Pyridine → HCID 178488195, compound

Participants

Reaction Steps

To (3R)-3-phenylbutanoic acid (376 mg, 2.29 mmol) in dichloromethane (7 mL) was added oxalyl chloride (2 mL, 22.9 mmol) and DMF (1 drop). The reaction mixture was stirred overnight. Solvent was evaporated and the residue was dissolved in dichloromethane (3 mL). The dichloromethane solution was added to a solution of trans-3-(4-amino-3-methoxyphenyl)-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (448 mg, 1.026 mmol) in pyridine (6 mL) at 0° C. After 2 hours, the reaction mixture was poured to ethyl acetate (60 ml) and the solid as collected by filtration. Water was then added to the solid and the pH of the solution was adjusted to 10 with sodium hydroxide (1.0N). The aqueous was extracted with dichloromethane. The combined organic layer was washed with water then brine, dried over MgSO4, filtered and evaporated. The residue was purified by flash column chromatography using dichloromethane/methanol (80:20) as mobile phase to give trans-N1-[(2R)-2-phenylpropyl]-4-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-2-methoxybenzamide (383 mg, 64%). 1H NMR (CDCl3) δ 1.40 (d, J=6.96, 3H), 1.57 (m, 2H), 2.08-2.21 (m, 6H), 2.30 (s, 3H), 2.50 (m, 5H), 2.63-2.74 (m, 6H), 3.40 (m, 1H), 3.88 (s, 3H), 4.74(m, 1H), 5.69 (bs, 2H), 7.16-7.34 (m, 7H), 7.66 (s, 1H), 8.34 (s, 1H), 8.49 (d, J=8.21, 1H).

Provenance & Evidence