氢溴酸沃替西汀的合成新工艺

A new synthetic method of vortioxetine hydrobromide

目的研究氢溴酸沃替西汀的新合成工艺。方法以邻氯苯腈与2,4-二甲基苯硫酚为起始原料,经亲核取代反应得到2-(2,4-二甲基苯硫基)苯腈,其氰基水解成酰胺后经霍夫曼降解生成2-(2,4-二甲基苯硫基)苯胺,再与二(2-氯乙基)胺盐酸盐环合,最后与氢溴酸成盐得到氢溴酸沃替西汀。结果与结论目标产物结构经1H-NMR、13C-NMR、MS确证。该路线原料价廉易得,操作简单,适合工业化生产,总收率约54%(以邻氯苯腈计)。

A newsynthetic method of vortioxetine hydrobromide was described.It was synthesized from 2-chlorobenzonitrile and 2,4-dimethylthiophenol via nucleophilic substitution,hydrolysis,Hofmann degradation followed by condensation with bis（2-chloroethyl） amine hydrochloride and salt formation with hydrobromic acid with an overall yield of 54%.The vortioxetine hydrobromide and its intermediates were confirmed by1H-NM R,13C-NM R and M S.The newroute was characterized with several advantages over reported procedures,including cheap and commercially available starting material,easier operations and improved yield.