吉非替尼的合成工艺改进  

An optimization synthesis of gefitinib

作　　者：许立兵[1] 游莉[1] 邓俊丰[1] 刘瑜[1] 张晓[1] 江洁滢 

机构地区：[1]成都大学四川抗菌素工业研究所,成都610052

出　　处：《中国抗生素杂志》2015年第10期744-746,共3页Chinese Journal of Antibiotics

摘　　要：目的优化吉非替尼的合成路线,为其工业化生产奠定基础。方法以6-羟基-7-甲氧基-3H-喹唑啉-4酮为原料经过乙酰化、氯代、胺代、脱乙酰化、缩合等5步反应制备吉非替尼。结果产品结构经IR、~1H-NMR、^(13)C-NMR和MS确认,总收率37.4%,产品HPLC纯度达到99.7%以上。结论改进后的工艺,反应条件更温和,操作简单,产品纯度高,有利于工业化生产。Objective To improve the routine of gefitinib synthesis, and lay a foundation for its industrialization. Methods The gefitinib was synthesized from 6-hydroxy-7-methoxy-3H-quinazolin-4-one, though a five-step process of acetylization, cholro, amination, deacetylization, etc. Results The overall yield was 37.4% and the final production was characterized by IR, 1H-NMR, 13C-NMR and MS, whose purity was over 99.7% through HPLC test. Conclusion Mild conditions were got with simple operation after improved routine, the final production had a higher purity thus would be conducive to commercial process.

关 键 词：吉非替尼 抗肿瘤药 工艺改进 

分 类 号：R979[医药卫生—药品]