摘要
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.
出处
《中国药物化学杂志》
CAS
CSCD
2012年第3期209-211,共3页
Chinese Journal of Medicinal Chemistry