Acetyl chloride → tert-butyl acetyl(5-(5-chloro-2-(4-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-2,5-difluorophenoxy)phenyl)benzo[d]isoxazol-3-yl)carbamate

Participants

Reaction Steps

A solution of tert-butyl (5-(5-chloro-2-(4-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-2,5-difluorophenoxy)phenyl)benzo[d]isoxazol-3-yl)carbamate (0.20 g, 0.25 mmol), triethylamine (105 μL, 0.75 mmol) and 4-(dimethylamino)pyridine (0.030 g, 0.25 mmol) in dichloromethane (20 mL) at 0° C. was treated with acetyl chloride (36 μL, 0.5 mmol). The resulting solution was stirred for 1 h. The reaction mixture was diluted with ethyl acetate (70 mL), washed with saturated ammonium chloride (2×50 mL) and brine (50 mL), dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by reverse phase HPLC to afford tert-butyl acetyl(5-(5-chloro-2-(4-(N-(2,4-dimethoxybenzyl)-N-(1,2,4-thiadiazol-5-yl)sulfamoyl)-2,5-difluorophenoxy)phenyl)benzo[d]isoxazol-3-yl)carbamate as a colourless solid in 35% yield (0.05 g): 1H NMR (300 MHz, CDCl3) δ 8.15 (s, 1H), 7.68-7.63 (, m, 1H), 7.63-7.58 (m, 1H), 7.56-7.54 (m, 1H), 7.50-7.45 (m, 2H), 7.42-7.38 (m, 1H), 7.15-7.10 (m, 1H), 7.03-6.99 (m, 1H), 6.33-6.25 (m, 2H),6.19-6.17 (m, 1H), 3.72 (s, 3H), 3.63 (s, 3H), 2.67 (s, 3H), 1.31 (s, 9H); MS (ES+) m/z 727.5 (M−100), 729.7 (M−100).

Provenance & Evidence