反应详情

温度

75 °C

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) (2.2 g, 7.1 mmol, 1.0 eq), [3-(ethoxycarbonyl)-2-fluorophenyl]boronic acid (3.0 g, 14 mmol, 2.0 eq), tripotassium phosphate (3.0 g, 14.2 mmol, 2.0 eq), S-Phos (0.29 g, 0.71 mmol, 0.1 eq), and palladium(II) acetate (0.080 mg, 0.36 mmol, 0.05 eq) were combined in THF (15 mL) and water (2 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 (100 mL), washed with water (10 mL) and brine (10 mL), dried over MgSO4, filtered and concentrated. The crude residue was purified by flash chromatography (120 g SiO2, 0-60% EtOAc in hexanes) to afford ethyl 3-{1-[(2,2-difluorocyclopropyl)methyl]-3-methyl-2,2-dioxido-1,3-dihydro[1,2,5]thiadiazolo[3,4-b]pyridin-5-yl}-2-fluorobenzoate (37-1) as a yellow solid. LRMS m/z (M+H) 442.2 found, 442.1 required.

1. temperatureto cool to room temperature
2. washwashed with water (10 mL) and brine (10 mL)
3. dry with materialdried over MgSO4
4. filtrationfiltered
5. concentrationconcentrated
6. customThe crude residue was purified by flash chromatography (120 g SiO2, 0-60% EtOAc in hexanes)