抗肝癌药盐酸诺拉曲噻的合成  

Synthesis of nolatrexed dihydrochloride

作　　者：赵学清[1] 庄伟平[1] 

机构地区：[1]福建省微生物研究所,福州350007

出　　处：《中国新药杂志》2007年第10期772-775,共4页Chinese Journal of New Drugs

基　　金：福建省科技计划项目(2004Y002)

摘　　要：目的:改进盐酸诺拉曲噻的合成工艺。方法:以2-溴-4-硝基甲苯为原料经Sandmeyer法合成靛红、氧化开环、环合成喹唑啉酮和Ullmann反应合成了盐酸诺拉曲噻。结果:有关中间体及目标化合物的结构经必要的图谱确证,或经含量分析;总收率为28．8％。结论:本合成路线简洁,工业成本低,所得产品纯度高,适合于工业化生产。Objective： To improve synthetic process of nolatrexed dihydrochloride. Methods： The target compound was synthesized from 2-bromo-4-nitrobenzene via several steps including Sandmeyer reaction, oxidative decyclization, cyclization, Ullmann reaction and acidification. Results： The structures of related intermediates and the target compound were verified by spectroscopic techniques. The total yield of target compound was for 28.8%. Conclusion： This economic and simplified synthetic process is feasible for further pilot manufacture.

关 键 词：抗肝癌药 诺拉曲噻 化学合成 

分 类 号：R979.1[医药卫生—药品] R914.5[医药卫生—药学]