摘要
目的改进和优化吉非替尼的合成工艺,便于工业化生产。方法以3,4-二甲氧基苯甲醛为原料,先硝化,后依次脱甲基、侧链烷基化、醛基转化为氰基、氰基氧化成酰胺、还原、闭环、氯代最后与3-氯-4-氟苯胺反应合成了抗肿瘤药物吉非替尼。结果总收率约23.6%,产物经核磁共振氢谱、质谱、元素分析确证其结构为目标产物。结论该工艺在分离纯化过程中不需过柱,原料价格便宜,条件温和,操作简单,适合于工业化生产。
Objective To optimize the synthesis method of Gefitinib,in order to provide an industrialized process.Methods Gefitinib was synthesized from 3,4-Dimethoxybenzaldehyde via nitration,demethylation and condensation with N-（3-chloropropyl）morpholine.Conversion of aldehyde to nitrile followed by amidation,reduction,and then cyclization which was finally subjected to be chlorinated and condensed with 3-chloro-4-fluoroaniline.Results Its structure was identified by 1HNMR、MS and EA.The total yield was 23.6%.Conclusion The synthetic method is acceptable for manufacturing with inexpensive materials,mild reaction conditions,simple operation and purification without chromatography.
出处
《今日药学》
CAS
2011年第12期741-744,共4页
Pharmacy Today
关键词
吉非替尼
表皮生长因子受体
合成
Gefitinib
epidermal growth factor receptor（EGFR）
synthesis
