Sodium Bicarbonate → HCID 178480961, 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 (0.970 g, 2.20 mmol, 1 equiv), 2-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenoxy]benzaldehyde (0.842 g, 2.60 mmol, 1.2 equiv), tetrakis(triphenylphosphine)palladium (0.186 g, 0.180 mmol, 0.08 equiv), DME (9 mL), and sodium carbonate monohydrate (0.655 g, 5.30 mmol, 2.4 equiv) in water (7 mL) was heated at 85° C. for 7 h then allowed to cool to ambient temperature. Saturated aqueous sodium bicarbonate solution (50 mL) was added, and the solution was extracted with EtOAc (25 mL). The organic extract was dried over MgSO4, filtered, and concentrated to afford a light brown solid. Trituration from Et2O (35 mL) afforded cis-2-(3-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenoxy)benzaldehyde as an off-white solid (0.830 g, 1.62 mmol): 1H NMR (d6 DMSO, 400 MHz): δH 10.42 (1H, s), 8.24 (1H, s), 7.89 (1H, d, J=7.7 Hz), 7.69-7.71 (3H, m), 7.30-7.36 (1H, m), 7.29 (2H, d, J=6.3 Hz), 7.16 (1H, d, J=8.2 Hz), 4.79-4.81 (1H, m), 2.18-2.55 (11H, m), 2.17 (3H, s), 2.05-2.09 (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 12.56 min. MS: MH+ 512.

Provenance & Evidence