Purification method of memantine hydrochloride

Abstract

The invention provides a purification method of memantine hydrochloride. The method includes: adding a memantine hydrochloride crude product into a mixed solvent of acetone / water, tetrahydrofuran / water, methanol / methyl tert-butyl ether or ethanol / methyl tert-butyl ether, conducting stirring and heating reflux until the solution is clarified, performing cooling to a temperature ranging from -15DEG C to 5DEG C, conducting crystallization for 2-3h, then carrying out filtering, washing and vacuum drying, thus obtaining the memantine hydrochloride with purity of greater than 99.9% and biggest single impurity of less than 0.1%. The method provided by the invention has the characteristics of simple operation and mild conditions, the obtained product has high purity, the impurities meet the quality control requirements, and the product is stable, thus providing reliable guarantee for improving the quality of memantine hydrochloride.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry, and in particular relates to a preparation method of high-purity memantine hydrochloride. Background technique [0002] Memantine hydrochloride is a new type, low-moderate affinity, voltage-dependent, non-competitive N-methyl-D-aspartate (NMDA) receptor antagonist, which can non-competitively block NMDA receptors, reduce Glutamate-induced over-excitation of NMDA receptors prevents apoptosis and improves memory. It is a new generation of drugs for improving cognitive function. It was launched in Germany in August 2002, and was approved by the US Food and Drug Administration (FDA) on October 17, 2003 for the treatment of patients with moderate and severe Alzheimer's disease. It has great development prospects in the future market . Memantine hydrochloride is commercially available in the form of crystal form I, the chemical name is 1-amino-3,5-dimethyladamantine hydrochloride, and the structure...

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Problems solved by technology

[0008] CN1488622 and CN101412678 adopt ethanol / ethyl acetate mixed solvent for recrystallization, and the solvent used is relatively safe, but the finished product obtained by repeating the operation is more than 0.27%. The control limit is 0.15%, so the memantine hydrochloride obtained by recrystallization with ethanol / ethyl acetate mixed solvent needs further purification

[0009] CN1566075A discloses a synthetic method for preparing amantadine compounds. The substituted halogenated adamantane is mixed with a substituted formamide compound, and undergoes a nucleophilic substitution reaction. The obtained compound removes formyl groups under acidic conditions to obtain the target product , the process of this route is simple and the pollution is small, but the purification of the target product in the examples only mentions recrystallization, and the solvent, ratio, heating temperature, crystallization time and other specific details of recrystallization are not recorded

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