Cesium carbonate → ethyl 5-[2-fluoro-4-(2-methoxy-4,6-dimethylpyridin-3-yl)phenyl]-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-carboxylate

Participants

Reaction Steps

Water (5 mL), 3-bromo-2-methoxy-4,6-dimethylpyridine obtained in Preparation Example 26 (784 mg), Pd(PPh3)4 (380 mg) and cesium carbonate (2.36 g) were added to a solution of ethyl 5-[2-fluoro-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]-1-(tetrahydro-2H-pyran-4-yl)-1H-pyrazole-4-carboxylate obtained in Preparation Example 3 (2.04 g) in 1,4-dioxane (20 mL), and the reaction mixture was reacted at 110° C. for two hours in a nitrogen atmosphere. The reaction mixture was returned to room temperature and then filtered through Celite™. The filtrate was concentrated under reduced pressure. Ethyl acetate (100 mL) and water (100 mL) were added to the residue. The aqueous layer was extracted with ethyl acetate (50 mL×2). The combined organic layers were dried over anhydrous magnesium sulfate and filtered, and the filtrate was concentrated under reduced pressure. The residue was purified by NH silica gel column chromatography (ethyl acetate/n-heptane, 10% to 23%). The title compound obtained by the same method (578 mg) was combined, and the combined product was purified again by silica gel column chromatography (ethyl acetate/n-heptane, 50% to 70%) to give the title compound (2.07 g).

Provenance & Evidence