Synthesis method of cinepazide maleate

Abstract

The invention relates to a method to synthesize maleic acid cinepazide. (2) reacts with 3,4,5- cinnamyl chloride, aquiring free alkali of cinepazide, the solvent is chosen from 5, add 6 and acquire the (7), the method for separating (1) is filtration. The invention uses safe solvent in the synthesis of (2), and the method of filtration and 8, making it suitable for industrialized production. The method uses the solvent with low toxicity and good safety, simplized productive condition and course, has high productivity and low cost.

Description

Technical field: [0001] The invention relates to a synthesis method of cinepazide maleate. Background technique: [0002] Cinepazide maleate is a peripheral vasodilator, clinically used for the treatment of cardiovascular and cerebrovascular diseases. Its English name is Cinepazide Maleate, and its chemical name is: trans-{(1-pyrrolidinecarbonyl)methyl}-4-(3,4,5-trimethoxycinnamoyl)-piperazinemaleate. [0003] The chemical structural formula (I) of cinepazide maleate is as follows: [0004] [0005] The synthetic route of cinepazide maleate reported in Patent Document 1 (C.P.Fauran et al: US 3634411) is shown in Synthetic Route 1: with trans-3,4,5-trimethoxycinnamoyl chloride (II) and 1-piperazine acetylpyrrolidine (III) is used as a starting material, anhydrous benzene is used as a solvent, and sodium bicarbonate is used as an acid absorbing agent to carry out condensation reaction to obtain cinepazide, which is then salted with maleic acid. [0006] [0007] The s...

AI Technical Summary

Problems solved by technology

Ether is known to have a very low boiling point and is very flammable;

[0014] The 3rd, when intermediate (III) is synthesized according to the method of literature (2,3), two vacuum distillations are needed in the process of product extraction and purification, which has higher requirements on production conditions and equipment, which is unfavorable for industrial production;

[0015] Fourth, because piperazine is very easy to crystallize during the distillation operation, the crystals are attached to the wall of the condenser tube, and the condenser tube is blocked, which brings great inconvenience to continued distillation and processing;

[0016] Fifth, in the whole production process of cinepazide maleate, the cost of raw material pyrrolidine (tetrahydropyrrole) is the highest

According to literature (2,3) method, can't reclaim excessive tetrahydropyrrole, so production cost is higher

Images