Synthesis process of nizofenone fumarate

Abstract

The invention belongs to the field of medical technology, and discloses a synthesis process line of an ischemic brain dysfunction improving medicine nizofenone fumarate. The synthesis process comprises the following steps: by adopting paranitroaniline as a start raw material, performing an amidation reaction, a Friedel-Crafts acylation reaction, a hydrolysis reaction, a diazotization reaction and a Sandmeyer reaction to obtain an important intermediate 2'-chloro-2-chloro-5-nitrobenzophenone (4); by adopting imidazole as a start raw material, performing N-benzyl protection, a hydroxymethylation reaction, a chlorination reaction, an amination reaction and a transfer hydrogenation debenzylation reaction to obtain another important intermediate 2-(diethylaminomethyl)imidazole (11); catalyzing the two intermediates with sodium hydride to obtain nizofenone; salifying with fumaric acid to generate a target compound.

Description

technical field [0001] The invention belongs to the technical field of medicine, and relates to a new synthesis process of nizophenone fumarate, a medicine for improving ischemic brain disorder. Background technique [0002] Nizophenone fumarate is a salt-forming product of compound 2ˊ-chloro-2-(2-diethylaminomethyl-1-imidazolyl)-5-nitrobenzophenone and fumaric acid, produced by Japan Jifu Developed by pharmaceutical companies. This product can protect brain tissue under ischemia and hypoxia, prolong the lifespan of nerve cells, and has the effect of treating brain trauma and promoting the recovery of nerve function, reducing the occurrence of complications caused by subarachnoid hemorrhage, and has the effect on cerebrovascular Spasm complications have a good curative effect, and it is a good neuroprotective agent. [0003] Patent US3,915,981 reports the synthesis route of nizophenone fumarate: 2-(2-chlorobenzyl)-4 -Nitroaniline, and then 3-(2-chlorobenzyl)-4-chloronitro...

AI Technical Summary

Problems solved by technology

In this route, bimolecular alkylation may occur in the Friedel-Crafts alkylation reaction step; the benzylic carbonyl group is introduced by the Jones oxidation reaction, and the reaction selectivity of this step may be poor, and the electron-rich imidazole ring or imidazole ring side chain All may be oxidized, and chromium trioxide is used as the oxidant in the reaction. The chromium compound is a heavy metal compound, which is highly toxic and pollutes the environment. At the same time, it also has certain dangers in use and operation.

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