The Synthesis And Qualitive Research Of Sertindole

Scrtindole,1- [2- [4- [5-chloro- 1-(4-fluorophenyl)- 1H-ind-ol-3-yl]-1-piperidinyl] ethyl]- 2-imidazolodinone, is an atypical antipsychotic drug developed by Lundbeck compand and introduced on the European market in 1996.Scrtindole is a serotonin 5-HT2A and 5-HT2C, dopamine D2 and 1-adrenergic antagonist with selective effects on mesolimbic but not on nigrostriatal dopaminergic neurons. Because of this neurologic selectivity, sertindole is effective in the treatment of both positive and negative symptoms in schizophrenia, with fewer extrapyramidal effects than classical neuroleptics. Based on these findings, sertindole is regarded as one of the atypical antipsychotic drugs such as risperidone, clozapine and olanzapine. This drug is therefore attractive to clinicians because of its efficacy on the symptoms of schizophrenia and its fewer extrapyramidal side effects.This study included of the synthetic work, structure confirmation and drug standards of Sertindole.A process of manufacturing sertidole comprising preparation of 5-chloro-1-(4-fluorophenyl)indole which used 5-chloroindole and 4-fluoro-l-bromobenzene as the raw material in the presence of a copper catalyst by the Ullmann reaction. 5-chloro-1-(4-fluorophenyl) indole was reacted with 4-piperidone in a mixture of an acetic acid and concentrated HCl to gaved the compound 5-chloro-1-(4-fluorophenyl)-3-(1,2,3,6-tetrahedro piperidinyl-4-yl]indole. Then, 5-chloro-l-(4-fluorophenyl)-3-(4-piperidinyl) indole was got by reduction reaction.At last, Sertidole was obtained by the N-alkyl reaction of this compound with 1-(2-chloroethyl)-2-imidazolidinon.The present research relates to some improvements and optimizations of manufacturing the compound 1-[2-[4-[5-chloro-l-(4-fluorophenyl)-1H-ind-ol-3-yl]-1-piperidinyl]ethyl]-2-imidazolodinone having the INN name sertidole.1. The synthesis of compound 5-chloro-1-(4-fluorophenyl) indole was been did used DMF as the solvent. The post-processing was simplified in large degree with the good yield and high purity.2. Compound of 5-chloro-l-(4-fluorophenyl)-3-(4-piperidinyl) indole was got by reduction reaction. The precess use NaBH4 as the reduction reactant that was suilable in large scale manufacture. Furthermore the subsidiary dechloro-product and the expensive reduction reactant PtO2 were avoided.3. A new method of 1-(2-Chloroethyl)-2-imidazolidinone was synthesized from urea and N- (hydroxyethyl) ethylenediamine as raw material by condensation and chlorination reactions. The total yield of it was reached 88.7%. The method has high industrial value for its low production cost, convenient steps, simplicity and high yield.The structure of Sertindole was performed by elemental analyzed, IR, UV, magnetic resonance and mass spectrometry.According to the requirement of Provisions for Drug Registration, the qualitative research of Sertindole has been done.