Sodium Carbonate → HCID 178481008, 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 (3.41 g, 7.74 mmol) in ethylene glycol dimethyl ether (50 mL) was treated with 4-(benzyloxy)phenylboronic acid (1.94 g, 8.51 mmol), tetrakis(triphenylphosphine)palladium (0.537 g, 0.464 mmol), and a solution of sodium carbonate (1.97 g, 18.58 mmol) in water (25 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 (300 mL) was added to the aqueous layer. The layers were partitioned, and the aqueous layer was extracted with ethyl acetate (200 mL). The combined organic layers were washed with water and brine (1 L each), dried over magnesium sulfate, filtered and evaporated under reduced pressure. Ethyl acetate was added to the solid. A significant amount of the solid was not soluble in ethyl acetate, and was subsequently filtered to give 2.95 g (77%) of cis-3-[4-(benzyloxy)phenyl]-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine. 1H NMR (DMSO-d6, 400 MHz) δ 8.217 (s, 1H), 7.592-7.570 (m, 2H), 7.504-7.483 (m, 2H), 7.440-7.369 (m, 3H), 7.206-7.184 (m, 2H), 5.186 (s, 2H), 4.802-4.755 (m, 1H), 2.497-2.354(m, 7H), 2.256-2.228(m, 4H), 2.151 (s, 3H), 2.076-1.989 (m, 2H), 1.694-1.673 (m, 2H), 1.607-1.545 (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 5.128 min (100%).

Provenance & Evidence