BMS-193885

Chemical Name: 4-[3-[3-[3-[4-(3-Methoxyphenyl)piperidin-1-yl]propyl]ureido]phenyl]-2,6-dimethyl-1,4-dihydropyridine-3,5-dicarboxylic acid dimethyl ester
项目整合开发状态: Preclinical
项目研究机构: Bristol-Myers Squibb (Originator)
合成路线:The Hantzsch cyclization of 3-nitrobenzaldehyde (I),methyl acetoacetate (II) and NH4OAc in refluxing ethanol or isopropanol gives 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylic acid dimethyl ester (III),which is reduced with H2 over sulfided carbon in ethanol or with Fe/NH4Cl in methanol/water to yield the corresponding amino derivative (IV).The reaction of (IV) with methyl chloroformate and pyridine in acetonitrile/dichloromethane affords the carbamate (V),which is treated with B-chlorocatecholborane in refluxing THF to provide the corresponding isocyanate (VI).Finally,this compound is condensed with 3-[4-(3-methoxyphenyl)piperidin-1-yl]propylamine (VII) in dichloromethane to furnish the target urea.The intermediate 3-[4-(3-methoxyphenyl)piperidin-1-yl]propylamine (VII) is obtained by condensation of 4-(3-methoxyphenyl)piperidine (VIII) with acrylonitrile (IX) in refluxing acetonitrile to give 3-[4-(3-methoxyphenyl)piperidin-1-yl]propionitrile (X),which is reduced with H2 over Raney-Ni in methanol/aq.NH3.