Method for synthesizing memantine hydrochloride

Abstract

The invention discloses a method for preparing memantine hydrochloride, which comprises the following steps: using 1, 3-dimethyl adamantane as a raw material; nitrifying and then reducing the 1, 3-dimethyl adamantane to synthesize an intermediate 1-amino-3, 5-dimethyl adamantane; and acidifying the intermediate by hydrochloric acid and recrystallizing the intermediate by ethanol-ethyl acetate to obtain the memantine hydrochloride through purification,. The method has the advantages of moderate reaction condition, simple post treatment, good safety, low cost and little environment pollution, and suitability for industrialized production.

Description

technical field [0001] The invention relates to the field of drug synthesis, in particular to a method for synthesizing memantine hydrochloride. Background technique [0002] Memantine hydrochloride (memantine hydrocloride), the chemical name is 3,5-dimethyltricyclic (3,3,1,13,7)-decyl-1-amine hydrochloride, which is developed by German Merz company. Therapeutic drug, noncompetitive antagonism with moderate affinity for N-methyl-D-aspartate receptors, protects nerve cells from the toxic effects of excess excitatory amino acids. Memantine hydrochloride is not only effective for mild Alzheimer's disease (AD), but also can significantly improve the clinical symptoms of severe AD. It can significantly increase the curative effect when used in combination with acetylcholinesterase inhibitors. It is a promising treatment for dementia ( Especially neuroprotective drugs for AD, which were approved by the FDA in 2003 for the treatment of moderate and severe AD. [0003] At present,...

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Problems solved by technology

[0009] (1) Bromine needs to be used in large quantities in production, and at the same time, toxic hydrogen bromide is produced, which has great environmental pollution;

[0010] (2) Acetonitrile and concentrated sulfuric acid are highly toxic, and strong heat and reddish-brown smoke are released during the reaction, the reaction is more violent, and the risk is higher;

[0012] (4) The recrystallization process uses ethanol-ether mixed solvent, which is easy to cause combustion and explosion accidents

[0024] These three methods all need to go through 3-step reactions from the raw material 1,3-dimethyladamantane to the intermediate 1-amino-3,5-dimethyladamantane, and then to 1-amino-3,5-dimethyladamantane Methyladamantane is acidified with hydrochloric acid to obtain the crude product of memantine hydrochloride, and an organic mixed solvent, such as ethanol-ether or ethanol-ethyl acetate, is used for recrystallization and purification to obtain memantine hydrochloride; each method has its own limitations It is difficult to meet the needs of industrial production and preparation of raw materials in terms of performance, operation and selected reagents

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