【作者】 冯菊红； 熊刚； 葛燕丽； 胡学雷；

【Author】 Juhong Feng;Gang Xiong;Yanli Ge;Xuelei Hu;School of Chemical Engineering and Pharmacy,Wuhan Insititute of Technology;Key Laboratory of Green Chemical Process of Ministry of Education,Wuhan Insititute of Technology;

【机构】 武汉工程大学化工与制药学院； 武汉工程大学绿色化工过程教育部重点实验室；

【摘要】 利伐沙班（Rivaroxaban,BAY 59-7939）是由拜尔公司和强生公司共同研发出的一种高效选择性的丝氨酸蛋白酶抑制剂,用于髋或膝关节置换手术后静脉血栓栓塞症的预防,有极好的体内活性和生物利用度^[1]。本合成工艺参考相关文献^[2,3],舍弃了原文献中昂贵的原料、有毒的试剂,并对原有的利伐沙班合成路线进行了改进。本文以2-苯胺基乙醇为原料,经过酰化,环合,硝化,还原得到中间体4-（4-氨基苯基）-3-吗啉酮,与（S）-N-（2,3-环氧丙基）邻苯二甲酰亚胺回流反应,再经过成环,脱胺保护,酰化反应得到最终产物利伐沙班。总收率提高至51%,降低了工业成本。更多还原

【Abstract】 Rivaroxaban,developed by Bayer and Johnson & Johnson company,is a highly selective serine protease inhibitors.It is used after hip or knee replacement surgery for the prevention of venous thromboembolism and shows excellent activity and bioavailability.[1]Referring to the relevant literatures⁽[2,3]’,the synthesis route of rivaroxaban was improved and the expensive raw materials and toxic reagents mentioned in these literatures were abandoned.Using N-phenylethanolamine as the starting material,the subsequent reaction of acetylation,cyclization,nitration and reduction gave the key intermediate 4-（4-aminophenyl）morpholin-3-one.This intermediate was refluxed with（S）-N-（2,3- epoxypropyl） phthalimide,then followed by cyclization,deprotection and acylation reaction,the final product rivaroxaban was obtained.The total yield reached 51%and the modified synthesis process reduced industrial costs.更多还原