📜4-氯-6-(2-氯乙氧基)-7-(2-甲氧基乙氧基)喹唑啉,3-氨基苯乙炔 以 甲苯 用作溶剂,化学反应生成6-(2-氯乙氧基)-N-(3-乙炔基苯基)-7-(2-甲氧基乙氧基)喹唑啉-4-胺盐酸盐
参考文献:Isolation Of Highly Pure Erlotinib Hydrochloride By Recrystallization After Nucleophilic Substitution Of An Impurity With Piperazine
标题:Isolation Of Highly Pure Erlotinib Hydrochloride By Recrystallization After Nucleophilic Substitution Of An Impurity With Piperazine
摘要:研究了厄洛替尼盐酸盐(n-(3-乙炔基苯基)-6,7-双(2-甲氧基乙氧基)喹唑啉-4-胺盐酸盐)的优化合成和纯化.高极性哌嗪与氯化中间副产物 N-(3-乙炔基苯基)-6(2-氯乙氧基)-7-(2-甲氧基乙氧基)喹唑啉-4-胺盐酸盐发生了亲核取代反应.结果,N-(3-乙炔基苯基)-6-(2-氯乙氧基)-7-(2-甲氧基乙氧基)喹唑啉-4-胺盐酸盐完全转化为 N-(3-乙炔基苯基)-6-(2-哌嗪基乙氧基)-7-(2-甲氧基乙氧基)喹唑啉-4-胺盐酸盐.N-(3-乙炔基苯基)-6-(2-哌嗪基乙氧基)-7-(2-甲氧基乙氧基)喹唑啉-4-胺盐酸盐的极性发生了变化,分子增大.通过重结晶,可以很容易地去除这种更大,极性更强的化合物.得到的盐酸厄洛替尼纯度高,杂质含量低(1%).盐酸厄洛替尼的纯度为99.9%.
Doi:10.1007/s11164-012-0757-9