反应详情

HATU (110 mg, 0.288 mmol) was added to a solution of 5-[3-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-1-methyl-1H-pyrrole-2-carboxylic acid (113 mg, 0.262 mmol) in dry THF (15 mL). Ammonia gas was bubbled through the solution. The mixture was stirred at room temperature under NH3 (g) for 16 h. The mixture was concentrated under reduced pressure. The residue was purified by preparative HPLC to give 5-[3-(6-tert-butyl-1-oxo-1H-phthalazin-2-yl)-2-hydroxymethyl-phenyl]-1-methyl-1H-pyrrole-2-carboxylic acid amide (25 mg, yield 22%) as a white solid. 1H NMR (300 MHz, CD3OD) δ 8.42 (s, 1H), 8.27 (d, J=8.5 Hz, 1H), 8.02-7.90 (m, 2H), 7.54-7.35 (m, 2H), 7.24-7.13 (m, 2H), 7.02 (d, J=1.9 Hz, 1H), 4.37 (s, 2H), 3.87 (s, 3H), 1.37 (s, 9H). LC-MS calcd for C25H26N4O3 (m/e) 430.20, obsd 883 [2M+Na]+.

1. customAmmonia gas was bubbled through the solution
2. concentrationThe mixture was concentrated under reduced pressure
3. customThe residue was purified by preparative HPLC