第 45 卷第 4 期 Vol. 45 No. 4 2015 年 8 月 Aug 2015

所属栏目：医药及中间体 5-（2-氟苯基）吡咯-3-甲醛的合成工艺研究

徐 成，周爱新，关 东，王桂艳* （佳木斯大学 药学院，黑龙江 佳木斯 154007）

摘　要：以1H吡咯为原料，经三异丙基氯硅烷N-烃化保护后，再与Vilsmeier试剂进行反应得3-醛基-1-H吡咯，再经N-溴代丁二酰亚胺（NBS）溴化与2-氟苯硼酸进行Suzuki偶联反应制得5-（2-氟苯基）吡咯-3-甲醛粗品，粗品用甲苯精制。总收率35.5%。该合成工艺操作简单，条件温和，试剂价廉易得，具有工业化前景。

关键词：抗胃酸；沃诺拉赞；Suzuki偶联反应

中图分类号：R975　　文献标识码：A　　文章编号：1009-9212（2015）04-0046-03

Synthesis of Important Intermediates for Anti-acid Drug Vonoprazan

XU Cheng, ZHOU Ai-xing, GUAN Dong, WANG Gui-yan* (College of Pharmacy, Jiamusi University, Jiamusi 154007, China)

Abstract：Vonoprazan important intermediates were prepared in a series of reactions. At first step intermediate 3 was obtained from the reaction of pyrrole with TIPSCl; and then intermediate 3 reacted with Vilsmeier reagents to give intermediate 4; followed by reacted with NBS, intermediate 5 was obtained; Finally, intermediate 5 reacted with 2-fluorophenyl boronic acid by coupling reaction to give the target compound with an overall yield of 35.5%. This process was suitable for industrial production due to the simple procedures, mild reaction conditions and lower cost.

Key words：anti-acid drug; vonoprazan; Suzuki coupling reaction

作者简介：徐 成（1989-），男，重庆人，硕士研究生，研究方向：创新药物分子设计、合成与构效关系研究（E-mail：464890862@qq.com）。

联 系 人：王桂艳，副教授，研究方向：有机合成研究（E-mail：374084560@qq.com）。

收稿日期：2015-01-02