反应详情

温度

80 °C

To a solution of [(3S,4R)-4-(4-chloro-phenyl)-1-(piperidine-4-carbonyl)-pyrrolidin-3-yl]-methyl-carbamic acid 4-fluoro-phenyl ester (186 mg, 0.40 mmol) in DMF (2 mL) was added 6-chloro-3-pyridazinecarbonitrile (67 mg, 0.48 mmol) and N,N-diisopropyl ethyl amine (208, 1.21 mmol). The resulting dark brown solution was stirred for 3 h at 80° C. After cooling to ambient temperature the reaction mixture was diluted with ethyl acetate (15 mL) and washed with aqueous sodium carbonate (1M, 15 mL), water (15 mL) and brine (15 mL). The aqueous layers were extracted with ethyl acetate (15 mL) and the combined organic layers dried over sodium sulfate. Concentration and purification by chromatography (SiO2, heptane:ethyl acetate=50:50 to 0:100) afforded the title compound (167 mg, 73%) as a white foam. MS m/e: 563.3 [M]+.

1. temperatureAfter cooling to ambient temperature the reaction mixture
2. washwashed with aqueous sodium carbonate (1M, 15 mL), water (15 mL) and brine (15 mL)
3. extractionThe aqueous layers were extracted with ethyl acetate (15 mL)
4. dry with materialthe combined organic layers dried over sodium sulfate
5. concentrationConcentration and purification by chromatography (SiO2, heptane:ethyl acetate=50:50 to 0:100)