反应详情

The 4-chloro-5,7-difluoro-3-methyl-2-(piperazin-1-yl)quinoline 2,2,2-trifluoroacetate (75 mg, 0.18 mmol), triethylamine (0.025 mL, 0.18 mmol) and cyclohexanone (0.019 mL, 0.18 mmol) were added to 3 mL of a 2:1 dichlorethane/MeOH mixture. The sodium triacetoxyborohydride (120 mg, 0.55 mmol) was added and the slurry was stirred at rt for 4.5 h. Sodium cyanoborohydride (55 mg, 0.87 mmol) was then added and the slurry was stirred at rt for 4.5 h. Another aliquot of sodium cyanoborohydride (55 mg, 0.87 mmol) was added and the reaction was heated to 80° C. and stirred overnight. The reaction was cooled and then diluted with DCM and water. The layers were separated and the aq. layer was extracted (2×75 mL) with EtOAc. The layers were combined and washed with brine (1×50 mL) and dried over magnesium sulfate. The crude product was purified by medium pressure chromatography (silica gel, 0 to 100% EtOAc:hexanes) to give 4-chloro-2-(4-cyclohexylpiperazin-1-yl)-5,7-difluoro-3-methylquinoline. Mass Spectrum (ESI) m/e=298.1 (M+1).

1. stirringthe slurry was stirred at rt for 4.5 h
2. temperaturethe reaction was heated to 80° C.
3. stirringstirred overnight
4. temperatureThe reaction was cooled
5. customThe layers were separated
6. extractionthe aq. layer was extracted (2×75 mL) with EtOAc
7. washwashed with brine (1×50 mL)
8. dry with materialdried over magnesium sulfate
9. customThe crude product was purified by medium pressure chromatography (silica gel, 0 to 100% EtOAc:hexanes)