合成路线:Alkylation of isonipecotamide (I) with n-butyl bromide in the presence of potassium carbonate gives the amide (II),which is reduced with lithium aluminum hydride to afford 1-butyl-4-piperidinylmethylamine (III).Conversion of indole-3-carboxylic acid (IV) to the acid chloride (V) is carried out with oxalyl chloride in dichloromethane containing N,N-dimethylformamide (DMF).Coupling of the amine (III) with the acid chloride (V) in dichloromethane in the presence of triethylamine gives N-[(1-butyl-4-piperidinyl)methyl]indole-3-carboxamide (VI).N-[(1-butyl-4-piperidinyl)methyl]-3,4-dihydro-2H-[1,3]-oxazino[3,2-a] indole-10-carboxamide (VIII) is formed by treatment of the amide (VI) with N-chlorosuccinimide in chloroform followed by reaction with 3-bromopropanol and cyclization of the intermediate ether (VII) with potassium carbonate in acetone.Conversion to N-[(1-butyl-4-piperidinyl)methyl]-3,4-dihydro-2H-[1,3]oxazino[3,2-a] indole-10-carboxamide hydrochloride (SB-207266) is effected by treatment of (VIII) with anhydrous HCl in ethanol.
参考文献标题:The 5-HT4 receptor
文献作者:Ford,A.P.D.W.; Clarke,D.E.
参考来源:Med Res Rev 1993,13633-62
合成路线:Alkylation of isonipecotamide (I) with n-butyl bromide in the presence of potassium carbonate gives the amide (II),which is reduced with lithium aluminum hydride to afford 1-butyl-4-piperidinylmethylamine (III).Conversion of indole-3-carboxylic acid (IV) to the acid chloride (V) is carried out with oxalyl chloride in dichloromethane containing N,N-dimethylformamide (DMF).Coupling of the amine (III) with the acid chloride (V) in dichloromethane in the presence of triethylamine gives N-[(1-butyl-4-piperidinyl)methyl]indole-3-carboxamide (VI).N-[(1-butyl-4-piperidinyl)methyl]-3,4-dihydro-2H-[1,3]-oxazino[3,2-a] indole-10-carboxamide (VIII) is formed by treatment of the amide (VI) with N-chlorosuccinimide in chloroform followed by reaction with 3-bromopropanol and cyclization of the intermediate ether (VII) with potassium carbonate in acetone.Conversion to N-[(1-butyl-4-piperidinyl)methyl]-3,4-dihydro-2H-[1,3]oxazino[3,2-a] indole-10-carboxamide hydrochloride (SB-207266) is effected by treatment of (VIII) with anhydrous HCl in ethanol.
参考文献标题:SB-204070: 5-HT4 receptor antagonists and their potential therapeutic utility
文献作者:Gaster,L.M.; Sanger,G.J.
参考来源:Drugs Fut 1994,19109-21
产品链接: CAS No. 178273-87-5›› 产品链接: CAS No.152811-62-6››