Synthesis process of nizofenone fumarate

A technology of nizophenone fumarate and process, which is applied in the field of medicine, and can solve problems such as polluting the environment, poor selectivity, and high toxicity

Inactive Publication Date: 2014-03-05
SHENYANG PHARMA UNIVERSITY +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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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 imi...

Method used

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  • Synthesis process of nizofenone fumarate

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Embodiment 1

[0020] Illustrate with respect to summary of the invention below, summary of the invention includes cited example but not limited to following example:

[0021] (1) Preparation of 2′-chloro-2-amino-5-nitrobenzophenone (1)

[0022] Reflux 34g (0.25mol) of zinc chloride and 100mL of thionyl chloride for 15 minutes, then evaporate the thionyl chloride to dryness to obtain a white powder, add 60.8mL (0.50mol) of o-chlorobenzoyl chloride, and heat up to 140°C, add 27.6g (0.20mol) p-nitroaniline in batches, after 0.5h, heat up to 205°C, react for 1h, add dropwise glacial acetic acid aqueous solution (78mL glacial acetic acid, 54mL water), 102mL concentrated sulfuric acid, reflux 4h, cooled, and left overnight. Transfer the solid to a 2000mL three-neck flask, add 300mL each of toluene, ethyl acetate, and water and heat to 70°C, pour the black liquid into a 2000mL separatory funnel, remove the water layer, and use (160mL*3) 4mol of the organic phase in turn / L hydrochloric acid, (16...

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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...

Claims

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Application Information

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IPC IPC(8): C07D233/64
CPCC07D233/64
Inventor 王钝
Owner SHENYANG PHARMA UNIVERSITY
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