来那度胺合成的新方法.pdfVIP

Chinese Journal ofN ew Drugs 2011, 20( 1) 1 1 2 1 , , , ( 1沈阳化工大学化学工程学院制药工程教研室, 沈阳 110142; 2 中油辽河工程有限公司油气加 工所, 盘锦 124010) [] : 优化来那度胺 合成路线: 2甲基3硝基苯甲酸( 4)经酯化反应溴代反应制得 2溴甲基3硝基苯甲酸甲酯( 6), 谷氨酸( 2)经酯化反应制得谷氨酸二甲酯( 3), 3和 6经分子间缩合反应, 1 分子内环合反应, 硝基还原反应得到最终产物来那度胺( 1): 目标化合物结构经核磁共振氢谱(H NMR)及质谱(MS)确证: 本方法反应条件温和, 缩短了反应步骤, 降低了生产成本, 并且提高了产率, 总收率约为 40% (以化合物 6计) [] 来那度胺; 免疫调节剂; 合成路线; 改进 [] R914. 5; R971. 1 [] A [] 1003- 3734( 2011) 01- 0075- 04 Improved syntheticmethod of lenalidom ide 1 1 2 1 SONG Yanling , JIANG Lulu, WANG X iaohuan, M NG Yanqiu ( 1D ep artm en t of P harm aceu tical Eng ineering, Co llege of chem ical Eng ineering, Shenyang University of Chem ical Technology, Shenyang 110142, China; 2Ch ina L iaohe P etroleum Eng ineering Co. , LTD, Panj in 124010, China [Abstract] Objective: To optmi ize the synthetic route of lenalidom ide. Methods: 2bromomethyl3nitro benzoate ( 6) was obtained from 2m ethyl3nitrobenzoic acid (4) via esterification and brom ination. Dmi ethyl gl utarate (3) was obtained from glutam ic aid ( 2). Compound 3 and 6 underwent intermolecular condensation and in tramolecular cyclization, followed by nitroreduction to give lenalidom ide ( 1). esults: The structure of the target 1 compound was confirmed by HNMR andMS. Conclusion: This syntheticmethod can shorten reaction steps, re duce production costs and mi prove yield to about40% ( based on compound 6) in a m ild reaction condition. [Key words] lenalidom ide; mi