抗癌药吉非替尼合成新工艺

A New Synthetic Process of Gefitinib-an Anticancer Drug

以7-甲氧基喹唑啉-4-酮为原料,通过"一锅法"成功制备出表皮生长因子受体(EGFR)酪氨酸激酶抑制剂吉非替尼。产品经m.p.,IR,NMR,MS及元素分析确证结构,HPLC纯度为98.5%。通过单因素变量法考查了试剂用量、反应物料比、反应温度、碱用量和反应时间对产物产率的影响,得出该反应的最佳工艺条件:第一步物料配比n_(氯化亚砜):n_(原料)=20:1,DMF用量2 m L,反应温度为80℃,反应时间为3 h;第二步物料配比n_(吗啉):n_(原料)=30:20,n_(苯胺):n_(原料)=30:20,碱用量60 mmol(当n_(原料)=20 mmol时),反应温度为90℃,反应时间为3 h,总收率可达到65%。

A tyrosine kinase inhibitor of EGFR gefitinib was synthesized by a one - pot approach from 7 - methoxylquinazolin -4 - one. Structure of the product was characterized by m. p. , IR, NMR, MS spectra and elemental analysis. HPLC purity is 98. 5 % . The effects of reactant ratio, amounts of reagent and base, reaction temperature and reaction time on the product yield were also investigated. The optimized reaction conditions are as follows： 20 equivalent of SOCl2, 2 mL DMF, reaction temperature of 80 ℃and reaction time of 3 h in the first step; 1.5 equivalent of reagents and 3 equivalent of base on starting mate-rial scale, reaction temperature of 90 ℃ and reaction time of 3 h in the following step. The total yield was achieved at 65 % .