反应详情

温度

-78 °C

A solution of N-[3-methyl-5-(1,3-thiazol-5-yl)phenyl]-4-(trifluoromethyl)pyrimidin-2-amine (Intermediate 4, 1.50 g, 4.46 mmol) in THF (10 mL) was added dropwise to a solution of lithium diisopropylamide (7.43 ml, 13.38 mmol) in THF (15 mL) at −78° C. and the resulting mixture was stirred at −78° C. for 30 minutes. Tetrahydrothiopyran-4-one (0.57 g, 4.91 mmol) in THF (5 mL) was then added, the dry ice bath was removed and the reaction was allowed to warm to room temperature. The reaction was quenched with aqueous saturated NH4Cl solution, and extracted with EtOAc (2×). The combined organic layers were washed with brine, dried (MgSO4), filtered and evaporated. Flash chromatography (SiO2, gradient elution 0 to 30% EtOAc in toluene) afforded 4-[5-(3-methyl-5-{[4-(trifluoromethyl)pyrimidin-2-yl]amino}-phenyl)-1,3-thiazol-2-yl]tetrahydro-2H-thiopyran-4-ol (1.21 g, 2.67 mmol, 60% yield) as a yellow foam. MS ESI: [M+H]+ m/z 453.0.

1. customthe dry ice bath was removed
2. temperatureto warm to room temperature
3. customThe reaction was quenched with aqueous saturated NH4Cl solution
4. extractionextracted with EtOAc (2×)
5. washThe combined organic layers were washed with brine
6. dry with materialdried (MgSO4)
7. filtrationfiltered
8. customevaporated
9. washFlash chromatography (SiO2, gradient elution 0 to 30% EtOAc in toluene)