A-349821
Chemical Name: 1-[4'-[3-[2(R),5(R)-Dimethylpyrrolidin-1-yl]propoxy]biphenyl-4-yl]-1-(4-morpholinyl)methanone
CAS No. 372513-99-0
项目整合开发状态: Preclinical
项目研究机构: Abbott (Originator)
合成路线:Fischer esterification of 4'-hydroxybiphenyl-4-carboxylic acid (I) with H2SO4/MeOH provides ester (II).The phenolic hydroxyl group is then alkylated with 1-bromo-3-chloropropane (III) in the presence of K2CO3 to furnish the chloropropyl ether (IV).Saponification of methyl ester (IV) with LiOH leads to carboxylic acid (V),which is further activated as the corresponding acid chloride (VI) upon heating in SOCl2.Acid chloride (VI) is subsequently coupled with morpholine (VII) to yield amide (VIII).Finally,alkyl chloride (VIII) is displaced with (R,R)-2,5-dimethylpyrrolidine (IX) in the presence of K2CO3 and KI to furnish the title compound.
📌 参考资料/链接：
参考文献标题:Aminoalkoxybiphenyl carboxamides as histamine-3 receptor ligands and their therapeutic applications
文献作者:Faghih,R.; Bennani,Y.L.(Abbott Laboratories Inc.)
参考来源:US 6316475; WO 0240461
📄 详细内容
合成路线:Fischer esterification of 4'-hydroxybiphenyl-4-carboxylic acid (I) with H2SO4/MeOH provides ester (II).The phenolic hydroxyl group is then alkylated with 1-bromo-3-chloropropane (III) in the presence of K2CO3 to furnish the chloropropyl ether (IV).Saponification of methyl ester (IV) with LiOH leads to carboxylic acid (V),which is further activated as the corresponding acid chloride (VI) upon heating in SOCl2.Acid chloride (VI) is subsequently coupled with morpholine (VII) to yield amide (VIII).Finally,alkyl chloride (VIII) is displaced with (R,R)-2,5-dimethylpyrrolidine (IX) in the presence of K2CO3 and KI to furnish the title compound.
参考文献标题:Aminoalkoxybiphenylcarboxamides as histamine-3 receptor ligands and their therapeutic applications
文献作者:Faghih,R.; Bennani,Y.
参考来源:US 2002111340
产品链接: CAS No. 372513-99-0››