2-(咪唑并[1, 2-a]吡啶-3-基)乙酸的合成工艺改进

目的 改进抗骨质疏松药米诺膦酸的关键中间体2-(咪唑并1, 2-a]吡啶-3-基)乙酸的制备方法。方法 以2-氧代戊二酸二乙酯为起始原料，经溴代、环合、水解和脱羧4步反应制得目标产物。结果 目标化合物的熔点与¹H-NMR 谱数据与文献报道相符，总收率为40.5%(以2-氧代戊二酸二乙酯计)。结论 与文献报道的方法相比，改进后的工艺路线后处理简单，更有利于工业化生产。

Improved synthesis of 2-(imidazo[1,2-a]pyridin-3-yl)acetic acid

Minodronic acid, a nitrogen-containing bisphosphonate, has been used for the treatment of osteoporosis,which caused by accelerated bone resorption in clinic. Its synthesis reported in literatures was from 2-(imidazo1, 2-a]pyridin-3-yl)acetic acid(1) by one step bisphosphonate esterification. The key intermediate 1 could be also prepared by many unsatisfied methods. In order to synthesize the intermediate 1, an improved synthetic method was designed based on the public patent literature. The target compound was synthesized from 2-oxopentanedioic acid via four steps through bromination, cyclization, hydrolysis and decarboxylation. The melting point and ¹H-NMR of final compound was in accordance with the literature, and the overall yield of was 40.5%. In comparison with the reported procedure, some drawbacks, such as high vacuum distillation, column chromatography isolation, low yield, were improved and the method was easy for synthesis and suitable for industrial manufacturing.