摘要
以4-甲氧基乙酰乙酸甲酯为起始物料,经缩合、取代、环合、选择性水解制备卡替拉韦关键起始原料1-(2,2-二甲氧基乙基)-5-甲氧基-6-甲氧羰基-4-氧代-1,4-二氢吡啶-3-羧酸,纯度高达99.5%,总收率为65.0%。同时重点对其制备工艺中生成的5个工艺杂质进行合成或制备分离,杂质结构经MS、NMR确证。并分析了杂质可能的来源,为该起始原料的工艺优化提供了方向,也为其质量控制提供了依据。
1-(2,2-Dimethoxyethyl)-5-methoxy-6-methoxycarbonyl-4-oxo-1,4-dihydropyridine-3-carboxylic acid,a key starting material for the synthesis of Cabotegravir,was prepared from methyl 4-methoxyacetoacetate through a sequence of condensation,substitution,cyclization,and selective hydrolysis steps.The final product achieved a purity of up to 99.5%with an overall yield of 65.0%.During the synthesis,five process-related impurities were either synthesized or isolated,and their structures were confirmed by mass spectrometry(MS)and nuclear magnetic resonance(NMR)spectroscopy.The possible origins of these impurities were analyzed,providing valuable insights for process optimization and establishing a solid foundation for quality control of the starting material.
作者
李晶晶
LI Jing-jing(Zhejiang Pharmaceutical University,Ningbo 315100,China)
出处
《精细化工中间体》
2025年第3期38-42,共5页
Fine Chemical Intermediates
关键词
卡替拉韦
起始原料
工艺杂质
合成研究
Cabotegravir
starting material
process impurity
synthesis study
