2-(咪唑并[1,2-a]吡啶-3-基)乙酸的合成工艺改进

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

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1、H-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。

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-（imidazopyridin-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.