Reaction SMILES: I[C:2]1[C:10]2[C:5](=[N:6][CH:7]=[N:8][C:9]=2[NH2:11])[N:4]([C@H:12]2[CH2:17][CH2:16][C@H:15]([N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)[CH2:14][CH2:13]2)[N:3]=1.CC1(C)C(C)(C)OB([C:33]2[CH:47]=[CH:46][C:36]([CH2:37][NH:38][C:39](=[O:45])[O:40][C:41]([CH3:44])([CH3:43])[CH3:42])=[CH:35][CH:34]=2)O1.C(=O)([O-])[O-].[Na+].[Na+]>O.COCCOC>[NH2:11][C:9]1[N:8]=[CH:7][N:6]=[C:5]2[N:4]([C@H:12]3[CH2:17][CH2:16][C@H:15]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)[CH2:14][CH2:13]3)[N:3]=[C:2]([C:33]3[CH:47]=[CH:46][C:36]([CH2:37][NH:38][C:39](=[O:45])[O:40][C:41]([CH3:42])([CH3:43])[CH3:44])=[CH:35][CH:34]=3)[C:10]=12
Reactant: CC(C)(C)OC(=O)NCc1ccc(B2OC(C)(C)C(C)(C)O2)cc1
Reactant: CN1CCN([C@H]2CC[C@H](n3nc(I)c4c(N)ncnc43)CC2)CC1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: COCCOC
Product: CN1CCN([C@H]2CC[C@H](n3nc(-c4ccc(CNC(=O)OC(C)(C)C)cc4)c4c(N)ncnc43)CC2)CC1
Temperature: 85 °C
Reaction time: 16 h

Procedure:
A mixture containing trans-3-iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (850 mg, 1.93 mmol), tert-butyl N-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzyl]carbamate (1.25 equiv., 812 mg, 2.41 mmol), tetrakis-(triphenylphosphine)palladium (135 mg) and sodium carbonate (2.5 equiv., 511 mg, 4.83 mmol) in degassed water (10 mL) and DME (30 mL) was heated and stirred at 85° C. for 16 h. The solvent was removed under reduced pressure to give a brown foam which was purified by column chromatography over silica gel using 10% methanol and 1% ammonium hydroxide in dichloromethane as the eluent. Trans-tert-butyl N-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}benzyl)carbamate was formed as an off white foam (800 mg, 80%). A solution of tert-butyl N-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}benzyl)carbamate (800 mg) in TFA (4 mL) and dichloromethane (4 mL) was stirred at ambient temperature for 2 h. The solvent was removed in vacuo and the oily residue was basified with saturated aqueous sodium hydrogen carbonate solution and the aqueous layer washed with dichloromethane (3×20 mL). The aqueous layer was concentrated and DMF added (20 mL). The salts were removed by filtration and the DMF was removed in vacuo. The residue was purified by column chromatography over silica gel using 10% methanol in dichloromethane as the eluent to afford 3-[4-(aminomethyl)phenyl]-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine as a yellow solid (70 mg, 11%). m-Tolyl isocyanate (1.1 equiv., 13.7 mg, 0.1 mmol) was added to a solution of 3-[4-(aminomethyl)phenyl]-t-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (35 mg, 0.083 mmol) in pyridine (0.5 mL) and then stirred for 2 days. The reaction mixture was purified using mass actuated preparative RP-HPLC (Micromass/Gilson, Hypersil BDS C18, 5 μm, 100×21.2 mm column; 0-100% acetonitrile and 0.05M ammonium acetate, buffered to pH 4.5, over 12.5 min at 25 mL/min) to give trans-N-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}benzyl)-N′-(3-methylphenyl)urea (17 mg, 37%); 1H NMR (DMSO-d6, 400 MHz) δ 1.46 (2H, m), 2.05 (4H, m), 2.18 (2H, m), 2.25 (3H, s), 2.33 (4H, m), 2.45-2.53 (8H, m), 4.38 (2H, br d), 4.65 (1H, m), 6.52 (1H, t), 6.66 (1H, d), 7.10 (1H, t), 7.19 (1H, br d), 7.26 (1H, br s), 7.46 (2H, d), 7.63 (2H, d), 8.23 (1H, s) and 8.51 (1H, s) and m/z (MH+) 554.2.