反应详情

Methyl 2-amino-3-bromobenzoate (1.0 eq, 652 mg, 2.61 mmol) and 4-(diisopropylcarbamoyl)pyridin-3-ylboronic acid (prepared according to the procedure described in PCT patent application WO2005/105814), 1.0 eq, 600 mg, 2.61 mmol) were combined with cesium carbonate (2.0 eq, 1.699 g, 5.21 mmol) in dioxane containing 5% of water (6 ml). The mixture was degassed by bubbling nitrogen for 10 minutes. PdCl2(dppf) (0.05 eq, 95 mg) was added and the reaction stirred at reflux for 2 hours. Dioxane was evaporated, water was added and the material extracted with CH2Cl2 (3×). The combined extracts were dried over Na2SO4 and the solvents removed in vacuo. The material was purified by flash chromatography on silica gel (eluant 0.5% MeOH in CH2Cl2) to afford methyl 2-amino-3-(4-(diisopropylcarbamoyl)pyridin-3-yl)benzoate as a greenish foam (244 mg, 31% yield). LCMS (ES): >95% pure, m/z 356 [M+1]+.

1. customThe mixture was degassed
2. customby bubbling nitrogen for 10 minutes
3. temperatureat reflux for 2 hours
4. customDioxane was evaporated
5. additionwater was added
6. extractionthe material extracted with CH2Cl2 (3×)
7. dry with materialThe combined extracts were dried over Na2SO4
8. customthe solvents removed in vacuo
9. customThe material was purified by flash chromatography on silica gel (eluant 0.5% MeOH in CH2Cl2)