雷沙吉兰甲磺酸盐的合成工艺研究

Synthetic Process of Rasagiline Mesylate

目的优化雷沙吉兰甲磺酸盐合成工艺。方法 1-茚酮经一锅法还原-胺化制得1-氨基茚满,然后与3-溴丙炔反应得N-炔丙基-1-氨基茚满,用L-酒石酸拆分得R-（＋）-N-炔丙基-1-氨基茚满酒石酸盐,最后碱化、成盐得雷沙吉兰甲磺酸盐。结果中间体及目标产物结构经^1H-NMR和MS确证结构,5步总收率达19.2%。结论此路线原料易得,反应条件温和,操作简便,收率高,适于工业化生产。

OBJECTIVE To optimize the synthetic process of rasagiline mesylate. METHODS First, 1-indanamine was synthesized from 1-indanone via reduction and amination. Then, R-（＋）-N-propargyl-1-indanamine tartrate was obtained from 1-indanamine by condensation with 3-propargyl bromide, followed by resolution with L-tartaric acid. Finally, Rasagiline mesylate was prepared by alkalization and mesylation of the R-isomer L-tartrate. The total yield was 19.2%. RESULTS The chemical structures of intermediates and target product were confirmed by ^1H-NMR and MS. CONCLUSION This synthetic process is characterized by cheap materials, mild condition, simple operation and high yield, and is fitting for industrial application.