含有吡咯烷侧链的喹啉衍生物合成研究  

Synthesis of quinoline derivatives containing pyrrolidine side chain

作　　者：唐文强 高艳蓉 徐小娜 仝红娟 刘斌[1] TANG Wen-qiang;GAO Yan-rong;XU Xiao-na;TONG Hong-juan;LIU Bin(School of Pharmacy,Shaanxi Institute of International Trade&Commerce,Xianyang 712046,China;School of pharmaceutical&Chemical Engineering,Xianyang Vocational Technical College,Xianyang 712000,China)

机构地区：[1]陕西国际商贸学院医药学院,陕西咸阳712046 [2]咸阳职业技术学院医药化工学院,陕西咸阳712000

出　　处：《化学研究与应用》2022年第12期2801-2806,共6页Chemical Research and Application

基　　金：陕西省自然科学基础研究计划项目(2021JQ-883,2021JM-540)资助;陕西省中药绿色制造技术协同创新中心重点培育项目(2019XT-1-02,2019XT-1-05)资助;陕西高校青年科技创新团队项目(陕教[2019]90号)资助;咸阳市分子影像与药物合成重点实验室资助项目(2021QXNL-PT-0008)资助。

摘　　要：本文报道了一类含有吡咯烷侧链的喹啉衍生物的合成方法。以5-甲氧基-2-硝基-4-[3-(吡咯烷-1-基)丙氧基]苯甲酸甲酯(2)为原料,依次经过硝基还原、酯水解、关环三步反应,合成得到目标化合物(1a~1c),并以2-氨基-5-甲氧基-4-[3-(吡咯烷-1-基)丙氧基]苯甲酸(4)与环戊酮(5a)为原料合成9-氯-7-甲氧基-6-[3-(吡咯烷-1-基)丙氧基]-2,3-二氢-1H-环戊[b]喹啉(1a)的关环反应为模型,考察影响产物1a收率的主要因素,确定该关环反应的最佳条件为:物料比n(5a)∶n(4)=1.6∶1;反应温度100℃;反应时间9 h。最后,以9-氯-7-甲氧基-6-[3-(吡咯烷-1-基)丙氧基]-1,2,3,4-四氢吖啶(1b)为例,初步探讨目标化合物在衍生化方面的应用,发现该结构母核可用于多种结构新颖的喹啉衍生物的合成。A method for the synthesis of quinoline derivatives containing pyrrolidine side chains was reported.The target compounds(1 a~1 c)were synthesized from methyl 5-methoxy-2-nitro-4-(3-(pyrrolidin-1-yl)propoxy)benzoate(2)by a three-step reaction,which involving nitro reduction,ester hydrolysis and ring closing reactions.Also,the synthesis of 9-chloro-7-methoxy-6-(3-(pyrrolidin-1-yl)propoxy)-2,3-dihydro-1H-cyclopenta[b]quinolone(1 a)from 2-amino-5-methoxy-4-(3-(pyrrolidin-1-yl)propoxy)benzoic acid(4)and cyclopentanone(5 a)by the cyclization reaction was used as a model reaction,the main factors affecting the yield of product 1 a were investigated.The optimum conditions of the ring closing reaction were determined as follows:mole ratio of material n(5 a)∶n(4)=1.6∶1;reaction temperature was 100℃;reaction time was 9 h.Finally,taking 9-chloro-7-methoxy-6-(3-(pyrrolidin-1-yl)propoxy)-1,2,3,4-tetrahydroacridine(1 b)as an example,the application of the target compound in derivatization was discussed,it was found that the target structure could be used for the synthesis of novel quinoline derivatives.

关 键 词：吡咯烷侧链 喹啉衍生物 还原反应 关环反应 

分 类 号：O626.323[理学—有机化学]