反应详情

To a solution of tert-butyl 3-(4-(2,5-difluoro-4-(1-(4-fluorophenylcarbamoyl)cyclopropanecarboxamido)phenoxy)pyridin-2-ylcarbamoyl)azetidine-1-carboxylate (220 mg, 0.35 mmol) in CH2Cl2 (4 mL) was added TFA (0.2 mL) at 0° C. and the reaction was stirred at room temperature overnight. Saturated NaHCO3 solution was added drop wise until pH>7 and the mixture with extracted with CH2Cl2 (2×50 mL). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The residue was purified by HPLC separation to give N-(4-(2-(azetidine-3-carboxamido)pyridin-4-yloxy)-2,5-difluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (16 mg, yield 8.7%). 1H-NMR (400 MHz, MeOH-d4): δ 9.50 (s), 8.46 (d, J=7.2 Hz, 1H), 8.33 (dd, J=7.2 Hz, 12.4 Hz, 1H), 7.53-7.43 (m, 3H), 7.26 (dd, J=7.2 Hz, 2.4 Hz, 1H), 7.10 (t, J=8.4 Hz, 2H), 6.75 (d, J=2.4 Hz, 1H), 4.61-4.54 (m, 1H), 3.63-3.58 (m, 1H), 3.49-3.44 (m, 1H), 3.31-3.29 (m, 1H), 3.27-3.25 (m, 1H), 1.75-1.73 (m, 4H); MS (ESI): m/z 443.2 [M+H]+.

1. extractionthe mixture with extracted with CH2Cl2 (2×50 mL)
2. washThe combined organic layers were washed with brine
3. dry with materialdried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated under reduced pressure
6. customThe residue was purified by HPLC separation