反应详情

温度

80 °C

To a stirred solution of 3-[(2-chloro-4-pyrimidinyl)acetyl]-N-(2,6-difluorophenyl)-benzamide (Intermediate Example 1, step B) (0.4 g, 1.03 mmol) in DCM (10 mL) at rt under N2 was added NBS (0.193 g, 1.09 mmol). The reaction was stirred approximately 30 min, then concentrated under vacuum to a foam like solid. The solid was dissolved in dioxane (10 mL) and 4-(trifluoromethyl)-2-pyridinamine (0.5 g, 3.10 mmol) was added. The reaction was stirred under nitrogen, heated to 80° C., and stirred for approximately 48 h, then cooled to rt. The reaction was diluted with EtOAc and half-saturated aqueous NaHCO3. The organic layer was separated and washed brine. The combined aqueous layers were extracted with EtOAc (3×). The combined organic layers were dried over MgSO4, filtered, and concentrated under vacuum. The residue was purified by silica gel chromatography to give a yellow solid. The solid was dissolved in minimal DCM and hexane was added until a precipitate formed. The slurry was filtered, washing the solids with cold hexane. The solids were dried under vacuum, however proton NMR indicates impurities so the solid was dissolved in minimal DCM and ether was added until a precipitate formed. The slurry was filtered, washing the solids with cold ether. The solids were dried under vacuum to give the title compound of step A (0.250 g, 0.47 mmol, 46%) as a white solid. MS (ESI): 530 [M+H]+.

1. concentrationconcentrated under vacuum to a foam like solid
2. dissolutionThe solid was dissolved in dioxane (10 mL)
3. stirringThe reaction was stirred under nitrogen
4. stirringstirred for approximately 48 h
5. temperaturecooled to rt
6. customThe organic layer was separated
7. washwashed brine
8. extractionThe combined aqueous layers were extracted with EtOAc (3×)
9. dry with materialThe combined organic layers were dried over MgSO4
10. filtrationfiltered
11. concentrationconcentrated under vacuum
12. customThe residue was purified by silica gel chromatography
13. customto give a yellow solid
14. customformed
15. filtrationThe slurry was filtered
16. washwashing the solids with cold hexane
17. customThe solids were dried under vacuum, however proton NMR
18. dissolutionwas dissolved in minimal DCM
19. additionether was added until a precipitate
20. customformed
21. filtrationThe slurry was filtered
22. washwashing the solids with cold ether
23. customThe solids were dried under vacuum