反应详情

温度

60 °C

6-Bromo-5-(2,4-difluorophenoxy)-1-(2-fluoro-2-methylpropyl)-1H-indazole (1.64 g, 4.11 mmol) was dissolved in 9:1 methanol/water degassed with carbon monoxide (27 mL). To this was added 1-((3-(diphenylphosphino)propyl)(phenyl)phosphino)benzene (85 mg, 0.21 mmol), palladium (II) acetate (46 mg, 0.21 mmol), and potassium carbonate (1.70 g, 12.3 mmol). The reaction mixture was heated to 60° C. for 20 hours. The reaction mixture was then acidified to pH 1 by the addition of 5M hydrochloric acid, and the crude reaction mixture was partitioned between ether and water. The aqueous layer was extracted with ether, and the combined organic layers were washed with brine. The combined organic layers were dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified on a silica gel column, eluting with a gradient of 0.2-10% methanol/dichloromethane to yield 5-(2,4-difluorophenoxy)-1-(2-fluoro-2-methylpropyl)-1H-indazole-6-carboxylic acid (7a) (724 mg, 48%).

1. customdegassed with carbon monoxide (27 mL)
2. customthe crude reaction mixture
3. customwas partitioned between ether and water
4. extractionThe aqueous layer was extracted with ether
5. washthe combined organic layers were washed with brine
6. dry with materialThe combined organic layers were dried over anhydrous sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated
9. customThe crude product was purified on a silica gel column
10. washeluting with a gradient of 0.2-10% methanol/dichloromethane