Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

3-(4-(4-substituted-piperazino)-1-butyryl)indolyl-5-formonitrile and application thereof

A piperazine and protecting group technology, applied in the field of medicinal chemistry, can solve problems such as unmentioned and increased synthesis costs, and achieve the effects of increased reactivity, low reaction cost, and mild reaction conditions

Active Publication Date: 2012-11-28
SICHUAN QINGMU PHARMA CO LTD
View PDF8 Cites 2 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] Chinese patent ZL99814385.5 mentions that 5-cyanindole and 4-chlorobutyryl chloride are used as raw materials to obtain 3-(4-chlorobutyl)-5 through Friedel-Crafts reaction and sodium borohydride reduction. - cyanindole, but no mention of a further method for the preparation of 3-(4-piperazin-1-ylbutyl)indole-5-carbonitrile (formula IV)
Wherein the method for preparing 3-(4-chlorobutyl)-5-cyanindole adopts the same idea as that of the patent ZL99814385.5, only slightly different in the catalyst, and also has the unavoidable side effect of Friedel-Crafts alkylation. Reaction product, and the problem that makes product purity reduce, and the yield of reduction deoxygenation is only 26%, makes synthesis cost greatly increase

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • 3-(4-(4-substituted-piperazino)-1-butyryl)indolyl-5-formonitrile and application thereof
  • 3-(4-(4-substituted-piperazino)-1-butyryl)indolyl-5-formonitrile and application thereof
  • 3-(4-(4-substituted-piperazino)-1-butyryl)indolyl-5-formonitrile and application thereof

Examples

Experimental program
Comparison scheme
Effect test

preparation example 1

[0044]Preparation Example 1 Preparation of 3-(4-(4-(4-methoxybenzyl)piperazine)-1-butyryl)indole-5-carbonitrile via ethyl bromobutyrate

[0045] 1) Preparation of ethyl 4-(4-(4-methoxybenzyl)piperazine)-1-butyrate

[0046]

[0047] At 25°C, add 1-(4-methoxybenzyl)piperazine (500.0g, 2.42mol) and ethyl 4-bromobutyrate (520.1g, 2.67mol) into 5L of acetonitrile, stir until completely dissolved , and potassium carbonate (501.7 g, 3.63 mol) was added. Heat up to 80°C and keep stirring for about 6 hours. TLC showed that the reaction was complete, filtered, and the filtrate was concentrated under reduced pressure. To the concentrated residue were added 3 L of 1N hydrochloric acid and 1 L of ethyl acetate, mixed thoroughly, and the aqueous layer was separated and washed with 1 L of ethyl acetate. The aqueous phase was adjusted to pH 10 with 6N sodium hydroxide solution, extracted twice with 2 L of dichloromethane, the organic phases were combined, washed with 1 L of saturated br...

preparation example 2

[0058] Preparation Example 2 Preparation of 3-(4-(4-(4-methoxybenzyl)piperazine)-1-butyryl)indole-5-carbonitrile via tert-butyl bromobutyrate

[0059] 1) Preparation of tert-butyl 4-(4-(4-methoxybenzyl)piperazine)-1-butyrate

[0060]

[0061] At 25°C, add 1-(4-methoxybenzyl)piperazine (20.0g, 97.0mmol), tert-butyl 4-bromobutyrate (22.7g, 101.8mmol) into 200ml of acetonitrile, stir, and dissolve After clearing, potassium carbonate (20.1 g, 145.4 mmol) was added. Warming up to 70° C. and stirring for about 8 hours. TLC showed that the reaction was complete, filtered, and the filtrate was concentrated under reduced pressure. Add 200ml of 0.1N hydrochloric acid and 100ml of ethyl acetate to the concentrated residue, mix well, separate the water layer, and wash with 100ml of ethyl acetate. The aqueous phase was adjusted to pH 10 with 6N sodium hydroxide solution, extracted twice with 200 ml of ethyl acetate, the organic phases were combined, washed with 100 ml of saturated br...

preparation example 33

[0069] Preparation Example 3 Preparation of 3-(4-(4-(2,4-dimethoxybenzyl)piperazine)-1-butyryl)indole-5-carbonitrile

[0070] 1) Preparation of 4-(4-(2,4-dimethoxybenzyl)piperazine)-1-butyrate

[0071] Referring to the first step in Preparation Example 1 or 2, using 1-(4-(2,4-dimethoxybenzyl))piperazine as raw material, 4-(4-(2,4-di Methoxybenzyl)piperazine)-1-butyric acid ethyl ester and 4-(4-(2,4-dimethoxybenzyl)piperazine)-1-butyric acid tert-butyl ester.

[0072] 2) Preparation of 4-(4-(2,4-dimethoxybenzyl)piperazine)-1-butanoic acid

[0073] Referring to the second step in Preparation Example 1 or 2, 4-(4-(2,4-dimethoxybenzyl)piperazine)-1-butyric acid can be prepared.

[0074] 3) Preparation of 4-(4-(2,4-dimethoxybenzyl)piperazine)-1-butyryl chloride hydrochloride

[0075] With reference to the third step in Preparation Example 1 or 2, 4-(4-(2,4-dimethoxybenzyl)piperazine)-1-butanoic acid reacts with thionyl chloride to obtain 4- (4-(2,4-dimethoxybenzyl)piperazine)-1...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention relates to the field of chemical synthesis of medicines, particularly a 3-(4-(4-substituted-piperazino)-1-butyryl)indolyl-5-formonitrile and a preparation method thereof, and application of the compound for preparing an intermediate 3-(4-piperazino-1-yl-butyl)indolyl-5-formonitrile for synthesizing vilazodone.

Description

technical field [0001] The invention belongs to the technical field of medicinal chemistry, and in particular relates to a 3-(4-(4-substituted piperazine)-1-butyryl)indole-5-carbonitrile and a preparation method thereof, and the compound is used for preparing synthetic vitamin Use of the intermediate 3-(4-piper-1-ylbutyl)indole-5-carbonitrile of razodone. Background technique [0002] Vilazodone is the first partial 5-HT1A receptor agonist and selective 5-HT reuptake inhibitor for the treatment of major depressive disorder in adults. [0003] [0004] Example 1 of Chinese patent ZL200680013816.1 discloses the use of Pd complexes to couple (5-bromobenzofuran-2-carboxamide) with 3-(4-piperazin-1-ylbutyl)indene through transition metal-catalyzed coupling. The method for preparing vilazodone from azole-5-carbonitrile (formula IV) is as follows: "Under protective gas, 20 ℃ and stirring, 80 mg of three (dibenzylidene acetone)-dipalladium and 65 mg of three Tert-butylphosphine...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/14
CPCY02P20/55
Inventor 王颖李泽林闫革新
Owner SICHUAN QINGMU PHARMA CO LTD
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com