反应详情

A capped vial was charged with 4-(7-(2-fluoro-4-(1-(4-fluorophenyl)-6-oxo-1,6-dihydropyridazine-5-carboxamido)phenoxy)thieno[3,2-b]pyridin-2-yl)benzoic acid (0.100 g, 0.168 mmol), HOBT-H2O (0.103 g, 0.671 mmol), EDCI (0.129 g, 0.671 mmol), and DMF (2 mL). After stirring for 45 minutes, (R)-pyrrolidin-3-ol (0.0584 g, 0.671 mmol) and Hunig's base (0.175 ml, 1.01 mmol) were added. After stirring for 18 hours, water (20 mL) was added. The formed precipitate was isolated by filtration. After drying, (62 mg, 55%) of product was isolated as orange solid. LRMS (esi+) 666 m/z (M+1) detected. 1H NMR (CDCl3, 400 MHz) δ 11.84 (s, 1H), 8.47 (s, 1H), 8.39 (d, J=4 Hz, 1H), 8.22 (d, J=4 Hz, 1H), 7.97 (m, 1H), 7.76 (m, 3H), 7.62 (m, 4H), 7.39 (d, J=9 Hz, 1H), 7.26 (m, 3H), 6.52 (d, J=6 Hz, 1H), 4.50 (br s, 1H), 3.72 (m, 5H), 2.07 (m, 2H).

1. stirringAfter stirring for 18 hours
2. customThe formed precipitate was isolated by filtration
3. customAfter drying