Method for preparing memantine hydrochloride

Abstract

The invention is a manufacturing method of diamante amine hydrochlorate. The invention adopts 1, 3-dimethyl adamantine to reacts with tert-butylchlorine and gets 1-chlorine-3, 5-dimethyl adamantine; then reacts with acetamide directly, the educt from water reacts with sodium hydroxide in ethanediol or glycerine solvent, extracts by acetic ester, condenses, and blow in dry hydrochloride gas and gets the coarse product. There gets the pure product through alcohol-acetic ester recrystallization.

Description

Technical field [0001] The invention relates to a preparation method of a drug for treating Alzheimer's disease (AD) and an N-methyl-D-aspartic acid (NMDA) receptor antagonist memantine hydrochloride. Background technique [0002] Memantine hydrochloride, its chemical name: 1-amino-3,5-dimethyladamantane hydrochloride, structural formula: [0003] [0004] Because its structure contains amino groups, it is usually called memantine hydrochloride. It is the first NMDA antagonist developed by Merz to have a significant effect on AD. It acts on the glutamine system in the brain and is a non-competitive NMDA antagonist with medium affinity. Clinical studies have shown that memantine hydrochloride is well tolerated in AD patients, and it also has a significant effect on severe AD. Acetylcholinease inhibitors can only be used for moderate AD, and there are no reports of drugs that have been proven to treat severe AD. At present, there are about 5 million AD patients in China, so it ca...

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Problems solved by technology

[0006] The first step in the above-mentioned method adopts bromination, because hydrogen bromide gas is produced in the reaction process, it is easy to cause harm to the human body, and it is easy to cause pollution to the environment, so the reaction process has high requirements on the ventilation performance of the equipment, and the redundant bromine reduction; Chinese patent CN1335299, CN1400205 also use 1-bromo-3,5-dimethyladamantane as raw material to prepare this product, and there is also a technical problem of bromination; Acetonitrile and concentrated sulfuric acid have strong heat and reddish-brown smoke during the reaction. The reaction is relatively violent and dangerous; the two-step post-treatment of acetamidolation and alcoholysis uses benzene, which is more harmful to the environment and human body, as the extraction Solvent; the expensive diethylene glycol was used as a proton donor in the alcoholysis process; the ethanol-ether mixed solvent was used in the recrystallization process. In the process of ethanol in the state, a large amount of ether is volatilized, the loss is huge, and it is easy to cause combustion and explosion accidents. Therefore, the method in this literature needs to be improved.

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