4-氯-6-甲氧基-7-[3-(4-吗啉基)丙氧基]喹啉的合成  

Synthesis of 4-Chloro-6-methoxy-7-(3-(4-morpholine)propoxy)quinoline

作　　者：赵培培 王刚 张帆 ZHAO Pei-pei;WANG Gang;ZHANG Fan(College of Pharmacy,Jinzhou Medical University,Jinzhou 121001,China)

机构地区：[1]锦州医科大学药学院,辽宁锦州121001

出　　处：《化学试剂》2022年第4期613-616,共4页Chemical Reagents

基　　金：辽宁省自然科学基金项目(2019-ZD-0834)。

摘　　要：标题化合物是合成c-Met激酶抑制剂Foretinib的重要中间体。以2-甲氧基-5-硝基苯酚为原料,在碳酸钾及碘化钾存在下与1-溴-3-氯丙烷发生醚化反应,然后再与吗啉发生亲核取代反应,且将醚化及亲核取代两步反应合为一锅反应。再经铁粉还原、与米氏酸缩合、高温环合、氯代共6步反应制得目标化合物,反应总收率为32.4%。所有化合物结构经MS和^(1)HNMR进行确证。该路线步骤简洁、耗时短、操作简单、收率较高。4-Chloro-6-methoxy-7-(3-(4-morpholine) propoxy)quinoline is an important intermediate for the synthesis of Foretinib,a c-Met kinase inhibitors.In this study,we provided a novel method for the synthesis of this compound.4-Chloro-6-methoxy-7-(3-(4-morpholine)propoxy)quinoline was synthesized from 2-methoxy-5-nitrophenol via a six-step reaction:etherification reaction with 1-bromo-3-chloropropane in the presence of potassium carbonate and potassium iodide,then nucleophilic substitution reaction with morpholine.The etherification and the nucleophilic substitution were combined into one pot reaction.And then the target compound was obtained from reduction by iron powder,condensation with Medrum′s acid,high temperature cyclization and chlorination.The total yield was 32.4%.The structures of all compounds were confirmed by MS and ^(1)HNMR.This synthetic process has the advantages of simple steps,short time consuming,simple operation and high yield.

关 键 词：4-氯-6-甲氧基-7-[3-(4-吗啉基)丙氧基]喹啉 Foretinib c-Met激酶抑制剂 抗肿瘤 合成 

分 类 号：O625[理学—有机化学]