Potassium Phosphate, Tribasic → Methyl 3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzoate

Participants

Reaction Conditions

Reaction Steps

5-chloro-1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridine 2,2-dioxide (29-1) (6.6 g, 21.3 mmol, 1.0 eq), methyl 4-methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzoate (8.8 g, 32.0 mmol, 1.5 eq), tripotassium phosphate (9.0 g, 42.6 mmol, 2.0 eq), S-Phos (875 mg, 2.1 mmol, 0.1 eq), and palladium(II) acetate (239 mg, 1.1 mmol, 0.05 eq) were combined in THF (90 mL) and water (15 mL). The resulting mixture was heated at 75° C. for 14 hours. The reaction mixture was allowed to cool to room temperature. The mixture was then diluted with EtOAc (300 mL), washed with water (100 mL) and brine (100 mL), dried over MgSO4, filtered and concentrated. The crude residue was purified by flash chromatography (330 g SiO2, 0-60% EtOAc in hexanes) to afford methyl 3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-4-methylbenzoate (38-1) as a yellow solid. HRMS m/z (M+H) 424.1135 found, 424.1137 required.

Provenance & Evidence