西达本胺的合成工艺研究

Study on the synthetic process of chidamide

目的改进西达本胺(chidamide)的合成工艺。方法以3-溴吡啶为起始原料,经无配体Heck反应、甲酯水解、与4-氨甲基苯甲酸进行酰胺化后,与4-氟-1,2-苯二胺再次酰胺化,制得西达本胺。结果与结论目标物西达本胺的结构经MS和^(1)H-NMR谱确证,纯度为99.6%(HPLC面积归一化法),总收率61%(以3-溴吡啶计)。本路线具有后处理简便、原子利用率高、高效经济、三废少等优势。

A practical and feasible method for the preparation of chidamide was described in this paper.3-Bromopyridine was used as the starting material.After ligand-free Heck reaction and methyl ester hydrolysis, the amidation with 4-aminomethylbenzoic acid and then with 4-fluoro-1,2-phenylenediamine yielded the target compound with a purity of 99.6%(HPLC) and an overall yield of 61%.The structure of chidamide was confirmed by MS and ^(1)H-NMR.This route has the advantages of easy post-processing, high atomic utilization, high efficiency and economy, and low waste disposal.