摘要
2-甲氧基-5-硝基苯酚经异丙基保护酚羟基及硝基还原制得3-异丙氧基-4-甲氧基苯胺(3),与3-乙氧基-2-氰基丙烯酸乙酯缩合后,以Dowtherm A为溶剂,经Gould-Jacobs环合后再经POCl3氯代、与2,4-二氯-5-甲氧基苯胺作用得7-异丙氧基-6-甲氧基-4-(2,4-二氯-5-甲氧基苯胺基)-3-氰基喹啉,最后经氢溴酸脱异丙基、1-溴3-氯丙烷取代及引入甲基哌嗪得伯舒替尼,总收率约21%。
Bosutinib was synthesized from 2-methoxy-5-nitrophenol by protection and reduction to give 3-isopropoxy-4-methoxyaniline, which was subjected to condensation with ethyl 3-ethoxy-2-cyanoacrylate, Gould-Jacobs cyclization in Dowtherm A, chlorination, reaction with 2,4-dichloro-5-methoxyaniline to afford 7-isopropoxy-6-methoxy- 4- （2,4-dichloro-5-methoxyanilinyl） quinoline-3-carbonitrile, followed by deprotection, substitution and condensation with 4-methylpyperizine with an overall yield of about 21%.
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2013年第11期1086-1088,共3页
Chinese Journal of Pharmaceuticals
