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New synthetic process of vilazodone intermediate 5-cyano-3(4-chlorobutyl)-indole

A technology of vilazodone and chlorobutyl is applied in the field of new synthesis process of vilazodone intermediate 5-cyano-3(4-chlorobutyl)-indole, and achieves great economic and social benefits, equipment Simple, environmentally friendly production procedures

Active Publication Date: 2014-06-25
ZHANG JIA GANG VINSCE BIO PHARM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The core problem to be solved in the present invention is to overcome the shortcomings of the existing vilazodone intermediate—5-cyano-3(4-chlorobutyl)-indole preparation process, to establish a green, environmentally friendly, high atom economy, and lower Low cost, better quality 5-cyano-3(4-chlorobutyl)-indole industrial production process

Method used

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  • New synthetic process of vilazodone intermediate 5-cyano-3(4-chlorobutyl)-indole

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] Example 2 Synthesis of 5-cyano-3 (4-chloro-butyryl)-indole

[0019] Add 400 L of solvent dichloromethane and 60.0 kg of raw material 5-amino-formyl-3(4-chloro-butyryl)-indole into the enamel reaction kettle, and add phosphorus oxychloride in an ice-salt bath to control the temperature below 10 °C 30.0 kg, added in about 0.5 h. Slowly raise the temperature and reflux the reaction for 4-6 h, and the intermediate 5-amino-formyl-3(4-chloro-butyryl)-indole spot disappears as monitored by thin-layer chromatography, and the dehydration reaction is considered complete. Then lower the temperature below 10°C, and add 5% sodium hydroxide aqueous solution to adjust the pH value to about 8. Stand to separate the layers, separate the dichloromethane, then extract once with 200 L of dichloromethane, combine the organic phases, dry, and concentrate under reduced pressure to obtain 5-cyano-3(4-chloro-butyryl)-indole Intermediate crude product 51.0 kg.

Embodiment 2

[0020] Example 3 Synthesis of 5-cyano-3 (4-chlorobutyl)-indole

[0021] Add 400 L of solvent dichloromethane and 50.0 kg of raw material 5-cyano-3(4-chloro-butyryl)-indole into the enamel reaction kettle. After stirring and dissolving, add 5.1 kg of diborane at room temperature for about 1 h, then slowly raised to reflux for 3 h, the spot of the intermediate 5-cyano-3 (4-chloro-butyryl-indole) disappeared as monitored by thin-layer chromatography, and the reduction reaction was considered complete. Concentration under reduced pressure gave 45.6 kg of solid 5-cyano-3 (4-chlorobutyl-indole) crude product. The crude product was dissolved in 200 L of methanol, filtered, concentrated, cooled to crystallize, filtered, and dried to obtain 41.2 kg of 5-cyano-3(4-chlorobutyl)-indole fine product.

Embodiment 3

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Abstract

The invention discloses a new synthetic process of a vilazodone intermediate 5-cyano-3(4-chlorobutyl)-indole. The synthetic process comprises the steps of enabling 5-amino-formyl-indole and 4-chlorobutyryl chloride undergo a 3-bit acylation reaction and a dehydration reaction of an amido bond in the presence of a catalyst to produce 5-bit cyan, then performing a decarbonylation reaction in the presence of a reducing agent to generate a product, and finally refining by the product by use of methanol to obtain high-purity high-content 5-cyano-3(4-chlorobutyl)-indole. The process is concise, simple to operate and applicable to large-scale industrial production.

Description

technical field [0001] The present invention relates to the synthesis of a novel vilazodone intermediate for the treatment of severe depression—5-cyano-3(4-chlorobutyl)-indole, in particular to the synthesis of 5-amino-formyl- Indole and 4-chlorobutyryl chloride complete the 3-position acylation reaction and the dehydration of the amide bond under the action of a catalyst to produce the 5-position cyano group, and then decarbonylate the product under the action of a reducing agent, and finally separate and purify to obtain high-purity, high-content 5-cyano-3(4-chlorobutyl)-indole. Background technique [0002] As a new type of antidepressant, vilazodone has a dual mechanism of action, being a selective serotonin reuptake inhibitor and a partial serotonin 1A receptor agonist. The drug can rapidly increase the extracellular concentration of 5-hydroxytryptamine receptors while stimulating 5-hydroxytryptamine receptors, and is currently the fastest-acting antidepressant drug. ...

Claims

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Application Information

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IPC IPC(8): C07D209/10
CPCC07D209/12
Inventor 彭学东张梅赵金召闫勇义
Owner ZHANG JIA GANG VINSCE BIO PHARM
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