喹啉多环系列化合物的一锅法合成  

One-pot synthesis of quinoline polycyclic compounds

作　　者：赵传武 杨金路 汪天洋 刘东志 杨汉煜 高清志[1,3] ZHAO Chuanwu;YANG Jinlu;WANG Tianyang;LIU Dongzhi;YANG Hanyu;GAO Qingzhi(Tianjin Key Laboratory for Modern Drug Delivery&High-Efficiency,School of Pharmaceutical Science and Technology,Tianjin University,Tianjin 300072,China;Collaborative Innovation Center of Chemical Science and Engineering(Tianjin),Tianjin 300072,China;CSPC Zhongqi Pharmaceutical Technology(Shijiazhuang)Co.,Ltd.,Shijiazhuang 050000,Hebei,China)

机构地区：[1]天津大学药物科学与技术学院天津市现代药物传递及功能高效化重点实验室,天津300072 [2]天津化学化工协同创新中心,天津300072 [3]石药集团中奇制药技术(石家庄)有限公司,河北石家庄050000

出　　处：《精细化工》2023年第2期456-464,共9页Fine Chemicals

基　　金：国家重点研发计划(2020YFA0907903)。

摘　　要：以5-氟取代-4-氯喹啉为母核结构,在双亲核试剂存在下,通过氯、氟双取代构建了一锅法合成新型喹啉并多环衍生物的方法。该方法的核心步骤以4-氯-5-氟喹啉-3-甲酸酯为原料,N,N-二甲基甲酰胺为溶剂,在缚酸剂N,N-二异丙基乙胺存在下与邻位取代苯胺等双亲核试剂在加热条件下反应,即可完成氯、氟联级取代,不需分离单取代中间产物,最终获得具有结构多样性的喹啉并多环衍生物,反应收率在56.3%~97.1%之间。该方法无需其他催化剂,简单高效,且对官能团的容忍性强。产物结构经1HNMR、13CNMR、HPLC和HRMS确证。A one-pot method for synthesis of novel quinoline polycyclic derivatives was constructed with5-fluorosubstituted-4-chloroquinoline derivatives and binucleophilic reagents as starting materials.The key step of this method was synthesis of diversified quinoline polycyclic derivatives with no need for mono-substituted intermediates’separation via a cascade substitution of chlorine and fluorine completed by the reaction of 4-chloro-5-fluoroquinoline-3-carboxylates with ortho-substituted anilines(binucleophilic reagents)in presence of the deacid reagent N,N-diisopropylethylamine in N,N-dimethylformamide solvent under heated conditions.The yields of products obtained were in the range from 56.3%to 97.1%.The method was simple and efficient with no requirement for catalysts and good tolerance of various functional groups.The structures of the products were further confirmed by~1HNMR,13CNMR,HPLC and HRMS.

关 键 词：多环喹啉 亲核取代 一锅法合成 精细化工中间体 

分 类 号：O626[理学—有机化学]