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Method of preparing vilazodone intermediate 5-piperazin-2-acyl substituted benzofuran

A technology of acyl-substituted benzofuran, which is applied in the field of preparation of vilazodone intermediate 5-piperazinyl-2-acyl-substituted benzofuran, can solve the problems of cumbersome preparation, high price, and seriousness, and achieve improvement The effect of product yield, simplification of reaction steps, and little environmental pollution

Inactive Publication Date: 2013-06-12
SHANGHAI AOBO PHARMTECH INC LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But there are many shortcomings in this method, firstly the preparation of raw material 5-nitro-substituted benzofuran-2-carboxylate ethyl ester is not only loaded down with trivial details, and because can use nitration process, not only has bigger danger but also pollutes seriously
In addition, it is necessary to use expensive N,N-bis(2-chloroethyl)amine, which greatly limits its industrial production

Method used

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  • Method of preparing vilazodone intermediate 5-piperazin-2-acyl substituted benzofuran
  • Method of preparing vilazodone intermediate 5-piperazin-2-acyl substituted benzofuran
  • Method of preparing vilazodone intermediate 5-piperazin-2-acyl substituted benzofuran

Examples

Experimental program
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Effect test

Embodiment 1

[0023] Example 1 Synthesis of 5-(4-N-tert-butoxycarbonylpiperazinyl)-2-carboxylic acid ethyl ester substituted benzofuran (Ia)

[0024] 27g 5-bromo-2-carboxylic acid ethyl ester substituted benzofuran (IIIa), 20g N-mono-tert-butoxycarbonyl substituted piperazine, 11.5g triphenylphosphine palladium, 5.2g triphenylphosphine and 22g tert-butyl Potassium alkoxide was added into 500 mL of toluene, and reacted at 100° C. for 24 hours. The solvent was removed under reduced pressure, 1 L of ether was added to the system, and a solid precipitated out. This solid was recrystallized from methanol to obtain 20.5 g of ethyl 5-(4-N-tert-butoxycarbonylpiperazinyl)-2-carboxylate substituted benzofuran (Ia).

Embodiment 2

[0025] Example 2 Synthesis of 5-(4-N-tert-butoxycarbonylpiperazinyl)-2-amide substituted benzofuran (Ib)

[0026] 24g 5-bromo-2-amide substituted benzofuran (IIIb), 20g N-mono-tert-butoxycarbonyl substituted piperazine, 2.5g palladium acetate, 12.5g 2,2'-bisdiphenylphosphino-1,1 '-Binaphthyl and 65g of cesium carbonate were added to 500mL of dimethylformamide and reacted at 100°C for 24 hours. The solvent was removed under reduced pressure, 1 L of ether was added to the system, and a solid precipitated out. This solid was recrystallized from methanol to obtain 24 g of 5-(4-N-tert-butoxycarbonylpiperazinyl)-2-amide substituted benzofuran (Ib).

Embodiment 3

[0027] Synthesis of Example Three 5-piperazinyl-2-carboxylic acid ethyl ester substituted benzofuran (Ic)

[0028] 27g 5-bromo-2-carboxylic acid ethyl ester substituted benzofuran (IIIa), 21g piperazine, 11.5g triphenylphosphine palladium, 5.2g triphenylphosphine and 65g cesium carbonate were added to 500mL toluene, at 100 °C for 24 hours. The solvent was removed under reduced pressure, 1 L of ether was added to the system, and a solid precipitated out. This solid was recrystallized from methanol to obtain 7.8 g of 5-piperazine-substituted-2-carboxylic acid ethyl ester-substituted benzofuran (Ic).

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Abstract

The invention discloses a new method of preparing vilazodone intermediate 5-piperazin-2-acyl substituted benzofuran. The method comprises a coupling reaction of 5-halogen substituted 2-acyl substituted benzofuran (III) and piperazine compound (IV) in the presence of a metal palladium catalyst, a ligand, a solvent and a base to obtain the 5-piperazin-2-acyl substituted benzofuran. The method has advantages of short route, convenient synthesis and high yield, and is suitable for industrial production.

Description

technical field [0001] The invention relates to a preparation method of vilazodone intermediate 5-piperazinyl-2-acyl substituted benzofuran (I). Background technique [0002] Depression is a disease caused by changes in brain biochemistry, and its clinical manifestations are low mood, pessimism, and sleep disturbance. Low levels of monoamine neurotransmitters such as 5-hydroxytryptamine (5-HT), dopamine, and low receptor function are considered to be the cause of depression. The latest drug for the treatment of depression is selective 5-HT reuptake inhibitor (SSRI), which can inhibit the reuptake of 5-HT in the presynaptic membrane, increase the concentration of 5-HT in the synaptic cleft, and improve the Postsynaptic 5-HT 1A Excitability of receptors, resulting in antidepressant effects. In addition, it does not affect other neurotransmitter receptors, so it is relatively safe. 5-HT 1A The receptor is 5-HT 1 One of the members of the receptor family, which is further ...

Claims

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Application Information

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IPC IPC(8): C07D307/85
Inventor 竺伟陈宇袁利
Owner SHANGHAI AOBO PHARMTECH INC LTD
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