应用化学2025，Vol.42Issue(6)：793-801,9.DOI:10.19894/j.issn.1000-0518.240357
盐酸美金刚-甲基-D6的合成与表征
Synthesis and Characterization of Memantine-Methyl-D6 Hydrochloride
摘要
Abstract
A synthetic method of deuterium labeled memantine-methyl-D6 hydrochloride was investigated.The Grignard reagent methyl-D3 magnesium iodide was used as a source of the isotope deuterium.The first methyl-D3 group of the key intermediate 1,3-dimethyl-D6 adamantane was introduced by a Grignard coupling reaction between methyl-D3 magnesium iodide and 1-bromoamantadane,and the second methyl-D3 group was introduced by bromination reaction and Grignard coupling reaction.Memantine-methyl-D6 hydrochloride was synthesized by chlorination method from 1,3-dimethyl-D6 adamantane,and the by-product demethyl memantine-methyl-D3 hydrochloride was obtained simultaneously.The yields of memantine-methyl-D6 hydrochloride and demethyl memantine-methyl-D3 hydrochloride were 47%and 39%based on 1-bromoadamantane consumed.The structure,chemical purity and deuterium isotopic enrichment of the product were identified as the target compound by nuclear magnetic resonance(NMR),hign performance liguid chromatography(HPLC)and electrospray ionization mass spectrometry(ESI-MS).The chemical purity of memantine-methyl-D6 hydrochloride is 99.32%,and the deuterium isotopic enrichment is 99.70%.The chemical purity and deuterium isotopic nrichment were higher than 99.00%.The result showed that the memantine-methyl-D6 hydrochloride could be used as isotope internal standard in the determination of memantine hydrochloride.关键词
盐酸美金刚/去甲盐酸美金刚/稳定同位素标记/合成/表征Key words
Memantine hydrochloride/Demethyl memantine hydrochloride/Stable isotope labeling/Synthesis/Characterization分类
化学引用本文复制引用
郭会,陈武炼..盐酸美金刚-甲基-D6的合成与表征[J].应用化学,2025,42(6):793-801,9.基金项目
上海市松江区"卡脖子"工程和颠覆性技术入库项目(No.QBZ2022-04)资助 Supported by the Bottleneck Project and Disruptive Technology Project of Shanghai-Songjiang District(No.QBZ2022-04) （No.QBZ2022-04）
