反应详情

温度

0 °C

To a solution of 3-hydroxypyridine (40 mg, 0.42 mmol) in DMF (1.2 mL) at 0° C. was added NaH (60% in mineral oil) (28 mg, 0.70 mmol). The heterogenous mixture was stirred for 10 min at 0° C., 3-(6-chloropyrazin-2-yl)-5-(2,6-difluorophenyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (Ex. 16a, 150 mg, 0.35 mmol) was added. The mixture was warmed to RT and stirred overnight. The mixture was then heated at 60° C. for 6 h. Ice was added and the mixture was extracted with EtOAc (3×) and CH2Cl2 (2×). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated. The crude was purified by silica gel chromatography, eluting with a gradient of 0-75% EtOAc in hexanes, to provide 5-(2,6-difluorophenyl)-3-(6-(pyridin-3-yloxy)pyrazin-2-yl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazole (74 mg, 0.15 mmol, 43% yield) as a white solid. MS (ESI, pos. ion) m/z: 486.0 (M+1).

1. temperatureThe mixture was warmed to RT
2. stirringstirred overnight
3. temperatureThe mixture was then heated at 60° C. for 6 h
4. additionIce was added
5. extractionthe mixture was extracted with EtOAc (3×) and CH2Cl2 (2×)
6. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe crude was purified by silica gel chromatography
10. washeluting with a gradient of 0-75% EtOAc in hexanes