3-Bromo-6-methoxy-2,4-dimethylpyridine → ethyl 5-(2,5-difluoro-4-(6-methoxy-2,4-dimethylpyridin-3-yl)phenyl)-1-[(S)-tetrahydrofuran-3-yl]-1H-pyrazole-4-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixture of ethyl 5-[2,5-difluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-[(S)-tetrahydrofuran-3-yl]-1H-pyrazole-4-carboxylate synthesized in accordance with Example 53 (430 mg), 3-bromo-6-methoxy-2,4-dimethylpyridine obtained in Preparation Example 23 (223 mg), potassium hydrogen fluoride (254 mg), Pd(PPh3)4 (90 mg) and tripotassium phosphate n-hydrate (400 mg) in DME (8 mL) and water (2 mL) was heated under reflux at 110° C. for seven hours. The reaction mixture was cooled to room temperature and partitioned by adding ethyl acetate and brine. The organic layer was dried over anhydrous magnesium sulfate and filtered. The filtrate was concentrated, and the residue was purified by NH silica gel column chromatography (ethyl acetate/n-heptane: 16% to 37% to 46%) and silica gel column chromatography (ethyl acetate/n-heptane: 28% to 49% to 54%) to give the title compound (144 mg). This compound was used for the next reaction without further purification.

Provenance & Evidence