Levocabastine hydrochloride, R-50547, Livostin, Livocab, Levophta, Levocon, Livostin Nasal Spray-药物合成数据库

【药物名称】Levocabastine hydrochloride, R-50547, Livostin, Livocab, Levophta, Levocon, Livostin Nasal Spray

化学结构式(Chemical Structure):

参考文献No.	51907
标题:	Process for obtaining a 4-amino-5-chloro-2-methoxybenzoic acid deriv.
作者:	Izquierdo Sanjos? M.; Mart韓 Escudero, U.
来源:	ES 2002640

合成路线图解说明: The title compound has been obtained by condensation of 4-amino-5-chloro-2-methoxybenzoic acid (I) with cis-1-[3-(4-fluorophenoxy)propyl]-3-methoxypiperidine-4-amine (II) by means of DCC in dichloromethane or PCl3 in benzene.

合成路线图解说明: The reductive amination of 4-cyano-4-(4-fluorophenyl)cyclohexanone (I) with (-)-benzyl 3-methyl-4-phenyl-4-piperidinecarboxylate (II) by means of H2 and Pt/C 5% in the presence of thiophene in isopropyl alcohol at normal pressure and at 50 C gives a 9:1 mixture of (-)-benzyl [3S-[1(cis)-3alpha,4beta]]-1-[4-cyano-4-(4-fluorophenyl)cyclohexyl]-3-methyl-4-phenyl-4-piperidinecarboxylate and (-)-benzyl [3S-[1(trans)-3alpha,4beta]]-1-[4-cyano-4-(4-fluorophenyl)cyclohexyl]-3-methyl-4-phenyl-4-piperidine-carboxylate. Chromatographic separation [dry column, silica gel, eluted with organic phase of a mixture of chloroform and methanol (99.0:1.0 by volume) yields the pure (-)-benzyl [3S-[1(cis)-3alpha,methyl-4-phenyl-4-piperidinecarboxylate (III), which is hydrogenolized in tetrahydrofuran at normal pressure and room temperature. The resulting free carboxylic acid is transformed to the monohydrochloric acid in methanol.

参考文献No.	700152
标题:	Levpcabastine (R 50 547): The prototype of a chemical series of compoundss with specific H1-antihistaminic activity
作者:	Sokbroekx, R.A.; et al.
来源:	Drug Dev Res 1986,887-93

合成路线图解说明: The reductive amination of 4-cyano-4-(4-fluorophenyl)cyclohexanone (I) with (-)-benzyl 3-methyl-4-phenyl-4-piperidinecarboxylate (II) by means of H2 and Pt/C 5% in the presence of thiophene in isopropyl alcohol at normal pressure and at 50 C gives a 9:1 mixture of (-)-benzyl [3S-[1(cis)-3alpha,4beta]]-1-[4-cyano-4-(4-fluorophenyl)cyclohexyl]-3-methyl-4-phenyl-4-piperidinecarboxylate and (-)-benzyl [3S-[1(trans)-3alpha,4beta]]-1-[4-cyano-4-(4-fluorophenyl)cyclohexyl]-3-methyl-4-phenyl-4-piperidine-carboxylate. Chromatographic separation [dry column, silica gel, eluted with organic phase of a mixture of chloroform and methanol (99.0:1.0 by volume) yields the pure (-)-benzyl [3S-[1(cis)-3alpha,methyl-4-phenyl-4-piperidinecarboxylate (III), which is hydrogenolized in tetrahydrofuran at normal pressure and room temperature. The resulting free carboxylic acid is transformed to the monohydrochloric acid in methanol.