Astemizole, MJD-30, R-43512, Hismanal
阿司咪唑Chemical Name: 1-(4-Fluorobenzyl)-2-[1-(4-methoxyphenethyl)piperidin-4-ylamino]benzimidazole; 1-(4-Fluorobenzyl)-N-[1-[2-(4-methoxyphenyl)ethyl]piperidin-4-yl]-1H-benzimidazol-2-amine
CAS No. 68844-77-9
项目整合开发状态: Withdrawn-1999
项目研究机构: Janssen (Originator), Mochida (Licensee)
合成路线:The reaction of 1-isothiocyanato-2-nitrobenzene (I) with ethyl 4-aminopiperidine-1-carboxylate (II) in ethanol gives N-(2-nitrophenyl)-N'-(1-ethoxycarbonyl-4-piperidyl)thiourea (III),which is reduced with H2 over Pd/C in methanol saturated with NH3 to afford N-(2-aminophenyl)-N'-(1-ethoxycarbonyl-4-piperidyl)thiourea (IV).The cyclization of (IV) with iodomethane in refluxing ethanol yields 2-(1-ethoxycarbonyl-4-piperidylamino)benzimidazole (V),which is then condensed with 4-fluorobenzyl chloride (VI) by means of Na2CO3 in hot DMF to yield 1-(fluorobenzyl)-2-(1-ethoxycarbonyl-4-piperidylamino)benzimidazole (VII).The decarboxylative hydrolysis of (VII) with 48% HBr in refluxing acetic acid gives 1-(p-fluorobenzyl)-2-(4-piperidylamino)benzimidazole (VIII),which is finally condensed with p-methoxyphenylethyl methanesulfonate (IX) by means of Na2CO3 - KI in hot DMF.
📌 参考资料/链接：
参考文献标题:N-Heterocyclyl-4-piperidinamines
文献作者:Janssens,F.; Stokbroekx,R.; Torremans,J.; Luyckx,M.(Janssen Pharmaceutica NV)
参考来源:EP 0005318
📄 详细内容
合成路线:The reaction of 1-isothiocyanato-2-nitrobenzene (I) with ethyl 4-aminopiperidine-1-carboxylate (II) in ethanol gives N-(2-nitrophenyl)-N'-(1-ethoxycarbonyl-4-piperidyl)thiourea (III),which is reduced with H2 over Pd/C in methanol saturated with NH3 to afford N-(2-aminophenyl)-N'-(1-ethoxycarbonyl-4-piperidyl)thiourea (IV).The cyclization of (IV) with iodomethane in refluxing ethanol yields 2-(1-ethoxycarbonyl-4-piperidylamino)benzimidazole (V),which is then condensed with 4-fluorobenzyl chloride (VI) by means of Na2CO3 in hot DMF to yield 1-(fluorobenzyl)-2-(1-ethoxycarbonyl-4-piperidylamino)benzimidazole (VII).The decarboxylative hydrolysis of (VII) with 48% HBr in refluxing acetic acid gives 1-(p-fluorobenzyl)-2-(4-piperidylamino)benzimidazole (VIII),which is finally condensed with p-methoxyphenylethyl methanesulfonate (IX) by means of Na2CO3 - KI in hot DMF.
参考文献标题:Astemizole
文献作者:Blancafort,P.; Hillier,K.; Serradell,M.N.; Castar,J.
参考来源:Drugs Fut 1982,7(1),10
产品链接: CAS No. 68844-77-9››