摘要
3-羟基-4-甲氧基苯甲醛在甲酸和盐酸羟胺作用下转化为3-羟基-4-甲氧基苄腈,后者在碳酸钾存在下与N-(3-氯丙基)吗啉缩合得4-甲氧基-3-[3-(吗啉-4-基)]丙氧基苄腈,再经硝化制得2-硝基-4-甲氧基-5-[3-(吗啉-4-基)]丙氧基苄腈,经还原得2-氨基-4-甲氧基-5-[3-(吗啉-4-基)]丙氧基苄腈,后与3-氯-4-氟苯胺成脒得2-氨基-4-甲氧基-5-[3-(吗啉-4-基)]丙氧基-N'-(3-氯-4-氟苯基)苄脒,在甲酸作用下闭环得吉非替尼,总收率约44%。
Gefitinib was synthesized from 3-hydroxy-4-methoxybenzaldehyde via conversion ot aldehyde to nitrile, condensation with N-（3-chloropropyl）morpholine, nitration and reduction to give 2-amino-4-methoxy-5-（3- morpholin-4-ylpropoxy） benzonitrile, which was subjected to amidination with 3-chloro-4-fluoroaniline and cyclization in the presence of formic acid with an overall yield of about 44 %.
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2013年第11期1081-1084,共4页
Chinese Journal of Pharmaceuticals
基金
江苏省"六大人才高峰"高层次人才项目(2011-JY-008)
连云港市工业攻关项目(CG1106)
