3-{[3,5-二(三氟甲基)苯基]氨基}-4-{[(1R,2R)-2-(哌啶-1-基)环己基]氨基}环丁-3-烯-1,2-二酮的合成  

Synthesis of 3-((3,5-bis(trifluoromethyl)phenyl)amino)-4-(((1R,2R)-2-(piperidin-1-yl)cyclohexyl)amino)cyclobut-3-ene-1,2-dione

作　　者：赵梅梅 高艳蓉 杜漠 唐文强 仝红娟 ZHAO Mei-mei;GAO Yan-rong;DU Mo;TANG Wen-qiang;TONG Hong-juan(Higher Vocational College,Shaanxi Institute of International Trade&Commerce,Xianyang 712046,China;Xianyang Key Laboratory of Molecular Imaging and Drug Synthesis,Xianyang 712046,China)

机构地区：[1]陕西国际商贸学院高职学院,陕西咸阳712046 [2]咸阳市分子影像与药物合成重点实验室,陕西咸阳712046

出　　处：《精细与专用化学品》2023年第11期43-46,共4页Fine and Specialty Chemicals

基　　金：陕西省教育厅2022年度专项科学研究计划(22JK0280);陕西国际商贸学院“中药药效物质研究”创新团队资助项目(SSY18TD02)。

摘　　要：报道一种手性方酰胺催化剂3-{[3,5-二(三氟甲基)苯基]氨基}-4-{[(1R,2R)-2-(哌啶-1-基)环己基]氨基}环丁-3-烯-1,2-二酮(化合物1)的合成方法。它是以方酸二甲酯(化合物2)为原料,首先与3,5-二(三氟甲基)苯胺(化合物3)反应得到中间体3-{[3,5-二(三氟甲基)苯基]氨基}-4-甲氧基环丁-3-烯-1,2-二酮(化合物4),化合物4再与(1R,2R)-2-(1-哌啶基)环己胺(化合物5)发生氨解反应,得到产物化合物1。化合物1结构经过1HNMR、13CNMR和ESI-MS表征。重点考察并确定影响产物收率的主要条件为:反应溶剂为二氯甲烷、n(化合物5)∶n(化合物4)=1.3∶1、室温反应20h,化合物1收率达到67%。The synthesis of 3-((3,5-bis(trifluoromethyl)phenyl)amino)-4-(((1R,2R)-2-(piperidin-1-yl)cyclohexyl)amino)cyclobut-3-ene-1,2-dione(compound 1)were reported.Using 3,4-dimethoxycyclobut-3-ene-1,2-dione(compound 2)as starting material,the intermediate 3-((3,5-bis(trifluoromethyl)phenyl)amino)-4-methoxycyclobut-3-ene-1,2-dione(compound 4)was obtained by reacting with 3,5-bis(trifluoromethyl)aniline(compound 3).Then,the target compound(compound 1)was obtained by the ammonolysis reaction of intermediate(compound 4)with(1R,2R)-2-(piperidin-1-yl)cyclohexan-1-amine(compound 5).The structure of product(compound 1)was characterized by~1HNMR,~(13)CNMR and ESI-MS.Then,the optimum conditions for the synthesis of the product(compound 1)were as follows:when the reaction solvent was dichloromethane,the ratio of n(compound 5)∶n(compound 4)=1.3∶1,and the reaction time was 20 h at room temperature,the yield of the product(compound 1)was up to 67%.

关 键 词：手性催化剂 方酰胺 氨解反应 合成条件 

分 类 号：TQ463[化学工程—制药化工]