Preparation method of non-chlorine gas of acetazolamide key intermediate 2-acetamido-5-chlorosulfonyl-1, 3, 4-thiadiazole

Abstract

The invention discloses a preparation method of non-chlorine gas of acetazolamide key intermediate 2-acetamido-5-chlorosulfonyl-1, 3, 4-thiadiazole. The preparation method comprises the steps of firstly adding hydrochloric acid into a reactor and then dropwise adding hydrogen peroxide to perform reaction so as to obtain a reaction solution; adding 2-acetamido-5-sulfydryl-1, 3, 4-thiadiazole into the obtained reaction solution in batch to perform reaction and obtaining a reactant after reaction is completed; directly conducting suction filtration, washing and drying on the reactant and performing drying to obtain the intermediate 2-acetamido-5-chlorosulfonyl-1, 3, 4-thiadiazole. The preparation method is more moderate in operate and more environment-friendly, and the obtained intermediate 2-acetamido-5-chlorosulfonyl-1, 3, 4-thiadiazole is good in color and luster and high in purity.

Description

technical field

[0001] The invention relates to a preparation method of a pharmaceutical intermediate, belonging to the field of medicinal chemistry, in particular to a non-chlorine gas of acetazolamide key intermediate 2-acetylamino-5-chlorosulfonyl-1,3,4-thiadiazole Preparation. Background technique

[0002] Acetazolamide was first synthesized in 1950 by Roblin and Clapp (Roblin, R.O.Jr&Clapp.J.W: J.Amer. Chem.Soc., 1950,72,4890), 2-amino-5-mercapto-1,3,4- Thiadiazole first reacts with acetic anhydride to obtain 2-acetylamino-5-mercapto-1,3,4-thiadiazole, and then obtains 2-acetylamino-5-chlorosulfonyl-1,3, 4-Thiadiazole, finally ammoniated with ammonia to obtain acetazolamide. In 1955, the patent of Span et al. (US222209) also disclosed the same method for preparing acetazolamide. This method has been used until now, but the biggest disadvantage of this method is the preparation of 2-acetylamino-5-chlorosulfonyl-1,3,4-thiadiazole by the chlorine gas method. Chlorine ga...