| 摘要 |
<p>A process of manufacturing sertindole comprising preparation of N-(4-nuorophenyl)-N-(2-carboxy-4-chlorophenyl)glycine, by reacting an alkalimetal salt of 2,5-dichlorobenzoic acid with an alkalimetal salt of N-(4-fluorophenyl)glycine in an aqueous, alkaline environment in the presence of a copper catalyst; cyclisation of N-(4-fluorophenyI)-N-(2-carboxy-4-chlorophenyl)glycine to the corresponding 3-acetoxy-indole; reduction of the 3-acetoxy-indole and subsequent elimination of H2O thereby obtaining 5-chloro-l-(4-nuorophenyl)indole which is reacted with 4-piperidone in a mixture of an acetic acid and concentrated HCl; reduction of the resulting 5-chloro-l-(4-nuorophenyl)-3-(l,2,3,6-tetrahydropyridin-4-yl)indole and reaction of this compound with l-(2-chloroethyl)-2-imidazolidinon in order to obtain sertindole. Alternatively, 5- chloro-l-(4-fluorophenyl)-3-(l,2,3,6- tetrahydropyridin-4-yl)indole is first reacted with I-(2-chlorpethyl)-2-imidazolidinon followed by reduction thereby obtaining sertindole. This process uses reactants and solvents that are suitable and allowed in large scale manufacture. Furthermore good total yields are obtained</p> |
