反应详情

温度

80 °C

A mixture of 6-bromo-1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid 4-methylsulfamoyl-benzylamide (0.1 g, 0.2 mmol), bis(pinacolato)diboron (0.1 g, 0.4 mmol), PdCl2(dppf) (0.04 g, 0.05 mmol), potassium acetate (0.05 g, 0.5 mmol) was charged in a sealed tube with anhydrous THF (7 mL). The solution was warmed at 80° C. for 16 hours. The reaction mixture was cooled to room temperature and quenched with water (15 mL) and diluted with CH2Cl2 (20 mL). The organic layer was separated and washed with brine (10 mL) and dried over sodium sulfate. The solvent was removed in vacuo. The residue was dissolved in THF (10 mL), and a solution of 30% H2O2 in water (0.15 mL, 0.5 mmol) and NaOH (0.01 g, 0.3 mmol) were added. The mixture was stirred at 10° C. for 3 hours and then quenched with water (10 mL) and diluted with CH2Cl2 (20 mL). The organic layer was washed with brine (10 mL) and dried over sodium sulfate. The solvent was removed in vacuo. The residue was purified by reversed-phase HPLC, eluting with a gradient of 5-100% CH3CN in water. The desired fractions were combined and diluted with saturated aqueous NaHCO3 (20 mL) and ethyl acetate (20 mL). The organic layer was separated, dried over sodium sulfate and concentrated to afford the title compound.

1. temperatureThe reaction mixture was cooled to room temperature
2. customquenched with water (15 mL)
3. additiondiluted with CH2Cl2 (20 mL)
4. customThe organic layer was separated
5. washwashed with brine (10 mL)
6. dry with materialdried over sodium sulfate
7. customThe solvent was removed in vacuo
8. dissolutionThe residue was dissolved in THF (10 mL)
9. customquenched with water (10 mL)
10. additiondiluted with CH2Cl2 (20 mL)
11. washThe organic layer was washed with brine (10 mL)
12. dry with materialdried over sodium sulfate
13. customThe solvent was removed in vacuo
14. customThe residue was purified by reversed-phase HPLC
15. washeluting with a gradient of 5-100% CH3CN in water
16. additiondiluted with saturated aqueous NaHCO3 (20 mL) and ethyl acetate (20 mL)
17. customThe organic layer was separated
18. dry with materialdried over sodium sulfate
19. concentrationconcentrated