Tert-butyl cis-(3-carbamoylcyclohexyl)carbamate → tert-butyl N-[(1R,3S)-3-[[4-(5,5-dimethyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyridin-3-yl)-5-fluoro-2-pyridinyl]carbamoyl]cyclohexyl]carbamate

参与物

反应条件

反应步骤

Tetrakis(triphenylphosphine)palladium(0) (0.496 g, 0.43 mmol) was added to 3-(2-chloro-5-fluoropyridin-4-yl)-5,5-dimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridine (1.2g, 4.29 mmol), tert-butyl ((1R,3S)-3-carbamoylcyclohexyl)carbamate (1.039 g, 4.29 mmol) and 9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.496 g, 0.86 mmol) and Cesium carbonate (4.19 g, 12.87 mmol) in 1,4-dioxane (10 mL)Degassed for 5 mins under nitrogen and the resulting suspension was stirred at 120 °C for 17 hours in the microwave reactor. The reaction mixture was partitioned between water (20ml) and ethyl acetate (100ml) filtered and separated. The organics were absorbed onto silica and purified by flash silica chromatography, elution gradient 1:1 EtOAc in heptane. Pure fractions were evaporated to dryness to afford tert-butyl ((1R,3S)-3-((4-(5,5-dimethyl-4,5,6,7-tetrahydropyrazolo[1,5-a]pyridin-3-yl)-5-fluoropyridin-2-yl)carbamoyl)cyclohexyl)carbamate (1.100 g, 52.8 %) as a white solid.

来源与证据