摘要
以2-胺基-5-碘苯甲酸为起始原料,经四步反应合成了新型喹唑啉类抗肿瘤药物拉帕替尼的关键中间体——N-{3-氯-4-[(3-氟苄基)氧基]苯基}-6-碘喹唑啉-4-胺,总收率77.9%,其结构经1H NMR和ESI-MS确证。Williamson醚化反应的最佳条件为:4-(6-碘喹唑啉-4-基氨基)-2-氯苯酚(5)30.0 mmol,K2CO324.8 g,18-冠-6 0.79 g,KI 0.49 g,丙酮250 mL,于35℃反应12 h,收率90.1%。
An important intermediate of synthesizing new anti-cancer drugs of quinazoline derivatives,N-{3-chloro-4-[（3-fluorobenzyl）oxy]phenyl}-6-iodoquinazolin-4-amine,was synthesized from 2-amino-5-iodobenzoic acid by a four-step reaction in overall yield of 77.9%.The structure was confirmed by 1H NMR and ESI-MS.The optimum reaction conditions of Williamson reaction at 35 ℃ for 12 h were as follows： 5 was 30 mmol,K2CO3 was 24.8 g,18-crown-6 was 0.79 g,KI was 0.49 g,acetone was 250 mL.The yield was 90.1% under the conditions.
出处
《合成化学》
CAS
CSCD
北大核心
2011年第3期421-424,共4页
Chinese Journal of Synthetic Chemistry
基金
天津市自然科学基金资助项目(09JCZDJC21700)
关键词
拉帕替尼
喹唑啉
药物中间体
合成
工艺改进
Lapatinib
quinazoline
intermediate
synthesis
process improvement
