WAY-174231
Chemical Name: N-[4-[4-[2(R)-Hydroxy-2-[4-hydroxy-3-(methylsulfonamido)phenyl]ethylamino]piperidin-1-yl]benzoyl]-L-leucine
项目整合开发状态: Preclinical
项目研究机构: Wyeth Pharmaceuticals (Originator)
合成路线:Condensation of ethyl 4-fluorobenzoate (I) with 4-piperidone ethylene ketal (II) afforded the N-arylpiperidine (III).Saponification of the ethyl ester group of (III),followed by acidic hydrolysis of the ethylene ketal function,yielded the benzoic acid derivative (V).Coupling of acid (V) with leucine ethyl ester (VI) using EDC gave amide (VII).Then,reductive amination of piperidone (VII) with the known arylethanolamine (VIII) using NaBH(OAc)3 furnished the aminopiperidine (IX).The ethyl ester group of (IX) was finally hydrolyzed with NaOH to provide the corresponding carboxylic acid.
📌 参考资料/链接：
参考文献标题:(4-Piperidin-1-yl)phenyl amides: Potent and selective human beta3 agonists
文献作者:Hu,B.; Ellingboe,J.; Han,S.; Largis,E.; Mulvey,R.; Oliphant,A.; Sum,F.W.; Tillett,J.
参考来源:J Med Chem 2001,44(9),1456
📄 详细内容
合成路线:Condensation of ethyl 4-fluorobenzoate (I) with 4-piperidone ethylene ketal (II) afforded the N-arylpiperidine (III).Saponification of the ethyl ester group of (III),followed by acidic hydrolysis of the ethylene ketal function,yielded the benzoic acid derivative (V).Coupling of acid (V) with leucine ethyl ester (VI) using EDC gave amide (VII).Then,reductive amination of piperidone (VII) with the known arylethanolamine (VIII) using NaBH(OAc)3 furnished the aminopiperidine (IX).The ethyl ester group of (IX) was finally hydrolyzed with NaOH to provide the corresponding carboxylic acid.
参考文献标题:A convenient synthesis of 1-aryl-4-piperidones
文献作者:Taylor,E.C.; Skotnicki,J.S.
参考来源:Synthesis 1981,606