used herein means a cyclobutene and 1,3-cyclobutadiene radical.

The term "5-carbon-cycloalkene" as used herein means a cyclopentene and 1,3-cyclopentadiene radical. The term "cycloalkuene of 6 carbon atoms" as used herein means a radical cyclohexene, 1,3-cyclohexadiene and 1,4-cyclohexadiene. The term "3-carbon-cycloalkenyl" as used herein means a cycloprop-1-en-1-yl and cycloprop-2-en-1-yl radical. The term "cycloalkenyl of 4 carbon atoms" as used herein, means a radical cyclobut-1-en-1-yl and cyclobut-2-en-1-yl. The term "5-carbon-cycloalkenyl" as used herein means a radical cyclopent-1-en-1-yl, cyclopent-2-en-1-yl, cyclopent-3-en-1-yl and cyclopenta-1,3-dien-1-yl. The term "C 6 -cycloalkenyl" as used herein means a cyclohex-1-en-1-yl radical, cyclohex-2-en-1-yl, cyclohex-3-en-1-yl , cyclohexa-1,3-dien-1-yl, cyclohexa-1,4-dien-1-yl, cyclohexa-1, 5-dien-1-yl, cyclohexa-2,4-dien-1-yl and cyclohexa -2, 5-dien-1-yl. The term "3-carbon-cycloalkyl," as used herein, means a cycloprop-1-yl radical. The term "cycloalkyl of 4 carbon atoms", as used herein, means cyclobut-1-yl.

The term "C 5 -cycloalkyl", as used herein, means cyclopent-1-yl. The term "C 6 -cycloalkyl", as used herein, means cyclohex-1-yl. The compounds of the present invention may contain asymmetrically substituted carbon atoms in the R or S configuration, wherein the terms "R" and "S" are defined in Puré Appl. Chem. (1 976) 45, 1 3-1 0. The atoms which are excessively one configuration with respect to the other, are assigned the excess configuration, preferably an excess of about 85-90%, more preferably about 95-99% and still more preferably an excess greater than about 99%. In accordance with the above, the present invention encompasses racemic mixtures and the relative and absolute diastereomers of the compounds thereof. The compounds of the present invention may also contain carbon-carbon double bonds or carbon-nitrogen double bonds, in the Z or E configuration, wherein the term "Z" represents the two largest substituents on the same side of a carbon double bond -carbon or carbon-nitrogen and the term "E" represents the two largest substituents on opposite sides of a carbon-carbon or carbon-nitrogen double bond. The compounds of the present invention may also exist as a mixture of "Z" and "E" isomers. The compounds of the present invention can also be exist as tautomers or mixtures in equilibrium thereof, where a proton of a compound changes from one atom to another. Examples of tautomers include, but are not limited to keto-enol tautomers, phenol-keto, oxime-nitroso, nitro-aci, imine-enamine and the like. The compounds of the present invention containing N H, C (O) OH, OH or SH moieties may have prodrug-forming moieties attached. The prodrug-forming portions are removed by metabolic processes and release the compounds having the free N H, C (O) OH, OH or SH groups in vivo. Prodrugs are useful for adjusting pharmacokinetic properties of compounds such as solubility and / or hydrophobicity, absorption in the gastrointestinal tract, bioavailability, tissue penetration and clearance rate. The metabolites of the compounds having the Formula I produced by metabolic processes in vitro or in vivo, may also have utility for the treatment of diseases associated with the effective excretion or lack of regulation of a kinase. Certain compounds that can be metabolized in vitro or in vivo to obtain compounds of Formula I may also have utility for the treatment of diseases associated with excessive excretion or lack of regulation of a kinase. The compounds having the Formula I may exist in the form of acid addition salts, basic addition salts or zwitterions. The salts of the compounds having the Formula I are prepare during their isolation or after their purification. The acid addition salts are those derived from the reaction of a compound of the Formula I with an acid. In accordance with the foregoing, salts including the acetate salt, adipate, alginate, bicarbonate, citrate, aspartate, benzoate, benzenesulfonate (besylate), bisulfate, butyrate, camphorate, canforosulfonato, digluconate, formate, fumarate, glycerophosphate, glutamate, hemisulfate, heptanoate, hexanoate, hydrochloride, hydrobromide, hydroiodide, lactobionate, lactate, maleate, mesitiletilensulfonato, methanesulfonate, naphthylenesulfonate, nicotinate, oxalate, pamoate, pectinate, persulfate, phosphate, picrate, propionate, succinate, tartrate, thiocyanate, trichloroacetic, trifluoroacetic, para Toluenesulfonate and undecanoate, of the compounds of Formula I, are encompassed by the present invention. The basic addition salts of the compounds are those derived from the reaction of the compounds of Formula I with the bicarbonate, carbonate, hydroxide or phosphate of cations such as lithium, sodium, potassium, calcium and magnesium. The compounds of Formula I can be administered, for example, bucally, ophthalmically, orally, osmotic, parenteral (intramuscular, intraperitoneal, intrasternal, intravenous, subcutaneous), rectal, topical, transdermal, vaginal and intraarterial as well as injection intra-articular, infusion and placement in the body, for example in the vasculature. The therapeutically effective amounts of a compound of Formula I depend on who receives the treatment, of the disease being treated and the severity thereof, the composition comprising them, the time of administration, the route of administration, the duration of treatment, the potency, the clearance rate and the if it is administered concomitantly or not, another drug. The amount of a compound of the Formula I used to prepare a composition to be administered daily to a mammal in a single dose or in divided doses is from about 0.001 to about 200 mg / kg of body weight. The single dose compositions contain these amounts or a combination of submultiples thereof. The compounds of Formula I can be administered with or without excipients. Excipients include but are not limited to encapsulating agents and additives such as absorption accelerators, antioxidants, binders, buffers, coating agents, coloring agents, diluents, disintegrants, emulsifiers, extenders, fillers, flavoring agents, wetting agents, lubricants, perfumes, preservatives, propellants, release agents, sterilizing agents, sweeteners, solubilizers, humectants, mixtures thereof and the like. The excipients for the preparation of compositions comprising a compound of Formula I to be administered orally include but are not limited to, agar, alginic acid, aluminum hydroxide, benzyl alcohol, benzyl benzoate, 1,3-butylene glycol, carbomers, castor oil, cellulose, cellulose acetate, lard cocoa, corn starch, corn oil, cottonseed oil, crospovidone, diglycerides, ethanol, ethylcellulose, ethyl laureate, ethyl oleate, fatty acid esters, gelatin, germ oil, glucose, glycerol, oil peanut, hydroxypropylmethylcellulose, isopropanol, isotonic saline, lactose, magnesium hydroxide, magnesium stearate, malt, mannitol, monoglycerides, olive oil, UATE peanut salts, potassium phosphate, potato starch, povidone, propylene glycol, Ringer's solution, safflower oil, sesame oil, sodium carboxymethyl cellulose, phosphate salts, sodium lauryl sulfate, sodium sorbitol, soybean oil, stearic acids, stearyl fumarate, sucrose, surfactants, talc, tragacanth, spirit tetrahidrofu rfurílico , triglycerides, water, mixtures thereof and the like. The excipients for the preparation of compositions comprising a compound of Formula I to be administered ophthalmic or orally, include, but are not limited to, 1, 3-butylene glycol, castor oil, corn oil, cottonseed oil, ethanol, sorbitan fatty acid esters, germ oil, peanut oil, glycerol, isopropanol, oil of olive, polyethylene glycols, propylene glycol, sesame oil, water, mixtures thereof and the like. The excipients for the preparation of compositions comprising a compound of Formula I to be osmotically administered, include but are not limited to chlorofluorohydrocarbons, ethanol, water, mixtures thereof and the like. The excipients for the preparation of compositions that comprise a compound of Formula I to be administered parenterally, include but not limited to 1,3-butanediol, castor oil, corn oil, cottonseed oil, dextrose, germ oil, peanut oil, liposomes, oleic acid, olive oil, peanut oil, Ringer's solution, safflower oil, sesame oil, soybean oil, sodium chloride solution U.S. P. or isotonic, water, mixtures thereof and the like. The excipients for the preparation of compositions comprising a compound of Formula I, to be administered rectally or vaginally, include but are not limited to cocoa butter, polyethylene glycol, wax, mixtures thereof and the like. The compounds of Formula I are also expected to be useful as chemotherapeutic agents, in combination with actinomycins, alkylating agents, anthracyclines, antifolates, antiestrogenic agents, antimetabolites, antiandrogens, antimicrotubule agents, aromatase enzyme inhibitors, bleomycins, Ca2 + inhibitors. adenosine triphosphate (ATP) asa, cytosine analogs, deltoids / retinoids, inhibitors of the enzyme dihydrofolate red uctase, inhibitors of the enzyme topoisomerase of deoxyribonucleic acid (DNA), dopaminergic neurotoxins, glucocorticoids, inhibitors of the enzyme histone deacetylase (H DAC ), hormonal therapies, immunotherapeutic agents, inhibitors of the enzyme inosine monophosphate (IMP) dehydrogenase, isoprenylation inhibitors, luteinizing hormone-releasing hormone agonists, rapamycin inhibitors (mtor) in mammals, multi-drug resistance inhibitors (MDR), mitomycins, photodynamic therapies, proteasome inhibitors, platinum-containing compounds, radiation, tyrosine kinase receptor inhibitors, ribonucleoside reductase enzyme inhibitors, thrombospondin mimics, uracil analogues , vinca alkaloids and vitamin D3 analogues, such as but not limited to radiation and / or an additional chemotherapeutic agent or additional chemotherapeutic agents such as N-Ac-Sar-Gly-Val-D-alolle-Thr-Nva-lle Arg-Pro-NHCH2CH3 or a salt thereof, actinomycin D, AG13736, 17-allylamino-17-demethoxy-geldanamycin, 9-aminocanphothecine, N- (4- (3-amino-1 H -indazol-4-yl) -phenyl) ) -N '- (2-fluoro-5-methylphenyl) -urea or a salt thereof, N- (4- (4-aminothieno- [2, 3-d] -pyrimidin-5-yl) -phenyl) -N '- (2-fluoro-5- (trifluoromethyl) -phenyl) -urea or a salt thereof, anastozole, AP-23573, asparaginase, azacitidine, bevacizumab, bicalutamide, bleomycin a2, ble omicin b2, bortezamib, busulfan, snuff, carboplatin, carmustine (BCNU), CB1093, cetyxumab, CHOP (C; Cytoxan® (cyclophosphamide); H: Adriamycin® (hydroxyloxorubicin); O: Vincristine (Oncovin®); P: prednisone), chlorambucil, CHI R258, cisplatin, CNF-101, CNF-1001, CNF-2024, CP547632, crisnatol, cytarabine, cyclophosphamide, cytosine, arabinoside, daunorubicin, dacarbazine, dactinomycin, dasatinib, daunorubicin, deferoxamine, desmethoxy hypocreclin A , depsipeptide, dexamethasone, 17-dimethylaminoethylamino-17-demethoxygendanamycin, docetaxel, doxifluridine, doxorubicin, EB1089, epothilone D, epirubicin, 5-ethynyl-1-β-D-ribofuranosylimidazole- 4-carboxamide (EICAR), erlotinib, etoposide, everolimus, 5-fluorouracil (5-FU), floxuridine, fludarabine, flutamide, gefitinib, geldanamycin, gencitabine, goserelin, N- (2- (4-hydroxyanilino) -3-pyridinyl) ) -4-methoxybenzenesulfonamide or salts thereof, hydroxyurea, idarubicin, ifosfamide, imatinab, interferon-a, interferon-y, IPI-504, irinotecan, KH1060, lapatanib, calcium leucovorin, LAQ824, leuprolide acetate, letrozole, lomustine ( CCNU), lovastatin, megestrol, melphalan, mercaptopurine, methotrexate, 1-methyl-4-phenylpyridinium, MG132, mitomycin, mitoxantrone, MLN-518, MS-275, mycophenolic acid, mitomycin C, nitrosoureas, oprelvekin, oxaliplatin, paclitaxel, PD98059 , peplomycin, Pc4 photosensitizer, phthalocyanine, pirarubicin, plicamycin, prednisone, procarbizine, PTK787, PU24FC1, PU3, radicicol, raloxifene, rapamycin, ratitrexed, retinoids such as feuretinide, ribavirin, rituximab (Rituxin®), sorafenib, staurosporine, steroids such as dexamethasone and prednisone, suberoylanilide hydroxamic acid , sunitinib, tamoxifen, taxol, temozolamide, temsirolimus, teniposides, tapsigargin, thioguanine, thrombospondin-1, thiazofurine, topotecan, trapoxin, trastuzumab, treosulfan, trichostatin A, trimetrexate, trofosfamide, tumor necrosis factor, valproic acid, VER49009, verapamil, vertoporfin, vinblastine, vincristine, vindesine, nivorelbine, vitamin D3, VX-680, zactime, ZK-EPO, zorubicin or combinations thereof. To determine the binding of the compounds of Formula I to a representative protein kinase, such as tyrosine protein kinase, the following assay was used: Time-resolved homogeneous fluorescence (HTRF) kinase fluorescence assays were employed in vitro to detect and measure the inhibition of kinase activity. The HTRF assays were carried out in the manner described in Mathis, G. , HTRF (R) Tech nology, J. Biomol. Screen, 1999, 4 (6): pp. 309-314). The protocol was adapted to determine the activity with respect to a specific protein tyrosine kinase (PTK). A preferred protocol for conducting the HTRF experiments is described below. The adaptation of these protocols to determine the activity of a compound for other kinases is within the capabilities of those skilled in the art. In a representative experiment, 10 μL of KDR, prepared in the manner described herein, were mixed with 10 μL of inhibitor (several concentrations, 2% final in DMSO) and 10 μL of ATP (1 25 μM, final concentration). in reaction buffer (50 mM H EPES, pH 7.5, MgCl 2, 2 mM MnCl 2, 0.1% BSA and 1 mM DTT, 40 μL final volume). The reaction was initiated by the addition of Bio-fgfr peptide (Genemed Biotechnologies, I nc., San Francisco, CA), 0.5 μM (final concentration) in a 96-well black plate (Packard). After incubation for 45 minutes at room temperature, the reaction was stopped by adding 60 μL of stop / develop buffer, to give 30 mM EDTA, 1 μg / mL of streptavidin-APC (Prozyme), 50 ng / mL of antibody monoclonal antiphosphotyrosine PT66-K mAb cryptate europium, 30 mM HEPES, pH 7.5, KF, 1 20 mM, 0.005% Tween-20, 0.05% BSA). The stopped reaction was allowed to stand at room temperature for 1 hour and then read in a resolved fluorescence detector over time (Envision, Perkin Elmer) at 61 5 nm and 665 nm, simultaneously. The relationship between the 615 nm signal and the 665 nm signal was used in the calculation of the IC50. The K values were calculated in the manner described in Biochem. Pharmacol. 1 973, 22, 3099-31 08. The coding sequence for the human KDR intracellular domain (aa789-1 354), was generated by polymerase catalyzed chain reaction (PCR) using cDNA isolated from HUVEC cells. A poly-H is6 sequence was also introduced at the N-terminus of this protein. This fragment was cloned into the transfection vector VI1 393 at the Xbal and Notl site. Recombinant baculovirus (BV) was generated by cotransfection, using the BaculoGold transfection reagent (PharMingen). The recombinant BV was purified on plates and verified by a Western analysis. For protein production, SF-9 cells were grown in SF-900-II medium, at 2 x 106 / mL, and infected at 0.5 plaque-forming units per cell (MOI). The cells were harvested at 48 hours after infection. The SF-9 cells were expressed (His) 6KDR (aa789-1 354), were used adding 50 mL of Triton X-1 00 lysis buffer (20 mM Tris, pH 8.0, 37 mM NaCl, 1% glycerol %, 1% Triton X-100, 1 mM PMSF, 10 μg / mL of aprotinin, 1 μg / mL of leupeptin) to the cell pellet formed 1 L of the cell culture. The lysate was centrifuged at 19,000 rpm in a Sorval SS-34 rotor for 30 min. at 4 ° C. The cell lysate was applied to a 5 mL NiCI2 chelating sepharose column, equilibrated with 50 mM HEPES, pH 7.5, 0.3 M NaCl. The KDR was eluted using the same buffer solution containing 0.25 M imidazole. The fractions from the column were analyzed. using EGPA-DSS and by an ELISA assay (see below), which measure the activity of the kinase. The purified KDR was passed through an exchange column with 25 mM HEPES, pH 7.5, 25 mM NaCl, 5 mM DTT buffer and stored at -80 ° C. The results are shown in Tables 1 and 2. TABLE 1 Inhibition of KDR (nM) TABLE 2 Inhibition of KDR (μM) 15 20 25 REACTION SCHEME 1 The 4-bromobenzene-1,2-diamine can be converted into these of Formula I by reacting it with RxC HO, oxona and a base. The bases include potassium carbonate and the like. The reaction is typically carried out in DM F / ag ua at room temperature. ESQU EMA OF REACTION 2 The 4-bromobenzene-1,2-diamine can be transformed into the compounds of Formula 2, by reacting it with RxCO2H, and an aqueous acid. The acids include and the like. The reaction is typically carried out at reflux temperature. REACTION SCHEME 3 The 4-bromobenzene-1,2-diamine can be converted to 6-bromo-2-phenoxy-1H-benzimidazole by reacting it with 1,1-dichloro-1,1-diphenoxymethane and a base. The bases include sodium carbonate and the like. The reaction is typically carried out in solvents such as ethyl acetate, at room temperature. The compound of Formula 1 A is another example of a precursor compound that can be used to prepare compound A1.

REACTION SCHEME 4 4- (4,4,5,5-tetramethyl-1,2,2-dioxaborolan-2-yl) -benzene-1,2-diamine (compound of Example 280A) can be transformed into the compounds of Formula 3 , making it react with RxCH2CO2H, and a coupling agent. The coupling agent includes 1,1 '-carbonyldiimidazole and the like. The reaction is typically carried out at 50 ° C in solvents such as THF and the like. REACTION SCHEME 5 The compounds of Formula 3 can be converted into compounds of Formula 5, by reacting them with compounds of Formula 4 (prepared in the manner described in International Patent Publication WO 2005/074603 and AF Burchat et al., Bioorg Med. Chem. Lett., 2002, 12, 1687-1 690), a base and a catalyst. The bases include sodium carbonate and the like. The catalysts include dichloro- [1,1'-bis- (diphenylphosphino) -ferrocene] -palladium (11) dichloromethane and the like. The reaction is typically carried out in a mixture of DM E and water, and the like, at about 1 30 ° C in a microwave reactor. REACTION SCHEME 6 The compounds of Formula 5 can be converted into compounds of Formula 6, by reacting them with acetic acid. The reaction is typically carried out at about 1000 ° C. REACTION SCHEME 7 (7) -Bromo-2-chloro-1 H-benzimidazole (compound of Example 1 33A), can be transformed into the compounds of Formula 7, by reacting it with RxSO3H. The reaction is typically carried out in solvents such as DM F, in a microwave reactor at about 1 70 ° C.

REACTION SCHEME 8 The compounds of Formulas 1, 1 A, 2, 7, 1 3, 1 5, 1 7, 1 9, 21 and 23 can be converted to the compounds of Formula 8 by reacting some of them with bis- ( pinacolato) -diboro, potassium acetate and a catalyst. The catalysts include dichloro- [1,1'-bis- (diphenylphosphino) -ferrocene] -palladium (11) dichloromethane and the like. Solvents include DMF and the like. The reaction is typically carried out at about 1000 ° C. ESQU EMA OF REACTION 9 The compounds of Formula 8 and Formula 1 1 can be converted into compounds of Formula 9, by reacting them or not with compounds of Formula 4, a base and a catalyst.

The bases include sodium carbonate and the like. The catalysts include dichlorobis (triphenylphosphino) palladium (11) and the like. The reaction typically it is carried out in solvents such as DM E, DM F, water or mixtures thereof, in a microwave reactor at about 1 30 ° C. REACTION SCHEME 10 The compounds of Formula 1 0 (prepared in the manner described in Example 1 88B) and 4- (4,4,5,5-tetramethyl-1,2,2-dioxaborolan-2-yl) -benzene-1, 2-diamine (compound of Example 280A), can be converted into compounds of Formula 1 1. The reaction is typically carried out at room temperature in solvents such as methanol and the like. REACTION SCHEME 1 1 (12) (13) The compounds of Formula 1 2 (prepared in the manner described in Example 1 85C) can be converted into compounds of Formula 1 3 by reacting them with triethyl orthoformate and an acid. The acids include trifluoroacetic acid and the like. The reaction is typically carried out at room temperature in solvents such as methylene chloride and Similar. REACTION SCHEME 1 2 The compounds of Formula 14 can be transformed into compounds of Formula 15, by reacting them with RXX7 (where X7 is a halide) and a base. The bases include sodium hydride and the like. The reaction is typically carried out in solvents such as DMF and the like, at a temperature between 0 ° C and room temperature. REACTION SCHEME 1 3 The compounds of Formula 1 can be converted into compounds of Formula 16, by reacting them with an acid. Acids include polyphosphoric acid and the like. The reaction is typically carried out at about 90-1 00 ° C. REACTION SCHEME 14 The 2-amino-5-bromophenol (prepared in the manner described in Example 58B) can be transformed into the compounds of Formula 1, by reacting it with RXNCS, copper sulfate and a base. The bases include triethylamine and the like. The reaction is typically carried out in solvents such as THF and the like, with silica gel at room temperature. REACTION SCHEME 14 The compounds of Formula 1 8 (prepared in the manner described in Example 57A) can be transformed into compounds of Formula 1 9 by reacting them with diethyl azodicarboxylate and triphenylphosphine. The reaction is typically carried out in solvents such as TH F, at room temperature. ESQU EMA OF REACTION 1 5 The compounds of Formula 20 (prepared in the manner described in Example 76B) can be transformed into compounds of Formula 21, by reacting them with a base in a microwave reactor. The bases include triethylamine and the like. The reaction is typically carried out in solvents such as acetonitrile at about 1 70 ° C. REACTION SCHEME 16 (22) (23) The compounds of Formula 22 can be converted into compounds of Formula 23, by reacting them with 4-chloro-2-aminobenzenethiol. The reaction is typically carried out in solvents such as benzene, at about 80 ° C. REACTION SCHEME 17 (4) (24) The 2-nitro-4- (4,4,5,5-tetramethyl-1,2,2-dioxaborolan-2-yl) -aniline can be converted into the compounds of Formula 24 by reacting it with compounds of the Formula 4, (Ph3P) 2PdCI2PdCI2 and a base. The bases include sodium carbonate and the like. The reaction is typically carried out in DM E / water at about 80 ° C. REACTION SCHEME 18 (25) The compounds of Formula 24 can be converted into compounds of Formula 25, by reacting them with RxCHO and Na2S2O4. The reaction is typically carried out in methanol, ethanol or mixtures thereof, at about 1 30 ° C. REACTION SCHEME 1 9 (24) (26) The compounds of Formula 24 can be transformed into compounds of Formula 26, by reacting them with hydrogen and a catalyst. The catalysts include palladium on carbon, Raney nickel and the like. The reaction typically takes performed in methanol, ethanol, tert-butanol, THF, ethyl acetate or mixtures thereof, at a temperature of about 40 ° C to about 100 ° C. The compounds of Formula 26 can be transformed into compounds of Formula 25, by reacting them with CH3C H2OC (N H) Rx »HCl. The reaction is typically carried out in methanol, ethanol, tert-butanol or mixtures thereof, at about 25 ° C. The compounds of Formula 26 can be converted into compounds of Formula 25, by reacting them with compounds of the formula (CH 3 CH 2 O) 3 CR x. The reaction is typically carried out in methanol, ethanol, tert-butanol or mixtures thereof, at about 80 ° C. The compounds of Formula 26 can be transformed into compounds of Formula 25, by reacting them with RXNCS and the product of this reaction by reacting with a coupling agent. Coupling agents include DCC, EDC I and the like. The reactions are typically carried out continuously in TH F, at a temperature of about 25 ° C to about 50 ° C for the first stage and about 50 ° C for the second stage.

ESQU EMA OF REACTION 20 3-Iodo-1 H-pyrazolo- [3,4-d] -pyrimidin-4-yl-amine (prepared in the manner described in A. F. Burchat et al., Bioorg, Med.Chem.Lett., 2002, 12, 1687-1600) can be transformed into compounds of Formula 27, by reacting it with an alcohol under the conditions of Mitsunobu, followed by a reductive alkylation or amination. REACTION SCHEME 21 3-Iodo-1 H-pyrazolo- [3,4-d] -pyrimidin-4-yl-amine (prepared in the manner described in AF Burchat et al., Bioorg, Med.Chem.Lett., 2002, 1 2, 1687-1690), can be transformed into compounds of Formula 28, by reacting it with 4-fluorobenzaldehyde, under standard alkylation conditions, followed by standard uctive network amination conditions, employing an amine ESQU EMA OF REACTION 22 (28A) The compounds of Formulas 27 and 28 can be transformed into compounds of Formula 28A, by typical methods such as those described in Palladium Reagents and Catalysts: New Perspectives for The 21st Century, by J. Tsuji, John Wiley & Sons, Ltd. , Chichester, 2004, 1-670. REACTION SCHEME 23 The compounds of Formula 29 (prepared in the manner described in Example 31B), can be transformed into compounds of Formula 30A and Formula 30B, by reacting them with RCN H2 and a reducing agent. Reductive agents include sodium cyanoborohydride and the like. The reaction is typically carried out in solvents such as methanol and the like, with a few drops of acetic acid. The reaction typically it is carried out at approximately 70 ° C. REACTION SCHEME 24 (31) The (3-chloropyrazin-2-yl) -methylamine (compound of Example 283A), can be transformed into compounds of Formula 31, by reacting it with B 1 CO 2 H, a catalyst and a coupling agent. The catalysts include DMAP and the like. Coupling agents include DCC, EDCI and the like. The reactions are typically carried out in solvents such as DM F, dichloromethane, DM E and the like, or mixtures thereof, at or above room temperature. REACTION SCHEME 25 The compounds of Formula 32 can be transformed into compounds of Formula 33, by reacting them with POCI3. The reaction is typically carried out in solvents such as acetonitrile, at about 55 ° C.

REACTION SCHEME 26 The compounds of Formula 33 can be transformed into compounds of Formula 34, by reacting them with N-iodosuccinimide. The reaction is typically carried out in solvents such as DM F, at about 25 ° C. REACTION SCHEME 27 The compounds of Formula 34 can be transformed into compounds of Formula 35 by reacting them with ammonia. The reaction is typically carried out in solvents such as isopropanol, dioxane and the like, or mixtures thereof, at about 25 ° C. REACTION SCHEME 28 The compounds of Formula 35 can be converted into compounds of Formula 36, by typical methods such as those described in Palladium Reagents And Catalysts: New Perspectives For The 21 st Century, by J. Tsuji, Joh n Wiley & Sons, Ltd. , Chichester, 2004, 1-670. REACTION SCHEME 29 The compound 6- (aminomethyl) -pyrimidin-2, 4- (1 H, 3H) -dione can be transformed into compounds of Formula 37, by reacting it with A1 COCI and a base. The bases include triethylamine and the like. The reaction is typically carried out in solvents such as DM F, at about 50 ° C. REACTION SCHEME 30 The compounds of Formula 37 can be transformed into compounds of Formula 38, by reacting them with POCI3.

The reaction is typically carried out in solvents such as toluene and the like, or mixtures thereof, at about 1000 ° C.

REACTION SCHEME 31 The compounds of Formula 38 can be converted into compounds of Formula 39, by reacting them with 1- (4-methoxyphenyl) -methanamine. The reaction is typically carried out in solvents such as dioxane and the like at about 80 ° C. 10 ESQU EMA OF REACTION 32 (39) (40) The compounds of Formula 39 can be transformed into compounds of Formula 40, by reacting them with hydrogen and a catalyst. The catalysts include palladium in carbon and the like. The reaction is typically carried out in methanol, ethanol, tert-butanol, THF, ethyl acetate or mixtures thereof. , at a temperature of about 25 to about 100 ° C. REACTION SCHEME 33 The compounds of Formula 40 can be converted into compounds of Formula 41, by reacting them with N-bromosuccinimide. The reaction is typically carried out in solvents such as DMF and the like, at about 25 ° C. REACTION SCHEME 34 The compounds of Formula 41 can be converted into compounds of Formula 42, by typical methods such as those described in Palladium Reagents and Catalysts: New Perspectives for The 21st Century, by J. Tsuji, John Wiley & Sons, Ltd. , Chichester, 2004, 1-670. REACTION SCHEME 35 The compounds of Formula 42 can be converted into compounds of Formula 42A, by reacting them with trifluoroacetic acid. The reaction is typically carried out in a microwave reactor, in solvents such as dichloromethane and the like, at about 1000 ° C.

REACTION SCHEME 36 The compound 6- (aminomethyl) -1,2,4-triazin-5- (4H) -one can be converted into compounds of Formula 43 by reacting it with B 1 CO 2 H, a catalyst and a coupling agent. The catalysts include DMAP and the like. Coupling agents include DCC, EDCI and the like. The reactions are typically carried out in solvents such as DMF, dichloromethane, DM E and the like, or mixtures thereof, at or above room temperature. REACTION SCHEME 37 The compounds of Formula 43 can be transformed into compounds of Formula 44, by reacting them with POCI3. The reaction is typically carried out in solvents such as acetonitrile, at about 80 ° C. ESQU EMA OF REACTION 38 The compounds of Formula 44 can be converted into compounds of Formula 45 by reacting them with N-iodosuccinimide. The reaction is typically carried out in solvents such as DMF, at about 25 ° C. REACTION SCHEME 39 The compounds of Formula 45 can be converted into compounds of Formula 46, by reacting them with POCI3, 1, 2,4-triazole and pyridine, followed by ammonia. The reaction is typically carried out in solvents such as isopropanol and the like. REACTION MODEL 40 The compounds of Formula 46 can be converted into compounds of Formula 47, by typical methods such as those described in Palladium Reagents and Catalysts: New Perspectives for The 21 st Century, by J. Tsuji, John Wiley & Sons, Ltd. , Chichester, 2004, 1-670.

REACTION SCHEME 41 Compounds of Formula 48 (J. Med. Chem. 1990, 33, 1984) can be transformed into compounds of Formula 49, by reacting them with B1X7 (where X7 is a halide), a base and a transfer catalyst. phase. The bases include potassium carbonate and the like. The phase transfer catalysts include 1, 4,7,10,13,16-hexaoxacyclooctadecane (18-crown-6) and the like. The reaction is typically carried out in solvents such as DMF, at 25 ° C or more. The compounds of Formula 48 (J. Med. Chem. 1990, 33, 1984) can be transformed into compounds of Formula 49, by reacting them with B1OH, DIAD and PPh3. The reaction is typically carried out in solvents such as THF, at 25 ° C or more. REACTION SCHEME 42 The compounds of Formula 49 can be converted into compounds of Formula 50, by reacting them with ammonia. The reaction is typically carried out in solvents such as isopropanol, dioxane and the like, or mixtures thereof, at about 25 ° C. REACTION SCHEME 43 The compounds of Formula 50 can be converted into compounds of Formula 51, by typical methods such as those described in Palladium Reagents and Catalysts: New Perspectives for The 21st Century, by J. Tsuji, John Wiley & Sons, Ltd. , Chichester, 2004, 1-670. Time-resolved homogeneous fluorescence kinase (HTRF) assays were also carried out in vitro to measure the inhibition of kinase activity. The HTRF assays can be carried out in accordance with known protocols (Technology, J. Biomol. Screen, 1999, 4 (6): pp 309-314). The protocol was adapted to determine the activity with respect to a specific PTK. For example, a preferred protocol for carrying out the experiments on HTRF is given below. The adaptation of these protocols to determine the activity of a compound for other kinases are within the capabilities of those skilled in the art. In a representative experiment, 10 μL of KDR, prepared in the manner described below, mixed with 10 μL of inhibitor (at various concentrations, 2% final concentration of DMSO) and 10 μL of ATP (final concentration 125 μM) in reaction buffer (50 mM HEPES, pH 7.5, 10 mM MgCl 2, 2 mM MnCl 2, 0.1% BSA and 1 mM DTT, final volume: 40 μL). The reaction was initiated by adding the peptide Bio-fgfr (purchased from Genemed Biotechnologies Inc., San Francisco, CA, concentration 0.5 μM) in a 96-well black plate (Packard). After incubation for 45 minutes at room temperature, the reaction was stopped by adding 60 μL of stop / develop buffer, to obtain 30 mM EDTA, 1 μg / mL of Streptavidin-APC (Prozyme), 50 ng / mL of the monoclonal antibody antiphosphotyrosine, PT66-K, europium cryptate, 30 mM HEPES, pH 7.5, 120 mM KF, 0.005% Tween-20, 0.05% BSA). The stopped reaction was allowed to stand at room temperature for 1 hour and was read in a fluorescence detector resolved over time (Envision, Perkin Elmer) at 615 nm and 665 nm, to calculate Cl50. The K i values were calculated in the manner described in Biochem, Pharmacol. 1973, 22, 3099-3108. The related procedures were used to evaluate the inhibitory effect of the compounds of the present invention on the tyrosine kinase activity of c-Kit, IGF-IR, EGFR, Src and ErbB2. The coding sequence of the human intracellular domain KDR (aa789-1354), was generated by PCR using cDNA isolated from HUVBC cells. A poly-His6 sequence was also introduced into the N-terminal end of this protein. This fragment was cloned into the transfection vector pVL1393, at the Xba I and Notl sites. Recombinant baculoviruses (BV) were generated through cotransfection using the BaculoGold transfection reagent (PharM ingen). The recombinant BV was purified on the plate and verified by Western analysis. For protein production, SF-9 cells were cultured in SF-900-I I medium, at 2 x 1 06 / mL and infected with 0.5 plaque-forming units per cell (MO I). The cells were harvested 48 hours after infection. SF-9 cells expressing (His) 6KDR (aa789-1 354) were used, adding 50 mL of Triton X-1 00 lysis buffer (20 mM Tris, pH 8.0, 37 mM NaCl, 1% glycerol %, Triton X-1 00 at 1%, 1 mM PMSF, 10 μg / mL of aprotinin, 1 μg / mL of leupeptin) to the cell pellet from 1 L of cell culture. The lysate was centrifuged at 1 9,000 rpm in a Sorval SS-34 rotor for 30 minutes at 4 ° C. The cell lysate was applied to a 5 mL NiCI2 chelating sepharose column equilibrated with 50 mM H EPES, pH 7.5 and NaCl 0.3M. The KDR was eluted using the same buffer solution containing 0.25M imidazole. Fractions from the column were analyzed by EG PA-DSS and an ELISA assay, which measured kinase activity. The purified KDR was applied to a 25 mM H EPES exchange column, pH 7.5, 25 mM NaCl and 5 mM DTT buffer and stored at -80 ° C. The data from these assays demonstrate the utility of the compounds of Formula I as inhibitors of protein kinase and, therefore, they are expected to be useful in the treatment of diseases in which any member of the kinase family is expressed. Diseases that involve excessive expression or lack of regulation of a member of the protein kinase family include, but are not limited to, acoustic neuroma, acute leukemia, acute lymphocytic leukemia, acute myelocytic leukemia (monocytic, myeloblastic, adenocarcinoma, angiosarcoma, astrocytoma, myelomonocytic and promyelocytic), acute T cell leukemia, basal cell carcinoma, bile duct carcinoma, bladder cancer, brain cancer, breast cancer, bronchogenic carcinoma, cervical cancer, chondrosarcoma, chondroma, choriocarcinoma, chronic leukemia, leukemia chronic lymphocytic, chronic myelocytic leukemia (granulocytic), chronic myelogenous leukemia, colon cancer, colorectal cancer, craniopharyngioma, cystadenocarcinoma, diffuse large B-cell lymphoma, proliferative changes (dysplasias and metaplasias), embryonal carcinoma, endometrial cancer, endotheliosarcoma, ependymoma, epithelial carcinoma, erythroleukemia, c esophageal cancer, breast cancer positive to estrogen receptors, essential thrombocytopenia, Ewing tumor, fibrosarcoma, follicular lymphoma, germ cell testicular cancer, glioma, heavy chain disease, hemangioblastoma, hepatoma, hepatocellular cancer, prostate cancer insensitive to hormones, leiomyosarcoma, liposarcoma, lung cancer, lymphomandotheliosarcoma, lymphangiosarcoma, lymphoblastic leukemia, lymphoma (Hodgkin's and non-Hodgkin's), malignant diseases and hyperproliferative disorders of the bladder, breast, colon, lung, ovaries, pancreas, prostate, skin and uterus, malignant lymphoid T-cell or B-cells, leukemia, lymphoma, medullary carcinoma, medulloblastoma, melanoma, meningioma, mesothelioma , multiple myeloma, myelogenous leukemia, myeloma, myxosarcoma, neuroblastoma, non-small cell lung cancer, oligodendroglioma, oral cancer, osteogenic sarcoma, ovarian cancer, pancreatic cancer, papillary adenocarcinomas, papillary carcinoma, pinealoma, polycythemia vera, prostate cancer, cancer rectal cancer, renal cell carcinoma, retinoblastoma, rhabdomyosarcoma, sarcoma, sebaceous gland carcinoma, seminoma, skin cancer, small cell lung cancer, solid tumors (carcinomas and sarcomas), small cell lung cancer, stomach cancer, carcinoma of the squamous cells, synovitis, carcinoma of sweat glands, cancer Thyroid, Waldenstrom macroglobulinemia, testicular tumors, uterine cancer and Wilm tumor. It is also expected that the compounds of Formula I inhibit the growth of cells derived from a cancer or neoplasia, such as breast cancer (including breast cancer positive to estrogen receptors), colorectal cancer, endometrial cancer, lung cancer (including small cell lung cancer), lymphoma (including follicular or diffuse large B-cell lymphoma), lymphoma (including non-Hodgkin's lymphoma), neuroblastoma, ovarian cancer, prostate cancer (including insensitive prostate cancer to hormones) and testicular cancer (including germ cell testicular cancer). It is also expected that the compounds of Formula I inhibit the growth of cells derived from a pediatric cancer or neoplasm, such as embryonic rhabdomyosarcoma, pediatric acute lymphoblastic leukemia, pediatric acute myelogenous leukemia, pediatric alveolar rhabdomyosarcoma, pediatric anaplastic ependymoma, large cell lymphoma. pediatric anaplastic, pediatric anaplastic medulloblastoma, atypical pediatric central nervous system teratoid / rhabdoid tumor, pediatric bifenotypic acute leukemia, pediatric Burkitt's lymphoma, pediatric cancers of the Ewing family of tumors, such as primitive neuroectodermal tumors, pediatric diffuse anaplastic Wilm tumor , Wilm tumor of pediatric favorable histologypediatric glioblastoma, pediatric medulloblastoma, pediatric neuroblastoma, pediatric neuroblastoma derived myelomitomatosis, pediatric pre-B cell cancers (such as leukemia), pediatric osteosarcoma, pediatric rhabdoid renal tumor, pediatric rhabdomyosarcoma, and pediatric T-cell cancers, such as lymphoma and skin cancer. For example, the involvement of protein kinases in bladder cancer, breast cancer, cervical cancer, colon cancer, endometrial cancer, esophageal cancer, lung cancer, ovarian cancer, pancreatic cancer, prostate cancer, rectal cancer, skin cancer, stomach cancer and thyroid cancer, are reported in Endocrine Rev. 21, 215 (2000), Br. J. Cancer 92, 1467 (2005), Cytokine Growth Factor Rev. 7, 133 (1996) and Biochem. Pharm. 51, 1101 (1996) (IGF1R-1); Biochem. Biophys. Acta 1198, 165 (1994), New Eng. J. Med. 344, 783 (2001) (ErbB2); Cancer Metastasis Rev. 22, 337 (2003), J. Clin. Invest. 91, 53 (1993) and BBRC 243,503 (1998) (SRC-1); Science 279, 577 (1998) and NELM 344, 1038 (2001). Yet another embodiment comprises methods for the treatment of a mammal having a disease characterized by a lack of regulation of protein kinase activity, which comprises administering thereto, a therapeutically effective amount of a compound of Formula (I) and one or more than other additional therapeutic agents, with or without the administration of radiation. The compounds of Formula (I) are also expected to be useful when used with alkylating agents, angiogenesis inhibitors, antibodies, antimetabolites, antimitotic, antiproliferative, aurora kinase inhibitors, Bcr-Abl kinase inhibitors, biological response modifiers. , cyclin-dependent kinase inhibitors, cell cycle inhibitors, cyclooxygenase-2 inhibitors, viral leukemia oncogene receptor homologous receptor (ErbB2) inhibitors, growth factor inhibitors, heat shock protein inhibitors (HSP) - 90, histone deacetylase enzyme inhibitors (HDAC), hormonal therapies, immunological agents, intercalated antibiotics, kinase inhibitors, rapomycin inhibitors in mammals, kinase inhibitors regulated by an extracellular signal activated by mitogens, nonsteroidal anti-inflammatory drugs (FAI NE), platinum chemotherapeutic agents, polo-like kinase inhibitors, proteasome inhibitors, purine analogs, pyrimidine analogs, tyrosine receptor inhibitors kinase, alkaloids of retinoid / deltoid plants, inhibitors of the topoisomerase enzyme, and the like. "Alkylating agents include altretamine, AM D-473, AP-5280, apazicuone, bendamustine, brostalicin, busulfan, carbocuone, carmustine (BCNU), chlorambucil, Cloretazine ™ (VN P 401 01 M), cyclophosphamide, decarbazine, estramustine, fotemustine , glufosfamide, ifosfamide, KW-2170, lomustine (CCN U), mafosfamide, melphalan, mitobronitol, mitolactol, nimustine, nitrogen mustard N-oxide, ranimustine, temozolomide, thiotepa, treosulfan, trofosfamide and the like .. Inhibitors of angiogenesis include inhibitors of specific tyrosine kinase endothelial receptors (Tie-2), epidermal growth factor receptor (EG FR) inhibitors, insulin-2 growth factor receptor (IG FR-2) inhibitors, metalloproteinase-2 enzyme inhibitors of matrix (MM P-2), inhibitors of matrix metalloproteinase-9 enzyme (MM P-9), inhibitors of platelet-derived growth factor (PDGFR), inhibitors of the growth factor receptor vascular endothelial tyrosine kinase (VEGFR) analogs to thrombospondin, and the like. Inhibitors of the aurora kinase enzyme include AZD-1152, mln-8054, VX-680 and the like. Inhibitors of Bcr-Abl kinase include DASATINIB® (BMS-354825), GLEEVEC® (imatinib) and the like. The CDK inhibitors include AZD-5438, BMI-1040, BMS-032, BMS-387, CVT-2584, flavopiridol, GPC-286199, MCS-5A, PD0332991, PHA-690509, seliciclib (CYC-202, R- roscovitine), ZK-304709 and the like. Inhibitors of COX-2 include ABT-963, ARCOXIA® (etoricoxib), BEXTRA® (valdecoxib), BMS347070, CELEBREX ™ (celecoxib), COS-189 (lumiracoxib), CT-3, DERAMAXX® (deracoxib), JTE- 522, 4-methyl-2- (3,4-dimethylphenyl) -1- (4-sulfamoylphenyl-1H-pyrrolo), MK-663 (etoricoxib), NS-398, parecoxib, RS-57067, SC-58125, SD -8381, SVT-2016, S-2474, T-614, VIOXX® (rofecoxib) and the like. EGFR inhibitors include ABX-EGF, anti-EGFr immunoliposomes, EGF vaccine, EMD-7200, ERBITUX® (cetuximab), HR3, IgA antibodies, IRESSA® (gefitinib), TARCEVA® (erlitinib or OSI-774), TF-38, fusion protein, TYKERB® (lapatinib) and the like. Inhibitors of the ErbB2 receptor include CP-724-714, CI-1033 (anertinib), Herceptin® (trastuzumab), TYKERB® (lapatinib), OMNITARG® (2C4, petuzumab), TAK-165, GW-572016 (ionafarmib), GW-282974, EKB-569, PI-166, dHER2 (HER2 vaccine), APC-8024 (HERB2 vaccine), anti-HER / 2neu bispecific antibody, B7.her21gB3, trifunctional bispecific antibodies AS HER2, mAB AR-209, mAB 2B-1 and the like.

Inhibitors of the histone deacetylase enzyme include the depsipeptide, LAQ-824, MS-275, trapoxin, suberoylanilide of hydroxamic acid (SAHA), TSA, valproic acid and the like. Inhibitors of HSP-90 include 17-AAG-nab, 17-AAG, CNF-101, CNF-1010, CNF 2024, 17-DMAG, geldanamycin, IPI-504, KOS-953, MYCOGRAB®, NCS-683664, PU24FC1 , PU-3, radicicol, SNX-2112, STA-9090 VER49009 and the like. MEK inhibitors include ARRY-142886, ARRY-438162, PD-325901, PD-98059 and the like. Inhibitors of mTOR include AP-23573, CCI-779, everolimus, RAD-001, rapamycin, temsirolimus and the like. Non-steroidal anti-inflammatory drugs include AMIGESIC® (salsalate), DOLOBID® (diflunisal), MOTRIN® (ibuprofen), ORUDIS® (ketoprofen), RELAFEN® (nabumetone), FELDENE® (piroxicam) ibuprofen cream, ALEVE® and NAPROSYN® ( naproxen), VOLTAREN® (diclofenac), INDOCIN® (indomethacin), CLINORIL® (sulindac), TOLECTIN® (tolmetin), LODINE® (etodolac), TORADOL® (ketorolac), DAYPRO® (oxaprozin) and the like. Inhibitors of PDGFR include C-451, CP-673, CP-868596 and the like. Platinum chemotherapeutic agents include cisplatin, ELOXATIN® (oxaliplatin) eptaplatin, lobaplatin, nedaplatin, PARAPLATIN® (carboplatin), satraplatin and the like. Inhibitors of the polo-like enzyme kinase include the BI-2536 and the like. Thrombospondin analogs include ABT-510, ABT-567, ABT-898, TSP-1 and the like. Inhibitors of VEGFR include AVASTIN® (bevacizumab), ABT-869, AEE-788, ANGIOZYME ™, axitinib (AG-13736), AZD-2171, CP-547,632, IM-862, Macugen (pegaptamib), NEXAVAR® (sorafenib , BAY43-9006), pazopanib (GW-786034), (PTK-787, ZK-222584), SUTENT® (sunitinib, SU-11248), VEGF trap, vatalanib, ZACTIMA ™ (vandetanib, ZD-6474) and the like. Antimetabolites include ALIMTA® (premetrexed disodium, LY231514, MTA), 5, azacitidine, XELODA® (capecitabine), carmofur, LEUSTAT® (cladribine), clofarabine, cytarabine, cytarabine ocphosphate, cytosine arabinoside, decitabine, deferoxamine, doxifluridine, eflornithine , EICAR, enocitabine, ethnilcitidina, fludarabina, hydroxyurea, 5-fluorouracil (5-FU) alone or in combination with leucovorin, GEMZAR® (gemcitabine), hydroxyurea, ALKERAN® (melphalan), mercaptopurine, 6-mercaptopurine riboside, methotrexate, acid mycophenolic, nelarabine, nolatrexed, ocfosate, pelitrexol, pentostatin, raltitrexed, ribavirin, triapine, trimetrexate, S-1, thiazofurin, tegafur, TS-1, vidaribine, UFT and the like. Antibiotics include intercalated antibiotics "aclarubicin, actinomycin D, amrubicin, annamicin, adriamycin, BLENOXANE® (bleomycin), daunorubicin, CAELYX® or MYOCET® (doxorubicin), elsamitrucina, epirbucin, glarbuicin, ZAVEDOS® (idarubicin), mitomycin C, remorubicin, neocarzinostatin, peplomycin, pirarubicin, rebeccamycin, estelamer, streptozocin, VALSTAR® (valrubicin), zinostatin and the like. Inhibitors of the topoisomerase enzyme include aclarubicin, 9-aminocaptothecin, amonafide, amsacrine, becatecarin, belotecan, BN-80915, CAMPTOSAR® (irinotecan hydrochloride), camptothecin, CARDIOXANE® (dexrazoxin), diflomotecan, edarcain, ELLENCE® or PHARMORUBICIN® (epirubicin), etoposide, exatecan, 10-hydroxycamptothecin, gimatecan, lurtotecan, mitoxantrone, orathecine, pirarbucin, pixantrone, rubitecan, sobuzoxan, SN-38, tafluposide, topotecan and the like. Antibodies include AVASTIN® (bevacizumab), specific antibodies against CD40, chTNT-1 / B, denosumab, ERBITUX® (cetuximab), HUMAX-CD4® (zanolimumab), antibodies specific against IGF1R, lintuzumab, PANOREX® (edrecolomab), RENCAREX® (WX G250), RITUXAN® (rituximab), ticilimumab, trastuzimab and the like. Hormone therapies include ARIMIDEX® (anastrozole), AROMASIN® (exemestane), arzoxifene, CASODEX® (bicalutamide), CETROTIDE® (cetrorelix), degarelix, deslorelin, DESOPAN® (trilostane), dexamethasone, DROGENIL® (flutamide), EVISTA® (raloxifene), fadrozole, FARESTON® (toremifene), FASLODEX® (fulvestrant), FEMARA® (letrozole), formestane, glucocorticoids, HECTOROL® or RENAGEL® (dosercalciferol), lasofoxifene, leuprolide acetate, MEGACE® (megesterol), MIFEPREX ® (mifepristone), NILANDRON ™ (nilutamide), NOLVADEX® (tamoxifen citrate), PLENAXIs ™ (abarelix), predisone, PROPECIA® (finasteride), rilostan, SUPREFACT® (buserelin), TRELSTAR® (luteinizing hormone-releasing hormone (LHRH)), vantas, VETORYL® (trilostan or modrastan), ZOLADEX® (foshrelin, goserelin) and the like. Deltoids and retinoids include seocalcitol (EB1089, CB1093), lexacalcitrol (KH1060), fenretinide, PANRETIN® (aliretinoin), ATRAGEN® (tretinoin liposomal), TARGRETIN® (bexarotene), LGD-1550, and the like. Plant alkaloids include, but are not limited to, vincristine, vinblastine, vindesine, vinorelbine and the like. Proteasone inhibitors include VELCADE® (bortezomib), MG132, NPI-0052, PR-171 and the like. Examples of immunological agents include interferons and other immune enhancing agents. Interferons include interferon alpha, interferon alpha-2a, interferon alpha-2b, interferon beta, interferon gamma-la, ACTIMMUNE® (interferon gamma-1b), or interferon gamma-n1, combinations thereof and the like. Other agents include ALFAFERONE®, BAM-002, BEROMUN® (tasonermin), BEXXAR® (tositunomab), CamPath® (alemtuzumab), CTLA4 (cytotoxic lymphocyte antigen-4), decarbazine, denileucine, epratuzumab, GRANOCYTE® (lenograstim), lentinan , leukocyte interferon alpha, imiquimod, MDX-010, melanoma vaccine, mitumomab, molgramostim, MYLOTARG ™ (ge tuzumab ozogamicin), NEUPOGEN® (filgrastim), OncoVAC-CL, OvaRex® (oregovomab), pemtumomab (Y.muHMFGI), PROVENGE®, sargaramostim, sizofilan, teceleucin, TheraCys®, ubenimex, VIRULIZIN®, Z-100, WF-10, PROLEUKIN® (aldesleukin), ZADAXIN® (timalfasin), ZENAPAX® (aclizumab), ZEVALIN® (90Y-lbritumomab tiuxetán) and the like. Biological response modifiers are agents that modify the defense mechanisms of living organisms or the biological response, such as the survival, growth or differentiation of tissue cells, to direct them to have antitumor activity, and include crestin, lentinan , sizofiran, picibanil PF-3512676 (CpG-8954), ubenimex and the like. Pyrimidine analogues include cytarabine (ara C), cytosine arabinoside, doxifluridine, FLUDARA® (fludarabine), 5-FU (5-fluorouracil), floxuridine, GEMZAR® (gemcitabine), TOMUDEX® (ratitrexed), TROXATYL ™ (triacetyluridine) troxacitabine) and the like. Purine analogues include LANVIS® (thioguanine) and PURI-NETHOL® (mercaptopurine). Antimitotic agents include batalbulin, epothilone D (KOS-862), N- (2 - ((4-hydroxyphenyl) -amino) -pyridin-3-yl) -4-methoxybenzenesulfonamide, ixabepilone (BMS 247550), paclitaxel, TAXOTERE® (docetaxel), PNU100940 (109881), patupilone, XRP-9881, vinflunine, ZK-EPO and the like. The compounds of the present invention are also intended to be used as radiosensitizers that enhance the effectiveness of radiotherapy. Examples of radiation therapy include, but are not limited to, external beam radiation therapy. teletherapy, brachytherapy and radiotherapy of sealed and unsealed source. Additionally, the compounds of Formula I can be combined with other chemotherapeutic agents, such as ABRAXANE ™ (ABI-007), ABT-100 (farnesyl transferase inhibitor), ADVEXIN®, ALTOCOR® or MEVACOR® (lovastatin), AMPLIGEN® (poly l: poly C12U, a synthetic RNA), APTOSYN ™ (exisulind), AREDIA® (pamidronic acid), arglabin, L-asparaginase, atamestana (1-methyl-3,17-dione-androsta-1, 4-diena ), AVAGE® (tazarotne), AVE-8062, BEC2 (mitomomab), cachectin or cachexin (tumor necrosis factor), canvaxin (vaccine), CeaVac ™ (cancer vaccine), CELEUK® (celmoleucin), CEPLENE® (dihydrochloride) of histamine), CERVARIX ™ (human papillomavirus vaccine), CHOP® (C: CYTOXAN® (cyclophosphamide); H: ADRIAMYCIN® (hydroxidexorubicin); O: Vincristine (ONCOVIN®); P: prednisone), CyPat ™, combrestatin A4P , DAB (389) EGF or TransMID-107R ™ (diphtheria toxins), dacarbazine, dactinomycin, 5,6-dimethylxanthenone-4-acetic acid (DMXAA), eniluracil, EVIZON ™ (squalamine lactate), D IMERICINE® (T4N5 liposomal lotion), discodermolide, DX-8951f (exatecan mesylate), enzastaurin, EPO906, GARDASIL® (recombinant human papillomavirus tetravalent vaccine (Types 6, 11, 16, 18)), gastrimmuna, genasensa, GMK ( ganglioside conjugate vaccine), CVAX® (prostatic cancer vaccine), halofuginone, histerelin, hydroxycarbamide, ibandronic acid, IGN-101, IL-13-PE38, IL-13-PE38QQR (cintredekin besudotox), IL-13-pseudomonas exotoxin, interferon-a, interferon- ?, JUNOVAN ™ or MEPACT ™ (mifamurtide), lonafarnib, 5,10-methylenetetrahydrofolate, miltefosine (hexadecylphosphocholine), NEOVASTAT®, (AE-941), NEUTREXIN® (trimetrexate glucuronate), NIPENT® (pentostatin), ONCONASE® (a ribonuclease enzyme), ONCOPHAGE® (melanoma treatment vaccine), OncoVAX (IL-2 vaccine), ORATHECIN ™ (rubitecan), OSIDEM® (antibody-based cell drug), OvaRex® MAb ( murine monoclonal antibody), paditaxel, PANDIMEX ™ (ginseng aglycone saponins comprising 20 (S) protopanaxadiol (aPPD) and 20 (S) protopanaxathiol (aPPT)), panitumumab, PANVAC®-VF (cancer research vaccine), pegaspargase, PEG Interferon A, phenoxodiol, procarbazine, revimastat, REMOVAB® (catumaxomab), REVLIMID® (lenalidomide), RSR13 (efaproxiral), SOMATULINE® LA (lanreotide), SORIATANE® (acitretin), staurosporine (Streptomyces staurospores), talabostat ( PT100), TARGRETIN® (bexarotene), Taxoprexin® (DHA-paclitaxel), TELCYTA ™ (TLK286), temilifena, TEMODAR® (temozolomide), tesmilifen, thalidomide, THERATOPE® (STn-KLH), timitaq (2-amino-3,4-dihydro-6-methyl-4-oxo-5- dihydrochloride ( 4-pyridylthio) -quinazoline), TNFerade ™ (adenovector: DNA vehicle containing the tumor necrosis factor-a gene), TRACLEER® or ZAVESCA® (bosentan), tretinoin (Retin-A), tetrandrine, TRISENOX® ( arsenic trioxide), VIRULIZIN®, ukrain (alkaloid derivative of the large celandin plant), vitaxin (anti-alphavbeta3 antibody), XCYTRIN® (motexafin gadolinium), XINLAY ™ (atrasentan), XYOTAX ™ (paclitaxel polyglumex), YONDELIS ™ (trabectedin), ZD-6126, ZI NECARD® (dexrazoxane), zometa (zolendronic acid), zorubicin and the like. It is also expected that the compounds of Formula (I) inhibit the growth of cells derived from a pediatric cancer or neoplasm, including embryonic rhabdomyosarcoma, pediatric water lymphoblastic leukemia, pediatric water myeloid leukemia, pediatric alveolar rhabdomyosarcoma, pediatric anaplastic ependymoma, cell lymphoma. large pediatric anaplastic, pediatric anaplastic medulloblastoma, pediatric central nervous system teratoid / rhabdoid atypical tumor, pediatric bifenotypic acute leukemia, pediatric Burkitt's lymphoma, pediatric cancers of the Ewing family of tumors, such as primitive neuroectodermal tumors, Wilm's diffuse anaplastic tumor pediatric, Wilm's tumor of pediatric favorable histology, pediatric glioblastoma, pediatric medulloblastoma, pediatric neuroblastoma, pediatric neuroblastoma derived myelomitomatosis, pediatric pre-B cell cancers (such leukemia), osteosarcoma pedi pedia Atrial, pediatric rhabdoid renal tumor, pediatric rhabdomyosarcoma and pediatric T-cell cancers, such as lymphoma and skin cancer and the like. The compounds of Formula I can be prepared by synthetic chemical processes, examples of which are shown below. It should be understood that the order of the steps in the process may vary, that the reactants, solvents and reaction conditions may be substituted instead of those mentioned. specifically, and that some portions of molecules and minerals can be protected and unprotected, as needed. Protecting groups for C (O) OH portions include, but are not limited to, acetoxymethyl, allyl, benzoylmethyl, benzyl, benzyloxymethyl, tert-butyl, tert-butyldiphenylsilyl, diphenylmethyl, cyclobutyl, cyclohexyl, cyclopentyl, cyclopropyl, diphenylmethylsilyl, ethyl, para-methoxybenzyl, methoxymethyl, methoxyethoxymethyl, methyl, methylthiomethyl, naphthyl, para-nitrobenzyl, phenyl, n-propyl, 2,2,2-trichloroethyl, triethylsilyl, 2- (trimethylsilyl) -ethyl, 2- (trimethylsilyl) -ethoxymethyl, triphenylmethyl and the like. Protecting groups for C (O) and C (O) H portions include, but are not limited to, 1,3-dioxyl ketal, diethyl ketal, dimethyl ketal, 1,3-dithianyl ketal, O-methyloxime, O-phenyloxime and the like. Protecting groups for NH portions include, but are not limited toacetyl, alanyl, benzoyl, benzyl (phenylmethyl), benzylidene, benzyloxycarbonyl (Cbz), tert-butoxycarbonyl (Boc), 3,4-dimethoxybenzyloxycarbonyl, diphenylmethyl, diphenylphosphoryl, formyl, methanesulfonyl, para-methoxybenzyloxycarbonyl, phenylacetyl, phthaloyl, succinyl, trichloroethoxycarbonyl, triethylsilyl, trifluoroacetyl, trimethylsilyl, triphenylmethyl, triphenylsilyl, para-toluenesulfonyl and the like. Protecting groups for OH and SH portions include, but are not limited to, acetyl, allyl, allyloxycarbonyl, benzyloxycarbonyl (Cbz), benzoyl, benzyl, tert-butyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl, 3,4-dimethoxybenzyl, , 4-dimethoxybenzyloxycarbonyl, 1,1-dimethyl-2-propenyl, diphenylmethyl, formyl, methanesulfonyl, methoxyacetyl, 4-methoxybenzyloxycarbonyl, para-methoxybenzyl, methoxycarbonyl, methyl, para-toluenesulfonyl, 2,2,2-trichloroethoxycarbonyl, 2,2,2-trichloroethyl, triethylsilyl, trifluoroacetyl, 2- (trimethylsilyl) -ethoxycarbonyl, 2-trimethylsilylethyl, triphenylmethyl, 2- (triphenylphosphonium) -ethoxycarbonyl and the like. The following abbreviations have the meanings indicated. ADDP means 1, 1 '- (azodicarbonyl) -dipiperidine; AD-mix-ß means a mixture of (DHQD) 2PHAL, K3Fe (CN) 6, K2CO3 and K2SO4); AI BN means 2,2'-azobis- (2-methylpropionitrile); 9-BBN means 9-borabicyclo- [3.3.1] -nonano; Cp means cyclopentadiene; (DHQD) 2PHAL means hydroquinidine 1,4-phthalazinodiyl diethyl ether; DBU means 1, 8-diazabicyclo- [5.4.0] -u ndec-7-ene; DCC means dicyclohexylcarbodiimide; DI BAL means diisobutylaluminum hydride; DI EA means diisopropylethylamine; DMAP means N, N-dimethylaminopyridine; DME means 1,2-dimethoxyethane; DM F means N, N-dimethylformamide; dmpe means 1,2-bis- (dimethylphosphino) -ethane; DMSO means dimethisulfoxide; dppa means diphenylphosphorylazide; dppb means 1,4-bis- (diphenylphosphino) -butane; dppe means 1,2-bis- (diphenylphosphino) -ethane; dppf means 1,1 '-bis- (diphenylphosphino) ferrocene; dppm means 1,1-bis- (diphenylphosphino) -methane; AGE means 1- (3-dimethylaminopropyl) -3-ethylcarbodiimide; Fmoc means fluorenylmethoxycarbonyl; HATU means O- (7-azabenzotriazol-1-yl) -N, N 'N'N'-tetramethyluronium hexafluorophosphate; H M PA means hexamethylphosphoramide; I PA means isopropyl alcohol; LDA means lithium diisopropylamide; LHM DS means bis- (hexamethyldisilylamide) lithium; M P-BH3 means macroporo triethylammonio-methylpolystyrene cyanoborohydride; LAH means lithium aluminum hydride; NCS means N-chlorosuccinimide; PyBOP means benzotriazol-1-yl-oxytripyrrolidinophosphonium hexafluorophosphate; TDA-1 means tris- (2- (2-methoxyethoxy) -ethyl) -amine; TEA means triethylamine; TFA means trifluoroacetic acid; THF means tetrahydrofuran; NCS means N-chlorosuccinimide; NMM means N-methylmorpholine; N MP means N-methylpyrrolidine; PPh3 means triphenylphosphine. Rx and the group to which it is bound, combine to form a substituent defined by A0 5 ESQU EMA OF REACTION 1 The 4-bromobenzene-1,2-diamine can be transformed into compounds of Formula I, making it react with RxCHO, oxone and a base. The bases include potassium carbonate and the like. The reaction is typically carried out in DMF / water at room temperature. REACTION SCHEME 2 The 4-bromobenzene-1,2-diamine can be converted into compounds of Formula 2 by reacting it with RxCO2H and an aqueous acid. The acids include HCl and the like. The reaction is typically carried out at reflux temperature. REACTION SCHEME 3 The 4-bromobenzene-1,2-diamine can be converted to 6-bromo-2-phenoxy-1H-benzimidazole by reacting it with 1,1-dichloro-1,1-diphenoxymethane and a base. The bases include sodium carbonate and the like. The reaction is typically carried out in solvents such as ethyl acetate, at room temperature. The compound of Formula IA is another example of a precursor compound that can be used to prepare compound AO REACTION SCHEME 4 The 4- (4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl) -benzene-1,2-diamine (compound of Example 280A) can be transformed into compounds of Formula 3, making it react with RxCH2CO2H and a coupling agent. Coupling agents include 1,1 '-carbonyldiimidazole and the like. The reaction is typically carried out at 50 ° C in solvents such as THF and the like. REACTION SCHEME 5 The compounds of Formula 3 can be transformed into compounds of Formula 5by reacting them with compounds of Formula 4 (prepared in the manner described in International Patent Publication WO 2005/074603 and AF Burchat et al., Bioorg Med. Chem. Lett. 2002, 12, 1687-1690), a base and a catalyst. The bases include sodium carbonate and the like. The catalysts include the adduct dichloro- [1,1'-bis- (diphenylphosphino) -ferrocene-platinum (I I) dichloromethane and the like. The reaction is typically carried out in a mixture of DM E and ag ua and the like, at about 1 30 ° C in a microwave reactor. REACTION SCHEME 6 The compounds of Formula 5 can be converted into compounds of Formula 6, by reacting them with acetic acid. The reaction is typically carried out at approximately 1000 ° C. REACTION SCHEME 7 (7) -Bromo-2-chloro-1H-benzimidazole (compound of Example 133A) can be transformed into compounds of Formula 7, by reacting it with RxSO3H. The reaction is typically carried out in solvents such as DMF in a microwave reactor, at about 170 ° C. REACTION SCHEME 8 The compounds of Formulas 1, 1A, 2, 7, 13, 15, 17, 19, 21 and 23 can be converted into compounds of Formula 8 by reacting one of them with bis- (pinacolato) -diboron, acetate of potassium and a catalyst. The catalysts include the adduct dichloro [1,1'-bis- (diphenylphosphino) -ferrocene] -palladium (II) dichloromethane and the like. Solvents include DMF and the like. The reaction is typically carried out at about 100 ° C. REACTION SCHEME 9 The compounds of Formula 8 and Formula 1 1 can be converted into compounds of Formula 9, by reacting them or not with compounds of Formula 4, a base and a catalyst. The bases include sodium carbonate and the like. The catalysts include dichlorobis- (triphenylphosphino) -palladium (II) and the like. The reaction is typically carried out in solvents such as DM E, DM F, water or mixtures thereof, in a microwave reactor, at approximately 130 ° C. REACTION SCHEME 10 The compounds of Formula 1 0 (prepared in the manner described in Example 188B) and 4- (4,4,5,5-tetramethyl-1,2,2-dioxaborolan-2-yl) -benzene-1, 2 -diamine (composed of Example 280A) can be transformed into compounds of Formula 1 1. The reaction is typically carried out at room temperature in solvents such as methanol and the like. REACTION SCHEME 1 1 (12) (13) The compounds of Formula 12 (prepared in the manner described in Example 1 85C) can be transformed into compounds of Formula 1 3 by reacting them with triethyl orthoformate and an acid. The acids include trifluoroacetic acid and the like. The reaction is typically carried out at room temperature in solvents such as methylene chloride and the like. REACTION SCHEME 1 2 The compounds of Formula 14 can be converted into compounds of Formula 1, by reacting them with RxX7 (where X7 is a halide) and a base. Bases include sodium hydride and the like. The reaction is typically carried out in solvents such as DM F and the like at a temperature between 0 ° C and ambient temperature. ESQU EMA REACTION 1 3 The compounds of Formula 1 can be converted into compounds of Formula 16, by reacting them with a acid. Acids include polyphosphoric acid and the like. The reaction is typically carried out at a temperature of about 90-100 ° C. REACTION SCHEME 14 The 2-amino-5-bromophenol (prepared in the manner described in Example 58B), can be transformed into compounds of Formula 1, by reacting it with RXNCS, copper sulfate and a base. The bases include triethylamine and the like. The reaction is typically carried out in solvents such as THF and the like, with silica gel at room temperature. REACTION SCHEME 14 The compounds of Formula 1 8 (prepared in the manner described in Example 57A) can be transformed into compounds of Formula 19, by reacting them with diethyl azodicarboxylate and triphenylphosphine. The reaction is typically carried out in solvents such as TH F, at room temperature.

REACTION SCHEME 15 The compounds of Formula 20 (prepared in the manner described in Example 76B), can be transformed into compounds of Formula 21, by reacting them with and a base in a microwave reactor. The bases include triethylamine and the like. The reaction is typically carried out in solvents such as acetonitrile, at about 70 ° C. REACTION SCHEME 16 (22) (23) The compounds of Formula 22 can be converted into compounds of Formula 23, by reacting them with 4-chloro-2-aminobenzenethiol. The reaction is typically carried out in solvents such as benzene, at about 80 ° C.

REACTION SCHEME 17 (4) (24) 2-Nitro-4- (4,4,5,5-tetramethyl-1,2,2-dioxaborolan-2-yl) -aniline can be converted into compounds of Formula 24 by reacting it with compounds of Formula 4 , (Ph3P) 2PdCI2PdCI2 and a base. The bases include sodium carbonate and the like. The reaction is typically carried out in DME / water, at approximately 80 ° C. ESQU EMA OF REACTION 1 8 (24) + RxCHO (25) The compounds of Formula 24 can be converted into compounds of Formula 25, by reacting them with RxCHO and Na2S2SO. The reaction is typically carried out in methanol, ethanol or mixtures thereof, at about 1 30 ° C.

REACTION SCHEME 19 (24) (26) The compounds of Formula 24 can be transformed into compounds of Formula 26, by reacting them with hydrogen and a catalyst. The catalysts include palladium on carbon, Raney niq uel and the like. The reaction is typically carried out in methanol, ethanol, tert-butanol, THF, ethyl acetate or mixtures thereof, at a temperature of about 40 ° C to about 1000 ° C. The compounds of Formula 26 can be transformed into compounds of Formula 25, by reacting them with CH 3 CH 2 OC (N H) R x CR x. The reaction is typically carried out in methanol, ethanol, tert-butanol or mixtures thereof, at about 25 ° C. The compounds of Formula 26 can be transformed into compounds of Formula 25, by making them transformed with compounds of Formula (CH3CH2O) 3CRx. The reaction is typically carried out in methanol, ethanol, tert-butanol or mixtures thereof, at about 80 ° C. The compounds of Formula 26 can be transformed in compounds of Formula 25, by reacting them with RXNCS and reacting the product with a coupling agent. Coupling agents include DCC, EDC I and the like. The reactions are typically carried out continuously in TH F, at a temperature of about 25 ° C to about 50 ° C for the first step and about 50 ° C for the second step. REACTION SCHEME 20 3-Iodo-1 H-pyrazolo- [3,4-d] -pyrimidin-4-ylamine (prepared in the manner described in AF Burchat et al., Bioorg Med. Chem. Lett 2002, 12, 1 687-1690) can be transformed into compounds of Formula 27, by reacting it with an alcohol under Mitsunobu conditions, followed by a reductive alkylation or amination. 3-Iodo-1 H-pyrazolo- [3,4-d] -pyrimidin-4-yl-amine (prepared in the manner described in AF Burchat et al., Bioorg Med. Chem. Lett. 2002, 12, 1709-1690) can be transformed into compounds of Formula 28, by reacting it with 4-fluorobenzaldehyde, under the conditions standard of alkylation, followed by a reductive amination under standard conditions, using an amine. ESQU EMA OF REACTION 22 (28A) The compounds of Formulas 27 and 28 can be transformed into compounds of Formula 28A, by typical methods such as those described in Palladium Reagents And Catalysts: New Perspectives For The 21st Century, by J. Tsuji, Joh n Wiley & Sons, Ltd , Chichester, 2004, 1-670. REACTION SCHEME 23 The compounds of Formula 29 (preparations of the the manner described in Example 31 B) can be transformed into compounds of Formula 30A and Formula 30B, by reacting them with RCN H2 and a reducing agent. Reducing agents include sodium cyanoborohydride and the like. The reaction is typically carried out in solvents such as methanol and the like, with a few drops of acetic acid. The reaction is typically carried out at about 70 ° C. REACTION SCHEME 24 (31) The (3-chloropyrazin-2-yl) -methylamine (compound of Example 283A) can be transformed into compounds of Formula 31 by reacting it with B 1 CO 2 H, a catalyst and a coupling agent. The catalysts include DMAP and the like. Coupling agents include DCC, EDCI and the like. The reactions are typically carried out in solvents such as DM F, dichloromethane, DME and the like or mixtures thereof, at or above room temperature. REACTION SCHEME 25 The compounds of Formula 32 can be transformed into compounds of Formula 33, by reacting them with POCI3. The reaction is typically carried out in solvents such as acetonitrile, at about 55 ° C. REACTION SCHEME 26 The compounds of Formula 33 can be transformed into compounds of Formula 34, by reacting them with N-iodosuccinimide. The reaction is typically carried out in solvents such as DMF, at about 25 ° C. REACTION SCHEME 27 The compounds of Formula 34 can be transformed into compounds of Formula 35 by reacting them with ammonia. The reaction is typically carried out in solvents such as isopropanol, dioxane and the like or mixtures thereof, at about 25 ° C.

REACTION SCHEME 28 The compounds of Formula 35 can be converted into compounds of Formula 36, by typical methods such as those described in Palladium Reagents And Catalysts: New Perspectives For The 21 st Century, by J. Tsuji, Joh n Wiley & Sons, Ltd. , Chichester, 2004, 1-670. REACTION SCHEME 29 The compound 6- (aminomethyl) -pyrimidin-2, 4- (1 H, 3H) -dione can be transformed into compounds of Formula 37, by reacting it with A1COCI and a base. The bases include triethylamine and the like. The reaction is typically carried out in solvents such as DM F, at about 50 ° C. REACTION SYSTEM 30 The compounds of Formula 37 can be transformed into compounds of Formula 38, by reacting them with POCI3.

The reaction is typically carried out in solvents such as toluene and the like or mixtures thereof, at about 100 ° C. REACTION SCHEME 31 The compounds of Formula 38 can be converted into compounds of Formula 39, by reacting them with 1- (4-methoxyphenyl) -methanamine. The reaction is typically carried out in solvents such as dioxane and the like, at about 80 ° C. REACTION SCHEME 32 (39) < 0) The compounds of Formula 39 can be transformed into compounds of Formula 40, by reacting them with hydrogen and a catalyst. The catalysts include palladium in carbon and the like. The reaction is typically carried out in methanol, ethanol, tert-butanol, THF, ethyl acetate or mixtures thereof, at a temperature of about 25 ° C. about 1 00 ° C. REACTION SCHEME 33 The compounds of Formula 40 can be converted into compounds of Formula 41, by reacting them with N-bromosuccinimide. The reaction is typically carried out in solvents such as DMF and the like, at about 25 ° C. REACTION SCHEME 34 The compounds of Formula 41 can be converted into compounds of Formula 42, by typical methods such as those described in Palladium Reagents and Catalysts: New Perspectives For The 21 st Centu ry, by J. Tsuj i, John Wiley & Sons, Ltd. , Chichester, 2004, 1-670. ESQU EMA OF REACTION 35 The compounds of Formula 42 can be converted into compounds of Formula 42A, by reacting them with trifluoroacetic acid. The reaction is typically carried out in a microwave reactor, in solvents such as dichloromethane and the like at about 1000 ° C. REACTION SCHEME 36 The compound 6- (aminomethyl) -1,2,4-triazin-5 (4H) -one can be converted into compounds of Formula 43 by reacting it with B 1 CO 2 H, a catalyst and a coupling agent. The catalysts include DMAP and the like. Coupling agents include DCC, EDCI and the like. The reactions are typically carried out in solvents such as DM F, dichloromethane, DM E and the like or mixtures thereof, at or above the ambient temperature. REACTION SCHEME 37 The compounds of Formula 43 can be transformed into compounds of Formula 44, by reacting them with POCI3.

The reaction is typically carried out in solvents such as acetonitrile, at about 80 ° C. REACTION SCHEME 38 The compounds of Formula 44 can be transformed into compounds of Formula 45, by reacting them with N-10 iodosuccinimide. The reaction is typically carried out in solvents such as DMF, at about 25 ° C. REACTION SCHEME 39 The compounds of Formula 45 can be transformed into compounds of Formula 46, by reacting them with POCI3, 1, 2, 4-triazole and pyridine, followed by ammonia. The reaction It is typically carried out in solvents such as isopropanol and the like. REACTION SCHEME 40 The compounds of Formula 46 can be converted into compounds of Formula 47, by typical methods such as those described in Palladium Reagents And Catalysts: New Perspectives For The 21st Century, by J. Tsuji, John Wiley & Sons, Ltd., Chichester, 2004, 1-670. REACTION SCHEME 41 Compounds of Formula 48 (J. Med. Chem. 1990, 33, 1984) can be transformed into compounds of Formula 49, by reacting them with B1X7 (where X7 is a halide), a base and a transfer catalyst. phase. The bases include potassium carbonate and the like. The phase transfer catalysts include 1, 4,7,10,13,16-hexaoxacyclooctadecane (18-crown-6) and the like. The reaction is typically carried out in solvents such as DMF, at a temperature of 25 ° C or higher. The compounds of Formula 48 (J. Med. Chem. 1990, 33, 1984) can be transformed into compounds of Formula 49, by reacting them with B1OH, DIAD and PPh3. The reaction is typically carried out in solvents such as THF, at a temperature of 25 ° C or higher.

REACTION SCHEME 42 The compounds of Formula 49 can be converted to compounds of Formula 50 by reacting them with ammonia. The reaction is typically carried out in solvents such as isopropanol, dioxane and the like and mixtures thereof, at a temperature of about 25 ° C. REACTION SCHEME 43 The compounds of Formula 50 can be transformed into compounds of Formula 51, by typical methods such as those described in Palladium Reagents And Catalysts: New Perspectives For The 21 st Centu ry, by J. Tsuji, John Wiley & Sons, Ltd. , Chichester, 2004, 1-670. The following Examples are presented to provide what is thought to be the most useful and easy to understand description of the methods and conceptual aspects of the present invention. EXAMPLE 1 A To a mixture of 4-bromobenzene-1,2-diamine (0.2 g) in DMF / water (2 mL / 50 μL), was added oxone (0.4 g) and benzaldehyde (0.12 g) in DMF (2 mL). After one hour, the mixture was diluted with water, treated with K2CO3 and filtered. The filtrate was dissolved in dichloromethane, and this mixture was dried (Na 2 SO 4), filtered and concentrated. The concentrate was chromatographed on silica gel, with a lntelliflash-280 purification system, with ethyl acetate / hexanes. EXAMPLE 1B A mixture of EXAMPLE 1A (0.095 g), bis (pinacolato) diboro (0.17 g), potassium acetate (0.10 g) and dichloro (1,1'-bis (diphenylphosphino) -ferrocene) palladium (II) »dichloromethane (0.007 g) in DMF (2.5 mL), was stirred at 160 ° C for 15 minutes in a microwave reactor. More bis (pinacolato) diboro (2 equivalents), potassium acetate (3 equivalents) and dichloro (1,1'-bis (diphenylphosphino) ferrocene) -palladium (I l) * d chloromethane (0.03 equivalents) were added, and The mixture was stirred at 180 ° C for another 20 minutes, cooled, filtered through diatomaceous earth (Celite®) and concentrated. The concentrate was purified on silica gel with a lntelliflash-280 purification system, with ethyl acetate / hexanes. To the product was added cis-4- (4- (4-amino-3-iodopyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) -1-methylpiperazin-2-one, prepared as described in International Patent Publication WO 05/074603, (0.11 g), Na 2 CO 3 2M (0.23 mL) and dichlorobis (triphenylphosphine) palladium (11) (8 mg) in ethanol / water (2 mL / 1 mL). The mixture was stirred at 120 ° C for 20 minutes in a microwave reactor, cooled, filtered through diatomaceous earth (Celite®), dried (Na2SO), filtered and concentrated. The concentrate was purified by reverse phase HPLC with CH3CN / water / 0.1% TFA. 1 H-NMR (300 MHz, DMSO-d 6) d 13.09 (d, 1H), 8.25-8.20 (m, 3H), 7.89-7.68 (m, 2H), 7.61-7.50 (m, 4H), 4.88-4.78 ( m, 1H), 3.07 (bs, 2H), 2.83 (s, 3H), 2.74-2.71 (m, 2H), 2.36-2.22 (m, 3H), 2.16-2.04 (m, 2H), 1.76-1.60 ( m, 4H). EXAMPLE 2A A mixture of 4-bromo-2-nitrophenylamine (1 g), bis (pinacolato) diboro (2.35 g), potassium acetate (2.3 g) and dichloro (1,1'-bis (diphenylphosphino) ferrocene) palladium ( ll) »dichloromethane (0.10 g) in DMF (9.2 mL) was stirred at 100 ° C for 45 minutes. The mixture was filtered through diatomaceous earth (Celite®). The filtrate was washed with water and with brine and dried (Na2SO), filtered and concentrated. The concentrate was purified on silica with a purification system lntelliflash-280, with ethyl acetate / hexanes. EXAMPLE 2B A mixture of EXAMPLE 2A (0.21 g), cis-4- (4- (4-amino-3-iodopyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) -1-methylpiperazin-2-one , prepared as described in International Patent Publication WO 05/074603 (0.18 g), Na2CO3 2M (0.38 mL) and dichlorobis (triphenylphosphine) palladium (ll) (0.014 g) in DME / water (3 mL / 1 mL) in a microwave reactor, it was stirred at 130 ° C for 15 minutes. The mixture was filtered through diatomaceous earth (Celite®), dried (Na2SO4), filtered and concentrated. The concentrate was purified on silica gel with a purification system lntelliflash-280, with dichloromethane / methanol.

EXAMPLE 2C A mixture of EXAMPLE 2B (0.11 g), 4-fluorobenzaldehyde (0.029 g) and 1M Na2S2O4 (0.71 mL) in ethanol (1 mL) was stirred at 130 ° C for 20 minutes in a microwave reactor, cooled , treated with NH OH 5M (2 mL), and filtered. 1 H-NMR (300 MHz, DMSO-d 6) 13.10 (d, 1H), 8.28-8.24 (m, 3H), 7.88-7.68 (m, 2H), 7.64-7.60 (m, 1H), 7.46-7.40 (m , 2H), 4.89-4.78 (m, 1H), 3.07 (bs, 2H), 2.83 (s, 3H), 2.74-2.71 (m, 2H), 2.33-2.22 (m, 3H), 2.15-2.08 (m , 2H), 1.79-1.61 (m, 4H). EXAMPLE 3 This example was prepared by substituting the 4-fluorobenzaldehyde of EXAMPLE 2C for cyclopropanecarboxyaldehyde. 1 H-NMR (300 MHz, DMSO-d 6) 12.39 (s, 1H), 8.27-8.18 (m, 1H), 7.68-7.52 (m, 2H), 7.40 (d, 1H), 4.87-4.75 (m, 1H ), 3.07 (bs, 2H), 2.85-2.83 (m, 3H), 2.76-2.76 (m, 2H), 2.32-2.07 (m, 6H), 1.73-1.61 (m, 4H). EXAMPLE 4 This example was prepared by substituting the 4-fluoro-benzaldehyde of EXAMPLE 2C for pyridine-2-carboxaldehyde. 1 H-NMR (300 MHz, DMSO-d 6) 13.24 (d, 1H), 8.7 (d, 1H), 8.38 (d, 1H), 8.25 (s, 1H), 8.06-8.00 (m, 1H), 7.92- 7.80 (m, 2H), 7.57-7.53 (m, 2H), 4.89-4.78 (m, 1H), 3.07 (s, 3H), 2.83 (s, 4H), 2.74-2.71 (m, 3H), 2.33- 2.25 (m, 4H), 2.12-2.08 (m, 3H), 1.75-1.60 (m, 5H). EXAMPLE 5A This example was prepared by substituting cis-4- (4- (4-amino- 3-iodopyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) -1-methylpiperazin-2-one from EXAMPLE 2B by trans-3-iodo-1- (4- (2-methoxy-ethoxy) cyclohexyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-yl-amine, prepared as described in International Patent Publication WO 05/074603. EXAMPLE 5B A mixture of EXAMPLE 5A (0.10 g), benzaldehyde (0.029 g) and 1M Na2S2O4 (0.70 mL) in ethanol (1.1 mL) was stirred at 130 ° C for 20 minutes in a microwave reactor. The reaction was treated with 5M NH 4 OH (2 mL) and the precipitate was dissolved in dichloromethane / IPA. The mixture was dried (Na2SO), filtered and concentrated. The concentrate was purified on silica gel with a lntelliflash-280 purification system, with ethyl acetate / methanol. 1 H-NMR (300 MHz, DMSO-d 6) 12.25 (s, 1H), 7.39-7.34 (m, 3H), 6.99-6.82 (m, 2H), 6.72-6.64 (m, 4H), 3.90-3.81 (m , 1H), 2.73-2.70 (m, 2H), 2.61-2.58 (m, 2H), 2.40 (s, 3H), 1.30-1.11 (m, 5H). EXAMPLE 6A This example was prepared by substituting cis-4- (4- (4-amino-3-iodopyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) -1-methylpiperazin-2-one from EXAMPLE 2B by cis-3-iodo-1- (4- (4-methyl-piperazin-1-yl) -cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidin-4-yl-amine, prepared as described in Bioorg Med. Chem Lett.2002, 12, 1687-1690. EXAMPLE 6B A mixture of EXAMPLE 6A (0.12 g), benzaldehyde (0.028 g) and 1M Na2S2O4 (0.68 mL) in ethanol (1 mL) was stirred at 130 ° C for 20 minutes in a microwave reactor. The mixture was treated with 5M NH 4 OH (2 mL), and the precipitate was dissolved in dichloromethane / IPA. The mixture was dried (MgSO), filtered and concentrated. The concentrate was purified on silica gel with a lntelliflash-280 purification system, with ethyl acetate / methanol / NH 4 OH. 1 H-NMR (300 MHz, DMSO-d 6) 13.10 (bs, 1H), 8.24-8.20 (m, 3H), 7.89-7.69 (m, 2H), 7.61-7.50 (m, 4H), 4.86-4.79 (m , 1H), 2.48-2.20 (m, 7H), 2.14 (s, 3H), 2.09-2.04 (m, 1H), 1.76-1.56 (m, 4H). EXAMPLE 7A This example was prepared by substituting cis-4- (4- (4-amino-3-iodopyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) -1-methylpiperazin-2-one from EXAMPLE 2B by trans-3-iodo-1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-yl-amine, prepared as described in the International Patent Publication WO 05/074603. EXAMPLE 7B A mixture of EXAMPLE 7A (0.14 g), benzaldehyde (35 mg) and 1M Na 2 S 2 O 4 (0.95 mL) in ethanol (1.5 mL) was stirred at 130 ° C for 20 minutes in a microwave reactor. The reaction was treated with 5M NH OH (2 mL), and the precipitate was dissolved in ethyl acetate / IPA. The mixture was dried (Na2SO), filtered and concentrated. The concentrate was purified on silica gel, with a lntelliflash-280 purification system, with ethyl acetate / methanol / NH 4 OH. 1 H-NMR (300 MHz, DMSO-d 6) 13.09 (bs, 1H), 8.25-8.20 (m, 3H), 7.83 (bs, 2H), 7.61-7.50 (m, 4H), 4.72-4.64 (m, 1H ), 3.58 (bs, 4H), 2.42-2.32 (m, 1H), 2.09-1.94 (m, 6H), 1.52-1.43 (m, 2H).

EXAMPLE 8 This example was prepared by substituting the benzaldehyde of EXAMPLE 7B by 4-methylbenzaldehyde. 1 H-NMR (300 MHz, DMSO-d 6) 13. 00 (bs, 1H), 8.24 (s, 1H), 8.10 (d, 2H), 7.87-7.65 (m, 2H), 7.52-7.49 (m, 1H), 7.39 (d, 2H), 4.69-4.63 ( m, 1H), 3.58 (bs, 4H), 2.40 (bs, 4H), 2.08-1.97 (m, 6H), 1.48-1.46 (m, 2H). EXAMPLE 9 This example was prepared by substituting the benzaldehyde of EXAMPLE 7B by 4-chlorobenzaldehyde. 1 H-NMR (300 MHz, DMSO-d 6) 13.18 (bs, 1H), 8.24-8.21 (m, 3H), 7.89-7.71 (m, 2H), 7.68-7.65 (d, 2H), 7.56-7.51 (m, 1H), 4.68 (bs, 1H), 3.60-3.55 (m, 4H), 2.44-2.27 (m, 1H), 2.10-1.97 (m, 5H), 1.54-1.45 (m, 1H). EXAMPLE 10 This example was prepared by substituting the benzaldehyde of EXAMPLE 7B for 4-methoxybenzaldehyde. 1 H-NMR (300 MHz, DMSO-de) 12.92 (s, 1H), 8.24 (s, 1H), 8.16 (d, 2H), 7.84-7.64 (m, 2H), 7.48 (d, 1H), 7.14 ( d, 2H), 4.67 (bs, 1H), 3.86 (s, 3H), 3.58 (bs, 5H), 2.10-1.97 (m, 7H), 1.50-1.45 (2H). EXAMPLE 11 This example was prepared by substituting the benzaldehyde of EXAMPLE 7B by 3,4-dichlorobenzaldehyde. 1 H-NMR (300 MHz, DMSO-d 6) 13.19 (s, 1H), 8.44 (d, 1H), 8.25 (bs, 1H), 8.19 (dd, 1H), 7.89-7.74 (m, 3H), 7.55 ( d, 1H), 4.66 (bs, 1H), 3.58 (bs, 4H), 2.41-2.34 (m, 1H), 2.09-1.97 (m, 6H), 1.50-1.44 (m, 2H).

EXAMPLE 12 This example was prepared by substituting the benzaldehyde of EXAMPLE 7B by phenylacetaldehyde. 1 H-NMR (300 MHz, DMSO-d 6) 12. 45 (bs, 1H), 8.22 (s, 1H), 7.76-7.56 (m, 2H), 7.44-7.31 (m, 5H), 7.27-7.22 (m, 1H), 4.65 (bs, 1H), 4.21 ( s, 2H), 4.13 (m, 4H), 2.43-2.32 (m, 1H), 2.08-1.95 (m, 6H), 1.52-1.41 (m, 2H). EXAMPLE 13 This example was prepared by substituting the benzaldehyde of EXAMPLE 7B for 3-phenylpropionaldehyde. 1 H-NMR (300 MHz, DMSO-d 6) 12.43 (d, 1H), 8.23 (s, 1H), 7.76-7.56 (m, 2H), 7.45-7.40 (m, 1H), 7.29 (d, 4H), 7.22-7.17 (m, 1H), 4.65 (bs, 1H), 3.59-3.57 (m, 4H), 3.22-3.11 (m, 7H), 2.39-2.28 (m, 2H), 2.08-1.96 (m, 6H) ), 1.54-1.40 (m, 2H). EXAMPLE 14 This example was prepared by substituting the benzaldehyde of EXAMPLE 7B by thiophen-2-yl-acetaldehyde (E. Winterfeldt et al., Chem. Berichte 1963, 96, 3349-3358). 1 H-NMR (300 MHz, DMSO-d 6) 12.50 (d, 1H), 8.22 (s, 1H), 7.78-7.57 (m, 2H), 7.45-7.39 (m, 2H), 7.06-7.03 (m, 1H ), 7.01-6.97 (m, 1H), 4.65 (bs, 1H), 4.44 (s, 2H), 3.58 (bs, 5H), 2.44-2.30 (m, 1H), 2.12-1.93 (m, 6H), 1.54-1.40 (m, 2H). EXAMPLE 15 This example was prepared by substituting the benzaldehyde of the EXAMPLE 7B by (3-chlorophenyl) acetaldehyde, prepared as described in Chem. Res. Toxicol. 1996, 9, 268-276. 1 H-NMR (300 MHz, DMSO-d 6) 12.48 (d, 1H), 8.22 (s, 1H), 7.77-7.57 (m, 2H), 7.46- 7. 30 (m, 5H), 4.65 (bs, 1H), 4.24 (s, 2H), 3.59-3.57 (m, 4H), 2.43-2.32 (m, 1H), 2.09-1.94 (m, 6H), 1.54- 1.39 (m, 2H). EXAMPLE 16 This example was prepared by substituting the benzaldehyde of EXAMPLE 7B for 4- (chlorophenyl) acetaldehyde, prepared as described in Chem. Res. Toxicol. 1996, 9, 268-276. 1 H-NMR (300 MHz, DMSO-d 6) 12.45 (bs, 1H), 8.23 (s, 1H), 7.76-7.56 (m, 2H), 7.44-7.39 (m, 5H), 4.66 (bs, 1H), 4.22 (s, 2H), 3.61-3.57 (m, 4H), 2.41-2.35 (m, 1H), 2.08-1.96 (m, 6H), 1.51-1.44 (m, 2H). EXAMPLE 17 This example was prepared by substituting the benzaldehyde of EXAMPLE 7B for 2-phenylpropionaldehyde. 1 H-NMR (300 MHz, DMSO-de) 12.36 (d, 1H), 8.22 (s, 1H), 7.80-7.53 (m, 2H), 7.44-7.30 (m, 5H), 7.23 (t, 1H), 4.65 (bs, 1H), 4.42 (q, 1H), 3.58 (bs, 4H), 2.35 (t, 1H), 2.07-1.96 (m, 7H), 1.74-1.71 (m, 4H), 1.50-1.43 ( m, 2H). EXAMPLE 18 This example was prepared by substituting the benzaldehyde of EXAMPLE 7B for (2-chlorophenyl) acetaldehyde. 1 H-NMR (300 MHz, DMSO-de) 12.47 (bs, 1H), 8.23 (s, 1H), 7.71-7.62 (m, 2H), 7.49-7.48 (m, 1H), 7.44-7.42 (m, 2H ), 7.85-7.81 (m, 2H), 4.69-4.61 (m, 1H), 4.35 (s, 2H), 3.58 (bs, 4H), 2.38-2.33 (m, 1H), 2.07-1.95 (m, 6H) ), 1.50-1.42 (m, 2H). EXAMPLE 19 This example was prepared by substituting the benzaldehyde of EXAMPLE 7B for (2-fluorophenyl) acetaldehyde. 1 H-NMR (300 MHz, DMSO-de) 12.49 (d, 1H), 8.22 (s, 1H), 7.75-7.56 (m, 2H), 7.45-7.39 (m, 2H), 7.35-7.30 (m, 1H), 7.20 (m, 2H ), 4.70-4.60 (m, 1H), 4.26 (s, 2H), 3.58 (bs, 4H), 2.40-2.30 (m, 1H), 2.10-1.94 (m, 6H), 1.54-1.39 (m, 2H) ). EXAMPLE 20 This example was prepared by substituting the benzaldehyde of EXAMPLE 7B for (2-methylphenyl) acetaldehyde. 1 H-NMR (300 MHz, DMSO-de) 12.35 (bs, 1H), 8.22 (s, 1H), 7.75-7.55 (m, 2H), 7.44-7.39 (m, 1H), 7.27-7.23 (m, 1H ), 7.19-7.14 (m, 3H), 4.69-4.60 (m, 1H), 4.20 (s, 2H), 3.58 (bs, 4H), 2.36-2.32 (bs, 4H), 2.08-1.93 (m, 6H) ), 1.52-1.40 (m, 2H). EXAMPLE 21 This example was prepared by substituting the benzaldehyde of EXAMPLE 7B for (3-fluorophenyl) acetaldehyde. 1 H-NMR (300 MHz, DMSO-de) 12.48 (bs, 1H), 8.22 (s, 1H), 7.73-7.60 (m, 2H), 7.45-7.34 (m, 2H), 7.23-7.18 (m, 2H ), 7.12-7.05 (m, 1H), 4.69-4.60 (m, 1H), 4.25 (s, 2H), 3.58 (bs, 4H), 2.37-2.26 (m, 1H), 2.08-1.94 (m, 6H) ), 1.54-1.40 (m, 2H). EXAMPLE 22 This example was prepared by substituting the benzaldehyde of EXAMPLE 7B by (3-methylphenyl) acetaldehyde. 1 H-NMR (300 MHz, DMSO-d 6) 12.43 (bs, 1H), 8.22 (s, 1H), 7.76-7.41 (m, 3H), 7.24-7.13 (m, 3H), 7.06 (d, 1H), 4.71-4.59 (m, 1H), 4.17 (s, 2H), 3.58 (bs, 4H), 2.40-2.31 (m, 1H), 2.28 (s, 3H), 2.08-1.94 (m, 7H), 1.54- 1.40 (m, 2H).

EXAMPLE 23 This example was prepared substituting the benzaldehyde of EXAMPLE 7B by (4-fluorophenyl) acetaldehyde. 1 H-NMR (300 MHz, DMSO-de) 12.47 (bs, 1H), 8.22 (s, 1H), 7.73-7.58 (m, 2H), 7.44-7.38 (m, 3H), 7.18-7.15 (m, 2H), 4.68-4.62 (m , 1H), 4.21 (s, 2H), 3.58 (bs, 4H), 2.38-2.33 (m, 1H), 2.09-1.95 (m, 6H), 1.51-1.41 (m, 2H). EXAMPLE 24 This example was prepared by substituting the benzaldehyde of EXAMPLE 7B by (4-methylphenyl) acetaldehyde. H-NMR (300 MHz, DMSO-d6) 12.40 (d, 1H), 8.22 (s, 1H), 7.75-7.54 (m, 2H), 7.44-7.40 (m, 1H), 7.24 (d, 2H), 7.13 (d, 2H), 4.69-4.60 (m, 1H), 4.16 (s, 2H), 2. 39-2.32 (m, 1H), 2.27 (s, 3H), 2.07-1.95 (m, 6H), 1.53-1.42 (m, 2H). EXAMPLE 25 This example was prepared by substituting the benzaldehyde of EXAMPLE 7B for (3,4-dichlorophenyl) acetaldehyde. 1 H-NMR (400 MHz, DMSO-de) d 12.47 (d, 1H), 8.22 (s, 1H), 7.77-7.66 (m, 3H), 7.62-7.57 (m, 1H), 7.46-7.42 (m, 1H), 7.39-7.35 (m, 1H), 4.68-4.61 (m, 1H), 4.26 (s, 2H), 3.58 (bs, 4H), 2.40-2.32 (m, 1H), 2.07-1.95 (m, 7H), 1.51-1.41 (m, 2H). EXAMPLE 26 This example was prepared by substituting the benzaldehyde of EXAMPLE 7B by (2,6-dichlorophenyl) acetaldehyde. 1 H-NMR (300 MHz, DMSO-de) 12.46 (s, 1H), 8.22 (s, 1H), 7.69 (bs, 1H), 7.61-7.53 (m, 3H), 7.44-7.37 (m, 2H), 4.71-4.58 (m, 1H), 4.52 (s, 2H), 3.58 (bs, 4H), 2.40-2.27 (m, 1H), 2.08-1.94 (m, 6H), 1.53-1.41 (m, 2H).

EXAMPLE 27A A mixture of 2- (2,3-dichlorophenyl) ethanol (0.50 g), NaHCO3 (0.438 g) and Dess-Martin periodinane (1.22 g) in dichloromethane (10 mL) and water (46 mL) were stirred for 1 hour. The reaction was quenched with an aqueous solution of NaHCO 3 and a saturated aqueous solution of Na 2 S 2 O 3, and subjected to extraction with dichloromethane. The extract was dried (Na2SO), filtered and concentrated. The concentrate was purified on silica gel with an Intelliflash-280 purification system, with hexanes / ethyl acetate. EXAMPLE 27B This example was prepared by substituting the benzaldehyde of the EXAMPLE 7B by the product of EXAMPLE 27A. 1 H-NMR (300 MHz, DMSO-d6) 12.48 (bs, 1H), 8.22 (s, 1H), 7.74-7.59 (m, 3H), 7.47-7.36 (m, 3H), 4.70-4.60 (m, 1H), 4.42 (s, 2H), 3.58 (bs, 4H), 2.41-2.28 (m, 1H), 2.08-1.93 (m, 6H), 1.54-1.39 (m, 2H). EXAMPLE 28 A mixture of EXAMPLE 7A (0.2 g), and 10% Pd / C (0.04 g) in methanol (20 mL) at 50 ° C in a Parr hydrogenation apparatus, was stirred under a hydrogen atmosphere (60 psi). ) for 1.5 hours. The mixture was filtered through diatomaceous earth (Celite®) and concentrated. The concentrate was purified on silica gel with a lntelliflash-280 purification system, with ethyl acetate / methanol / NH OH.

The product (0.13 g) and 1-fluoro-3-isothiocyanatobenzene (0.051 g) in THF (4 mL) was stirred for 3 hours at room temperature and at 50 ° C for 2 hours, treated with N- (3-dimethylaminopropyl) -N'- ethylcarbodiimide (0.091 g), stirred for 2 hours, cooled and diluted with water and with ethyl acetate. The extract was dried over MgSO 4, filtered and concentrated. The concentrate was purified on silica gel with a lntelliflash-280 purification system, with ethyl acetate / methanol / NH 4 OH). 1 H-NMR (300 MHz, DMSO-d 6) 11.18 (d, 1H), 9.84 (d, 1H), 8.23 (s, 1H), 7.95-7.88 (m, 1H), 7.63-7.51 (m, 2H), 7.46-7.29 (m, 4H), 6.75 (t, 1H), 4.72-4.59 (m, 1H), 3.58 (bs, 5H), 2.44-2.27 (m, 1H), 2.10-1.94 (m, 7H), 1.53-1.39 (m, 2H). EXAMPLE 29A This example was prepared by substituting the 4-bromo-2-nitrophenylamine of EXAMPLE 2A for 4-bromo-2-methyl-6-nitrophenylamine. EXAMPLE 29B This example was prepared by substituting cis-4- (4- (4-amino-3-iodopyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) -1-methylpiperazin-2-one and the product of the EXAMPLE 2A by trans-3-iodo-1- (4-morpholin-4-yl-cyclohexyl) -1H-pyrazolo [3,4-d] pyrim id in-4-i-amine, prepared as described in Bioorg Med. Chem. Lett. 2002, 12, 1687-1690 and the compound of EXAMPLE 29A, respectively, in EXAMPLE 2B. EXAMPLE 29C This example was prepared by substituting the compound of EXAMPLE 7A and benzaldehyde, for the compound of EXAMPLE 29B and phenylacetaldehyde, respectively, in EXAMPLE 7B. 1 H-NMR (400 MHz, DMSO-de) 12.42 (d, 1H), 8.21 (s, 1H), 7.52 (d, 1H), 7.38-7.31 (m, 4H), 7.27-7.22 (m, 2H), 4.69-4.60 (m, 1H), 4.21 (s, 2H), 3.58 (bs, 4H), 2.40-2.30 (m, 1H), 2.09-1.94 (m, 6H), 1.52-1.41 (m, 2H). EXAMPLE 30A This example was prepared by substituting the 4-bromo-2-nitrophenylamine of EXAMPLE 2A for (4-bromo-2-nitrophenyl) -methylamine, prepared as described in J. Chem. Soc, Perkin Trans 1, 1974, 903- 908 EXAMPLE 30B This example was prepared by substituting cis-4- (4- (4-amino-3-iodopyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) -1-methylpiperazin-2-one and the EXAMPLE 2A, by trans-3-iodo-1- (4-morpholin-4-yl-cyclohexyl) -1 H) -pyrazolo [3,4-d] pyrimidin-4-yl-amine prepared as described in Bioorg. Med. Chem. Lett. 2002, 12, 1687-1690 and the product of EXAMPLE 30A, respectively, in EXAMPLE 2B. EXAMPLE 30C This example was prepared by substituting the compound of EXAMPLE 7A and benzaldehyde, by the compound of EXAMPLE 30B and phenylacetaldehyde, respectively, in EXAMPLE 7B. 1 H-NMR (300 MHz, DMSO-de) 8.23 (s, 1H), 7.80 (bs, 1H), 7.65 (d, 1H), 7.50 (dd, 1H), 7.36-7.29 (m, 4H), 7.28- 7.21 (m, 1H), 4.70-4.60 (m, 1H), 4.35 (s, 2H), 3.76 (s, 3H), 3.58 (bs, 4H), 2.40-2.31 (m, 1H), 2.09-1.95 ( m, 6H), 1.55-1.39 (m, 2H). EXAMPLE 31A This example was prepared by substituting cis-4- (4- (4-amino-3-iodopyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) -1-methylpiperazin-2-one from EXAMPLE 2B, by 3-iodo-1- (4-oxocyclohexyl) -1 H-pyrazolo [3,4- d] pyrimidin-4-yl-amine, prepared as described in Bioorg Med. Chem. Lett. 2002, 12, 1687-1690. EXAMPLE 31B This example was prepared by substituting the compound of EXAMPLE 7A and benzaldehyde, for the compound of EXAMPLE 31A and phenylacetaldehyde, respectively, in EXAMPLE 7B. EXAMPLE 31C A mixture of EXAMPLE 31B (0.0437 g), 3-hydroxypyrrolidine (0.087 g) and NaCNBH3 (0.031 g), in methanol / acetic acid 10: 1 (3 mL), was stirred at 70 ° C for 2.5 hours and concentrated. The concentrate was purified by reverse phase HPLC with a Shimadzu LC10 HPLC system with a Phenomínex Luna 10 micras C18 (2) 100 apparatus, column 150x30 mm, with 5-45% acetonitrile in water, with 0.15% TFA for 25 minutes , at a flow rate of 20 mL / minute. The first diastereoisomer that eluted was isolated. 1 H-NMR (300 MHz, DMSO-d 6) d 9.62 &; 9.71 (brs, 1H), 8.28 (s, 1H), 7.84 (s, 1H), 7.79 (d, 1H), 7.62 (d, 1H), 7.41-7.30 (m, 5H), 4.73 (m, 1H) , 4.48 (m, 1H), 4.43 (s, 2H), 4.39 (m, 1H), 3.31 (m, 5H), 2.24 (m, 4H), 2.08 (m, 4H), 1.91 (m, 2H), 1.70 (m, 2H). EXAMPLE 32 This example was the slower eluting diastereomer of EXAMPLE 31. 1 H-NMR (300 MHz, DMSO-d 6) 9.85 and 9.53 (brs, 1H), 8.31 (s, 1H), 7.92 and 7.89 (s, 1H), 7.81 (m, 1H), 7.71 (m, 1H), 7. 43-7.31 (m, 5H), 4.94 (m, 1H), 4.47 (m, 1H), 4.44 (s, 2H), 4.38 (m, 1H), 3.69 (m, 1H), 3.60 (m, 1H) , 3.34 (m, 1H), 3.22 (m, 1H), 3.06 (m, 1H), 2.42 (m, 1H), 2.22 (m, 1H), 2.07-1.91 (m, 8H). EXAMPLE 33 This example was the fastest eluting diastereomer, prepared by substituting the 3-hydroxypyrrolidine of EXAMPLE 31C, for 4-ethanesulfonylpiperazine. 1 H-NMR (300 MHz, DMSO-d 6) 9.83 (brs, 1H), 8.32 (s, 1H), 7.91-7.84 (m, 2H), 7.70 (m, 1H), 7.45-7.33 (m, 5H), 4.79 (m, 1H), 4.49 (s, 2H), 3.8 (m, 1H), 3.55 (m, 4H), 3.22 (m, 6H), 2.20 (m, 1H), 2.14 (m, 4H), 1.95 (m, 2H), 1.80 (m, 1H), 1.24 (t, 3H). EXAMPLE 34 This example was the slowest eluting diastereomer, prepared by substituting the 3-hydroxypyrrolidine of EXAMPLE 31C, for 4-ethanesulfonylpiperazine. 1 H-NMR (300 MHz, DMSO-d 6) 9.50 (brs, 1H), 8.31 (s, 1H), 7.90 (s, 1H), 7.81 (d, 1H), 7.70 (d, 1H), 7.42-7.30 ( m, 5H), 4.98 (m, 1H), 4.44 (s, 2H), 3.78 (m, 1H), 3.64 (m, 4H), 3.19 (m, 6H), 2.42 (m, 2H), 2.13-1.99 (m, 6H), 1.22 (t, 3H). EXAMPLE 35 This example was the fastest eluting diastereomer, prepared by substituting the 3-hydroxypyrrolidine of EXAMPLE 31C, for 4- (2-methoxyethyl) piperazine. 1 H-NMR (300 MHz, DMSO-d 6) 8.30 (s, 1H), 7.86 (s, 1H), 7.81 (d, 1H), 7.65 (d, 1H), 7.42-7.32 (m, 5H), 4.75 ( m, 1H), 4.45 (s, 2H), 3.59 (m, 6H), 3.40 (m, 1H), 3.30 (s, 3H), 3.06 (m, 6H), 2.11 (m, 6H), 1.70 (m , 2H). EXAMPLE 36 This example was the slowest eluting diastereomer, prepared by substituting the 3-hydroxypyrrolidine of EXAMPLE 31C, for 4- (2-methoxyethyl) -piperazine. 1 H-NMR (300 MHz, DMSO-d 6) 8.35 (s, 1H), 7.91 (s, 1H), 7.85 (d, 1H), 7.72 (d, 1H), 7.45-7.33 (m, 5H), 4.94 ( m, 1H), 4.50 (s, 2H), 3.61 (m, 3H), 3.48 (m, 4H), 3.29 (s, 3H), 3.19 (m, 4H), 3.05 (m, 2H), 2.37 (m , 2H), 2.07 (m, 3H), 1.91 (m, 3H). EXAMPLE 37 This example was the fastest eluting diastereomer, prepared by substituting the 3-hydroxypyrrolidine of EXAMPLE 31C, for (2R, 6S) -2,6-dimethylpiperazine. H-NMR (300 MHz, DMSO-d6) 9.20 (brs, 1H), 8.62 (brs, 1H), 8.31 (s, 1H), 7.86 (s, 1H), 7.83 (d, 1H), 7.67 (d, 1H), 7.44-7.25 (m, 5H), 4.76 (m, 1H), 4.47 (s, 2H), 3.0 (m, 1H), 2.89 (m, 2H), 2.73 (m, 2H), 2.11 (m , 6H), 1.73 (m, 2H), 1.26 (d, 6H). EXAMPLE 38 This example was the slowest eluting diastereomer, prepared by substituting the 3-hydroxypyrrolidine of EXAMPLE 31C, for (2R, 6S) -2,6-dimethylpiperazine. 1 H-NMR (300 MHz, DMSO-d 6) 9.10 (brs, 1H), 8.31 (s, 1H), 7.86 (s, 1H), 7.78 (d, 1H), 7.65 (d, 1H), 7.42-7.31 ( m, 5H), 4.92 (m, 1H), 4.43 (s, 2H), 3.41 (m, 5H), 2.33 (m, 2H), 2.10 (m, 4H), 1.87 (m, 2H). EXAMPLE 39 This example was the fastest eluting diastereomer, prepared by substituting the 3-hydroxypyrrolidine from EXAMPLE 31C, by 4-acetylpiperazine. 1 H-NMR (300 MHz, DMSO-d 6) 9.65 (brs, 1H), 8.30 (s, 1H), 7.86 (s, 1H), 7.82 (d, 1H), 7.65 (d, 1H), 7.42-7.32 (m, 5H), 4.68 (m, 1H), 4.51 (m, 1H), 4.45 (s, 2H), 4.06 (m, 1H), 3.20 (m, 3H), 2.97 (m, 4H), 2.13 ( m, 6H), 2.06 (s, 3H), 1.80 (m, 2H). EXAMPLE 40 This example was the slower eluting diastereomer, prepared by substituting the 3-hydroxypyrrolidine of EXAMPLE 31C, for 4-acetylpiperazine. H-NMR (300 MHz, DMSO-d6) 9.45 (brs, 1H), 8.30 (s, 1H), 7.89 (s, 1H), 7.81 (d, 1H), 7.69 (d, 1H), 7.41-7.31 ( m, 5H), 4.97 (m, 1H), 4.46 (m, 1H), 4.43 (s, 2H), 4.01 (m, 1H), 3.46 (m, 2H), 3.13 (m, 1H), 2.85 (m , 4H), 2.42 (m, 2H), 2.06 (m, 6H), 2.04 (s, 3H). EXAMPLE 41 This example was the fastest eluting diastereomer, prepared by substituting 3-hydroxypyrrolidine from EXAMPLE 31C, for 3- trifluoromethyl-5,6,7,8-tetrahydro- (1,2,4) triazolo- [4,3] -a] pyrazine, prepared as described in J. Med. Chem., 2005, 48, 141-151. 1 H-NMR (300 MHz, DMSO-d 6) 8.31 (s, 1H), 7.89 (s, 1H), 7.84 (d, 1H), 7.70 (d, 1H), 7.43-7.34 (m, 5H), 4.76 ( m, 1H), 4.48 (s, 2H), 4.19 (m, 2H), 4.14 (m, 2H), 3.18 (m, 2H), 2.92 (m, 1H), 2.06 (m, 6H), 1.68 (m , 2H). EXAMPLE 42 This example was the slower eluting diastereomer, prepared by substituting 3-hydroxypyrrolidine from EXAMPLE 31C, for 3-trifluoromethyl-5,6,7,8-tetrahydro- (1, 2, 4) triazolo- [4, 3 -a] pyrazine, prepared as described in J. Med. Chem., 2005, 48, 141-151. 1 H-NMR (300 MHz, DMSO-d 6) 8.31 (s, 1H), 7.88 (s, 1H), 7.82 (d, 1H), 7.68 (d, 1H), 7.42-7.33 (m, 5H), 4.90 ( m, 1H), 4.48 (s, 2H), 4.18 (m, 2H), 4.04 (m, 2H), 3.11 (m, 2H), 2.70 (m, 1H), 2.27 (m, 2H), 2.18 (m, 2H), 1.79 (m, 4H). EXAMPLE 43A To a solution of 3-iodo-1H-pyrazolo [3,4-d] pyrimidin-4-yl-amine, prepared as described in Bioorg Med. Chem. Lett. 2002, 12, 1687-1690, (1,044 g), tert-butylester of 4-hydroxypiperidine-1-carboxylic acid (2.42 g) and triphenylphosphine (2.1 g) in THF (40 mL), DIAD (1.6 mL) was added. The mixture was stirred for 18 hours, then subjected to partition extraction in ethyl acetate and brine. The extract was dried, filtered and concentrated. The concentrate was eluted through a pad of silica gel with 30-50% ethyl acetate / hexanes, then with 5% methanol / ethyl acetate. The eluent was concentrated, and the concentrate was recrystallized from dichloromethane / ether. EXAMPLE 43B The product of EXAMPLE 43A (0.56 g) in 4M HCl in dioxane (10 mL) was stirred at room temperature for 1.5 hours and filtered. EXAMPLE 43C The product of EXAMPLE 43B (0.17 g), iodoacetamide (0.1 g), K2CO3 (0.35 g) and tatrabutylammonium iodide (0.01 g) in DMF (5 mL), was stirred for 18 hours. The reaction mixture was diluted with ethyl acetate and washed with water and with brine. The concentrate was dried, filtered and concentrated.

EXAMPLE 43D This example was prepared by substituting cis-4- (4- (4-amino-3-iodopyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) -1-methylpiperazin-2-one from EXAMPLE 2B, for the product of EXAMPLE 43C. EXAMPLE 43E A mixture of EXAMPLE 43D (0.11 g), phenylacetaldehyde (0.02 mL) and Na2S2O4 (0.09 g) in ethanol (2 mL) and water (2 mL) was stirred at 120 ° C for 20 minutes in a microwave reactor. and concentrated. The concentrate was purified by reverse phase HPLC, with a Shimadzu LC10 HPLC system, with a Phenominex Luna 10 microns C18 (2) 100 apparatus, column 150x30 mm, with 5-45% acetonitrile in water, with 0.15% TFA during 25 minutes, at a flow rate of 20 mL / minute. 1 H-NMR (300 MHz, DMSO-d 6) 9.84 (brs, 1H), 8.31 (s, 1H), 7.93 (m, 1H), 7.87 (s, 1H), 7.82 (d, 1H), 7.69 (d, 1H), 7.64 (m, 1H), 7.42-7.31 (m, 5H), 5.03 (m, 1H), 4.45 (s, 2H), 3.95 (s, 2H), 3.37 (m, 4H), 2.44 (m , 2H), 2.18 (m, 2H). EXAMPLE 44 This example was the fastest eluting diastereomer, prepared by substituting the 3-hydroxypyrrolidine of EXAMPLE 31C, for piperidine-3-carboxamide. 1 H-NMR (300 MHz, DMSO-d 6) 9.21 (brs, 1H), 8.32 (s, 1H), 7.89 (s, 1H), 7.85 (d, 1H), 7.69 (d, 1H), 7.57 (s, 1H), 7.45-7.29 (m, 5H), 7.12 (s, 1H), 4.80 (m, 1H), 4.49 (s, 2H), 3.45 (m, 2H), 3.17 (m, 1H), 3.01 (m , 2H), 2.66 (m, 1H), 2.13 (m, 6H), 1.93 (m, 2H), 1.81 (m, 3H), 1.51 (m, 1H).

EXAMPLE 45 This example was the slower eluting diastereomer, prepared by substituting the 3-hydroxypyrrolidine of EXAMPLE 31C, for piperidine-3-carboxamide. 1 H-NMR (300 MHz, DMSO-d 6) 9.15 (brs, 1H), 8.34 (s, 1H), 7.93 (s, 1H), 7.86 (d, 1H), 7.76 (d, 1H), 7.60 (s, 1H), 7.45-7.29 (m, 5H), 7.12 (s, 1H), 5.03 (m, 1H), 4.50 (s, 2H), 3.51 (m, 2H), 3.24 (m, 1H), 3.00 (m , 2H), 2.66 (m, 1H), 2.36 (m, 2H), 2.18 (m, 2H), 1.97 (m, 5H), 1.76 (m, 2H), 1.48 (m, 1H). EXAMPLE 46 This example was the fastest eluting diastereomer, prepared by substituting the 3-hydroxypyrrolidine of EXAMPLE 31C, for piperidine-4-carboxamide. 1 H-NMR (300 MHz, DMSO-d 6) 9.07 (brs, 1H), 8.31 (s, 1H), 7.88 (s, 1H), 7.83 (d, 1H), 7.67 (d, 1H), 7.42-7.29 ( m, 6H), 6.95 (s, 1H), 4.79 (m, 1H), 4.48 (s, 2H), 3.31 (m, 2H), 3.01 (m, 4H), 2.40 (m, 2H), 2.12 (m , 6H), 2.0 (m, 2H), 1.80 (m, 2H). EXAMPLE 47 This example was the slower eluting diastereomer, prepared by substituting the 3-hydroxypyrrolidine of EXAMPLE 31C, for piperidine-4-carboxamide. 1 H-NMR (300 MHz, DMSO-d 6) 8.98 (brs, 1H), 8.35 (s, 1H), 7.94 (s, 1H), 7.87 (d, 1H), 7.75 (d, 1H), 7.45-7.29 ( m, 6H), 6.93 (s, 1H), 5.0 (m, 1H), 4.50 (s, 2H), 3.52 (m, 2H), 3.34 (m, 2H), 2.99 (m, 2H), 2.38 (m , 2H), 2.12 (m, 2H), 1.99 (m, 6H), 1.82 (m, 2H). EXAMPLE 48A A mixture of 3-iodo-1 H-pyrazolo [3,4-d] pyrimidin-4-yl- amine, prepared as described in Bioorg Med. Chem. Lett.2002, 12, 1687-1690, (1 g) and NaH (0.17 g) in DMF (17 mL), stirred for 1 hour, treated with 4-fluorobenzaldehyde (0.45 mL), stirred at 100 ° C for 18 hours , it was cooled, diluted with water and filtered. EXAMPLE 48B A mixture of EXAMPLE 48A (0.18 g), morpholine (0.44 mL) and NaCNBH3 (0.16 g) in methanol / acetic acid (5: 0.5 mL), was stirred at 70 ° C for 2.5 hours, and was subjected to extraction by partition in ethyl acetate and brine. The extract was dried, filtered and concentrated. The concentrate was triturated with ether. EXAMPLE 48C This example was prepared by substituting cis-4- (4- (4-amino-3-iodopyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) -1-methylpiperazin-2-one from EXAMPLE 2B, for the product of EXAMPLE 48B. EXAMPLE 48D A mixture of EXAMPLE 48C (0.074 g), phenylacetaldehyde (0.02 mL) and Na2S2O4 (0.09 g) in ethanol (2 mL) and water (2 mL) was stirred at 120 ° C for 20 minutes in a microwave reactor. and concentrated. The concentrate was purified by reverse phase HPLC with a Shimadzu LC10 HPLC system, with a Phenominex Luna 10 micron C18 (2) 100 apparatus, column 150x30 mm, with 5-45% acetonitrile in water, with 0.15% TFA for 25 hours. minutes, at a flow rate of 20 mL / minute. 1 H-NMR (300 MHz, DMSO-d 6) 10.02 (brs, 1H), 8.43 (s, 1H), 8.37 (d, 2H), 8.0 (s, 1H), 7.89 (d, 1H), 7.78 (d, 1H), 7.70 (d, 2H), 7.43-7.34 (m, 5H), 4.49 (s, 2H), 4.43 (s, 2H), 3.99 (m, 4H), 3.64 (m, 2H), 3.30 (m, 1H), 3.18 (m, 1H). EXAMPLE 49 This example was the fastest eluting diastereomer, prepared by substituting the 3-hydroxypyrrolidine of EXAMPLE 31C, for 4-methanesulfonylpiperazine. 1 H-NMR (300 MHz, DMSO-d 6) 9.68 (brs, 1H), 8.30 (s, 1H), 7.86 (s, 1H), 7.81 (d, 1H), 7.65 (d, 1H), 7.42-7.32 ( m, 5H), 4.79 (m, 1H), 4.45 (s, 2H), 3.74 (m, 4H), 3.17 (m, 5H), 3.05 (s, 3H), 2.24 (m, 2H), 2.13 (m , 4H), 1.78 (m, 2H). EXAMPLE 50 This example was the slower eluting diastereomer, prepared by substituting the 3-hydroxypyrrolidine of EXAMPLE 31C, for 4-methanesulfonylpiperazine. 1 H-NMR (300 MHz, DMSO-d 6) 9.40 (brs, 1H), 8.30 (s, 1H), 7.88 (s, 1H), 7.79 (d, 1H), 7.67 (d, 1H), 7.43-7.30 ( m, 5H), 4.98 (m, 1H), 4.42 (s, 2H), 3.70 (m, 4H), 3.15 (m, 5H), 3.02 (s, 3H), 2.43 (m, 2H), 2.03 (m , 6H). EXAMPLE 51A The product of EXAMPLE 43B (0.12 g), 4-morpholinecarbonyl chloride (0.06 mL) and DIPEA (0.26 mL) in CH3CN (10 mL) was stirred for 18 hours and partitioned in ethyl acetate. and NaHCO3. The extract was washed with brine, dried, filtered and concentrated. The concentrate was recrystallized from diethyl ether. EXAMPLE 51B This example was prepared by substituting cis-4- (4- (4-amino-3-iodopyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) -1-methylpiperazin-2-one of EXAMPLE 2B, by the product of EXAMPLE 51A. EXAMPLE 51C A mixture of EXAMPLE 51B (0.075 g), phenylacetaldehyde (0.02 mL) and Na2S2O4 (0.09 g) in ethanol (2 mL) and water (2 mL) was stirred at 120 ° C for 20 minutes in a microwave reactor. and concentrated. The concentrate was purified by reverse phase HPLC with a Shimadzu LC10 HPLC system, with a Phenominex Luna 10 micron C18 (2) 100 apparatus, column 150x30 mm, with 5-45% acetonitrile in water, with 0.15% TFA, during 25 minutes, at a flow rate of 20 mL / minute. 1 H-NMR (300 MHz, DMSO-d 6) 8.32 (s, 1 H), 7.91 (s, 1 H), 7.85 (d, 1 H), 7.72 (d, 1 H), 7.43-7.33 (m, 5 H), 4.94 ( m, 1H), 4.50 (s, 2H), 3.72 (m, 4H), 3.17 (m, 4H), 3.02 (m, 4H), 2.12 (m, 2H), 1.95 (m, 2H). EXAMPLE 52A To a solution of 3-iodo-1H-pyrazolo [3,4-d] pyrimidin-4-yl-amine, prepared as described in Bioorg Med. Chem. Lett. 2002, 12, 1687-1690 (0.82 g. ), tert-butylester of 3-hydroxypyrrolidine-1-carboxylic acid, (1.17 g) and triphenylphosphine (1.65 g) in THF (40 mL), DIAD (1.2 mL) was added. The mixture was stirred for 18 hours and subjected to partition extraction in ethyl acetate and brine. The extract was dried, filtered and concentrated. The concentrate was eluted through a pad of silica gel with 30-50% ethyl acetate / hexanes, then with 5% methanol / ethyl acetate. The eluent was concentrated, and the concentrate was recrystallized from dichloromethane / ether.

EXAMPLE 52B The product of EXAMPLE 52A (0.54 g) in 4M HCl in dioxane (10 mL) was stirred at room temperature for 1.5 hours and filtered. EXAMPLE 52C A mixture of EXAMPLE 52B (0.18 g), iodoacetamide (0.1 g), K2CO3 (0.35 g) and tetrabutylammonium iodide (0.01 g) in DMF (5 mL) was stirred at room temperature for 18 hours. The reaction mixture was diluted with ethyl acetate, washed with water and with brine and dried, filtered and concentrated. The concentrate was recrystallized from diethyl ether. EXAMPLE 52D This example was prepared by substituting cis-4- (4- (4-amino-3-iodopyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) -1-methylpiperazin-2-one from EXAMPLE 2B, for the product of EXAMPLE 52C. EXAMPLE 52E A mixture of EXAMPLE 52D (0.11 g), phenylacetaldehyde (0.02 mL) and Na 2 S 2 O (0.09 g) in ethanol (2 mL) and water (2 mL) was stirred at 120 ° C for 20 minutes in a microwave reactor and concentrated. The concentrate was purified by reverse phase HPLC with a Shimadzu LC10 HPLC system, with a Phenominex Luna apparatus microns C18 (2) 100, column 150x30 mm, with 5-45% acetonitrile in water, with 0.15% TFA, for 25 minutes, at a flow rate of 20 mL / minute. 1 H-NMR (300 MHz, DMSO-d 6) 10.38 (brs, 1H), 8.32 (s, 1H), 7.93 (s, 1H), 7.90 (s, 1H), 7.83 (d, 1H), 7. 71 (d, 1H), 7.66 (s, 1H), 7.42-7.31 (m, 5H), 5.70 (m, 1H), 4.45 (s, 2H), 4.13 (m, 6H), 2.53 (m, 2H) . EXAMPLE 53 This example was the fastest eluting diastereomer, prepared by substituting the 3-hydroxypyrrolidine of EXAMPLE 31C, for 4- (2-hydroxyethyl) piperazine. 1 H-NMR (300 MHz, DMSO-d 6) 8.29 (s, 1 H), 7.85 (s, 1 H), 7.80 (d, 1 H), 7.65 (d, 1 H), 7.41-7.31 (m, 5 H), 4.75 ( m, 1H), 4.44 (s, 2H), 3.70 (m, 8H), 3.08 (m, 6H), 2.10 (m, 6H), 1.68 (m, 2H). EXAMPLE 54 This example was the slowest eluting diastereomer, prepared by substituting the 3-hydroxypyrrolidine of EXAMPLE 31C, for 4- (2-hydroxyethyl) piperazine. H-NMR (300 MHz, DMSO-d6) 8.31 (s, 1H), 7.87 (s, 1H), 7.81 (d, 1H), 7.66 (d, 1H), 7.42-7.32 (m, 5H), 4.92 ( m, 1H), 4.44 (s, 2H), 3.70 (m, 4H), 3.51 (m, 4H), 3.12 (m, 6H), 2.35 (m, 1H), 2.07 (m, 3H), 1.87 (m , 4H). EXAMPLE 55 A mixture of EXAMPLE 31B (43.7 mg) and NaBH 4 (0.019 g) in methanol (3 mL) was stirred for 2.5 hours and concentrated. The concentrate was purified by reverse phase HPLC with a system Shimadzu LC10 HPLC, with a Phenominex Luna 10 micron apparatus C18 (2) 100, column 150x30 mm, with 5-45% acetonitrile in water and with 0.15% TFA, for 25 minutes, at a flow rate of mL / minute. 1 H-NMR (300 MHz, DMSO-d 6) 8.31 (s, 1H), 7.89 (s, 1H), 7.84 (d, 1H), 7.70 (d, 1H), 7.43-7.33 (m, 5H), 4.68 ( m, 1H), 4.48 (s, 2H), 4.07 (m, 1H), 3.55 (m, 1H), 1.95 (m, 6H), 1.42 (m, 2H). EXAMPLE 56A This example was prepared by substituting cis-4- (4- (4-amino-3-iodopyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) -1-methylpiperazin-2-one from EXAMPLE 1B, by cis-4-chloro-5-iodo-7- (4- (4-methyl-piperazin-1-yl) -cyclohexyl-7H-pyrrolo [2,3-d] pyrimidine, prepared as described in the International Patent Publication WO 05/074603 EXAMPLE 56B A mixture of EXAMPLE 56A (0.048 g) and 30% NH4OH (5 mL) in dioxane (5 mL) was stirred at 120 ° C in a sealed tube for 24 hours, cooled and The concentrate was purified by reverse phase HPLC, EXAMPLE 57A A mixture of 4-bromo-benzene-1,2-diamine (3 g), and 3-phenylpropionic acid (3.61 g) in 4N HCl (15 mL), it was stirred at reflux temperature for 3 hours, cooled and filtered.The filtrate was stirred in a separatory funnel with dichloromethane and water.The water was adjusted to pH 7 with 30% NH4OH, and subjected to extraction with acetate The extract was dried, filtered and concentrated. chromatographed on silica gel with hexanes / ethyl acetate 2: 1. EXAMPLE 57B A mixture of EXAMPLE 57A (1128 g), bis (pinacolato) diboro (2.86 g), potassium acetate (2.2 g) and dichloro (1,1'-bis (diphenylphosphino) ferrocene) -palladium (II) »dichloromethane (0.367 g) in DMF (24 mL), stirred at 85 ° C for 20 hours, cooled, filtered through diatomaceous earth (Celite®) and concentrated. The concentrate was subjected to flash chromatography on silica gel with hexanes / ethyl acetate 1: 1. The eluent was concentrated and the concentrate was triturated with heptane. EXAMPLE 57C A mixture of EXAMPLE 57B (0.435 g), cis-4-chloro-5-iodo-7- (4- (4-methyl-piperazin-1-yl) -cyclohexyl) -7H-pyrrolo [2,3-d] pyrimidine, prepared as described in International Patent Publication WO 05/074603 (0.383 g), Na 2 C 3 'H 2 O, (0.258 g) and tetrakis (triphenylphosphine) palladium (0) (0.1 1 6 g) in DME (8 mL) and water (4 mL), was heated at 80 ° C for 18 hours, cooled and concentrated. The concentrate was treated with water and extracted with ethyl acetate. The extract was washed with brine and dried, filtered and concentrated. The concentrate was subjected to flash chromatography on silica gel with 10% methanol / dichloromethane. EXAMPLE 57D This example was prepared by substituting cis-4-chloro-7- (4- (4-methyl-piperazin-1-yl) -cyclohexyl) -5- (2-phenyl-1H-benzolimidazol-5-yl) -7H- pyrrolo [2,3-d] pyrimidine from EJ EMPLO 56B, by the product of EJ EM PLO 57C. EXAMPLE 58A To a solution of H2SO (28.9 mL) at 0 ° C, a solution of sodium nitrite (22.4 g) in water (57 mL) was added, while maintaining the internal temperature below 25 ° C. Later 3-Bromophenol (25 g) was added to the mixture in ethanol, while maintaining the internal temperature below 25 ° C. The mixture was warmed to room temperature and stirred for 2 hours, treated with water and extracted with dichloromethane. The extract was dried (MgSO4), filtered and concentrated. The concentrate was subjected to flash chromatography on silica gel with 5% ethyl acetate / hexanes. EXAMPLE 58B A mixture of the EJ EM PLO 58A (1 g) in ethanol (23 mL) was treated with a suspension of Raney's Nickel in water (0.1 mL), stirred for 3 hours under an atmosphere of hydrogen. (1 atmosphere), filtered through diatomaceous earth (Celite®) and concentrated. The concentrate was subjected to flash chromatography on silica gel with 20% ethyl acetate / hexanes. EXAMPLE 58C The product of EJ E M P LO 58B (0.42 g) in TH F (25 μL) was treated with phenyl isothiocyanate (0.4 μL) and stirred for 1 8 hours. The mixture was treated with CuSO4 (3.2 g), silica gel (3 g) and TEA (0.31 mL), stirred for 1 8 hours and concentrated. The concentrate was subjected to flash chromatography on silica gel with 1% ethyl acetate / hexanes. EXAMPLE 58D This example was prepared by substituting the 4-bromo-2-nitrophenylamine of EXEM PLO 2A for the product of EJ EMPLO 58C.

EXAMPLE 58E This example was prepared by substituting the product of the EXAMPLE 2A and cis-4- (4- (4-amino-3-iodopyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) -1-methylpiperazin-2-one, by the product of EXAMPLE 58D and cis-3-iodo-1- (4- (4-methylpiperazin-1-yl) cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-yl-amine prepared as described in Bioorg. Chem. Lett. 2002, 12, 1687-1690, respectively, in EXAMPLE 2B ,. 1 H-NMR (300 MHz, DMSO-d 6) 8.22 (s, 1H), 7.73-7.70 (m, 2H), 7.55 (m, 1H), 7.45-7.38 (m, 2H), 7.34-7.29 (m, 2H ), 6.96-6.91 (m, 1H), 4.88-4.78 (m, 1H), 2.45 (bs, 3H), 2.37-2.32 (m, 4H), 2.28 (bs, 1H), 2.25 (bs, 1H), 2.21 (bs, 1H), 2.14 (s, 3H), 2.11-2.05 (m, 2H), 1.76-1.66 (m, 2H), 1.65-1.52 (m, 3H). EXAMPLE 59 This example was prepared by substituting the product of EXAMPLE 2A and cis-4- (4- (4-amino-3-iodopyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) -1-methylpiperazine-2. -one, by the product of EXAMPLE 58D and trans-3-iodo-1- (4- (4-methylpiperazin-1-yl) cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-yl -amine prepared as described in Bioorg Med. Chem. Lett. 2002, 12, 1687-1690, respectively in EXAMPLE 2B. 1 H-NMR (300 MHz, DMSO-d 6) 10.79 (bs, 1H), 8.23 (s, 1H), 7.79 (d, 2H), 7.70 (s, 1H), 7.60-7.55 (m, 1H), 7.53- 7.47 (m, 1H), 7.39 (t, 2H), 7.05 (t, 1H), 4.73-4.59 (m, 1H), 2.40-2.25 (m, 6H), 2.14 (s, 3H), 2.09-1.90 ( m, 7H), 1.74 (s, 1H), 1.55-1.39 (m, 3H). EXAMPLE 60 This example was prepared by substituting the product of the EXAMPLE 2A and cis-4- (4- (4-amino-3-iodopyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) -1-methylpiperazin-2-one, by the product of EXAMPLE 58D and trans-3-iodo-1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-yl-amine prepared as described in International Patent Publication WO 05/074603, respectively, in EXAMPLE 2B. 1 H-NMR (300 MHz, DMSO-d 6) 10.76 (bs, 1H), 8.24 (s, 1H), 7.79 (d, 2H), 7.71 (s, 1H), 7.62-7.55 (m, 1H), 7.53- 7.47 (m, 1H), 7.44-7.36 (m, 2H), 7.06 (t, 1H), 4.73-4.59 (m, 1H), 3.61-3.54 (m, 5H), 2.43-2.29 (m, 1H), 2.14-1.95 (m, 7H), 1.55-1.39 (m, 3H). EXAMPLE 61 This example was prepared by substituting the product of EXAMPLE 2A and cis-4- (4- (4-amino-3-iodopyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) -1-methylpiperazine. -2-one, by the product of EXAMPLE 58D and trans-3-iodo-1- (4- (2-methoxyethoxy) cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-yl-amine prepared as described in International Patent Publication WO 05/074603, respectively, in EXAMPLE 2B. 1 H-NMR (300 MHz, DMSO-d 6) 10.76 (bs, 1H), 8.24 (s, 1H), 7.79 (d, 2H), 7.71 (s, 1H), 7.61-7.56 (m, 1H), 7.53- 7.48 (m, 1H), 7.40 (t, 2H), 7.06 (t, 1H), 4.76-4.63 (m, 1H), 3.61-3.54 (m, 2H), 3.48-3.43 (m, 2H), 3.26 ( s, 3H), 2.20-1.91 (m, 6H), 1.50-1.34 (m, 3H). EXAMPLE 62 This example was prepared by substituting the benzaldehyde of EXAMPLE 7B, for 2-chloro-6-fluorophenylacetaldehyde. H-NMR (300 MHz, DMSO-de) 12.51 (bs, 1H), 8.22 (s, 1H), 7.73-7.55 (m, 3H), 7.48-7.36 (m, 4H), 7.35-7.26 (m, 1H) ), 4.72-4.58 (m, 1H), 4.40-4.35 (m, 2H), 3.62-3.53 (m, 5H), 2.42-2.29 (m, 1H), 2.11-1.92 (m, 6H), 1.57-1.37 (m, 3H). EXAMPLE 63A To 4-bromoindole (400 mg) in DMF (5 mL) at 0 ° C, 60% oily sodium hydride (88 mg) was added. The mixture was stirred for 5 minutes, warmed to room temperature, stirred for 10 minutes, cooled in an ice bath, treated with 2-chlorobenzyl bromide, stirred at room temperature during 16 hours and subjected to extraction by partition with ethyl acetate and brine. The extract was washed with brine and dried (Na2SO4), filtered and concentrated. EXAMPLE 63B A mixture of EXAMPLE 63A (640 mg), dichloro (1,1'-bis (d ifen i lphosfino) -ferrocene) palladium (I l) «d-chloromethane (44 mg), bis (pinacolato) -d boron (1.52 g) and potassium acetate (980 mg) in DMF (8 mL) at 100 ° C, stirred for 16 hours and subjected to partition extraction in ethyl acetate and brine. The extract was washed with brine and dried (MgSO), filtered and concentrated. The concentrate was subjected to flash chromatography on silica gel, with 5% ethyl acetate / hexanes. EXAMPLE 63C A mixture of EXAMPLE 63B (138 mg), cis-3-iodo-1- (4-morfol i n-4-i I-cyclohexy I) -1 H -pyrazolo [3,4-d] pyrimidine- 4-yl-amine, prepared as described in International Patent Publication WO 05/074603 (0.11 g), sodium carbonate (53 mg) and tetrakis (Ph3P) palladium (0) (17 mg) in 1,2-dimethoxyethane / water 1: 1 (2 mL) at 130 ° C, stirred for 30 minutes in a microwave reactor and subjected to extraction by partition with ethyl acetate and brine. The extract was washed with brine and dried (Na2SO), filtered and concentrated. The concentrate was purified by HPLC (column: Phenomenex, 00F-4253-U0, 10 microns, C-18, 150x30 mm, solvent A: 100% water with 0.1% TFA, solvent B: 100% acetonitrile with TFA 0.1%, gradient B 20-60% for 25 minutes). The fractions with product were lyophilized. 1 H-NMR (300 MHz, DMSO-de) 9.63 (bs, 1H), 8.33 (s, 1H), 7.52-7.58 (m, 3H), 7.22-7.36 (m, 4H), 6.76 (dd, 1H), 6.65 (d, 1H), 5.61 (s, 2H), 4.77-4.88 (m, 1H), 4.00-4.08 (m, 3H), 3.41-3.52 (m, 4H), 3.10-3.24 (m, 3H), 2.22-2.33 (m, 2H), 2.09-2.21 (m, 3H), 1.70-1.84 (m, 2H). EXAMPLE 64 This example was prepared by substituting the 4-bromoindole of the EXAMPLE 63A, by 6-bromoindole. 1 H-NMR (300 MHz, DMSO-d 6) 9.83 (bs, 1H), 8.36 (s, 1H), 7.78 (d, 1H), 7.65 (s, 1H), 7.59 (d, 1H), 7.51 (dd, 1H), 7.22-7.38 (m, 3H), 6.73 (dd, 1H), 6.66 (d, 1H), 5.59 (s, 2H), 4.73-4.82 (m, 1H), 4.00-4.08 (m, 3H) , 3.66-3.75 (m, 2H), 3.37-3.50 (m, 3H), 3.17 (br.m, 2H), 2.22-2.28 (m, 2H), 2.07-2.16 (m, 3H), 1.70-1.81 ( m, 2H). EXAMPLE 65 This example was prepared by substituting the 4-bromoindole of EXAMPLE 63A for 5-bromoindole. 1 H-NMR (300 MHz, DMSO-d 6) 9.86 (bs, 1H), 8.38 (s, 1H), 7.88 (d, 1H), 7.56-7.63 (m, 2H), 7.54 (dd, 1H), 7. 42 (dd, 1H), 7.31-7.36 (m, 1H), 7.24-7.28 (m, 1H), 6.81 (dd, 1H), 6.67 (d, 1H), 5.59 (s, 2H), 4.74-4.83 ( m, 1H), 4.00-4.08 (m, 3H), 3.66-3.76 (m, 2H), 3.39-3.49 (m, 2H), 3.11-3.22 (br.m, 2H), 3.01-3.07 (t, 1H) ), 2.22-2.29 (m, 2H), 2.09-2.18 (m, 3H), 1.72-1.82 (m, 2H). EXAMPLE 66 This example was prepared by substituting 4-bromoindole and 2-chlorobenzyl bromide for 5-bromoindole and 3-chlorobenzyl bromide, respectively in EXAMPLE 53A. 1 H-NMR (300 MHz, DMSO-de) 9.71 (bs, 1H), 8.34 (s, 1H), 7.85 (d, 1H), 7.64-7.69 (m, 2H), 7.31-7.44 (m, 4H), 7.20-7.25 (m, 1H), 6.81 (dd, 1H), 6.65 (d, 1H), 5.51 (s, 2H), 4.72-4.83 (m, 1H), 4.00-4.08 (m, 3H), 3.70 ( t, 2H), 3.38-3.49 (m, 2H), 3.10-3.22 (br.m, 2H), 3.01-3.07 (t, 1H), 2.22-2.29 (m, 2H), 2.06-2.17 (m, 3H ), 1.69-1.82 (m, 2H). EXAMPLE 67A A mixture of 2-amino-4-chlorophenol (1.44 g), triethylamine (1.74 mL) and phenylacetyl chloride (1.32 mL) in dichloromethane (30 mL), was stirred for 16 hours and treated with ethyl acetate and with brine. The extract was washed with water, with brine, with 10% sodium bicarbonate, with 10% potassium hydrogen sulfate and dried (Na 2 SO 4), filtered and concentrated. The concentrate was recrystallized from ethyl acetate. EXAMPLE 67B The product of EXAMPLE 67A (0.65 g), triphenylphosphine (980 mg) and diethyl azodicarboxylate (0.59 ml) in THF (15mL) was stirred for 16 hours and concentrated. The concentrate was subjected to flash chromatography on silica gel with 20% ethyl acetate in hexanes. EXAMPLE 67C A mixture of EXAMPLE 67B (244 mg), bis (dibenzylidene ketone) palladium (0) (16.3 mg), trichiohexylphosphine (20 mg), bis (pinacolato) diboron (383 mg) and potassium acetate (150 mg) in dioxane (4 mL), was heated twice at 130 ° C for 50 minutes and subjected to partition extraction in ethyl acetate and brine.

The extract was washed with brine and dried (Na2SO4), filtered and concentrated. The concentrate was subjected to flash chromatography on silica gel, with 5% ethyl acetate in hexanes. EXAMPLE 67D This example was prepared by substituting the N- (2-chlorobenzyl) -4- (4,4,5,5-tetramethyl [1,3,2] dioxaborolan-2-yl) indole of EXAMPLE 53C, by the product of the EXAMPLE 67C. EXAMPLE 68A A mixture of 6-bromo-1 H-indazole (1 g), bis (pinacolato) diboro (3.87 g), potassium acetate (2.49 g), dichloro (1,1'-bis (diphenylphosphino) ferrocene) palladium (ll) (112 mg) in DMF (20 mL), stirred at 100 ° C for 18 hours, cooled and extracted with ethyl acetate. The extract was washed with brine, dried (Na2SO), filtered and concentrated. The concentrate was subjected to flash chromatography on silica gel twice with 15% ethyl acetate / hexanes.

EXAMPLE 68B A mixture of EXAMPLE 68A (122 mg), potassium carbonate (415 mg) and 2-chlorobenzyl bromide (0.136 mL) in acetone (10 mL) at reflux temperature was stirred for 2 days and subjected to extraction. with ethyl acetate. The extract was washed with brine and dried (Na2SO) filtered and concentrated. The concentrate was subjected to flash chromatography on silica gel with 5% ethyl acetate / hexanes. EXAMPLE 68C This example was prepared by substituting the N- (2-chlorobenzyl) -4- (4,4,5,5-tetramethyl (1,3,2) dioxaborolan-2-yl) indole of EXAMPLE 63C, by the product of the EXAMPLE 68B. 1 H-NMR (300 MHz, DMSO-dβ) 9.70 (bs, 1H), 8.33 (s, 1H), 8.26 (d, 1H), 7.98 (d, 1H), 7.91 (s, 1H), 7.45-7.52 ( m, 2H), 7.23-7.36 (m, 2H), 6.88 (dd, 1H), 5.80 (s, 2H), 4.74-4.84 (m, 1H), 4.00-4.08 (m, 3H), 3.70 (t, 2H), 3.39-3.49 (m, 2H), 3.10-3.22 (br.m, 2H), 2.20-2.29 (m, 2H), 2.08-2.17 (m, 3H), 1792-1.82 (m, 2H). EXAMPLE 69A This example was prepared by substituting the 2-chlorobenzyl bromide of EXAMPLE 68B for 3-chlorobenzyl bromide. EXAMPLE 69B This example was prepared by substituting the N- (2-chlorobenzyl) -4- (4,4,5,5-tetramethyl (1,3,2) dioxaborolan-2-yl) indole of EXAMPLE 63C, by the product of the EXAMPLE 69A. 1 H-NMR (300 MHz, DMSO-d 6) 9.68 (bs, 1H), 8.33 (s, 1H), 8.25 (d, 1H), 7.94-7.97 (m, 2H), 7.43 (dd, 1H), 7.32-7.37 (m, 3H), 7.17-7.23 (m, 1H), 5.74 (s, 2H), 4.74-4.84 (m, 1H), 4.00-4.08 (m, 3H), 3.66-3.76 ( m, 2H), 3.39-3.50 (m, 2H), 3.11-3.22 (br.m, 2H), 2.22-2.29 (m, 2H), 2.08-2.18 (m, 3H), 1.69-1.82 (m, 2H) ). EXAMPLE 70 This example was prepared by substituting the 2-amino-4-chlorophenol of EXAMPLE 67A for 2-amino-5-chlorophenol. 1 H-NMR (300 MHz, DMSO-de) 9.64 (bs, 1H), 8.29 (s, 1H), 7.82-7.87 (m, 1H), 7.25-7.32 (m, 5H), 7.15 (d, 1H), 7.05 (dd, 1H), 4.39 (s, 2H), 4.70-4.81 (m, 1H), 4.00-4.08 (m, 3H), 3.66-3.76 (m, 2H), 3.39-3.49 (m, 2H), 3.08-3.24 (br.m, 2H), 2.18-2.29 (m, 2H), 2.03-2.18 (m, 3H), 1.67-1.82 (m, 2H). EXAMPLE 71A A mixture of EXAMPLE 68A (73 mg), cis-3-iodo-1- (4-morphol-n-4-yl-cyclohexy I) -1 H -pyrazolo [3,4-d] pyrimidine-4- il-amine, prepared as described in International Patent Publication WO 05/074603 (0.11 g), sodium carbonate (53 mg) and tetrakis (triphenylphosphine) palladium (0) (17 mg) in dimethoxyethane / water 1: 1 (2 mL), at 130 ° C, was stirred for 20 minutes in a microwave reactor and subjected to partition extraction in ethyl acetate and brine. The extract was washed with brine and dried (Na2SO), filtered and concentrated. The product was purified by HPLC (column: Penomenex 00F-4253-U0, 10 microns, C-18, 150x30 mm, solvent A: 100% water with 0.1% TFA, solvent B: 100% acetonitrile with 0.1% TFA %, gradient B 0-50% for 25 minutes).

The fractions containing the product were lyophilized. 1 H-NMR (300 MHz, DMSO-dβ) 13.24 (br, 1H), 9.66 (bs, 1H), 8.32 (s, 1H), 8.17 (d, 1H), 7.93 (dd, 1H), 7.77 (d, 1H), 7.43 (dd, 1H), 4.73-4.84 (m, 1H), 4.00-4.08 (m, 3H), 3.70 (t, 2H), 3.40-3.52 (m, 3H), 3.07-3.23 (m, 2H), 2.21-2.27 (m, 2H), 2.09-2.19 (m, 3H), 1.70-1.84 (m, 2H). EXAMPLE 71B A mixture 71A (20 mg), 3-fluorobenzyl bromide (0.0072 mL) and potassium carbonate (27 mg) in acetone (5 mL) at reflux temperature, stirred for 2 days and subjected to partition extraction with ethyl acetate and brine. The extract was washed with brine and dried (Na2SO), filtered and concentrated. The concentrate was purified by HPLC (column: Phenomenex, 00F-4253-U0, 10 microns, C-18, 150x30 mm, solvent A: 100% water with 0.1% TFA, solvent B: 100% acetonitrile with 0.1% TFA; gradient B 15-70% for 25 minutes). The fractions containing the product were lyophilized. EXAMPLE 72A The product of EXAMPLE 43B (0.057 g), methanesulfonyl chloride (0.015 mL) and diisopropylethylamine (0.13 mL) in dichloromethane (3 mL), was stirred for 16 hours, diluted with ethyl acetate and washed with water and brine. The extract was dried, filtered and concentrated. The concentrate was recrystallized from diethyl ether. EXAMPLE 72B This example was prepared by substituting cis-4- (4- (4-amino- 3-iodopyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) -1-methylpiperazin-2-one from EXAMPLE 2B, by the product of EXAMPLE 72A. EXAMPLE 72C This example was prepared by substituting 2- (4- (4-amino-3- (4-amino-3-nitrophenyl) pyrazolo [3,4-d] pyrimidin-1-yl) piperidin-1-yl) acetamide of EXAMPLE 43E, by the product of EXAMPLE 72B. 1 H-NMR (300 MHz, DMSO-d 6) 8.31 (s, 1H), 7.91 (s, 1H), 7.85 (d, 1H), 7.72 (d, 1H), 7.43-7.33 (m, 5H), 4.89 ( m, 1H), 4.49 (s, 2H), 3.71 (m, 2H), 3.04 (m, 2H), 2.94 (s, 3H), 2.24 (m, 2H), 2.08 (m, 2H). EXAMPLE 73A A mixture of 3-iodo-1 H-pyrazolo [3,4-d] pyrimidin-4-yl-amine (0.12 g), prepared as described in Bioorg Med. Chem. Lett. 2002, 12, 1687-1690, and NaH (0.02 g), in DMF (5 mL), was stirred for 30 minutes at room temperature, treated with 4-nitrobenzenesulfonic acid oxiranylmethyl ester (0.11 g), stirred for 16 hours , it was extracted by partition in ethyl acetate and brine and extracted with dichloromethane. The extract was dried (Na2SO4), filtered and concentrated. The concentrate was purified by reverse phase HPLC with a Shimadzu LC10 HPLC system, with a Phenominex Luna 10 micron C18 (2) 100 apparatus, column 150x30 mm, with 5-45% acetonitrile in water and with 0.15% TFA for 25 hours. minutes at a flow rate of 20 mL / minute. EXAMPLE 73B A mixture of EXAMPLE 73A (0.04 g) and morpholine (0.06 mL) in ethanol (3 mL), was stirred at 90 ° C for 18 hours, cooled and it was extracted by partition in ethyl acetate and brine. The extract was dried (Na2SO4), filtered and concentrated. EXAMPLE 73C This example was prepared by substituting cis-4- (4- (4-amino-3-iodopyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) -1-methylpiperazin-2-one from EXAMPLE 2B, for the product of EXAMPLE 73B. EXAMPLE 73D This example was prepared by substituting 2- (4- (4-amino-3- (4-amino-3-nitrophenyl) pyrazolo [3,4-d] pyrimidin-1-yl) piperidin-1-yl) acetamide of EXAMPLE 43E, by the product of EXAMPLE 73C. 1 H-NMR (300 MHz, DMSO-d 6) 9.73 (brs, 1H), 8.32 (s, 1H), 7.88 (s, 1H), 7.82 (d, 1H), 7.68 (d, 1H), 7.42-7.32 ( m, 5H), 6.02 (brs, 1H), 4.49 (m, 2H), 4.45 (s, 2H), 4.38 (m, 1H), 3.91 (m, 4H), 3.76 (m, 1H), 3.31 (m , 4H), 3.16 (m, 1H). EXAMPLE 74 This example was prepared by substituting the benzaldehyde of EXAMPLE 7B, by (2,6-difluorophenyl) acetaldehyde. 1 H-NMR (300 MHz, DMSO-d6) 12.52 (d, 1H), 8.22 (s, 1H), 7.72-7.56 (m, 2H), 7.46-7.39 (m, 2H), 7.16 (t, 2H), 4.71-4.59 (m, 1H), 4.27 (s, 2H), 3.61-3.55 (brs, 4H), 2.44-2.46 (m, 1H), 2.10-1.94 (m, 6H), 1.54-1.37 (m, 2H). EXAMPLE 75 This example was prepared by substituting the benzaldehyde of the EXAMPLE 7B, by (3-trifluoromethylphenyl) acetaldehyde. 1 H-NMR (300 MHz, DMSO-de) 12.52 (bs, 1H), 8.22 (s, 1H), 7.78-7.75 (m, 21H), 7.71-7.55 (m, 5H), 7.46-7.41 (m, 1H), 4.71-4.59 (m, 1H), 4.35 (s, 2H), 3. 59-3.56 (brs, 4H), 2.43-2.27 (m, 1H), 2.08-1.943 (m, 6H), 1.54-1.41 (m, 2H). EXAMPLE 76A A mixture of 2,4-dimethylaniline (0.51 g), pyridine (1 g) and 4-bromo-2-fluorobenzoyl chloride (1 g) in dichloromethane (9 mL) was stirred for 18 hours. The reaction was quenched with 1 N HCl and concentrated. The concentrate was recrystallized from ethyl acetate / hexanes. EXAMPLE 76B To a Milestone Microsynth microwave vessel, PCI5 (0.92 g), the product of EXAMPLE 76A (1.25 g) and toluene (21 mL) were added. The vessel was sealed and heated to 150 ° C with a time rise of 10 minutes and a holding time of 15 minutes, cooled and concentrated. The concentrate was dissolved immediately in THF (20 mL) and added to a solution of hydrazine (1.35 g) in THF (20 mL). This mixture was stirred for 3 days, treated with ethyl acetate, washed with a saturated aqueous solution of sodium bicarbonate and brine, and dried (MgSO), filtered and concentrated. The concentrate was subjected to flash chromatography on silica gel with dichloromethane / methanol. EXAMPLE 76C A mixture of EXAMPLE 76B (1.3 g) and TEA (1.3 g, 12.6 mL) in acetonitrile (42 mL) in a microwave vessel was stirred in a Milestone Microsynth microwave oven with a temperature rise time of 10 minutes. minutes and a time of minute maintenance at 170 ° C, cooled and concentrated. The concentrate was purified by flash chromatography with dichloromethane / methanol. The eluent was concentrated, and the concentrate was purified by reverse phase HPLC with CH3CN / water / 0.15% TFA. EXAMPLE 76D A mixture of bis (pinacolato) diboro (0.87 g), potassium acetate (0.84 g), PdCI2 (dppf) "dichloromethane (0.038 g) and the product of EXAMPLE 76C (0.54 g) in DMF (3.5 mL), it was stirred at 100 ° C for 1-3 days. The mixture was filtered through a pad of silica gel with ethyl acetate. The concentrate was subjected to flash chromatography on silica gel with dichloromethane / methanol. EXAMPLE 76E A mixture of trans-3-iodo-1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-yl-amine, prepared as described in International Patent Publication WO 05/074603 (0.05 g) the product of EXAMPLE 76D (0.055 g), Na2CO3 (0.025 g), PdCI2 (PPh3) 2 (0.005 g) and DME / water (0.34 mL / 0.17 mL). The mixture was sealed and stirred in a Personal Chemistry Smith Synthesizer system for 20 minutes at 150 ° C, cooled and concentrated. The concentrate was filtered through a pad of silica gel with ethyl acetate. The eluent was concentrated and the concentrate was purified by reverse phase HPLC with CH3CN / water / 0.15% TFA. 1 H NMR (300 MHz, DMSO-d 6) 12.16 (s, 1H), 9.64 (s, 1H), 8.30 (s, 1H), 7.88 (d, 1H), 7.60 (s, 1H), 7.58 (s, 1H), 7.47 (d, 1H), 7.28 (dd, 1H), 6.98 (s, 1H), 6.90 (dd, 1H), 4.72-4.87 (m, 1H), 4.04 (d, 2H), 3. 64-3.76 (m, 2H), 3.46 (d, 1H), 3.09-3.24 (m, 2H), 2.30 (s, 3H), 2.27 (d, 2H), 2.23 (s, 3H), 2.14 (t, 4H), 1.66-1.85 (m, 2H). EXAMPLE 77 This example was prepared by substituting 2,4-dimethylaniline and 4-bromo-2-fluorobenzoyl chloride, for 2-chloraniline and 5-bromo-2-fluorobenzoyl chloride, respectively, in the EXAMPLE 76A. 1 H-NMR (300 MHz, DMSO-d 6) 12.58 (2, 1H), 9.76 (s, 1H), 8.32 (s, 1H), 8.03 (d, 2H), 7.83 (dd, 1H), 7.60-7.64 (m, 2H), 7.42 (dd, 1H), 7.16-7.28 (m, 1H), 6.86 (td, 1H), 4.78 (dt, 2H), 4.04 (d, 2H), 3.70 (t, 2H), 3.43 (t, 3H), 3.06-3.26 (m, 2H), 2.24 (d, 2H), 2.13 (t, 3H), 1.66-1.86 (m, 2H). EXAMPLE 78 This example was prepared by substituting 2,4-dimethylaniline and 4-bromo-2-fluorobenzoyl chloride, for 3-chloraniline and 5-bromo-2-fluorobenzoyl chloride, respectively, in the EXAMPLE 76A ,. 1 H NMR (300 MHz, DMSO-d 6) 12.34 (s, 1H), 9.79 (s, 1H), 9.29 (s, 1H), 8.33 (s, 1H), 8.29 (s, 1H), 7.99 (t, 1H), 7.58-7.64 (m, 1H), 7.57 (s, 1H), 7.51-7.56 (m, 1H), 7.29 (t, 1H), 6.85 (dd, 1.70 Hz, 1H), 4.79 (dt, 1H), 4.04 (d, 2H), 3.64-3.76 (m, 2H), 3.47 (t, 3H), 3.09-3.26 (m, 2H), 2.20-2.32 (m, 2H), 2.09-2.20 (m, 4H), 1.64-1.89 (m, 2H). EXAMPLE 79 This example was prepared by substituting 2,4-dimethylaniline and 4-bromo-2-fluorobenzoyl chloride for 2-fluoroaniline and 5-bromo-2-fluorobenzoyl chloride, respectively, in EXAMPLE 76A. 1 H-NMR (300 MHz, DMSO-d 6) 12.34 (s, 1H), 9.85 (s, 1H), 9.31 (s, 1H), 8.35 (s, 1H), 8.30 (s, 1H), 7.74 (ddd, 1H), 7.52-7.63 (m, 2H), 7.39 (dt, 1H), 7.22-7.34 (m, 1H), 6.53-6.68 (m, 1H), 4.71-4.87 (m, 1H), 4.04 (d, 2H), 3.71 (t, 2H), 3.35-3.54 (m, 3H), 3.07-3.28 (m, 2H), 2.26 (d, 2H), 2.08-2.20 (m, 4H), 1.69-1.86 (m, 2H). EXAMPLE 80 This example was prepared by substituting 2,4-dimethylaniline and 4-bromo-2-fluorobenzoyl chloride, for 3-nitroaniline and 5-bromo-2-fluorobenzoyl chloride, respectively, in EXAMPLE 76A ,. 1 H-NMR (300 MHz, DMSO-d 6) 12.47 (s, 1H), 9.67 (s, 2H), 8.81 (t, 1H), 8.31 (s, 1H), 8.29 (s, 1H), 8.03 (ddd, 1H), 7.51-7.72 (m, 4H), 4.71-4.86 (m, 1H), 4.05 (d, 2H), 3.69-3.76 (m, 2H), 3.39-3.48 (m, 3H), 3.12-3.25 ( m, 2H), 2.25 (ddd, 2H), 2.15 (t, 4H), 1.69-1.86 (m, 2H). EXAMPLE 81 This example was prepared by substituting 2,4-dimethylaniline and 4-bromo-2-fluorobenzoyl chloride for ortho-anisidine and 5-bromo-2-fluorobenzoyl chloride, respectively, in EXAMPLE 76A. 1 H-NMR (300 MHz, DMSO-d 6) 12.32 (s, 1H), 9.62 (s, 1H), 8.31 (s, 1H), 8.16 (s, 1H), 8.08 (dd, 1H), 7.79 (s, 1H), 7.60 (dd, 1H), 7.55 (d, 1H), 7.00 (dd, 1H), 6.90 (td, 1H), 6.82 (td, 1H), 4.70-4.87 (m, 1H), 4.04 (d , 2H), 3.90 (s, 3H), 3.63-3.75 (m, 2H), 3.44 (t, 3H), 3.16 (q, 2H), 2.19-2.31 (m, 2H), 2.15 (t, 4H), 1.66-1.86 (m, 2H). EXAMPLE 82 This example was prepared by substituting 2,4-dimethylaniline and 4-bromo-2-fluorobenzoyl chloride for 3-amino-6- (trifluoromethyl) pyridine and 5-bromo-2-fluorobenzoyl chloride, respectively, in EXAMPLE 76A. 1 H-NMR (300 MHz, DMSO-d 6) 12.55 (s, 1H), 9.85 (s, 1H), 9.61 (s, 1H), 8.92 (d, 1H), 8.42-8.49 (m, 1H), 8.30 ( s, 2H), 7.82 (d, 1H), 7.64 (dd, 1H), 7.59 (ddd, 1H), 4.79 (ddd, 1H), 4.04 (d, 2H), 3.65-3.75 (m, 2H), 3.46 (d, 3H), 3.12-3.25 (m, 2H), 2.20-2.30 (m, 2H), 2.08-2.20 (m, 4H), 1.69-1.85 (m, 2H). EXAMPLE 83 This example was prepared by substituting 2,4-dimethylaniline from EXAMPLE 76A for benzylamine. 1 H-NMR (300 MHz, DMSO-d 6) 11.64 (s, 1H), 9.62 (s, 2H), 9.31 (s, 1H), 8.93 (d, 1H), 7.39-7.48 (m, 3H), 7.28- 7.36 (m, 2H), 7.17-7.27 (m, 2H), 4.70-4.85 (m, 1H), 4.51 (s, 2H), 4.02 (d, 2H), 3.63-3.76 (m, 2H), 3.45 ( d, 3H), 3.08-3.24 (m, 2H), 2.19-2.30 (m, 2H), 2.09-2.19 (m, 4H), 1.65-1.85 (m, 2H). EXAMPLE 84 This example was prepared by substituting 2,4-dimethylaniline and 4-bromo-2-fluorobenzoyl chloride for 4- (trifluoromethyl) aniline and 5-bromo-2-fluorobenzoyl chloride, respectively, in EXAMPLE 76A. 1 H-NMR (300 MHz, DMSO-d 6) 12.43 (s, 1H), 9.72 (s, 2H), 9.52 (s, 1H), 8.30 (s, 1H), 8.29 (s, 1H), 7.86 (d, 2H), 7.57-7.65 (m, 4H), 4.72-4.86 (m, 1H), 4.04 (d, 2H), 3.64-3.78 (m, 2H), 3.39-3.47 (m, 3H), 3.08-3.26 ( m, 2H), 2.21-2.31 (m, 2H), 2.09-2.21 (m, 4H), 1.66-1.87 (m, 2H). EXAMPLE 85 This example was prepared by substituting 2,4-dimethylaniline and 4-bromo-2-fluorobenzoyl chloride for 4-tert-butylaniline and chloride of 5-bromo-2-fluorobenzoyl, respectively, in EXAMPLE 76A ,. 1 H-NMR (300 MHz, DMSO-d 6) 12.14 (s, 1 H), 9.68 (s, 1 H), 8.90 (s, 1 H), 8.31 (s, 1 H), 8.29 (s, 1 H), 7.60-7.68 ( m, 2H), 7.54-7.60 (m, 1H), 7.48-7.54 (m, 1H), 7.25-7.34 (m, 2H), 4.79 (dt, 1H), 4.04 (d, 2H), 3.64-3.76 ( m, 2H), 3.36-3.50 (m, 3H), 3.09-3.24 (m, 2H), 2.20-2.31 (m, 2H), 2.10-2.20 (m, 4H), 1.68-1.86 (m, 2H), 1.27 (s, 9H). EXAMPLE 86 This example was prepared by substituting 2,4-dimethylaniline and 4-bromo-2-fluorobenzoyl chloride, for 3-aminophenol and 5-bromo-2-fluorobenzoyl chloride, respectively, in EXAMPLE 76A. 1 H-NMR (300 MHz, DMSO-d 6) 12.16 (s, 1 H), 9.63 (s, 1 H), 9.16 (s, 1H), 8.85 (s, 1H), 8.28 (s, 2H), 7.54-7.62 (m, 1H), 7.48-7.54 (m, 1H), 7. 27-7.31 (m, 1H), 7.00-7.05 (m, 1H), 6.23 (dt, 1H), 4.70-4.85 (m, 1H), 4.04 (d, 2H), 3.70 (t, 2H), 3.40-3.45 (m, 3H), 3.10-3.25 (m, 2H), 2.19-2.30 (m, 2H), 2.09-2.20 (m, 4H), 1.64-1.86 (m, 2H). EXAMPLE 87 This example was prepared by substituting 2,4-dimethylaniline from EXAMPLE 76A for 2-fluoro-5-methylaniline. 1 H-NMR (300 MHz, DMSO-de) 12.34 (s, 1H), 9.63 (s, 1H), 8.44 (s, 1H), 8.31 (s, 1H), 8.14 (d, 1H), 7.93 (dd, 1H), 7.62 (s, 1H), 7.33 (dd, 1H), 7.08 (dd, 1H), 6.61-6.69 (m, 1H), 4.80 (dt, 1H), 4.04 (d, 2H), 3.63-3.80 (m, 2H), 3.46 (d, 3H), 3.08-3.26 (m, 2H), 2.26 (2, 2H), 2.10-2.25 (m, 4H), 1.67-1.86 (m, 2H). EXAMPLE 88 This example was prepared by substituting 2,4-dimethylaniline of EXAMPLE 76A, by 2,5-dimethylaniline. H NMR (300 MHz, DMSO-de) d 12.26 (s, 1H), 9.63 (s, 1H), 8.31 (s, 1H), 7.91 (d, 1H), 7.58-7.63 (m, 2H), 7.44 ( d, 1H), 7.31 (dd, 1H), 7.03 (d, 1H), 6.63 (dd, 1H), 4.80 (ddd, 1H), 451 (s, 2H), 4.04 (dd, 2H), 3.64-3.77 (m, 2H), 3.46 (d, 3H), 3.09-3.27 (m, 2H), 2.30 (s, 3H), 2.22-2.39 (m, 2H), 2.20 (s, 3H), 2.07-2.19 (m , 4H), 1.66-1.85 (m, 2H). EXAMPLE 89 This example was prepared by substituting 2,4-dimethylaniline from EXAMPLE 76A, for 2,5-difluoroaniline. 1 H-NMR (300 MHz, DMSO-d 6) 12.50 (s, 1 H), 9.63 (s, 1 H), 8.89 (s, 1 H), 8.31 (s, 1 H), 8.21 (d, 1 H), 8.06 (ddd, 1H), 7.64 (s, 1H), 7.36 (dd, 1H), 7.25 (ddd, 1H), 6.59-6.69 (m, 1H), 4.72-4.88 (m, 1H), 4.04 (d, 2H), 3.65 -3.76 (m, 2H), 3.46 (d, 3H), 3.08-3.25 (m, 2H), 2.25 (dd, 2H), 2.15 (t, 4H), 1.67-1.89 (m, 2H). EXAMPLE 90 This example was prepared by substituting 2,4-dimethylaniline from EXAMPLE 76A for 4-fluoro-2-methylaniline. 1 H-NMR (300 MHz, DMSO-de) 12.18 (s, 1H), 9.65 (s, 1H), 8.31 (s, 1H), 7.91 (d, 1H), 7.72 (s, 1H), 7.56-7.64 ( m, 2H), 7.30 (dd, 1H), 7.05 (dd, 1H), 6.94 (td, 1H), 4.71-4.89 (m, 1H), 4.04 (d, 2H), 3.69-3.84 (m, 2H) , 3.48 (m, 3H), 3.08-3.25 (m, 2H), 2.35 (s, 3H), 2.20-2.31 (m, 2H), 2.07-2.20 (m, 4H), 1.67-1.89 (m, 2H) . EXAMPLE 91A A mixture of 4-bromo-ortho-phenylenediamine (1 g) and sodium carbonate (0.28 g) in ethyl acetate (5.5 mL) was treated with 1,1-Dichloro-1,1-diphenoxymethane (1.44 g) in ethyl acetate (2.7 mL). The mixture was stirred for 5 hours and filtered. The filtrate was concentrated, and the concentrate was recrystallized from ethyl acetate / hexanes. EXAMPLE 91B This example was prepared by substituting 6-bromo-1H-indazol-3-yl- (2,4-dimethylphenyl) amine from EXAMPLE 76D for the product of EXAMPLE 91A. 1 H-NMR (300 MHz, DMSO-d 6) (s, 1 H), 9.65 (s, 1 H), 8.29 (s, 1 H), 7.60 (d, 1 H), 7.53 (d, 1 H), 7.46-7.52 (m , 3H), 7.38-7.44 (m, 3H), 7.31 (tt, 1H), 4.77 (ddd, 1H), 4.04 (d, 2H), 3.64-3.75 (m, 2H), 3.44 (t, 3H), 3.08-3.24 (m, 2H), 2.19-2.32 (m, 2H), 2.08-2.18 (m, 4H), 1.65-1.84 (m, 2H). EXAMPLE 92 3- (2-Benzyl-1H-benzimidazol-5-yl) -1- (1- (methylsulfonyl) piperidin-4-yl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 92A This compound was prepared by substituting the iodoacetamide of EXAMPLE 43C for methanesulfonyl chloride. EXAMPLE 92B This compound was prepared by substituting (cis) -4- (4- (4-amino-3-iodo-pyrazolo [3,4-d] pyrimidin-1-yl) -cyclohexyl) -1-methylpiperazin-2 one of EXAMPLE 2B, by the product of EXAMPLE 92A. EXAMPLE 92C This compound was prepared by substituting the product of EXAMPLE 43D in EXAMPLE 43E, by the product of EXAMPLE 92B. 1 H-NMR (300 MHz, DMSO-d 6) 8.31 (s, 1H), 7.91 (s, 1H), 7.85 (d, 1H), 7.72 (d, 1H), 7.43-7.33 (m, 5H), 4.89 ( m, 1H), 4.49 (s, 2H), 3.71 (m, 2H), 3.04 (m, 2H), 2.94 (s, 3H), 2.24 (m, 2H), 2.08 (m, 2H). EXAMPLE 93 (fraps) -3- (1- (2-chlorobenzyl) -1 H -indol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1H-pyrazolo [3,4-d] ] pyrimidin-4-amine EXAMPLE 93A The desired product was synthesized as described in EXAMPLES 63A and 63B, substituting 4-bromoindole in EXAMPLE 63A, for 5-bromoindole. H-NMR (300 MHz, DMSO-d6) 7.99 (s, 1H), 7.17-7.52 (m, 6H), 6.59 (m, 2H), 5.53 (s, 2H), 1.30 (s, 12H). EXAMPLE 93B Frans-3-iodo-1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] -pyrimidin-4-ylamine prepared as described in PCT Patent Application WO 2005/074603, 224 mg, 0.5 mmol), the product of EXAMPLE 93A (220 mg, 0.5 mmol), sodium carbonate (106 mg, 1 mmol) and Pd (PPh3) (34 mg) were placed in a microwave tube and 4 mL of DME / water (1: 1) was added. It was heated in a microwave oven at 130 ° C for 20 minutes. After being partitioned in ethyl acetate and brine, the ethyl acetate phase was washed with brine (3x), dried and purified by HPLC to obtain 360 mg of the title compound. 1H-NMR (300 MHz, DMSO-de) 9.67 (br s, 1H), 8.33 (s, 1H), 7.88 (brs, 1H), 7.25-7.43 (m, 3H), 7.46 (dd, 1H), 7.23-7.36 (m, 2H), 6.79 (dd, 1H), 6. 66 (d, 1H), 5.59 (s, 2H), 4.78 (br m, 1H), 4.04 (br d, 2H), 3.70 (br t, 2H), 3.46 (s, 3H), 3.17 (br m, 2H), 2.24 (m, 2H), 2.08-2.17 (br m, 4H), 1.66-1.84 (br m, 2H). EXAMPLE 94 (frans) -3- (1- (2-chlorobenzyl) -1H-indazol-6-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4-d] ] pirim idin-4-a mine EXAMPLE 94A The desired product was synthesized by substituting the 2-chlorobenzyl bromide in EXAMPLE 121B, for 3-fluorobenzyl bromide. EXAMPLE 94B The desired product was synthesized by substituting the product of EXAMPLE 121B in EXAMPLE 121C, for the product of EXAMPLE 94A. 1 H-NMR (300 MHz, DMSO-d 6) 9.76 (br s, 1 H), 8.38 (s, 1 H), 8.27 (s, 1 H), 8.05 (d, 1 H), 7.93 (d, 1 H), 7.69 (dd) , 1H), 7.35-7.42 (m, 1H), 7.08-7.14 (m, 3H), 5.76 (s, 2H), 4.80 (m, 1H), 3.98-4.09 (m, 2H), 3.64-3.76 (br t, 2H), 3.35-3.50 (m, 3H), 3.08-3.24 (m, 2H), 2.19-2.30 (m, 2H), 2.06-2.17 (br m, 4H), 1.68-1.83 (br m, 2H ). EXAMPLE 95 3- (2-Benzyl-1 H-benzimidazol-6-yl) -1- (2-morpholin-4-yl-ethyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 95A This compound was prepared by substituting 3-hydroxy-pyrrolidine-1-carboxylic acid ferf-butylester in EXAMPLE 52A for N- (2-hydroxyethyl) morpholine. 1 H-NMR (400 MHz, DMSO-d 6) 8.20 (s, 1H), 4. 38 (t, 2H), 3.47 (m, 4H), 2.72 (t, 2H), 2.40 (m, 4H). EXAMPLE 95B 3- (2-Benzyl-1H-benzimidazol-6-yl) -1- (2-morpholin-4-yl-ethyl) -1H-pyrazolo [3,4-d] pyrimidin-4-mine The product of the EXAMPLE 95A (93 mg, 0.25 mmol), that of EXAMPLE 188C (85 mg, 0.15 mmol) and CsF (113 mg, 0.75 mmol), were mixed with DME (3 mL) and MeOH (2 mL). The mixture was purged with argon and Pd (PPh3) 4 (15 mg) was added. The sealed container was heated at 150 ° C for 5 minutes in a Personal Chemistry microwave instrument. Water (10 mL) was added to the reaction mixture, and the mixture was subsequently extracted with EtOAc. The EtOAc solution was dried, filtered and concentrated. The residue was taken up in 1N HCl (20 mL) and washed with EtOAc. The aqueous solution was subsequently neutralized to pH -13 with an aqueous solution of NaOH; it was then extracted with EtOAc. The EtOAc solution was dried, filtered and evaporated to obtain the title compound as a white solid. 1 H-NMR (400 MHz, DMSO-de) 12.45 (s, 1H), 8.23 (s, 1H), 7.66 (d, 1H), 7.44 (d, 1H), 7.29-7.36 (m, 6H), 4.45 ( t, 2H), 4.20 (s, 2H), 3.49 (m, 4H), 2.80 (t, 2H), 2.44 (m, 4H). EXAMPLE 96 3- (2-Benzyl-1H-benzimidazol-6-yl) -1- (1-pyrimidin-2-yl-piperidin-4-yl) -1H-pyrazolo [3,4-d] pyrimidin-4- amine EXAMPLE 96A This compound was prepared by substituting the ferf-butylester of 3-hydroxy-pyrrolidine-1-carboxylic acid of EXAMPLE 52A by N- (2-pyrimidinyl) -4-hydroxypiperidine. 1 H-NMR (400 MHz, DMSO-d 6) 8.38 (d, 2H), 8.20 (s, 1H), 6.65 (t, 1H), 4.96 (m, 1H), 4.77 (m, 2H), 3.14 (m, 2H), 1.94-1.99 (m, 4H). EXAMPLE 96B 3- (2-Benzyl-1H-benzimidazol-6-yl) -1- (1-pyrimidin-2-yl-piperidin-4-yl) -1H-pyrazolo [3,4-d] pyrimidin-4- amine The product of EXAMPLE 96A 105 mg, 0.25 mmol), that of EXAMPLE 188C (85 mg, 0.15 mmol) and CsF (113 mg, 0.75 mmol), were mixed with DME (3 mL) and MeOH (2 mL). The mixture was purged with argon and Pd (PPh3) (15 mg) was added. The sealed container was heated to 150 ° C for 5 minutes in a microwave instrument Personal Chemistry. The reaction mixture was subjected to processing in an aqueous medium and the crude product was purified by reverse phase HPLC, using a TFA buffer as a mobile phase, obtaining the TFA salt of the title compound as a white solid. . 111 mg, 85% yield. 1 H-NMR (400 MHz, DMSO-d 6) 8.42 (s, 1 H), 8.40 (d, 2 H), 7.94 (s, 1 H), 7. 87 (d, 1H), 7.75 (dd, 1H), 7.40-7.45 (m, 5H), 5.09-5.15 (m, 1H), 4.82 (m, 2H), 3.16-3.23 (m, 2H), 2.05- 2.11 (m, 4H). EXAMPLE 97 (frans) -3- (2- (2,3-difluorobenzyl) -1H-benzimidazol-6-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1H-pyrazolo [3,4-] d] pyrimidin-4-amine This example was prepared as described in EXAMPLE 7, substituting the benzaldehyde of EXAMPLE 7B, for 2,3- difluorophenylacetaldehyde. 1 H-NMR (400 MHz, DMSO) (s, 1H), 8.23 (s, 1H), 7.67-7.19 (m, 8H), 4.65 (m, 1H), 4.32 (s, 2H), 3.60 (bs, 4H ), 2.51 (bs, 4H), 2.00 (m, 7H), 1.50 (m, 2H). EXAMPLE 98 (frans) -3- (2- [3,4-difluorobenzyl] -1H-benzimidazol-6-yl) -1- (4-morpholin-4-yl-cyclohexy I) - 1 H-pyrazolo [ 3, 4-d] pyrimidin-4-a-mine This example was prepared as described in EXAMPLE 7, substituting the benzaldehyde of EXAMPLE 7B, for 3,4-difluorophenylacetaldehyde. MS ((+) - IEA) 545.3 m / z (M + H) 0 H-NMR (400 MHz, DMSO) (s, 1H), 8.22 (s, 1H), 7.49-7.21 (m, 8H), 4.65 (m, 1H), 4.24 (s, 2H), 3.58 (bs, 4H), 1.99 (m, 7H), 1.47 (m, 2H). EXAMPLE 99 (frans) -3- (2- (3,5-difluorobenzyl) -1 H -benzimidazol-6-yl) -1- (4-morphol n-4-yl-cyclohexyl) -1 H-pyrazolo [ 3,4-d] pyrimidin-4-amine This example was prepared as described in the EXAMPLE 7, substituting the benzaldehyde of EXAMPLE 7B, for 3,5-difluorophenylacetaldehyde. MS ((+) - IEA) 545.4 m / z (M + H) J 1 H-NMR (400 MHz, DMSO) (bs, 1H), 8.23 (s, 1H), 7.72-7.10 (m, 8H), 4.65 (m, 1H), 4.28 (s, 2H), 3.58 (bs, 4H), 2.00 (m, 7H), 1.47 (m, 2H). EXAMPLE 100 (fra / 7s) -3- (2-benzyl-1H-benzimidazol-5-yl) -1- (4-. {(2- (methylsulfonyl) ethyl) amino.} Cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine This example was prepared by substituting the 3-hydroxypyrrolidine of EXAMPLE 31C for 2- (methanesulfonyl) ethylamine. It was isolated isomer that eluted first. MS (ESI) m / e 545 (M + H) J 1 H-NMR (300 MHz, DMSO-de) d 8.74 (bs, 2H), 8.29 (s, 1H), 7.85 (s, 1H), 7.81 (d, 1H), 7.64 (d, 1H), 7.41-7.33 (m, 5H), 4.76 (m, 1H), 4.44 (s, 2H) ), 3.51 (m, 2H), 3.42 (m, 2H), 3.32 (m, 1H), 3.16 (s, 3H), 2.22 (m, 2H), 2.10 (m, 4H), 1.64 (m, 2H) . EXAMPLE 101 (c / s) -3- (2-Benzyl-1H-benzimidazol-5-yl) -1- (4-. {(2- (methylsulfonyl) ethyl) amino.}. Cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine This compound was obtained as the slowest eluting diastereomer of EXAMPLE 100. MS (ESI) m / e 545 (M + H) J 1 H-NMR (300 MHz, DMSO- d6) d 8.61 (bs, 2H), 8.29 (s, 1H), 7.86 (s, 1H), 7.78 (d, 1H), 7.64 (d, 1H), 7.40-7.32 (m, 5H), 4.90 (m , 1H), 4.39 (s, 2H), 3.50 (m, 2H), 3.41 (m, 3H), 3.13 (s, 3H), 2.33 (m, 3H), 1.98 (m, 5H). EXAMPLE 102 3- (2-Benzyl-1H-benzimidazol-5-yl) -1- (4- (1,1-dioxidothomorpholin-4-yl) cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidin-4 -amine This example was prepared as a mixture of diastereoisomers, substituting the 3-hydroxypyrrolidine of EXAMPLE 31C for dioxothiomorpholine. MS (ESI) m / e 557 (M + H) J 1 H-NMR (300 MHz, DMSO-de) d 8.32 (s, 1 H), 7.91 (s, 1 H), 7.86 (m, 1 H), 7.71 (m , 1H), 7.43-7.33 (m, 5H), 4.95 and 4.73 (m, 1H), 4.49 (s, 2H), 3.37 (m, 9H), 2.32 (m, 2H), 2.07 (m, 3H), 1.85-1.71 (m, 3H).

EXAMPLE 103 3- (2-Benzyl-1H-benzimidazol-5-yl) -1- (4- (. {(2- (methylsulfonyl) ethyl) amino} methyl) phenyl) -1H-pyrazolo [3, 4-d] pyrimidin-4-amine EXAMPLE 103A This example was prepared by substituting the morpholine of EXAMPLE 48B for 2- (methanesulfonyl) ethylamine. EXAMPLE 103B This example was prepared by substituting (c / s) -4- (4- (4-amino-3-iodo-pyrazolo [3,4-d] pyrimidin-1-yl) -cyclohexyl) -1-methylpiperazine- 2-one of EXAMPLE 2B, by the product of EXAMPLE 103A. EXAMPLE 103C This example was prepared by substituting the product of EXAMPLE 48C in EXAMPLE 48D, by the product of EXAMPLE 103B. MS (ESI) m / e 553 (M + H) J 1 H-NMR (300 MHz, DMSO-dβ) d 9.06 (bs, 2H), 8.41 (s, 1H), 8.36 (d, 2H), 7.95 (s) , 1H), 7.82 (d, 1H), 7.71 (m, 3H), 7.41-7.33 (m, 5H), 4.42 (s, 2H), 4.30 (m, 2H), 3.43 (m, 4H), 3.15 ( s, 3H). EXAMPLE 104 (frans) -2- (4- (4-. {4-amino-3- (2- (2-fluorobenzyl) -1H-benzimidazol-5-yl) -1H-pyrazolo [3,4-d] ] pyrimidin-1-yl}. cyclohexyl) piperazin-1-yl) ethanol EXAMPLE 104 A This example was prepared by substituting the product of EXAMPLE 7A and benzaldehyde for the product of EXAMPLE 31A and 2-fluorophenylacetaldehyde, respectively, in EXAMPLE 7B. EXAMPLE 104B This example was prepared by substituting the product of the EXAMPLE 31B and 3-hydroxypyrrolidine, by the product of EXAMPLE 104A and 1- (2-hydroxyethyl) piperazine, respectively, in the EXAMPLE 31C. The diastereomer that eluted faster was isolated.

MS (ESI) m / e 570 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 8.30 (s, 1H), 7.82 (s, 1H), 7.76 (d, 1H), 7.60 (d, 1H), 7.49 (m, 1H), 7.39 (m, 1H), 7.26 (m, 2H), 4.77 (m, 1H), 4.45 (s, 2H), 3.71-3.61 (m, 8H), 3.11 (m, 5H), 2.11 (m, 6H), 1.70 (m , 2H). EXAMPLE 105 (c / s) -2- (4- (4- { 4-amino-3- (2- (2-fluorobenzyl) -1H-benzimidazol-5-yl) -1H-pyrazolo [3,4 -d] pyrimidin-1-yl.} cyclohexyl) piperazin-1-yl) ethanol This example is the isomer that eluted slower in EXAMPLE 104. MS (IEA) m / e 570 (M + H) J 1 H- NMR (300 MHz, DMSO-de) d 8.30 (s, 1H), 7.81 (s, 1H), 7.74 (d, 1H), 7.58 (d, 1H), 7.47 (m, 1H), 7.39 (m, 1H) ), 7.25 (m, 2H), 4.91 (m, 1H), 4.41 (s, 2H), 3.71-3.56 (m, 8H), 3.10 (m, 5H), 2.35 (m, 2H), 2.07 (m, 3H), 1.85 (m, 3H). EXAMPLE 106 (frans) -3- (2- (2-Chloro-3-fluorophenyl) -1H-benzimidazol-6-yl) -1- (4-morphol-n-4-I-cyclohexy I) - 1 H-pyrazolo [3,4-d] pyrimidin-4-amine This example was prepared as described in EXAMPLE 7, substituting the benzaldehyde of EXAMPLE 7B, for 2-chloro-3-fluorobenzaldehyde. IEA (+) m / e 547 (M + H) 0 1 H-NMR (300 MHz, DMSO-d 6) 12.98 (bs, 1H), 8.24 (s, 1H), 7.88-7.85 (bm, 1H), 7.83- 7.78 (m, 2H), 7.63-7.54 (m, 3H), 4.67 (m, 1H), 3.60-3.57 (bm, 5H), 2.45-2.34 (m, 2H), 2.09-1.96 (m, 8H), 1.53 -1.44 (m, 2H). EXAMPLE 107 (frans) -1- (4-morpholin-4-yl-cyclohexyl) -3-. { 2- (3- (trifluoromethyl) benzyl) -1H-benzimidazol-6-yl} -1 H-pyrazolo [3,4-d] pyrimidin-4-amine This example was prepared as described in EXAMPLE 7, substituting the benzaldehyde of EXAMPLE 7B, for 2- (3- (trifluoromethyl) phenyl) acetaldehyde. (ESI (+)) m / e 577 (M + H) 0 1 H-NMR (300 MHz, DMSO-de) 12.52 (s, 1H), 8.22 (s, 1H), 7.76 (s, 1H), 7.70- 7.56 (m, 5H), 7.43 (d, 1H), 4.65 (m, 1H), 4.35 (s, 2H), 3.57 (m, 4H), 2.43-2.31 (m, 2H), 2.08-195 (m, 7H), 1.50-1.41 (m, 2H). EXAMPLE 108 N-. { 4- (4-amino-3- (2-benzyl-1H-benzimidazol-5-yl) -1H-pyrazolo [3,4- d] pyrimidin-1-yl) cyclohexyl} methanesulfonamide EXAMPLE 108A This compound was prepared by substituting the product of EXAMPLE 31B for the product of EXAMPLE 31A and the 3-hydroxypyrrolidine of EXAMPLE 31C by ammonium acetate. MS (ESI) m / e 359 (M + H); 1 H-NMR (300 MHz, DMSO-d 6) 8.21 (s, 1 H), 7.84 (m, 4 H), 4.74 and 4.60 (m, 1 H), 3.36 and 3.17 (m, 1 H), 2.23 (m, 1 H), 2.02 (m, 4H), 1.87 (m, 2H), 1.54 (m, 1H). EXAMPLE 108B This compound was prepared by substituting the product of EXAMPLE 43B in EXAMPLE 72A, by the product of EXAMPLE 108A. MS (ESI) m / e 437 (M + H); 1 H-NMR (300 MHz, DMSO-d 6) 8.19 (s, 1H), 7.08 (m, 1H), 4.68 - 4.52 (m, 1H), 3.35 and 3.25 (m, 1H), 2.93 and 2.94 (s, 3H), 2.25 (m, 1H), 2.02 (m , 2H), 1.91 (m, 2H), 1.72 (m, 1H), 1.46 (m, 1H), 1.16 (m, 1H). EXAMPLE 108C This example was prepared by substituting the product of the EXAMPLE 63B by the product of EXAMPLE 188C and (c / s) -3-iodo-1- (4-morphol in -4-i I-cyclohexy I) -1 H -pyrazolo [3,4-d] pyrimidine 4-yl-amine by the product of EXAMPLE 108B, respectively, in EXAMPLE 63C. MS (ESI) m / e 517 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 8.30 (s, 1 H), 7.89 (s, 1 H), 7.84 (d, 1 H), 7.70 (d , 1H), 7.43-7.33 (m, 5H), 7.11 (d, 1H), 4.68 (m, 1H), 4.48 (s, 2H), 3.17 (m, 1H), 2.95 (s, 3H), 2.15- 1.95 (m, 6H), 1.51 (m, 2H). EXAMPLE 109 4- (4-amino-3- (2-benzyl-1 H-benzimidazol-5-yl) -1 H-pyrazolo [3,4- d] pyrimidin-1-yl) cyclohexylcarbamate ethyl EXAMPLE 109 A This compound was prepared by substituting the product of EXAMPLE 43B for the product of EXAMPLE 108A and methanesulfonyl chloride for ethyl chloroformate, in EXAMPLE 72A. EXAMPLE 109B This example was prepared by substituting the product of the EXAMPLE 63B by the product of EXAMPLE 188C and the (c / 's) -3-iodo-1- (4-morpholin-4-yl) -cyclohexyl) -1 H-pi razo [3,4-d] pirim id in-4-i I-amine by the product of EXAMPLE 109A, respectively, in EXAMPLE 63C. MS (ESI) m / e 511 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 8.30 (s, 1H), 7.90 (s, 1H), 7.84 (d, 1H), 7.71 (m, 2H), 7.42-7.33 (m, 5H), 4.71 (m, 1H), 4.49 (s, 2H), 3.98 (m, 2H), 2.0 (m, 5H), 1.78 (m, 2H), 1.40 (m, 1H), 1.15 (m, 3H). EXAMPLE 110 3- (2-Benzyl-1H-benzimidazol-5-yl) -1-. { - (2- (methylsulfonyl) ethyl) pyrrolidin-3-yl} 1H-pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 110A This compound was prepared by substituting the iodoacetamide of EXAMPLE 52C for methylvinylsulfone. MS (ESI) m / e 437 (M + H); 1 H-NMR (300 MHz, DMSO-d 6) d 8.20 (s, 1 H), 5.31 (m, 1 H), 3.28 (m, 2 H), 3.06 (s, 3 H), 2.98 (m, 1 H), 2.85 (m , 4H), 2.68 (m, 1H), 2.34-2.19 (m, 2H). EXAMPLE 110B This compound was prepared by substituting (c / s) -4- (4- (4-amino-3-iodo-pyrazolo [3,4-d] pyrimidin-1-yl) -cyclohexyl) -1-methylpiperazine- 2-one of EXAMPLE 2B, by the product of EXAMPLE 110A. EXAMPLE 110C This compound was prepared by substituting the product of EXAMPLE 52D in EXAMPLE 52E, by the product of EXAMPLE 110B. MS (ESI) m / e 517 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 8.32 (s, 1 H), 7.89 (s, 1 H), 7.84 (d, 1 H), 7.68 (d , 2H), 7.40-7.31 (m, 5H), 5.71 (m, 1H), 4.42 (s, 2H), 3.71-3.43 (m, 8H), 3.12 (s, 3H), 2.57 (m, 2H).

EXAMPLE 111 3- (2- (2-Fluorobenzyl) -1H-benzimidazol-5-yl) -1-. { - (2- (methylsulfonyl) ethyl) pyrrole id in-3-il} 1H-pyrazolo [3,4-d] pyrimidin-4-amine This compound was prepared by substituting the phenylacetaldehyde of EXAMPLE 52E for 2-fluorophenylacetaldehyde and the product of EXAMPLE 52D, by the product of EXAMPLE 110B. MS (ESI) m / e 535 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 8.32 (s, 1 H), 7.85 (s, 1 H), 7.75 (d, 1 H), 7.63 (d , 2H), 7.48 (m, 1H), 7.40 (m, 1H), 7.25 (m, 2H), 5.72 (m, 1H), 4.42 (s, 2H), 3.70-3.51 (m, 8H), 3.12 ( s, 3H), 2.57 (m, 2H). EXAMPLE 112 (frans) -3- (2-Benzyl-1H-benzimidazol-5-yl) -1-. { - (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl} 1H-pyrazolo [3,4-d] pyrimidin-4-amine This example was the fastest eluting diastereomer prepared as described in EXAMPLE 31, substituting the 3-hydroxypyrrolidine of EXAMPLE 31C for 4- (3-methoxypropyl) piperazine . MS (ESI) m / e 580 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 8.28 (s, 1 H), 7.84 (s, 1 H), 7.79 (d, 1 H), 7.64 (d , 1H), 7.41-7.33 (m, 5H), 4.75 (m, 1H), 4.43 (s, 2H), 3.52-3.36 (m, 6H), 3.25 (s, 3H), 2.98-2.85 (m, 6H) ), 2.09 (m, 6H), 1.83 (m, 2H), 1.66 (m, 2H). EXAMPLE 113 (c / s) -3- (2-Benzyl-1H-benzimidazol-5-yl) -1-. { - (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl} 1H-pyrazolo [3,4-d] pyrimidin-4-amine This example was the diastereomer that eluted slower from EXAMPLE 112. MS (ESI) m / e 580 (M + H) J 1 H-NMR (300 MHz, DMSO-de) d 8.30 (s, 1H), 7.86 (s, 1H), 7.80 (d, 1H), 7.65 (d, 1H), 7. 41-7.33 (m, 5H), 4.90 (m, 1H), 4.43 (s, 2H), 3.52-3.36 (m, 6H), 3.23 (s, 3H), 2.98-2.85 (m, 6H), 2.34 ( m, 2H), 2.07 (m, 3H), 1.84 (m, 5H). EXAMPLE 114 (f? Ar? S) -3- (1-benzyl-1 H-indol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4- d] pyrimidin-4-amine EXAMPLE 114A The desired product was synthesized by substituting the 2-fluorobenzyl bromide of EXAMPLE 210A for the benzyl bromide. EXAMPLE 114B fra? S-3-iodo-1- (4-morpholin-4-yl-cyclohexyl) -1H-pyrazolo [3,4-d] -pyrimidin-4-yl-amine prepared in the manner described in PCT Patent Application WO 2005/074603, 112 mg, 0.25 mmol), the product of EXAMPLE 114A (126 mg, 0.3 mmol), sodium carbonate (53 mg, 0.5 mmol) and Pd (PPh3) 4 (17 mg, 0.0007 mmol) were placed in a microwave tube and 2 mL of DME / water (1: 1) were added. It was heated in a microwave oven at 130 ° C for 20 minutes.

Then it was extracted by partition in ethyl acetate and brine; the ethyl acetate phase was washed with brine (3x), dried and purified by HPLC. 60 mg of the title compound were obtained. MS ESI (+) m / e 508.3 (M + H) J 1 H-NMR (300 MHz, DMSO-dβ) 9.60 (br s, 1H), 8.28 (s, 1H), 7.83 (br s, 1H), 7.62 -7.66 (m, 2H), 7.25- 7. 41 (m, 6H), 6.62 (d, 1H), 5.59 (s, 2H), 4.76 (br m, 1H), 4.03 (br d, 2H), 3.46 (br m, 2H), 3.07-3.24 (m , 3H), 2.19-2.29) m, 2H), 2.06-2.17 (br m, 4H), 1.66-1.83 (br m, 2H). EXAMPLE 115 (frans) -3- (1- (2-methylbenzyl) -1H-indol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 115A The desired product was synthesized by substituting the 2-fluorobenzyl bromide of EXAMPLE 210A, for 2-methylbenzyl bromide. EXAMPLE 115B The desired product was synthesized by substituting the product of EXAMPLE 114A in EXAMPLE 114B, by the product of EXAMPLE 115A. ESMS (+) m / e 522.4 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) 9.68 (br s, 1H), 8.30 (s, 1H), 7.54-7.67 (m, 3H), 7.45 (d, 1H), 7.40 (dd, 1H), 7.15-7.26 (m, 2H), 7.10 (t, 1H), 6.65 (d, 1H), 6.61 (d, 1H), 5.44 (s, 2H) , 4.78 (br m, 1H), 4.04 (br d, 2H) 3.70 (br m, 2H), 3.45 (m, 3H), 3.16 (br, 2H), 2.36 (s, 3H), 2.19-2.30 (m ,), 2.08-2.19 (br m, 4H), 1.69-1.84 (br m, 2H). EXAMPLE 116 (fra? S) -3- (1- (3-methylbenzyl) -1H-indol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1H-pyrazolo [3,4 -d] pyrimidin-4-amine EXAMPLE 116A The desired product was synthesized by substituting the 2-fluorobenzyl bromide of EXAMPLE 210A, for 3-bromide. methylbenzyl. EXAMPLE 116B The desired product was synthesized by substituting the product of EXAMPLE 114A in EXAMPLE 114B by the product of EXAMPLE 116A. MS: ESI (+) m / e 522.4 (M + H) J 1 H-NMR (300 MHz, DMSO-de) 9.69 (br s, 1H), 8.30 (s, 1H), 7.84 (br s, 1H), 7.61-7.66 (m, 2H), 7.40 (m, 1H), 7.21 (t, 1H), 7.03-7.12 (m, 3H), 6.62 (d, 1H), 5.44 (s, 2H), 4.76 (br m , 1H), 4.04 (br d, 2H), 3.70 (br m, 2H), 3.09-3.24 (m, 3H), 2.19-2.30 (m, 5H includes = 2.26, s, 3H), 2.08-2.18 (br m, 4H), 1.69-1.85 (br m, 2H). EXAMPLE 117 (fraps) -3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4-d] ] pyrimidin-4-amine The desired product was synthesized by substituting the product of EXAMPLE 114A in EXAMPLE 114B, by the product of EXAMPLE 210A. MS: ESI (+) m / e 526.4 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) 9.61 (br s, 1 H), 8.29 (s, 1 H), 7.84 (d, 1 H), 7.67. (d, 1H), 7.58 (d, 1H), 7.42 (dd, 1H), 7.31-7.37 (m, 1H), 7.24 (m, 1H), 7.13-7.16 (m, 2H), 6.62 (d, 1H) ), 5.54 (s, 2H), 4.76 (br m, 1H), 4.04 (br d, 2H), 3.69 (br m, 2H), 3.09-3.25 (br, 2H), 2.36 (s, 3H), 2.19 -2.29 (m,), 2.07-2.17 (br m, 4H), 1.67-1.83 (br m, 2H). EXAMPLE 118 (f? A ?? s) -3- (1- (3-fluorobenzyl) -1H-indol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1H-pyrazolo [3 , 4-d] pyrimidin-4-amine EXAMPLE 118A The desired product was synthesized by substituting the 2-fluorobenzyl bromide of EXAMPLE 210A for 3-fluorobenzyl bromide. EXAMPLE 118B The desired product was synthesized by substituting the product of EXAMPLE 114A in EXAMPLE 114B, by the product of EXAMPLE 118A. MS: ESI (+) m / e 526.3 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) 9.66 (br s, 1H), 8.30 (s, 1H), 7.85 (d, 1H), 7.63 -7.67 (m, 2H), 7.34-7.43 (m, 2H), 7.21 (t, 1H), 7.06-7.13 (m, 3H), 6.64 (d, 1H), 5.52 (s, 2H), 4.76 (br m, 1H), 4.04 (br d, 2H), 3.69 (br m, 2H), 3.08-3.24 (m, 3H), 2.19-2.30 (m, 2H), 2.07-2.18 (br m, 4H), 1.67 -1.84 (br m, 2H). EXAMPLE 119 (trans) -1- (4-morpholin-4-yl-cyclohexyl) -3-. { 1- (2- (trifluoromethyl) benz I) - 1 H- indol-5-yl} -1H-pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 119A The desired product was synthesized by substituting the 2-fluorobenzyl bromide of EXAMPLE 210A for 3-fluorobenzyl bromide. EXAMPLE 119B The desired product was synthesized by substituting the product of EXAMPLE 114A in EXAMPLE 114B, by the product of the EXAMPLE 119A. MS: IEA (+) m / e 576.3 (M + H) +; 1 H-NMR (300 MHz, DMSO-de) 9.66 (br s, 1H), 8.31 (s, 1H), 7.90 (s, 1H), 7.82-7.85 (m, 1H), 7.59 (d, 1H), 7.51-7.54 (m, 2H), 7.24 (s, 2H), 6.71 (d, 1H), 6.59 (d, 1H), 5.71 (s, 2H), 4.77 (br m, 1H), 4.04 (br d, 2H), 3.69 (br m, 2H), 3.36-3.51 (m, 3H), 3.08-3.24 (m, 2H), 2.19-2.29 (m, 2H), 2.07- 2.17 (br m, 4H), 1.69-1.83 (br m, 2H). EXAMPLE 120 (trans) -3- (1 - (2-f luorobenzyl) -1 H -indazol-5-yl) -1 - (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4 -d] pyrimidin-4-amine EXAMPLE 120 A The desired product was synthesized by substituting the 2-chlorobenzyl bromide of EXAMPLE 121B, for 2-fluorobenzyl bromide. EXAMPLE 120B The desired product was synthesized by substituting the product of EXAMPLE 121B in EXAMPLE 121C, by the product of EXAMPLE 120A. MS: IEA (+) m / e 527.4 (M + H) J IEA (+) m / e 525.6 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 9.69 (br s, 1 H), 8.33 (s, 1 H), 8.24 (s, 1H), 8.03 (d, 1H), 7.89 (d, 1H), 7.70 (dd, 1H), 7.55-7.66 (m, 1H), 7. 34-7.41 (m, 1H), 6.93 (dd, 1H), 5.77 (s, 2H), 4.79 (m, 1H), 3.35- 3.50 (m, 4H), 3.07-3.24 (m, 2H), 2.19- 2.30 (m, 2H), 2.06-2.17 (br m, 4H), 1.68-1.83 (br m, 2H). EXAMPLE 121 (frans) -3- (1- (2-chlorobenzyl) -1H-indazol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4-d] ] pyrimidin-4-amine EXAMPLE 121A A solution of 5-bromo-1 H-indazole (1.00 g, 5.08 mmol), bis (pinacolato) diboro (3.87 g, 15.24 mmol), potassium acetate (KOAc, 2.49 g, 25.40 mmol) and PdCI2 (dppf) (112 mg, 0.152 mmol) in 20 mL of DMF, was stirred at 100 ° C for 16 hours. EtOAc was added and the organic phase was washed with brine (x4) and dried over MgSO4. After evaporating to dryness, the residue was purified on a column of silica gel, eluting with 10% EtOAc in hexane, to obtain 1.2 g. MS: IQD (+) m / e 245.0 (M + H) J m / e 262.1 (M + NH 4) 0 EXAMPLE 121B The product of EXAMPLE 121A (122 mg, 0.5 mmol) and potassium carbonate (415 mg, 3 mmol ), were added to 10 mL of acetone. 2-Chlorobenzyl bromide (130 mL, 1 mmol) was added, and the mixture was stirred at 60 ° C for 3 days. After filtration, the filtrate was concentrated in vacuo and the residue was dried. EXAMPLE 121C The desired product was synthesized by substituting the product of EXAMPLE 114 a in EXAMPLE 114B for the product of EXAMPLE 121 B. MS: IEA (+) m / e 543.3 (M + H) 0 1 H-NMR (300 MHz, DMSO -de) 9.69 (br s, 1H), 8.34 (s, 1H), 8.28 (s, 1H), 8.05 (d, 1H), 7.87 (d, 1H), 7.70 (dd, 1H), 7.52 (dd, 1H), 7.25-7.38 (m, 2H), 6.93 (dd, 1H), 5.81 (s, 2H), 4.79 (m, 1H), 3.64-3.77 (br t, 4H), 3.35-3.50 (m, 4H) ), 3.07-3.24 (m, 2H), 2.19-2.30 (m, 2H), 2.06-2.17 (br m, 4H), 1.67-1.83 (br m, 2H). EXAMPLE 122 (frans) -3- (1- (3-chlorobenzyl) -1H-indazol-5-yl) -1- (4-morpholin-4-yl- cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine 'EXAMPLE 122A The desired product was synthesized by substituting the 2-chlorobenzyl bromide of EXAMPLE 121B, for 3-chlorobenzyl bromide. EXAMPLE 122B The desired product was synthesized by substituting the product of EXAMPLE 121B in EXAMPLE 121C, by the product of EXAMPLE 122A. MS: IEA (+) m / e 543.3 (M + H) +; IEA (-) m / e 541.5 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 9.70 (br s, 1 H), 8.35 (s, 1 H), 8.27 (s, 1 H), 8.04 (d, 1 H), 7.94 (d, 1 H), 7.69 (dd) , 1H), 7.36-7.37 (m, 3H), 7.22-7.27 (m, 1H), 5.75 (s, 2H), 4.79 (m, 1H), 4.00-4.09 (m, 2H), 3.64-3.76 (br t, 2H), 3.35-3.50 (m, 3H), 3.08-3.24 (m, 2H), 2.19-2.30 (m, 2H), 2.06-2.17 (br m, 4H), 1.68-1.83 (br m, 2H ). EXAMPLE 123 (frar? S) -3- (1-benzyl-1 H-indazol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H- pi-reason [3, 4-d] ] pyrim id-n-4-amine EXAMPLE 123A The desired product was synthesized by substituting the 2-chlorobenzyl bromide of EXAMPLE 121B for benzyl bromide. EXAMPLE 123B The desired product was synthesized by substituting the product of EXAMPLE 121 B in EXAMPLE 121C, by the product of EXAMPLE 123A. MS: IEA (+) m / e 509.3 (M + H) 0 IEA (+) m / e 507.5 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 9.64 (br s, 1 H), 8.32 (s, 1 H), 8.24 (s, 1 H), 8.03 (d, 1 H), 7.90 (d, 1 H), 7.68 (dd) , 1H), 7.55-7.64 (m, 1H), 7. 21-7.36 (m, 4H), 5.72 (s, 2H), 4.79 (m, 1H), 4.00-4.08 (m, 2H), 3.37-3.50 (m, 3H), 3.10-3.24 (m, 2H), 2.19-2.30 (m, 2H), 2.06-2.17 (br m, 4H), 1.68-1.83 (br m, 2H). EXAMPLE 124 3- (2-benzyl 1-1 H-benzimidazol-5-yl) -1-. { 1- (2- (methylsulfonyl) ethyl) piperidin-4-yl} -1 H-pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 124A This compound was prepared by substituting the iodoacetamide of EXAMPLE 43C for methylvinylsulfone. MS (ESI) m / e 451 (M + H); 1 H-NMR (300 MHz, DMSO-d 6) d 8.19 (s, 1 H), 4.60 (m, 1 H), 3.28 (m, 2 H), 3.06 (s, 3 H), 3.01 (m, 2 H), 2.76 (t , 2H), 2.21-2.02 (m, 4H), 1.86 (m, 2H). EXAMPLE 124B This compound was prepared by substituting (c / 's) -4- (4- (4-amino-3-iodo-pyrazolo [3,4-d] pyrimidin-1-yl) -cyclohexyl) -1-methylpiperazine -2-one of EXAMPLE 2B, by the product of EXAMPLE 124A. EXAMPLE 124C This compound was prepared by substituting the product of EXAMPLE 43D in EXAMPLE 43E, by the product of EXAMPLE 92B. MS (ESI) m / e 531 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 9.65 (m, 1 H), 8.30 (s, 1 H), 7.82 (s, 1 H), 7.77 (d , 1H), 7.60 (d, 1H), 7.40-7.31 (m, 5H), 5.04 (m, 1H), 4.38 (s, 2H), 3.68 (m, 4H), 3.39 (m, 4H), 3.14 ( s, 3H), 2.25 (m, 4H).

EXAMPLE 125 3- (2- (2-Fluorobenzyl) -1H-benzimidazol-5-yl) -1-. { 1- (2- (methylsulfonyl) ethyl) piperidin-4-yl} -1H-pyrazolo [3,4-d] pyrimidin-4-amine This compound was prepared by substituting the phenylacetaldehyde of EXAMPLE 43E for 2-fluorophenylacetaldehyde and the product of EXAMPLE 43D by the product of EXAMPLE 92B. MS (ESI) m / e 549 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 9.67 (m, 1 H), 8.30 (s, 1 H), 7.81 (s, 1 H), 7.75 (d , 1H), 7.59 (d, 1H), 7.48 (m, 1H), 7.39 (m, 1H), 7.23 (m, 2H), 5.05 (m, 1H), 4.42 (s, 2H), 3.68 (m, 4H), 3.39 (m, 4H), 3.14 (s, 3H), 2.25 (m, 4H). EXAMPLE 126 (fra / 7S) -3- (1- (cyclohexylmethyl) -1H-indol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4- d] pyrimidin-4-amine EXAMPLE 126A The desired product was synthesized by substituting the 2-fluorobenzyl bromide of EXAMPLE 210A for bromomethylcyclohexane. EXAMPLE 126B The desired product was synthesized by substituting the product of EXAMPLE 114A in EXAMPLE 114B, by the product of EXAMPLE 126A. MS: IEA (+) m / e 514.4 (M + H) 0 IEA (-) m / e 512.4 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 9.66 (br s, 1 H), 8.32 (s, 1 H), 7.82 (d, 1 H), 7.66 (d, 1 H), 7.35-7.52 (m, 4 H), 6.71 (d, 1H), 6.54 (d, 1H), 4.77 (br m, 1H), 4.02-4.08 (m, 4H), 3.05-3.26 (m, 3H), 2.20-2.30 (m, 2H), 2.07- 2.18 (br m, 4H), 1.51-1.89 (m, 7H), 0.97-1.22 (m, 4H).

EXAMPLE 127 (frans) -3- (1-cyclopentyl-1H-indol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidine-4- amine EXAMPLE 127A The desired product was synthesized by substituting the 2-fluorobenzyl bromide of EXAMPLE 210A, for bromocyclopentane. EXAMPLE 127B The desired product was synthesized by substituting the product of EXAMPLE 114A of EXAMPLE 114B, by the product of EXAMPLE 127A. MS: ESI (+) m / e 486.3 (M + H) J 1 H-NMR (300 MHz, DMSO-de) 9.66 (br s, 1 H), 8.32 (s, 1 H), 7.82 (d, 1 H), 7.71. (d, 1H), 7.57 (d, 1H), 7.42 (dd, 1H), 6.58 (d, 1H), 4.96 (m, 1H), 4.78 (m, 1H), 4.04 (m, 2H), 3.07- 3.25 (m, 2H), 2.08-2.31 (m, 8H), 1.67-1.95 (m, 8H). EXAMPLE 128 (fra / 7S) -3- (1 - (2,3-difluorobenzyl) -1 H -indol-5-yl) -1- (4-morpholon-4-yl-cyclohexyl) -1H- pyrazolo [3,4-d] pyrim idin-4-amine EXAMPLE 128A The desired product was synthesized by substituting the 2-fluorobenzyl bromide of EXAMPLE 210A for 2,3-difluorobenzyl bromide. EXAMPLE 128B The desired product was synthesized by substituting the product of EXAMPLE 114A of EXAMPLE 114B for the product of EXAMPLE 128A. MS: IEA (+) m / e 544.4 (M + H) +; IEA (-) m / e 542.3 (M-H); 1H-NMR (300 MHz, DMSO-de) 9.69 (br s, 1H), 8.32 (s, 1H), 7.85 (d, 1H), 7.68 (d, 1H), 7.59 (d, 1H), 7.43 (dd, 1H) , 7.34-7.40 (m, 1H), 7.12-7.20 (m, 1H), 6.91-6.97 (m, 1H), 6.64 (d, 1H), 5.61 (s, 2H), 4.77 (m, 1H), 4.04 (m, 2H), 3.46 (m, 3H), 3.09-3.24 (m, 2H), 2.19-2.29 (m, 2H), 2.07-2.18 (m, 4H), 1.67-1.84 (m, 2H). EXAMPLE 129 (trans) -3- (1 - (2,5-difluorobenzyl) -1 H-indol-5-yl) -1- (4-morphol i n-4-yl-cyclohexyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 129A The desired product was synthesized by substituting the 2-fluorobenzyl bromide of EXAMPLE 210A, for 2,5-difluorobenzyl bromide. EXAMPLE 129B The desired product was synthesized by substituting the product of EXAMPLE 114A in EXAMPLE 114B, by the product of the EXAMPLE 129A. MS: EIA (+) m / e 544.4 (M + H) J IEA (-) m / e 542.3 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 9.74 br s, 1 H), 8.34 (s, 1 H), 7.86. (d, 1H), 7.69 (d, 1H), 7.59 (d, 1H), 7.44 (dd, 1H), 7.29-7.36 (m, 1H), 7. 16-7.24 (m, 1H), 6.93-6.99 (m, 1H), 6.64 (d, 1H), 5.64 (s, 2H), 4.78 (m, 1H), 4.04 (m.), 3.70 (m, 2H) ), 3.46 (m, 3H), 3.08-3.24 (m, 2H), 2. 20-2.29 (m, 2H), 2.07-2.18 (m, 4H), 1.67-1.84 (m, 2H). EXAMPLE 130 (trans) -3- (1- (2,6-difluorobenzyl) -1 H -indol-5-yl) -1 - (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3, 4-d] pirim id in-4-a mine EXAMPLE 130A The desired product was synthesized by substituting the 2-fluorobenzyl bromide of EXAMPLE 210A, for 2,6-difluorobenzyl bromide. EXAMPLE 130B The desired product was synthesized by substituting the product of EXAMPLE 114A in EXAMPLE 114B, by the product of EXAMPLE 130A. MS: EIA (+) m / e 544.4 (M + H) J IEA (-) m / e 542.4 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 9.69 (br s, 1H), 8.32 (s, 1H), 7.82 (d, 1H), 7.68 (d, 1H), 7.42-7.52 (m, 3H), 7.13 -7.22 (m, 2H), 6.59 (d, 1H), 5.53 (s, 2H), 4.77 (m, 1H), 4.04 (m.), 3.70 (m, 2H), 3.46 (m, 3H), 3.08 -3.26 (m, 2H), 2.19-2.29 (m, 2H), 2.07-2.18 (m, 4H), 1.70-1.84 (m, 2H). EXAMPLE 131 (f? Aps) -3- (1- (2,5-dichlorobenzyl) -1H-indol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3 , 4-d] pyrimidin-4-amine EXAMPLE 131A The desired product was synthesized by substituting the 2-fluorobenzyl bromide of EXAMPLE 210A, for 2,5-dichlorobenzyl bromide. EXAMPLE 131B The desired product was synthesized by substituting the product of EXAMPLE 114A in EXAMPLE 114B, by the product of the EXAMPLE 131A. MS: ESI (+) m / e 576.4 (M + H) J IEA (-) m / e 574.4 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 9.70 (br s, 1 H), 8.33 (s, 1 H), 7.89 (d, 1H), 7.58-7.63 (m, 2H), 7.34-7.53 (m, 3H), 6.77 (d, 1H), 6.68 (d, 1H), 5.59 (s, 2H), 4.78 (m, 1H) ), 4.04 (m.), 3.70 (m, 2H), 3.46 (m, 3H), 3.08-3.76 (m, 2H), 2.19-2.30 (m, 2H), 2.06-2.18 (m, 4H), 1.69 -1.84 (m, 2H). EXAMPLE 132 (fra? S) -3- (1- (2,6-dichlorobenzyl) -1H-indol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3 , 4-d] pyrimidin-4-amine EXAMPLE 132A The desired product was synthesized by substituting the 2-fluorobenzyl bromide of EXAMPLE 210A, for 2,6-dichlorobenzyl bromide. EXAMPLE 132B The desired product was synthesized by substituting the product of EXAMPLE 114A in EXAMPLE 114B, by the product of EXAMPLE 132A. MS: ESI (+) m / e 576.3 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) 9.67 (br s, 1 H), 8.32 (s, 1 H), 7.84 (s, 1 H), 7.77 (d, 1H), 7.61-7.64 (m, 2H), 7.46 -7.53 (m, 2H), 7.11 (d, 1H), 6.58 (d, 1H), 5.63 (s, 2H), 4.78 (m, 1H) ), 4.04 (m.), 3.70 (m.), 3.46 (m, 3H), 3.09-3.26 (m, 2H), 2.19-2.31 (m, 2H), 2.07-2.18 (m, 4H), 1.66- 1.84 (m, 2H).

EXAMPLE 133 (trans) -1- (4-morphol-n-4-yl-cyclohexy I) -3- (2- (Fe or Isulfo or I) - 1 H- benzimidazol-5-yl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 133A 5-bromo-2-chloro-1 H -benzo [d] imidazole To a 1 L flask was added 2-chlorobenzimidazole (25.7 g, 0.169 mol) and DMF (0.8 L). To the stirring solution was slowly added N-bromosuccinimide (33.0 g, 0.185 mol), and the reaction mixture was allowed to stir overnight. To the reaction mixture was added 1L of ethyl acetate and the organic phases were washed twice with 0.5 liters of water. The organic fraction was washed with 0.5 L of brine, dried over magnesium sulfate, filtered and reduced in vacuo to obtain the desired product as a white solid. (IQD (+)) m / e 231, 233 (M + H) 0 1 H-NMR (300 MHz, DMSO-de) 13.47 (bs, 1H), 7.73 (s, 1H), 7.48 (d, 1H), 7.37 (dd, 1H). EXAMPLE 133B 5-Bromo-2- (phenylsulfonyl) -1H-benzo [d] imidazole The product of EXAMPLE 133A (0.5 g, 2.16 mmol), sodium benzenesulfinic acid salt (0.71 g, 4.32 mmol) and DMF (2.2 mL) , they were heated at 170 ° C for 20 minutes in a microwave reactor. Ethyl acetate was added to the reaction mixture, and the organic phases were washed 2X with water and with brine. The organic fraction was dried over magnesium sulfate, filtered and reduced in vacuo. The residue was purified by reverse phase HPLC and dehydrated by freezing, to obtain the desired product as a white solid. (IEA (+)) m / e 337, 339 (M + H) +; (IEA (-)) m / e 335, 337 (MH) J 1 H-NMR (300 MHz, DMSO-dβ) 14.36 (bs, 1H), 8.11-8.00 (m, 2H), 7.85-7.65 (m, 4H ), 7.63 (bs, 1H), 7.51 (d, 1H). EXAMPLE 133C 2- (phenylsulfonyl) -5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -1H-benzo [d] imidazole In a 20 mL vial was placed the product of the EXAMPLE 133B (0.328 g, 0.97 mmol), bis (pinacolato) diboro (0.493 g, 1.94 mmol), potassium acetate (0.476 g, 4.85 mmol), the adduct dichloro (1,1'-bis (diphenylphosphino) ferrocene) palladium ( ll) dichloromethane (0.042 g, 0.058 mmol) and DMF (2 mL). The reaction mixture was heated at 100 ° C overnight until the reaction was complete by LCMS. The reaction mixture was diluted with ethyl acetate and the resulting organic phases were washed with water and then with brine. The organic extracts were dried over magnesium sulfate, filtered and reduced in vacuo. The residue was purified by reverse phase HPLC and dehydrated by freezing, to obtain the desired product as a white solid. (ESI (+)) m / e 385 (M + H)? EXAMPLE 133D 1 - ((1R, 4R) -4-morpholinocyclohexyl) -3- (2- (phenylsulfonyl) -1H-benzo [d] imidazole-6 -yl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine 3-iodo-1 - ((1 R, 4R) -4-morpholinocyclohexyl) -1 H-pyrazolo [was placed in a microwave vial. 3,4-d] pyrimidin-4-amine (0.075 g, 0.175 mmol), the product of EXAMPLE 133C (0.037 g, 0.35 mmol), dichlorobis (triphenylphosphine) -palladium (ll) (0.006 g, 0.009 mmol), DME (11.4 mL), and water (0.7 mL). The solvent was reduced in vacuo and the residue was purified by reverse phase HPLC and dehydrated by freezing, to obtain the desired product as a colored solid.

White. (IEA (+)) m / e 559 (M + H) *; (ESI (-)) m / e 557 (MH) J 1 H-NMR (300 MHz, DMSO-de) 9.62 (bs, 1H), 8.29 (d, 1H), 8.12-8.06 (m, 2H), 7.89- 7.77 (m, 3H), 7.76-7.69 (m, 2H), 7.64 (d, 1H), 4.85-4.70 (m, 1H), 4.03 (dd, 2H), 3.76-3.67 (m, 2H), 3.45 ( d, 2H), 3.24-3.08 (m, 3H), 2.29-2.18 (m, 2H), 2.13 (m, 4H), 1.75 (s, 2H). EXAMPLE 134 (f? Aps) -2- (4- (4- { 4-amino-3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1H-pírazolo [3,4 -d] pyrimidin-1-yl.}. cyclohexyl) piperazin-1-yl) ethanol EXAMPLE 134A 3-Iodo-1- (4-oxocyclohexyl) -1 H -pyrazole or [3,4-d] pyrim id i n 4-yl-amine prepared as described in AF Burchat et al., Bioorg Med. Chem. Lett. 2002, 12, 1687-1690 (178.5 mg, 0.5 mmol), the product of EXAMPLE 93A (220 mg, 0.6 mmol), sodium carbonate (106 mg, 1 mmol), and Pd (PPh3) 4 (34 mg, 0.0015 mmol), were mixed in 4 mL of DME / water (1: 1), and subjected to microwave heating at 130 ° C for 20 minutes. After extraction by partition in EtOAc and brine, the ethyl acetate phase was washed with brine (x3) and dried over MgSO4. After filtration, the filtrate was evaporated to dryness, to obtain 140 mg of the title compound. EXAMPLE 134B The product of EXAMPLE 134A (47 mg, 0.1 mmol) and 1- (2-hydroxyethyl) piperazine (123 mL, 1 mmol) was stirred in 2 mL of methanol and 0.2 mL of acetic acid at room temperature for 30 minutes. minutes Then sodium cyanoborohydride was added (31 mg, 0.5 mmol) and stirred at 70 ° C for 1 hour. After extraction by partition in EtOAc and a saturated solution of sodium bicarbonate, the filtrate was evaporated to dryness and purified by HPLC. The diastereomer that eluted the fastest was isolated, yielding 4 mg of the title compound. MS: ESI (+) m / e 585.4 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) 8.27 (s, 1H), 7.87 (s, 1H), 7.52-7.60 (m, 3H), 7.41 (dd, 1H), 7.31-7.38 (dt, 1H), 7.23-7.28 (m, 1H), 6.78 (dd, 1H), 6.67 (dd, 1H), 5.59 (s, 2H), 4.74 (m, 1H), 4.04 (m.), 2.73 (m, 2H), 2.57-2.61 (m, 2H), 2.41-2.25 (m, 1H), 2.25-2.28 (m, 1H), 2.02-2.15 (m, 8H ). EXAMPLE 135 (frans) -3- (1- (2-fluorobenzyl) -1H-indazol-6-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4-d] ] pyrimidin-4-amine EXAMPLE 135A The desired product was synthesized by substituting the 5-bromo-1H-indazole of EXAMPLE 121A, for 6-bromo-1 H-indazole. EXAMPLE 135B The desired product was synthesized by substituting the 2-chlorobenzyl bromide of EXAMPLE 121B, for 2-fluorobenzyl bromide and the product of EXAMPLE 121A for the product of EXAMPLE 135A. EXAMPLE 135C The desired product was synthesized by substituting the product of the EXAMPLE 114A in EXAMPLE 114B, by the product of the EXAMPLE 135A. 1 H-NMR (300 MHz, DMSO-d 6) 9.53 (br s, 1H), 8.57 (s, 1H), 8.27 (s, 1H), 7.86 (m, 1H), 7.59 (m, 1H), 7.40-7.35 (m, 3H), 7.24 (m, 1H), 5.75 (s, 2H), 4.79 (m, 1H), 3.35-3.50 (m, 4H), 3.07-3.24 (m, 2H), 2. 19-2.30 (m, 2H), 2.06-2.17 (br m, 4H), 1.68-1.83 (br m, 2H). 941297 EXAMPLE 136 Megumi Kawai 3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1-. { 4- (4- (2-ethoxyethyl) piperazin-1-yl) cyclohexyl} -1 H-pyrazolo [3,4-d] pyrimidin-4-amine The desired product was synthesized as a mixture of diastereoisomers, substituting the 1- (2-ethoxyethyl) piperazine of EXAMPLE 134B, for 1- (2-ethoxyethyl) piperazine. MS: ESI (+) m / e 613.4 (M + H) J IEA (-) m / e 611.4 (MH) J 1 H-NMR (300 MHz, DMSO-d 6) 8.29 (s, 0.6H), 8.28 (s) , 0.4H), 7.84-7.89 (m, 1H), 7.51-7.60 (m, 3H), 7.38-7.44 (m, 1H), 7.30-7.36 (dt, 1H), 7.22-7.28 (m, 1H), 6.78 (d, 1H), 6.66 (d, 1H), 5.59 (s, 2H), 4.91 (m, 0.6H), 4.73 (m, 0.4H), 3.76 (t, 3H), 3.07-3.17 (m) , 2.73 (m, 2H), 2.57-2.61 (m, 2H), 2.41-2.25 (m, 1H), 2.25-2.28 (m, 1H), 2.02-2.15 (m, 6H), 1.62-1.95 (m, 2H), 1.09-1.17 (m, 3H). 941303 EXAMPLE 137 Megumi Kawai (c / s) -2- (4- (4- { 4-amino-3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [ 3,4-d] pyrimidin-1-y.}.) Cyclohexyl) piperazin-1-yl) ethanol This example was the diastereomer that eluted slower from EXAMPLE 134B. MS: ESI (+) m / e 585.4 (M + H) J 1 H-NMR (300 MHz, DMSO-de) 8.29 (s, 1H), 7.87 (s, 1H), 7.52-7.60 (m, 3H), 7.41 (dd, 1H), 7.31-7.38 (dt, 1H), 7.23-7.28 (m, 1H), 6.78 (dd, 1H), 6.67 (dd, 1H), 5.59 (s, 2H), 4.91 (m, 1H), 3.68 (m.), 2.73 (m, 2H), 2.25-2.40 (m, 4H), 2.02-2.15 (m, 2H), 1.71-1.95 (m, 6H).

EXAMPLE 138 4-. { 4-amino-3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4- d] pyrim id-n-1-M} Cyclohexanol The product of EXAMPLE 134A (47 mg, 0.1 mmol) and sodium cyanoborohydride (31 mg, 0.5 mmol) was stirred in 2 mL of methanol and 0.2 mL of acetic acid at 70 ° C for 1 hour. After extraction by partition in EtOAc and a saturated solution of sodium bicarbonate, the ethyl acetate phase was washed with brine (x3) and dried over MgSO. After filtration, the filtrate was then evaporated to dryness and purified by HPLC. MS: IEA (+) m / e 473.2 (M + H) +; 1 H-NMR (300 MHz, DMSO-d 6) 8.31 (s, 1H), 7.87 (s, 1H), 7.52-7.59 (m, 3H), 7.41 (dd, 1H), 7.31-7.38 (dt, 1H), 7.23-7.28 (m, 1H), 6.77 (dd, 1H), 6.66 (dd, 1H), 5.59 (s, 2H), 4.69 (m, 1H), 1.92-2.08 (m, 6H). EXAMPLE 139 3- (2-Benzyl-1H-benzimidazol-6-yl) -1- (3-pyridin-3-yl-propyl) -1H-pi-rally [3,4-d] pyrim id in-4-ami EXAMPLE 139A 3-Iodo-1- (3- (pyridin-3-yl) propyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine A suspension of 3-iodo-1 H-pyrazolo [3 , 4-d] pyrimidin-4-ylamine prepared as described in AF Burchat et al. Bioorg Med. Chem. Lett.2002, 12, 1687-1690 (0.392 g, 1.5 mmol), 3- (pyridin-3-yl) propan-1-ol (0.388 mL, 3 mmol) and triphenylphosphine (0.983 g, 3.75 mmol ) in THF (10 mL) under an inert atmosphere, cooled in a ice bath and diisopropyl azodicarboxylate (0.581 mL, 3 mmol) was added dropwise, and the reaction mixture was subsequently stirred for 72 hours at room temperature. The mixture was concentrated and the residue was acidified with 1 M HCl and washed with EtOAc. The aqueous phase was basified with solid Na2CO3 and extracted with EtOAc. The EtOAc layer was washed over Na2SO4, filtered and concentrated. The residue was purified on silica gel, using an ISCO Companion chromatography system, eluting with 0-20% MeOH / CH2Cl2, to obtain the title compound as an off-white solid (310 mg, 54%). MS (ESI (+)) m / e 381 (M + H) 0 (IEA (-)) m / e 379 (MH) J 1 H-NMR (300 MHz, DMSO-d 6) 8.39 (m, 2H), 8.20 (s, 1H), 7.61 (dd, 1H), 7.28 (m, 1H), 4.19 (t, 2H), 2.60 (m, 2H), 2.17 (m, 2H). EXAMPLE 139B 3- (2-Benzyl-1H-benzimidazol-6-yl) -1- (3-pyridin-3-yl-propyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine A suspension of the EXAMPLE 139A (57 mg, 0.15 mmol), the product of EXAMPLE 188C (55 mg, 0.165 mmol), cesium fluoride (68 mg, 0.45 mmol) and tetrakis (triphenylphosphine) palladium (0) (9 mg, 0.0075 mmol) in a mixture of DME (3 mL) and MeOH (1.5 mL) was sealed in a microwave vial under an argon atmosphere and heated by microwave at 150 ° C for 6 minutes. The reaction mixture was subjected to partition extraction in brine and EtOAc. The EtOAc phase was dried (Na2SO4), filtered and concentrated. The residue was purified by reverse phase preparative HPLC to obtain the compound of the title in the form of a white solid (54 mg, 78%). MS (ESI (+)) m / e 461 (M + H) \ (IEA (-)) m / e 459 (MH) J 1 H-NMR (300 MHz, DMSO-de) 8.65 (d, 1H), 8.54 (dd, 1H), 8.33 (s, 1H), 8.14 (d, 1H), 7.90 (s, 1H), 7.86 (d, 1H), 7.71 (d, 1H), 7.67 (m, 1H), 7.42 ( m, 4H), 7.34 (m, 1H), 4.50 (s, 2H), 4.43 (t, 2H), 3.95 (vbr s, 3H), 2.79 (t, 2H), 2.27 (dt, 2H). EXAMPLE 140 3- (2-Benzyl-1H-benzimidazol-6-yl) -1- (1-benzylpiperidin-4-yl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine; The title compound, as a white solid, was prepared as described in EXAMPLE 139, substituting 3- (pyridin-3-yl) propan-1-ol of EXAMPLE 139A, for 1-benzylpiperidin-4- ol. MS (ESI (+)) m / e 515 (M + H) J (IEA (-)) m / e 513 (MH) J 1 H-NMR (300 MHz, DMSO-de) 9.78 (br s, 1H), 8.31 (s, 1H), 7.85 (d, 1H), 7.82 (d, 1H), 7.64 (d,? H), 7.52 (m, 5H), 7.41 (m, 4H), 7.35 (m, 1H), 5.06 (m, 1H), 4.52 (s, 2H), 4.45 (s, 2H), 4.37 (m, 2H), 4.02 (v br s, 2H), 3.54 (m, 2H), 3.30 (m, 2H) 2.20 (m, 2H). EXAMPLE 141 3- (2-Benzyl-1H-benzimidazol-6-yl) -1- (2- (4-methyl-1,3-thiazol-5-yl) ethyl) -1H-pyrazolo [3,4-d] ] pyrimidin-4-amine The title compound, as a white solid, was prepared as described in EXAMPLE 139, substituting the 3- (pyridin-3-yl) propan-1-ol of EXAMPLE 139A, 2- (4-methylthiazol-5-yl) ethanol. MS (ESI (+)) m / e 467 (M + H) J (IEA (-)) m / e 465 (MH) J 1 H-NMR (300 MHz, DMSO-d 6) 8.75 (s, 1H), 8.26 (s, 1H), 7.89 (m, 1H), 7. 87 (d, 1H), 7.70 (d, 1H), 7.42 (m, 4H), 7.35 (m, 1H), 4.58 (t, 2H), 4.51 (s, 2H), 4.22 (v br s, 3H) , 3.41 (t, 2H), 2.15 (s, 3H). EXAMPLE 142 3- (2-Benzyl-1H-benzimidazol-6-yl) -1- (1- (6-chloropyridazin-3-yl) piperidin-4-yl) -1 H -pyrazolo [3,4-d] pyrimidine -4-amine The title compound, as a yellow solid, was prepared as described in EXAMPLE 139, substituting the 3- (pyridin-3-yl) propan-1-ol of EXAMPLE 139A, for 1- (6-chloropyridazin-3-yl) piperidin-4-ol. MS (ESI (+)) m / e 537 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) 8.37 (s, 1 H), 7.92 (s, 1 H), 7.86 (d, 1 H), 7.73. (d, 1H), 7.56 (d, 1H), 7.49 (d, 1H), 7.41 (m, 4H), 7.35 (m, 1H), 5.18 (m, 1H), 4.53 (s, 2H), 4.50 ( m, 2H), 3.85 (v br s, 3H), 3.27 (t, 2H), 2.16 (m, 2H), 2.07 (m, 2H). EXAMPLE 143 3- (2-Benzyl-1H-benzimidazol-6-yl) -1- (4-morpholin-4-yl-but-2-ynyl) -1H-pyrazolo [3,4-d] pyrimidine-4- amine EXAMPLE 143A 1- (4-Chlorobut-2-ynyl) -3-iodo-1H-pyrazolo [3,4-d] pyridin-4-amine The title compound was prepared as described in EXAMPLE 52A, substituting the 3-hydroxypyrrolidine-1-carboxylic acid ferf-butylester for 4-chloro-but-2-in-1-ol. The title compound was obtained in the form of a mixture with triphenylphosphine oxide with -70% purity. 1 H NMR (400 MHz, DMSO-d 6) 8.24 (s, 1 H), 5.24 (s, 2 H), 4.47 (s, 2 H).

EXAMPLE 143B 3-Iodo-1- (4-morpholin-but-2-ynyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine A solution of EXAMPLE 143A (0.4 g) and morpholine (0.4 mL, excess) in anhydrous DMF (5 mL), was stirred at 70 ° C for 5 hours.

The mixture was evaporated to dryness and the residue was taken up in HCl 1N (25 mL) and washed with EtOAc. The aqueous solution was then basified (~ pH 13) and extracted with EtOAc. The EtOAc solution was dried, filtered and evaporated to obtain the title compound as a white solid (140 mg). EM (IQD) m / e 399 (M + H) 0 1 H-NMR (400 MHz, DMSO-d 6) 8.30 (s, 1 H), 5.23 (s, 2 H), 3. 61 (m, 4H), 3.31 (s, 2H), 2.44 (m, 4H). EXAMPLE 143C 3- (2-Benzyl-1H-benzimidazol-6-yl) -1- (4-morpholin-4-yl-but-2-ynyl) -1H-pyrazolo [3,4-d] pyrimidine-4- amine The title compound, as a brown solid, was prepared as described in EXAMPLE 139B, substituting the product of EXAMPLE 139A, for the product of EXAMPLE 143B. MS (ESI (+)) m / e 479 (M + H) J (IEA (-)) m / e 477 (MH) J 1 H-NMR (300 MHz, DMSO-d 6) 8.33 (s, 1 H), 7.89 (s, 1H), 7.84 (d, 1H), 7.68 (d, 1H), 7.41 (m, 4H), 7.33 (m, 1H), 5.39 (s, 2H), 4.47 (s, 2H), 4.11 ( s, 2H), 3.99 (br s, 3H), 3.77 (m, 4H), 3.19 (m, 4H). EXAMPLE 144 3- (2-Benzyl-1H-benzimidazol-6-yl) -1-. { 4- (4- (ethylsulfonyl) piperazin-1-yl) but-2-ynyl} -1 H-pyrazolo [3,4-d] pyrimidin-4-amine The title compound, as a brown solid, was prepared as described in EXAMPLE 143, substituting the morpholine of EXAMPLE 143B, for 4-ethylsulfonylpiperazine. MS (ESI +) m / e 570 (M + H) 0 (IEA (-)) m / e 568 (MH) J 1 H-NMR (300 MHz, DMSO-d 6) 8.34 (s, 1H), 7.91 (s, 1H), 7.86 (d, 1H), 7.71 (d, 1H), 7.41 (m, 4H), 7.34 (m, 1H), 5.36 (s, 2H), 4.47 (s, 2H), 4.09 (br s, 3H), 3.96 (s, 2H), 3.89 (m, 2H), 3.32 (m, 4H), 3.10 (q, 2H), 3.00 (m, 2H), 1.19 (t, 3H). EXAMPLE 145 (c / s) -5- (2- (2-Chlorobenzyl) -1 H -benzi mid azo l-6-yl) -7- (4- (4-meti I pipe ration-1-il) cyclohexyl) -7H-pyrrolo [2,3-d] pyrimidin-4-amine This example was prepared as described in EXAMPLE 6, substituting the benzaldehyde of EXAMPLE 6B, for 2-chlorophenylacetaldehyde. MS (ESI (+)) 555.4 m / z (M + H) 0 1 H-NMR (400 MHz, DMSO) 8.13 (s, 1 H), 7.55-6.53 (m, 9 H), 6.05 (bs, 1 H), 4.67. (m, 1H), 4.33 (s, 2H), 2.37-1.99 (m, 16H), 1.74-1.48 (m, 4H). EXAMPLE 146 (frans) -3- (4-. {4- (4-amino-3- (2-benzyl-1H-benzimidazol-5-yl) -1H-pyrazolo [3,4-d] pyrimidin-1 -yl) cyclohexyl}. piperazin-1-yl) propan-1-ol This example was the diastereomer that eluted faster, prepared as described in EXAMPLE 31, substituting the 3-hydroxypyrrolidine of EXAMPLE 31C, for 1- ( 3-hydroxypropyl) piperazine. MS (ESI) m / e 566 (M + H) J 1 H-NMR (300 MHz, DMSO-de) d 8.29 (s, 1H), 7.85 (s, 1H), 7.80 (d, 1H), 7.64 (d, 1H), 7.41-7.33 (m, 5H), 4.74 (m, 1H) , 4.44 (s, 2H), 3.52-3.36 (m, 6H), 3. 05-2.85 (m, 6H), 2.09 (m, 6H), 1.80-1.60 (m, 4H). EXAMPLE 147 (c / s) -3- (4-. {4- (4-Amino-3- (2-benzyl-1 H-benzimidazol-5-yl) -1 H-pi-reason [3, 4- d] pyrim id in-1-yl) cyclohexyl. piperazin-1-yl) propan-1-ol This example was the slowest eluting diastereomer prepared as described in EXAMPLE 31, substituting the 3-hydroxypyrrolidine of EXAMPLE 31C, by 1- (3-hydroxypropyl) piperazine. MS (ESI) m / e 566 (M + H) J 1 H-NMR (300 MHz, DMSO-de) d 8.31 (s, 1 H), 7.87 (s, 1 H), 7.81 (d, 1 H), 7.65 (d , 1H), 7.42-7.33 (m, 5H), 4.86 (m, 1H), 4.44 (s, 2H), 3.84 (m, 6H), 3.47 (t, 2H), 3.10-2.90 (m, 5H), 2.35 (m, 2H), 2.07 (m, 4H), 1.85 (m, 2H), 1.75 (m, 2H). EXAMPLE 148 (c / s) -3- (4- (4- { 4-amino-3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4 -d] pyrimidin-1-yl.} cyclohexyl) piperazin-1-yl) propan-1-ol The desired product was synthesized by substituting the 1- (2-hydroxyethyl) piperazine of EXAMPLE 134B, by hydroxypropylpiperazine. The diastereomer that eluted faster was isolated. MS: ESI (+) m / e 599.4 (M + H) 0 1 H-NMR (300 MHz, DMSO-d 6) 8.31 (s, 1 H), 7.87 (d, 1 H), 7.52-7.59 (m, 3 H), 7.42 (dd, 1H), 7.34 (dt, 1H), 7.25 (dt, 1H), 6.77 (dd, 1H), 6.67 (d, 1H), 5.59 (s, 1H), 4.90 (m, 1H), 3.42 -3.53 (m, 4H, includes = 3.46, t, 2H), 2.90-3.16 (m, 4H), 2.24-2.43 (m, 2H), 2.01-2.15 (m, 2H), 1.67-1.94) m, 4H ). EXAMPLE 149 (frans) -3- (4- (4- { 4-amino-3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1H- pyrazolo [3,4-d] pyrimidin-1-yl} cyclohexyl) piperazin-1-yl) propan-1-ol This example was the slowest eluting diastereomer of EXAMPLE 148. MS: IEA (+) m / e 599.4 (M + H) J 1 H-NMR (300 MHz, DMSO -de) 8.29 (s, 1H), 7.87 (d, 1H), 7.52-7.59 (m, 3H), 7.42 (dd, 1H), 7.34 (dt, 1H), 7.25 (dt, 1H), 6.78 (dd) , 1H), 6.67 (d, 1H), 5.59 (s, 1H), 4.73 (m, 1H), 3.42-3.53 (m, 4H, includes = 3.48, t, 2H), 2.90-3.16 (m, 4H) , 2.02-2.17 (m, 6H), 1.61-1.84 (m, 4H). EXAMPLE 150 (c / s) -2- (1- (4- { 4-amino-3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4 -d] pyrimidin-1-yl}. cyclohexyl) piperidin-4-yl) ethanol This example was the unresolved diastereomer mixture produced in EXAMPLE 148. EXAMPLE 151 (fraps) -2- (1- (4- {4-amino-3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] pyrimidin-1-yl}. Cyclohexyl) piperidin-4- il) ethanol The desired product was synthesized, substituting the 1- (2-hydroxyethyl) piperazine of EXAMPLE 134B, for 4-piperidinyl ethanol. The diastereomer that eluted faster was isolated. MS: IEA (+) m / e 584.4 (M + H) +; 1 H-NMR (300 MHz, DMSO-d 6) 8.27 (s, 1H), 7.87 (d, 1H), 7.52-7.60 (m, 3H), 7.39 (dt, 1H), 7.32 (dt, 1H), 7.25 ( dt, 1H), 6.75 (dd, 1H), 6.65 (dd, 1H), 5.58 (s, 1H), 4.75 (m, 1H), 2.98-3.08 (m, 4H), 2.06-2.20 (m, 4H) , 1.63-2.00 (m), 1.32-1.43 (m, 2H). EXAMPLE 152 (c / s) - (1- (4- { 4-amino-3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] ] pyrimidin-1-yl.}. cyclohexyl) piperidin-4-yl) methanol The desired product was synthesized by substituting the 1- (2-hydroxyethyl) piperazine of EXAMPLE 134B, by 4-piperidinylmethanol. The diastereomer that eluted faster was isolated. MS: ESI (+) m / e 584.4 (M + H) \ 1 H-NMR (300 MHz, DMSO-d 6) 8.75 (br.lH), 8.28 (s, 1H), 7.90 (d, 1H), 7.52- 7.60 (m, 3H), 7.43 (dt, 1H), 7.33 (dt, 1H), 7.25 (dt, 1H), 6.80 (dd, 1H), 6.66 (dd, 1H), 5.58 (s, 1H), 4.96 (m, 1H). EXAMPLE 153 (fraps) - (1- (4- { 4-amino-3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] pyrimidine -1-yl.} Cyclohexyl) piperidin-4-yl) methanol This example was the diastereomer that eluted slower from EXAMPLE 152. MS: IEA (+) m / e 570.4 (M + H) 0 EXAMPLE 154 (c / s) -3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1-. { 4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl} -1H-pyrazolo [3,4-d] pyrimidin-4-amine The desired product was synthesized by substituting the 1- (2-hydroxyethyl) piperazine of EXAMPLE 134B, for 1- (3-methoxypropyl) piperazine. The fastest eluting diastereomer was isolated. MS: ESI (+) m / e 613.5 (M + H) J 1 H-NMR (300 MHz, DMSO-dβ) 8.30 (s, 1H), 7.88 (s, 1H), 7.52-7.59 (m, 3H), 7.42 (dd, 1H), 7.34 (dt, 1H), 7.25 (dt, 1H), 6.76 (dd, 1H), 6.66 (d, 1H), 5.59) s, 1H), 4.90 (m, 1H), 3.42 -3.53 (m, 4H, includes = 3.36, t, 2H), 3.23 (s, 3H), 2.90-3.16 (m, 4H), 2.25-2.45 (m, 2H), 2.01-2.14 (m, 2H), 1.67-1.92 (m, 4H). EXAMPLE 155 (frar &ss) -3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1-. { 4- (4- (3- methoxy propi I) pipe razin-1 -i l) cycle hexi I.}. - 1 H - Pi [3, 4-d] pyrim id i n-4-amine This example was the diastereoisomer eluting slower from EXAMPLE 154. EM: IEA (+) m / e 613.5 (M + H) 0 1 H-NMR (300 MHz, DMSO-de) 8.30 (s, 1H), 7.87 (d, 1H), 7.52-7.60 (m, 3H), 7.41 (dd, 1H), 7.33 (dt, 1H), 7.25 (dt, 1H), 6.78 (dd, 1H), 6.66 (d, 1H), 5.59 (s, 1H), 4.74 (m, 1H), 3.42-3.53 (m, 4H, includes = 3.39, t, 2H) , 3.25 (s, 3H), 2.90-3.16 (m, 4H), 2.04-2.17 (m, 6H), 1.78-1.90 (m, 2H), 1.60-1.74 (m, 2H). EXAMPLE 156 3- (1- (2-Chlorobenzyl) -1H-indol-5-yl) -1- (4-pyrrolidin-1-yl-cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidine-4- amine The desired product was synthesized as a mixture of diastereoisomers, substituting the 1- (2-hydroxyethyl) piperazine of EXAMPLE 134B, for pyrrolidine. MS: ESI (+) m / e 526.3 (M + H) 0 1 H-NMR (300 MHz, DMSO-d 6) 9.59 (br, 0.4H), 9.33 (br 0.6H), 8.32 (s, 0.6H) , 8.31 (s, 0.4H), 7.88 (dd, 1H), 7.52-7.60 (m, 3H), 7.43 (dt, 1H), 7u.34 (dt, 1H), 7.25 (dt, 1H), 6.77 ( dd, 1H), 6.66-6.67 (m, 1H), 5.59 (s, 1H), 4.94 (m, 0.6H), 4.77 (m, 0.4H), 3.50-3.67 (m, 2H), 3.25-3.36 (m, m, 1H), 3.01-3.20 (m, 2H), 2.31-2.46 (m, 1H), 2.19-2.30 (m, 1H), 1.93-2.16 (m, 6H), 1.80-1.93 (m, 3H), 1.61-1.76 (m, 1H). EXAMPLE 157 3- (4- (4- { 4-amino-3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4- d] pyrimidin-1 -yl.}. cyclohexyl) piperazin-1-yl) propanenitrile The desired product was synthesized by substituting the 1- (2- hydroxyethyl) piperazine of EXAMPLE 134B, by 3-piperazinpropionitrile. The title compound was obtained as a mixture of diastereoisomers. MS: IEA (+) m / e 594.4 (M + H) +; 1 H-NMR (300 MHz, DMSO-de) 9.28 (br, 0.4H), 9.06 (br, 0.6H), 8.33 (s, 0.6H), 8.33 (s, 0.4H), 7.88 (dd, 1H), 7.52-7.60 (m, 3H), 7.43 (dt, 1H), 7.34 (dt, 1H), 7.26 (dt, 1H), 6.78 (dd, 1H), 6.66-6.67 (m, 1H), 5.59 (s, 1H), 4.98 (m, 0.6H), 4.74 (m, 0.4H), 3.48-3.61 (m, 2H), 3.25-3.36 (m, 1H), 3.32-3.45 (m, 1H), 2.98-3.18 ( m, 4H), 2.63-2.77 (M, 4H), 2.34-2.44 (m, 2H), 2.19-2.30 (m, 1H), 1.90-2.16 (m, 4H), 1.69-1.84 (m, 1H). EXAMPLE 158 3- (1 - (2-f luoro be ncil) -1 H -indo l-5-yl) -1-. { 4- (4- (3-m-ethoxypropyl) pipe-razin-1-yl) cyclohexyl} -1 H-p i raz [3, 4-d] pyrimidin-4-amine The desired product was synthesized by substituting the 3-aminobenzyl alcohol of EXAMPLE 210C for 1- (3-methoxypropyl) piperazine. 1 H-NMR (300 MHz, DMSO-d 6) 8.31 (s, 0.6H), 8.30 (s, 0.4H), 7.84 (br, 1H), 7.66 (d, 1H), 7.57-7.59 (m, 1H), 7.33-7.44 (m, 2H), 7.26 (d, 1H), 7.14-7.17 (m, 2H), 6.63 (s, 1H), 5.55 (s, 2H), 4.90 (brm, 0.5H), 4.74 ( br m, 0.5H), 4.14 (s, 2H), 3.42-3.53 (m, 4H, includes = 3.38, t, 2H), 3.25 (s, 1.5H), 3.23 (s, 1.5H), 2.80-3.16 (m, 4H), 2.02-2.18 (m, 4H), 1.70-1.94 (m, 4H). EXAMPLE 159 1-. { 4- (4- (2-ethoxyethyl) piperazin-1-yl) cyclohexyl} -3- (1 - (2-f luorobenzyl) -1 H- indol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine The desired product was synthesized by substituting the 3-aminobenzyl alcohol of EXAMPLE 210C, by 1- (2-ethoxyethyl) piperazine.

MS: IEA (+) m / e 597.5 (M + H) +; 1 H-NMR (300 MHz, DMSO-d 6) 8.32 (s, 0.6H), 8.31 (s, 0.4H), 7.84-7.85 (br, 1H), 7.66 (d, 1H), 7.54-7.67 (m, 3H ), 7.40-7.45 (m, 1H), 7.32-7.37 (m, 1H), 7.26 (d, 1H), 7.12-7.16 (m, 2H), 6.63 (s, 0.4H), 6.62 (s, 0.6H) ), 5.55 (s, 2H), 4.92 (br m, 0.6H), 4.75 (br m, 0.4H), 3.42-3.53 (m, 4H), 3.00-3.20 (m, 3H), 2.28-2.40 (m , 2H), 2.02-2.18 (m, 4H), 1.78-1.94 (m, 2H), 1.70-1.76 (m, 2H), 1.10-1.17 (m, 3H). EXAMPLE 160 (c / s) -2- (4- (4- { 4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4 -d] pyrimidin-1-yl}. cyclohexyl) piperazin-1-yl) ethanol The desired product was synthesized by substituting the 3-aminobenzyl alcohol of EXAMPLE 210C for 1- (2-hydroxyethyl) piperazine. The diastereomer that eluted first was isolated. MS ESI (+) m / e 569.4 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) 8.32 (s, 1 H), 7.85 (d, 1 H), 7.66 (d, 1 H), 7.60 (d , 1H), 7.43 (dd, 1H), 7.32-7.38 (m, 1H), 7.26 (d, 1H), 7.13-7.16 (m, 2H), 6.63 (d, 1H), 5.55 (s, 2H), 4.91 (br m, 1H), 3.68-3.71 (m, 2H), 3.42-3.6 (m, 2H), 2.95-3.20 (m, 4H), 2.26-2.40 (m, 2H), 2.02-2.18 (m, 2H), 1.77-1.96 (m, 4H). EXAMPLE 161 (fraps) -2- (4- (4- { 4-amino-3- (1- (2-fluorobenzyl) -1 H -indol-5-yl) -1 H- pyrazolo [3,4 -d] pyrimidin-1-yl}. cyclohexyl) piperazin-1-yl) ethanol This example was the diastereomer that eluted slower from EXAMPLE 160. MS: IEA (+) m / e 569.4 (M + H) 0 1H -RMN (300 MHz, DMSO-de) 8.30 (s, 1H), 7.84 (d, 1H), 7.66 (d, 1H), 7.58 (d, 1H), 7.43 (dd, 1H), 7.32-7.38 (m, 1H), 7.24 (d, m, 1H), 7.13-7.16 (m, 2H), 6.63 (d, 1H), 5.55 (s, 2H), 4.74 (br m, 1H), 3.68-3.73 (m, 2H), 3.42-3.6 (m, 2H), 2.95-3.20 (m, 4H), 2.26-2.40 (m , 2H), 2.04-2.20 (m, 4H), 1.60-1.78 (m, 2H). EXAMPLE 162 (c / s) -3- (4- (4- { 4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4 -d] pyrimidin-1-yl}. cyclohexyl) piperazin-1-yl) propan-1-ol The desired product was synthesized by substituting the 3-aminobenzyl alcohol of EXAMPLE 210C for 1- (3-hydroxypropyl) piperazine. The diastereomer that eluted first was isolated. MS: ESI (+) m / e 583.4 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) 8.32 (s, 1 H), 7.85 (d, 1 H), 7.66 (d, 1 H), 7.60 ( d, 1H), 7.43 (dd, 1H), 7.32-7.38 (m, 1H), 7.26 (d, 1H), 7.13-7.16 (m, 2H), 6.63 (d, 1H), 5.55 (s, 2H) , 4.91 (br m, 1H), 3.36-3.58 (m, 4H), 2.84-3.12 (m, 4H), 2.26-2.40 (m, 2H), 2.00-2.15 (m, 2H), 1.68-1.95 (m , 4H). EXAMPLE 163 (frans) -3- (4- (4-. {4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3 , 4-d] pyrimidin-1-yl}. Cyclohexyl) piperazin-1-yl) propan-1-ol This example was the slowest eluting diastereomer of EXAMPLE 162. MS: IEA (+) m / e 583.5 ( M + H) J 1 H-NMR (300 MHz, DMSO-de) 8.30 (s, 1H), 7.84 (d, 1H), 7.66 (d, 1H), 7.58 (d, 1H), 7.43 (dd, 1H) , 7.32-7.38 (m, 1H), 7.24 (m, 1H), 7.13-7.16 (m, 2H), 6.63 (d, 1H), 5.54 (s, 2H), 4.74 (br m, 1H), 3.68- 3.73 (m, 2H), 3.42-3.6 (m, 2H), 2.85-3.15 (m, 4H), 2.02-2.18 (m, 6H), 1.60-1.78 (m, 4H). EXAMPLE 164 3- (4- (4- { 4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4- d] pyrimidin-1-yl} -cyclohexyl) piperazin-1-yl) propanenitrile The desired product was synthesized by substituting the 3-aminobenzyl alcohol of EXAMPLE 210C for 1- (2-cyanoethyl) piperazine. MS: (ESI (+) m / e 578.4 (M + H) +; 1 H-NMR (300 MHz, DMSO-d 6) 8.33 (s, 0.6H), 8.33 (s, 0.4H), 7.86 (dd, 1H ), 7.67 (d, 1H), 7.57-7.60 (m, 1H), 7.41-7.48 (m, 1H), 7.32-7.38 (m, 1H), 7.22-7.28 (m, 1H), 7.14-7.17 (m , 2H), 6.62-6.64 (d, 1H), 5.55 (s, 2H), 4.96 (br m, 0.6H), 4.76 (m, 0.4H), 3.326-3.60 (m, 4H), 2.95-3.17 ( m, 2H), 2.62-2.78 (m, 2H), 2.33-2.48 (m, 2H), 2.19-2.29 (m, 2H), 2.20-2.29 (m, 1H), 1.88-2.16 (m, 3H), 1.68-1.55 (m, 1H) EXAMPLE 165 3- (2-Benzyl-1H-benzimidazol-6-yl) -1 - ((2-pyridin-3-yl-1,3-thiazol-4-yl) methyl) ) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine The title compound, as an off-white solid, was prepared as described in EXAMPLE 139, substituting 3- (pyridine-3) il) propan-1-ol of EXAMPLE 139A, by (2- (pyridin-3-yl) thiazol-4-yl) methanol MS (IEA +) m / e 516 (M + H) J (IEA (-)) m / e 514 (MH) J 1 H-NMR (300 MHz, DMSO-d 6) 9.08 (d, 1H), 8.66 (dd, 1H), 8.37 (s, 1H), 8.25 (m, 1H), 7.94 (s) , 1H), 7.86 (d, 1H), 7.74 (dd, 1H), 7.59 (s, 1H), 7.53 (dd, 1H), 7.41 (m, 4H) , 7.33 (m, 1H), 5.77 (s, 2H), 4.50 (s, 2H), 3.88 (br s, 3H). EXAMPLE 166 3- (2-Benzyl-1H-benzimidazol-6-yl) -1 - ((4-benzylmorpholin-2-yl) methyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine The compound of the title, in the form of a white solid, was prepared as described in EXAMPLE 139, substituting 3- (pyridin-3-yl) propan-1-ol of EXAMPLE 139A, for (4-benzylmorpholin-2-yl) methanol. MS (ESI (+)) m / e 531 (M + H) +; (IEA (-)) m / e 529 (MH) J 1 H-NMR (300 MHz, DMSO-d 6) 8.36 (s, 1 H), 7.87 (s, 1 H), 7.85 (d, 1 H), 7.64 (d, 1H), 7.46 (m, 5H), 7.42 (m, 4H), 7.34 (m, 1H), 4.51 (s, 2H), 4.47 (s, 2H), 4.36 (s, 2H), 4.25 (v br s , 3H), 3.99 (m, 2H), 3.66 (m, 1H), 3.41 (m, 1H), 3.16 (m, 1H), 3.06 (m, 2H). EXAMPLE 167 3- (1- (2-Chlorobenzyl) -1H-indol-5-yl) -1- (3- (1,1-dioxidothiomorpholin-4-yl) propyl) -1 H-pyrazolo [3,4- d] pyrimidin-4-amine The title compound, as a white solid with red dyes, was prepared as described in EXAMPLE 139, substituting 3- (pyridin-3-yl) propan-1-ol of EXAMPLE 139A, by 3- (1,1-dioxothiomorpholino) -1-propanol, and the product of EXAMPLE 188C in EXAMPLE 139B, by the product of EXAMPLE 63B. MS (ESI +) m / e 550 (M + H) J (IEA (-)) m / e 548 (MH) J 1 H-NMR (300 MHz, DMSO-de) 8.37 (s, 1H), 7.89 (d, 1H), 7.58 (m, 2H), 7.53 (d, 1H), 7.43 (d, 1H), 7.34 (m, 1H), 7.25 (m, 1H), 6.79 (dd, 1H), 6.67 (d, 1H) ), 5.59 (s, 2H), 4.86 (vbr s, 2H), 43.44 (t, 2H), 3.28 (br s, 8H), 2.97 (m, 2H), 2.18 (m, 2H). EXAMPLE 168 1- (4- (4-acetylpiperazin-1-yl) but-2-ynyl) -3- (2-benzyl-1H-benzimidazol-6-yl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine The title compound, as a white solid, was prepared as described in EXAMPLE 143, substituting the morpholine of EXAMPLE 143B by 1- (piperazin-1-yl) ethanone. MS (ESI +) m / e 520 (M + H) J (IEA (-)) m / e 518 (MH) J 1 H-NMR (300 MHz, DMSO-de) 8.34 (s, 1H), 7.91 (s, 1H), 7.86 (d, 1H), 7.69 (d, 1H), 7.42 (m, 4H), 7.38 (m, 1H), 5.38 (s, 2H), 4.48 (s, 2H), 4.06 (s, 2H) ), 3.97 (br s, 3 H), 3.62 (m, 4 H), 3.17 (M, 4 H), 2.01 (s, 3 H). EXAMPLE 169 3- (2-Benzyl-1 H-benzimidazol-6-yl) -1-. { 4- (4- (2-methoxyethyl) piperazin-1-yl) but-2-ynyl} -1 H-pyrazolo [3,4-d] pyrimidin-4-amine The title compound, as a yellow-brown solid, was prepared as described in EXAMPLE 143, substituting the morpholine of EXAMPLE 143B for 1 - (2-methoxyethyl) piperazine. MS (ESI +) m / e 536 (M + H) 0 (IEA (-)) m / e 534 (MH) J 1 H-NMR (300 MHz, DMSO-d 6) 8.34 (s, 1 H), 7.91 (s, 1H), 7.86 (d, 1H), 7.70 (d, 1H), 7.42 (m, 4H), 7.34 (m, 1H), 5.29 (s, 2H), 4.66 (br s, 3H), 4.49 (s, 2H), 3.62 (t, 2H), 3.44 (s, 4H), 3.29 (s, 3H), 3.24 (m, 2H), 3.02 (m, 2H), 2.88 (m, 2H), 2.57 (m, 2H) ). EXAMPLE 170 3- (1- (2-Chlorobenzyl) -1H-indol-5-yl) -1- (4- (1,1-dioxidothiomorpholin-4-yl) but-2-ynyl) -1 H-pyrazolo [ 3,4-d] pyrimidin-4-amine EXAMPLE 170A 3-iodo-1- (4- (1,1-dioxidothiomorpholin-4-yl) but-2-ynyl) -1 H-pyrazolo [3,4- d ] pyrimidin-4-amine The title compound, as a white solid, was prepared as described in EXAMPLE 143, substituting the morpholine of EXAMPLE 143B, for 1, 1-thiomorpholine dioxide. EM (IEA (+)) m / e 447 (M + H) +; 1 H-NMR (300 MHz, DMSO-d 6) 8.24 (s, 1H), 6.85 (vbr s, 2H), 5.19 (s, 2H), 3.45 (s, 2H), 3.11 (m, 4H), 2.89 (m , 4H). EXAMPLE 170B 3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1- (4- (1,1-dioxidothiomorpholin-4-yl) but-2-ynyl) -1 H-pyrazolo [ 3,4-d] pyrimidin-4-amine The title compound, as a white solid, was prepared as described in EXAMPLE 139B, substituting the product of EXAMPLE 188C for that of EXAMPLE 63B and the product of EXAMPLE 139A by that of EXAMPLE 170A. MS (ESI +) m / e 560 (M + H) J (IEA (-)) m / e 558 (MH) J 1 H-NMR (300 MHz, DMSO-d 6) 8.34 (s, 1H), 7.91 (s, 1H), 7.57 (m, 3H), 7.44 (d, 1H), 7.33 (m, 1H), 7.25 (m, 1H), 6.78 (d, 2H), 6.67 (d, 1H), 5.60 (s, 2H) ), 5.27 (s, 2H), 2.59 (br s, 2H), 2.50 (s, 2H), 3.10 (m, 4H), 2.91 (m, 4H). EXAMPLE 171 1 - (4- (4-a cetyl pipe razin-1-yl) but-2-i ni l) -3- (1 - (2-chloro benzyl) -1H-indol-5- il) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 171A 1- (4- (4- (4-amino-3-iodo-1 H-pyrazolo [3,4-d] pyrimidin-1 -yl) but-2-ynyl) piperazin-1-yl) ethanone The title compound, as a white solid, was prepared as described in EXAMPLE 143, substituting the morpholine of EXAMPLE 143B, for 1- ( piperazin-1-yl) ethanone. EM (ESI (+)) m / e 440 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) 8.23 (s, 1H), 6.95 (vbr s, 2H), 5.16 (s, 2H), 3.40 (m, 4H), 3.28 (s, 2H), 2.39 (m, 2H), 2.33 (m, 2H), 1.97 (s, 3H). EXAMPLE 171B 1- (4- (4-Acetylpiperazin-1-yl) but-2-ynyl) -3- (1- (2-chlorophenyl) -1H-indol-5-yl) -1H-pyrazolo [3, 4-d] pyrimidin-4-amine The title compound, as a yellow-brown solid, was prepared as described in EXAMPLE 139B, substituting the product of EXAMPLE 188C for that of EXAMPLE 63B and the product of EXAMPLE 139A by that of EXAMPLE 171A. MS (ESI +) m / e 553 (M + H) +; (ESI (-)) m / e 551 (MH) J 1 H-NMR (300 MHz, DMSO-d 6) 8.33 (s, 1H), 7.89 (s, 1H), 7.60 (m, 2H), 7.54 (d, 1H), 7.44 (d, 1H), 7.34 (m, 1H), 7.26 (m, 1H), 6.79 (d, 1H), 6.68 (d, 1H), 5.60 (s, 2H), 5.37 (s, 2H) ), 4.10 (s, 2H), 3.99 (br s, 2H), 3.64 (m, 4H), 3.16 (m, 4H), 2.00 (s, 3H). EXAMPLE 172 3- (1- (2-Chlorobenzyl) -1H-indol-5-yl) -1-. { 4- (4- (2-methoxyethyl) piperazin-1-yl) but-2-ynyl} -1H-pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 172A 3-iodo-1- (4- (4- (2-methoxyethyl) piperazin-1-yl) but-2-ynyl) -1H- pyrazolo [3,4- d] pyrimidin-4-amine The title compound, as a brown solid, was prepared as described in EXAMPLE 143, substituting the morpholine of EXAMPLE 143B, for 1- (2-methoxyethyl) ) piperazine. MS (ESI (+)) m / e 456 (M + H) +; 1 H-NMR (300 MHz, DMSO-de) 8.23 (s, 1H), 6.56 (vbr s, 2H), 5.16 (s, 2H), 3.40 (t, 2H), 3.23 (s, 2H), 3.21 (s) , 3H), 2.48-2.24 (m, 10H).

EXAMPLE 172B 3- (1- (2-Chlorobenzyl) -1H-indol-5-yl) -1-. { 4- (4- (2-methoxyethyl) piperazin-1-yl) but-2-ynyl} -1H-pyrazolo [3,4-d] pyrimidin-4-amine The title compound, as a whitish solid, was prepared as described in EXAMPLE 139B, substituting the product of EXAMPLE 188C for that of EXAMPLE 63B and the product of EXAMPLE 139A by that of EXAMPLE 172A. MS (ESI +) m / e 569 (M + H) J (IEA (-)) m / e 567 (MH) J 1 H-RN (300 MHz, DMSO-de) 8.33 (s, 1H), 7.89 (s, 1H), 7.58 (m, 2H), 7.54 (d, 1H), 7.43 (d, 1H), 7.33 (m, 1H), 7.25 (m, 1H), 6.79 (d, 1H), 6.68 (d, 1H) ), 5.59 (s, 2H), 5.28 (s, 2H), 4.00 (vbr s, 2H), 3.62 (t, 2H), 3.44 (s, 2H), 3.41 (m, 2H), 3.28 (s, 3H) ), 3.24 (m, 2H), 3.02 (m, 2H), 2.89 (m, 2H), 2.57 (m, 2H). EXAMPLE 173 1 - ((4-benzylmorpholin-2-yl) methyl) -3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1H-pi-lo [3,4-d] pyrim id-4-amine The title compound, as a white solid with red dyes, was prepared as described in EXAMPLE 139, substituting the product of EXAMPLE 188C in EXAMPLE 139B for the product of EXAMPLE 63B and the 3- (pyridin-3-yl) propan-1-ol of the EXAMPLE 139A by (4-benzylmorpholin-2-yl) methanol. MS (IEA +) m / e 564 (M + H) J (IEA (-)) m / e 562 (M-H) J 1 H-NMR (300 MHz, DMSO-d 6) 8. 31 (s, 1H), 7.86 (d, 1H), 7.59 (m, 2H), 7.54 (d, 1H), 7.45 (m, 5H), 7. 39 (d, 1H), 7.34 (m, 1H), 7.26 (m, 1H), 6.81 (dd, 1H), 6.68 (d, 1H), 5.59 (s, 2H), 4.48 (m, 1H), 4.37 (s, 2H), 4.14 (vbr s, 2H), 4.00 (m, 2H), 3.66 (m, 2H), 3.43 (m, 1H), 3.27 (m, 1H), 3.07 (m, 2H). EXAMPLE 174 (fra 7 S) -3- (2- (2-chlorobenzyl) -1 H -benzimidazol-6-yl) -1-. { 4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl} -1 H-pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 174A 3-iodo-1- (4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl) -1 H-pyrazolo [ 3,4-d] pyrimidin-4-amine The desired product was synthesized as a mixture of diastereoisomers, substituting the 1- (fe? F -butoxycarbonyl) piperazine of EXAMPLE 318A, for 1- (3-methoxypropyl) piperazine. EXAMPLE 174B 3- (4-amino-3-nitrophenyl) -1- (4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidine-4 -amine A mixture of EXAMPLE 174A (0.3 g, 0.6 mmol), the product of EXAMPLE 2A (0.32 g, 1.24 mmol), (Ph3P) 2PdCl2 (0.021 g, 0.03 mmol) and an aqueous solution of 2M Na2CO3 (0.62 mL, 1.24 mmol), was heated at 130 ° C for 20 minutes in a microwave reactor. The reaction mixture was filtered on a pad of Celite® and washed with CH 2 Cl 2. The organic phases were reduced in vacuo directly in MeOH / NH 4 OH), to obtain the desired trans-diastereomeric product. EXAMPLE 174C A mixture of EXAMPLE 174B (?) (0.12 g, 0.23 mmol), 2- (2-chlorophenyl) acetaldehyde (0.036 g, 0.23 mmol), Na2S2O4 (0.7 mL, 0. 70 mmol) and EtOH (1 mL) was placed in a microwave reactor and heated at 130 ° C for 20 minutes. The reaction was stopped by the addition of 5M NH 4 OH and diluted with CH 2 Cl 2 / IPA (4: 1, v / v). The organic phases were extracted with CH2Cl2 (3 x 10 mL). The organic extracts were combined and the combined was dried over MgSO4, filtered and reduced in vacuo. The material was purified by reverse phase HPLC, using the following column conditions: 0.15% TFA in CH3CN / 0.15% in H2O, to obtain the desired product. (ESI (+)) m / e 614 (M + H) 0 1 H-NMR (300 MHz, DMSO-de) 8.30 (s, 1H), 7.82 (s, 1H), 7.77 (d, 1H), 7.60 ( d, 1H), 7.55-7.51 (m, 2H), 7.42-7.39 (m, 2H), 4.75 (m, 1H), 4.54 (s, 2H), 3.39 (m, 2H), 3.25 (s, 3H) , 2.58 (m, 1H), 2.14-2.06 (m, 5H), 2.14-2.06 (m, 5H), 1.88-1.80 (m, 2H), 1.175-1.62 (m, 2H). EXAMPLE 175 3- (2-Benzyl-1H-benzimidazol-5-yl) -1- (1- (3-methoxypropyl) pyrrolidin-3-yl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 175A A mixture of EXAMPLE 52B (0.3 g, 0.82 mmol), 1-bromo-3-methoxypropane (0.25 g, 1.64 mmol) and K2CO3 (0.56 g, 4.1 mmol) in CH3CN (10 mL), was stirred at room temperature during one night. The reaction mixture was diluted with EtOAc and washed with brine. The crude product was recrystallized in ether, to obtain 0.22 g of the material with a yield of 68%. MS (ESI) m / e 403 (M + H); 1 H-NMR (300 MHz, DMSO-d 6) 8.19 (s, 1 H), 5.28 (m, 1 H), 3.35 (m, 2 H), 3.22 (s, 3 H), 3.03 (m, 1 H), 2.68 (m, 4H), 2.30-2.16 (m, 3H), 1.67 (m, 2H). EXAMPLE 175B This compound was prepared by substituting (c / s) -4- (4- (4-amino-3-iodo-pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexyl) -1-methylpiperazine-2 -one of EXAMPLE 2B, by the product of EXAMPLE 175A. EXAMPLE 175C This compound was prepared by substituting the product of EXAMPLE 52D in EXAMPLE 52E, by the product of EXAMPLE 175B. MS (ESI) m / e 483 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 9.86 (br, 1 H), 8.32 (s, 1 H), 7.88 (s, 1 H), 7.80 (d , 1H), 7.67 (d, 2H), 7.41-7.33 (m, 5H), .5.71 (m, 1H), 4.42 (s, 2H), 4.14-4.02 (m, 2H), 3.42-3.32 (m, 6H), 3.23 (d, 3H), 2.45 (m, 2H), 1.92 (m, 2H). EXAMPLE 176 (frans) -3- (2-benzyl-1H-benzimidazol-5-yl) -1- (4-. {4- (2- (1,3-dioxolan-2-yl) ethyl) piperazine- 1-yl.) Cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine This example was the fastest eluting diastereomer prepared as described in EXAMPLE 31, substituting 3-hydroxypyrrolidine from EXAMPLE 31C by 1- (2- (1, 3-dioxolan-2-yl) ethyl) piperazine. MS (ESI) m / e 608 (M + H) J 1 H-NMR (300 MHz, DMSO-de) d 8.29 (s, 1 H), 7.85 (s, 1 H), 7.81 (d, 1 H), 7.65 (d , 1H), 7.42-7.33 (m, 5H), 4.88 (t, 1H), 4.74 (m, 1H), 4.45 (s, 2H), 3.91 (m, 2H), 3.79 (m, 2H), 3.39 ( m, 5H), 2.89 (m, 6H), 2.10 (m, 6H), 1.92 (m, 2H), 1.69 (m, 2H). EXAMPLE 177 (c / s) -3- (2-Benzyl-1 H-benzimidazol-5-yl) -1- (4-. {4- (2- (1,3-dioxolan-2-) il) ethyl) piperazin-1-yl} cyclohexyl) -1H-pyrazolo [3,4-d] pyrim id in-4-am ina This example was the slowest eluting diastereomer prepared as described in EXAMPLE 31, substituting the 3-hydroxypyrrolidine of EXAMPLE 31C, for 1 - (2- (1, 3-dioxolan-2-yl) ethyl) piperazine. MS (ESI) m / e 608 (M + H) -; 1 H-NMR (300 MHz, DMSO-de) d 8.31 (s, 1H), 7.88 (s, 1H), 7.82 (d, 1H), 7.68 (d, 1H), 7.42-7.33 (m, 5H), 4.92 (m, 1H), 4.87 (t, 1H), 4.46 (s, 2H), 3.90 (m, 2H), 3.79 (m, 2H), 3.41 (m, 5H), 2.98 (m, 6H), 2.35 ( m, 2H), 2.06 (m, 2H), 1.91 (m, 6H). EXAMPLE 178 (trans) -1- (4-morpholin-4-yl-cyclohexyl) -3- (1- (tetrah id ro-2H-pi ran-2-ylmethyl) -1 H-indol-5-yl ) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 178A The desired product was synthesized by substituting the 2-fluorobenzyl bromide of EXAMPLE 210A, for 2- (bromomethyl) tetrahydro-2H-pyran. EXAMPLE 178B The desired product was synthesized by substituting the product of EXAMPLE 93A in EXAMPLE 93B, by the product of EXAMPLE 178A. MS: ESI (+) m / e 516.4 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) 9. 64 (br s, 1H), 8.31 (s, 1H), 7.81 (d, 1H), 7.67 (d, 1H), 7.39-7.44 (m, 2H), 6.55 (d, 1H), 4.78 (br m, 1H), 4.23 (t, 2H), 4.04 (br d, 2H), 3.46 (br m, 2H), 3.10-3.32 (m, 4H), 2.19-2.30 (m, 2H), 2.06-2.18 (br m, 4H), 1.70-1.84 (br m, 3H), 1.57-1.64 (m, 1H), 1.38-1.50 (m, 3H), 1.15-1.30 (m, 1H).

EXAMPLE 179 (fra / 7s) -1- (4-morpholin-4-yl-cyclohexyl) -3- (1- (pyridin-3-yl-methyl) -1 H -indol-5-yl) -1 H- pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 179A The desired product was synthesized by substituting the 2-fluorobenzyl bromide of EXAMPLE 210A for 3- (bromomethyl) pyridine. EXAMPLE 179B The desired product was synthesized by substituting the product of EXAMPLE 93A in EXAMPLE 93B, by the product of EXAMPLE 179A. MS: ESI (+) m / e 509.3 (M + H) +; 1 H-NMR (300 MHz, DMSO-de) 9.74 (br s, 1H), 8.65 (d, 1H), 8.54-8.58 (m, 2H), 8.37 (s, 1H), 7.86 (d, 1H), 7.76-7.82 (d, 1H), 7.69-7.71 (m, 1H), 7.47-7.51 (m, 1H), 7.39-7.44 (m, 1H), 6.55 (d, 1H), 5.59 (s, 2H), 4.78 (br m, 1H), 3. 99-4.09 (m, 2H), 3.65-3.77 (m, 2H), 3.37-3.51 (m, 3H), 3.11-3.24 (m, 2H), 2.19-2.30 (m, 2H), 2.06-2.18 (m , 4H), 1.68-1.84 (m, 2H). EXAMPLE 180 (frans) -1- (4-morpholin-4-yl-cyclohexyl) -3- (1- (pyridin-2-yl-methyl) -1 H -indol-5-yl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 180A The desired product was synthesized by substituting the 2-fluorobenzyl bromide of EXAMPLE 210A for 2- (bromomethyl) pyridine. EXAMPLE 180B The desired product was synthesized by substituting the product of EXAMPLE 93A in EXAMPLE 93B, by the product of the EXAMPLE 180A. MS: ESI (+) m / e 509.3 (M + H) 0 1 H-NMR (300 MHz, DMSO-de) 9-72 (br s, 1H), 8.56 (m, 1H), 8.36 (s, 1H) , 7.85 (d, 1H), 7.76 (dt, 1H), 7.62-7.65 (m, 2H), 7.40 (dd, 1H), 7.29-7.33 (m, 1H), 7.11 (d, 1H), 6.64 (d , 1H), 5.58 (s, 2H), 4.78 (br m, 1H), 4.00-4.09 (m, 2H), 3645-3.76 (m, 2H), 3.37-3.51 (m, 3H), 3.11-3.24 ( m, 2H), 2.19-2.30 (m, 2H), 2.06-2.18 (m, 4H), 1.70-1.84 (m, 2H). EXAMPLE 181 3- (2-Benzyl-1H-benzimidazol-5-yl) -1-ferf-butyl-1H-pyrazolo [3,4- d] pyrimidin-4-amine To a reaction vessel for microwaves, were added 3-b romo-1-ferf-b uti 1-1 H-pyrazolo [3,4-d] pyrimidin-4-yl-amine prepared as described in the US Pat. Application US20060025383 (0.047 g, 0.18 mmol), the product of EXAMPLE 188C (0.063 g, 0.19 mmol), K2CO3 (0.069 g, 0.50 mmol), Pd (PPh3) 4 (0.005 g, 0.004 mmol) and DME / H2O 2: 1 (3.3 mL / 1.7 mL). The reaction vessel was sealed and heated at a controlled temperature in a Personal Chemistry Smith System for a total of 20 minutes, at a temperature of 150 ° C. The reaction mixture was diluted with CH2Cl2, and the organic phases were washed sequentially with an aqueous solution of NaHCO3 and with brine, then dried over MgSO4. The solvent was removed under reduced pressure and the residue was purified by reverse phase HPLC, using CH3CN / water / 0.15% TFA, to obtain the TFA salt of the title compound, as a white solid (0.030 g) . MS (ESI (+)) m / e 398 (M + H) *; (IEA (-)) m / e 396 (M-H) J 1 H-NMR (300 MHz, DMSO-de) 8.31 (s, 1H), 7.88 (d, 1H), 7.83 (s, 1H), 7.70 (m, 1H), 7.42 (m, 3H), 7.36 (m, 2H), 4.49 ( s, 2H), 1.77 (s, 9H). EXAMPLE 182 5- (2-Benzyl-1H-benzimidazol-5-yl) -7-ferf-butyl-7H-pyrrolo [2,3- d] pyrimidin-4-amine The desired product was prepared by substituting the 3-bromo- 1-Ferf-butyl-1 H-pyrazolo [3,4-d] pyrimidin-4-yl-amine from EXAMPLE 181, by 7-ferf-butyl-5-iodo-7H-pyrrolo [3,4-d] pyrimidine 4-yl-amine prepared as described in the North American Patent Application US20060025383. 1 H-NMR (300 MHz, DMSO-d 6) d 8.39 (s, 1 H), 7.76 (d, 1 H), 7.72 (m, 1 H), 7.64 (s, 1 H), 7.52 (m, 1 H), 7.41 (m , 3H), 7.34 (m, 2H), 4.44 (s, 2H), 1.77 (s, 9H). EXAMPLE 183 5- (2-Benzyl-1 H-benzimidazol-5-yl) -7- (4- (4-methyl-piperazin-1-yl) -cyclohexyl) -7H-pyrrolo [2,3-d] pyrimidin-4- amine The desired product was prepared by substituting 3-bromo-1-phe-f-butyl-1H-pyrazolo [3,4-d] pyrimidin-4-yl-amine from EXAMPLE 181, by 3-iodo-1- (4 - (4-methylpiperazin-1-yl) cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-yl-amine prepared as described in AF Burchat et al. Bioorg Med. Chem. Lett. 2002, 12, 1687-1690. 1 H-NMR (300 MHz, DMSO-d 6) d 8.40 (s, 1 H), 7.78 (m, 2 H), 7.71 (s, 1 H), 7.62 (s, 1 H), 7.48 (m, 1 H), 7.41 (m , 3H), 7.35 (m, 1H), 4.86-4.79 (m, 1H), 4.44 (s, 2H), 2.48-2.20 (m, 8H), 2.14 (s, 3H), 2.09-2.04 (m, 1H) ), 1.76-1.56 (m, 4H). EXAMPLE 184 (frar? s) -3- (1-benzyl-1H-benzimidazol-5-yl) -1- (4-morphol-n-4-yl-cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidine -4-amine EXAMPLE 184A 4-Bromo-1-fluoro-2-nitrobenzene (2.46 mL, 20 mmol) was dissolved in 20 mL of acetonitrile at room temperature. Benzylamine (2.28 mL, 21 mmol) and triethylamine (4.18 mL, 30 mmol) were added to the mixture and stirred at 50 ° C for 16 hours. EtOAc was added followed by water, and the organic phase was washed with brine (x4), dried over Na2SO4 and evaporated to dryness. 6.16 g of the title compound were obtained. EXAMPLE 184B The desired compound was synthesized by substituting the product of EXAMPLE 185A in EXAMPLE 185B, by the product of EXAMPLE 184A. EXAMPLE 184C The desired product was synthesized by substituting the product of EXAMPLE 185B in EXAMPLE 185C, by the product of EXAMPLE 184B. EXAMPLE 184D The desired product was synthesized by substituting the product of EXAMPLE 185C in EXAMPLE 185D, by the product of EXAMPLE 184C. MS: IQD (+) m / e 335.4 (M + H) *. EXAMPLE 184E The desired compound was synthesized by substituting the product of EXAMPLE 185D in EXAMPLE 185E, by the product of EXAMPLE 184D. MS: IEA (+) m / e 509.3 (M + H) *; IEA (-) m / e 507.3 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 9.62 (br, 1H), 8.88 (s, 1H), 8.30 (s, 1H), 7.94 (d, 1H), 7.82 (d, 1H), 7.61 (dd, 1H), 7.32-7.44 (m, 5H), 5.63 (s, 2H), 4.77 (m, 1H), 4.04 (m.), 3.36-3.49 (m, 3H), 3.09-3.23 (m, 2H), 2.19-2.29 (m, 2H), 2.07-2.18 (m, 4H), 1.67-1.83 (m, 2H). EXAMPLE 185 (fra /? S) -3- (1- (2-Chlorobenzyl) -1H-benzimidazol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 185A 4-Bromo-2-nitroaniline (2.17 g, 10 mmol) was dissolved in DMF at room temperature. Sodium hydride (0.44 g, 11 mmol) was added. After stirring at room temperature for 30 minutes, 2-chlorobenzyl bromide (1.43 mL, 11 mmol) was added and stirred at 50 ° C for 17 hours. EtOAc was added followed by brine, and the EtOAc layer was washed with brine (x4), dried over MgSO4 and evaporated to dryness. The crude product was purified on a column of silica gel, eluting with 5% EtOAc in hexane, to obtain 1.54 g. 1 H-NMR (300 MHz, DMSO-d 6) 8.70 (t, 1H), 8.21 (d, 1H), 7.61 (dd, 1H), 7.50 (m, 1H), 7.27-7.34 (m, 3H), 6.77 (d, 1H), 4.69 (d, 2H). EXAMPLE 185B The product of EXAMPLE 185A (680 mg, 2 mmol) was suspended in 15 mL of EtOH / water (4: 1) and iron (680 mg) was added.

It was gently subjected to reflux temperature at 90 ° C for 2.5 hours. EtOAc was added followed by brine, and the aqueous phase it was washed with brine (x4), dried over MgSO and evaporated to dryness, yielding 620 mg of the title compound. MS: IQD (+) m / e 312.6 (M + H) *; 1 H-NMR (300 MHz, DMSO-d 6) 7.43-7.46 (m, 1H), 7.26-7.38 (m, 3H), 6.72 (d, 1H), 6.51 (dd, 1H), 6.11 (d, 1H), 5.32 (t, 1H), 4.93 (s, 2H), 4.34 (d, 2H). EXAMPLE 185C The product of EXAMPLE 185B (620 mg, 2 mmol) was dissolved in 2 mL of methylene chloride. Triethyl orthoformate (1.66 mL, 10 mmol) was added, followed by trifluoroacetic acid (77 mL, 1 mmol). The mixture was stirred for 2 hours at room temperature. EtOAc was added followed by a 10% sodium bicarbonate solution, and the organic phase was washed with brine (x4), dried over MgSO4 and evaporated to dryness, yielding 620 mg of the title compound. MS: IQD (+) m / e 288.9 (M + H) *; H-NMR (300 MHz, DMSO-d6) 8.47 (s, 1H), 7.86 (d, 1H), 7.49 (s, 1H), 7.26-7.38 (m, 5H), 6.72 (d, 1H), 5.51 ( s, 2H). EXAMPLE 185D The product of EXAMPLE 185C (610 mg, 1.9 mmol), potassium acetate (0.56 g, 5.7 mmol), bis (pinacolato) diboro (0.58 g, 2.28 mmol), dppf (31 mg, 0.057 mmol) and the complex PdCI2 (dppf) »CH2Cl2 (47 mg, 0.057 mmol), was added to 10 mL of dioxane. The mixture was stirred at 95 ° C for 4 hours. The solvent was removed, and the residue was purified directly by chromatography on a column of silica gel, eluting with 2% methanol in methylene chloride. 610 mg of the compound were obtained. EM: IQD (+) m / e 369.4 (M + H) *. EXAMPLE 185E-tra-3-iodo-1- (4-morpholin-4-yl-cyclohexy I) -1H-pyrazolo [3,4-d] pyrimidin-4-yl-amine prepared as described in PCT Patent Application WO 2005/074603 (86 mg, 0.2 mmol), the product of the EXAMPLE 185D (88.5 mg, 0.24 mmol), sodium carbonate (42 mg, 0. 4 mmol) and Pd (PPh3) (14 mg, 0.0006 mmol), were dissolved in 2 mL of DME / water (1: 1) and heated in the microwave at 130 ° C for 20 minutes. After partitioning into ethyl acetate and brine, the ethyl acetate phase was washed with brine (3x), dried and the crude product was purified by HPLC, to obtain 60 mg of the title compound. MS: IEA (+) m / e 543.3 (M + H) *; IEA (-) m / e 541.3 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 9.66 (br, 1H), 8.74 (s, 1H), 8.32 s, 1H), 7.95 (d, 1H), 7.75 (d, 1H), 7.55.7.61 (m, 2H), 7.32-7.43 (m, 2H), 7.21 (dd, 1H), 5.72 ( s, 2H), 4.78 (m, 1H), 4.04 (m.), 3. 70 (m, 3H), 3.36-3.49 (m, 3H), 3.09-3.23 (m, 2H), 2.19-2.29 (m, 2H), 2.05-2.17 (m, 4H), 1.68-1.82 (m, 2H). EXAMPLE 186 (fra A7S) -3- (1 - (2-f-Ioorobenzyl) -1H-benzimidazol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3, 4-d] pyrimidin-4-amine EXAMPLE 186A 4-Bromo-1-fluoro-2-nitrobenzene (2.46 mL, 20 mmol) was dissolved in 20 mL of acetonitrile, at room temperature. To the mixture, 2-fluorobenzylamine (2.40 mL, 21 mmol) and triethylamine (4.18 mL, 30 mmol) were added, and it was stirred at 50 ° C for 16 hours.

EtOAc was added followed by water, and the EtOAc layer was washed with brine (x4), dried over Na2SO and evaporated to dryness. 6.48 g of the title compound were obtained. EXAMPLE 186B The desired compound was synthesized by substituting the product of EXAMPLE 185A in EXAMPLE 185B, for the compound of EXAMPLE 186A. EXAMPLE 186C The desired compound was synthesized by substituting the product of EXAMPLE 185B in EXAMPLE 185C, by the product of EXAMPLE 186B. EXAMPLE 186D The desired compound was synthesized by substituting the product of EXAMPLE 185C in EXAMPLE 185D, by the product of EXAMPLE 186C. MS: IQD (+) m / e 353.2 (M + H) *. EXAMPLE 186E fra / 7s-3-iodo-1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-yl-amine prepared as described in Application PCT Patent WO 2005/074603 (86 mg, 0.2 mmol), the product of EXAMPLE 186D (100 mg, 0.24 mmol), sodium carbonate (42 mg, 0.4 mmol) and Pd (PPh3) 4 (14 mg, 0.0006 mmol) , were dissolved in 2 mL of DME / water (1: 1) and heated in microwave at 130CC for 20 minutes. After subjecting to partition extraction in ethyl acetate and brine, the ethyl acetate phase was washed with brine (3x), dried and the crude product was purified by HPLC to obtain 55 mg of the title compound. MS: IEA (+) m / e 527.4 (M + H) *; IEA (-) m / e 525.3 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 9.65 (br, 1H), 8.74 (s, 1H), 8.31 (s, 1H), 7.93 (d, 1H), 7.78 (d, 1H), 7.60 (dd, 1H), 7.38-7.46 (m, 2H), 7.20-7.38 (m, 2H), 5.68 (s, 2H), 4.78 (m, 1H), 4.03 (m.), 3.70 (m, 3H), 3.36- 3.48 (m, 3H), 3.09-3.23 (m, 2H), 2.19-2.29 (m, 2H), 2.07-2.17 (m, 4H), 1.68-1.83 (m, 2H). EXAMPLE 187 3- (1- (2-Chlorobenzyl) -1H-indol-5-yl) -1-tetrahydro-2H-pyran-4-yl-1H-pi-rane [3, 4-d] pyrim id in-4 -amine The desired product was prepared by substituting (c / 's) -3-iodo-1- (4-morpholin-4-yl-cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidin-4-yl- amine of EXAMPLE 63C, by the product of EXAMPLE 190A. (IEA (+)) m / e 459 (M + H) *; 1 H-NMR (300 MHz, DMSO-d 6) 8.39 (s, 1H), 7.90 (d, 1H), 7.60 (d, 1H), 7.57 (d, 1H), 7.53 (dd, 1H), 7.43 (dd, 1H), 7.33 (td, 1H), 7.25 (td, 1H), 6.79 (dd, 1H), 6.67 (d, 1H), 5.59 (s, 2H), 4.98 (m, 1H), 4.01 (dd, 2H) ), 3.56 (td, 2H), 2.22 (m, 2H), 1.92 (dd, 2H). EXAMPLE 188 3- (2-Benzyl-1 H-benzimidazol-5-yl) -1- (3-methoxypropyl) -1 H -pi-radical [3,4-d] pyrimidin-4-amine EXAMPLE 188A To a solution of 3-iodo-1 H-pyrazolo [3,4-d] pyrimidin-4-yl-amine prepared as described in AF Burchat et al. Bioorg.

Med. Chem. Lett. 2002, 12, 1687-1690 (0.500 g, 1.9 mmol), 3-methoxypropanol (0.55 mL, 5.7 mmol) and triphenylphosphine (1.01 g, 3.8 mmol) in 24 mL of TH F, DIAD (0.75 mL, 3.8 mmol) was added slowly. The reaction mixture was stirred at room temperature overnight. Additional triphenylphosphine (0.500 g) and DIAD (0.37 mL) were added, and the reaction mixture was stirred overnight. The solvent was then removed under reduced pressure and the residue was purified on silica in a Flashmaster Solo purification system (C H2Cl2 / MeOH), to obtain 492.3 mg of the title compound. EXAMPLE 188B A solution of 2-phenylacetonitrile (40 mg, 341 mmol) in EtOH (22 mL) was cooled to 0 ° C, then HCl gas was bubbled into the reaction mixture for 10 minutes. The reaction mixture was then allowed to warm to room temperature and left to stand overnight. Then, ether was added, and the solvent was removed under reduced pressure. The resulting solid was treated with ether and filtered. The filtrate pellet was washed with ether and dried over NaOH / P2O5 overnight under vacuum to obtain 58 g of the desired compound as a white solid. EXAMPLE 1 88C To a solution of EXAMPLE 280A (6.9 g, 29.6 mmol) in MeOH (150 mL), the product of EJ EM PLO 1 88B (6.40 g, 32.5 mmol) was added and the resulting reaction mixture it stirred for 1.5 hours. The reaction mixture was concentrated under reduced pressure and CH2Cl2 was added. The resulting mixture was filtered, and the filtrate was concentrated on silica gel. The reaction mixture was purified on silica through a purification system l ntelliflash-280 (EtOAc / hexanes), to obtain the desired product (6.50 g) as a white solid. EXAMPLE 188D The desired product was prepared by substituting (c / s) -3-iodo-1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-yl-amine for the product of EXAMPLE 188A and the product of EXAMPLE 63B for that of EXAMPLE 188C, respectively, in EXAMPLE 63C.

(IEA (+)) m / e 414 (M + H) *; 1 H-NMR (300 MHz, DMSO-d 6) 8.34 (s, 1H), 7. 92 (s, 1H), 7.86 (d, 1H), 7.72 (m, 1H), 7.42 (m, 4H), 7.34 (m, 1H), 4.50 (s, 2H), 4.43 (t, 2H), 3.36 (t, 2H), 3.22 (s, 3H), 2.08 (m, 2H). EXAMPLE 189 3- (1- (2-Chlorobenzyl) -1H-indol-5-yl) -1- (3-methoxypropyl) -1 H -pyrazolo [3,4- d] pyrimidin-4-amine The desired product is prepared by substituting the product of EXAMPLE 63B for that of EXAMPLE 93C and (c / 's) -3-iodo-1- (4-morpholin-4-yl-cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidin-4-yl-amine by the product of EXAMPLE 188A, respectively, in EXAMPLE 63C.

(IEA (+)) m / e 414 (M + H) *; 1 H NMR (300 MHz, DMSO-d 6) 8.38 (s, 1 H), 7. 89 (s, 1H), 7.58 (m, 2H), 7.54 (d, 1H), 7.44 (d, 1H), 7.33 (m, 1H), 7.25 (m, 1H), 6.80 (m, 1H), 6.66 (m, 1H), 5.59 (s, 2H), 4.43 (t, 2H), 3. 37 (t, 2H), 3.22 (s, 3H), 2.09 (m, 2H). EXAMPLE 190 3- (2-Benzyl-1H-benzimidazol-5-yl) -1-tetrahydro-2H-pyran-4-yl-1H-pyrazolo [3,4-d] pyrim id in-4-amine EXAMPLE 190 A This example was prepared by substituting 3-methoxypropanol from EXAMPLE 188A for tetrahydro-2H-pyran-4-ol. EXAMPLE 190B This example was prepared by substituting the product of the EXAMPLE 63B by that of EXAMPLE 188C and (c / s) -3-iodo-1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-yl- amine by the product of EXAMPLE 190A, respectively, in EXAMPLE 63C. (IEA (+)) m / e 426 (M + H) *; 1 H-NMR (300 MHz, DMSO-d 6) 8.30 (s, 1 H), 7.90 (s, 1 H), 7.84 (d, 1 H), 7.71 (d, 1 H), 7.42 (m, 4 H), 7.35 (m, 1H), 4.97 (m, 1H), 4.48 (s, 2H), 4.01 (m, 2H), 3.56 (m, 2H), 2.22 (m, 2H), 1.91 (m, 2H). EXAMPLE 191 3- (2-Benzyl-1 H-benzimidazol-5-yl) -1- (1-methylpiperidin-4-yl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 191A East Example was prepared by substituting 3-methoxypropanol in EXAMPLE 188A for 1-methylpiperidin-4-ol. EXAMPLE 191B This example was prepared by substituting the product of the EXAMPLE 63B by that of EXAMPLE 188C and (c / s) -3-iodo-1- (4-morphol-n-4-yl-cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidin-4-i I-amine by the product of EXAMPLE 191A, respectively, in EXAMPLE 63C. (IEA (+)) m / e 439 (M + H) *; 1 H-NMR (300 MHz, DMSO-d 6) 8.30 (s, 1 H), 7.84 (s, 1 H), 7.80 (d, 1 H), 7.62 (d, 1 H), 7.40 (M, 4 H), 7.32 (m, 1 HOUR), . 03 (m, 1H), 4.42 (s, 2H), 3.60 (m, 2H), 3.28 (m, 2H), 2.84 (d, 2H), 2.44 (m, 2H), 2.21 (m, 2H). EXAMPLE 192 3- (1- (2-Chlorobenzyl) -1H-indol-5-yl) -1- (1-methylpiperidin-4-yl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine Example was prepared by substituting (c / s) -3-iodo-1- (4-morphol in -4-i-cyclohexy I) -1 H -pyrazolo [3,4-d] pyrimidin-4-yl- amine EXAMPLE 63C, by the product of EXAMPLE 192A. (IEA (+)) m / e 472 (M + H) +; 1 H-NMR (300 MHz, DMSO-d 6) 9.45 (br s, 1H), 8.30 (s, 1H), 7.87 (d, 1H), 7.59 (d, 1H), 7.57 (d, 1H), 7.52 (dd) , 1H), 7.41 (dd, 1H), 7.33 (td, 1H), 7.25 (td, 1H), 6.78 (d, 1H), 6.67 (d, 1H), 5.59 (s, 2H), 5.02 (m, 1H), 3.61 (m, 2H), 3.28 (m, 2H), 2.84 (d, 2H), 2.42 (m, 2H), 2.20 (m, 2H). EXAMPLE 193 3- (2-Benzyl-1H-benzimidazol-5-yl) -1- (3- (dimethylamino) propyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 193A This example was prepared substituting 3-methoxypropanol from EXAMPLE 188A for 3- (dimethylamino) propan-1-ol. EXAMPLE 193B This example was prepared by substituting the product of the EXAMPLE 63B by that of EXAMPLE 188C and (c / s) -3-iodo-1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-yl- amine by the product of EXAMPLE 193A, respectively, in EXAMPLE 63C. (IEA (+)) m / e 427 (M + H) *; (IEA (-)) m / e 425 (M-H) *; 1 H-NMR (300 MHz, DMSO-d6) 9.37 (br s, 1H), 8.32 (s, 1H), 7.87 (s, 1H), 7.82 (d, 1H), 7.68 (d, 1H), 7.41 (m, 4H), 7.33 (m , 1H), 4.45 (m, 4H), 3.14 (m, 2H), 2.78 (s, 3H), 2.77 (s, 3H), 2.24 (m, 2H). EXAMPLE 194 3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1- (3- (dimethylamino) propyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine This example was prepared by substituting (c / s) -3-iodo-1- (4-morfol i n-4-i I-cyclohexy I) - 1 H -pyrazolo [3,4-d] pyrimidin-4-i I -amine EXAMPLE 63C, by the product of EXAMPLE 193A. (IEA (+)) m / e 460 (M + H) *; 1 H-NMR (300 MHz, DMSO-d 6) 9.32 (br s, 1 H), 8.31 (s, 1 H), 7.89 (d, 1 H), 7.59 (d, 1 H), 7.57 (d, 1 H), 7.53 (dd) , 1H), 7.43 (dd, 1H), 7.33 (td, 1H), 7.25 (td, 1H), 6.80 (dd, 1H), 6.66 (d, 1H), 5.59 (s, 2H), 4.44 (t, 2H), 3.14 (m, 2H), 2.78 (s, 3H), 2.77 (s, 3H), 2.24 (m, 2H). EXAMPLE 195 (fraps) -3- (2- (2-bromobenzyl) -1H-benzimidazol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4-d] ] pyrimidin-4-amine This example was prepared as described in EXAMPLE 7, substituting the benzaldehyde of EXAMPLE 7B, for (2-bromophenyl) -acetaldehyde. MS (ESI) m / e 587 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 9.63 (bs, 1H), 8.29 (s, 1H), 7.81 (s, 1H), 7.75 (d , 1H), 7.70 (d, 1H), 7.61 (d, 1H), 7.48 (m, 2H), 7.32 (m, 1H), 4.79 (m, 1H), 4.53 (s, 2H), 4.04 (m, 2H), 3.69 (m, 2H), 3.46 (m, 2H), 3.18 (m, 2H), 2.27 (m, 2H), 2.13 (m, 4H), 1.76 (m, 2H). EXAMPLE 196 (frans) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-5-yl) -1- (4-morpholin-4-yl- cycle hexi l) -1 H-pi razo lo [3, 4-d] pirim din-4-a mi This example was prepared as described in EXAMPLE 7, substituting the benzaldehyde of EXAMPLE 7B, for (2- methoxyphenyl) acetaldehyde. MS (ESI) m / e 539 (M + H) J 1 H-NMR (300 MHz, DMSO-de) d 9.74 (bs, 1H), 8.31 (s, 1H), 7.88 (s, 1H), 7.84 (d , 1H), 7.71 (d, 1H), 7.38 (m, 2H), 7.08 (d, 1H), 7.02 (t, 1H), 4.79 (m, 1H), 4.45 (s, 2H), 4.04 (m, 2H), 3.70 (m, 2H), 3.46 (m, 2H), 3.18 (m, 2H), 2.26 (m, 2H), 2.13 (m, 4H), 1.76 (m, 2H). EXAMPLE 197 (c / s) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-5-yl) -1-. { 4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl} -1H-pyrazolo [3,4-d] pyrimidin-4-amine This compound is the slowest eluting isomer of EXAMPLE 198. MS (ESI) m / e 610 (M + H) J 1 H-NMR (300 MHz, DMSO-d6) d 8.31 (s, 1H), 7.88 (s, 1H), 7.83 (d, 1H), 7.72 (d, 1H), 7.38 (m, 2H), 7.08 (d, 1H), 7.02 (t , 1H), 4.92 (m, 1H), 4.44 (s, 2H), 3.78 (s, 3H), 3.47 (m, 5H), 3.37 (t, 2H), 3.24 (s, 3H), 3.00 (m, 5H), 2.34 (m, 3H), 2.06 (m, 3H), 1.86 (m, 4H). EXAMPLE 198 (frans) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-5-yl) -1-. { 4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl} -1 H-pyrazolo [3,4-d] pyrimidin-4-amine The desired product was prepared by substituting 2- (trifluoromethyl) -5,6,7,8-tetrahydroimidazo [1,2-a] pyrazine from EXAMPLE 338 , by 1- (3-methoxypropyl) piperazine. The elution isomer was isolated faster. MS (ESI) m / e 610 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 8.29 (s, 1 H), 7.86 (s, 1 H), 7.82 (d, 1 H), 7.71 (d , 1H), 7.38 (m, 2H), 7.08 (d, 1H), 7.02 (t, 1H), 4.75 (m, 1H), 4.44 (s, 2H), 3.78 (s, 3H), 3.65 (m, 5H), 3.39 (t, 2H), 3.25 (s, 3H), 2.95 (m, 5H), 2.09 (m, 6H), 1.83 (m, 2H), 1.67 (m, 4H). EXAMPLE 199 (fra / 7s) -3- (2- (2-bromobenzyl) -1H-benzimidazol-5-yl) -1-. { - (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl} 1 H-pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 199A The desired product was prepared by substituting the product of EXAMPLE 7A and benzaldehyde, for 2-bromophenylacetaldehyde and the product of EXAMPLE 31A, respectively, in EXAMPLE 7B . EXAMPLE 199B The desired product was prepared by substituting the product of EXAMPLE 31B and the 3-hydroxypyrrolidine for 1- (3-methoxypropyl) piperazine and the product of EXAMPLE 199A, respectively, in EXAMPLE 31C. The fastest eluting diastereomer was isolated. MS (ESI) m / e 660 (M + H) J 1 H-NMR (300 MHz, DMSO-de) d 8.30 (s, 1 H), 7.82 (s, 1 H), 7.76 (d, 1 H), 7.71 (d , 1H), 7.61 (d, 1H), 7.48 (m, 2H), 7.32 (t, 1H), 4.75 (m, 1H), 4.55 (s, 2H), 3.45 (m, 5H), 3.39 (t, 2H), 3.25 (s, 3H), 2.98 (M, 5H), 2.10 (m, 6H), 1.84 (m, 2H), 1.67 (m, 2H).

EXAMPLE 200 (c / s) -3- (2- (2-bromobenzyl) -1H-benzimidazol-5-yl) -1-. { 4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl} -1H-pyrazolo [3,4-d] pyrimidin-4-amine The desired product was the slower elution isomer of EXAMPLE 199B. MS (ESI) m / e 660 (M + H) J 1 H-NMR (300 MHz, DMSO-de) d 8.29 (s, 1 H), 7.81 (s, 1 H), 7.74 (d, 1 H), 7.70 (d , 1H), 7.59 (d, 1H), 7.45 (m, 2H), 7.31 (t, 1H), 4.90 (m, 1H), 4.50 (s, 2H), 3.62 (m, 5H), 3.37 (t, 2H), 3.23 (s, 3H), 2.98 (m, 5H), 2.33 (m, 2H), 2.06 (m, 3H), 1.84 (m, 5H). EXAMPLE 201 3- (1- (2-Chlorobenzyl) -1H-indol-5-yl) -1- (1'-methyl-1,4'-bipiperidin-4-yl) -1H-pyrazolo [3,4- d] pyrimidin-4-amine EXAMPLE 201A 4- (4-Amino-3-iodo-1H-pyrazolo [3,4-d] pyrimidin-1-yl) piperidine-1-ferf-butyl carboxylate The title compound, in the form of an off-white solid, it was prepared as described in EXAMPLE 139A, substituting 3- (pyridin-3-yl) propan-1-ol for 4-hydroxypiperidine-1-carboxylate of ferf-butyl. MS (ESI +) m / e 445 (M + H) *; (ESI (-)) m / e 443 (MH) J 1 H-NMR (300 MHz, DMSO-d 6) 8.20 (s, 1H), 7.77 (vbr s, 2H), 4.80 (m, 1H), 4.06 (m , 2H), 2.94 (m, 2H), 1.89 (m, 2H), 1.67 (m, 2H), 1.43 (s, 9H). EXAMPLE 201B 4- (4-amino-3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4- d] pyrimidin-1-yl) piperidine-1-carboxylate ferf-butyl The title compound, in the form of a yellow solid foam, was prepared in the manner described in EXAMPLE 139B, substituting the compound of EXAMPLE 139A for the compound of EXAMPLE 201A and the compound of EXAMPLE 188C for the compound of EXAMPLE 63B, except that the purification was performed on normal-phase silica gel. MS (ESI +) m / e 558 (M + H) *; (ESI (-)) m / e 556 (M-H) J 1 H-NMR (300 MHz, DMSO-d 6) 8.24 (s, 1H), 7. 88 (s, 1H), 7.56 (m, 3H), 7.42 (d, 1H), 7.37 (m, 1H), 7.24 (m, 1H), 6.75 (dd, 1H), 6.66 (d, 1H), 6.28 (vbr s, 2H), 5.58 (s, 2H), 4.90 (m, 1H), 4.10 (m, 2H), 2.97 (m, 2H), 2.05 (m, 2H), 1.95 (m, 2H), 1.42 (s, 9H). EXAMPLE 201C 3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1- (piperidin-4-yl) -1H-pyrazolo [3,4- d] pyrimidin-4-amine A solution of the Compound of EXAMPLE 201 B (1.28 g, 2.3 mmol) in anhydrous CH 2 Cl 2 (30 mL) was cooled in an ice bath and TFA (7.5 mL) was added dropwise under an inert atmosphere. After stirring for 15 min., The ice bath was stirred and the reaction mixture was allowed to warm to room temperature under stirring for 1 hour. The reaction mixture was concentrated and the residue was dissolved in 1M HCl. The solution was washed with EtOAc, basified with Na2CO31M (pH 9-10) and subjected to extraction with 5% MeOH / CH2Cl2 (3 x 100 mL). The extracts were combined and the combined was dried over Na2SO4, filtered, concentrated and dried, to obtain the title compound in the form of a brown foam (70%). MS (ESI +) m / e 458 (M + H) *; 1 H-NMR (300 MHz, DMSO-de) 8.22 (s, 1H), 7.88 (s, 1H), 7.55 (m, 3H), 7.42 (d, 1H), 7.33 (m, 1H), 7.25 (m, 1H), 6.74 (dd, 1H), 6.67 (d, 1H), 6.24 (vbr s, 3H), 5.59 (s, 2H), 4.73 (m, 1H), 3.07 (m, 2H), 2.63 (m, 2H), 2.04 (m, 2H), 1.82 (m, 2H). EXAMPLE 201D 3- (1- (2-Chlorobenzyl) -1H-indol-5-yl) -1- (1'-methyl-1,4'-bipiperidin-4-yl) -1 H-pyrazolo [3,4 -d] pyrimidin-4-amine A 20 mL vial was loaded with the compound of the EXAMPLE 201C (79 mg, 0.17 mmol), DMF (5 mL), CICH2CH2CI (5 mL), acetic acid (40 mL, 0.7 mmol) and l-methylpiperidin-4-one (80 mL, 0.7 mmol). The vial was purged with argon and sodium triacetoxyborohydride (110 mg, 0.5 mmol) was added in portions over a period of 5 minutes. The vial was sealed and the mixture was stirred for 18 hours. The reaction mixture was concentrated and the residue was purified by reverse phase preparative HPLC to obtain the title compound as a brown solid (89%). MS (ESI +) m / e 555 (M + H) *; (ESI (-)) m / e 553 (MH) J 1 H-NMR (300 MHz, DMSO-d 6) 9.80 (br s, 2 H), 8.30 (s, 1 H), 7.88 (s, 1 H), 7.57 (m , 3H), 7.43 (d, 1H), 7.34 (m, 1H), 7.26 (m, 1H), 6.81 (dd, 1H), 6.66 (d, 1H), 5.59 (s, 2H), 5.11 (m, 1H), 3.63 (m, 4H), 3.45 (m, 1H), 3.34 (m, 2H), 3.02 (m, 2H), 2.78 (s, 3H), 2.51 (m, 2H), 2.27 (m, 4H) ), 1.90 (m, 2H). EXAMPLE 202 3- (1- (2-Chlorobenzyl) -1H-indol-5-yl) -1- (1'-ethyl-1,4'-bipiperidin-4-yl) -1H- pi [3, 4-d] pyrim idin-4-amine The title compound, as a whitish solid, was prepared in the manner described in EXAMPLE 201, substituting 1-methylpiperidin-4-one. of EXAMPLE 201 D, by 1-ethylpiperidin-4-one. MS (ESI +) m / e 569 (M + H) *; (ESI (-)) m / e 567 (M-H) J 1 H-NMR (300 MHz, DMSO-d 6) 9.82 (br s, 1H), 9.58 (br s, 1H), 8. 30 (s, 1H), 7.88 (s, 1H), 7.57 (m, 3H), 7.43 (d, 1H), 7.34 (m, 1H), 7. 25 (m, 1H), 6.80 (dd, 1H), 6.67 (d, 1H), 5.59 (s, 2H), 5.11 (m, 1H), 3. 66 (m, 4H), 3.48 (m, 1H), 3.35 (m, 2H), 3.12 (m, 2H), 2.96 (m, 2H), 2.54 (m, 2H), 2.29 (m, 4H), 1.93 (m, 2H), 1.23 (t, 3H). EXAMPLE 203 3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1- (1'-propyl-1,4'-bipiperidin-4-yl) -1H-pyrazolo [3,4- d] pyrimidin-4-amine The title compound, as an off-white solid, was prepared in the manner described in EXAMPLE 201, substituting the 1-methylpiperidin-4-one of EXAMPLE 201D, for 1-propylpiperidine- 4-one. MS (ESI +) m / e 583 (M + H) *; (IEA (-)) m / e 581 (M-H) J 1 H-NMR (300 MHz, DMSO-d 6) 9.78 (br s, 1H), 9.57 (br s, 1H), 8. 30 (s, 1H), 7.89 (s, 1H), 7.57 (m, 3H), 7.43 (d, 1H), 7.34 (m, 1H), 7.26 (m, 1H), 6.80 (dd, 1H), 6.67 (d, 1H), 5.59 (s, 2H), 5.12 (m, 1H), 3. 64 (m, 4H), 3.49 (m, 1H), 3.35 (m, 2H), 3.00 (m, 4H), 2.55 (m, 2H), 2. 28 (m, 4H), 1.94 (m, 2H), 1.67 (m, 2H), 0.91 (t, 3H). EXAMPLE 204 3- (1- (2-chlorobenzyl) -1 H -indol-5-yl) -1- (1'-isopropyl-1,4'-bipiperidin-4-yl) -1 H-pyrazolo [3, 4-d] pyrimidin-4-amine The title compound, as a brown solid, was prepared in the manner described in EXAMPLE 201, substituting the 1-methylpiperidin-4-one of EXAMPLE 201D for 1-isopropylpiperidin-4-one. MS (ESI +) m / e 583 (M + H) *; (ESI (-)) m / e 581 (MH) J 1 H-NMR (300 MHz, DMSO-d 6) 9.83 (br s, 1H), 9.42 (br s, 1H), 8.30 (s, 1H), 7.89 ( s, 1H), 7.57 (m, 3H), 7.43 (d, 1H), 7.34 (m, 1H), 7.25 (m, 1H), 6.80 (dd, 1H), 6.66 (d, 1H), 5.58 (s) , 2H), 5.13 (m, 1H), 3.56 (m, 6H), 3.36 (m, 2H), 3.04 (m, 2H), 2.54 (m, 2H), 2.29 (m, 4H), 1.97 (m, 2H), 1.25 (d, 6H). EXAMPLE 205 3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1- (1, -isobutyl-1,4'-bipiperidin-4-yl) -1H-pyrazolo [3,4 -d] pyrimidin-4-amine The title compound, as an off-white solid, was prepared in the manner described in EXAMPLE 201, substituting l-methylpiperidin-4-one from EXAMPLE 201D for 1-isobutylpiperidine. -4-one. MS (ESI +) m / e 597 (M + H) *; (ESI (-)) m / e 595 (MH) J 1 H-NMR (300 MHz, DMSO-d 6) 9.82 (br s, 1 H), 9.22 (br s, 1 H), 8.29 (s, 1 H), 7.88 ( s, 1H), 7.57 (m, 3H), 7.43 (d, 1H), 7.35 (m, 1H), 7.25 (m, 1H), 6.80 (dd, 1H), 6.67 (d, 1H), 5.58 (s) , 2H), 5.12 (m, 1H), 3.65 (m, 4H), 3.38 (m, 2H), 2.92 (m, 4H), 2.53 (m, 2H), 2.25 (m, 4H), 2.05 (m, 4H), 0.96 (d, 6H). EXAMPLE 206 (f-ans) -3- (2-benzyl-1H-indol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidine- 4-amine EXAMPLE 206A 5-Bromoindole (1.96 g, 10 mmol) was dissolved in 20 mL of or DMF and 60% sodium hydride (440 mg, 11 mmol) was added. It was stirred at room temperature for 30 minutes. After adding benzyl bromide (1.31 mL, 11 mmol), the mixture was stirred at 50 ° C overnight. EtOAc was added, followed by brine. The EtOAc phase was washed with water (x2), with brine (x3), dried over Na2SO and then evaporated to dryness, to obtain 2.82 g of the title compound. MS: IQD (+) m / e 287.9 (M + H) *; IEA (-) m / e 285.9 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 7.74 (d, 1H), 7.56 (d, 1H), 7.42 (d, 1H), 7.15-7.32 (m, 6H), 6.48 (dd, 1H), 5.43 ( s, 2H). EXAMPLE 206B The compound of EXAMPLE 206A (140 mg, 0.5 mmol) was added to 10 mL of polyphosphoric acid (PPA) and stirred at 90 ° C for 16 hours. The mixture was emptied in ice-water. The product was extracted with feri-butyl methyl ether (x3) and the organic phase was washed with 10% sodium bicarbonate (x3), with brine (x3) and dried over Na2SO4. The reaction mixture was evaporated to dryness to obtain 120 mg of the title compound. MS: IQD (+) m / e 287.9 (M + H) *; IEA (-) m / e 285.9 (M-H); 1 H-NMR (300 MHz, DMSO-de) 11.14 (br, 1H), 7.59 (d, 1H), 7.22-7.34 (m, 7H), 7.09 (dd, 1H), 6.13 (d, 1H), 4.06 ( s, 2H). EXAMPLE 206C The desired product was synthesized by substituting the 4-bromo-2-nitrophenylamine of EXAMPLE 2A for the compound of EXAMPLE 206B. MS: IQD (+) m / e 333.7 (M + H) *. EXAMPLE 206D The desired product was synthesized by substituting the compound of EXAMPLE 318A for frans-3-iodo-1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-] - pyrimidin-4-yl. -amine prepared in the manner described in PCT Patent Application WO 2005/074603 and the compound of EXAMPLE 217C by the compound of EXAMPLE 206C, respectively, in EXAMPLE 318B. MS: IEA (+) m / e 508.3 (M + H) *; IEA (-) m / e 506.3 (M-H); 1 H-NMR (300 MHz, DMSO-de) 11.24 (s, 1H), 9.64 (br, 1H), 8.30 (s, 1H), 7.69 (d, 1H), 7.44 (d, 1H), 7.21- 7.33 ( m, 6H), 6.28 (d, 1H), 4.76 (m, 1H), 4.11 (s, 2H), 4.03 (m, 2H), 3. 64-3.75 (m, 2H), 3.32-3.49 (m, 3H), 3.10-3.23 (m, 2H), 2.20-2.29 (m, 2H), 2.07-2.19 (m, 4H), 1.70-1.83 (m, 2H). EXAMPLE 207 (fra / 7s) -3- (2-benzyl-1 H-indol-6-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 207A The desired product was synthesized by substituting the 5-bromoindole of EXAMPLE 206A for 6-bromoindole. EXAMPLE 207B The desired product was synthesized by substituting the compound of EXAMPLE 206A, for the compound of the EXAMPLE 207A, in EXAMPLE 206B. MS: IQD (+) m / e 287.8 (M + H) *; IEA (-) m / e 285.8 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 11.13 (br, 1H), 7.44 (d, 1H), 7.36 (d, 1H), 7.19-7.34 (m, 5H), 7.04 (dd, 1H), 6.16 ( d, 1H), 4. 06 (s, 2H). EXAMPLE 207C The desired product was synthesized by substituting the compound of EXAMPLE 206B, for the compound of EXAMPLE 207B, in EXAMPLE 206C. MS: IQD (+) m / e 334.3 (M + H) *. EXAMPLE 207D The desired product was synthesized by substituting the compound of EXAMPLE 318A for frans-3-iodo-1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-yl. -amine prepared in the manner described in PCT Patent Application WO 2005/074603 and the compound of EXAMPLE 217C by the compound of EXAMPLE 207C, respectively, in EXAMPLE 318B. MS: IEA (+) m / e 508.3 (M + H) *; IEA (-) m / e 506.2 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 11.24 (s, 1H), 9.63 (br, 1H), 8.30 (s, 1H), 7.54-7.60 (m, 2H), 7.32-7.33 (m, 4H), 7.22-7.27 (m, 2H), 6.25 (d , 1H), 4.77 (m, 1H), 4.11 (s, 2H), 4.03 (m, 2H), 3.64-3.75 (m, 2H), 3.40-3.50 (m, 3H), 3.10-3.23 (m, 2H), 2. 19-2.29 (m, 2H), 2.07-2.18 (m, 4H), 1.70-1.83 (m, 2H). EXAMPLE 208 3- (1- (2-Chlorobenzyl) -1H-indol-5-yl) -1- (4-. {(4- (3-methoxypropyl) piperazin-1-yl) methyl} phenyl) - 1 H-pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 208A 4- (4-amino-3-iodo-1 H -pyrazolo [3,4-d] pyrimidin-1-yl) benzaldehyde To a slurry NaH (1.68 g, 42.1 mmol, 60% in oil) in 300 mL of DMF at RT, was added 3-iodo-1 H -pyrazolo [3,4-d] pyrimidin-4-amine (10 g, 38.3 mmol) through a funnel addition of solids, in a period of 45 minutes. After concluding the addition of the amine, 4-fluorobenzaldehyde (5.0 g, 40.2 mmol) was added dropwise to the reaction mixture. The reaction mixture was heated at 1000 ° C for 24 hours, additional NaH (0.25 equivalents) was added and the mixture was stirred at 100 ° C for another 24 hours. The reaction mixture was cooled to room temperature for 2 hours, a precipitate formed after cooling. The reaction mixture was filtered, washed sequentially with water, then Et2O, to obtain a brown solid, 6.5 g, 47% yield. EXAM PLO 208B 3-iodo-1 - (4 - ((4- (3-methoxypropyl) piperazin-1-yl) methyl) phenyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine A solution of 1- (3-methoxypropyl) piperazine (1.30 g, 8.22 mmol) and the compound of EX EMPLO 208A (1.0 g, 2.74 mmol), was mixed with 1.5 mL of a solution of CH3OH / AcOH (9 mL). : 1, v / v) and heated at 70 ° C for 3 hours. The reaction mixture was cooled to room temperature, diluted with a mixture of CH2Cl2 / I PA (4: 1, v / v) and washed with a saturated aqueous solution of NaHCO3. The phases were separated and the organic phase was dried over MgSO, filtered and reduced in vacuo directly on silica. The reaction mixture was purified by a purification system l ntelliflash-280 (CH2Cl2 / MeOH), to obtain a white solid, 0.45 g, 33% yield.

EXAMPLE 208C The compound of EXAMPLE 208B (0.2 g, 0.39 mmol) and the EXAMPLE 93A (0.22 g, 0.59 mmol) were mixed in a solution 0. 3M DME / H2O (2: 1, v / v), 2M Na2CO3 in aqueous solution (0.39 mL, 0.39 mmol) was added and the reaction mixture was heated to 130 ° C for 20 minutes in a microwave reactor. The crude reaction mixture was filtered over Celite®. The pad was washed with CH2Cl2 and MeOH, the filtrate was dried over MgSO, filtered and reduced in vacuo. The material was purified by a purification system lntelliflash-280 (CH2Cl2 / MeOH), to obtain the desired product.

(IEA (+)) m / e 621 (M + H) *; 1 H-NMR (300 MHz, DMSO-d 6) 8.37 (s, 1H), 8. 18 (d, 2H), 7.98 (s, 1H), 7.62-7.45 (m, 6H), 7.34-7.24 (m, 2H), 6.78 (d, 1H), 6.70 (d, 1H), 5.61 (s, 2H), 3.51 (s, 2H), 3.20 (s, 3H), 2.39 (bs, 6H), 2.29 (t, 3H), 1.63 (m, 2H). EXAMPLE 209 (fra /? S) -3- (2- (2-Chlorobenzyl) -1H-indol-6-yl) -1- (4-morpholin-4-yl-cyclohexyl) - 1 Hp i razolo [3, 4-d] pyrim id-n-4-amine EXAMPLE 209A The desired product was synthesized by substituting 5-bromoindole for 6-bromoindole and benzyl bromide of EXAMPLE 206A, for 2-chlorobenzyl bromide. EXAMPLE 209B The desired product was synthesized by substituting the compound of EXAMPLE 206A for the compound of EXAMPLE 209A in EXAMPLE 206B. MS: IQD (+) m / e 319.9 (M + H) *; IEA (-) m / e 317. 9 (M-H). EXAMPLE 209C The desired product was synthesized by substituting the 4-bromo-2-nitrophenylamine of EXAMPLE 2A for the compound of EXAMPLE 209B. MS: IQD (+) m / e 368.3 (M + H) *. EXAMPLE 209D The devised product was synthesized by substituting the compound of EXAMPLE 318A for frar) s-3-iodo-1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4-] - pyrimidine 4-yl-amine prepared in the manner described in Patent Application WO 2005/074603 and the compound of EXAMPLE 217C by the compound of EXAMPLE 209C, in EXAMPLE 318B. MS: IEA (+) m / e 542.3 (M + H) *; IEA (-) m / e 540. 3 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 11.29 (s, 1 H), 9.72 (br, 1H), 8.33 (s, 1H), 7.57-7.60 (m, 2H), 7.47-7.75 (m, 2H), 7.25-7.41 (m, 4H), 6.16 (s, 1H), 4.78 (m, 1H) , 4.24 (s, 2H), 4.04 (m, 2H), 3.64-3.75 (m, 2H), 3.40-3.50 (m, 3H), 3.10-3.23 (m, 2H), 2.19-2.29 (m, 2H), 2. 07-2.18 (m, 4H), 1.70-1.83 (m, 2H). EXAMPLE 210 { 3 - ((4- {4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4- d] pyrimidin-1-yl}. cyclohexyl) amino) phenyl} methanol 5-Bromoindole (1.96 g, 10 mmol) was dissolved in 20 mL of DMF, 60% NaH (0.44 g, 11 mmol) was added. The reaction mixture was stirred for 30 minutes and then 2-fluorobenzyl bromide (1.33 mL, 11 mmol) was added. Stirring was continued at 50 ° C for 5 hours. After diluting with EtOAc, the organic phase was washed with brine (5x), dried over MgSO4. After evaporating to dryness, the mixture was dried under high vacuum to obtain N-2-fluorobenzyl-5-bromoindole in quantitative yield. The title compound was prepared by substituting the 4-bromo-2-nitrophenylamine of EXAMPLE 2A for N-2-fluorobenzyl-5-bromoindole (3.04 g, 10 mmol). The crude material was purified by column chromatography on silica gel, eluting with 2.5% EtOAc in hexane. 2.18 g of the title compound were obtained. MS: IEA (+) m / e 352.1 (M + H) *. EXAMPLE 210B 3-Iodo-1- (4-oxo-cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidin-4-yl-amine prepared as described in A. F. Burchat et al. Bioorg Med. Chem. Lett. 2002, 12, 1687-1690 (1192 g, 3.34 mmol), the compound of EXAMPLE 210A (1.29 g, 3.67 mmol), Na2CO3 (708 mg, 6.68 mmol) and Pd (PPh3) (227 mg, 0.1 mmol) in a Microwave reaction tube and 30 mL of DME / water (1: 1) were added. The mixture was heated with microwaves at 130 ° C for 20 minutes. 50 mL of EtOAc and 20 mL of water were added. The solid precipitate was collected by filtration, washed with water and dried, to obtain 600 mg of the title compound. MS: IQD (+) m / e 455.07 (M + H) *. EXAMPLE 210C The compound of EXAMPLE 210B (45 mg, 0.1 mmol) and 3-aminobenzyl alcohol (123 mg, 1 mmol), were dissolved in 2 mL of methanol and 0.2 mL of acetic acid. After stirring at room temperature for 30 minutes, sodium cyanoborohydride was added (31 mg, 0.5 mmol) and the mixture was stirred at 70 ° C for 16 hours. The mixture was partitioned into EtOAc and brine, the EtOAc layer was washed with brine (3x) and dried over MgSO. The crude product was purified by high performance liquid chromatography (HPLC) to obtain 46 mg of the title compound as a mixture of diastereoisomers. MS: IEA (+) m / e 562.4 (M + H) *; IEA (-) m / e 560.3 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 8.40 (s, 0.6H), 8.38 (s, 0.4H), 7.87 (m, 1H), 7.68 (d, 1H), 7.59 (t, 1H), 7.45 ( m, 1H), 7.34 (m, 1H), 7.26 (m, 1H), 7.07-7.19 (m, 3H), 6.64 (m, 1H), 5.56 (s, 2H), 4.44 (s, 0.4H), 4.41 (s, 0.6H), 3.62 (br, 0.6H), 3.40-3.51 (m, 0.4H), 2.26-2.43 (m, 1H), 1.95-2.18 (m, 3H), 1.77-1.91 (m, 2H). EXAMPLE 211 4 - ((4- {4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4- d] pyrimidin-1-yl .) cyclohexyl) amino) -3-methylphenol The desired product was prepared as a mixture of diastereoisomers, substituting the 3-aminobenzyl alcohol of EXAMPLE 210C, for 4-amino-m-cresol. MS: IEA (+) m / e 562.3 (M + H) *; IEA (-) m / e 560.3 (M-H); H-NMR (300 MHz, DMSO-d6) 8.32 (s, 1H), 7.91 (m, 1H), 7.22-7.71 (m, 5H), 7.07-7.18 (m, 3H), 6.61-6.76 (m, 3H) ), 5.57 (s, 2H), 4.92 (br, 1H), 3.52 (br, 1H), 2.31 (s, 3H), 1.92-2.13 (m, 6H). EXAMPLE 212 3 - ((4- {4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4- d] pyrimidin-1-yl .}. cyclohexyl) amino) phenol The desired product was prepared as a mixture of diastereoisomers, substituting the 3-aminobenzyl alcohol of EXAMPLE 210C, for 3-aminophenol. MS: IEA (+) m / e 548.3 (M + H) *; IEA (-) m / e 546.3 (M-H); H-NMR (300 MHz, DMSO-d6) 8.39 (s, 0.6H), 8.37 (s, 0.4H), 7.88 (m, 1H), 7.68 (d, 1H), 7.58 (dd, 1H), 7.42- 7.47 (m, 1H), 7.32-7.38 (m, 1H), 7.22-7.28 (m, 1H), 7.14-7.17 (m, 2H), 6.86-7.06 (br m, 1H), 6.63-6.65 (m, 1H), 6.07-6.42 (br 2H), 5.55 (s, 2H), 4.70-4.90 (br 1H), 2.25-2.41 (m, 1H), 1.92-2.19 (m, 4H), 1.75-1.92 ( m, 2H), 1.42-1.60 (m, 1H). EXAMPLE 213 4 - ((4- {. {4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4- d] pyrimidin-1-yl ethyl cyclohexyl) amino) benzoate The desired product was prepared as a mixture of diastereoisomers, substituting the 3-aminobenzyl alcohol of EXAMPLE 210C, for 4-aminophenylacetic acid ethyl ester. MS: IEA (+) m / e 618.4 (M + H) *; IEA (-) m / e 616.6 (M-H); 1 H-NMR (300 MHz, DMSO-de) 8.40 (s, 0.6H), 8.39 (s, 0.4H), 7.88 (m, 1H), 7.68 (d, 1H), 7.58 (d, 1H), 7.43- 7.47 (m, 1H), 7.32-7.39 (m, 1H), 7.22-7.28 (m, 1H), 7.14-7.17 (m, 2H), 7.02-7.04 (br, 1H), 6.74 (br, 1H), 6.64 (d.1H), 5.55 (s, 2H), 4.78-4.89 (br.1H), 4.01-4.09 (m, 2H), 3.42-3.61 (m, 3H), 2.26-2.43 (m, 1H), 1.92-2.21 (m, 4H), 1.76-1.91 (m, 3H), 1.15-1.20 (m, 3H). EXAMPLE 214 Acid (frans) -3 - ((4- {4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] pyrimidin-1-yl.}. cyclohexyl) amino) benzoic The desired product was prepared by substituting the alcohol 3- aminobenzyl ester of EXAMPLE 210C, by 4-aminobenzoic acid. The diastereomer that eluted first was isolated. MS: IEA (+) m / e 618.4 (M + H) *; IEA (-) m / e 616.6 (M-H); 1 H-NMR (300 MHz, DMSO-dβ) 8.40 (s, 0.6H), 8.39 (s, 0.4H), 7.88 (m, 1H), 7.68 (d, 1H), 7.58 (d, 1H), 7.43- 7.47 (m, 1H), 7.32-7.39 (M, 1H), 7.22-7.28 (m, 1H), 7.14-7.17 (m, 2H), 7.02-7.04 (br, 1H), 6.74 (br, 1H), 6.64 (d.1H), 5.55 (s, 2H), 4.78-4.89 (br.1H), 4.01-4.09 (m, 2H), 3.42-3.61 (m, 3H), 2.26-2.43 (m, 1H), 1.92-2.21 (m, 4H), 1.76-1.91 (m, 3H), 1.15-1.20 (m, 3H). EXAMPLE 215 Acid (c / s) -3 - ((4- {4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4] d] pyrimidin-1-yl}. cyclohexyl) amino) benzoic The desired product was the diastereomer eluting slower in EXAMPLE 214. MS: IEA (+) m / e 576.3 (M + H) *; IEA (-) m / e 574.3 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 8.42 (s, 1H), 7.88 (d, 1H), 7.69 (d, 1H), 7.58 (d, 1H), 7.46 (dd, 1H), 7.32-7.38 ( m, 1H), 7.09-7.28 (m, 6H), 6.89 (dd, 1H), 6.64 (dd, 1H), 5.55 (s, 2H), 4.84 (br 1H), 3.62 (m, 1H), 2.28 -2.42 (m, 2H), 1.93-2.05 (m, 2H), 1.78-1.92 (m, 4H). EXAMPLE 216 Cfra / 7s) -3- (2- (2-chlorobenzyl) -1H-indol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4 -d] pyrimidin-4-amine EXAMPLE 216A The desired product was synthesized by replacing the benzyl bromide of EXAMPLE 206A with 2-chlorobenzyl bromide.

EXAMPLE 216B The desired product was synthesized by substituting the compound of EXAMPLE 206A, for the compound of EXAMPLE 216A, in EXAMPLE 206B. EXAMPLE 216C The desired product was synthesized by substituting the 4-bromo-2-nitrophenylamine of EXAMPLE 2A for the compound of EXAMPLE 216B. EXAMPLE 216D The desired product was synthesized by substituting the compound of EXAMPLE 218A for f / -a / 7S-3-iodo-1- (4-morpholin-4-yl-cyclohexyl) -1H-pyrazolo [3,4-d] -pyrimidin-4-ylamine prepared in the manner described in PCT Patent Application WO 2005/074603 and the compound of EXAMPLE 217C by the compound of EXAMPLE 216C, in EXAMPLE 318B. 1 H-NMR (300 MHz, DMSO-de) 11.30 (s, 1 H), 9.64 (br, 1 H), 8.30 (s, 1 H), 7.68 (d, 1 H), 7.46 (d, 1 H), 7.32 (m, 3H), 7.29 (m, 2H), 6.19 (s, 1H), 4.76 (m, 1H), 4.23 (s, 2H), 4.02 (m, 2H), 3.44 (m, 3H), 3.17 (m, 2H) ), 2.26 (m, 2H), 2.13 (m, 4H), 1.75 (m, 2H). EXAMPLE 217 (frans) -3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4-d] ] pyrimidin-4-amine EXAMPLE 217A The desired product was synthesized by substituting the benzyl bromide of EXAMPLE 206A, for 2-fluorobenzyl bromide.

EXAMPLE 217B The desired product was synthesized by substituting the compound of EXAMPLE 206A, for the compound of EXAMPLE 217A, in EXAMPLE 206B. EXAMPLE 217C The desired product was synthesized by substituting the 4-bromo-2-nitrophenylamine of EXAMPLE 2A for the compound of EXAMPLE 217B. MS: IQD (+) m / e 352.4 (M + H) *. EXAMPLE 217D The desired product was synthesized by substituting the compound of EXAMPLE 218A for f / -a / 7s-3-iodo-1- (4-morpholin-4-yl-cyclohexyl) -1H-pyrazolo [3,4-d] -pyrimidin-4-ylamine prepared in the manner described in PCT Patent Application WO 2005/074603 and the compound of EXAMPLE 217C by the compound of EXAMPLE 217C, in EXAMPLE 318B. After it was purified by CLAR, to obtain mg, of the title compound. MS: IEA (+) m / e 526.4 (M + H) *; IEA (-) m / e 524.4 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 11.28 (s, 1 H), 9.61 (br, 1H), 8.29 (s, 1H), 7.68 (d, 1H), 7.46 (d, 1H), 7.28-7.38 (m, 3H), 7. 15-7.24 (m, 2H), 6.22 (s, 1H), 4.76 (m, 1H), 4.14 (s, 2H), 4.03 (m, 2H), 3.40-3.50 (m, 3H), 3.10-3.24 ( m, 2H), 2.20-2.29 (m, 2H), 2.07-2.28 (m, 4H), 1.68-1.83 (m, 2H). EXAMPLE 218 3 - ((4- {4-amino-3- (1- (2-fluorobenzyl) -1 H -indol-5-yl) -1 H- pi-reason [3, 4-d] -pyrim acid idin-1-yl.}. cyclohexyl) amino) -4-chlorobenzoic The desired product was prepared by substituting the alcohol 3- aminobenzyl ester by 3-amino-4-chlorobenzoic acid, in EXAMPLE 210C. MS: IEA (+) m / e 610.5 (M + H) *; IEA (-) m / e 608.5 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 8.38 (s, 0.4H), 8.37 (s, 0.6H), 7.88 (M, 1H), 7.69 (d, 1H), 7.13-7.48 (m, 10H), 6.64 (d, 1H), 5.55 (s, 2H), 4.78-4.89 (br, 1H), 4.01-4.09 (m, 2H), 2.22-2.34 (m, 2H), 2.01-2.19 (m, 4H), 1.84-1.97 (m, 2H). EXAMPLE 219 (fraps) -3- (2- (4-methylphenoxy) -1H-benzimidazol-6-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4-d] ] pyrimidin-4-amine EXAMPLE 219A 5-b rom o-2- (p-tolyloxy) -1H-benzo [d] im id azol To a microwave vial was added p-cresol (0.326 g, 3. 02 mmol), 60% sodium hydride in dispersion (0.12 g, 3.02 mmol), DMF (2.2 mL), and the solution was allowed to stir at room temperature for 30 minutes. To the reaction mixture was added the compound of EXAMPLE 133A (0.5 g, 2.16 mmol) and heated at 170 ° C for 20 minutes, in a microwave reactor.

To the reaction mixture was added ethyl acetate, and the organic phase was washed 2X with water and with brine. The organic fraction was dried over magnesium sulfate, filtered and reduced in vacuo. The residue was purified by LC with a gradient of hexane / ethyl acetate; the solvent was reduced in vacuo to obtain the desired product as a white solid. (IEA (+)) m / e 303, 305 (M + H) *.

EXAMPLE 219B 5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -2- (p-tolyloxy) -1H-benzo [d] imidazole The desired product was prepared by substituting the composed of EXAMPLE 133B by the compound of example 219A, in EXAMPLE 133C. (IEA (+)) m / e 351 (M + H) *. EXAMPLE 219C 1 - ((1R, 4R) -4-morpholinocyclohexyl) -3- (2- (p-tolyloxy) -1H-benzo [d] imidazol-6-yl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine The desired product was prepared by substituting the compound of EXAMPLE 133C for the compound of EXAMPLE 219B, in EXAMPLE 133D. (IEA (+)) m / e 525 (M + H) *; (IEA (-)) m / e 523 (MH) J 1 H-NMR (500 MHz, ACETONA-d 6) 10.96 (bs, 1H), 8.46 (s, 1H), 7.71 (s, 1H), 7.57-7.47 ( m, 2H), 7.34-7.23 (m, 4H), 5.34 (bs, 2H), 4.93 (ddd, 1H), 4.03 (bs, 4H), 3.65-3.55 (m, 2H), 3.50 (t, 2H) , 3.28 (s, 2H), 2.49 (d, 2H), 2.35 (s, 3H), 2.32-2.26 (m, 4H), 2.07 (m, 2H). EXAMPLE 220 (frans) -3- (2- (3-methylphenoxy) -1H-benzimidazol-6-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [3,4-d] ] pyrimidin-4-amine EXAMPLE 220A 5-bromo-2- (m-tolyloxy) -1H-benzo [d] imidazole The desired product was prepared by substituting 5-bromo-2- (phenylsulfonyl) -1H-benzo [d] -imidazole for 5-bromo-2- (m-tolyloxy) -1 H -benzo [d] -imidazole, in EXAMPLE 219A. (IEA (+)) m / e 351 (M + H) *.

EXAMPLE 220B 5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) -2- (m-tolyloxy) -1H-benzo [d] imidazole The desired product was prepared by substituting the composed of EXAMPLE 133D by the compound of EXAMPLE 220A, in EXAMPLE 133C. (IEA (+)) m / e 351 (M + H) *. EXAMPLE 220C 1 - ((1 R, 4R) -4-morpholinocyclohexyl) -3- (2- (m-tolyloxy) -1 H- benzo [d] imidazol-6-yl) -1 H -pyrazolo [3,4- d] pyrimidin-4-amine The desired product was prepared by substituting the compound of EXAMPLE 133C for the compound of EXAMPLE 220B, in EXAMPLE 133D. (IEA (+)) m / e 525 (M + H) *; (IEA (-)) m / e 523 (MH) J 1 H-NMR (500 MHz, ACETONA-d 6) 10.93 (bs, 1H), 8.47 (s, 1H), 7.74 (d, 1H), 7.58-7.55 ( m, 1H), 7.53-7.49 (m, 1H), 7.35 (t, 1H), 7.27-7.23 (m, 2H), 7.12 (d, 1H), 4.98-4.88 (m, 1H), 4.03 (bs, 4H), 3.66-3.55 (m, 2H), 3.54-3.45 (m, 2H), 3.28 (s, 2H), 2.49 (d, 2H), 2.38 (s, 3H), 2.33-2.25 (m, 4H) , 2.07 (m, 2H). EXAMPLE 221 3- (4- (4- { 4-amino-3- (3- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4- d] pyrimidin-1 -yl.}. cyclohexyl) piperazin-1-yl) propan-1-ol The title product was isolated as a by-product in EXAMPLE 223. MS: IEA (+) m / e 583.4 (M + H) *; IEA (-) m / e 581.5 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 11.33-11.36 (m, 1H), 8.31 (s, 1H includes 8.30), 7.43-7.47 (m, 1H), 7.26-7.34 (m, 2H), 7.11-7.23 (m, 3H), 6.20 (d, 1H), 4.92 (m, 0.6H), 4.75 (m, 0.4H), 4.12 (s, 2H), 3.42- 3. 53 (m, 4H), 2.82-3.16 (m, 4H), 2.24-2.41 (m, 2H), 2.02-2.15 (m, 4H), 1.60-1.95 (m, 4H). EXAMPLE 222 (c / s) -3- (4- (4- { 4-amino-3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4 -d] pyrimidin-1-yl}. cyclohexyl) piperazin-1-yl) propan-1-ol The desired product was the diastereomer eluting slower in EXAMPLE 223. MS: IEA (+) m / e 583.4 ( M + H) *; IEA (-) m / e 581.5 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 11.30 (s, 1H), 8.31 (s, 1H), 7.70 (s, 1H), 7.48 (d, 1H), 7.28-7.38 (m, 3H), 7.15- 7.24 (m, 2H), 6.22 (d, 1H), 4.94 (m, 1H), 4.15 (s, 2H), 3.42-3.53 (m, 4H, includes = 3.46, t, 2H), 2.89-3.16 (m , 4H), 2.24-2.41 (m, 2H), 2.02-2.14 (m, 2H), 1.68-1.94 (m, 4H). EXAMPLE 223 (frans) -3- (4- (4-. {4-amino-3- (2- (2-fluorobenzyl) -1H-indol-5-M) -1H-pyrazolo [3,4-d] ] pyrimidin-1-yl}. cyclohexyl) piperazin-1-yl) propan-1-ol EXAMPLE 223A The desired product was synthesized by substituting the compound of EXAMPLE 318A for 3-iodo-1- (4-oxo-cyclohexyl) - 1 H-pyrazolo [3,4-d] pyrimidin-4-yl-amine prepared in the manner described in AF Burchat et al. Bioorg Med. Chem. Lett. 2002, 12, 1687-1690, in EXAMPLE 318B. MS: IEA (+) m / e 455.5 (M + H) *. EXAMPLE 223B The desired product was synthesized by substituting 1- (2-hydroxyethyl) piperazine for 1- (3-hydroxypropyl) -piperazine, in EXAMPLE 134B. The diastereomer that eluted first was isolated.

MS: IEA (+) m / e 583.5 (M + H) *; IEA (-) m / e 581.6 (M-H); 1 H-NMR (300 MHz, DMSO-de) 11 25 (s, 1H), 8.27 (s, 1H), 7.68 (d, 1H), 7.47 (d, 1H), 7.28-7.38 (m, 3H), 7.16 -7.25 (m, 2H), 6.22 (d, 1H), 4.72 (m, 1H), 4.14 (s, 2H), 3.42-3.53 (m, 4H, includes = 3.48, t, 2H), 2.90-3.16 ( m, 4H), 2.02-2.17 (M, 6H), 1.61-1.84 (m, 4H). EXAMPLE 224 3- (3- (2-Fluorobenzyl) -1H-indol-5-yl) -1-. { 4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl} -1H-pyrazolo [3,4-d] pyrimidin-4-amine The title product was isolated as a by-product in EXAMPLE 225. MS: IEA (+) m / e 597.5 (M + H) *; IEA (-) m / e 595.4 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 11.31-11.36 (m, 1H), 8.30 (s, 0.6H), 8.29 (s, 0.4H), 7.43-7.47 (m, 1H), 7.25-7.34 (m , 2H), 7.13-7.22 (m, 3H), 6.20 (d, 1H), 4.92 (m, 0.6H), 4.78 (m, 0.4H), 4.12 (s, 2H), 3.33-3.41 (m, 4H ), 3.25 (s, 1.3H), 3.22 (s, 1.7H), 2.82-3.16 (m, 4H), 2.24-2.41 (m, 2H), 2.02-2.15 (m, 4H), 1.60-1.95 (m , 4H). EXAMPLE 225 3- (2- (2-Fluorobenzyl) -1H-indol-5-yl) -1-. { 4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl} -1H-pyrazolo [3, 4-d] pyrimidin-4-amine The desired product was synthesized as a mixture of diastereoisomers, substituting 1- (2-hydroxyethyl) piperazine for 1- (3-methoxypropyl) piperazine, in EXAMPLE 134B. MS: IEA (+) m / e 597.4 (M + H) *; IEA (-) m / e 595.5 (M-H); 1 H-NMR (300 MHz, DMSO-de) 11.29 (s, 1H), 8.29 (s, 1H includes 8.30, s), 7.69 (br d, 1H), 7.47 (dd, 1H), 7.28-7.38 (m, 3H), 7.15-7.24 (m, 2H), 6.22 (s, 1H), 4.94 (brm, 0.5H), 4.73 (brm, 0.5H), 4.14 (s, 2H), 3.42-3.53 (m, 4H, includes = 3. 37, t, 2H), 3.25 (s, 1.5H), 3.23 (s, 1.5H), 2.90-3.16 (m, 4H), 2.02-2.18 (m, 4H), 1.60-1.94 (m, 4H). EXAMPLE 226 2- (4- (4- { 4-amino-3- (3- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4- d] pyrimidin-1 -yl.} cyclohexyl) piperazin-1-yl) ethanol The title product was isolated as a by-product in EXAMPLE 227. MS: IEA (+) m / e 569.4 (M + H) +; IEA (-) m / e 567.4 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 11.33-11.38 (m, 1H), 8.31 (s, 0.6H), 8.30 (s, 0.4H), 7.43-7.47 (m, 1H), 7.25-7.33 (m , 2H), 7.12-7.23 (m, 3H), 6.19 (d, 1H), 4.94 (m, 0.6H), 4.77 (m,., 0.4H), 4.13 (s, 2H), 3.38-3.54 (m , 4H), 2.92-3.20 (m, 4H), 2.24-2.40 (m, 2H), 1.98-2.17 (m, 4H), 1.65-1.95 (m, 2H). EXAMPLE 227 (c / s) -2- (4- (4- { 4-amino-3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4 -d] pyrimidin-1-yl.} cyclohexyl) piperazin-1-yl) ethanol The desired product was synthesized by substituting the compound of EXAMPLE 134A for the compound of EXAMPLE 223A, in EXAMPLE 134B. The diastereomer that eluted first was isolated. MS: IEA (+) m / e 569.4 (M + H) *; IEA (-) m / e 567.4 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 11.29 (s, 1H), 8.30 (s, 1H), 7.69 (br d, 1H), 7.47 (dd, 1H), 7.29-7.37 (m, 3H), 7.15 -7.24 (m, 2H), 6.22 (s, 1H), 4.89 (br m, 1H), 4.15 (s, 2H), 3.42-3.53 (m, 4H, includes = 3.69, t, 2H), 3.34-3.59 (m, 3H), 2.98-3.18 (m, 4H), 2.26-2.40 (m, 2H), 2.02-2.18 (m, 4H), 1.74-1.94 (m, 4H).

EXAMPLE 228 (frarjs) -2- (4- (4- { 4-amino-3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] ] pyrimidin-1-yl}. cyclohexyl) piperazin-1-yl) ethanol The desired product was the diastereomer eluting slower in EXAMPLE 227. MS: IEA (+) m / e 569.4 (M + H) *; IEA (-) m / e 567.4 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 11.30 (s, 1H), 8.32 (s, 1H), 7.68 (d, 1H), 7.47 (d, 1H), 7.28-7.39 (m, 3H), 7.15- 7.24 (m, 2H), 6.22 (d, 1H), 4.75 (m, 1H), 4.15 (s, 2H), 3.42-3.53 (m, 4H, includes = 3.72, t, 2H), 3.01-3.19 (m , 4H), 2.04-2.20 (m, 4H), 1.52-1.64 (m, 2H). EXAMPLE 229 (c / s) -3- (4- { 4-4-amino-3- (2-benzyl-1H-indol-5-yl) -1H-pyrazolo [3,4- d] pyrimidine- 1-yl) cyclohexyl} piperazin-1-il} propan-1-ol EXAMPLE 229A The desired product was synthesized by substituting the compound of EXAMPLE 318A for 3-iodo-1- (4-oxo-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-yl- amine prepared in the manner described in AF Burchat et al. Bioorg Med. Chem. Lett. 2002, 12, 1687-1690 and the compound of EXAMPLE 217C by the compound of EXAMPLE 207C, in EXAMPLE 318B. MS: IEA (+) m / e 437.2 EXAMPLE 229B The desired product was synthesized by substituting the compound of EXAMPLE 223A for the compound of EXAMPLE 229A, in EXAMPLE 134B. The diastereomer that eluted first was isolated. MS: IEA (+) m / e 565.4 (M + H) *; IEA (-) m / e 563.4 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 11.26 (s, 1 H), 8.32 (s, 1 H), 7.70 (s, 1 H), 7. 45 (d, 1H), 7.22-7.33 (m, 6H), 6.23 (d, 1H), 4.90 (m, 1H), 4.11 (s, 2H), 3.40-3.58 (m, 4H, includes = 3.47, t 2H); 2.26-2.40 (m, 1H), 2.09-3.13 (m, 3H), 2.24-2.41 (m, 1H), 2.03-2.16 (m, 2H), 1.68-1.94 (m, 4H). EXAMPLE 230 (frans) -3- (4-. {4- (4-amino-3- (2-benzyl-1H-indol-5-yl) -1H-pyrazolo [3,4- d] pyrimidin-1 -yl) cyclohexyl.} piperazin-1-yl) propan-1-ol This example was the diastereomer eluting slower in EXAMPLE 229. MS: IEA (+) m / e 565.5 (M + H) *; IEA (-) m / e 563.4 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 11.26 (s, 1H), 8.34 (s, 1H), 7.69 (d, 1H), 7.46 (d, 1H), 7.21-7.33 (m, 6H), 6.28 ( d, 1H), 4.76 (m, 1H), 4.11 (s, 2H), 3.41-3.65 (m, 4H, includes = 3.49, t, 2H), 3.01-3.18 (m, 4H), 2.04-2.18 (m , 4H), 1.64-1.83 (m, 2H). EXAMPLE 231 3- (2-Benzyl-1H-indol-5-yl) -1-. { 4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl} -1 H-pyrazolo [3,4-d] pyrimidin-4-amine The desired product was synthesized as a mixture of diastereoisomers, substituting 1- (3-hydroxypropyl) piperazine for 1- (3-methoxypropyl) piperazine and the compound of EXAMPLE 223A by the compound of EXAMPLE 229A, in EXAMPLE 134B. MS: IEA (+) m / e 579.5 (M + H) *; IEA (-) m / e 577.4 (M-H); 1 H-NMR (300 MHz, DMSO-de) 11.26 (s, 1H), 8.31 (s, 0.6H), 8.30 (s, 0.4), 7.43-7.47 (m, 1H), 7.21-7.33 (m, 7H) , 6.28 (s, 1H), 4.90 (br m, 0.6H), 4.74 (br m, 0.4H), 4.11 (s, 2H), 3.42-3.53 (m, 4H, includes = 3.38, q, 2H), 3.25 (s, 1.5H), 3.23 (s, 1.5H), 2.82-3.12 (m, 4H), 2.26-2.40 (m, 2H), 2.02-2.18 (m, 4H), 1.60-1.94 (m, 4H). EXAMPLE 232 (c / s) -2- (4-. {4- (4-amino-3- (2-benzyl-1H-indol-5-yl) -1H-pyrazolo [3,4- d] pyrimidine -1-yl) cyclohexyl. Piperazin-1-yl) ethanol The desired product was synthesized by substituting the compound of EXAMPLE 134A for the compound of EXAMPLE 229A, in EXAMPLE 134B. The diastereomer that eluted first was isolated. MS: IEA (+) m / e 551.5 (M + H) *; IEA (-) m / e 549.4 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 11.27 (s, 1H), 8.33 (s, 1H), 7.71 (br d, 1H), 7.46 (dd, 1H), 7.22-7.33 (m, 6H), 6.28 (s, 1H), 4.92 (br m, 1H), 4.11 (s, 2H), 3.70 (t, 2H), 3.42-3.61 (m, 2H), 3.05-3.20 (m, 4H), 2.30-2.41 ( m, 1H), 2.02-2.18 (m, 2H), 1.80-1.94 (m, 2H). EXAMPLE 233 (f? Ans) -2- (4-. {4- (4-amino-3- (2-benzyl-1H-indol-5-yl) -1H-pyrazolo [3,4- d] pyrimidine -1-yl) cyclohexyl. Piperazin-1-yl) ethanol This example was the diastereomer that eluted slower in EXAMPLE 232. MS: IEA (+) m / e 551.4 (M + H) *; IEA (-) m / e 549.5 (M-H); 'H-NMR (300 MHz, DMSO-d6) 11-25 (s, 1H), 8.30 (s, 1H), 7.69 (d, 1H), 7.54-7.65 (m, 2H), 7.45 (d, 1H) , 7.21-7.33 (m, 4H), 6.28 (d, 1H), 4.74 (m, 1H), 4.11 (s, 2H), 3.71 (t, 2H), 3.42-3.61 (m, 2H), 3.00-3.20 (M, 4H), 2.02-2.18 (m, 4H), 1.60-1.77 (m, 2H). EXAMPLE 234 (c / s) -4- (4- { 4-amino-5- (1- (2-fluorobenzyl) -1H-indol-5-yl) -7H-pyrrolo [2,3- d] pyrimidin-7-yl.}. cyclohexyl) -1-isopropylpiperazin-2-one The desired product was synthesized by substituting 3-iodo-1- (4-oxo-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-yl-amine by (c / s) -4- (4- (4-amino-3-iodo-pyrazolo [3] , 4-d] pyrimidin-1-yl) -cyclohexyl) -1-isopropyl-piperazin-2-one prepared in the manner described in International Patent Publication WO 2005/074603, in EXAMPLE 210B. MS (ESI) m / e 580 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 8.39 (s, 1 H), 7.68 (s, 1 H), 7.62 (d, 1 H), 7.56 (m , 2H), 7.34 (m, 1H), 7.28 (s, 1H), 7.24 (m, 1H), 7.15 (m, 2H), 6.56 (d, 1H), 5.53 (s, 2H), 4.84 (m, 1H), 4.62 (m, 1H), 3.44 (m, 6H), 2.18 (m, 4H), 1.91 (m, 4H), 1.10 (d, 6H). EXAMPLE 235 (c / s) -4- (4- { 4-amino-5- (1- (2-chlorobenzyl) -1H-indol-5-yl) -7H-pyrrolo [2,3- d] pyrimidin-7-yl.} cyclohexyl) -1-isopropylpiperazin-2-one The desired product was synthesized by substituting trans-3-iodo-1- (4-morpholin-4-yl-cyclohexyl) -1H-pyrazolo [3 , 4-d] pyrimidin-4-yl-amine by (c / s) -4- (4- (4-amino-3-iodo-pyrazolo [3,4-d] pyrimidin-1-yl) -cyclohexyl) -1-isopropyl-piperazin-2-one prepared in the manner described in International Patent Publication WO 2005/074603, in EXAMPLE 93B. MS (ESI) m / e 596 (M + H) J 1 H-NMR (300 MHz, DMSO-de) d 8.40 (s, 1H), 7.71 (s, 1H), 7.56 (m, 4H), 7.33 (t , 1H), 7.26 (m, 2H), 6.77 (d, 1H), 6.59 (d, 1H), 5.57 (s, 2H), 4.85 (m, 1H), 4.62 (m, 1H), 3.45 (m, 6H), 2.18 (m, 4H), 1.91 (m, 4H), 1.10 (d, 6H). EXAMPLE 236 (c / 's) -4- (4- { 4-amino-5- (1 - (2-f luorobenzyl) -1H-indol-5-yl) -7H-pyrrolo [2, 3 d] pyrimidin-7-yl.}. cyclohexyl) -1-ethylpiperazin-2-one The desired product was synthesized by substituting 3-iodo-1- (4-oxo-cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidin-4-yl-amine by (c / 's) -4- (4- (4-amino-3-iodo-pyrazolo [ 3,4-d] pyrimidin-1-yl) -cyclohexyl) -1-ethylpiperazin-2-one prepared in the manner described in International Patent Publication WO 2005/074603, in EXAMPLE 210B. MS (ESI) m / e 566 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 8.39 (s, 1 H), 7.68 (s, 1 H), 7.62 (d, 1 H), 7.56 (m , 2H), 7.35 (m, 1H), 7.28 (s, 1H), 7.24 (m, 1H), 7.15 (m, 2H), 6.56 (d, 1H), 5.53 (s, 2H), 4.84 (m, 1H), 3.66 (m, 6H), 3.39 (q, 2H), 2.17 (m, 4H), 1.91 (m, 4H), 1.07 (t, 3H). EXAMPLE 237 (c / 's) -4- (4- { 4-amino-5- (1- (2-chlorobenzyl) -1H-indol-5-yl) -7H-pyrrolo [2,3- d ] pyrimidin-7-yl}. cyclohexyl) -1-ethylpiperazin-2-one The desired product was synthesized by substituting trans-3-iodo-1- (4-morpholin-4-yl-cyclohexyl) -1H-pyrazolo [ 3, 4-d] pyrim id in-4-yl-amine by (c / 's) -4- (4- (4-amino-3-iodo-pyrazolo [3,4-d] pyrimidin-1-M ) -cyclohexyl) -1-ethylpiperazin-2-one prepared in the manner described in International Patent Publication WO 2005/074603, in EXAMPLE 93B. MS (ESI) m / e 582 (M + H) J 1 H-NMR (300 MHz, DMSO-de) d 8.39 (s, 1 H), 7.71 (s, 1 H), 7.54 (m, 4 H), 7.34 (t , 1H), 7.27 (m, 2H), 6.78 (d, 1H), 6.59 (d, 1H), 5.57 (s, 2H), 4.85 (m, 1H), 3.66 (m, 6H), 3.39 (q, 2H), 2.17 (m, 4H), 1.91 (m, 4H), 1.07 (t, 3H). EXAMPLE 238 5- (1 - (2-f luorobenzyl) -1 H-indol-5-yl) -7- (4- (4-methyl piperazin-1-yl) cyclohexyl) -7H-pyrrolo [2,3- d] pyrimidin-4-amine The desired product was synthesized by substituting 3-iodo-1- (4-oxo-cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidin-4-yl-amine by 3-iodo-1- (4- (4- (methyl-piperazin-1-yl) -cyclohexyl) - 1H-pyrazolo [3,4-d] pyrimidin-4-yl) -amine prepared in the manner described in AF Burchat et al. Bioorg Med. Chem. Lett. 2002, 12, 1687-1690, in EXAMPLE 210B. MS (ESI) m / e 538 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) δ 8.42, 8.41 (s, 1H), 7.67, 7.68 (s, 1H), 7.62 (d, 1H). , 7.56 (m, 2H), 7.35 (m, 1H), 7.27 (m, 2H), 7.15 (m, 2H), 6.56 (d, 1H), 5.53 (s, 2H), 4.80, 4.67 (m, 1H) ), 3.42 (m, 4H), 3.25, 3.07 (m, 4H), 2.77 (s, 3H), 2.04 (m, 4H), 1.91-1.59 (m, 4H). EXAMPLE 239 5- (1- (2-Chlorobenzyl) -1 H -indol-5-yl) -7- (4- (4-methyl-piperazin-1-yl) -cyclohexyl) -7H-pyrrolo [2,3-d] pyrimidin-4-amine The desired product was synthesized by substituting trans-3-iodo-1- (4-morpholin-4-yl-cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidin-4-yl-amine for 3-Iodo-1- (4- (4-methyl-piperazin-1-yl) -cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-yl) -amine prepared in the manner described in AF Burchat ef to the. Bioorg Med. Chem. Lett. 2002, 12, 1687-1690, in EXAMPLE 93B. MS (ESI) m / e 554 (M + H) J 1 H-NMR (300 MHz, DMSO-de) d 8.41, 8.40 (s, 1H), 7.70 (m, 2H), 7.56 (m, 3H), 7.34. (m, 1H), 7.25 (m, 2H), 6.78 (m, 1H), 6.60 (d, 1H), 5.57 (s, 2H), 4.80, 4.67 (m, 1H), 3.42 (m, 4H), 3.24, 3.06 (m, 4H), 2.77 (s, 3H), 2.04 (m, 4H), 1.91-1.59 (m, 4H). EXAMPLE 240 7-Ferf-butyl-5- (1- (2-fluorobenzyl) -1H-indol-5-yl) -7H-pyrrolo [2,3-d] pyrimidin-4-amine The desired product was synthesized by substituting 3-iodo-1- (4-oxo-cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidin-4-yl-amine for 1-tert-butyl-5-iodo- 7H-pyrrolo [3,4-d] pyrimidin-4-yl-amine prepared in the manner described in the US Patent Application US20060025383, in EXAMPLE 210B. MS (EAI) m / e 414 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 8.40 (s, 1 H), 7.68 (s, 1 H), 7.62 (d, 1 H), 7.55 (m , 2H), 7.35 (m, 1H), 7.26 (m, 2H), 7.15 (m, 2H), 6.56 (d, 1H), 5.53 (s, 2H), 1.76 (s, 9H). EXAMPLE 241 7-Ferf-butyl-5- (1- (2-chlorobenzyl) -1H-indol-5-yl) -7H-pyrrolo [2,3-dyrimidin-4-amine The desired product was synthesized by substituting the trans 3-iodo-1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-yl-amine by 7-ferf-butyl-5-iodo-7H-pyrrolo [3,4-d] pyrimidin-4-yl-amine prepared in the manner described in the US Patent Application US20060025383, in EXAMPLE 93B. MS (EAI) m / e 430 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 8.40 (s, 1 H), 7.71 (s, 1 H), 7.54 (m, 3 H), 7.33 (m , 1H), 7.25 (m, 2H), 6.78 (m, 1H), 6.60 (d, 1H), 5.57 (s, 1H), 1.77 (s, 9H). EXAMPLE 242 3- (1- (2-Fluorobenzyl) -1H-indol-5-yl) -1- (4- (morpholin-4-yl-methyl) phenyl) -1H-pyrazolo [3,4-d] pyrimidine -4-amine The desired product was synthesized by substituting 3-iodo-1- (4-oxo-cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidin-4-yl-amine for the compound of EXAMPLE 48B, in EXAMPLE 210B. EM (LEA) m / e 534 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 9.83 (bs, 1 H), 8.41 (m, 3 H), 7.79 (s, 1 H), 7.71 (m, 3 H), 7.61 (d , 1H), 7.53 (d, 1H), 7.35 (m, 1H), 7.25 (m, 1H), 7.16 (m, 2H), 6.66 (d, 1H), 5.57 (s, 1H), 4.42 (s, 2H), 3.97 (m, 2H), 3.64 (m, 2H), 3.31 (m, 2H), 3.17 (m, 2H). EXAMPLE 243 Acid (frans) -4 - ((4- {4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] pyrimidin-1-yl}. cyclohexyl) amino) benzoic The desired product was prepared by substituting 3-aminobenzyl alcohol for 4-aminobenzoic acid, in EXAMPLE 210C. The diastereomer that eluted first was isolated. MS: IEA (+) m / e 576.4 (M + H) *; IEA (-) m / e 574.4 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 8.39 (s, 1H), 7.88 (d, 1H), 7.65-7.71 (m, 3H), 7.59 (d, 1H), 7.46 (dd, 1H), 7.31- 7.40 (m, 1H), 7.22-7.28 (m, 1H), 7.12-7.20 (m, 2H), 6.62-6.65 (m, 3H), 5.55 (s, 2H), 4.78 (br 1H), 3.46 ( m, 1H), 2.10-2.28 (M, 4H), 1.97-2.08 (m, 2H), 1.39-1.55 (m, 2H). EXAMPLE 244 Acid (c / s) -4 - ((4- {4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4] d] pyrimidin-1-yl}. cyclohexyl) amino) benzoic The desired product was the diastereomer eluting slower in EXAMPLE 243. MS: IEA (+) m / e 576.4 (M + H) *; IEA (-) m / e 574.4 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 8.40 (s, 1H), 7.88 (d, 1H), 7.65-7.70 (m, 3H), 7.59 (d, 1H), 7.45 (dd, 1H), 7.32- 7.40 (m, 1H), 7.22-7.28 (m, 1H), 7.12-7.20 (m, 2H), 6.62-6.69 (m, 3H), 5.55 (s, 2H), 4.85 (br 1H), 3.67 ( m, 1H), 2.24-2.41 (m, 2H), 1.93-2.09 (m, 2H), 1.80-1.93 (m, 4H).

EXAMPLE 245 3- (2- (2-Chlorobenzyl) -1H-benzimidazol-5-yl) -1- (4- (morpholin-4-ylmethyl) phenyl) -1H-pyrazolo [3,4-d] pirim idin-4-a mine The desired product was prepared in the manner described in EXAMPLE 48, substituting phenylacetaldehyde for 2-chlorophenylacetaldehyde, in EXAMPLE 48D. MS (EAI) m / e 551 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 9.85 (bs, 1H), 8.41 (m, 3H), 7.92 (s, 1H), 7.78 (d , 1H), 7.69 (m, 3H), 7.53 (m, 2H), 7.40 (m, 2H), 4.51 (s, 2H), 4.43 (s, 2H), 4.00 (m, 2H), 3.64 (m, 2H), 3.32 (m, 2H), 3.18 (m, 2H). EXAMPLE 246 3- (2- (3-methylbenzyl) -1H-benzimidazol-5-yl) -1- (4- (morpholin-4-yl-methyl) phenyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine The desired product was prepared in the manner described in EXAMPLE 48, substituting phenylacetaldehyde for 3-methylphenylacetaldehyde, in EXAMPLE 48D. MS (LEA) m / e 531 (M + H) -; 1 H-NMR (300 MHz, DMSO-d 6) d 9.91 (bs, 1H), 8.42 (s, 1H), 8.38 (d, 2H), 7.97 (s, 1H), 7.86 (d, 1H), 7.75 (d , 1H), 7.70 (d, 2H), 7.24 (m, 3H), 7.14 (d, 1H), 4.43 (s, 2H), 4.40 (s, 2H), 3.98 (m, 2H), 3.64 (m, 2H), 3.32 (m, 2H), 3.17 (m, 2H). EXAMPLE 247 3- (2- (2-Bromobenzyl) -1H-benzimidazol-5-yl) -1- (4- (morpholin-4-yl-methyl) phenyl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine The desired product was prepared in the manner described in EXAMPLE 48, substituting phenylacetaldehyde for 2- bromophenylacetaldehyde, in EXAMPLE 48D. MS (EAI) m / e 597 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 9.92 (bs, 1H), 8.42 (s, 1H), 8.38 (d, 2H), 7.95 (s) , 1H), 7.81 (d, 1H), 7.72 (m, 4H), 7.50 (m, 2H), 7.32 (m, 1H), 4.56 (s, 2H), 4.43 (s, 2H), 3.98 (m, 2H), 3.64 (m, 2H), 3.32 (m, 2H), 3.17 (m, 2H). EXAMPLE 248 3- (2- (2-methoxybenzyl) -1 H -benzimidazol-5-yl) -1- (4- (morpholin-4-ylmethyl) phenyl) -1 H-pyrazolo [3,4-d ] pyrimidin-4-amine The desired product was prepared in the manner described in EXAMPLE 48, substituting phenylacetaldehyde for 2-methoxyphenylacetaldehyde, in EXAMPLE 48D. MS (EAI) m / e 547 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 9.86 (bs, 1H), 8.42 (s, 1H), 8.38 (d, 2H), 7.96 (s) , 1H), 7.85 (d, 1H), 7.76 (m, 1H), 7.70 (d, 2H), 7.36 (m, 2H), 7.00 (m, 1H), 4.43 (s, 2H), 4.40 (s, 2H), 3.98 (M, 2H), 3.64 (m, 2H), 3.32 (m, 2H), 3.17 (m, 2H). EXAMPLE 249 (frans) -4- (4-. {4- (4-amino-3- (2-benzyl-1 H-benzimidazol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidine- 1-yl) cyclohexyl.}. P.perazin-1-yl) -2-methylbutan-2-ol The desired product was the diastereomer that eluted faster, prepared in the manner described in EXAMPLE 31, substituting 3-hydroxypyrrolidine for 1- (3-hydroxy-3-methylbutyl) piperazine, in EXAMPLE 31C. MS (LEA) m / e 594 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 8.30 (s, 1 H), 7.86 (s, 1 H), 7.81 (d, 1H), 7.67 (d, 1H), 7.42-7.34 (m, 5H), 4.75 (m, 1H), 4.45 (s, 2H), 3.56-3.36 (m, 4H), 3.11-2.97 (m, 6H) , 2.10 (m, 6H), 1.69 (m, 4H), 1.15 (s, 6H). EXAMPLE 250 Cc / s) -4- (4-. {4- (4-amino-3- (2-benzyl-1 H-benzimidazol-5-yl) -1 H-pyrazolo [3,4- d] pyrimidin-1-yl) cyclohexyl] piperazin-1-yl) -2-methylbutan-2-ol The desired product was the diastereomer eluting slower, prepared in the manner described in EXAMPLE 31, substituting the -hydroxypyrrolidine by 1- (3-hydroxy-3-methylbutyl) piperazine, in EXAMPLE 31C. MS (EAI) m / e 594 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 8.33 (s, 1 H), 7.89 (s, 1 H), 7.83 (d, 1 H), 7.68 (d , 1H), 7.42-7.31 (m, 5H), 4.92 (m, 1H), 4.47 (s, 2H), 3.56 (m, 5H), 3.14 (m, 5H), 2.35 (m, 2H), 2.07 ( m, 3H), 1.87 (m, 3H), 1.70 (m, 2H), 1.13 (s, 6H). EXAMPLE 251 (c / s) -3 - ((4- {4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] ] pyrimidin-1-yl}. cyclohexyl) amino) propan-1-ol The desired product was the diastereomer eluting slower in EXAMPLE 252. MS: IEA (+) m / e 514.3 (M + H) *; IEA (-) m / e 512.4 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 8.32 (s, 1H), 8.30 (br.lH), 7.88 (d, 1H), 7.67 (d, 1H), 7.58 (d, 1H), 7.46 (dd, 1H), 7.33-7.38 (m, 1H), 7.22-7.28 (m, 1H), 7.13-7.18 (m, 2H), 6.63 (d, 1H), 5.55 (s, 2H), 4.91 (br. , 3.49 (t, 1H), 3.29 (br. 1H), 3.03 (br.2H), 2.28-2.40 (m, 2H), 2.18-2.24 (m, 6H), 1.71-1.81 (m, 2H). EXAMPLE 252 (frans) -3 - ((4- {4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-] d] pyrimidin-1-yl.}. cyclohexyl) amino) propan-1-ol The desired product was prepared by substituting 3-aminobenzyl alcohol for 3-amino-1-propanol, in EXAMPLE 210C. The diastereomer that eluted first was isolated. MS: IEA (+) m / e 514.3 (M + H) *; IEA (-) m / e 512.3 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 8.38 (br.lH), 8.30 (s, 1H), 7.84 (d, 1H), 7.67 (d, 1H), 7.58 (d, 1H), 7.42 (dd, 1H), 7.32-7.38 (m, 1H), 7.21-7.28 (m, 1H), 7.13-7.16 (m, 2H), 6.62 (d, 1H), 5.54 (s, 2H), 4.73 (br 1H) , 3.51 (t, 1H), 3.24 (br 1H), 3.03 (br 2H), 2.18-2.20 (m, 2H), 2.02-2.16 (m, 3H), 1.90-2.01 (br 1H), 1.70 -1.81 (m, 2H), 1.53-1.67 (br m, 2H). EXAMPLE 253 2 - ((4- {. {4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4- d] pyrimidin-1-yl .) cyclohexyl) amino) ethanol The desired product was prepared by substituting 3-aminobenzyl alcohol for 2-amino-1-ethanol, in EXAMPLE 210C. MS: IEA (+) m / e 500.3 (M + H) *; IEA (-) m / e 498.3 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 8.50 (br.lH), 8.40 (br.lH), 8.33 (s, 1H), 7.86 (d, 1H), 7.67 (d, 1H), 7.58 (t, 1H), 7.32-7.49 (m, 2H), 7.22-7.28 (m, 1H), 7.14-7.18 (m, 2H), 6.63 (m, 1H), 5.55 (s, 2H), 4.91 (br 0.5H) ), 4.71 (br 0.5H), 3.28 (br 1H), 3.05 (br 2H), 2.31-2.41 (m, 1H), 2.16-2.27 (m, 1H), 1.89-2.12 (m, 6H) , 1.56-1.70 (br m, 2H). EXAMPLE 254 2-. { 2 - ((4- {4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4- d] pyrimidin-1-yl} cyclohexyl) amino) ethoxy} Ethanol The desired product was prepared by substituting the 3-aminobenzyl alcohol for 2- (2-aminoethoxy) ethanol, in EXAMPLE 210C.

MS: IEA (+) m / e 544.4 (M + H) *; IEA (-) m / e 542.4 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 8.50 (br 0.7H), 8.40 (br. 0.3H), 8.32 (s, 1H), 7.84-7.89 (m, 1H), 7.67 (d, 1H), 7.55-7.60 (m, 1H), 7.40-7.49 (m, 1H), 7.34-7.38 (m, 1H), 7.22-7.28 (m, 1H), 7.13-7.18 (m, 2H), 6.62 (m, 1H) ), 5.55 (s, 2H), 4.91 (br 0.3H), 4.71 (br 0.7H), 3.66-3.71 (m, 2H), 3.49-3.59 (m, 4H), 3.14-3.34 (m, 2H) ), 2.17-2.28 (m, 1H), 1.88-2.15 (m, 6H), 1.41-1.72 (br m, 2H). EXAMPLE 255 (c / s) - (2R) -3 - ((4- {4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3 , 4-d] pyrimidin-1-yl}. Cyclohexyl) amino) propane-1,2-diol The desired product was prepared by substituting 3-aminobenzyl alcohol for S - (-) - 3-amino-1, 2- propanediol, in EXAMPLE 210C. The diastereomer that eluted first was isolated. MS: IEA (+) m / e 530.4 (M + H) *; IEA (-) m / e 528.4 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 8.40 (br.lH), 8.31 (s, 1H), 7.89 (d, 1H), 7.67 (d, 1H), 7.59 (d, 1H), 7.47 (dd, 1H), 7.32-7.38 (m, 1H), 7.22-7.28 (m, 1H), 7.13-7.16 (m, 2H), 6.62 (m, 1H), 5.55 (s, 2H), 4.90 (br. , 3.41-3.47 (m, 1H), 3.24-3.36 (m, 2H), 3.07-3.19 (br 1H), 2.77-2.90 (br 1H), 2.30-2.46 (br.2H), 1.87-2.14 ( m, 6H). EXAMPLE 256 (f? Aps) - (2R) -3 - ((4- {4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3 , 4-d] pyrimidin-1-yl}. Cyclohexyl) amino) propane-1,2-diol The desired product was the diastereomer eluting slower in EXAMPLE 255. MS: IEA (+) m / e 530.4 ( M + H) *; IEA (-) m / e 528.4 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 8.47 (br.lH), 8.33 (s, 1H), 7.84 (d, 1H), 7.67 (d, 1H), 7.57 (d, 1H), 7.42 (dd, 1H), 7.32-7.38 (m, 1H), 7.22-7.28 (m, 1H), 7.13 -7.16 (m, 2H), 6.62 (m, 1H), 5.55 (s, 2H), 4.70 (br 1H), 3.80 (br 1H), 3.43-3.49 (m, 1H), 3.31-3.37 (m , 1H), 3.19-3.29 (br 1H), 3.06-3.17 (br 1H), 2.81-2.94 (br 1H), 2.14-2.30 (br.2H), 1.89-2.13 (m, 5H), 1.54 -1.77 (br m, 2H). EXAMPLE 257 2.2, - (4- (4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4- d] pyrimidin-1-yl ) cyclohexylazanodiyl) diethanol The desired product was prepared by substituting 3-aminobenzyl alcohol for diethanolamine, in EXAMPLE 210C. MS: IEA (+) m / e 544.4 (M + H) *; IEA (-) m / e 542.4 (M-H); 1 H-NMR (300 MHz, DMSO-de) 8.68-8.83 (br. 1H), 8.32 (s, 1H), 7.87 (d, 1H), 7.67 (d, 1H), 7.57-7.59 (m, 1H), 7.41-7.49 (m, 1H), 7.32-7.38 (m, 1H), 7.22-7.28 (m, 1H), 7.14-7.18 (m, 2H), 6.62 (m, 1H), 5.55 (s, 2H), 5.04 (br, 0.6H), 4.91 (br 0.4H), 3.76-3.80 (m, 4H), 3.28-3.36 (m, 4H), 1.81-2.35 (m, 8H). EXAMPLE 258 (c / s) -N- (4- { 4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3, 4-d] pyrim id in-1-yl.} cyclohexyl) -beta-alanna The desired product was prepared by substituting 3-aminobenzyl alcohol for -alanine, in EXAMPLE 210C. The diastereomer that eluted first was isolated. MS: IEA (+) m / e 528.4 (M + H) *; IEA (-) m / e 526.4 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 8.34 (br.lH), 8. 30 (s, 1H), 7.87 (s, 1H), 7.67 (d, 1H), 7.58 (d, 1H), 7.46 (dd, 1H), 7.32-7.38 (m, 1H), 7.22-7.28 (m, 1H), 7.13-7.16 (m, 2H), 6.62 (m, 1H), 5.55 (s, 2H), 4.90 (br 1H), 3.15-3.24 (br.3H), 2.64 (t, 2H), 2.24-2.39 (m, 2H), 1.88-2.08 (m, 6H) . EXAMPLE 259 (fra? S) -N- (4- { 4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] ] pyrimidin-1-yl.} cyclohexyl) -beta-alanine The desired product was the diastereomer eluting slower in EXAMPLE 258. MS: IEA (+) m / e 528.3 (M + H) *; IEA (-) m / e 526.4 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 8.45 (br.lH), 8.29 (s, 1H), 7.84 (d, 1H), 7.67 (d, 1H), 7.58 (d, 1H), 7.42 (dd, 1H), 7.32-7.38 (m, 1H), 7.22-7.28 (m, 1H), 7.13-7.16 (m, 2H), 6.62 (m, 1H), 5.55 (s, 2H), 4.66-4.71 (br. 1H), 3.14-3.29 (br.3H), 2.67 (t, 2H), 1.91-2.33 (m, 6H), 1.54-1.69 (m, 2H). EXAMPLE 260 (frans) -4-. { 4-amino-3- (2- (2-methoxybenzyl) -1 H -benzimidazol-5-yl) -1 H- pyrazolo [3,4-d] pyrimidin-1-yl} Cyclohexanol To the compound of EXAMPLE 339C (0.13 g, 0.28 mmol) in a 0.2M solution of MeOH / AcOH (9: 1, v / v), NaCNBH3 (0.035, 0.558 mmol) was added. The reaction mixture was stirred at room temperature for 1.5 hours, diluted with CH2Cl2 and washed with a saturated aqueous solution of NaHCO3. The organic phase was dried over MgSO 4, filtered, reduced in vacuo and purified by reverse phase HPLC. MS (LEA) m / e 470 (M + H) J 1 H-NMR (300 MHz, DMSO-de) d 8.31 (s, 1H), 7.89 (s, 1H), 7.84 (d, 1H), 7.75 (d , 1H), 7.39 (m, 2H), 7.09 (d, 1H), 7.03 (t, 1H), 4.69 (m, 1H), 4.46 (s, 2H), 3.78 (s, 3H), 2.06-1.91 ( m, 6H), 1.42 (m, 2H).

EXAMPLE 261 N- (4-. {4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4- d] pyrimidin-1-yl} cyclohexyl) -L-alanine The desired product was prepared by substituting 3-aminobenzyl alcohol for L-alanine, in EXAMPLE 210C. MS: IEA (+) m / e 528.4 (M + H) *; IEA (-) m / e 526.4 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 8.93 (br.lH), 8.81 (br.lH), 8.34 (br.lH), 8.30 (s, 1H), 7.86 (s, 1H), 7.67 (d, 1H), 7.57-7.59 (m, 1H), 7.41-7.49 (m, 1H), 7.32-7.38 (m, 1H), 7.22-7.28 (m, 1H), 7.13-7.16 (m, 2H), 6.62 ( m, 1H), 5.55 (s, 2H), 4.89 (br 0.4H), 4.69 (m, 0.6H), 4.17 (m, 1H), 3.30 (br 2H), 2.35-2.46 (br m, 1H ), 1.90-2.28 (m, 6H), 1.67-1.77 (br m, 1H), 1.47 (m, 3H). EXAMPLE 262 (c / 's) -N- (4- { 4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pi-ralk [3, 4- d] pyrim id in-1-yl.} cyclohexyl) -D-alanine The desired product was prepared by substituting the 3-aminobenzyl alcohol of EXAMPLE 1011C for D-alanine. The diastereomer that eluted first was isolated. MS: IEA (+) m / e 528.4 (M + H) *; IEA (-) m / e 526.4 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 8.82 (br 2 H), 8.30 (s, 1 H), 7.88 (s, 1 H), 7.67 (d, 1 H), 7.58 (d, 1 H), 7.48 (dd, 1H), 7.32-7.38 (m, 1H), 7.22-7.28 (m, 1H), 7.13-7.15 (m, 2H), 6.62 (m, 1H), 5.55 (s, 2H), 4.89 (br 1H) , 4.16 (m, 1H), 3.31 (br.2H), 2.33-2.47 (br m, 2H), 1.90-2.09 (m, 6H), 1.46 (d, 3H). EXAMPLE 263 (frat7s) -N- (4- { 4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] pyrimidine- 1-yl.} Cyclohexyl) -D-alanine The desired product was the diastereomer that eluted slower in EXAMPLE 258. MS: IEA (+) m / e 528.4 (M + H) *; IEA (-) m / e 526.4 (MH), 1 H-NMR (300 MHz, DMSO-d 6) 8.92 (br 2 H), 8.29 (s, 1 H), 7.84 (s, 1 H), 7.67 (d, 1 H) , 7.56 (d, 1H), 7.44 (dd, 1H), 7.32-7.38 (m, 1H), 7.21-7.28 (m, 1H), 7.13-7.16 (m, 2H), 6.62 (m, 1H), 5.55 (s, 2H), 4.69 (br. 1H), 4.18 (m, 1H), 1.89-2.27 (m, 8H), 1.55-1.75 (m, 2H), 1.48 (d, 3H). EXAMPLE 264 N- (4-. {4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4- d] pyrimidin-1-yl} cyclohexyl) -N-methylglycine The desired product was prepared by substituting 3-aminobenzyl alcohol for sarcosine, in EXAMPLE 210C. MS: IEA (+) m / e 528.4 (M + H) *; IEA (-) m / e 526.4 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 9.63 (br.lH), 8.30 (s, 1H), 7.87 (dd, 1H), 7.67 (d, 1H), 7.57-7.59 (m, 1H), 7.40- 7.49 (m, 1H), 7.32-7.38 (M, 1H), 7.21-7.28 (m, 1H), 7.12-7.18 (m, 2H), 6.62 (m, 1H), 5.55 (s, 2H), 5.00 ( br 0.4H), 4.78 (m, 0.6H), 4.15 (m, 1H), 3.49 (br 2H), 2.85 (s, includes 2.82, s, 3H), 2.30-2.38 (br m, 1H), 2.06-2.22 (m, 4H), 1.91-2.04 (m, 2H), 1.76-1.90 (br m, 1H). EXAMPLE 265 (frans) - 1 -. { 4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl} -3- (2- (t-ene-2-I-methyl) -1 H -benzimidazol-6-yl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 265A 4- ( 4-amino-3- (2- (thiophen-2-yl-methyl) -1H-benzo [d] imidazol-6-yl) -1H-pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexanone A slurry of the compound of EXAMPLE 31A (0.88 g, 2.4 mmol), 2- (thiophen-2-yl) acetaldehyde (0.32 g, 2.5 mmol), 1M Na 2 S 2 O (7.2 mL, 7.2 mmol) in EtOH (8 mL), placed in a microwave reactor and heated at 130 ° C for 20 minutes. The reaction was stopped by the addition of 5M NH OH, diluted with CH2Cl2 / IPA (4: 1, v / v). The resulting phases were separated, the organic phases were dried over MgSO, filtered and reduced in vacuo to obtain the desired product as a brown solid (0.2 g, 20% yield). EXAMPLE 265B To a mixture of the compound of EXAMPLE 265A (0.22 g, 0.5 mmol) and 1- (3-methoxypropyl) piperazine (0.39 g, 2.48 mmol) in a 0.3M solution of MeOH / AcOH (9: 1, v / v ), NaCNBH3 (0.094 g, 1.5 mmol) was added. The reaction mixture was heated to 80 ° C. After heating for 2 hours, the reaction mixture was cooled to room temperature, purified directly by reverse phase HPLC, using the following column conditions: TFA 0.15% in CH3CN / 0.15% in H2O, to obtain 55 mg of the desired material. IEA (+)) m / e 586 (M + H) *; 1 H-NMR (300 MHz, DMSO-d 6) 8.32 (s, 1 H), 7.85 (s, 1 H), 7.80 (d, 1 H), 7.63 (d, 1 H), 7.49 (d, 1 H), 7.13 (m, 1H), 7.05 (dd, 1H), 4.76 (m, 2H), 4.66 (s, 2H), 3.39 (t, 2H), 3.25 (s, 3H), 3.01 (bm, 3H), 2.11 (bm, 5H) ), 1.89-1.82 (m, 2H), 1.75-1.65 (m, 2H). EXAMPLE 266 3- (2-Benzyl-1H-benzimidazol-6-yl) -1- (1 '- (3-methoxypropyl) - 1, 4'-bipiperidin-4-yl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 266A The title compound, as a brown solid, was prepared in the manner described in EXAMPLE 139B, substituting the compound of EXAMPLE 139A for the compound of EXAMPLE 201A, except that the purification was carried out on normal phase silica gel. MS (ESI +) m / e 525 (M + H) *; (IEA (-)) m / e 523 (M-H) J 1 H-NMR (300 MHz, DMSO-d 6) 12.45 (br s, 1H), 8.24 (s, 1H), 7. 70 (m, 2H), 7.33 (m, 6H), 4.90 (m, 1H), 4.21 (s, 2H), 4.09 (m, 2H), 3.00 (m, 2H), 1.96 (m, 4H), 1.43 (s, 9H), 1.25 (m, 2H). EXAMPLE 266B 3- (2-Benzyl-1H-benzo [d] imidazol-6-yl) -1- (piperidin-4-yl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine The compound of the title, in the form of a brown foam, was prepared in the manner described in EXAMPLE 201C, substituting the compound of EXAMPLE 201B for the compound of EXAMPLE 266A. MS (ESI +) m / e 425 (M + H) *; (IEA (-)) m / e 423 (MH) J 1 H-NMR (300 MHz, DMSO-d 6) 8.78 (m, 1H), 8.47 (m, 1H), 8.34 (s, 1H), 7.91 (s, 1H), 7.87 (d, 1H), 7.70 (d, 1H), 7.42 (m, 4H), 7.33 (m, 1H), 5.09 (m, 1H), 4.87 (vbr s, 2H), 4.51 (s, 2H), 3.45 (m, 2H), 3.22 (m, 2H), 2.35 (m, 2H), 2.15 (m, 2H). EXAMPLE 266C 3- (2-Benzyl-1H-benzimidazol-6-yl) -1- (1, - (3-methoxypropyl) -1,4'-bipiperidin-4-yl) -1 H-pyrazolo [3,4 -d] pyrimidin-4-amine The title compound, as a solid of color Brown, was prepared in the manner described in EXAMPLE 201D, substituting the compound of EXAMPLE 201C for the compound of EXAMPLE 266B and 1-methylpiperidin-4-one for 1- (3-methoxypropyl) piperidin-4-one. MS (ESI +) m / e 580 (M + H) *; (ESI (-)) m / e 578 (MH) J 1 H-NMR (300 MHz, DMSO-d 6) 9.79 (br s, 1H), 9.48 (br s, 1H), 8.29 (s, 1H), 7.80 ( s, 1H), 7.74 (d, 1H), 7.56 (d, 1H), 7.37 (m, 4H), 7.28 (m, 1H), 5.12 (m, 1H), 4.36 (s, 2H), 3.65 (m , 3H), 3.40 (vbr s, 1H), 3.25 (s, 3H), 3.12 (m, 4H), 2.99 (m, 4H), 2.28 (m, 6H), 1.90 (m, 6H). EXAMPLE 267 (c / s) -2-. { 4- (4- (4-amino-3-. {1- (2- (difluoromethoxy) benzyl) -1H-indol-5-yl.} - 1 H -pyrazolo [3,4-d] pyrimidine- 1-yl) cyclohexyl) piperazin-1-yl} Ethanol EXAMPLE 267A The desired product was synthesized by substituting 2-fluorobenzyl bromide for 2- (difluoromethoxy) benzyl bromide in EXAMPLE 210A. EXAMPLE 267B The desired product was synthesized by substituting the compound of EXAMPLE 210A for the compound of EXAMPLE 267A, in EXAMPLE 210B. EXAMPLE 267C The compound of EXAMPLE 267B (75 mg, 0.15 mmol) was dissolved in 3 mL of methanol and 0.3 mL of acetic acid, at room temperature. 1- (2-hydroxyethyl) piperazine (184 mL, 1.5 mmol) was added and the mixture was stirred for another 30 minutes. Added (polystyrylmethyl) trimethylammonium cyanoborohydride (4.2 mmol / g, 180 mg, 0.75 mmol), and the mixture was stirred for 16 hours. After removing the insoluble material, the filtrate was concentrated in vacuo and the residue was purified by HPLC. The diastereomer that eluted first was isolated, obtaining 19 mg of the title product. MS: IEA (+) m / e 617.4 (M + H) *; 1 H-NMR (300 MHz, DMSO-d 6) 8.32 (s, 1H), 7.86 (d, 1H), 7.57-7.61 (m, 2H), 7.35-7.43 (m, 2H), 7.25 (dd, 1H), 7.16 (dt, 1H), 6.93 (dd, 1H), 6.64 (d, 1H), 5.52 (s, 1H), 4.91 (m, 1H), 3.69 (t, 2H), 3.42-3.59 (m, 4H) , 3.00-3.20 (m, 4H), 2.26-2.40 (m, 2H), 2.00-2.14 (m, 2H), 1.75-1.93 (m, 2H). EXAMPLE 268 (f? Aps) -2-. { 4- (4- (4-amino-3-. {1- (2- (difluoromethoxy) benzyl) -1H-indol-5-yl.} - 1 H -pyrazolo [3,4-d] pyrimidin-1 -yl) cyclohexyl) piperazin-1-yl} Ethanol The desired product was the diastereomer eluting most slowly in EXAMPLE 267. MS: IEA (+) m / e 617.4 (M + H) *; IEA (-) m / e 615.4 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 8.31 (s, 1H), 7.85 (d, 1H), 7.55-7.62 (m, 2H), 7.34-7.43 (m, 2H), 7.26 (d, 1H), 7.16 (dt, 1H), 6.96 (dd, 1H), 6.64 (d, 1H), 5.51 (s, 1H), 4.75 (m, 1H), 3.72 (t, 2H), 3.42-3.59 (m, 4H) , 3.00-3.20 (m, 4H), 2.04-2.20 (m, 6H), 1.60-1.78 (m, 2H). EXAMPLE 269 (c / s) -3-. { 4- (4- (4-amino-3-. {1- (2- (difluoromethoxy) benzyl) -1H-indol-5-yl.} - 1 H -pyrazolo [3,4-d] pyrimidin-1 -yl) cyclohexyl) piperazin-1-yl} propan-1-ol The desired product was synthesized by replacing the hydroxyethylpiperazine of EXAMPLE 268C with 1- (3-hydroxypropyl) - piperazine. The diastereomer that eluted first was isolated. MS: IEA (+) m / e 631.5 (M + H) *; 1 H-NMR (300 MHz, DMSO-d 6) 8.32 (s, 1H), 7.86 (d, 1H), 7.57-7.61 (m, 2H), 7.35-7.43 (m, 2H), 7.26 (dd, 1H), 7.16 (dt, 1H), 6.95 (dd, 1H), 6.64 (d, 1H), 5.52 (s, 1H), 4.91 (m, 1H), 3.42-3.57 (m, 4H, includes 3.47, t, 2H) , 3.00-3.20 (m, 4H), 2.26-2.40 (m, 2H), 2.00-2.14 (m, 2H), 1.75-1.96 (m, 4H). EXAMPLE 270 (frar / s) -3-. { 4- (4- (4-amino-3-. {1- (2- (difluoromethoxy) benzyl) -1H-indol-5-yl.} - 1 H -pyrazolo [3,4-d] pyrimidine- 1-yl) cyclohexyl) piperazin-1-yl} propan-1-ol The desired product was the diastereomer eluting slower in EXAMPLE 269. MS: IEA (+) m / e 631.4 (M + H) *; IEA (-) m / e 629.4 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 8.31 (s, 1H), 7.85 (d, 1H), 7.55-7.62 (m, 2H), 7.34-7.42 (m, 2H), 7.26 (d,., 1H ), 7.16 (dt, 1H), 6.96 (dd, 1H), 6.64 (d, 1H), 5.51 (s, 1H), 4.75 (m, 1H), 3.49 (t, 2H), 3.42-3.59 (m, 4H), 2.93-3.20 (m, 4H), 2.00-2.20 (m, 6H), 1.60-1.82 (m, 4H). EXAMPLE 271 3- (2- (2,6-difluorobenzyl) -1H-benzimidazol-5-yl) -1- (4- (morpholin-4-yl-methyl) phenyl) -1 H-pyrazolo [3,4- d] pyrimidin-4-amine The desired product was prepared in the manner described in EXAMPLE 48, substituting the phenylacetaldehyde of EXAMPLE 48D, for 2,6-difluorophenylacetaldehyde. MS (LEA) m / e 553 (M + H) J 1 H-NMR (300 MHz, DMSO-d6) d 9.84 (bs, 1H), 8.41 (m, 3H), 7.87 (s, 1H), 7.71 (m, 3H), 7.61 (d, 1H), 7.45 (m, 1H), 7.18 (m, 2H), 4.42 (s, 2H), 4.38 (s, 2H), 3.99 (m, 2H), 3.62 (m, 2H), m, 2H), 3.32 (m, 2H), 3.16 (m, 2H).

EXAMPLE 272 2-. { 4- (4-amino-3- (2-benzyl-1H-benzimidazol-6-yl) -1H-pyrazolo [3,4- d] pyrimidin-1-yl) -1,4'-bipiperidin-1'- il} Ethanol The title compound, as a yellowish orange solid, was prepared in the manner described in EXAMPLE 266, substituting the 1- (3-methoxypropyl) -piperidin-4-one of EXAMPLE 266C, for 1- ( 2-hydroxyethyl) -piperidin-4-one. MS (ESI +) m / e 552 (M + H) *; (ESI (-)) m / e 550 (MH) J 1 H-NMR (300 MHz, DMSO-d 6) 9.79 (br s, 1H), 9.48 (br s, 1H), 8.28 (s, 1H), 7.78 ( s, 1H), 7.71 (d, 1H), 7.52 (d, 1H), 7.36 (m, 4H), 7.28 (m, 1H), 5.42 (br s, 1H), 5.12 (m, 1H), 4.30 ( s, 2H), 3.73 (m, 3H), 3.62 (m, 4H), 3.45 (vbr s, 3H), 3.17 (m, 4H), 3.03 (m, 4H), 2.26 (m, 4H), 2.00 ( m, 2H). EXAMPLE 273 3-. { 4- (4-amino-3- (2-benzyl-1H-benzimidazol-6-yl) -1H-pyrazolo [3,4- d] pyrimidin-1-yl) -1,4'-bipiperidin-1'- il} propan-1-ol The title compound, in the form of a yellow solid, was prepared in the manner described in EXAMPLE 266, substituting the 1- (3-methoxypropyl) -piperidin-4-one of EXAMPLE 266C, by 1- (3-hydroxypropyl) -piperidin-4-one. MS (ESI +) m / e 566 (M + H) *; (ESI (-)) m / e 564 (MH) J 1 H-NMR (300 MHz, DMSO-de) 9.79 (br s, 1H), 9.48 (br s, 1H), 8.29 (s, 1H), 7.79 ( s, 1H), 7.72 (d, 1H), 7.53 (d, 1H), 7.37 (m, 4H), 7.28 (m, 1H), 5.12 (m, 1H), 4.80 (vbr s, 1H), 4.32 ( s, 2H), 3.65 (m, 6H), 3.49 (m, 3H), 3.39 (vbr s, 1H), 3.13 (m, 4H), 2.99 (m, 2H), 2.27 (m, 4H), 1.93 ( m, 2H), 1.80 (m, 2H).

EXAMPLE 274 3- (2-Benzyl-1H-benzimidazol-6-yl) -1- (1, - (2-methoxyethyl) -1,4'-bipiperidin-4-yl) -1H-pyrazolo [3,4- d] pyrimidin-4-amine The title compound, as an off-white solid, was prepared in the manner described in EXAMPLE 266, substituting the 1- (3-methoxypropyl) -piperidin-4-one of EXAMPLE 266C , by 1- (2-methoxyethyl) -piperidin-4-one. MS (ESI +) m / e 566 (M + H) *; (ESI (-)) m / e 564 (MH) J 1 H-NMR (300 MHz, DMSO-d 6) 9.82 (br s, 1 H), 9.67 (br s, 1 H), 8.28 (s, 1 H), 7.78 ( s, 1H), 7.71 (d, 1H), 7.52 (d, 1H), 7.37 (m, 4H), 7.29 (m, 1H), 5.12 (m, 1H), 4.30 (s, 2H), 3.66 (m , 6H), 3.46 (vbr s, 4H), 3.32 (s, 3H), 3.28 (m, 4H), 3.03 (m, 2H), 2.26 (m, 4H), 1.98 (m, 2H). EXAMPLE 275 2- (4- { 4-amino-3- (1- (2-chlorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4- d] pyrimidin-1-yl} -1, 4'-bipiperidin-1'-yl) ethanol The title compound, as a brown solid, was prepared in the manner described in EXAMPLE 201, substituting 1-methylpiperidin-4-one of EXAMPLE 201D, by 1- (2-hydroxyethyl) -piperidin-4-one. MS (ESI +) m / e 585 (M + H) *; (ESI (-)) m / e 583 (MH) J H-NMR (300 MHz, DMSO-d 6) 9.74 (br s, 1H), 9.45 (br s, 1H), 8.28 (s, 1H), 7.87 ( s, 1H), 7.58 (m, 3H), 7.43 (d, 1H), 7.33 (m, 1H), 7.25 (m, 1H), 6.79 (dd, 1H), 6.66 (d, 1H), 5.58 (s) , 2H), 5.40 (br s, 1H), 5.11 (m, 1H), 3.73 (m, 4H), 3.64 (m, 2H), 3.56 (m, 2H), 3.47 (m, 3H), 3.16 (m , 2H), 3.03 (m, 2H), 2.27 (m, 4H), 2.00 (m, 2H).

EXAMPLE 276 3- (1- (2-Chlorobenzyl) -1H-indol-5-yl) -1- (1 '- (2-methoxyethyl) -1,4'-bipiperidin-4-yl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine The title compound, as a brown solid, was prepared in the manner described in EXAMPLE 201, substituting the 1-methylpiperidin-4-one of EXAMPLE 201D, by 1- (2-methoxyethyl) -piperidin-4-one. MS (ESI +) m / e 599 (M + H) *; (ESI (-)) m / e 597 (MH) J H-NMR (300 MHz, DMSO-d 6) 9.80 (br s, 1 H), 9.65 (br s, 1 H), 8.28 (s, 1 H), 7.88 ( s, 1H), 7.57 (m, 3H), 7.43 (d, 1H), 7.33 (m, 1H), 7.25 (m, 1H), 6.80 (dd, 1H), 6.66 (d, 1H), 5.58 (s) , 2H), 5.11 (m, 1H), 3.65 (m, 4H), 3.59 (m, 2H), 3.49 (m, 3H), 3.33 (s, 3H), 3.28 (m, 2H), 3.02 (m, 2H), 2.54 (m, 2H), 2.26 (m, 4H), 1.98 (m, 2H). EXAMPLE 277 3- (1 - (2-f luorobenzyl) -1 H-indol-5-yl) -1- (4- (4-pyridin-2-yl-piperazin-1-yl) -cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine The desired product was prepared by substituting the 3-aminobenzyl alcohol of EXAMPLE 210C for 1- (2-pyridyl) -piperazine. MS ((+) - IEA) 602.4 m / z (M + H) *; 1 H-NMR (400 MHz, DMSO) 8.23 (s, 1H), 8.10 (m, 1H), 7.84 (s, 1H), 7.66-7.09 (m, 8H), 6.80 (m, 1H), 6.62 (m, 2H), 4.84-4.65 (m, 1H), 3.48 (bs, 4H), 2.70-2.60 (m, 3H), 2.32-1.52 (m, 10H). EXAMPLE 278 (fraps) -3- (2-Benzyl-1H-benzimidazol-5-yl) -1- (4- (4-pyridin-2-yl-piperazin-1-yl) cyclohexyl) -1H-pyrazolo [3 , 4-d] pyrimidin-4-amine The desired product was prepared by substituting the 3- hydroxypyrrolidine of EXAMPLE 31C, by 1- (2-pyridyl) -piperazine. The diastereomer that eluted faster was isolated. MS ((+) - IEA) 585.4 m / z (M + H) *; 1 H-NMR (400 MHz, DMSO) 8.23 (s, 1H), 8.11 (m, 1H), 7.71-7.23 (m, 11H), 6.81 (m, 1H), 6.62 (m, 1H), 4.67 (m, 1H), 4.22 (s, 2H), 3.46 (m, 4H), 2.63 (m, 4H), 2.09-1.99 (m, 6H), 1.53 (m, 2H). EXAMPLE 279 (c / s) -3- (2-Benzyl-1 H-benzimidazol-5-yl) -1- (4- (4-pyridin-2-yl-piperazin-1-yl) cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine This is the diastereomer that eluted the slowest in EXAMPLE 278. MS ((+) - IEA) 585.4 m / z (M + H) *; 1 H-NMR (400 MHz, DMSO) 8.24 (s, 1H), 8.11 (m, 1H), 7.82-7.55 (m, 11H), 6.79 (m, 1H), 6.61 (m, 1H), 4.83 (m, 1H), 4.21 (s, 2H), 3.51 (m, 4H), 2.58 (m, 4H), 2.31 (m, 3H), 2.09 (m, 2H), 1.82-1.58 (m, 4H). EXAMPLE 280 (rans) -1- (4-morpholin-4-yl-cyclohexyl) -3- (2- (pyridin-2-yl-methyl) -1H-benzimidazol-6-yl) -1H-pyrazolo [3, 4-d] pyrimidin-4-amine EXAMPLE 280A The 4- (4,4,5,5-tetramethyl-1, 3,2-dioxaborolan-2-yl-benzene-1,2-diamine of EXAMPLE 2A (5 g 18.5 mmol), dissolved in 100 mL of EtOAc, treated with 10% Pd / C (2 g, 1.89 mmol) The mixture was placed in a Parr hydrogenation apparatus at 60 psi H2 at room temperature. The mixture was filtered and reduced in vacuo, the product was triturated with Et2O / hexanes and subsequently used without further purification.

EXAMPLE 280B 2- (Pyridin-2-yl) -acetic acid hydrochloride (0.81 g, 4.7 mmol) was mixed with THF (7 mL) at room temperature and Et3N (0.47 mL, 4.7 mmol) was added. After 10 min., CDI (0.7 g, 4.48 mmol) was added and the mixture was heated to 50 ° C. After 30 min., The compound of EXAMPLE 280A (1 g, 4.2 mmol) was added and the reaction mixture was stirred for 1 hour at 50 ° C. The mixture was cooled, the reaction was quenched with water and diluted with EtOAc. The organic phase was separated and extracted with EtOAc (2x30 mL). The organic phases were combined and the combined was dried over MgSO, filtered and reduced in vacuo on silica. The reaction mixture was purified by a purification system lntelliflash-280 (hexanes / EtOAc), to obtain a mixture of the desired amide products. EXAMPLE 280C To a slurry of 3-iodo-1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] -pyrimidin-4-yl-amine (0.27 g, 0.63 mmol, prepared in the manner described in International Patent Publication WO2005 / 074603), the compound of EXAMPLE 280B (0.45 g, 1.27 mmol) and the dichloro (1,1'-bis (diphenylphosphino) -ferrocene) palladium (II) dichloromethane adduct (0.022 g, 0.03 mmol) in DME 0.3 M / water (2: 1, v / v), was added Na 2 C 3 3 M in aqueous solution (0.63 mL, 1.27 mmol). The reaction mixture was heated in a microwave reactor for 20 min. at 130 ° C. The mixture was filtered over celite and the pad washed with CH2Cl2. The filtrate was dried over MgSO 4, filtered and reduced in vacuo on silica. The reaction mixture was purified by a purification system lntelliflash-280 (CH2Cl2 / MeOH), to obtain a mixture of the desired products. EXAMPLE 280D The compound of EXAMPLE 280C (0.25 g, 0.47 mmol) was mixed with AcOH (2 mL) and heated at 100 ° C for 1.5 hours. The contents were cooled to room temperature, diluted with CH2Cl2 / IPA (4: 1) and washed with a saturated aqueous solution of NaHC? 3. The organic phase was separated, dried over MgSO 4, filtered and reduced in vacuo. The material was purified by reverse phase HPLC, using the following column conditions: 0.15% TFA in CH3CN / 0.15% in H2O, to obtain the desired product.

(IEA (+)) m / e 510 (M + H) *; 1 H-NMR (300 MHz, DMSO-d 6) 12.49 (s, 1H), 8. 53-8.51 (m, 1H), 8.22 (s, 1H), 7.80-7.75 (m, 2H), 7.68-7.75 (m, 1H), 7. 45-7.40 (m, 3H), 7.30-7.26 (m, 1H), 4.70-4.60 (m, 1H), 4.39 (s, 2H), 5.39-3.56 (m, 5H), 2.41-2.31 (m, 2H) ), 2.08-1.96 (m, 8H), 1.53-1.40 (m, 3H). EXAMPLE 281 3- (2-Benzyl-1H-benzimidazol-6-yl) -1- (1'-isobutyl-1,4, -bipiperidin-4-yl) -1H-pyrazolo [3,4-d] ] pyrimidin-4-amine The title compound, as a white solid, was prepared in the manner described in EXAMPLE 266, substituting the 1- (3-methoxypropyl) piperidin-4-one of EXAMPLE 266C, by 1-isobutylpiperidin-4-one. MS (ESI +) m / e 564 (M + H) *; (ESI (-)) m / e 562 (MH) J 1 H-NMR (300 MHz, DMSO-d 6) 9.85 (br s, 1H), 9.20 (br s, 1H), 8.31 (s, 1H), 7.89 ( s, 1H), 7.79 (d, 1H), 7.62 (d, 1H), 7.40 (m, 4H), 7.30 (m, 1H), 5.14 (m, 1H), 4.42 (s, 2H), 3.83 (v, s, 2H), 3.63 (m, 4H), 3.39 (m, 2H), 2.97 (m, 4H), 2.54 (m, 2H), 2.26 (m, 4H), 2.06 (m, 2H), 0.97 (d, 6H). EXAMPLE 282 (trans) -1- (4-morpholin-4-yl-cyclohexyl) -3- (2- (pyridin-3-yl-methyl) -1 H- benzimidazol-6-yl) -1 H-pyrazolo [ 3,4-d] pyrimidin-4-amine EXAMPLE 282A The desired product was prepared by substituting 2- (pyridin-2-yl) -acetic acid hydrochloride of EXAMPLE 280B, by 2- (pyridin-3-yl hydrochloride )-acetic. EXAMPLE 282B The desired product was prepared by substituting the compound of EXAMPLE 280B for the compound of EXAMPLE 282A, in EXAMPLE 280C. EXAMPLE 282D The desired product was prepared by substituting the compound of EXAMPLE 280C for the compound of EXAMPLE 282B, in EXAMPLE 280D. (IEA (+)) m / e 510 (M + H) *; 1 H-NMR (300 MHz, DMSO-d 6) 9.84 (bs, 1H), 8.77 (m, 1H), 8.66-8.64 (m, 1H), 8.37 (s, 1H), 8.07-8.04 (m, 1H), 7.87-7.81 (m, 2H), 7.66-7.60 (m, 2H), 4.85-4.74 (m, 1H), 4.57 (s, 2H), 4.06-4.02 (m, 2H), 3.75-3.67 (t, 2H) ), 3.48-3.38 (m, 3H), 3.22-3.11 (m, 2H), 2.30-2.20 (m, 2H), 2.16-2.07 (m, 2H), 1.83-1.70 (m, 2H). EXAMPLE 283 (c / s) -1- (1- (2-chlorobenzyl) -1H-indol-5-yl) -3- (3- (4-methyl-piperazin-1- il) cyclobutyl) imidazo [1,5-a] pyrazin-8-amine EXAMPLE 283A (3-Chloropyrazin-2-yl) methanamine dihydrochloride To a solution of (3-chloropyrazin-2-yl) -methanol (B. Klein et al., J. Org. Chem. 1963, 28, 1682) (10.78 g, 74.6 mmol), phthalimide (13.18 g, 89.7 mmol) and triphenylphosphine (23.78 g, 90.8 mmol) in THF (350 mL) were added. DIAD (17.8 mL, 90.8 mmol) was added and the mixture was stirred at room temperature for 16 hours. The mixture was concentrated in a rotary evaporator. The intermediate 2 - ((3-chloropyrazin-2-yl) -methyl) -isoindolin-1,3-dione was taken up with CH2Cl2 (300 mL) and methanol (450 mL) and treated with anhydrous hydrazine (6.0 mL, 190 mmol) at room temperature for 18 hours. The mixture was filtered and the precipitate was discarded. The filtrate was concentrated in a rotary evaporator, the material was collected with EtOAc and refiltered. The filtrate was concentrated to dryness, 600 mL of EtOAc was dissolved and then treated with 40 mL of 4 N HCl in dioxane. The precipitated solids were collected, washed with ether and dried in vacuo to obtain 12.53 g of a brown solid. EXAMPLE 283B N - ((3-chloropyrazin-2-yl) methyl) -3-methylenecyclobutanecarboxamide EDCI (13.47 g, 70 mmol), DMAP (1.19 g, 9.8 mmol) and the compound of EXAMPLE 283A (12.5 g, 58) were treated. mmol) in CH2Cl2 (300 mL), ethyl-diisopropylamine (20 mL, 170 mmol) and 3-methylene-cyclobutanecarboxylic acid (Caserio et al., J. Am. Chem. Soc. 1958, 80, 5507) (6.59 g, 59 mmol) . After 8 h at temperature environment, an additional 2.88 g of EDCI was added and the mixture was stirred at room temperature for 16 hours. The mixture was concentrated in a rotary evaporator, diluted with EtOAc (600 mL) and then washed sequentially with water (2x), with an aqueous solution of NaHC 3 (2x) and with brine (2x), and dried (Na 2 S). ?4) . Removal of the solvent produced a reddish-brown oil, which was purified by silica gel column chromatography, eluting with 0-70% EtOAc / hexanes, to obtain 6.55 g of the product. EXAMPLE 283C 8-chloro-3- (3-methylenecyclobutyl) imidazo [1,5-a] pyrazine The compound of the EX MS PLO 283B (6.55 g, 27.6 mmol) in acetonitrile (1 30 mL) was treated with DM F ( 0.3 mL) and POCI3 (1 3 mL, 1.38 mmol) and the mixture was stirred in an oil bath at 55 ° C for 30 min. The mixture was cooled and concentrated in a rotary evaporator, and the residue was treated with an aqueous solution of Na 2 C 3 and then extracted twice with CH 2 Cl 2. The organic phases were combined and the combined was washed with, dried ( Na2SO_j). The crude product was adsorbed on celite and subjected to chromatography on silica gel, eluting with 0-50% EtOAc / hexanes, to obtain the product as a whitish solid (4.36 g). EXAMPLE 283D 3- (8-Chloroimidazo [1,5-a] pyrazin-3-yl) -1 - (hydroxymethyl) cyclobutanol The compound of EJ EM PLO 283C (4.36 g, 1 9.8 mmol) in THF (240 mL) and water (25 mL), treated with NMMO (4.8 mL, 20 mmol) and potassium formate dihydrate (0.290 g, 0.87 mmol) and the mixture was stirred vigorously at room temperature for 24 hours. Sodium sulfate (11.5 g) was added and the mixture was stirred vigorously for 30 min. and then he concentrated on a rotary evaporator. The residues were subjected to extraction by partition in EtOAc (400 mL) and water (250 mL), and the organic phases were washed with brine. The aqueous washings were combined and the combined was back extracted with 4x100 mL EtOAc, and the EtOAc extracts were combined and the combined was dried over Na2SO4. Removal of the solvent produced the product in the form of a white foam (2.55 g). EXAMPLE 283E 3- (8-Chloro-1-iodoimidazo [1,5-a] pyrazin-3-yl) -1- (hydroxymethyl) cyclobutanol The compound of EXAMPLE 283D (2.55 g, 10.1 mmol) and N-iodosuccinimide (2.87) g, 12.8 mmol) in DMF (25 mL) was stirred at 60 ° C for 4.5 hours. The mixture was dried in vacuo and the residues were adsorbed on celite and subjected to chromatography on silica gel, eluting with 0-5% CH3OH / CH2Cl2, to obtain the product as a light brown gum (3.60 g. ). EXAMPLE 283F 3- (8-chloro-1-iodoimidazo [1,5-a] pyrazin-3-yl) cyclobutanone A solution of the compound of EXAMPLE 283E (3.60 g, 9. 5 mmol) in THF (100 mL) and water (25 mL), cooled to 0 ° C in an ice bath and treated with sodium periodate (2.42 g, 11.3 mmol).

The ice bath was removed and the mixture was stirred for 3.5 hours. The mixture was diluted with EtOAc (200 mL), washed with brine (3x) and then dried (MgSO). Removal of the solvent and dehydration under vacuum produced the product as a brown solid (2.68 g). EXAMPLE 283G 8-chloro-1-iodo-3 - ((1 S, 3S) -3- (4-methylpiperazin-1-yl) cyclobutyl) imidazo [1,5-a] pyrazine The compound of EJ EM PLO 283F ( 2.68 g, 7.7 mmol), N-methylmorpholine (0.90 mL, 8.1 mmol) and NaBH (OAc) 3 (3.34 g, 1 5.8 mmol), in 1,2-dichloroethane (1 50 mL), were stirred at room temperature During 4 hours. The mixture was concentrated in a rotary evaporator and the residue was subjected to partition extraction in CH2CI2 and NaHC? 3 in aqueous solution. The organic phases were combined and the combined was washed with brine and dried over Na2SO4. Removal of the solvent afforded the product as a light yellow solid (2.94 g). EXAMPLE 283H 1 -iodo-3 - ((1 S, 3S) -3- (4-methylpiperazin-1-yl) cyclobutyl) imidazo [1, 5 a] pyrazin-8-amine A pressure pump was charged with the compound of EJ EM PLO 283G (2.94 g, 6.8 mmol), 2 N ammonia in isopropanol (50 mL) and anhydrous ammonia (20 mL) and heated at 1 10 ° C for 48 hours. After removing the solvent, the residue was purified by chromatography on silica gel, with a mixture of 7% saturated ammonia solution in methanol / CH 2 Cl 2, to obtain the product as a yellow solid (1. 85 g).

EXAMPLE 2831 (c / s) -1- (1- (2-chlorobenzyl) -1H-indol-5-yl) -3- (3- (4-methylpiperazin-1-yl) cyclobutyl) imidazo [1, 5 a] pyrazin-8-amine The compound of EXAMPLE 283H (0.049 g, 0.12 mmol), the compound of EXAMPLE 93A (0.096 g, 0.26 mmol), K2CO3 (0.078 g, 0.56 mmol) was added to a microwave reaction vessel. ), Pd (PPh3) (0.015 g, 0.012 mmol) and DME / H2O, 2: 1 (2 mL: 1 mL). The reaction vessel was sealed and heated by controlling the temperature on a Personal Chemistry Smith synthesizer for 20 min., At a temperature of 150 ° C. The reaction mixture was diluted with EtOAc and the organic phase was washed sequentially with aqueous Na 2 CO 3 solution (2x), with brine, and then dried over MgSO4. The solvent was removed under reduced pressure and the residue was purified by reverse phase HPLC, using CH3CN / water / 0.15% TFA, to obtain the TFA salt of the title compound as a white solid (0.040 g). . 1 H-NMR (300 MHz, DMSO-d 6) d 7.88 (d, 1 H), 7.75 (d, 1 H), 7.60 (d, 1 H), 7.59 (s, 1 H), 7.54 (m, 1 H), 7. 42 (dd, 1H), 7.34 (td, 1H), 7.26 (td, 1H), 7.07 (d, 1H), 6.81 (d, 1H), 6. 66 (d, 1H), 5.60 (s, 2H), 3.80-3.60 (m, 8H), 3.46 (m, 1H), 3.00 (m, 1H), 2.76 (s, 3H), 2.65-2.58 (m, 2H), 2.29-2.25 (m, 2H). EXAMPLE 284 (c / s) -1- (2-Benzyl-1H-indol-5-yl) -3- (3- (4-methyl-piperazin-1-yl) cyclobutyl) imidazo [1,5-a] pyrazine- 8-amine The desired product was prepared by substituting the compound of EXAMPLE 93A for the compound of EXAMPLE 206C, in the EXAMPLE 2831. 1 H-NMR (300 MHz, DMSO-d 6) d 11.31 (s, 1H), 7.74 (d, 1H), 7.70 (s, 1H), 7.45 (d, 1H), 7.34 (s, 2H), 7.32 (m, 2H), 7.28 (dd, 1H), 7.23 (m, 1H), 7.06 (d, 1H), 6.28 (s, 1H), 4.11 (s, 2H), 3.80-3.60 (m, 8H) , 3.46 (m, 1H), 3.00 (m, 1H), 2.76 (s, 3H), 2.65-2.58 (m, 2H), 2.29-2.25 (m, 2H). EXAMPLE 285 (c / s) -1- (2-Benzyl-1 H-benzimidazol-5-yl) -3- (3- (4-methylpiperazin-1-yl) cyclobutyl) imidazo [1,5-a] pyrazin -8-amine The desired product was prepared by substituting the compound of EXAMPLE 93A for the compound of EXAMPLE 188C, in EXAMPLE 283I. 1 H-NMR (300 MHz, DMSO-d 6) d 7.86 (d, 1H), 7.81 (d, 1H), 7.78 (d, 1H), 7.61 (dd, 1H), 7.45-7.36 (m, 4H), 7.32 (m, 1H), 7.13 (d, 1H), 4.11 (s, 2H), 3.80-3.60 (m, 8H), 3.46 (m, 1H), 3.00 (m, 1H), 2.77 (s, 3H), 2.65-2.58 (m, 2H), 2.29-2.25 (m, 2H). EXAMPLE 286 (frans) -1- (4-morpholin-4-yl-cyclohexyl) -3- (2- (thien-3-yl-methyl) -1H-benzimidazol-6-yl) -1H-pyrazolo [3, 4-d] pyrimidin-4-amine EXAMPLE 286A To a slurry of the compound of EXAMPLE 7A (2.9 g, 6.62 mmol) in THF / MeOH (30 mL / mL) was added Pd / C (0.6 g, 0.05% by weight of Pd). The sample was purged with H2 and then evacuated (3 times). The reaction mixture was placed on a Parr hydrogenation stick at 60 psi H2 for 1.5 hours. The reaction was filtered on a Teflon filter and washed with THF. The organic washes were combined and the combined was reduced in silica vacuum.

The material was purified by a purification system lntelliflash-280 (CH2Cl2 / MeOH / NH4OH), to obtain the desired intermediate in the form of a brown solid (2 g, 75% yield). EXAMPLE 286B 2- (Thiophene-3-yl) -acetic acid (0.057 g, 0.4 mmol) and CDI (0.062 g, 0.38 mmol) were dissolved in 1 mL of NMP and the reaction mixture was immediately heated to 50 ° C. 30 min. The compound of EXAMPLE 286A (0.15 g, 0.36 mmol) was added and the mixture was stirred at 50 ° C for 1.5 hours. AcOH (1 mL) was added to the crude reaction mixture and the reaction was heated at 90 ° C for 12 hours. The reaction mixture was cooled to room temperature, diluted with CH2Cl2 / IPA (4: 1, v / v) and the reaction was quenched with 1M NaOH. The resulting phases were separated, the aqueous phase was subjected to CH2Cl2 / IPA extraction (2 x 25 mL). The organic extracts were combined and the combined was dried over MgSO4 filtered and reduced in vacuo. The crude reaction mixture was purified by reverse HPLC, using the following conditions: 0.15% TFA in CH3CN / 0.15% in H2O, to obtain the desired product. (IEA (+)) m / e 515 (M + H) *; 1 H-NMR (300 MHz, DMSO-de) 12.42 (bs, 1H), 8.22 (s, 1H), 7.73-7.68 (m, 1H), 7.67-7.60 (m, 1H), 7.51-7.49 (m, 1H ), 7.44-7.41 (dd, 1H), 7.44 (d, 1H), 7.11 (dd, 1H), 4.65 (m, 1H), 4.22 (s, 2H), 3.59-3.56 (m, 5H), 2.40- 2.32 (bm, 1H) 2.08-1.96 (m, 8H), 1.53-1.41 (m, 3H).

EXAMPLE 287 (frans) -3- (2- (1,3-Benzodioxol-5-yl-methyl) -1H-benzimidazol-6-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine The desired product was prepared by substituting the 2- (thiophen-3-yl) -acetic acid of EXAMPLE 286B, for 2- (benzo [d]) acid (1, 3 ) -dioxol-5-yl) -acetic. (IEA (+)) m / e 553 (M + H) *; 1 H-NMR (300 MHz, DMSO-de) 12.38 (d, 1H), 8.22 (s, 1H), 7.68-7.64 (m, 1H), 7.42 (m, 1H), 6.93 (m, 1H, 6.88-6.83 (m, 3H), 5.98 (s, 2H), 4.65 (m, 1H), 2.48 (s, 2H), 3.58 (m, 5H), 2.41-2.29 (m, 2H), 2.08-1.93 (m, 8H) ), 1.53-1.40 (m, 3H) EXAMPLE 288 (frans) -3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1-. {4- (4- (3- methoxypropyl) piperazin-1-yl) cyclohexyl.) -1 Hp i razo lo [3,4-d] pyrim id i n-4-amine The desired product was prepared by substituting 2- (2-ethoxyethoxy) bromide - ethyl of EXAMPLE 318D, by 1-bromo-3-methoxypropane MS: IEA (+) m / e 613.5 (M + H) *; 1 H-NMR (300 MHz, DMSO-de) 11.29 (s, 1H), 8.31 (s, 1H), 7.68 (br s, 1H), 7.46 (d, 1H), 7.28-7.38 (m, 3H), 7.15-7.24 (m, 2H), 6.22 (s, 1H), 4.74 (br m , 1H), 4.14 (s, 2H), 3.39 (br m, 2H), 3.25 (s, 3H), 3.01 (br m, 4H), 2.05-2.16 (m, 6H), 1.77-1-90 (br m, 2H), 1.60-1.78 (br m, 2H) EXAMPLE 289 (c / s) -3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1-. (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl} -1 H -pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 289A The cis isomer formed in EXAMPLE 318A (1.25 g, 2.37 mmol), the compound of EXAMPLE 217C (1.0 g, 2.84 mmol), sodium carbonate (0.5 g, 4.71 mmol), palladium tetrakis-triphenylphosphine (82 mg) , 0.07 mmol), were suspended in 30 mL of DME / water (1: 1). This material was heated by microwave at 130 ° C for 20 minutes. After partition by extraction in ethyl acetate and brine, the ethyl acetate phase was washed with brine (3x), dried and purified by silica gel column chromatography, eluting with 7% methanol in acetate of ethyl. EXAMPLE 289B The desired product was synthesized by substituting the compound of EXAMPLE 382B for the compound of EXAMPLE 289A, in EXAMPLE 382C. MS: IEA (+) m / e 597.5 (M + H) *; IEA (-) m / e 595.5 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 11.31 (s, 1H), 8.33 (s, 1H), 7.70 (br s, 1H), 7.47 (d, 1H), 7.28-7.38 (m, 3H), 7.15 -7.24 (m, 2H), 6.21 (s, 1H), 4.91 (br m, 1H), 4.15 (s, 2H), 3.40.3.60 (br m, 4H), 3.24 (s, 3H), 2.90-3.10 (m, 4H), 2.28-2.41 (m, 2H), 2.00-2.15 (m, 2H), 1.79-1.95 (m, 4H), 2.19-2.07 (m, 6H), 1.79-1.64 (br m, 2H) ). EXAMPLE 290 (frans) -4- (4-amino-3-. {2- (2- (trifluoromethoxy) benzyl) -1H-benzimidazol-5-yl.} -1 H-pyrazolo [3,4-d] ] pyrimidin-1-yl) cyclohexanol EXAMPLE 290A The desired product was prepared by substituting the phenylmethylacetonitrile of EXAMPLE 118B, for 2-trifluoromethoxy- phenylacetonitrile. EXAMPLE 290B The desired product was prepared by substituting the compound of EXAMPLE 339A for the compound of EXAMPLE 290A, in EXAMPLE 339B. EXAMPLE 290C The desired product was prepared by substituting the compound of EXAMPLE 339B for the compound of EXAMPLE 290B, in EXAMPLE 339C. EXAMPLE 290D The desired product was prepared by substituting the 339C compound for the compound of EXAMPLE 290C, in EXAMPLE 260.

MS (LEA) m / e 524 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 8.32 (s, 1H), 7.84 (s, 1H), 7.78 (d, 1H), 7.64 (d, 1H), 7.54 (m, 1H), 7.46 (m, 3H), 4.68 (m, 1H), 4.50 (s, 2H) ), 2.08-1.91 (m, 6H), 1.42 (m, 2H). EXAMPLE 291 (trans) - 1-. { 4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl} -3-. { 2- (2- (t-Rifluoromethoxy) benz I) - 1 H-benzimidazol-5-yl} -1 H-p i razo [3, 4- d] pyrimidin-4-amine The desired product was prepared by substituting the compound of EXAMPLE 265A for the compound of EXAMPLE 290C, in EXAMPLE 265B. The diastereomer that eluted faster was isolated. MS (EAI) m / e 664 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 8.30 (s, 1 H), 7.80 (s, 1 H), 7.74 (d, 1 H), 7.57 (d , 1H), 7.53 (d, 1H), 7.45 (m, 3H), 4.75 (m, 1H), 4.45 (s, 2H), 3.66 (m, 5H), 3.39 (t, 2H), 3.25 (s, 3H), 2.98 (m, 5H), 2.09 (m, 6H), 1.84 (m, 2H), 1.67 (m, 2H). EXAMPLE 292 (cis) -1-. { 4- (4- (3-methoxypropyl I) p i perazin-1 -i I) cycle hexi l} -3-. { 2- (2- (trifluoromethoxy) benzyl) -1 H -benzimidazol-5-yl} -1 H-pyrazolo [3,4- d] pyrimidin-4-amine This compound is the diastereomer that eluted slower in EXAMPLE 291. MS (LEA) m / e 664 (M + H) J 1 H-NMR (300 MHz, DMSO-de) d 8.31 (s, 1H), 7.82 (s, 1H), 7.74 (d, 1H), 7.58 (d, 1H), 7.54 (d, 1H), 7.46 (m, 3H), 4.91 (m, 1H), 4.44 (s, 2H), 3.47 (m, 5H), 3.39 (t, 2H), 3.24 (s, 3H), 3.00 (m, 5H), 2.35 (m, 3H), 2.05 ( m, 3H), 1.85 (m, 4H). EXAMPLE 293 (frans) -1- (4-morpholin-4-yl-cyclohexyl) -3- (2- (2-naphthylmethyl) -1H-benzimidazol-6-yl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine The desired product was prepared by substituting the 2- (thiophen-3-yl) -acetic acid of EXAMPLE 286B, for 2- (naphthalen-2-yl) -acetic acid. (IEA (+)) m / e 559 (M + H) *; H-NMR (300 MHz, DMSO-de) 12. 48 (s, 1H), 8.22 (s, 1H), 7.90-7.87 (m, 4H), 7.67-7.65 (m, 1H), 7. 55-7.41 (m, 5H), 4.65 (m, 1H), 4.40 (s, 2H), 3.59-3.56 (m, 5H), 2.40-2.20 (m, 2H), 1.99-1.96 (m, 8H), 1.56-1.48 (m, 2H). EXAMPLE 294 (frans) -3- (2- (2,6-difluorobenzyl) -1H-benzimidazol-5-yl) -1-. { 4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl} -1H-pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 294A The desired product was prepared by substituting the phenylmethylacetonitrile of EXAMPLE 118B, for 2,6-difluorophenylacetonitrile. EXAMPLE 294B The desired product was prepared by substituting the compound of EXAMPLE 339A for the compound of EXAMPLE 294A, in EXAMPLE 339B. EXAMPLE 294C The desired product was prepared by substituting the compound of EXAMPLE 339B for the compound of EXAMPLE 294B, in EXAMPLE 339C. EXAMPLE 294D The desired product was prepared by substituting the compound of EXAMPLE 265A for the compound of Example 294C, in the EXAMPLE 265B. The diastereomer that eluted faster was isolated.

MS (EAI) m / e 616 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 8.30 (s, 1H), 7.77 (s, 1H), 7.71 (d, 1H), 7.54 (d, 1H), 7.47 (m, 1H), 7.19 (m, 2H), 4.76 (m, 1H), 4.40 (s, 2H), 3.42 (m, 5H), 3.39 (t, 2H), 3.25 (s, 3H), 2.98 (m, 5H), 2.10 (m, 6H) ), 1.84 (m, 2H), 1.68 (m, 2H). EXAMPLE 295 (c / 's) -3- (2- (2,6-difluorobenzyl) -1H-benzimidazol-5-yl) -1-. { 4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl} -1 H-pyrazolo [3,4-d] pyrimidin-4-amine This compound is the diastereomer that eluted most slow in EXAMPLE 294. MS (LEA) m / e 616 (M + H) J 1 H-NMR (300 MHz, DMSO-de) d 8.31 (s, 1H), 7.78 (s, 1H), 7.70 (d, 1H), 7.53 (d, 1H), 7.46 (m, 1H), 7.18 (m, 2H), 4.92 (m, 1H), 4.38 (s, 2H), 3.70 (m, 5H), 3.37 (t, 2H) ), 3.24 (s, 3H), 3.00 (m, 5H), 2.34 (m, 2H), 2.07 (m, 3H), 1.86 (m, 5H). EXAMPLE 296 (frans) -2- (. {6- (4-amino-1- (4-morpholin-4-yl-cyclohexyl) -1H-pyrazolo [3,4- d] pyrimidin-3-yl) - 1 H-benzimidazol-2-yl.} Methyl) phenol The desired product was prepared by substituting the 2- (thiophene-3-yl) -acetic acid of EXAMPLE 286B, for 2- (2-hydroxyphenyl) -acetic acid. (IEA (+)) m / e 525 (M + H) *; 1 H-NMR (300 MHz, DMSO-d 6) 8.28 (s, 1H), 7.85-7.79 (m, 2H), 7.70-7.63 (m, 1H), 7.31-7.28 (m, 1H), 7.22-7.17 (m , 1H), 6.90-6.84 (m, 2H), 4.77 (m, 1H), 4.38 (s, 2H), 4.08-3.99 (m, 2H), 3.74-3.64 (m, 1H), 2.28-2.20 (m , 3H), 2.16-2.08 (m, 7H), 1.81-1.68 (m, 3H). EXAMPLE 297 3- (2- (2-methoxybenzyl) -1H-benzimidazol-5-yl) -1- (4-. {(4- (3-methoxypropyl) piperazin-1-yl) methyl} phenyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 297A The desired product was prepared by substituting the morpholine of EXAMPLE 48B for 1- (3-methoxypropyl) -piperazine. EXAMPLE 297B The desired product was prepared by substituting (cis) -4- (4- (4-amino-3-iodopyrazolo- [3,4-d] -pyrimidin-1-yl) -cyclohexyl) -1- methylpiperazin-2-one from EXAMPLE 2B, by the compound of EXAMPLE 297A. EXAMPLE 297C The desired product was prepared by substituting the compound of EXAMPLE 48C for the compound of EXAMPLE 297B and phenylacetaldehyde for 2-methoxyphenylacetaldehyde, in EXAMPLE 48D.

MS (EAI) m / e 618 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 8.40 (s, 1H), 8.21 (d, 2H), 7.98 (s, 1H), 7.88 (d, 1H), 7.81 (d, 1H), 7.54 (d, 2H), 7.39 (m, 2H), 7.09 (d, 1H), 7.03 (t, 1H), 4.45 (s, 2H), 3.79 (s, 3H), 3.46 (m, 4H), 3.38 (m, 2H) ), 3.24 (s, 3H), 3.06 (m, 8H), 1.85 (m, 2H). EXAMPLE 298 1- (4- (. {4- (2- (1,3-dioxolan-2-yl) ethyl) piperazin-1-yl}. Methyl) phenyl) -3- (2- (2- methoxybenzyl) -1H-benzimidazol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 298A The desired product was prepared by substituting the morpholine of EXAMPLE 48B, for 1- (2- (1 , 3-dioxolan-2-yl) -ethyl) -piperazine. EXAMPLE 298B The desired product was prepared by substituting (cis) -4- (4- (4-amino-3-iodopyrazolo- [3,4-d] -pyrimidin-1-yl) -cyclohexyl) -1-methylpiperazine- 2-one of EXAMPLE 2B, by the compound of EXAMPLE 298A. EXAMPLE 298C The desired product was prepared by substituting the compound of EXAMPLE 48C by the compound of EXAMPLE 298B and phenylacetaldehyde by 2-methoxyphenylacetaldehyde, in EXAMPLE 48D. MS (LEA) m / e 646 (M + H) '; 1 H-NMR (300 MHz, DMSO-d 6) d 8.41 (s, 1H), 8.23 (d, 2H), 8.00 (s, 1H), 7.87 (m, 2H), 7.56 (d, 2H), 7.40 (m , 2H), 7.09 (d, 1H), 7.03 (t, 1H), 4.89 (t, 1H), 4.48 (s, 2H), 3.90 (m, 4H), 3.80 (m, 2H), 3.79 (s, 3H), 3.10 (m, 10H), 1.99 (m, 2H). EXAMPLE 299 (frans) -3-. { 2 - ((2-methyl-1,3-thiazol-4-yl) methyl) -1H-benzimidazol-6-yl} -1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine The desired product was prepared by substituting 2- (thiophene-3-yl) -acetic acid of EXAMPLE 286B, by 2- (2-methylthiazol-4-yl) -acetic acid. (IEA (+)) m / e 530 (M + H) *; 1 H-NMR (300 MHz, DMSO-d 6) 12. 44 (s, 1H), 8.23 (s, 1H), 7.73-7.61 (m, 2H), 7.45-7.41 (m, 1H), 7. 31 (s, 1H), 4.70-4.61 (m, 1H), 4.30 (s, 2H), 3.59-3.56 (m, 5H), 2.40-2.31 (m, 1H), 2.07-1.96 (m, 6H), 1.53-1.42 (m, 2H). EXAMPLE 300 3- (2- (2-methoxybenzyl) -1H-benzimidazol-5-yl) -1- (4-. {(4- (methylsulfonyl) piperazin-1-yl) methyl} phenyl) -1H -pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 300A The desired product was prepared by substituting the morpholine of EXAMPLE 48D for 1- (methanesulfonyl) -piperazine. EXAMPLE 300B The desired product was prepared by substituting (cis) -4- (4- (4-amino-3-iodopyrazolo- [3,4-d] -pyrimidin-1-yl) -cyclohexyl) -1- methylpiperazin-2-one from EXAMPLE 2B, by the compound of EXAMPLE 300A. EXAMPLE 300C The desired product was prepared by substituting the compound of EXAMPLE 48C for the compound of EXAMPLE 300B and the phenylacetaldehyde for 2-methoxyphenylacetaldehyde, in EXAMPLE 48D.

MS (EAI) m / e 624 (M + H) J H-NMR (300 MHz, DMSO-d6) d 8.43 (s, 1H), 8.37 (d, 2H), 8.01 (s, 1H), 7.86 (m, 2H), 7.69 (d, 2H), 7.40 (m, 2H), 7.09 (d, 1H), 7.03 (t, 1H), 4.48 (s, 2H), 4.45 (s, 2H), 3.79 (s, 3H), 3.24 (m, 8H), 3.02 (s, 3H) ). EXAMPLE 301 2- (4-. {4-amino-3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4- d] pyrimidin-1-yl} -1,4, -bipiperidin-1'-yl) ethanol EXAMPLE 301A 4- (4-amino-3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [ 3,4-d] pyrimidin-1-yl) piperidine-1-carboxylate of ferf-butyl The title compound, in the form of a brown solid foam, was prepared in the manner described in EXAMPLE 139B, substituting the compound of EXAMPLE 139A, and the compound of EXAMPLE 201A and the compound of EXAMPLE 188C, by the compound of EXAMPLE 217C, except that the purification was performed on normal phase silica gel. MS (ESI +) m / e 542 (M + H) *; (IEA (-)) m / e 540 (MH) J 1 H-NMR (300 MHz, DMSO-d 6) 11.26 (s, 1H), 8.22 (s, 1H), 7.68 (s, 1H), 7.45 (d, 1H), 7.32 (m, 3H), 7.19 (m, 2H), 6.21 (s, 1H), 4.89 (m, 1H), 4.13 (s, 2H), 4.10 (m, 2H), 3.32 (s, 2H) ), 3.00 (m, 2H), 2.04 (m, 2H), 1.94 (m, 2H), 1.43 (s, 9H). EXAMPLE 301B 3- (2-82-Fluorobenzyl) -1H-indol-5-yl) -1- (piperidin-4-yl) -1H-pyrazolo [3,4- d] pyrimidin-4-amine The title compound , in the form of a white solid with a purple dye, was prepared in the manner described in EXAMPLE 201C, substituting the compound of EXAMPLE 201 B for the compound of EXAMPLE 301A. MS (ESI +) m / e 442 (M + H) *; (ESI (-)) m / e 440 (MH) J 1 H-NMR (300 MHz, DMSO-d 6) 11.32 (s, 1H), 8.77 (m, 1H), 8.43 (m, 1H), 8.14 (s, 1H), 7.70 (s, 1H), 7.48 (d, 1H), 7.32 (m, 3H), 7.19 (m, 2H), 6.23 (s, 1H), 5.08 (m, 1H), 4.24 (vbr s, 1H), 4.15 (s, 2H), 3.47 (m, 2H), 3.22 (m, 2H), 2.37 (m, 2H), 2.14 (m, 2H). EXAMPLE 301C 2- (4-. {4-amino-3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4- d] pyrimidin-1-yl} -1, 4'-bipiperidin-1'-yl) ethanol The title compound, as a brown solid, was prepared in the manner described in EXAMPLE 201 D, substituting the compound of EXAMPLE 201C for the composed of EXAMPLE 301B, and 1-methylpiperidin-4-one by 1 - (2-hydroxyethyl) -piperidin-4-one. MS (ESI +) m / e 569 (M + H) *; (ESI (-)) m / e 567 (MH) J 1 H-NMR (300 MHz, DMSO-d 6) 11.32 (s, 1H), 9.75 (m, 1H), 9.46 (m, 1H), 8.31 (s, 1H), 7.70 (s, 1H), 7.48 (d, 1H), 7.34 (m, 3H), 7.19 (m, 2H), 6.22 (s, 1H), 5.12 (m, 1H), 4.15 (s, 2H) ), 3.75 (m, 4H), 3.56 (vbr s, 2H), 3.36 (m, 4H), 3.28 (m, 2H), 3.03 (m, 2H), 2.56 (m, 2H), 2.28 (m, 4H) ), 2.00 (m, 2H).

EXAMPLE 302 3- (4- { 4-amino-3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4- d] pyrimidin-1-yl} -1, 4'-bipiperidin-1'-yl) propan-1-ol The title compound, in the form of a brown solid, was prepared in the manner described in EXAMPLE 301, substituting the 1- ( 2-hydroxyethyl) -piperidin-4-one of EXAMPLE 301C, by 1- (3-hydroxypropyl) -piperidin-4-one. MS (ESI +) m / e 583 (M + H) *; (IEA (-)) m / e 581 (M-H) J 1 H-NMR (300 MHz, DMSO-d 6) 11.32 (s, 1H), 9. 74 (m, 1H), 9.43 (m, 1H), 8.32 (s, 1H), 7.70 (s, 1H), 7.47 (d, 1H), 7.33 (m, 3H), 7.19 (m, 2H), 6.22 (s, 1H), 5.12 (m, 1H), 4.14 (s, 2H), 3. 75 (m, 4H), 3.60 (vbr s, 2H), 3.34 (m, 4H), 3.13 (m, 2H), 3.00 (m, 2H), 2.53 (m, 2H), 2.29 (m, 4H), 1.93 (m, 2H), 1.80 (m, 2H). EXAMPLE 303 3- (2- (2-Fluorobenzyl) -1H-indol-5-yl) -1- (1, - (2-methoxyethyl) -1,4'-bipiperidin-4-yl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine The title compound, as a brown solid, was prepared in the manner described in EXAMPLE 301, substituting 1- (2-hydroxyethyl) -piperidine-4 -one of EXAMPLE 301C, by 1- (2-methoxyethyl) -piperidin-4-one. MS (ESI +) m / e 583 (M + H) *; (ESI (-)) m / e 581 (MH) J 1 H-NMR (300 MHz, DMSO-d 6) 11 32 (s, 1 H), 9.78 (m, 1 H), 9.62 (m, 1 H), 8.32 (s) , 1H), 7.69 (s, 1H), 7.47 (d, 1H), 7.32 (m, 3H), 7.19 (m, 2H), 6.21 (s, 1H), 5.12 (m, 1H), 4.14 (s, 2H), 4.00 (vbr s, 5H), 3.65 (m, 4H), 3.33 (s, 3H), 3.30 (m, 2H), 3.03 (m, 2H), 2.53 (m, 2H), 2.27 (m, 4H), 2.00 (m, 2H).

EXAMPLE 304 3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1- (1 '- (3-methoxypropyl) -1,4'-bipiperidin-4-yl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine The title compound, as a brown solid, was prepared in the manner described in EXAMPLE 301, substituting 1- (2-hydroxyethyl) -piperidine-4 -one of EXAMPLE 301C, by 1- (3-methoxypropyl) -piperidin-4-one. MS (ESI +) m / e 597 (M + H) *; (ESI (-)) m / e 595 (MH) J 1 H-NMR (300 MHz, DMSO-d 6) 11.30 (s, 1H), 9.74 (m, 1H), 9.53 (m, 1H), 8.31 (s, 1H), 7.69 (s, 1H), 7.47 (d, 1H), 7.31 (m, 3H), 7.19 (m, 2H), 6.21 (s, 1H), 5.12 (m, 1H), 4.14 (s, 2H) ), 3.86 (vbr s, 3H), 3.66 (m, 4H), 3.39 (m, 2H), 3.24 (s, 3H), 3.13 (m, 2H), 3.00 (m, 2H), 2.55 (m, 2H) ), 2.26 (m, 4H), 1.89 (m, 4H). EXAMPLE 305 3- (2- (2-Fluorobenzyl) -1H-indol-5-yl) -1- (1'-isobutyl-1,4'-bipiperidin-4-yl) -1H-pyrazolo [3,4 -d] pyrimidin-4-amine The title compound, in the form of a brown solid, was prepared in the manner described in EXAMPLE 301, substituting the 1- (2-hydroxyethyl) -piperidin-4-one of EXAMPLE 301C, by 1-isobutylpiperidin-4-one. MS (ESI +) m / e 581 (M + H) *; (ESI (-)) m / e 579 (MH) J 1 H-NMR (300 MHz, DMSO-d 6) 11.30 (s, 1H), 9.76 (m, 1H), 9.15 (m, 1H), 8.37 (s, 1H), 7.70 (s, 1H), 7.47 (d, 1H), 7.33 (m, 3H), 7.20 (m, 2H), 6.22 (s, 1H), 5.12 (m, 1H), 4.15 (s, 2H) ), 3.80 (vbr s, 2H), 3.65 (m, 4H), 3.37 (m, 2H), 2.93 (m, 2H), 2.56 (m, 2H), 2.25 (m, 4H), 2.06 (m, 4H) ), 0.96 (d, 6H).

EXAMPLE 306 2- (4- (4- { 4-amino-3- (2- (2,5-difluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] pyrimidine -1-yl.} Cyclohexyl) piperazin-1-yl) ethanol EXAMPLE 306A The desired product was synthesized by replacing the benzyl bromide of EXAMPLE 206A with 2,5-difluorobenzyl bromide. EXAMPLE 306B The desired product was synthesized by substituting the compound of EXAMPLE 206A for the compound of EXAMPLE 306A, in EXAMPLE 206B. EXAMPLE 306C The desired product was synthesized by substituting the 4-bromo-2-nitrophenylamine of EXAMPLE 2A for the compound of EXAMPLE 306B. EXAMPLE 306D The desired product was synthesized by substituting the compound of EXAMPLE 318A for 3-iodo-1- (4-oxocyclohexyl) -1H-pyrazolo- [3,4-d] -pyrimidin-4-yl-amine prepared in the manner described in AF Burchat et al., Bioorg Med. Chem. Lett. 2002, 12, 1687-1690, and the compound of EXAMPLE 217C by the compound of EXAMPLE 306C, in EXAMPLE 318B. EXAMPLE 306E The desired product was synthesized by substituting the compound of EXAMPLE 267B for the compound of EXAMPLE 306D, in EXAMPLE 267C. H-NMR (300 MHz, DMSO-d6) 11-37 (s, 1H), 8. 35 (s, 1H), 7.47 (m, 1H), 7.28-7.10 (m, 5H), 6.23 (d, 1H), 4.95 (m, 1H), 4.13 (s, 2H), 3.42-3.58 (m, 4H), 2.89-3.19 (m, 4H), 2.24-2.41 (m, 2H), 2.02-2.14 (m, 2H), 1.68-1.94 (m, 4H). EXAMPLE 307 3- (4- (4- { 4-amino-3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4- d] pyrimidin-1 -yl.}. cyclohexyl) piperazin-1-yl) propan-1-ol The desired product was the mixture of diastereoisomers that was generated in EXAMPLE 223. MS: IEA (+) m / e 583.4 (M + H) *; IEA (-) m / e 581.5 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 11-29 (s, 1H), 8.32 (s, 1H), 7.69 (s, 1H), 7.46 (d, 1H), 7.28-7.38 (m, 3H), 7.15-7.24 (m, 2H), 6.22 (d, 1H), 4.90 (m, 1H), 4.15 (s, 2H), 3.42-3.53 (m, 4H, includes = 3.46, t, 2H), 2.89-3.16 (m, 4H), 2.24-2.41 (m, 2H), 2.02-2.14 (m, 2H), 1.68-1.94 (m, 4H). EXAMPLE 308 (c / s) -1- (4- (. {2- (2- (2-Aminoethoxy) ethoxy) ethyl} amino) cyclohexyl) -3- (2- (2-fluorobenzyl) -1H -indol-5-yl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine The desired product was synthesized by substituting the 1- (3-hydroxypropyl) -piperazine of EXAMPLE 223B, by 2.2 '- ( ethylenedioxy) -bis- (ethylamine). The diastereomer that eluted first was isolated. MS: IEA (+) m / e 587.4 (M + H) *; IEA (-) m / e 585.5 (M-H); 1 H-NMR (300 MHz, DMSO-de) 11 30 (s, 1 H), 8.51 (br, 1 H), 8.31 (s, 1 H), 7.80 (br, 2 H), 7.73 (br s, 1 H), 7.47 ( d, 1H), 7.28-7.38 (m, 3H), 7.15-7.24 (m, 2H), 6.22 (s, 1H), 4.90 (brm, 1H), 4.14 (s, 2H), 3.68 (t, 2H) ), 3.58 (t, 2H), 3.26-3.36 (br m, 1H), 3.12-3.21 (m, 2H), 2.93-3.02 (m, 2H), 2.32-2.44 (m, 2H), 1.87-2.13 ( m, 6H).

EXAMPLE 309 1- (4- (. {2- (2- (2-Aminoethoxy) ethoxy) ethyl} amino) cyclohexyl) -3- (2- (2-fluorobenzyl) -1 H -indole-5- il) -1 Hp i razolo [3, 4-d] pirim din-4-a na The desired product was the mixture of unresolved diastereoisomers generated in EXAMPLE 308. 1 H-NMR (300 MHz, DMSO-de) 11.29 (s, 1H), 8.57-8.48 (br, 1H), 8.29 (s, 1H), 7.78-7.70 (br, 2H), 7.67 (br s, 1H), 7.46 (d, 1H), 7.27-7.37 (m, 3H), 7.14-7.23 (m, 2H), 6. 22 (s, 1H), 4.89-4.70 (br m, 1H), 4.14 (s, 2H), 3.24-3.36 (br m, 3H), 2.94-3.04 (m, 2H), 2.17-2.28 (m, 2H) ), 2.03-2.16 (m, 6H), 1.57-1.73 (m, 2H). EXAMPLE 310 (frans) -1- (4- (. {2- (2- (2-ami-no-ethoxy) -ethoxy) -ethyl} -amino) -cyclohexyl) -3- (2- (2-fluorobenzyl) -1H- indol-5-yl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine The desired product was the diastereomer that eluted slower in EXAMPLE 308. MS: IEA (+) m / e 587.4 (M + H) *; 1 H NMR (300 MHz, DMSO-d 6) 11.28 (s, 1 H), 8.57 (br, 1 H), 8.28 (s, 1 H), 7. 78 (br, 2H), 7.67 (br s, 1H), 7.46 (d, 1H), 7.27-7.37 (m, 3H), 7.14- 7.23 (m, 2H), 6.21 (s, 1H), 4.70 (br m, 1H), 4.14 (s, 2H), 3.24-3.36 (br m, 3H), 2.94-3.04 (m, 2H), 2.17-2.28 (m, 2H), 2.03-2.16 (m, 6H), 1.57 -1.73 (m, 2H). EXAMPLE 311 2-. { 2 - ((4- {. {4-amino-3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4- d] pyrimidin-1-yl}. cyclohexyl) amino) ethoxy} ethanol The desired product was synthesized by substituting the 1- (3-hydroxypropyl) -piperazine of EXAMPLE 223B, by 2- (2-hydroxyethoxy) - ethylamine. MS: IEA (+) m / e 544.4 (M + H) *; 1 H-NMR (300 MHz, DMSO-de) 11.31 (s, 1H), 8.53 (br, 1H), 8.44 (br, 1H), 8.34 (s, 1H), 7.74 (d, 0.5H), 7.69 (s) , 0.5H), 7.54-7.65 (m, 1H), 7.45-7.49 (m, 1H), 7.28-7.38 (m, 3H), 7.15-7.24 (m, 2H), 6.22 (s, 1H), 4.90 ( br m, 0.5H), 4.71 (m, 0.5H), 4.14 (s, 2H), 3.66-3.71 (m, 2H), 3.48-3.59 (m, 4H), 3.12-3.36 (m, 3H), 2.31 -2.41 (m, 1H), 2.16-2.28 (m, 2H), 1.87-2.14 (m, 6H), 1.55-1.70 (m, 1H). EXAMPLE 312 2- (1- (4- { 4-amino-3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4- d] pyrimidin-1 -yl.} cyclohexyl) piperidin-4-yl) ethanol The desired product was synthesized by substituting the 1- (2-hydroxyethyl) -piperazine of EXAMPLE 267C, by 4- (2-hydroxyethyl) -piperidine. MS: IEA (+) m / e 568.4 (M + H) *; 1 H-NMR (300 MHz, DMSO-de) 11.31 (s, 1H), 8.99 (br, 0.5H), 8.84 (br, 0.5H), 8.33 (s, 1H), 7.73 (d, 0.5H), 7.68 (s, 0.5H), 7.45-7.50 (m, 1H), 7.28-7.38 (m, 3H), 7.15-7.24 (m, 2H), 6.22 (s, 1H), 4.98 (br m, 0.5H), 4.76 (m, 0.5H), 4.14 (s, 2H), 3.37-3.52 (m, 3H), 3.15-3.36 (m, 3H), 2.89-3.05 (m, 2H), 2.31-2.43 (m, 1H) , 2.15-2.22 (m, 3H), 1.58-2.44 (m, 6H), 1.30-1.45 (m, 3H). EXAMPLE 313 (1- (4- { 4-amino-3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4- d] pyrimidin-1-yl .) cyclohexyl) piperidin-4-yl) methanol The desired product was synthesized by substituting 1- (2-hydroxyethyl) -piperazine from EXAMPLE 267C, by 4-hydroxymethylpiperidine. MS: IEA (+) m / e 554.4 (M + H) *; 1 H-NMR (300 MHz, DMSO-de) 11 33 (s, 1H), 8.95 (br, 0.5H), 8.82 (br, 0.5H), 8.33 (s, 1H), 7.73 (d, 0.5H), 7.69 (s, 0.5 H), 7.45-7.50 (m, 1H), 7.28-7.38 (m, 3H), 7.15-7.24 (m, 2H), 6.22 (s, 1H), 4.98 (br m, 0.5H), 4.76 (m, 0.5H), 4.15 (s, 2H), 3.22-3.54 (m, 8H), 2.90-3.07 (m, 2H), 2.07-2.23 (m, 2H), 1.78-2.05 (m, 6H), 1.56-1.71 (m, 1H), 1.33-1.52 (m, 1H). EXAMPLE 314 (frans) -3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1- (4-. {4- (2- (2-methoxyethoxy) ethyl) piperazin-1- il.) cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine The desired product was prepared by substituting the 2- (2-ethoxyethoxy) -ethyl bromide of EXAMPLE 318D, for 1-bromo- 2- (2-methoxyethoxy) -ethane. MS: IEA (+) m / e 627.5 (M + H) *; IEA (-) m / e 625.6 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 11.30 (s, 1 H), 8.33 (s, 1 H), 7.68 (br s, 1 H), 7.46 (d, 1 H), 7.39-7.28 (m, 3 H), 7.24 -7.15 (m, 2H), 6.22 (s, 1H), 4.79-4.67 (br m, 1H), 4.61 (s, 3H), 4.14 (s, 2H), 3.69 (br t, 2H), 3.59-3.55 (m, 2H), 3.50-3.46 (m, 2H), 3.15 (br m, 1H), 2.19-2.07 (m, 6H), 1.79-1.64 (br m, 2H). EXAMPLE 315 (frans) -3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1- (4-. {4- (2- (methoxymethoxy) ethyl) piperazin-1-yl} cyclohexyl) -1 H-pyrazole or [3, 4-d] pyrimidin-4-amine The desired product was prepared by substituting bromide 2- (2-Ethoxyethoxy) -ethyl from EXAMPLE 318D, by 2-bromoethylmethoxymethylether. MS: IEA (+) m / e 613.5 (M + H) *; 1 H-NMR (300 MHz, DMSO-d 6) 11.28 (s, 1 H), 8.31 (s, 1 H), 7.68 (br s, 1 H), 7.46. (d, 1H), 7.38-7.28 (m, 3H), 7.24-7.15 (m, 2H), 6.22 (s, 1H), 4.79-4.67 (br m, 1H), 4.61 (s, 3H), 4.14 ( s, 2H), 3.75 (br m), 3.15-3.00 (br m, 1H), 2.19-2.05 (m, 6H), 1.79-1.62 (br m, 2H). EXAMPLE 316 3- (4- (4- { 4-amino-3- (2- (2,5-difluorobenzyl) -1 H -indol-5-yl) -1 H-pyrazolo [3,4-d] ] pyrimidin-1-yl}. cyclohexyl) piperazin-1-yl) propan-1-ol The desired product was synthesized by replacing the compound of EXAMPLE 267B with the compound of EXAMPLE 306D and 1- (2-hydroxyethyl) -piperazine by 1- (3-hydroxypropyl) -piperazine, in EXAMPLE 267C. 1 H-NMR (300 MHz, DMSO-d 6) 11.37 (s, 1H), 8.36 (s, 1H), 7.47 (m, 1H), 7.28-7.10 (m, 5H), 6.24 (d, 1H), 4.95 ( m, 1H), 4.13 (s, 2H), 3.42.3.53 (m, 4H, includes = 3.46, t, 2H), 3.01-3.17 (m, 4H), 2.24-2.41 (m, 2H), 2.02-2.14 (m, 2H), 1.68-1.94 (m, 4H). EXAMPLE 317 2- (4- (4- { 4-amino-3- (2- (2-fluorobenzyl) -1 H -indol-5-yl) -1 H -pyrazolo [3,4- d] pyrimidine -1-yl.) Cyclohexyl) piperazin-1-yl) ethanol The desired product is the mixture of the diastereomers generated in EXAMPLE 227. 1 H-NMR (300 MHz, DMSO-d 6) 11.29 (s, 1 H), 8.33 (s, 1H), 7.70 (s, 1H), 7.46 (d, 1H), 7.28-7.38 (m, 3H), 7.15-7.24 (m, 2H), 6.22 (d, 1H), 4.91 (m, 1H) ), 4.14 (s, 2H), 3.42-3.58 (m, 4H), 2.89-3.19 (m, 4H), 2.24-2.41 (m, 2H), 2.02-2.14 (m, 2H), 1.68-1.94 (m , 4H). EXAMPLE 318 (frans) -1- (4-. {4- (2- (2-ethoxyethoxy) ethyl) piperazin-1-yl}. Cyclohexyl) -3- (2- (2-f luorobenzyl) -1H -indol-5-yl) -1H-pyrazolo [3,4-d] pyrimidin-4-a mine EXAMPLE 318A 3-Iodo-1- (4-oxocyclohexyl) -1 H -pyrazolo- [3,4-d] -pyrimidin-4-ylamine prepared in the manner described in AF Burchat et al., Bioorg Med Chem. Lett. 2002, 12, 1687-1690 (1785 g, 5 mmol) and tert-butyl 1-piperazinecarboxylate (4.65 g, 25 mmol) in 70 mL of methanol and 7 mL of acetic acid and stirred at room temperature for 20 min. Cyanoborohydride (polystyryl) -tmethyl ammonium resin (4.2 mmol / g, 4.5 g) was added and the mixture was stirred at 70 ° C for 16 hours. The resin was removed by filtration, the filtrate was concentrated in vacuo and the residue was purified on a column of silica gel, eluting with 7% methanol in ethyl acetate, to obtain the trans diastereomer (1.08 g). EXAMPLE 318B The compound of EXAMPLE 318A (1.25 g, 2.37 mmol), the compound of EXAMPLE 217C (1.0 g, 2.84 mmol), sodium carbonate (0.5 g, 4.71 mmol) and palladium tetrakis-triphenylphosphine (82 mg, 0. 07 mmol), were suspended in 30 mL of DME / water (1: 1). This material was heated by microwave at 130 ° C for 20 minutes.

After partition by extraction in ethyl acetate and brine, the ethyl acetate phase was washed with brine (3x), dried and purified by silica gel column chromatography, eluting with 7% methanol in acetate of ethyl, obtaining 720 mg of the title compound. EXAMPLE 318C The compound of EXAMPLE 318B (312 mg, 0.5 mmol) was treated with 1.25 mL of trifluoroacetic acid (TFA) and 5 mL of methylene chloride for 1 hour. The solvent was removed and the residue was triturated with ether and dried under high vacuum to obtain the title compound in quantitative yield. EXAMPLE 318D The compound of EXAMPLE 318C (94 mg, 0.15 mmol), 2- (2-ethoxyethoxy) -ethyl bromide (44 mg, 0.225 mmol), sodium iodide (56 mg, 0.375 mmol) and potassium carbonate (104 mg, 0.75 mmol), were mixed in 5 mL of acetonitrile. The solution was stirred at 65 ° C for 16 hours. The insoluble material was filtered and purified by HPLC. 54 mg of the title compound were obtained. MS: IEA (+) m / e 641.5 (M + H) *; IEA (-) m / e 639.6 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 11.28 (s, 1 H), 8.30 (s, 1 H), 7.68 (br s, 1 H), 7.46 (d, 1 H), 7.38-7.28 (m, 3 H), 7.24 -7.15 (m, 2H), 6.22 (s, 1H), 4.80.4.67 (br m, 1H), 4.14 (s, 2H), 3.58-3.49 (m, 8H), 3.45 (q, 2H), 3.15- 3.00 (br m, 1H), 2.18-2.05 (m, 6H), 1.76-1.61 (br m, 2H), 1.11 (t, 3H). EXAMPLE 319 1- (4-. {4-amino-3- (2- (2-methoxybenzyl) -1 H -benzimidazol-5-yl) -1 H-pyrazolo [3,4-d] pyrimidin-1- il.) cyclohexyl) piperidin-4-ol The desired product was prepared by substituting 2- (trifluoromethyl) -5,6,7,8-tetrahydroimidazo- [1,2-a] -pyrazine from the EXAMPLE 338, by 4-hydroxypiperidine. MS (EAI) m / e 553 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 9.0 (bs, 1H), 8.32 (s, 1H), 7.92 (s, 1H), 7.85 (d , 1H), 7.77 (d, 1H), 7.39 (m, 2H), 7.08 (d, 1H), 7.02 (t, 1H), 5.00 (m, 1H), 4.45 (s, 2H), 3.78 (s, 3H), 3.42 (m, 2H), 3.30 (m, 1H), 3. 18 (m, 1H), 3.04 (m, 1H), 2.40 (m, 2H), 2.11-1.96 (m, 7H), 1.79 (m, 2H), 1.58 (m, 1H). EXAMPLE 320 (frans) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-5-yl) -1-. { 4- (4- (4-methoxyphenyl) piperazin-1-yl) cyclohexyl} -1H-pyrazolo [3,4-d] pyrimidin-4-amine The desired product was prepared by substituting 2- (trifluoromethyl) -5,6,7,8-tetrahydroimidazo- [1,2-a] -pyrazine from the EXAMPLE 338, by 1- (4-methoxyphenyl) -piperazine. The isomer that eluted faster was isolated. MS (EAI) m / e 644 (M + H) J 1 H-NMR (300 MHz, DMSO-de) d 9.46 (bs, 1H), 8.30 (s, 1H), 7.87 (s, 1H), 7.83 (d , 1H), 7.72 (d, 1H), 7.38 (m, 2H), 7.08 (d, 1H), 7.00 (m, 3H), 6.87 (d, 2H), 4.80 (m, 1H), 4.44 (s, 2H), 3.78 (s, 3H), 3.70 (s, 3H), 3.28 (m, 4H), 2.92 (m, 4H), 2.27 (m, 2H), 2.14 (m, 4H), 1.82 (m, 2H) ). EXAMPLE 321 (c / s) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-5-yl) -1-. { 4- (4- (4-methoxyphenyl) piperazin-1-yl) cyclohexyl} -1 H -pyrazole or [3,4-d] pyrim id in -4-amine This compound is the slowest eluting diastereomer of EXAMPLE 320. MS (LEA) m / e 644 (M + H) J 1 H-NMR (300 MHz, DMSO-de) d 9.30 (bs, 1H), 8.32 (s, 1H), 7.91 (s, 1H), 7.84 (d, 1H), 7.77 (d, 1H), 7.38 (m, 2H) , 7.08 (d, 1H), 7.02 (t, 1H), 6.95 (d, 2H), 6.86 (d, 2H), 5.00 (m, 1H), 4.43 (s, 2H), 3.78 (s, 3H), 3.70 (s, 3H), 3.23 (m, 4H), 2.90 (m, 4H), 2.08 (m, 8H).

EXAMPLE 322 (frans) -4- (4-. {4-amino-3- (2- (2-methoxybenzyl) -1H-benzimidazol-5-yl) -1H-pyrazolo [3,4-d] pyrimidine- 1-yl.) Cyclohexyl) piperazin-2-one The desired product was prepared by substituting 2- (trifluoromethyl) -5,6,7,8-tetrahydroimidazo [1,2-a] pyrazine from EXAMPLE 338, 2- oxopiperazine. The isomer that eluted faster was isolated. MS (EAI) m / e 552 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 8.49 (bs, 1H), 8.31 (s, 1H), 7.88 (s, 1H), 7.84 (d , 1H), 7.72 (d, 1H), 7.38 (m, 2H), 7.08 (d, 1H), 7.02 (t, 1H), 4.80 (m, 1H), 4.45 (s, 2H), 3.87 (m, 2H), 3.78 (s, 3H), 3.45 (m, 4H), 2.12 (m, 6H), 1.83 (m, 2H). EXAMPLE 323 (c / s) -4- (4-. {4-amino-3- (2- (2-methoxybenzyl) -1H-benzimidazol-5-yl) -1H-pyrazolo [3,4-d] pyrimidin-1-yl}. cyclohexyl) piperazin-2-one This compound is the slowest eluting diastereomer of EXAMPLE 322. MS (LEA) m / e 552 (M + H) J 1 H-NMR (300 MHz, DMSO -d6) d 8.46 (bs, 1H), 8.31 (s, 1H), 7.90 (s, 1H), 7.82 (d, 1H), 7.75 (d, 1H), 7.38 (m, 2H), 7.08 (d, 1H), 7.02 (t, 1H), 4.97 (m, 1H), 4.43 (s, 2H), 3.84 (m, 2H), 3.78 (s, 3H), 3.40 (m, 4H), 2.36 (m, 2H) ), 2.12 (m, 3H), 1.97 (m, 3H). EXAMPLE 324 (frans) -5- (2- (2-methoxybenzyl) -1H-benzimidazol-5-yl) -7-. { 4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl} -7H-pyrrolo [2,3-d] pyrimidin-4-amine EXAMPLE 324A The desired product was prepared by substituting the 4- (4- amino-3-iodo-1 H-pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexanone from EXAMPLE 339C, by 4- (4-amino-5-iodo-pyrrolo [2,3-d] pyrimidin-7-yl) -cyclohexanone prepared as described in International Patent Publication WO 2005/074603. MS (LEA) m / e 467 (M + H); 1 H-NMR (300 MHz, DMSO-d 6) 12.17 (bs, 1H), 8.16 (s, 1H), 7.57 (m, 1H), 7.43 (m, 2H), 7.23 (m, 3H), 7.02 (m, 1H), 6.91 (m, 1H), 5.18 (m, 1H), 4.14 (s, 2H), 3.81 (s, 3H), 2.76 (m, 2H), 2.34 (m, 4H), 2.22 (m, 2H) ). EXAMPLE 324B The desired product was prepared by substituting 2- (trifluoromethyl) -5,6,7,8-tetrahydroimidazo [1,2-a] pyrazine for 1- (3-methoxypropyl) piperazine and the product of EXAMPLE 339C for the product of EXAMPLE 324A, in EXAMPLE 338. The isomer that eluted the fastest was isolated. MS (EAI) m / e 609 (M + H) J 1 H-NMR (300 MHz, DMSO-de) d 8.40 (s, 1H), 7.79 (m, 2H), 7.72 (s, 1H), 7.54 (d , 1H), 7.38 (m, 2H), 7.08 (d, 1H), 7.02 (t, 1H), 4.68 (m, 1H), 4.44 (s, 2H), 3.78 (s, 3H), 3.67 (m, 5H), 3.39 (t, 2H), 3.25 (s, 3H), 2.99 (m, 5H), 2.07 (m, 6H), 1.85 (m, 2H), 1.67 (m, 2H). EXAMPLE 325 (c / s) -5- (2- (2-methoxybenzyl) -1H-benzimidazol-5-yl) -7-. { 4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl} -7H-pyrrolo [2,3-d] pyrimidin-4-amine The desired product was the isomer that eluted slower in EXAMPLE 324B. MS (EAI) m / e 609 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 8.42 (s, 1 H), 7.78 (d, 1 H), 7.72 (s, 1 H), 7.65 (s) , 1H), 7.54 (d, 1H), 7.38 (m, 2H), 7.08 (d, 1H), 7.02 (t, 1H), 4.80 (m, 1H), 4.44 (s, 2H), 3.78 (s, 3H), 3.68 ( m, 5H), 3.38 (t, 2H), 3.24 (s, 3H), 3.06 (m, 5H), 2.18-2.07 (m, 4H), 1.86-1.76 (m, 6H). EXAMPLE 326 (frans) -3- (2- (2-methoxybenzyl) -1 H -benzimidazol-5-yl) -1-. { 4- (4- (tetrahydrofuran-2-yl-methyl) piperazin-1-yl) cyclohexyl} -1 H-pyrazolo [3,4- d] pyrimidin-4-amine The desired product was prepared by substituting 2- (trifluoromethyl) -5,6,7,8-tetrahydroimidazo- (1, 2-a) -pyrazine from the EXAMPLE 338, by 1- (cyclopent-2-yl-methyl) -piperazine. The isomer that eluted faster was isolated. MS (LEA) m / e 622 (M + H) J 1 H-NMR (300 MHz, DMSO-de) d 8.29 (s, 1H), 7.87 (s, 1H), 7.81 (d, 1H), 7.70 (d, 1H), 7.38 (m, 2H), 7.08 (d, 1H), 7.02 (t, 1H), 4.77 (m, 1H), 4.44 (s, 2H), 4.12 (m, 1H), 3.80 (m, 2H), 3.78 (s, 3H), 3.71 (m, 6H), 3.02 (m, 5H), 2.11 (m, 6H), 2.01 (m, 1H) ), 1.84 (m, 2H), 1.70 (m, 2H), 1.50 (m, 1 HOUR). EXAMPLE 327 (c / 's) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-5-yl) -1-. { 4- (4- (tetrahydrofuran-2-yl-methyl) piperazin-1-yl) cyclohexyl} -1H-pyrazolo [3,4- d] pyrimidin-4-amine The desired product was the diastereomer eluting slower in EXAMPLE 326. MS (LEA) m / e 622 (M + H) J 1 H-NMR (300 MHz, DMSO-de) d 8.33 (s, 1H), 7.90 (s, 1H), 7.84 (d, 1H), 7.75 (d, 1H), 7.38 (m, 2H), 7.08 (d, 1H), 7.02 (t, 1H), 4.93 (m, 1H), 4.45 (s, 2H), 4.15 (m, 1H), 3.81 ( m, 2H), 3.78 (s, 3H), 3.71 (m, 2H), 3.48 (m, 4H), 3.05 (m, 4H), 2.37 (m, 2H), 2.02 (m, 4H), 1.86 (m, 5H), 1.49 (m, 1H). EXAMPLE 328 (frans) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-5-yl) -1-. { 4- (4- (tetrahydrofuran-2-yl-carbonyl) piperazin-1-yl) cyclohexyl} -1H- pyrazolo [3,4-d] pyrimidin-4-amine The desired product was prepared by substituting 2- (trifluoromethyl) -5,6,7,8-tetrahydroimidazo- [1,2-a] -pyrazine from the EXAMPLE 338, by 1- (cyclopent-2-yl) -piperazine. The isomer that eluted faster was isolated. MS (LEA) m / e 636 (M + H) J 1 H-NMR (300 MHz, DMSO-de) d 9.80 (bs, 1H), 8.31 (s, 1H), 7.88 (s, 1H), 7.84 (d, 1H), 7. 72 (d, 1H), 7.38 (m, 2H), 7.08 (d, 1H), 7.02 (t, 1H), 4.79 (m, 1H), 4. 72 (m, 2H), 4.45 (s, 2H), 4.23 (m, 2H), 3.78 (s, 3H), 3.74 (m, 2H), 3. 49 (m, 4H), 3.04 (m, 2H), 2.19 (m, 2H), 2.13 (m, 4H), 2.02 (m, 2H), 1.84 (m, 2H), 1.79 (m, 2H). EXAMPLE 329 (c / 's) -3- (2- (2-methoxy-benzyl) -1H-benzimidazole-5-l) -1-. { 4- (4- (tetrahydrofuran-2-yl-carbonyl) piperazin-1-yl) cyclohexyl} -1 H- pyrazolo [3,4-d] pyrimidin-4-amine This compound is the slowest eluting diastereomer of EXAMPLE 328. MS (IEA) m / e 636 (M + H) J 1 H-NMR (300 MHz, DMSO-d6) d 9.60 (bs, 1H), 8.32 (s, 1H), 7.91 (s, 1H), 7.84 (d, 1H), 7.77 (d, 1H), 7.38 (m, 2H), 7.08 (d, 1H), 7.02 (t, 1H), 4.98 (m, 1H), 4.69 (m, 2H), 4.45 (s, 2H), 4.18 (M, 2H), 3.78 (s, 3H), 3.74 (m, 2H), 3.54 (m, 2H), 3.42 (m, 2H) ), 3.01 (m, 2H), 2.42 (m, 2H), 2.03 (m, 8H), 1.83 (m, 2H). EXAMPLE 330 (c / s) -2-. { 2 - ((4- {4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] pyrimidin-1-yl} cyclohexyl) amino) ethoxy} ethanol The desired product was synthesized by substituting the 3-aminobenzyl alcohol of EXAMPLE 210C for 2- (2-hydroxyethoxy) ethylamine. The diastereomer that eluted first was isolated. MS: IEA (+) m / e 544.3 (M + H) *; 1 H-NMR (300 MHz, DMSO-d 6) 8.41 (br, 1H), 8.32 (s, 1H), 7.78 (d, 1H), 7.67 (d, 1H), 7.58 (d, 1H), 7.47 (dd, 1H), 7.31-7.38 (m, 1H), 7.21-7.28 (m, 1H), 7.13-7.16 (m, 2H), 6.63 (s, 1H), 5.55 (s, 2H), 4.91 (br m, 1H ), 4.15 (s, 2H), 3.48-3.56 (m, 6H), 3.24-3.36 (m, 2H), 3.13-3.23 (m, 2H), 2.28-2.43 (m, 3H), 1.86-2.09 (m , 6H). EXAMPLE 331 (frans) -2-. { 2 - ((4- {. {4-amino-3- (1- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pi-branzo [3,4-d] pyrim id in-1 -yl.}. cyclohexyl) amino) ethoxy} Ethanol The desired product was the slower eluting diastereomer of EXAMPLE 330. MS: IEA (+) m / e 544.3 (M + H) *; 1 H-NMR (300 MHz, DMSO-de) 8.52 (br, 1H), 8.33 (s, 1H), 7.84 (d, 1H), 7.67 (d, 1H), 7.58 (d, 1H), 7.42 (dd, 1H), 7.31-7.38 (m, 1H), 7.22-7.28 (m, 1H), 7.13-7.16 (m, 2H), 6.63 (s, 1H), 5.55 (s, 2H), 4.71 (br m, 1H ), 3.69 (t, 2H), 3.51-3.58 (m, 4H), 3.13-3.23 (m, 4H), 2.13-2.28 (m, 2H), 2.03-2.14 (m, 4H), 1.56-1.71 (m , 2H). EXAMPLE 332 (frans) -3- (4- (4- { 4-amino-3- (2- (2-fluorobenzyl) -1H-indol-6-yl) -1H-pyrazolo [3,4-d] ] pyrimidin-1-yl}. cyclohexyl) -piperazin-1-yl) propan-1-ol The desired product was prepared by substituting the 2- (2-ethoxyethoxy) ethyl bromide of EXAMPLE 318D, for 3-bromo-1-propanol. MS: IEA (+) m / e 583.4 (M + H) *; 1 H-NMR (300 MHz, DMSO-de) 11.28 (s, 1H), 8.30 (s, 1H), 7.58 (d, 1H), 7.56 (s, 1H), 7.28-7.38 (m, 2H), 7.15- 7.27 (m, 3H), 6.19 (s, 1H), 4.75 (br m, 1H), 4.15 (s, 2H), 2.90-3.17 (m, 3H), 2.02-2.20 (br m, 6H), 1.58- 1.83 (br m, 4H). EXAMPLE 333 (frans) -3- (2- (2-fluorobenzyl) -1H-indol-6-yl) -1-. { 4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl} -1 H-pyrazolo [3,4-d] pyrimidin-4-amine The desired product was prepared by substituting the 2- (2-ethoxyethoxy) ethyl bromide of EXAMPLE 318D, for 1-bromo-3-methoxypropane. MS: IEA (+) m / e 597.5 (M + H) *; 1 H-NMR (300 MHz, DMSO-de) 11-27 (s, 1H), 8.30 (s, 1H), 7.58 (d, 1H), 7.56 (s, 1H), 7.28-7.38 (m, 2H), 7.15-7.27 (m, 3H), 6.19 (s, 1H), 4.74 (br m, 1H), 4.15 (s, 2H), 3.25 (s, 3H), 2.90-3.17 (m, 3H), 2.02-2.20 (br m, 6H), 1.78-1.90 (m, 2H), 1.58-1.75 (br m, 2H). EXAMPLE 334 (frans) -2- (4- (4- { 4-amino-3- (2- (2-fluorobenzyl) -1H-indol-6-yl) -1H-pyrazolo [3,4-d] ] pyrimidin-1-yl}. cyclohexyl) piperazin-1-yl) ethanol EXAMPLE 334A The desired product was prepared by substituting 5-bromoindole for 6-bromoindole and 2-methoxybenzyl bromide for 2-fluorobenzyl bromide, EXAMPLE 341A. EXAMPLE 334B The title product was prepared by substituting the product of EXAMPLE 341A for the product of EXAMPLE 334A, in EXAMPLE 341B. EXAMPLE 334C The desired product was prepared by substituting the product of EXAMPLE 382A for the product of EXAMPLE 334B, in EXAMPLE 382B. EXAMPLE 334D The desired product was prepared by substituting the product of EXAMPLE 341C for the product of EXAMPLE 334C, in the EXAMPLE 341D. MS: IEA (+) m / e 569.4 (M + H) *; IEA (-) m / e 567.4 (M-H); 1 H NMR (300 MHz, DMSO-d 6) 11.29 (s, 1 H), 8.32 (s, 1 H), 7.58 (d, 1H), 7.56 (s, 1H), 7.28-7.38 (m, 2H), 7.15-7.27 (m, 3H), 6.19 (s, 1H), 4. 76 (br m, 1H), 4.15 (s, 2H), 3.72 (br.t, 2H), 3.10-3.20 (M, 3H), 2.07-2.22 (br, 4H), 1.64-1.82 (br m, 2H ). EXAMPLE 335 (frans) -1- (4- { 4-amino-3- (2- (2-fluorobenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] pyrimidine- 1-yl.) Cyclohexyl) piperidin-4-ol The desired product was synthesized by substituting the 1- (2-hydroxyethyl) piperazine of EXAMPLE 267C, by 4-hydroxypiperidine. MS: IEA (+) m / e 540.4 (M + H) *; 1 H NMR (300 MHz, DMSO-d 6) 11.28 (s, 1H), 9.00 (br, 0.4H), 8.84 (br, 0.6H), 8.29 (s, 0.4H), 8.28 (s, 0.6H), 7.72 (d, 0.6H), 7.68 (s, 0.4H), 7.45-7.49 (m, 1H), 7.28-7.38 (m, 3H), 7.14-7.24 (m, 2H), 6.22 (s, 1H), 4.97 (br m, 0.6H), 4.76 (m, 0.4H), 4.14 (s, 2H), 3.00-3.14 (m, 2H), 2.34-2.45 (m, 1H), 2.06-2.23 (m, 3H) , 1. 92-2.04 (m, 3H), 1.72-1.89 (m, 3H), 1.72-1.88 (m, 2H), 1.50-1.48 (m, 1H). EXAMPLE 336 (frans) -1- (4-. {4- (2- (1,3-dioxolan-2-yl) ethyl) piperazin-1-yl}. Cyclohexyl) -3- (2- (2 -methoxybenzyl) -1H-benzimidazol-5-yl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine The desired product was prepared by substituting 2- (trifluoromethyl) -5,6-8,7-tetrahydroimidazo [1,2-a] pyrazine from EXAMPLE 338, by 1- (1- (1,3-dioxolan-2-yl) ethyl) piperazine. MS (EAI) m / e 638 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 8.29 (s, 1 H), 7.87 (s, 1 H), 7.82 (d, 1 H), 7.70 (d , 1H), 7.38 (m, 2H), 7.08 (d, 1H), 7.02 (t, 1H), 4.89 (t, 1H), 4.75 (m, 1H), 4.44 (s, 2H), 3.91 (m, 2H), 3.80 (m, 2H), 3.78 (s, 3H), 2.92 (m, 10H), 2.10 (m, 6H), 1.91 (m, 2H), 1.68 (m, 2H). EXAMPLE 337 (c / s) -1- (4-. {4- (2- (1,3-dioxolan-2-yl) ethyl) piperazin-1-yl}. Cyclohexyl) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-5-yl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine This compound is the slowest eluting diastereomer of EXAMPLE 336. MS (IEA) m / e 638 (M + H) J 1 H-NMR (300 MHz, DMSO-de) d 8.32 (s, 1H), 7.89 (s, 1H), 7.84 (d, 1H), 7.73 (d, 1H), 7.38 ( m, 2H), 7.09 (d, 1H), 7.02 (t, 1H), 4.92 (m, 1H), 4.88 (t, 1H), 4.45 (s, 2H), 3.91 (m, 2H), 3.80 (m , 2H), 3.78 (s, 3H), 2.98 (m, 10H), 2.36 (M, 2H), 2.06 (m, 2H), 1.93 (m, 6H). EXAMPLE 338 (frans) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-6-yl) -1-. { 4- (2- (trifluoromethyl) -5,6-dihydroimidazo [1,2-a] pyrazin-7 (8H) -yl) cyclohexyl} - 1 H-pyrazolo [3,4-d] pyrimidin-4-amine To a mixture of the product of EXAMPLE 339C (0.13 g, 0. 28 mmol) and 2- (trifluoromethyl) -5,6,7,8-tetrahydroimidazo [1,2-a] pyrazine (0.16 g, 0.83 mmol), a 0.2M solution of MeOH / AcOH (9: 1, v / v). The mixture was stirred for 15 minutes and NaCNBH3 (0.035, 0.558 mmol) was added. The reaction was allowed to stir at RT for 1.5 hours. The mixture was diluted with CH2Cl2, washed with a saturated aqueous solution of NaHCO3. The organic phase was dried over MgSO, filtered, reduced in vacuo and purified by Reverse phase CLAR. The fastest elution isomer was isolated.

(IEA (+)) m / e 643 (M + H) *; 1 H-NMR (300 MHz, DMSO-d 6) 12.26 (bs, 1H), 8.23 (s, 1H), 7.70 (s, 2H), 7.64-7.61 (m, 1H), 7.41 (m, 1H), 7.29- 7.24 (m, 1H), 7.20-7.18 (1H, m) , 7.02 (d, 1H), 6.91 (t, 1H), 4.71 (bm, 1H), 4.17 (s, 2H), 4.01 (bm, 2H), 3.81 (bs, 5H), 3.00 (m, 2H), 2.73 (m, 1H), 2.05 (m, 6H), 1.67-1.55 (m, 2H). EXAMPLE 339 4-. { 4-amino-3- (2- (2-methoxybenzyl) -1H-benzimidazol-6-yl) -1H-pyrazolo [3,4-d] pyrimidin-1-yl} Cyclohexanone EXAMPLE 339A The desired product was synthesized by replacing the phenylacetonitrile of EXAMPLE 118B with 2-methoxyphenylacetonitrile. EXAMPLE 339B To a mixture of EXAMPLE 280A (3.0 g, 12.76 mmol) and EXAMPLE 339A (3.21 g, 14.04 mmol), was added MeOH (63 mL), The resulting solution was stirred at RT for 2 hours. The reaction was reduced in vacuo, redissolved in EtOAc and washed with a saturated aqueous solution of NaHCO 3. The resulting organic phases were dried over MgSO 4, filtered and reduced under vacuum on silica gel. The mixture was purified through a purification system lntelliflash-280 (hexanes / EtOAc), to obtain 2.7 g of the desired product as a white solid. EXAMPLE 339C To a mixture of EXAMPLE 339B (2 g, 5.49 mmol) and 4- (4-amino-3-iodo-1 H-pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexanone prepared as described in AF Burchat ef al. Bioorg Med. Chem. Lett. 2002, 12, 1687-1690 (1.63 g, 4.57 mmol) and (Ph3P) 2PdCI2 (0.16 g, 0.228 mmol) in a 0.3M solution of DME / H2O (2: 1, v / v), was added Na2CO32M ( 4.5 mL, 9.14 mmol). The reaction was heated in a microwave reactor for 20 min. at 130 ° C. The mixture was filtered through Celite and washed with CH2Cl2. The filtrate was dried over MgSO, filtered and reduced in vacuo on silica gel. The mixture was purified through an Intelliflash-280 purification system (EtOAc / MeOH), to obtain 1.7 g of the desired product as a white solid with an 80% yield. (IEA (+)) m / e 468 (M + H) *; 1 H-NMR (300 MHz, DMSO-d 6) 12.35 (bs, 1H), 8.26 (s, 1H), 7.76-7.55 (bm, 2H), 7.44-7.41 (m, 1H), 7.29-7.17 (m, 2H ), 7.04-7.00 (m, 1H), 6.94-6.88 (m, 1H), 5.25 (m, 1H), 4.17 (s, 2H), 3.81 (s, 3H), 2.72-2.70 (m, 2H), 2.45-2.36 (m, 4H), 2.29-2.24 (m, 2H).

EXAMPLE 340 (c / s) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-6-yl) -1-. { 4- (2- (trifluoromethyl) -5,6-dihydroimidazo [1,2-a] pyrazin-7 (8H) -yl) cyclohexyl} - 1 H-pyrazolo [3,4-d] pyrimidin-4-amine The desired product is the slowest elution isomer of the EXAMPLE 338: (IEA (+)) m / e 643 (M + H) *; 1 H-NMR (300 MHz, DMSO-de) 12.19 (bs, 1H), 8.23 (s, 1H), 7.70 (s, 2H), 7.67-7.63 (m, 1H), 7.40 (d, 1H), 7.24 ( d, 1H), 7.18 (m, 1H), 7.01 (m, 1H), 6.90 (t, 1H), 4.85 (m, 1H), 4.16 (s, 2H), 4.04 (m, 2H), 3.80 (s) , 3H), 3.75 (m, 2H), 2.98-2.96 (m, 2H), 2.74-2.72 (m, 2H), 2.28-2.26 (m, 2H), 2.22-2.13 (m, 2H), 1.81-1.66 (m, 3H). EXAMPLE 341 (frans) -2- (4- (4- { 4-amino-3- (2- (2-methoxybenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] ] pyrimidin-1-yl}. cyclohexyl) piperazin-1-yl) ethanol EXAMPLE 341A 5-Bromoindole (1.96 g, 10 mmol) and 2-methoxybenzyl chloride (1.53 mL, 11 mmol) were dissolved in 20 mL of DMF. A solution of 60% sodium hydride (0.44 g, 11 mmol) was added to the mixture. The mixture was stirred at 60 ° C for 16 hours. 150 mL of EtOAc and 50 mL of brine were added, and the EtOAc layer was washed with brine (3x), dried over MgSO4 and evaporated to dryness, to obtain N- (2-methoxy) benzyl-indole with a quantitative performance. This was suspended in 50 mL of polyphosphoric acid at 93 ° C for 16 hours. After cooling to room temperature, the mixture was poured into ice water. The product was submitted to Extraction with ferrous methyl ester (TBME). The organic phase was washed with 10% NaHCO3 (3x), dried over MgSO and evaporated to dryness to obtain 3.12 g of the title compound. EXAMPLE 341B The title product was prepared by substituting the 4-bromo-2-nitrophenylamine of EXAMPLE 2A for the product of EXAMPLE 341A (3.16 g, 10.0 mmol). MS: IQD (+) m / e 364.44 (M + H) *; 1 H-NMR (300 MHz, DMSO-de) 10.99 (s, 1H), 7.79 (s, 1H), 7.19-34 (m, 3H), 7.09 (dd, 1H), 7.00 (dd, 1H), 6.87 ( dt, 1H), 6.09 (s, 1H), 4.01 (s, 2H), 3.81 (s, 3H), 1.30 (s, 12H). EXAMPLE 341C The desired product was prepared by substituting the product of EXAMPLE 382A in EXAMPLE 382B, by the product of EXAMPLE 341B. MS: IQD (+) m / e 637.50 (M + H) *. EXAMPLE 341D The product of EXAMPLE 341C (90 mg, 0.15 mmol) was treated with 2 mL of CH2CI2 and 0.6 mL of TFA at room temperature for 1 hour. This evaporated to dryness. The product obtained was dissolved in 5 mL of MeCN. Sodium iodide (56 mg, 0.375 mmol), K2CO3 (104 mg, 0.75 mmol) and bromoethanol (32 mL, 0.45 mmol) were added, and the mixture was stirred at 50 ° C for 16 hours. The reaction mixture was extracted by partition in EtOAc and brine, the EtOAc layer was washed with brine (3x) and dried over MgSO4. The crude product was purified by High Performance Liquid Chromatography (HPLC), to obtain 48. 3 mg of the title compound. MS: IEA (+) m / e 581.4 (M + H) *; IEA (-) m / e 579.4 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 11.16 (s, 1H), 8.32 (s, 1H), 7.67 (s, 1H), 7.46 (d, 1H), 7.28 (dd, 1H), 7.23 (dd, 1H), 7.14 (dd, 1H), 7.02 (d, 1H), 6.89 (dt, 1H), 6.18 (s, 1H), 4.75 (br m, 1H), 4.06 (s, 2H), 3.83 (s, 3H), 3.72 (m, 2H), 3.14 (br m, 2H), 2.11 (br, 6H), 1.71 (m, 2H). EXAMPLE 342 (frans) -3- (4- (4-. {4-amino-3- (2- (2-methoxybenzyl) -1H-indol-5-yl) -1H-pyrazolo [3,4-d] ] pyrimidin-1-yl}. cyclohexyl) piperazin-1-yl) propan-1-ol The desired product was prepared by replacing the bromoethanol of EXAMPLE 341D with 3-bromo-1-propanol. MS: IEA (+) m / e 581.4 (M + H) *; IEA (-) m / e 579.4 (M-H); 1 H-NMR (300 MHz, DMSO-de) 11.16 (s, 1H), 8.32 (s, 1H), 7.67 (s, 1H), 7.46 (d, 1H), 7.28 (dd, 1H), 7.23 (dd, 1H), 7.14 (dd, 1H), 7.02 (d, 1H), 6.89 (dt, 1H), 6.19 (s, 1H), 4.75 (br m, 1H), 4.06 (s, 21H), 3.83 (s, 3H), 3.49 (t, 2H), 3.7 (br m, 2H), 2.11 (br, 6H), 1.69-1.82 (m, 4H). EXAMPLE 343 (frans) -3- (2- (2-methoxybenzyl) -1H-indol-5-yl) -1-. { 4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl} -1 H-pyrazolo [3,4-d] pyrimidin-4-amine The desired product was prepared by substituting the bromoethanol of EXAMPLE 341D for 1-bromo-3-methoxypropane. EM: IEA (+) m / e 609.4 (M + H) *; 1 H-NMR (300 MHz, DMSO-d 6) 11.16 (s, 1H), 8.31 (s, 1H), 7.67 (s, 1H), 7.46 (d, 1H), 7.28 (dd, 1H), 7.23 (dd, 1H), 7.14 (dd, 1H), 7.02 (d, 1H) ), 6.89 (dt, 1H), 6.18 (s, 1H), 4.74 (br m, 1H), 4.06 (s, 2H), 3.83 (s, 3H), 3.39 (t, 2H), 3.25 (s, 3H), 2.10 (br, 6H), 1.84 (br m, 2H), 1.69 ( br.2H). EXAMPLE 344 (frans) -2- (4- (4-. {4-amino-3- (2- (2-methoxybenzyl) -1H-indol-6-yl) -1H-pyrazolo [3,4-d] ] pyrimidin-1-yl}. cyclohexyl) piperazin-1-yl) ethanol EXAMPLE 344A The desired product was prepared by substituting the 5-bromoindole of EXAMPLE 341A for 6-bromoindole. EM IDQ (+) m / e 317.43 (M + H) *. EXAMPLE 344B The title product was prepared by substituting the product of EXAMPLE 341A in EXAMPLE 341B, by the product of EXAMPLE 344A. MS: IQD (+) m / e 364.44 (M + H) *; 1 H-NMR (300 MHz, DMSO-d 6) 10.97 (s, 1H), 7.65 (s, 1H), 7.37 (d, 1H), 7.20-7.26 (m, 2H), 7.09 (dd, 1H), 7.00 (s) dd, 1H), 6.87 (dt, 1H), 6.05 (s, 1H), 4.04 (s, 2H), 3.81 (s, 3H), 1.29 (s, 12H). EXAMPLE 344C The desired product was prepared by substituting the product of EXAMPLE 382A in EXAMPLE 382B, by the product of EXAMPLE 344B. MS: IQD (+) m / e 637.13 (M + H) *. EXAMPLE 344D The desired product was prepared by substituting the product of EXAMPLE 341C in EXAMPLE 341D, by the product of the EXAMPLE 344C. MS: IEA (+) m / e 581.4 (M + H) *; IEA (-) m / e 579.4 (M-H); 1 H NMR (300 MHz, DMSO-d 6) 11.14 (s, 1 H), 8.33 (s, 1 H), 7.55- 7. 58 (m, 2H), 7.22-7.27 (m, 2H), 7.15 (dd, 1H), 7.02 (d, 1H), 6.89 (dt, 1H), 6.15 (s, 1H), 4.75 (brm, 1H), 4.06 (s, 2H), 3.82 (s, 3H), 3.73 (br.t.2H), 3.17 (m, 2H), 2.07-2.19 (br, 4H), 1.66-1.78 (br m, 2H). EXAMPLE 345 (frans) -3- (4- (4- { 4-amino-3- (2- (2-methoxybenzyl) -1 H -indol-6-yl) -1 H-pyrazolo [3,4 -d] pyrimidin-1-yl.} cyclohexyl) piperazin-1-yl) propan-1-ol The desired product was prepared by substituting bromoethanol for 3-bromo-1-propanol and the product of EXAMPLE 341C for the product of EXAMPLE 344C, respectively, in EXAMPLE 341D. MS: IEA (+) m / e 595.4 (M + H) *; IEA (-) m / e 593.5 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 11.14 (s, 1H), 8.30 (s, 1H), 7.55-7.57 (m, 2H), 7.22-7.27 (m, 2H), 7.15 (dd, 1H), 7.02 (d, 1H), 6.90 (dt, 1H), 6.15 (s, 1H), 4.75 (br m, 1H), 4.06 (s, 2H), 3.83 (s, 3H), 3.49 (m, 2H), 2.05-2.16 (br, 6H), 1.61-1.81 (br m, 4H). EXAMPLE 346 (frans) -3- (2- (2-methoxybenzyl) -1H-indol-6-yl) -1-. { 4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl} -1H-pyrazolo [3,4-d] pyrimidin-4-amine The desired product was prepared by substituting bromoethanol for 1-bromo-3-methoxypropane and the product of the EXAMPLE 341C by the product of EXAMPLE 344C, respectively, in EXAMPLE 341D. MS: IEA (+) m / e 609.5 (M + H) *; IEA (-) m / e 607.5 (M-H); 1 H-NMR (300 MHz, DMSO-d 6) 11.14 (s, 1H), 8.31 (s, 1H), 7.55-7.57 (m, 2H), 7.22-7.27 (m, 2H), 7.15 (dd, 1H), 7.02 (d, 1H), 6.90 (dt, 1H) ), 6.15 (s, 1H), 4.75 (br m, 1H), 4.06 (s, 2H), 3.82 (s, 3H), 3.39 (t, 2H), 3.25 (s, 3H), 2.05-2.16 (br., 6H), 1.84 (br m, 2H), 1.69 (br.2H). EXAMPLE 347 (frans) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-5-yl) -1- (4-piperazin-1-yl-cyclohexy I) -1 H-pyrazolo [3,4 -d] pyrimidin-4-amine EXAMPLE 347A The product of EXAMPLE 318A (2.91 g, 5.52 mmol) was dissolved in CH2Cl2 (60 mL) and cooled to 0 ° C for 15 minutes. TFA (23 g, 201 mmol) was added dropwise at 0 ° C, after completion of the addition, the mixture was rapidly heated to RT. The reaction was stirred at RT for 3 hours. Once the reaction had consumed the raw material, the mixture was partitioned into CH2Cl2 / IPA (4: 1, v / v) and 3M NaOH. The organic phases were separated and the aqueous phase was extracted with CH2Cl2 / IPA (3 x 50 mL). The organic phases were combined and the combined was dried over MgSO 4, filtered and reduced in vacuo to obtain 1.97 g of the desired product as a white solid, which was used without further purification. EXAMPLE 347B To a mixture of the product of EXAMPLE 347A (0.1 g, 0.23 mmol), the product of EXAMPLE 339B (0.10 g, 0.28 mmol), (Ph3P) 2PdCI2 (0.008 g, 0.011 mmol) in a 0.3M solution of DME / H2O (2: 1, v / v), an aqueous solution of Na2CO32M (0.23 mL, 0.46 mmol) was added. The mixture was heated in a microwave reactor at 130 ° C for 20 minutes. The mixture was filtered over Celite was washed with CH2Cl2 and MeOH. The filtrate was reduced in vacuo and purified directly by reverse phase HPLC (CH3CN / 0.05% NH OH, in water), to obtain the desired product. (IEA (+)) m / e 538 (M + H) *; 1 H-NMR (300 MHz, DMSO-d 6) 12.25 (d, 1H), 8.22 (s, 1H), 7.74 (m, 0.5H), 7.65-7.63 (m, 1H), 7.57 (d, 0.5H), 7.43-7.39 (m, 1H), 7.29-7.24 (m, 1H), 7.21-7.17 (m, 1H), 7.02 (d, 1H), 6.91 (t, 1H), 4.64 (m, 1H), 4.17 ( s, 2H), 3.81 (s, 3H), 2.73 (bm, 5H), 2.06-1.90 (m, 7H), 1.54-1.45 (m, 2H). EXAMPLE 348 (frans) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-5-yl) -1- (4- (4-methyl-piperazin-1-yl) -cyclohexyl) -1 H-pi-reazoo [ 3, 4-d] pyrim-din -4-a mi na A mixture of (frans) -3-iodo-1- (4 - (- methylpiperazin-1-yl) -cyclohexyl) -1 H-pyrazolo [3 , 4-d] pyrimidin-4-yl-amine prepared as described in AF Burchat et al. Bioorg Med. Chem. Lett. 2002, 12, 1687-1690 (0.1 g, 0.23 mmol), the product of EXAMPLE 339B (0.098 g, 0.27 mmol), (Ph3P) 2PdCI2 (0.008 g, 0.011 mmol) in a 0.3M solution of DME / H2O (2 : 1, v / v), an aqueous 2M Na2CO3 solution (0.23 mL, 0.46 mmol) was added. The mixture was heated in a microwave reactor at 130 ° C for 20 minutes. The mixture was filtered over Celite, washed with CH2Cl2 and MeOH. The filtrate was reduced in vacuo and purified directly by reverse phase HPLC (CH3CN / 0.05% NH4OH, in water), to obtain the desired product. IEA (+)) m / e 551 (M + H) *; 1 H-NMR (300 MHz, DMSO-d 6) 12.15 (d, 1H), 8.12 (s, 1H), 7.60-7.58 (m, 1H), 7.51-7.46 (m, 1H), 7.28-7.16 (m, 5H ), 7.04-7.01 (m, 1H), 6.93-6.88 (m, 1H), 6.05-5.97 (m, 2H), 4.69 (m, 1H), 4.15 (s, 2H), 3.81 (s, 4H), 2.45-2.32 (m, 7H), 2.18 (m, 1H), 2.14 (s, 3H), 2.11-2.03 (m, 4H), 1.75-1.67 (m, 2H), 1.63-1.51 (m, 2H). EXAMPLE 349 (frans) -. { 5- (4-amino-1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4- d] pyrimidin-3-yl) -1-benzofuran-2-yl} (phenyl) methanone EXAMPLE 349A Phenyl- (5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzofuran-2-yl) methanone A mixture of 5-bromo-2- benzoyl-benzofuran purchased from Indefine Chemicals (0.251 g, 0.83 mmol), bis (pinacolato) diboro (0.33 g, 1.3 mmol), potassium acetate (0.26 g, 2.7 mmol), 1,3-bis (diisopropylphenyl) imidazolium (0.032 g, 0.075 mmol) and palladium acetate (11) (0.011 g, 0.05 mmol) in THF (4 mL), was heated at 125 ° C for 20 minutes in a reactor. microwave. The reaction mixture was diluted with EtOAc, and the organic phases were sequentially washed with brine, subsequently dried over MgSO4. The solvent was removed under reduced pressure, and the residue was purified by chromatography on silica gel, eluting with 10-50% EtOAc / hexanes, to obtain the title compound as a white solid. EXAMPLE 349B (frans) -. { 5- (4-amino-1- (4-morpholin-4-yl-cyclohexyl) -1H-pyrazolo [3,4- d] pyrimidin-3-yl) -1-benzofuran-2-yl} (phenyl) methanone The desired product was prepared by substituting 3-bromo-1- ferf-butyl-1 H-pyrazolo [3,4-d] pyrimidin-4-yl-amine by (frans) -3-iodo-1- (4-morpholin-4-yl-cyclohexyl) -1 H-pyrazolo [ 3,4-] pyrimidin-4-yl-amine prepared as described in International Patent Publication WO 2005/074603 and the product of EXAMPLE 188C by the product of EXAMPLE 349A, in EXAMPLE 181. 1 H-NMR (300 MHz , methanol-d4) 8.38 (s, 1H), 8.14 (s, 1H), 8.09 (m, 2H), 7.88 (s, 2H), 7.80 (s, 1H), 7.72 (m, 1H), 7.61 (m , 2H), 4.95 (m, 1H), 4.12 (m, 2H), 3.80 (m, 2H), 3.58-3.38 (m, 4H), 2.44-2.38 (m, 2H), 2.38-2.25 (m, 4H) ), 1.94-1.82 (m, 2H). EXAMPLE 350 (frans) -3- (2-benzyl-1,3-benzothiazol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidine- 4-amine EXAMPLE 350A 2-benzyl-5-chlorobenzo [d] thiazole A balloon flask equipped with a Dean-Stark trap was charged with 4-chloro-2-aminobenzenethiol (3.47 g, 21.7 mmol) and phenacyl chloride (3.0 mL, 22.7 mmol) in benzene (40 mL), and the mixture was heated 18 h in an oil bath at 80 ° C. The reaction mixture was diluted with CH2Cl2, and the organic phases were washed sequentially with an aqueous solution of Na2CO3 and with brine, then dried over MgSO. The solvent was removed under pressure reduced, and the residue was purified by chromatography on silica gel, eluting with 35-100% CH2Cl2 / hexanes, to obtain the title compound as a white solid (1.94 g). EXAMPLE 350B 2-Benzyl-5- (4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl) benzo [d] thiazole The desired product was prepared by substituting 5-bromo-2-benzoyl -benzofuran of EXAMPLE 349B, by the product of EXAMPLE 350A. EXAMPLE 350C (frans) -3- (2-benzyl-1,3-benzothiazol-5-yl) -1- (4-morpholin-4-yl-cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidine -4-amine The desired product was prepared by substituting 3-bromo-1-ferf-butyl-1 H-pyrazolo [3,4-d] pyrimidin-4-yl-amine for (trans) -3-iodo-1- (4-morpholin-4-yl-cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidin-4-yl-amine prepared as described in International Patent Publication WO 2005/074603 and the product of EXAMPLE 188C by the product of EXAMPLE 350B, in EXAMPLE 181. 1 H-NMR (300 MHz, methanol-d 4) 8.40 (s, 1H), 8.23 (d, 1H), 8.12 (d, 1H), 7.72 (dd, 1H), 7.43-7.30 (m, 5H), 4.95 (m, 1H), 4.51 (s, 2H), 4.12 (m, 2H), 3.80 (m, 2H), 3.58-3.38 (m, 4H), 2.44-2.38 ( m, 2H), 2.38-2.25 (m, 4H), 1.94-1.82 (m, 2H). EXAMPLE 351 (frans) -3-dibenzo (b, d) thien-3-yl-1- (4-morpholin-4-yl-cyclohexyl) -1H-pi-rally [3, 4-d] pyrim idin-4- amine The desired product was prepared by substituting 3-bromo-1- ferf-butyl-1 H-pyrazolo [3,4-d] pyrimidin-4-yl-amine by (trans) -3-iodo-1- (4-morpholin-4-yl-cyclohexyl) -1H-pyrazolo [3 , 4-d] pyrimidin-4-yl-amine prepared as described in International Patent Publication WO 2005/074603 and the product of EXAMPLE 188C by dibenzo (b, d) thiophen-3-yl-boronic acid (purchased in Maybridge Chemicals), in EXAMPLE 181. 1 H-NMR (300 MHz, methanol-d 4) 8.56 (d, 1H), 8.40 (s, 1H), 8.34 (m, 1H), 8.12 (d, 1H), 7.96 ( m, 1H), 7.80 (d, 1H), 7.54 (m, 2H), 4.95 (m, 1H), 4.12 (m, 2H), 3.80 (m, 2H), 3.58-3.38 (m, 4H), 2.44 -2.38 (m, 2H), 2.38-2.25 (m, 4H), 1.94-1.82 (m, 2H). EXAMPLE 352 (frans) -1- (4- (4-ethylpiperazin-1-yl) cyclohexyl) -3- (2- (2-methoxybenzyl) -1 H- benzimidazol-6-yl) -1 H-pyrazolo [3 , 4-d] pyrimidin-4-amine The desired product was prepared by substituting 2- (trifluoromethyl) -5,6,7,8-tetrahydroimidazo [1,2-a] pyrazine from EXAMPLE 338, for 1-ethylpiperazine. The fastest elution isomer was isolated: (IEA (+)) m / e 566 (M + H) *; 1 H-NMR (300 MHz, DMSO-d 6) 8.31 (s, 1H), 7.88-7.83 (m, 2H), 7.73-7.70 (m, 1H), 7.40-7.36 (m, 2H), 7.10-7.07 (m , 1H), 7.02 (t, 1H), 4.76 (m, 1H), 4.45 (s, 2H), 3.78 (s, 3H), 3.14-3.05 (m, 5H), 2.14-2.05 (m, 7H), 1.74-1.63 (m, 3H), 1.21 (t, 3H). EXAMPLE 353 (c / s) -1- (4- (4-ethylpyridin-1-yl) cyclohexyl) -3- (2- (2-methoxy-benzyl) -1H-benzimidazol-6-yl) - 1 H-pyrazolo [3,4-d] pyrimidin-4-amine The desired product is the slower elution isomer of the EXAMPLE 352: (IEA (+)) m / e 566 (M + H) *; 1 H-NMR (300 MHz, DMSO-d 6) 8.31 (s, 1 H), 7.88-7.81 (m, 2 H), 7.73-7.70 (m, 1 H), 7.40-7.35 (m, 2H), 7.10-7.07 (m, 1H), 7.04-6.99 (m, 1H), 4.91 (m, 1H), 4.43 (s, 2H), 3.78 (s, 3H), 3.14-3.04 (m, 3H) , 2.40-2.25 (m, 2H), 2.14-1.99 (m, 2H), 1.94-1.76 (m, 3H), 1.19 (t, 3H). EXAMPLE 354 (frans) -5- (2- (2-methoxybenzyl) -1 H -benzimidazol-5-yl) -7- (4- (2-methoxyethoxy) cyclohexyl) -7H-pyrrolo [2,3-d] pyrimidin-4-amine The desired product was prepared by substituting the 4- (4-amino-3-iodo-1 H-pyrazolo [3,4-d] pyrimidin-1-yl) cyclohexanone of the EXAMPLE 339C, by (frans) -3-iodo-1- (4- (2-methoxyethoxy) -cyclohexyl) -1 H -pyrazolo [3,4-d] pyrimidin-4-yl-amine prepared as described in International Patent Publication WO 2005/074603. MS (EAI) m / e 527 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 8.39 (s, 1 H), 7.80 (d, 1 H), 7.77 (s, 1 H), 7.71 (s) , 1H), 7.54 (d, 1H), 7.38 (m, 2H), 7.08 (d, 1H), 7.01 (t, 1H), 4.66 (m, 1H), 4.43 (s, 2H), 3.78 (s, 3H), 3.58 (m, 2H), 3.45 (m, 2H), 3.26 (s, 3H), 2.12 (m, 2H), 1.97 (m, 4H), 1.40 (m, 2H). EXAMPLE 355 (trans) -1- (4- (4-acetylpiperazin-1-yl) cyclohexyl) -3- (2- (3-methoxybenzyl) -1 H-benzimidazol-6-yl) -1 H -pyrazolo [3, 4-d] pyrimidin-4-amine The desired product was prepared by substituting 2- (trifluoromethyl) -5,6,7,8-tetrahydroimidazo [1, 2-a] pyrazine from EXAMPLE 338, by 1-acetylpiperazine. The fastest elution isomer was isolated: MS: (IEA (+)) m / e 580 (M + H) *; 1 H-NMR (300 MHz, DMSO-d 6) 9. 67 (bs, 1H), 8.30 (s, 1H), 7.87-7.82 (m, 2H), 7.72-7.69 (m, 1H), 7.40-7.36 (m, 2H), 7.10-6.99 (m, 2H), 4.79 (m, 1H), 4.53-4.48 (m, 1H), 4.44 (m, 2H), 4.10-4.01 (m, 1H), 3.78 (s, 3H), 3.20-3.14 (m, 3H), 3.05-2.87 (m, 3H), 2.26-2.09 (m, 7H), 2.06 (m, 3H), 1.87-1.73 (m, 2H). EXAMPLE 356 (frans) -4- (4- (4. {4-amino-3- (2- (2-methoxybenzyl) -1H-benzimidazol-6-yl) -1H-pyrazolo [3,4-d] ] pyrimidin-1-yl}. cyclohexyl) piperazin-1-yl) -2-methylbutan-2-ol The desired product was prepared by substituting 2- (trifluoromethyl) -5,6,7,8-tetrahydroimidazo [1, 2-a] pyrazine from EXAMPLE 338, by 2-methyl-4- (piperazin-1-yl) butan-2-ol. The fastest elution isomer was isolated: MS (IEA (+)) m / e 624 (M + H) *; 1 H-NMR (300 MHz, DMSO-d6) 8.29 (s, 1H), 7.86-7.81 (m, 2H), 7.72-7.69 (m, 1H), 7.40-7.35 (m, 2H), 7.10-7.07 (m, 1H), 7.01 (t , 1H), 4.75 (m, 1H), 4.44 (s, 2H), 3.78 (s, 3H), 3.13-3.08 (m, 3H), 2.97-2.88 (m, 2H), 2.12-2.04 (m, 5H), 1.74-1.68 (m, 4H), 1.15 (s, 6H). EXAMPLE 357 (c / 's) -4- (4- (4- { 4-amino-3- (2- (3-methoxybenzyl) -1H-benzimidazol-6-yl) -1H-pyrazolo [3, 4-d] pyrimidin-1-yl}. Cyclohexyl) piperazin-1-yl) -2-methylbutan-2-ol The desired product is the slower elution isomer of EXAMPLE 356. (IEA (+)) m / e 624 (M + H) *; 1 H-NMR (300 MHz, DMSO-de) 8.31 (s, 1H), 7.88-7.81 (m, 2H), 7.73-7.70 (m, 1H), 7.40-7.35 (m, 2H), 7.10-7.07 (m , 1H), 7.01 (t, 1H), 4.91 (m, 1H), 4.43 (s, 2H), 3.78 (s, 3H), 3.15-3.09 (m, 3H), 3.02-2.91 (m, 2H), 2.35 (m, 1H), 2.11-2.02 (m, 2H), 1.90-1.81 (m, 3H), 1.73-1.67 (m, 2H), 1.13 (s, 6H).

EXAMPLE 358 (c / s) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-6-yl) -1- (4- (4-pyrazin-2-yl-piperazin-1-yl) cyclohexyl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine The desired product was prepared by substituting 2- (trifluoromethyl) -5,6,7,8-tetrahydroimidazo [1, 2-a] pyrazine from EXAMPLE 338, by 1- (2-pyrizinyl) piperazine. The slowest elution isomer was isolated: 1 H-NMR (300 MHz, DMSO-d 6) d 8.31 (s, 1H), 8.23 (s, 1H), 7.91 (s, 1H), 7.84 (d, 1H), 7.65 (d, 1H), 7.40 (d, 1H), 7.25 (d, 1H), 7.17 (d, 1H), 7.03 (t, 1H), 6.90 (d, 2H), 5.00 (m, 1H), 4.43 ( s, 2H), 3.78 (s, 3H), 3.23 (m, 4H), 2.90 (m, 4H), 2.08 (m, 8H). EXAMPLE 359 (c / s) -2- (4- (4- { 4-amino-3- (2- (2-methoxybenzyl) -1H-benzimidazol-6-yl) -1H-pyrazolo [3,4 -d] pyrimidin-1-yl}. cyclohexyl) piperazin-1-yl) ethanol The desired product is the slower elution isomer of EXAMPLE 360. MS (IEA (+)) m / e 582 (M + H) *; 1 H-NMR (300 MHz, DMSO-de) 8.31 (s, 1H), 7.88 (s, 1H), 7.82 (d, 1H), 7.72 (d, 1H), 7.40-7.35 (m, 2H), 7.08 ( d, 1H), 7.01 (t, 1H), 4.92 (bm, 1H), 4.43 (s, 2H), 3.78 (s, 3H), 3.70 (m, 5H), 3.06 (m, 3H), 2.41-2.29 (m, 2H), 2.14-2.00 (m, 2H), 1.95-1.81 (m, 3H). EXAMPLE 360 (frans) -2- (4- (4- { 4-amino-3- (2- (2-methoxybenzyl) -1H-benzimidazol-6-yl) -1H-pyrazolo [3,4-d] ] pyrimidin-1-yl}. cyclohexyl) piperazin-1-yl) ethanol The desired product was prepared by substituting 2- (trifluoromethyl) -5,6,7,8-tetrahydroimidazo [1,2-a] pyrazine from EXAMPLE 338, by 1-hydroxyethylpiperazine. The elution isomer was isolated more fast: MS (ESI (+)) m / e 582 (M + H) *; 1 H-NMR (300 MHz, DMSO-d 6) 12.23 (s, 1H), 8.22 (s, 1H), 7.73-7.54 (m, 2H), 7.43-7.40 (m, 1H), 7.30-7.24 (m, 1H ), 7.21-7.18 (m, 1H), 7.04-7.01 (m, 1H), 6.91 (t, 1H), 4.64 (bm, 1H), 4.33 (t, 1H), 4.14 (s, 2H), 3.81 ( s, 3H), 3.51-3.45 (m, 2H), 2.41-2.33 (m, 8H), 2.07-1.93 (m, 6H), 1.53-1.39 (m, 2H). EXAMPLE 361 (frans) -4- (4-. {4-amino-3- (2- (2-methoxybenzyl) -1H-benzimidazol-6-yl) -1H-pyrazolo [3,4-d] pyrimidine- 1-yl.) Cyclohexyl) -N, N-dimethylpiperazine-1-carboxamide The desired product was prepared by substituting 2- (trifluoromethyl) -5,6,7,8-tetrahydroimidazo [1,2-a] pyrazine from EXAMPLE 338, by N, N-dimethylpiperazine-1-carboxamide. The fastest elution isomer was isolated: MS (IEA (+)) m / e 609 (M + H) *; 1 H-NMR (300 MHz, DMSO-de) 9.53 (bs, 1H), 8.29 (s, 1H), 7.86-7.81 (m, 2H), 7.72-7.69 (m, 1H), 7.41-7.36 (m, 2H ), 7.10 (d, 1H), 7.02 (t, 1H), 4.78 (m, 1H), 4.44 (s, 2H), 3.78 (s, 3H), 3.13-3.03 (m, 5H), 2.80 (m, 7H), 2.27 (m, 2H), 2.16-2.07 (m, 4H), 1.85-1.71 (m, 2H). EXAMPLE 362 (c / s) -4- (4- { 4-amino-3- (2- (2-methoxybenzyl) -1H-benzimidazol-6-yl) -1H-pyrazolo [3,4-d] pyrimidin-1-yl.} cyclohexyl) -N, N-dimethylpiperazine-1-carboxamide The desired product is the slowest elution isomer of the EXAMPLE 361. MS (ESI (+)) m / e 609 (M + H) *; 1 H-NMR (300 MHz, DMSO-de) 9.38 (m, 1H), 8.31 (s, 1H), 7.90 (s, 1H), 7.82-7.85 (m, 1H), 7.75 (d, 1H), 7.41-7.35 (m, 2H), 7.08 (d, 1H), 7.02 (t, 1H), 4.98 (m, 1H), 4.44 (s, 2H), 3.78 (s, 3H), 3.11-3.00 (m, 5H), 2.77 (m, 7H), 2.14-1.96 (m, 6H). EXAMPLE 363 4- (4- { 4-amino-3- (2- (2-methoxybenzyl) -1 H -benzimidazol-6-yl) -1 H-pyrazolo [3,4-d] pyrimidin-1- il.) cyclohexyl) piperazine-1-carboxylate (frans) -ethyl The desired product was prepared by substituting 2- (trifluoromethyl) -5,6,7,8-tetrahydroimidazo [1,2-a] pyrazine from EXAMPLE 338 , by ethyl piperazine-1-carboxylate. The fastest elution isomer was isolated: MS (IEA (+)) m / e 610 (M + H) *; 1 H-NMR (300 MHz, DMSO-de) 12.24 (bs, 1H), 8.22 (s, 1H), 7.70-7.56 (m, 2H), 7.42-7.39 (m, 1H), 7.29-7.24 (m, 1H ), 7.20-7.17 (m, 1H), 7.02 (d, 1H), 6.91 (t, 1H), 4.64 (m, 1H), 4.17 (s, 2H), 4.03 (q, 2H), 3.81 (s, 3H), 3.36-3.34 (m, 5H), 2.09-1.90 (m, 6H), 1.55-1.41 (m, 2H), 1.18 (t, 3H). EXAMPLE 364 4- (4- { 4-amino-3- (2- (2-methoxybenzyl) -1H-benzimidazol-6-yl) -1H-pi just [3,4-d] pyrimidin-1-yl .) cyclohexyl) piperazine-1-carboxylic acid (cis) -ethyl ester The desired product is the slower elution isomer of EXAMPLE 363. MS (IEA (+)) m / e 610 (M + H) *; 1 H-NMR (300 MHz, DMSO-de) 12.24 (m, 1H), 8.22 (s, 1H), 7.70-7.59 (m, 2H), 7.41-7.39 (m, 1H), 7.29-7.24 (m, 1H), 7.20-7.17 (m, 1H), 7.04-7.01 (m, 1H), 6. 90 (t, 1H), 4.82 (m, 1H), 4.17 (s, 2H), 4.02 (q, 2H), 3.81 (s, 3H), 3. 40-3.35 (m, 4H), 2.46-2.40 (m, 6H), 2.31-2.21 (m, 4H), 2.13-2.02 (m, 2H), 1.78-1.68 (m, 2H), 1.67-1.55 (m , 2H), 1.17 (t, 3H).

EXAMPLE 365 (c / s) -3- (7-Chloro-2- (2-methoxybenzyl) -1H-benzimidazol-5-yl) -1-. { 4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl} -1H-pyrazolo [3,4-d] pyrimidin-4-amine EXAMPLE 365A A mixture of the product of EXAMPLE 31A (0.3 g, 0.8 mmol) and NCS (0.11 g, 0.8 mmol) in DMF (3 mL) was stirred at room temperature overnight. The reaction mixture was diluted with EtOAc, washed with water and subsequently with brine. The crude product was purified by chromatography on a column of silica gel, eluting with EtOAc, to obtain the title compound (0.15 g). MS (LEA) m / e 402 (M + H); 1 H-NMR (300 MHz, DMSO-de) 11.90 (s, 2H), 9.11 (s, 1H), 8.48 (s, 1H), 7.94 (s, 1H), 7.48 (s, 2H), 5.19 (m, 1H), 2.69 (m, 2H), 2.38 (m, 4H), 2.24 (m, 2H). EXAMPLE 365B The desired product was prepared as described in EXAMPLE 7, substituting the product of EXAMPLE 7A and benzaldehyde, by the product of EXAMPLE 365A and 2-methoxyphenylacetaldehyde, respectively, in EXAMPLE 7B. EXAMPLE 365C The desired product was prepared by substituting 2- (trifluoromethyl) -5,6,7,8-tetrahydroimidazo [1,2-a] pyrazine for 1- (3-methoxypropyl) -piperazine and the product of EXAMPLE 339C by product of EXAMPLE 365B, in EXAMPLE 338. The slowest elution isomer was isolated: MS (IEA) m / e 644 (M + H) J 1 H-NMR (300 MHz, DMSO-de) d 8.35 (s, 1H), 7.67 (s, 1H), 7.52 (s, 1H), 7.29 (t, 1H), 7.21 (d, 1H), 7.04 (d, 1H) , 6.93 (t, 1H), 4.93 (m, 1H), 4.24 (s, 2H), 3.81 (s, 3H), 3.56 (m, 5H), 3.38 (t, 2H), 3.24 (s, 3H), 3.06 (m, 5H), 2.35 (m, 2H), 2.07 (m, 3H), 1.86 (m, 5H). EXAMPLE 366 (frans) -1-. { 4- (4- (ethylsulfonyl) piperazin-1-yl) cyclohexyl} -3- (2- (2-methoxybenzyl) -1 H -benzimidazol-6-yl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine The desired product was prepared by substituting 2- (trifluoromethyl) -5,6,7,8-tetrahydroimidazo [1,2-a] pyrazine from EXAMPLE 338, by 1-ethanesulfonylpiperazine. The fastest elution isomer was isolated: MS (IEA (+)) m / e 630 (M + H) *; H-NMR (300 MHz, DMSO-d6) 12. 25 (m, 1H), 8.22 (s, 1H), 7.74-7.55 (m, 2H), 7.43-7.40 (m, 1H), 7. 30-7.24 (m, 1H), 7.21-7.18 (m, 1H), 7.04-7.02 (m, 1H), 6.91 (m, 1H), 4.66 (bm, 1H), 4.17 (s, 2H), 3.81 ( s, 3H), 3.19-3.15 (m, 6H), 2. 64-2.56 (m, 4H), 2.10-1.89 (m, 7H), 1.57-1.44 (m, 2H), 1.22 (t, 3H). EXAMPLE 367 (c / s) -1-. { 4- (4- (ethylsulfonyl) piperazin-1-yl) cyclohexyl} -3- (2- (2-methoxybenzyl) -1 H -benzimidazol-6-yl) -1 H -pyrazolo [3,4-d] pyrimidin-4-amine The desired product is the slower elution isomer of the EXAMPLE 366. MS (ESI (+)) m / e 610 (M + H) *; 1 H-NMR (300 MHz, DMSO-de) 12.27 (m, 1H), 8.23 (s, 1H), 7.73-7.57 (m, 2H), 7.43-7.39 (m, 1H), 7.29-7.25 (m, 1H), 7.20-7.18 (m, 1H), 7.04-7.02 (m, 1H), 6.94-6.89 (m, 1H), 4.82 (m, 1H), 4.17 (s, 2H), 3.81 (s, 3H), 3.22-3.17 (m, 6H), 3.03 (q, 2H), 2.73-2.71 (m, 1H), 2.34-2.24 (m, 4H), 2.15-2.04 (m, 2H), 1.79-1.59 (m, 4H), 1.20 (t, 3H). EXAMPLE 368 (frans) -3- (7-chloro-2- (2-methoxybenzyl) -1H-benzimidazol-5-yl) -1-. { 4- (4- (3-methoxypropyl) piperazin-1-yl) cyclohexyl} -1 H-Pi Ra [3, 4-d] pyrim id i n-4-amine The desired product was prepared by substituting 2- (trifluoromethyl) -5,6,7,8-tetrahydromidezide [1, 2-a] pyrazine by 1- (3-methoxypropyl) piperazine and the product of EXAMPLE 339C by the product of EXAMPLE 365B, in EXAMPLE 338. The fastest elution isomer was isolated: MS (IEA) m / e 644 (M + H) J 1 H-NMR (300 MHz, DMSO-de) d 8.29 (s, 1H), 7.65 (s, 1H), 7.50 (s, 1H), 7.30 (t, 1H), 7.21 (d, 1H), 7.05 (d, 1H), 6.94 (t, 1H), 4.76 (m, 1H), 4.23 (s, 2H), 3.81 (s, 3H), 3.73 (m, 5H), 3.39 (t, 2H), 3.25 (s, 3H), 2.98 (m, 5H), 2.11 (m, 6H), 1.85 (m, 2H) ), 1.69 (m, 2H). EXAMPLE 369 (trans) -1- (4- (4-. {2- (2- (2-Aminoethoxy) ethoxy) eti.] Piperazin-1 -i I) cid or hexy I) -3- ( 2- (2-methoxybenzyl) -1H-benzimidazol-6-yl) -1H-pyrazolo [3,4- d] pyrimidin-4-amine The desired product was prepared by substituting 2- (trifluoromethyl) -5,6,7 , 8-tetrahydroimidazo [1,2-a] pyrazine from EXAMPLE 338, by 1- (2- (2- (2-aminoethyl) ethoxy) ethoxy) piperazine. The fastest elution isomer was isolated: 1 H-NMR (300 MHz, DMSO-dβ) d 8.34 (s, 1 H), 7.90 (s, 1 H), 7.85 (s, 1 H), 7.38 (m, 2 H), 7.08 (d, 1H), 7.02 (t, 1H), 4.78 (m, 1H), 4.47 (s, 2H), 3.78 (s, 3H), 3.70 (m, 6H), 3.59 (m, 6H), 3.12 (m, 4H), 2.98 (m, 3H), 2.12 (m, 6H), 1.74 (m, 4H). EXAMPLE 370 (frans) -1-. { 4- (4- (cyclopropylmethyl) piperazin-1-yl) cyclohexyl} -3- (2- (2-methoxybenzyl) -1 H -benzimidazol-6-yl) -1 Hp i razolo [3,4-d] pyrim id i n-4-amine The desired product was prepared by substituting the 2- (trifluoromethyl) -5,6,7,8-tetrahydroimidazo [1,2-a] pyrazine from EXAMPLE 338, by 1-cyclopropylmethylpiperazine. The fastest elution isomer was isolated: MS (IEA (+)) m / e 592 (M + H) *; 1 H-NMR (300 MHz, DMSO-d 6) 8.32 (s, 1H), 7.89-7.84 (m, 2H), 7.74-7.72 (m, 1H), 7.41-7.36 (m, 2H), 7.10-7.07 (m , 1H), 7.05-7.00 (m, 1H), 4.78 (m, 1H), 4.47 (s, 2H), 3.78 (s, 3H), 3.69-3.45 (m, 6H), 3.05-2.97 (m, 4H) ), 2.17-2.07 (m, 7H), 1.79-1.62 (m, 2H), 1.09-1.02 (m, 1H), 0.68-0.62 (m, 2H), 0.38-0.34 (m, 2H). EXAMPLE 371 (c / s) -1-. { 4- (4- (cyclopropylmethyl) piperazin-1-yl) cyclohexyl} -3- (2- (2-methoxybenzyl) -1H-benzimidazol-6-yl) -1H-pyrazolo [3,4-d] pyrimidin-4-amine The desired product is the slower elution isomer of EXAMPLE 370. MS (ESI (+)) m / e 592 (M + H) *; 1 H-NMR (300 MHz, DMSO-de) 8.34 (s, 1H), 7.90-7.83 (m, 2H), 7.76-7.73 (m, 1H), 7.41-7.36 (m, 2H), 7.10-7.04 (m, 1H), 7.02-7.00 (m, 1H), 4.93 (m, 1H), 4. 46 (m, 2H), 3.78 (s, 3H), 3.67-3.43 (m, 3H), 3.01-2.99 (m, 2H), 2. 41-2.30 (m, 2H), 2.14-2.03 (m, 2H), 1.96-1.82 (m, 3H), 1.03 (m, 1H), 0.66-0.60 (m, 2H), 0.36-0.32 (m, 2H) ).

EXAMPLE 372 (frans) -4- (4- (4-. {4-a-my-3- (2- (2,6-difluorobenzyl) -1H-benzim idazol-5-yl) -1 H- pyrazolo [3,4-d] pyrimidin-1-yl.} cyclohexyl) piperazin-1-yl) -2-methylbutan-2-ol The desired product was prepared by substituting the product of EXAMPLE 265A for the product of EXAMPLE 294C and 1- (3-methoxypropyl) -piperazine by 1- (3-hydroxy-3-methylbutyl) piperazine, in EXAMPLE 265B. The fastest eluting diastereomer was isolated. MS (EAI) m / e 630 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 8.33 (s, 1 H), 7.78 (s, 1 H), 7.72 (d, 1 H), 7.57 (d , 1H), 7.48 (m, 1H), 7.19 (m, 2H), 4.77 (m, 1H), 4.43 (s, 2H), 3.63 (m, 6H), 3.17 (m, 4H), 2.11 (m, 6H), 1.72 (m, 4H), 1.15 (s, 6H). EXAMPLE 373 (c / 's) -4- (4- (4- { 4-amino-3- (2- (2,6-difluorobenzyl) -1H-benzimidazol-5-yl) -1 Hp i reason [3, 4-d] pyrim idin-1-yl.} Cyclohexyl) piperazin-1-yl) -2-methylbutan-2-ol This product was the slowest eluting diastereomer of EXAMPLE 372. MS (IEA) m / e 630 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 8.33 (s, 1 H), 7.80 (s, 1 H), 7.71 (d, 1 H), 7.57 (d, 1 H), 7.47 (m, 1H), 7.18 (m, 2H), 4.92 (m, 1H), 4.41 (s, 2H), 3.56 (m, 6H), 3.15 (m, 4H), 2.36 (m, 2H), 2.07 ( m, 2H), 1.88 (m, 4H), 1.71 (m, 2H), 1.13 (s, 6H). EXAMPLE 374 (frans) -2- (4- (4- { 4-amino-3- (2- (2,6-difluorobenzyl) -1H-benzimidazol-5-yl) -1H-pyrazolo [3,4 -d] pyrimidin-1-yl.}. cyclohexyl) piperazin-1-yl) ethanol The desired product was prepared by substituting the product of EXAMPLE 265A for the product of EXAMPLE 294C and 1- (3-methoxypropyl) -piperazine for 1- (2-hydroxyethyl) -piperazine, in EXAMPLE 265B. The fastest eluting diastereomer was isolated. MS (EAI) m / e 588 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 8.34 (s, 1 H), 7.80 (s, 1 H), 7.74 (d, 1 H), 7.58 (d , 1H), 7.48 (m, 1H), 7.19 (m, 2H), 4.78 (m, 1H), 4.45 (s, 2H), 3.75 (t, 2H), 3.5-3.3 (m, 6H), 3.19 ( m, 4H), 2.12 (m, 6H), 1.74 (m, 2H). EXAMPLE 375 (c / s) -2- (4- (4- { 4-amino-3- (2- (2,6-difluorobenzyl) -1H-benzimidazol-5-yl) -1H-pyrazolo [ 3,4-d] pyrimidin-1-yl.} Cyclohexyl) piperazin-1-yl) ethanol This product was the slowest eluting diastereomer of EXAMPLE 374. MS (LEA) m / e 588 (M + H) J 1 H-NMR (300 MHz, DMSO-de) d 8.34 (s, 1H), 7.81 (s, 1H), 7.72 (d, 1H), 7.57 (d, 1H), 7.47 (m, 1H), 7.19 (m, 2H), 4.93 (m , 1H), 4.41 (s, 2H), 3.71 (t, 2H), 3.56 (m, 6H), 3.17 (m, 4H), 2.36 (m, 2H), 2.07 (m, 2H), 1.91 (m, 4H). EXAMPLE 376 (frans) -3- (2- (2,6-difluorobenzyl) -1H-benzimidazol-5-yl) -1- (4- (4-ethylpiperazin-1-yl) cyclohexyl) -1 Hp i reason [ 3, 4-d] pyrim id-n-4-amine The desired product was prepared by substituting the product of EXAMPLE 265A for the product of EXAMPLE 294C and 1- (3-methoxypropyl) piperazine for 1-ethylpiperazine, in EXAMPLE 265B .

The fastest eluting diastereomer was isolated. EM (LEA) m / e 572 (M + H) J 1 H-NMR (300 MHz, DMSO-d 6) d 8.33 (s, 1 H), 7.79 (s, 1 H), 7.73 (d, 1 H), 7.56 (d, 1 H), 7.48 (m , 1H), 7.19 (m, 2H), 4.77 (m, 1H), 4.43 (s, 2H), 3.61 (m, 6H), 3.12 (m, 4H), 2.11 (m, 6H), 1.71 (m, 2H), 1.22 (t, 3H). EXAMPLE 377 (c / s) -3- (2- (2,6-difluorobenzyl) -1H-benzimidazol-5-yl) -1- (4- (4-ethylpiperazin-1-yl) cyclohexyl) -1 H- pyrazolo [3,4-d] pyrimidin-4-amine This product was the slowest eluting diastereomer of EXAMPLE 376. MS (LEA) m / e 572 (M + H) J 1 H-NMR (300 MHz, DMSO-de) d 8.35 (s, 1H), 7.81 (s, 1H), r7.73 (d, 1H), 7.58 (d, 1H), 7.48 (m, 1H), 7.19 (m, 2H), 4.93 (m, 1H), 4.42 (s, 2H), 3.55 (m, 6H), 3.12 (m, 4H), 2.34 (m, 2H), 2.07 ( m, 2H), 1.89 (m, 4H), 1.20 (t, 3H). EXAMPLE 378 (frans) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-6-yl) -1-. { 4- (4- (2-methoxyethyl) piperazin-1-yl) cyclohexyl} -1H-pyrazolo [3,4-d] pyrimidin-4-amine The desired product was prepared by substituting 2- (trifluoromethyl) -5,6,7,8-tetrahydroimidazo [1,2-a] pyrazine from EXAMPLE 338, by 1- (2-methoxyethyl) piperazine. The fastest elution isomer was isolated: MS (IEA (+)) m / e 596 (M + H) *; 1 H-NMR (300 MHz, DMSO-de) 8.31 (s, 1H), 7.88-7.83 (m, 1H), 7.74-7.71 (m, 1H), 7.41-7.35 (m, 1H), 7.10-7.07 (m , 1H), 7.05-6.99 (m, 1H), 4.77 (m, 1H), 4.46 (s, 2H), 3.78 (s, 3H), 3.63-3.60 (m, 2H), 3.30 (s, 3H), 3.18-3.11 (m, 2H), 2.19-2.06 (m, 4H), 1.78-1.66 (m, 1H). EXAMPLE 379 (c / s) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-6-yl) -1-. { 4- (4- (2-methoxyethyl) piperazin-1-yl) cyclohexyl} -1H-pyrazolo [3,4-d] pyrimidine-4- Amine The desired product is the slower elution isomer of EXAMPLE 378. 1 H-NMR (300 MHz, DMSO-d 6) 8.33 (s, 1H), 7.90-7.83 (m, 2H), 7.77-7.74 (m, 1H) , 7.40-7.35 (m, 2H), 7.10-7.07 (m, 1H), 7.02-6.99 (m, 1H), 4.93 (m, 1H), 4.45 (m, 2H), 3.78 (s, 3H), 3.62 -3.59 (m, 2H), 3.52-3.37 (m, 3H), 3.21-3.13 (m, 2H), 2.40-2.31 (m, 2H), 2.13-1.98 (m, 2H), 1.95-1.85 (m, 3H). EXAMPLE 380 (frans) -1- (4- (4-isopropylpiperazin-1-yl) cyclohexyl) -3- (2- (2-methoxybenzyl) -1 H -benzimidazol-6-yl) -1 H-pyrazolo [3 , 4-d] pyrimidin-4-amine The desired product was prepared by substituting 2- (trifluoromethyl) -5,6,7,8-tetrahydroimidazo [1,2-a] pyrazine from EXAMPLE 338, by 1- (isopropyl) -piperazine. The fastest elution isomer was isolated: 1 H-NMR (300 MHz, DMSO-d 6) 8.31 (s, 1 H), 7.88-7.83 (m, 2 H), 7.73-7.70 (m, 1 H), 7.41-7.36 (m , 2H), 7.10-7.04 (m, 1H), 7.04-7.00 (m, 1H), 4.77 (m, 1H), 4.45 (m, 2H), 3.78 (s, 3H), 3.59-3.42 (m, 5H) ), 3.28-2.98 (m, 5H), 2.19-2.06 (m, 6H), 1.78-1.64 (m, 2H), 1.25 (d, 6H). EXAMPLE 381 (cis) -1- (4- (4-isopro pi I pipe-rain-1 -i I) cyclohexy I) -3- (2- (2-methoxy-benzyl) - 1H-benzimidazol-6-yl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine The desired product is the slowest elution isomer of the EXAMPLE 380. 1 H-NMR (300 MHz, DMSO-d 6) 8.32 (s, 1H), 7.89-7.82 (m, 2H), 7.75-7.72 (m, 1H), 7.40-7.36 (m, 2H), 7.10- 7.07 (m, 1H), 7. 04-6.99 (m, 1H), 4.93 (m, 1H), 4.45 (s, 2H), 3.78 (s, 3H), 3.54-3.40 (m, 5H), 3.16-3.00 (m, 3H), 2.39- 2.28 (m, 2H), 2.12-2.03 (m, 2H), 1.95-1.82 (m, 4H), 1.23 (d, 6H). EXAMPLE 382 EXAMPLE 382A Cyclohexylacetic acid (313 mg, 2.2 mmol) was dissolved in THF (3 L) and N, N'-carbonyldiimidazole (340 mg, 2.1 mmol) was added. The mixture was stirred at 50 ° C for 30 minutes. Subsequently, the product of EXAMPLE 280A (470 mg, 2 mmol) was added and the mixture was stirred continuously at 50 ° C. After 2 hours, 3 mL of glacial acetic acid was added to the reaction mixture, which was heated to 90 ° C with stirring overnight. The mixture was diluted with EtOAc, and the organic phase was washed with a saturated solution of sodium bicarbonate (3x), with brine (2x), and dried over anhydrous magnesium sulfate (MgSO). The obtained crude product was purified on a column of silica gel, eluting with 40% EtOAc in hexane, to obtain 270 mg of the title compound. EXAMPLE 382B The product of EXAMPLE 382A (100 mg, 0.3 mmol), the product of EXAMPLE 318A (132 mg, 0.25 mmol), sodium carbonate (53 mg, 0.5 mmol) and palladium tetrakistriphenylphosphine (15 mg, 0.0125 mmol), they were mixed in 4 mL of dimethoxyethane / water (1: 1), and heated in a microwave oven at 130 ° C for 20 minutes. Then, the mixture was partitioned into ethyl acetate and brine; the ethyl acetate phase was washed with Brine (3x), dried and purified by chromatography on a silica gel column, eluting with 7% methanol in ethyl acetate, to obtain 150 mg of the title compound. EXAMPLE 382C The product of EXAMPLE 382B (150 mg, 0.244 mmol) was treated with 5 mL of 25% trifluoroacetic acid (TFA) in methylene chloride (CH2Cl2) for 1 hour, and evaporated to dryness. The residue was dissolved in 5 mL of acetonitrile (MeCN). To the above solution, sodium iodide (Nal, 93 mg, 0.625 mmol), potassium carbonate (K2CO3, 173 mg, 1.25 mmol) and (methoxy) propyl bromide (57 mL, 0.375 mmol) were added. The mixture was stirred at 50 ° C for 16 hours. The mixture was extracted by partition in EtOAc and brine; the EtOAc phase was washed with brine and dried over MgSO4. The crude product was purified by High Performance Liquid Chromatography (HPLC). 81 mg of the title compound were obtained. 1 H-NMR (300 MHz, DMSO-dβ) 8.33 (s, 1H), 7.89-7.93 (m, 2H), 7.75 (d, 1H), 4.76 (br m, 1H), 3.39 (t, 2H), 3.25 (s, 3H), 3.04 (br, 4H), 2.11 (br., 6H), 1.81-1.95 (m, 3H), 1.60-1.76 (br m, 6H), 1.01-1.30 (m, 4H). EXAMPLE 383 EXAMPLE 383A The desired product was prepared by substituting the cyclohexylacetic acid of EXAMPLE 382A for cyclopentyl acetic acid. EXAMPLE 383B The desired product was prepared by substituting the product of EXAMPLE 382A by the product of EXAMPLE 383A, in EXAMPLE 382B. EXAMPLE 383C The desired product was prepared by substituting the product of EXAMPLE 382B for the product of EXAMPLE 383B, in EXAMPLE 382C. 1 H-NMR (300 MHz, DMSO-d 6) 8.31 (s, 1 H), 7.88-7.93 (m, 2 H), 7.75 (d, 1 H), 4.77 (br m, 1 H), 3.39 (t, 2 H), 3.26 (s, 3H), 3.13 (d, 2H), 3.00 (br, 2H), 2.39-2.44 (m, 2H), 2.11 (br., 6H), 1.54-1.88 (m, 6H), 1.26-1.34 ( m, 2H). EXAMPLE 384 EXAMPLE 384A The desired product was synthesized by substituting the 2-chlorobenzyl bromide of EXAMPLE 121B, for 3-fluorobenzyl bromide. EXAMPLE 384B The desired product was synthesized by substituting the product of EXAMPLE 121 B for the product of EXAMPLE 384A, in EXAMPLE 121C. 1 H-NMR (300 MHz, DMSO-d 6) 9.76 (br s, 1 H), 8.38 (s, 1 H), 8.27 (s, 1 H), 8.05 (d, 1 H), 7.93 (d, 1 H), 7.69 (dd) , 1H), 7.35-7.42 (m, 1H), 7.08-7.14 (m, 3H), 5.76 (s, 2H), 4.80 (m, 1H), 3.98-4.09 (m, 2H), 3.64-3.76 (br t, 2H), 3.35-3.50 (m, 3H), 3.08-3.24 (m, 2H), 2.19-2.30 (m, 2H), 2.06-2.17 (br m, 4H), 1.68-1.83 (br m, 2H). EXAMPLE 385 EXAMPLE 385A The desired product was synthesized by replacing the bromide of 2-chlorobenzyl from EXAMPLE 121B, by 2-methylbenzyl bromide. EXAMPLE 385B The desired product was synthesized by substituting the product of EXAMPLE 121B in EXAMPLE 121C, by the product of EXAMPLE 385A. 1 H-NMR (300 MHz, DMSO-d 6) 9.67 (br s, 1 H), 8.34 (s, 1 H), 8.25 (s, 1 H), 8.05 (d, 1 H), 7.83 (d, 1 H), 7.67 (dd) , 1H), 7.55-7.64 (m, 3H), 7.22-7.27 (m, 1H), 5.72 (s, 2H), 4.79 (m, 1H), 3.64-3.76 (br.t, 2H), 3.35-3.50 (m, 3H), 3.08-3.24 (m, 2H), 2.39 (s, 3H), 2.19-2.30 (m, 2H), 2.06-2.17 (br m, 4H), 1.68-1.84 (br m, 2H) . EXAMPLE 386 EXAMPLE 386A The desired product was synthesized by substituting the 2-chlorobenzyl bromide of EXAMPLE 121B, for 3-methylbenzyl bromide. EXAMPLE 386B The desired product was synthesized by substituting the product of EXAMPLE 121B for the product of EXAMPLE 386A, in EXAMPLE 121C. 1 H-NMR (300 MHz, DMSO-d 6) 9.66 (br s, 1 H), 8.33 (s, 1 H), 8.23 (s, 1 H), 8.02 (d, 1 H), 7.89 (d, 1 H), 7.67 (dd) , 1H), 7.07-7.21 (m, 4H), 5.67 (s, 2H), 4.78 (m, 1H), 3.64-3.75 (br.t, 2H), 3.35-3.50 (m, 3H), 3.08-3.24 (m, 2H), 2.19-2.30 (m, 5H includes 2.26, s, 3H), 2.06-2.17 (br m, 4H), 1.68-1.84 (br m, 2H). EXAMPLE 387 (frans) -1- (4- (4-phenylpiperazin-1-yl) cyclohexyl) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-6-yl) -1 H-pyrazolo [3, 4-d] pyrimidin-4-amine The desired product was prepared by substituting the 2- (trifluoromethyl) -5,6,7,8-tetrahydroimidazo [1,2-a] pyrazine from EXAMPLE 338, by 1-phenylpiperazine. The fastest elution isomer was isolated. 1 H-NMR (300 MHz, DMSO-d 6) 12.25 (bm, 1H), 8.23 (s, 1H), 7.73-7.56 (m, 2H), 7.43-7.41 (m, 1H), 7.30-7.18 (m, 5H) ), 7.04-7.01 (m, 1H), 6.95-6.89 (m, 4H), 6.79-6.74 (m, 1H), 4.67 (m, 1H), 4.17 (s, 2H), 3.81 (m, 3H), 3.14-3.11 (m, 4H), 2.70-2.67 (m, 4H), 2.07-1.97 (m, 5H), 1.60-1.47 (m, 2H). EXAMPLE 388 (trans) -1- (4- (4-phenylpiperazin-1-yl) cyclohexyl) -3- (2- (2-methoxybenzyl I) - 1 H- benzimidazol-6-yl) -1 H- pyrazolo [3,4-d] pyrimidin-4-amine The desired product is the slower elution isomer of EXAMPLE 387. 1 H-NMR (300 MHz, DMSO-d 6) 12.23 (m, 1H), 8.23 (s, 1H ), 7.73-7.54 (m, 2H), 7.42-7.39 (m, 1H), 7.26-7.16 (m, 5H), 7.03-7.00 (m, 1H), 6.93-6.88 (m, 4H), 6.75 (t , 1H), 4.83 (m, 1H), 4.16 (s, 2H), 3.79 (s, 3H), 3.17-3.14 (m, 4H), 2.63-2.59 (m, 3H), 2.33-2.26 (m, 3H) ), 2.17-2.07 (m, 2H), 1.76-1.60 (m, 3H). EXAMPLE 389 (trans) -1- (4- (4-ethylpiperazin-1-yl) cyclohexyl) -3- (2- (2-methoxybenzyl) -1 H- benzimidazol-6-yl) -1 H-pyrazolo [3 , 4-d] pyrimidin-4-amine EXAMPLE 389A The desired product was prepared by substituting the phenylmethylacetonitrile of EXAMPLE 118B, for 2-chlorophenylacetonitrile. EXAMPLE 389B The desired product was prepared by substituting the product of EXAMPLE 339A for the product of EXAMPLE 389A, EXAMPLE 339B. EXAMPLE 389C The desired product was prepared by substituting the product of EXAMPLE 339B for the product of EXAMPLE 389B, in EXAMPLE 339C. EXAMPLE 389D To a mixture of the product of EXAMPLE 389C (0.10 g, 0. 21 mmol) and N-ethylpiperazine (0.12 g, 1.06 mmol), a 0.2M solution of MeOH / AcOH (9: 1, v / v) was added. The mixture was stirred for 15 min., Then NaCNBH3 (0.040 mg, 0.639 mmol) was added, and the mixture was stirred at RT for 1.5 h. The mixture was diluted with CH2Cl2 and washed with a saturated aqueous solution of NaHCO3.

The organic phase was dried over MgSO 4, filtered, reduced in vacuo and purified by reverse phase HPLC. The fastest elution isomer was isolated. 1 H-NMR (300 MHz, DMSO-d 6) 8.31 (s, 1 H), 7.83-7.77 (m, 2H), 7.64-7.61 (m, 1H), 7.56-7.52 (m, 2H), 7.43-7.40 (m, 2H), 4.76 (m 1H), 4.56 (s, 2H), 3.64-3.50 (m, 4H), 3.14-3.05 (m, 3H), 3.03-2.90 (m, 3H), 2.15-2.05 (m, 6H), 1.74-1.61 (m, 2H), 1.21 (t, 3H). EXAMPLE 390 (frans) -1- (4- (4-ethylpiperazin-1-yl) cyclohexyl) -3- (2- (2-methoxybenzyl) -1 H -benzimidazol-6-yl) -1 H-pyrazolo [3 , 4-d] pyrimidin-4-amine The desired product is the slowest elution isomer of the EXAMPLE 389. 1 H-NMR (300 MHz, DMSO-d 6) 8.32 (s, 1 H), 7.84 (bm, 1H), 7.76 (d, 1H), 7.62 (dd, 1H), 7.55-7.51 (m, 2H), 7.42-7.39 (m, 2H), 4.92 (m, 1H), 4.54 (bs, 2H), 3.59 -3.40 (bm, 5H), 3.14-3.05 (m, 3H), 2.40-2.26 (m, 2H), 2.12-2.01 (m, 2H), 1.91-1.78 (m, 3H), 1.19 (t, 3H). EXAMPLE 391 (trans) -1- (4- (4- (2-h idroxyethyl) piperazin-1-yl) cyclohexyl) -3- (2- (2-methoxybenzyl) -1H-benzimidazol-6-yl) - 1H-pyrazolo [3,4-d] pyrimidin-4-amine The desired product was prepared by substituting the ethylpiperazine of EXAMPLE 389D for 1- (2-hydroxyethyl) piperazine. The fastest elution isomer was isolated: 1 H-NMR (300 MHz, DMSO-dβ) 8.30 (s, 1H), 7.82 (bm, 1H), 7.76 (d, 1H), 7.63 (dd, 1H), 7.55- 7.51 (m, 2H), 7.42-7.39 (m, 2H), 4.76 (m, 1H), 4.55 (bs, 2H), 3.75 (m, 7H), 3.16-3.07 (m, 6H), 2.17-2.04 ( m, 7H), 1.29-1.62 (m, 2H). EXAMPLE 392 (trans) -1- (4- (4- (2-hydroxyethyl) piperazin-1-yl) cyclohexyl) -3- (2- (2-methoxybenzyl) -1 H -benzimidazol-6-yl) -1 H-pyrazolo [3,4-d] pyrimidin-4-amine The desired product is the slowest elution isomer of the EXAMPLE 391. 1 H-NMR (300 MHz, DMSO-d 6) 8.34 (s, 1 H), 7.85 (bs, 1 H), 7. 78 (d, 1H), 7.66-7.63 (dd, 1H), 7.56-7.52 (m, 2H), 7.43-7.40 (m, 2H), 4.93 (m, 1H), 4.56 (bs, 2H), 3.71 ( m, 3H), 3.61-3.46 (m, 4H), 3.19-3.13 (m, 3H), 2. 42-2.31 (m, 2H), 2.13-2.02 (m, 2H), 1.97-1.85 (m, 3H). With the above it is intended to illustrate the invention, but not limit it. It is intended that the variations and obvious changes for a person skilled in the art, fall within the scope of the invention, as defined in the claims.

Claims (1)

CLAIMS 1. A com ponent of the form I ), or a salt of the same, where u is not from X1 or X2 is C, and the other is C or N; X3 is C (H), C (alkyl of 1 to 4 carbon atoms), or N; X4 is N or C; X5 is C (H) or N; X6 is C (H) or N; A1 is R1 or R2; R1 is a phenyl radical, which is fused with benzene, heteroarene or heterocycloalkane, which is fused or not with benzene; R2 is a heteroaryl radical, which is fused with benzene or heteroarene; B1 is R3, R4, R5 or W1; R3 is phenyl which is fused or not with benzene, heteroarene or R3A; R3A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R 4 is a heteroaryl radical, which is or is not fused with benzene, heteroarene or R A; R 4A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R5 is a cycloalkyl radical, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl, each of which is or is not fused with benzene, heteroarene or R5A; R5A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; W is an alkyl, alkenyl or alkynyl radical, each of which is unsubstituted or substituted by one or two groups which are independently selected from W2, W3, W4, OH, OW5, SW5, S (O) W5, SO2W5, NH2, N HW5, N (W5) 2, C (O) N H2, C (O) N HW5, C (O) N (W5) 2, N HC (O) W5 or NW5C (O) W5; W2 is a phenyl radical, which is or is not fused with benzene, heteroarene or W2A; W2A is a cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene radical; W3 is a heteroaryl radical, which is or is not fused with benzene, heteroarene OW3A; W3A is a cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene radical; W4 is a cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl radical, each of which is or is not fused with benzene, heteroarene or W5A; W5A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; W5 is an alkyl, alkenyl or alkynyl radical; Where the portions represented by A1, B1, W2, W3 and W4 are independently substituted or unsubstituted with one or two or three or four groups that are independently selected from R6, OR6, SR6, S (O) R6, SO2R6, N H2, N HR6, N (R6) 2, C ( O) R6, C (O) O R6, C (O) N H2, C (O) NH R6, C (O) N (R6) 2, N HC (O) R6, NR6C (O) R6, N HSO2R6 , N R6SO2R6; NHC (O) OR6, N R6C (O) OR6, SO2N H2, SO2N H R6, SO2N (R6) 2, NHC (O) NH2, NHC (O) NHR6, NHC (O) N (R6) 2, NR6C (O) N (R6) 2, C (N) NH2, C (N) NHR6, C (N) N ( R6) 2, NHC (N) NH2, NHC (N) NHR6, NHC (N) N (R6) 2, OH, (O), C (O) H, C (O) OH, NO2, CN, CF3, OCF3, CF2CF3, F, Cl, Br or I; R6 is R7, R8, R9, or R10; R7 is a phenyl radical which is or is not fused with benzene, heteroarene, or R7A; R7A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R8 is a heteroaryl radical, which is or is not fused with benzene, heteroarene or R8A; R8A is a cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene radical; R9 is a cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl radical, each of which is or is not fused with benzene, heteroarene; or R9A; R9A is cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene; R10 is an alkyl, alkenyl or alkynyl radical, each of which is or is not substituted with or two groups that are independently selected from R1, OR11, SR11, S (O) R11, SO2R1 \ NH2, NHR11 N (R11) 2, C (O) R1C (O) NH2, C (O) NHR11, C (O) N (R11) 2, NHC (O) R11 NR11C (O) R11, NHSO2R1 \ NR11SO2R1 \ NHC (O) OR11 NR11, C (O) OR11 SO2NH2, SO2NHR1 \ SO2N (R11) 2, NHC (O) NH2, NHC (O) NHR | 11 NHC (O) N (R11) 2, NR11C (O) N (R1) 2, OH, (O), C (O) OH, CN, CF3, OCF CF2CF3, F, Cl, Br or I; R11 is alkyl, alkenyl, alkynyl R12, R3, R4 or T1; R12 is a phenyl radical, which is or is not fused with benzene, heteroarene or R 2A; R12A is a cycloalkane radical, cycloalkene heterocycloalkane or heterocycloalkene; R 1 3 is a heteroaryl radical which is or is not fused with benzene, heteroarene or R 1 3A; R13A is a cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene radical; and R14 is a cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl radical, each of which is or is not fused with benzene, heteroarene; or R14A; R14A is a cycloalkane, cycloalkene, heterocycloalkane or heterocycloalkene radical; T1 is an alkenyl or alkynyl alkyl radical, each of which is substituted with one or two groups which are independently selected from OH, OT2, ST2, S (O) T2, N H2, N HT2 or N (T2) 2; T2 is an alkyl, alkenyl or alkynyl radical; Wherein the portions represented by R7, R8, R9 and R1 are independently or independently substituted with one or two or three or four groups that are independently selected from R15, OR15, SR15, S (O) R15, SO2R15, C (O ) R15, C (O) (O) R15, C (O) N H2, C (O) NH R15, C (O) N (R1 5) 2, OH, (O), C (O) OH, CN , C F3OCF3, CF2CF3 F, Cl, Br or I, wherein R1 is an alkyl, alkenyl, alkynyl radical, each of which is unsubstituted or substituted by phenyl, hetero, cycloalkyl, heterocycloalkyl, OH, OR16, C ( O) NH 2, C (O) NH R 16, C (O) N (R 16) 2; wherein R16 is an alkyl, alkenyl or alkynyl radical; and wherein the phenyl, hetero, cycloalkyl and heterocycloalkyl radicals of R15 are unsubstituted or substituted with O (alkyl). Another embodiment refers to compounds having the formula I, wherein one of X1 or X2 is C, and the other is C or N; X3 is C (H) or N; X4 is N or C; X5N; X6 is C (H); A1 is R1 or R2; R1 is a phenyl radical which is fused with benzene, heteroarene or heterocycloalkane, which is or is not fused with benzene; R2 is a heteroaryl radical, which is fused with benzene or heteroarene; B1 is R3, R4, R5 or W1; R3 is a phenyl radical, which is or is not fused with benzene or heteroarene; R 4 is a heteroaryl radical which is fused or not with benzene or heteroarene; R5 is a cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl radical, each of which is or is not fused with benzene or heteroarene; W1 is an alkyl, alkenyl, or alkynyl radical, each of which is or is not substituted with W2, W3, W4, OH, OW5, SW5, S (O) W5, SO2W5, NH2, N HW5, N (W5) 2, C (O) NH2, C (O) N HW5, C (O) N (W5) 2, N HC (O) W5 or NW5C (O) W5; W2 is a phenyl radical, which is or is not fused with benzene or heteroarene; W3 is a heteroaryl radical, which is or is not fused with benzene or heteroarene; W4 is a cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl radical, each of which is or is not fused with benzene or heteroarene; W5 is an alkyl, alkenyl or alkynyl radical; wherein the portions represented by A \ B0 W2, W3 and W4 are independently substituted or unsubstituted with one or two or three or four groups which are independently selected from R6, OR6, SR6, S (O) R6, SO2R6, NH2, NHR6, N (R6) 2, C (O) R6, C (O) OR6, C (O) NH2, C (O) NHR6, C (O) N (R6) 2, NHC (O) R6, NR6C ( O) R6, NHSO2R6, NR6SO2R6, NHC (O) OR6, NR6C (O) OR6, SO2NH2, SO2NHR6, SO2N (R6) 2, OH, (O), C (O) H, C (O) OH, NO2, CN, CF3, OCF3, CF2CF3, F, Cl, Br or I; R6 is R7, R8, R9, or R10; R7 is a phenyl radical, which is or is not fused with benzene or heteroarene; R8 is a heteroaryl radical, which is or is not fused with benzene or heteroarene; R9 is a cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl radical, each of which is or is not fused with benzene or heteroarene, R10 is an alkyl, alkenyl or alkynyl radical, each of which is or is not substituted with one or two groups which are independently selected from R11, OR11, SR11, S (O) R1 \ SO2R1 \ NH2, NHR11, N (R11) 2, C (O) R11, C (O) NH2, C (O) NHR11, C (O) ) N (R11) 2, NHC (O) R11, NR11C (O) R11, NHSO2R11, NR11S2R11NHC (O) OR11 NR11, C (O) OR11, SO2NH2, SO2NHR11, SO2N (R11) 2, OH, (O), C (O) OH, CN, CF3, OCF3CF2CF3, F, Cl, Br or I; R11 is an alkyl, alkenyl, alkynyl, R12, R13, R14 or T1 radical; R 12 is a phenyl radical, which is or is not fused with benzene or heteroarene; R 13 is a heteroaryl radical, which is or is not fused with benzene or heteroarene; R14 is a cycloalkyl, cycloalkenyl, heterocycloalkyl or heterocycloalkenyl radical, each of which is or is not fused with benzene or heteroarene; T1 is an alkyl, alkenyl, or alkynyl radical, each of which is substituted with one or two groups which is independently selected from OH, OT2, ST2, S (O) T2, NH2, NHT2 or N (T2) 2; T2 is an alkyl, alkenyl or alkynyl radical; wherein the portions represented by R7, R8, R9 and R1 are independently substituted or not with one or two or three or four groups that are independently selected from R15, OR15, SR15, S (O) R15, SO2R15, C (O ) R15, C (O) (O) R15, C (O) NH2, C (O) NHR15, C (O) N (R15) 2, OH, (O), C (O) OH, CN, CF3, OCF3, CF2CF3, F, Cl, Br or I; wherein R15 is an alkyl, alkenyl, alkynyl radical, each of which is unsubstituted or substituted by phenyl, heteroaryl, cycloalkyl, heterocycloalkyl OH, OR16, C (O) NH2, C (O) NHR16, C (O) N (R16) 2; where R16 is an alkyl, alkenyl, or alkynyl radical; and wherein the phenyl, heteroaryl, cycloalkyl and heterocycloalkyl radicals of R1 are or are not substituted with O (alkyl). 2. A composition comprising an excipient and a therapeutically effective amount of a compound of claim 1. 3. A method for the treatment of a mammal suffering from bladder cancer, breast cancer, cervical cancer, colon cancer, endometrial cancer, esophageal cancer, lung cancer, ovarian cancer, pancreatic cancer, prostate cancer, rectal cancer , skin cancer, stomach cancer or thyroid cancer, which comprises administering thereto a therapeutically effective amount of a compound of claim

1.