Preparation method of cimetidine

Abstract

The invention discloses a preparation method of cimetidine. The method comprises the following steps: (1) carrying out condensation reaction on 2-(methylimidazole-4-yl) methyl thioethylamine and N-cyanamide dialkyl carbonate in hot alcohol dehydratum, distilling out alcohol at ordinary pressure, cooling to a room temperature, crystallizing and filtering to obtain N-cyanogroup-N'-[2-(5-methylimidazole-4-yl) sulphur methyl ethyl]-O-R isourea; (2) carrying out amination reaction on the N-cyanogroup-N'-[2-(5-methylimidazole-4-yl) sulphur methyl ethyl]-O-R isourea and methylamine in a reaction medium, after reaction is ended, distilling methylamine at ordinary pressure, cooling to room temperature and crystallizing to obtain a cimetidine crude product; and (3) decoloring the cimetidine crude product in absolute ethyl alcohol, cooling, crystallizing, drying in vacuum, and crushing to obtain a cimetidine refined product. According to the preparation method, the environment pollution caused by by-product methyl mercaptan / sodium methyl mercaptide in an existing cimetidine production process can be solved; the production process is simplified; the cost is reduced; and the product quality is improved.

Description

technical field [0001] The invention relates to the technical field of biomedicine, in particular to an environmentally friendly and low-cost method for preparing cimetidine. Background technique [0002] Cimetidine, listed in 1975, is the first selective H2 receptor antagonist for the treatment of peptic ulcer. It mainly has the function of inhibiting the secretion of gastric acid and reducing its acidity, preventing and protecting corrosive gastritis caused by chemical stimulation, and has obvious curative effect on stress gastric ulcer and upper gastrointestinal bleeding. However, the existing production processes at home and abroad are accompanied by a foul smell, which is harmful to the human body, and at the same time seriously pollutes the environment to produce methyl mercaptan, or the raw materials are difficult to obtain from the market, the cost is high, and it is difficult to produce on a large scale. [0003] Domestic patent CN200910119586.2 announces a kind of...

AI Technical Summary

Problems solved by technology

However, the existing production processes at home and abroad are accompanied by a foul smell, which is harmful to the human body, and at the same time seriously pollutes the environment. Methyl mercaptan is produced, or the raw materials are difficult to obtain from the market, the cost is high, and it is difficult to produce on a large scale

[0003] Domestic patent CN200910119586.2 announces a kind of preparation method of cimetidine, this method prepares 4-methylimidazolol with 4-methylimidazole and formaldehyde reaction, prepares a condensate with cysteamine hydrochloride reaction again, and then Dimethyl N-cyanamide reacts to form a dicondensate, and reacts with methylamine to generate cimetidine. This scheme produces a large amount of volatile, toxic, and malodorous methyl mercaptan during the formation and amination of the dicondensate. serious pollution to the environment and

[0004] CN200710134901.X announces a kind of cimetidine preparation method, with N-cyano-N'-[2-(5-methylimidazole-4-methylthio] ethyl}-N"-methylisothiourea Reacting with methylamine to prepare cimetidine, the method prepares cimetidine and produces a large amount of volatile and foul-smelling methyl mercaptan simultaneously, causing serious pollution to the environment;

[0005] Foreign US4413129 has announced a kind of preparation method of cimetidine, is that raw material prepares cimetidine with N-cyanamide-O-hydrocarbyl-S-hydrocarbyl and (5-methylimidazole-4-methyl)-S-ethylamine Tidine, the invention also produces volatile and foul-smelling mercaptans, which is difficult to produce on a large scale

[0006] US4158031 is similar to US4447621 and has announced a kind of cimetidine preparation method, with 4-methyl-5-methyl chloride (methyl mercaptan) and N-cyanamide-N'-methyl-N "-(2-ethane Sulfuryl)-guanidine intermediates are difficult to obtain in the market, the cost is high, and there is no industrial production significance

[0007] US4305067 discloses a kind of cimetidine preparation method, generates cimetidine with 4-methylimidazolol and N-cyanamide-N'-methyl-N "-(2-ethylthio)-guanidine reaction, the In the method, N-cyanamide-N'-methyl-N"-(2-ethylthio)-guanidine intermediate is difficult to obtain on the market, the cost is high, and there is no industrial production significance

[0008] US4381395 has announced a kind of synthetic cimetidine method, with N-cyanamide-N'-methyl-N "-(chlorine, bromine, iodine) and (5-methylimidazole-4-methyl) cysteamine Reaction to prepare cimetidine, because the N-cyanamide-N'-methyl-N"-(chlorine, bromine, iodine) intermediate is unstable, it is easy to eliminate a part of cyanogen halide, and at the same time, it is difficult to obtain the market and it is difficult to produce on a large scale