厄洛替尼合成工艺改进

Optimization of the synthesis for erlotinib

目的改进和优化厄洛替尼的合成工艺,以便于工业化生产。方法以3,4-二羟基苯甲醛为原料,依次通过醛基还原缩合、侧链烷氧基化、硝化、硝基还原和关环等反应步骤合成目标化合物。结果与结论目标产物总收率约为48.5%,其结构经核磁共振氢谱、质谱、元素分析确证。该路线操作简便,条件温和,有利于工业化生产。

Erlotinib is a new EGFR-tyrosine kinase inhibitor for the treatment of non-small-cell lung cancer.The synthetic route of erlotinib suitable for industrial manufacturing was optimized.In this paper,a five-step procedure started from 3,4-dihydroxybenzaldehyde as initial material was used to synthesize the desired compound through a series of procedures,such as aldehyde reduction,side chain alkylation,nitration,nitro reduction and cyclization.The process gave a purer product than that of the former methods described,and the overall yield was 48.5%.The structure of erlotinib was characterized by 1H-NMR,MS and elemental analysis.The purity was determined by HPLC.The procedure developed has several advantages such as mild reaction conditions and easy availability of the material.