富马酸沃诺拉赞的合成工艺改进

Improved synthesis of vonoprazan fumarate

目的改进抑酸药富马酸沃诺拉赞的合成工艺。方法以5-(2-氟苯基)-1H-吡咯-3-甲醇为起始原料,经氧化、与吡啶-3-磺酰氯缩合、胺化还原、与富马酸成盐制得富马酸沃诺拉赞。结果与结论目标化合物的结构经1H-NMR和MS谱确证,总收率为53%[以5-(2-氟苯基)-1H-吡咯-3-甲醇计],纯度为99.5%。改进后的工艺无需色谱纯化,避免使用高毒试剂和昂贵催化剂,更适宜工业化生产。

To improve the synthesis of vonoprazan fumarate,vonoprazan fumarate was synthesized from[5-（2-fluorophenyl）-1H-pyrrol-3-yl]methanol by oxidation,condensation with 3-pyridine sulphonyl chloride,followed by reductive amination,salt forming by fumarate. The structure of vonoprazan fumarate was verified by 1H-NMR and MS,with an overall yield of 53% and a purity of 99. 5%（HPLC）. The synthetic route was successful without using column chromatography for purification,avoiding highly toxic and expensive agents. It is suitable for industrial production.