反应详情

A solution of n-BuLi (2.5 M in hexanes, 1.25 mL. 3.12 mmol) was added dropwise by syringe to a solution of 4-((6-bromo-4-chloro-2-methoxyquinolin-3-yl)methyl)benzonitrile (1.211 g, 3.125 mmol, Intermediate 8: step d) in dry THF (15 mL) in a dry ice-acetone bath. After 1-2 minutes, a solution of 4-formylbenzonitrile (498.8 mg, 3.804 mmol) in dry THF (2 mL) was added dropwise. The reaction was stirred for 5 minutes and then removed from the cold bath and allowed to warm to room temperature. The reaction was quenched with saturated aqueous ammonium chloride. The mixture was partitioned between water and dichloromethane. The separated aqueous phase was further extracted with dichloromethane. The combined organic phase was dried (Na2SO4), filtered, and concentrated. Crude product was purified by flash column chromatography (silica gel, 100% EtOAc, followed by 0-5% MeOH-DCM), to provide the title compound. 1H NMR (500 MHz, CDCl3) δ 8.13-8.11 (m, 1H), 7.79 (d, J=8.6 Hz, 1H), 7.63-7.59 (m, 2H), 7.56-7.51 (m, 5H), 7.38-7.34 (m, 2H), 6.03 (d, J=3.2 Hz, 1H), 4.33 (s, 2H), 4.05 (s, 3H); MS m/e 440.0 [M+H]+.

1. customremoved from the cold bath
2. customThe reaction was quenched with saturated aqueous ammonium chloride
3. customThe mixture was partitioned between water and dichloromethane
4. extractionThe separated aqueous phase was further extracted with dichloromethane
5. dry with materialThe combined organic phase was dried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated
8. customCrude product was purified by flash column chromatography (silica gel, 100% EtOAc, followed by 0-5% MeOH-DCM)