flumethiazide

Originator

Ademol,Squibb,US,1959

Definition

ChEBI: Flumethiazide is a benzothiadiazine.

Manufacturing Process

Chilled 3-trifluoromethylaniline (32.2 g) is added dropwise over a 45-minute period to 150 ml of chlorosulfonic acid with stirring and cooling. The ice bath is removed and 140 g of sodium chloride is added over 3 hours. The mixture is heated on a water bath for 30 minutes, then gradually up to 160°C over 6 hours. The cooled reaction mixture is diluted with 500 ml of an ice water slurry and taken into ether. The ether is dried and evaporated to leave 5- trifluoromethylamine-2,4-disulfonyl chloride.
The crude residue is heated on the steam bath for 1 hour with 75 ml of concentrated ammonium hydroxide. Cooling and filtration gives 2,4- disulfamyl-5-trifluoromethylaniline, MP 241°C to 243°C.
This intermediate is treated with an excess of 98% formic acid at steam bath temperature for 3 hours. Evaporation and dilution with water gives 7-sulfamyl- 6-trifluoromethyl-1,2,4-benzothiadiazine-1,1-dioxide, MP 304°C to 308°C.

Therapeutic Function

Carbonic anhydrase inhibitor