Pyridine → HCID 20071725, compound

Participants

Reaction Steps

Acetazolamide (50 g) was stirred and heated at reflux in 500 ml 3N hydrochloric acid for half an hour. The cooled solution was made basic with 50% sodium hydroxide. The precipitated white solid 5-amino-1,3,4-thiadiazole-2-sulfonamide was collected (Compound 1, 28 g). It was dried further at 70° C. in a vacuum oven overnight. To a mixture of Compound 1 (4.5 g, 0.025 mole) and pyridine (2.42 ml, 0.03 mole) in 70 ml acetonitrile was added acetylsalicyloyl chloride (98%, 5 g, 0.025 mole). The reaction mixture warmed and became a clear solution. Solid deposits occurred slowly after stirring at room temperature for 1/2 hour. After two hours the solvent was evaporated; the residue was triturated with isopropyl alcohol/water for two hours and then filtered, rinsed in succession with isopropyl alcohol/water, isopropyl alcohol/isopropyl ether, 2×isopropyl ether. From the combined mother liquor and rinsings, a second crop was collected. Both the first and second crops were combined and dissolved in 50 ml N-methyl-2-pyrrolidone. The solution was filtered and the filtrate was treated with 15 ml 3N hydrochloric acid at 70° C. for half an hour. Upon dilution with 200 ml water, a white solid precipitated. The solid was collected, rinsed with water, and dried in a vacuum over at 80° C. overnight to 4.4 g of title compound, mp>250° C.

Provenance & Evidence