Fischer吲哚合成法合成舒马普坦

Fischer Indole Synthesis of Sumatriptan

舒马普坦是一种起效快耐受性好的治疗偏头痛的标准药物,目前市场前景看好。本研究用Fischer吲哚合成法,以4-肼基-N-甲基苯甲烷磺酰胺盐酸盐(Ⅰ)和4-N,N-二甲胺基丁醛缩二甲醇(Ⅱ)为原料,在甲醇/乙酸溶剂中先缩合形成腙不经分离在浓盐酸催化下一步直接得到了舒马普坦。实验表明,该方法操作简单且重复性好,粗产品通过高效液相色谱测定其含量为56%;产品经柱色谱纯化后产率为37%。产物结构经红外光谱、氢核磁共振谱分析得以确认。

Sumatriptan, a sort of selective 5-HT1B / 1D-like receptor agonist, is used in the treatment of migraine, and now the market prospect is very good. In this paper, the Fischer indole synthesis routine of sumatriptan was studied. It was synthesized from 4-hydrazino-n-meth ylbenzenmeth-anesulfonamide hydrochloride （Ⅰ） 4-N,N-di-methylaminobutanal dimethylacetal （ Ⅱ ） via Fischer indole synthesis, in the medium of methanol / acetic acid / hydrochloric acid, and the purity of crude product determined by HPLC is 56%. Purified by flash chromatography, the yield of sumatriptan crystal was about 37%. The structures of the final products were characterized by IR, 1^H-NMR.