1,2-Dimethoxyethane → HCID 178480993, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of cis-3-iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (2.29 g, 5.19 mmol, 1 equiv), 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]benzonitrile (2.0 g, 6.2 mmol, 1.2 equiv), tetrakis(triphenylphosphine)palladium (0.329 g, 0.311 mmol, 0.06 equiv), DME (21 mL), and sodium carbonate monohydrate (1.54 g, 12.5 mmol, 2.4 equiv) in water (16 mL) was heated at 85° C. for 60 h. Additional tetrakis(triphenylphosphine)palladium (0.100 g, 0.02 equiv) was added and the reaction mixture was heated at 85° C. for 6.5 h. The reaction mixture was allowed to cool to ambient temperature and was partitioned between saturated aqueous sodium bicarbonate solution (25 mL) and EtOAc (25 mL). The organic extract was dried over MgSO4, filtered, and concentrated. The residue was triturated from Et2O and purified by column chromatography on silica gel (elution with 1 L of 5% MeOH/CH2Cl2, 1L of 10% MeOH/CH2Cl2, 1 L of 20% MeOH/CH2Cl2, and 1 L of 25% MeOH/CH2Cl2) to give cis-2-(4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenoxy)benzonitrile as a pale yellow solid (1.79 g, 3.52 mmol): 1H NMR (d6 DMSO, 400 MHz): δH 8.24 (1H, s), 7.94 (1H, d, J=7.7 Hz), 7.68-7.73 (3H, m), 7.31-7.34 (3H, m), 7.18 (1H, d, J=8.5 Hz), 4.78-4.83 (1H, m), 2.21-2.51 (11H, m), 2.19 (3H, s), 2.05-2.08 (2H, m), 1.56-1.71 (4H, m); RP-HPLC (Delta Pak C18, 5 μm, 300 Å, 15 cm; 5%-85% acetonitrile-0.1M ammonium acetate over 20 min, 1 mL/min) Rt 13.16 min. MS: MH+ 509.

Provenance & Evidence