Method for synthesizing indapamide

Abstract

The invention discloses a method for preparing indapamide from chloro-1,3-dimethyl-2-climiqualine as a condensing agent, comprising the following concrete steps of: under the action of a condensing agent of chloro-1,3-dimethyl-2-climiqualine and organic base, reacting 4-chloro-3-sulfamoylbenzoic acid with N-amido-2-methylene indoline or corresponding salts thereof in inert solvent at room temperature and carrying out purification treatment to obtain a target product of the indapamide, wherein the corresponding salts of the 4-chloro-3-sulfamoylbenzoic acid and the N-amido-2-methylene indoline are hydrochloride, hydrobromide, mesylate or paraaminomethyl benzene sulfonate. The invention has the advantages of high yield in the technological process, low cost and simple and convenient operation, and can meet the requirement of large-scale production.

Description

technical field

[0001] The invention belongs to the field of pharmaceutical and chemical product production, in particular to a method for synthesizing diuretic and antihypertensive drug indapamide. Background technique

[0002] The chemical name of Indapamide is 4-chloro-3-sulfamoyl-N-(2,3-dihydro-2-methyl-1H-indol-1-yl)benzamide, which is Diuretic and antihypertensive drugs are mainly used clinically for patients with mild to moderate hypertension, and have the characteristics of strong drug efficacy and small adverse reactions.

[0003] The structural formula of indapamide:

[0004]

[0005] As an existing preparation method, in U.S. Patent (US 5101040, US 5110946), it is introduced that under the action of triethylamine, 4-chloro-3-sulfamoylbenzoyl chloride and N-amino-2-methylindole In the process of preparing indapamide by reaction of phylloline salt, the reaction yield is 80.5%. Due to the poor stability of 4-chloro-3-sulfamoylbenzoyl chloride, the reaction yiel...

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