反应详情

To a solution of (R)-2-methoxy-propionic acid (300 mg, 2.88 mmol) and N-methylmorpholine (432 mg, 4.32 mmol) in anhydrous CH2Cl2 was added drop wise isobutyl chloroformate (588 mg, 4.32 mmol). The resultant mixture was stirred at RT for 1 h. N-(4-(2-Chloropyridin-4-yloxy)-2,5-difluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (200 mg, 0.452 mmol) was added and the resulting mixture was stirred at RT for 12 h. The reaction mixture was concentrated under vacuo and purified by HPLC separation to give (R)—N-(2,5-difluoro-4-((2-(2-methoxypropanamido)pyridin-4-yl)oxy)phenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (50 mg, 21%). 1H NMR (400 MHz, CDCl3): δ 9.79 (s, 1H), 9.07 (s, 1H), 8.51 (s, 1H), 8.32-8.27 (m, 1H), 8.16 (d, J=5.6 Hz, 1H), 7.83 (d, J=2 Hz, 1H), 7.48-7.44 (m, 2H), 7.06-6.98 (m, 3H), 6.66-6.64 (m, 1H), 3.82 (q, J=6.8 Hz, 1H), 3.50 (s, 3H), 1.75-1.67 (m. 4H), 1.42 (d, J=6.8 Hz, 3H); MS (ESI): m/z 529.1[M+H]+.

1. concentrationThe reaction mixture was concentrated under vacuo
2. custompurified by HPLC separation