摘要
目的研究抗凝血药利伐沙班-D_(4)的合成工艺。方法以苯胺-D5为起始原料,通过取代、环合、硝化、还原得到关键氘代中间体4-(4-氨基苯基)吗啡啉-3-酮-D_(4),在苯基上引入稳定的氘代基团,再用此氘代化合物进行环氧开环、环合、脱Boc保护和缩合反应制备利伐沙班-D_(4)。结果成功制备了利伐沙班-D_(4),9步反应的总收率为8.8%。结论该合成方法的原料便宜易得,步骤简单,操作方便,可用于利伐沙班-D_(4)的制备。
OBJECTIVE To investigate synthesis of Rivaroxaban-D_(4).METHODS The key deuterated intermediate 4-(4-aminophenyl)morpholine-3-ketone-D_(4) was synthesized from the starting material phenylamine-D5 via substitution,ring closing,nitrification and reduction reactions.Conjugation to the benzene ring with a stable deuterium group followed by epoxy ring opening,ring closing,Boc deprotection and condensation reactions provided the final product of Rivaroxaban-D_(4).RESULTS Rivaroxaban-D_(4) was successfully synthesized after 9-step reactions,obtaining 8.8%yield.CONCLUSION All starting materials used in this study are commercially available and cheap.With simple and convenient operations,the synthesis procedure is suitable for the laboratory production of Rivaroxaban-D_(4).
作者
潘立立
尹洪海
张琨皓
李云春
吴小艾
PAN Lili;YIN Honghai;ZHANG Kunhao;LI Yunchun;WU Xiaoai(Department of Nuclear Medicine,West China Hospital,SichuanUniversity,Chengdu,Sichuan,610041 P.R.China;Laboratory of Clinical Nuclear Medicine,West China Hospital,Sichuan University,Chengdu,Sichuan,610041 P.R.China)
出处
《华西药学杂志》
CAS
CSCD
2021年第4期371-374,共4页
West China Journal of Pharmaceutical Sciences
基金
四川省科技厅重点项目(编号:2017JY0324)。
