反应详情

温度

-78 °C

A mixture of 3-(4-(1H-pyrazol-1-yl)benzyl)-6-bromo-2,4-dichloro-8-methylquinoline (393 mg, 0.880 mmol, Intermediate 19: step a) and (1-methyl-1H-imidazol-5-yl)(6-(trifluoromethyl)pyridin-3-yl)methanone (224 mg, 0.880 mmol, Intermediate 36: step c) in dry degassed THF (16 mL, THF was degassed with nitrogen for 1 h) was cooled to −78° C. and n-BuLi (1.6 M in hexane, 0.5 mL, 0.8 mmol) was added over 1.5 minutes. Stirring was continued at −78° C. for 10 minutes and the dry ice bath was replaced with an ice water bath. Stirring was continued for 1 hour after which the reaction mixture was quenched with saturated aqueous NH4Cl solution. EtOAc was added and the layers were separated and the aqueous mixture again extracted with EtOAc. The combined organic extracts were dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification using flash column chromatography (5% MeOH in dichloromethane) yielded the substantially pure title compound. MS (ESI) 623.2.

1. customdegassed THF (16 mL, THF was degassed with nitrogen for 1 h)
2. stirringStirring
3. waitwas continued for 1 hour
4. customafter which the reaction mixture was quenched with saturated aqueous NH4Cl solution
5. additionEtOAc was added
6. customthe layers were separated
7. extractionthe aqueous mixture again extracted with EtOAc
8. dry with materialThe combined organic extracts were dried over MgSO4
9. filtrationfiltered
10. customthe solvents were removed under reduced pressure
11. customPurification