反应详情

A solution of N-[5-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]-2-(methyloxy)phenyl]-2,2,2-trifluoroacetamide (250 mg, 0.56 mmol) and 1M LiOH (1.30 mL, 1.39 mmol) in 10:1 THF:H2O (5 mL) was heated at 50° C. overnight. After removal of THF by rotary evaporation, the reaction mixture was redissolved in EtOAc and washed with water (25 mL) and brine (25 mL). The organic layer was dried over MgSO4. Following filtration, the solvent was removed by rotary evaporation. After high vacuum removal of the residual solvent, the crude mixture was dissolved in THF (5 mL) and to this was added thiophene-2-acetylchloride (0.10 mL, 0.84 mmol). After overnight stirring, water (0.5 mL) was added and THF removed by rotary evaporation. The reaction mixture was redissolved in DCM (25 mL) washed with saturated NaHCO3 (10 mL), water (10 mL) and brine (10 mL). Organics were dried over MgSO4, filtered and filtrate concentrated under reduced pressure to afford the desired amide (210 mg, 79%) as an off-white solid. ES-LC/MS m/z=476 [M+H]−.

1. customAfter removal of THF
2. customby rotary evaporation
3. dissolutionthe reaction mixture was redissolved in EtOAc
4. washwashed with water (25 mL) and brine (25 mL)
5. dry with materialThe organic layer was dried over MgSO4
6. filtrationfiltration
7. customthe solvent was removed by rotary evaporation
8. customAfter high vacuum removal of the residual solvent
9. dissolutionthe crude mixture was dissolved in THF (5 mL)
10. customTHF removed by rotary evaporation
11. dissolutionThe reaction mixture was redissolved in DCM (25 mL)
12. washwashed with saturated NaHCO3 (10 mL), water (10 mL) and brine (10 mL)
13. dry with materialOrganics were dried over MgSO4
14. filtrationfiltered
15. concentrationfiltrate concentrated under reduced pressure