Method for preparing sertindole by using alkyl imidazole type ionic liquid as solvent

Abstract

The invention discloses a method for preparing sertindole, which belongs to the technical field of organic synthesis. The method comprises the following steps of: using alkyl imidazole type ionic liquid as a solvent; and under the catalysis of a solid base, reacting 5-chloro-1-(4-fluorophenyl)-3-(1,2,3,6-tetrahydropyridine-4-yl)-1H-indole (IA) or a salt thereof, or 5-chloro-1-(4-fluorophenyl)-3-(4-piperidinyl)-1H-indole (IB) or a salt thereof with 1-(2-chloroethyl)-2-imidazole azululanone (II) to generate 1-[2-[4-[5-chloro-1-(4-fluorophenyl)-1-H-indole-3-yl]-5,6-dihydro-piperidine-1(2H)-yl]ethyl]-2-imidazolidinone (IIIA) or 1-[2-[4-[5-chloro-1-(4-fluorophenyl)-1-H-indole-3-yl]-1-piperidinyl]ethyl]-2-imidazolidinone (IIIB, sertindole). The method can prepare the sertindole and a structuralanalog thereof with high selectivity and high yield, the purity of the prepared sertindole is over 99.5 percent, and the yield can reach 85 to 90 percent. The method is simple and convenient to operate, has an easily controllable reaction condition and high selectivity, is environment-friendly, and is suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of sertindole, in particular to a method for preparing sertindole by using an alkylimidazole type ionic liquid as a solvent, and belongs to the technical field of organic synthesis. Background technique [0002] Sertindole (sertindole) is an atypical antipsychotic drug, its chemical name is: 1-[2-[4-[5-chloro-1-(4-fluorophenyl)-1H-indole-3 -yl]-1-piperidinyl]ethyl-2-imidazolidinone, the English name is: 5-Chloro-1-(4-fl uorophenyl)-3-[1-(2-oxoimidazolidin-1-ylethyl) -4-piperidyl]-1H-indoe. The structural formula of sertindole is: [0003] [0004] The mechanism of action of sertindole is the dual blockade of 5-hydroxytryptamine (5-HT) and dopamine (DA) receptors, which is not only reflected in the treatment of patients with acute attacks, but also in the maintenance treatment to prevent relapse of psychosis , less side effects, no need to cooperate with anticholinergic drugs, better tolerance and comp...

AI Technical Summary

Problems solved by technology

[0006] (1) The reaction yield is low, and the yield is 74%;

[0007] (2) The reaction selectivity is not high, and a large amount of by-products are arranged to generate, which directly affects the purity of the product;

[0008] (3) A large amount of organic solvents need to be consumed during reaction and aftertreatment, and 12ml methyl isobutyl ketone is needed for every 1g of product; the safety performance of the used solvent methyl isobutyl ketone is poor, and its vapor forms an explosive mixture with air. Thermal energy can cause combustion and explosion, and can react strongly with oxidants

In case of high heat, the internal pressure of the container will increase, and there is a danger of cracking and explosion

[0009] (4) The post-processing operation is complicated. After the reaction, a large amount of solvent washing is required, and the product needs to be recrystallized and purified.

The problem of solvent recovery and purification when preparing sertindole in large quantities needs further study

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