Formaldehyde → 4-(4-chloro-2-(3-(dimethylamino)benzo[d]isoxazol-5-yl)phenoxy)-N-(2,4-dimethoxybenzyl)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide

Participants

Reaction Steps

To a mixture of 4-(2-(3-aminobenzo[d]isoxazol-5-yl)-4-chlorophenoxy)-N-(2,4-dimethoxybenzyl)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide (0.686 g, 1.0 mmol) and paraformaldehyde (0.30 g, 10.0 mmol) in acetic acid (3 mL) was added sodium cyanoborohydride (0.19 g, 3.0 mmol) and the reaction mixture was stirred at ambient temperature for 16 h. The mixture was diluted with ethyl acetate (100 mL) and 1 M aqueous sodium hydroxide (10 mL) was added. The organic phase was washed with 1 M aqueous sodium hydroxide (10 mL) and brine (10 mL), dried over anhydrous sodium sulphate, filtered and concentrated in vacuo. The residue was purified by column chromatography, eluting with a 25-100% gradient of ethyl acetate in hexanes to afford 4-(4-chloro-2-(3-(dimethylamino)benzo[d]isoxazol-5-yl)phenoxy)-N-(2,4-dimethoxybenzyl)-2,5-difluoro-N-(1,2,4-thiadiazol-5-yl)benzenesulfonamide as a beige solid 35% yield (0.25 g): MS (ES+) m/z 713.3 (M+1), 715.7 (M+1).

Provenance & Evidence