Preparation method of vilazodone

The technology of vilazodone and nitro group is applied in the field of improved preparation of antidepressant drug vilazodone, can solve the problems of unobtainable reagents, complicated operation, low yield and the like, and achieves convenient industrial production and simple post-processing. , the effect of high yield

Inactive Publication Date: 2012-08-01
上海泛凯生物医药科技有限公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0028] In summary, the prior art using 5-cyanindole as a raw material to synthesize vilazodone has defects such as many steps, cumbersome operation, low yield, and difficult availability of reagents.

Method used

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  • Preparation method of vilazodone
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  • Preparation method of vilazodone

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0060] Example 1 Preparation of compound 1-benzenesulfonyl-1H-indole-5-carbonitrile

[0061] Add 60% sodium hydrogen (5.6g, 0.14mol) and tetrahydrofuran (200ml) into a 500mL three-neck reaction flask, and then lower the temperature to below 0°C. Add 5-cyanindole (20 g, 0.14 moL) slowly, and stir for 20 minutes after the degassing is complete. Slowly add benzenesulfonyl chloride (49.5 g, 0.28 mol). After the addition is complete, slowly raise the temperature to 40°C for reaction. TLC monitors that the reaction of the raw materials is complete. The reaction solution was extracted with saturated ammonium chloride solution, the aqueous phase was extracted twice with ethyl acetate, the organic phases were combined, washed with water, and dried overnight. After filtration, the filtrate was concentrated to dryness under reduced pressure to obtain compound 1-benzenesulfonyl-1H-indole-5-carbonitrile (39 g, 0.14 moL).

[0062] The structure of the compound obtained in this example is...

Embodiment 2

[0064] Example 2 Preparation of compound 3-(4-chlorobutyryl)-1-(benzenesulfonyl)-1H-indole-5-carbonitrile

[0065] Aluminum trichloride (56.7g, 0.43mol) and dichloromethane (800ml) were added to a 1L three-neck reaction flask, and 4-chlorobutyryl chloride (61.2g, 0.43mol) was slowly added at room temperature, and stirred for 20 minutes. A solution of 1-benzenesulfonyl-1H-indole-5-carbonitrile (40 g, 0.14 mol) in dichloromethane (200 ml) was slowly added. After the addition was complete, the stirring reaction was continued, and the reaction of the raw materials was monitored by TLC. The reaction solution was extracted with ice water, the aqueous phase was extracted twice with dichloromethane, the organic phases were combined, washed with water, and dried overnight. After filtration, the filtrate was concentrated to dryness under reduced pressure to obtain the compound 3-(4-chlorobutyryl)-1-(benzenesulfonyl)-1H-indole-5-carbonitrile (39.8g, 0.1moL).

[0066] The structure of ...

Embodiment 3

[0068] The preparation of embodiment 3 compound 3-(4-chlorobutyl)-1-(benzenesulfonyl)-1H-indole-5-carbonitrile

[0069] Add 3-(4-chlorobutyryl)-1-(benzenesulfonyl)-1H-indole-5-carbonitrile (1g, 2.6mmol), triethylsilane (0.9g, 7.8 mmol) and trifluoroacetic acid (20ml), the temperature was raised to 50°C, and the reaction was stirred. TLC monitored the completion of the raw material reaction. The reaction solution was extracted with 2N hydrochloric acid solution. The aqueous phase was extracted twice with ethyl acetate. The organic phases were combined, washed with water, and dried overnight with anhydrous sodium sulfate. Filtration, the filtrate was concentrated under reduced pressure until a solid precipitated, stirred for 0.5 hours, and filtered to obtain the compound 3-(4-Chlorobutyl)-1-(benzenesulfonyl)-1H-indole-5-carbonitrile (0.9g, 2.4mmol).

[0070] The structure of the compound obtained in this example is , Yield: 93%.

[0071] 1 H NMR (CDCl3)δ8.4(d, 1H...

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Abstract

The invention provides a preparation method of vilazodone, which comprises the following steps: reacting 5-cyanoindole, which is used as the initial raw material, with substituted phenylsulfonyl chloride under alkaline conditions, carrying out Friedel-Crafts reaction under the catalytic action of Lewis acid, reducing the product, and carrying out substitution reaction with 5-(1-piperazino)-benzofuryl-2-formamide to obtain the vilazodone. The invention also provides three intermediate compounds related to the vilazodone preparation method. The preparation method provided by the invention has the advantages of low cost, high yield and simple after-treatment, and is easy to operate and convenient for industrial production; and all the reagents are conventional reagents.

Description

technical field [0001] The invention belongs to the field of medicine preparation, and in particular relates to an improved preparation method of antidepressant medicine vilazodone. Background technique [0002] Vilazodone is a selective serotonin reuptake and serotonin 1A receptor inhibitor and partial agonist. In January 2011, the U.S. Food and Drug Administration (FDA) approved the listing for the treatment of major depressive disorder in adults. [0003] The chemical name of vilazodone is: 5-[4-[4-(5-cyanindolyl-3-yl)butyl]piperazinyl-1-yl]benzofuran-2-carboxamide ( CAS NO: 163521-12-8), its chemical structure is as follows: [0004] [0005] At present, the disclosed methods for preparing vilazodone at home and abroad mainly contain the following: [0006] 1) Preparation method using 3-(4-hydroxybutyl)indole-5-carbonitrile as intermediate [0007] The Chinese patent document with publication number CN101163698A discloses a method for preparing vilazodone using 3-...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D405/12C07D209/08
Inventor 王刚李永东
Owner 上海泛凯生物医药科技有限公司
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