Sodium Carbonate → HCID 178481009, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of trans-3-iodo-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (1.50 g, 3.4 mmol) in ethylene glycol dimethyl ether (100 mL) was treated with 4-(benzyloxy)phenylboronic acid (0.853 g, 3.74 mmol), tetrakis(triphenylphosphine)palladium (0.236 g, 0.204 mmol), and a solution of sodium carbonate (0.864 g, 8.16 mmol) in water (35 mL). The reaction mixture was stirred over night at 85° C. under a nitrogen atmosphere. The organic solvent was removed under reduced pressure. Ethyl acetate (100 mL) was added to the aqueous layer. The layers were partitioned and the aqueous layer was extracted with ethyl acetate (300 mL). The combined organic layers were washed with water and brine (500 mL each), dried over magnesium sulfate, filtered, and evaporated under reduced pressure. The crude product was purified by flash chromatography on silica gel eluting with 5% methanol in dichloromethane, 10% methanol in dichloromethane, 20% methanol in dichloromethane, then 30% methanol in dichloromethane. The column afforded 0.817 g (49%) of trans-3-[4-(benzyloxy)phenyl]-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine. 1H NMR (DMSO-d6, 400 MHz) δ 8.22 (s, 1H), 7.59-7.57 (m, 2H), 7.53-7.50 (m, 2H), 7.48-7.21 (m, 3H), 7.19-7.17 (d, 2H, J=8 Hz), 5.18 (s, 2H), 4.65-4.60 (m, 1H), 2.5 (s, 3H), 2.45-2.25 (m, 5H), 2.15 (s, 3H), 2.04-1.92 (m, 7H), 1.50-1.44 (m, 2H); HPLC Waters 2690 Alliance HPLC (Symmetry Shield RP18 3.5 μm, 2.1×50 mm; 5%-95% acetonitrile-0.1 M ammonium acetate over 15 min, 0.5 mL/min) Rt 5.021 min (95%).

Provenance & Evidence