反应详情

Into a 25-mL round-bottom flask purged and maintained with an inert atmosphere of nitrogen, was placed a solution of 3-benzyl-6-bromo-2,4-dichloroquinoline (500 mg, 1.36 mmol, Intermediate 2: step c) in tetrahydrofuran (10 mL). n-BuLi (0.6 mL, 2.5 M in hexanes) was then added at −78° C. The resulting solution was stirred for 1 hour at −78° C. (4-Chlorophenyl)(1-methyl-1H-imidazol-5-yl)methanone (301 mg, 1.36 mmol, Intermediate 1: step b) was added to this solution. The resulting solution was allowed to react, with stirring, for an additional 8 hours at room temperature. The reaction was then quenched by the addition of 10 mL of water/ice. The resulting solution was extracted with 3×20 mL of ethyl acetate. The combined organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under vacuum. The residue was purified by chromatography over a silica gel column with dichloromethane/methanol to give the title compound as a white solid. 1H NMR (400 MHz, DMSO-d6) δ=8.20 (s, 1H), 8.01 (d, J=8.5 Hz, 1H), 7.69-7.79 (m, 2H), 7.44 (d, J=7.5 Hz, 2H), 7.25-7.37 (m, 4H), 7.14-7.25 (m, 4H), 6.20 (s, 1H), 4.47 (s, 2H), 3.31 (s, 3H); MS m/e 508 [M+H]+.

1. customInto a 25-mL round-bottom flask purged
2. temperaturemaintained with an inert atmosphere of nitrogen
3. additionwas added to this solution
4. customto react
5. customThe reaction was then quenched by the addition of 10 mL of water/ice
6. extractionThe resulting solution was extracted with 3×20 mL of ethyl acetate
7. dry with materialThe combined organic layer was dried over anhydrous sodium sulfate
8. filtrationfiltered
9. concentrationconcentrated under vacuum
10. customThe residue was purified by chromatography over a silica gel column with dichloromethane/methanol