盐酸替罗非班的合成工艺改进  

Improved Synthetic Process of Tirofiban Hydrochloride

作　　者：贾海军 张洒洒 韩忠丽 张贵民 时江华 JIA Haijun;ZHANG Sasa;HAN Zhongli;ZHANG Guimin;SHI Jianghua(National Engineering and Technology Research Center of Chirality Pharmaceutical,Lunan Pharmaceutical Group Co.,Ltd.,Linyi273400)

机构地区：[1]鲁南制药集团股份有限公司,国家手性制药工程技术研究中心,山东临沂273400

出　　处：《中国医药工业杂志》2024年第11期1499-1504,共6页Chinese Journal of Pharmaceuticals

摘　　要：对血小板凝集抑制剂盐酸替罗非班(1)的合成工艺进行了优化。以L-酪氨酸乙酯(4)为起始物,经磺酰化得N-正丁基磺酰基-L-酪氨酸乙酯(5),5与O-(4-吡啶基)-4-甲基苯磺酸丁酯(3)经取代、氢氧化锂水解,得N-正丁基磺酰基-O-[4-(4-吡啶基)丁基]-L-酪氨酸(6),6经钯炭催化氢化还原、盐酸成盐,得目标产物1。总收率63.5%(以4计),纯度99.80%,ee值99.8%。该工艺步骤短,收率高,原料经济、易得,条件温和、可控,适合工业化生产。The synthesis of the antiplatelet aggregation inhibitor tirofiban hydrochloride(1)has been optimized.Ethyl n-butylsulfonyl-L-tyrosinate(5)was synthesized from ethyl L-tyrosinate(4)by sulfonylation.After the substitution of 5 with 4-(pyridin-4-yl)butyl-4-methyl benzenesulfonate(3),followed by the hydrolysis with lithium hydroxide,N-n butylsulfonyl-O-[4-(4-pyridyl)butyl]-L-tyrosine(6)was obtained.Then,6 was reduced by hydrogen in the presence of Pd/C and salted with hydrochloric acid to obtain the target compound 1.The overall yield was 63.5%(based on 4)with purity of 99.80%,and ee value of 99.8%.The improved process has short steps with high product yield,economical and easily accessible raw materials,and mild and controllable reaction conditions,which is suitable for industrial production.

关 键 词：血小板GPⅡb/Ⅲa受体拮抗药 盐酸替罗非班 合成 

分 类 号：R973.2[医药卫生—药品] TQ460.6[医药卫生—药学]