反应详情

温度

100 °C

2-(Dimethylamino)acetamide (0.100 g, 0.974 mmol), N-(4-(2-chloropyridin-4-yloxy)-2,5-difluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (0.15 g, 0.325 mmol) (as prepared in Example 1), cesium carbonate (0.159 g, 0.487 mmol), and xantphos (0.018 g, 0.032 mmol) were combined in dry dioxane (2.5 mL) and argon was bubbled through the mixture for 5 minutes. Palladium acetate (5.47 mg, 0.024 mmol) was added and the solution was degassed for an additional 5 minutes. The reaction flask was fitted with a reflux condenser and a balloon of argon and heated at 100° C. for 15 hours. The mixture was cooled to room temperature and then diluted with ethyl acetate (75 mL) and water (45 mL). The water layer was removed and extracted again with ethyl acetate (25 mL). The combined organic layers were washed with brine (50 mL) and dried over magnesium sulfate. Evaporation of the solvent yielded a lavender-colored oil which was purified by silica gel chromatography (0 to 7% methanol in dichloromethane) to give N-(4-(2-(2-(dimethylamino)acetamido)pyridin-4-yloxy)-2,5-difluorophenyl)-N′-(4-fluorophenyl)cyclopropane-1,1-dicarboxamide (0.0823 g, 48% yield). 1H NMR (400 MHz, DMSO-d6): δ 11.02 (s, 1H), 9.97 (s, 1H), 9.79 (s, 1H), 8.20 (d, 1H), 8.09 (dd, 1H), 7.65 (d, 1H), 7.57 (m, 3H), 7.16 (m, 2H), 6.76 (dd, 1H), 3.06 (s, 2H), 2.25 (s, 6H), 1.63 (m, 2H), 1.57 (m, 2H); MS (ESI) ink: 528.2 (M+H+).

1. customargon was bubbled through the mixture for 5 minutes
2. customthe solution was degassed for an additional 5 minutes
3. customThe reaction flask was fitted with a reflux condenser
4. temperatureThe mixture was cooled to room temperature
5. additiondiluted with ethyl acetate (75 mL) and water (45 mL)
6. customThe water layer was removed
7. extractionextracted again with ethyl acetate (25 mL)
8. washThe combined organic layers were washed with brine (50 mL)
9. dry with materialdried over magnesium sulfate
10. customEvaporation of the solvent
11. customyielded a lavender-colored oil which
12. customwas purified by silica gel chromatography (0 to 7% methanol in dichloromethane)