摘要
目的合成抗癌药neratinib。方法以2-氯-4-硝基苯酚和2-氯甲基吡啶为起始原料,经醚化、硝基还原得到3-氯-4-(吡啶-2-甲氧基)苯胺,3-氯-4-(吡啶-2-甲氧基)苯胺与3-氰基-6-乙酰氨基-7-乙氧基-4-氯喹啉反应得到3-氰基-6-乙酰氨基-4-[3-氯-4-(吡啶-2-甲氧基)苯氨基]-7-乙氧基喹啉,3-氰基-6-乙酰氨基-4-[3-氯-4-(吡啶-2-甲氧基)苯氨基]-7-乙氧基喹啉去乙酰保护基后,与(E)-4-二甲氨基-2-丁烯酰氯经酰化反应得到ner-atinib。结果与结论目标物neratinib的总收率为56.0%,其结构经核磁共振氢谱、质谱确证。
Aim To synthesize neratinib. Methods Starting from 2-chloro-4-nitrophenol and 2-（chloromethyl） pyridine hydrochlorid, 3-chloro-4-（pyridin-2-ylmethoxy）aniline was obtained via etherization and reduction. The obtained aniline coupled with N-（4-chloro-3-cyano-7-ethoxyquinolin-6-yl） acetamide to give 4-[3- chloro-4-（2-pyridylmethoxy） phenylamino]-3-cyano-7-ethoxy-6-N-acetylaminoquinoline. And then it was deacetylated, followed by reacting with （E）-4-（dimethylamino）but-2-enoyl chloride to yield the target compound neratinib. Results and conclusion The overall yield of this method is 56.0 %. The structure of neratinib was confirmed by ^1H-NMR, and MS.
出处
《中国药物化学杂志》
CAS
CSCD
2008年第5期355-357,共3页
Chinese Journal of Medicinal Chemistry
