第 52 卷第 5 期 Vol. 52 No. 5 2022 年 10 月 Oct 2022

所属栏目：医药及中间体 吡咯喹啉醌关键中间体的合成工艺研究

毛联岗 （连云港杰瑞药业有限公司，江苏 连云港 222000）

摘　要：以1-甲氧基-5-甲基-2，4-二硝基苯（2）为原料，经缩合、还原和环合制得6-氨基-5-甲氧基-1H-吲哚-2-甲酸乙酯（4），优化条件下收率70%；4与乙醛酸酯和丙酮酸酯发生三组分一锅反应得到吡咯喹啉醌关键中间体5-甲氧基-1H-吡咯［2，3-f］喹啉-2，7，9-三甲酸2-乙酯7，9二烷基酯（1），优化条件下收率90%。对影响收率的催化剂结构、反应温度、溶剂、乙醛酸酯和丙酮酸酯结构等因素进行了考察。通过IR、1H NMR、13C NMR和ESI-MS确证了1及中间体的结构。该制备工艺原料价廉、环保，收率高，具有工业化应用前景。

关键词：吡咯喹啉醌；5-甲氧基-1H-吡咯［2，3-f］喹啉-2，7，9-三甲酸2-乙酯7，9二烷基酯；一锅反应

中图分类号：TQ28　　文献标识码：A　　文章编号：1009-9212（2022）05-0035-05

Synthesis of Key Intermediate of Pyrroloquinoline Quinone

MAO Lian-gang (Lianyungang Jari Pharmaceutical Co., Ltd., Lianyungang 222000, China)

Abstract：Ethyl 6-amino-5-methoxy-1H-indole-2-carboxylate (4) was obtained from 1-methoxy-5-methyl-2,4-dinitrobenzene (2) through condensation, reduction and cyclization with a yield of 70%. Then 2-ethyl,7,9-dialkyl 5-methoxy-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid ester (1) was synthesized from 4 and glyoxylic ester, pyruvate through a simple one-pot reaction with a yield of 90%. The affecting factors including the structures of the catalysts, the reaction temperature, the solvent, and the structures of glyoxylic ester and pyruvate were investigated. The structures of the compound 1 and intermediate were characterized by IR, 1H NMR, 13C NMR and ESI-MS. The synthetic process had the advantages including low in raw material cost, environment-friendly, high yield and suitable for industrial production.

Key words：pyrroloquinoline quinone; 2-ethyl,7,9-dialkyl 5-methoxy-1H-pyrrolo[2,3-f]quinoline-2,7,9-tricarboxylic acid ester; one-pot reaction

作者简介：毛联岗（1976—），男，山西昔阳人，高级工程师，研究方向：药物合成及质量控制（E-mail：718838263@qq.com）。

收稿日期：2022-06-10