Synthesis method of indapamide

Abstract

The present invention relates to Indapamide synthesizing process. The synthesis process includes the following steps: dissolving N-amido-2-methyl indoline hydrochloride in non-protonic organic solvent, and dropping triethylamine via stirring; the subsequent adding 4-chloro-3-sulphonylamino -benzoic acid and dewatering condensing agent and reaction at 0-20 deg.c for 2.0-20 hr to obtain coarse Indapamide product; and final refining in isopropanol-water to obtain Indapamide product. Compared with traditional process, the present invention has raised safety, less pollution and corrosion to environment and apparatus, lowered cost and raised yield.

Description

technical field [0001] The invention relates to a synthesis method of indapamide, which belongs to the technical field of medicine and chemical industry. Background technique [0002] The more common synthetic method for preparing indapamide is to use 4-chloro-3-sulfonylamino-benzoic acid as starting material, and first carry out acyl chloride with thionyl chloride to prepare 4-chloro-3-sulfonyl Aminobenzoyl chloride, followed by condensation of 4-chloro-3-sulfonamidobenzoyl chloride with 2-methylindoline hydrochloride to prepare indapamide. [0003] The current general synthetic route of indapamide is: [0004] [0005] This method has the following main disadvantages: [0006] 1. In the acyl chloride reaction, a large amount of thionyl chloride is used. Thionyl chloride is a dangerous chemical. It is easy to release a large amount of hydrogen chloride and sulfur dioxide gas when it is mixed with moist air and water, and it is violently exothermic, which is easy to cau...

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Problems solved by technology

[0006] 1. In the acyl chloride reaction, a large amount of thionyl chloride is used. Thionyl chloride is a dangerous chemical. It is easy to release a large amount of hydrogen chloride and sulfur dioxide gas when it is mixed with moist air and water, and it is violently exothermic, which is easy to cause an explosion and is harmful to The environment and equipment are highly corrosive, and the safety factor is low

[0007] 2. When 4-chloro-3-sulfonylaminobenzoyl chloride is condensed with N-amino-2-methylindoline hydrochloride, the reaction is required to be absolutely anhydrous. In order to ensure that the reagent is anhydrous, it must be used before use Metal sodium is dehydrated and distilled, so it is easy to cause safety accidents and bring inconvenience to production operations

[0008] 3. The chemical intermediate 4-chloro-3-sulfonylaminobenzoyl chloride has poor stability, is easy to decompose when wet, and is irritating. When it is dry, it will seriously corrode the equipment and is not easy to store

[0009] 4. The production cycle is long and the yield is not high

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