Dichloromethane → N-((R)-1-{5-[5-Chloro-3-fluoro-2-(5-methyl-[1,2,4]oxadiazol-3-yl)-phenyl]-3-fluoro-pyridin-2-yl}-ethyl)-acetamide

Participants

Reaction Conditions

Reaction Steps

A stream of argon was bubbled through a mixture of N—[(R)-1-(5-bromo-3-fluoro-pyridin-2-yl)-ethyl]-acetamide (200 mg, 0.766 mmol, intermediate 12) potassium acetate (226 mg, 2.3 mmol) and bis(pinacolato)diboron (253 mg, 0.996 mmol) in DMSO (1.5 ml) in a sealed tube for 10 min. Then [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride 1:1 complex with DCM (31.3 mg, 0.0383 mmol) was added and again a stream of argon was bubbled through the reaction mixture for 10 min. The tube was then sealed and heated to 90° C. for 1.5 h. After cooling to room temperature, potassium carbonate (212 mg, 1.53 mmol), water (198 μl), 3-(2-bromo-4-chloro-6-fluoro-phenyl)-5-methyl-[1,2,4]oxadiazole (246 mg, 0.843 mmol, intermediate 10) and additional [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) chloride 1:1 complex with DCM (31.3 mg, 0.0383 mmol) were added and the reaction mixture was heated to 80° C. for 3 h. The mixture was cooled to room temperature, diluted with water and extracted three times with EtOAc. The combined organic layers were washed two times with water and brine, dried with Na2SO4 and evaporated. The remaining brown gum was purified by chromatography (silica gel; heptane/EtOAc 35:65-10:90) and the title compound was obtained as off white foam (200 mg, 66%). MS: 393.1 [M+H]+.

Provenance & Evidence