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

Aripiprazole intermediate synthesis method

A synthesis method and dihydrogen technology are applied in the field of medicine and chemical industry, which can solve the problems of reducing the reaction yield and achieve the effect of saving cost.

Inactive Publication Date: 2014-03-26
DISHA PHARMA GRP +1
View PDF3 Cites 3 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] WO200814156A reports the synthesis method of 7-(4-bromobutoxy)-3,4-dihydro-2(1H)quinolinone with low 7-BQB content, which is unique in that it adds Adsorb silica gel to process the reaction crude product, and then undergo recrystallization and purification. Although the content of 7-BQB in the obtained product is lower than 0.6%, the reaction yield is also lower, and the highest is only 49.2%.

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
  • Aripiprazole intermediate synthesis method
  • Aripiprazole intermediate synthesis method
  • Aripiprazole intermediate synthesis method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0017] 7-Hydroxy-3,4-dihydro-2(1H)quinolinone (81.5g, 0.5mol), potassium carbonate (138g, 1mol), hexadecyltributylphosphine bromide (25.35g, 0.05mol ), 1,4-dibromobutane (324g, 1.5mol), and reflux reaction in 800mL methyl isobutyl ketone for 1.5 hours. Cool to room temperature, filter, and beat the filter cake with methyl tert-butyl ether for 30 minutes, combine the mother liquor and concentrate to dryness, add n-heptane, crystallize for 3 hours, and filter. Blast dried overnight to obtain 136 g of white solid with a yield of 92.3% (HPLC purity 99.2%, impurity 7-BQB, 0.58%).

Embodiment 2

[0019] 7-Hydroxy-3,4-dihydro-2(1H)quinolinone (81.5g, 0.5mol), potassium carbonate (138g, 1mol), triphenylpropylphosphine bromide (1.93g, 0.005mol), 1,4-Dibromobutane (324g, 1.5mol) was reacted in 800mL methyl isobutyl ketone at 40°C for 1 hour. Cool to room temperature, stir overnight, filter, filter the cake with methyl isobutyl ketone for 30 minutes, combine the mother liquor and concentrate to dryness, add n-heptane, crystallize for 3 hours, and filter. Blast dried overnight to obtain 135 g of white solid with a yield of 91.3% (HPLC purity 99.15%, impurity 7-BQB, 0.62%).

Embodiment 3

[0021] 7-Hydroxy-3,4-dihydro-2(1H)quinolinone (81.5g, 0.5mol), potassium carbonate (138g, 1mol), triphenylethylphosphine iodide (4.18g, 0.025mol), 1,4-Dibromobutane (324g, 1.5mol) was reacted in 800mL methyl isobutyl ketone at 70°C for 1 hour. After filtering, the filter cake was beaten with butyl acetate for 30 minutes, the combined mother liquor was concentrated to dryness, n-heptane was added, crystallized for 3 hours, and filtered. Blast dried overnight to obtain 137.8 g of white solid with a yield of 92.7% (HPLC purity 99.04%, impurity 7-BQB, 0.61%).

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 provides a synthesis method for an aripiprazole intermediate namely 7-(4-bromobutoxy)-3,4-dihydro-2(1H)-quinolinone as shown in the formula I. In the aripiprazole intermediate synthesized through the synthesis method, the content of impurities shown in the formula II is less than 0.8%, the HPLC purity of the aripiprazole intermediate is larger than 99.0%, the reaction yield is 90-93%, the operation is simple, the cost can be controlled, and the aripiprazole intermediate is suitable for large-scale industrialized application.

Description

Technical field: [0001] The invention relates to a synthesis method of an aripiprazole intermediate 7-(4-bromobutoxy)-3,4-dihydro-2(1H)quinolinone, which belongs to the field of medicine and chemical industry. Background of the invention: [0002] Aripiprazole, the chemical name is 7-[4-[4-(2,3-dichlorophenyl)-1-piperazinyl]butoxy]-3,4-dihydroquinolinone, produced by Japan Developed by Otsuka Pharmaceutical Co., Ltd. and launched in the United States in 2002, it belongs to atypical antipsychotic drugs and mainly treats schizophrenia. [0003] U.S. Patent US5006528 provides a kind of synthetic method of aripiprazole, and route is as follows: [0004] [0005] According to the method described in US5006528, aripiprazole is obtained through two-step synthesis, the first step is the synthesis of 7-(4-bromobutoxy)-3,4-dihydro-2(1H)quinolinone, potassium carbonate In the presence of 7-hydroxyl-3,4-dihydro-2(1H)quinolinone and 3 times the amount of 1,4-dibromobutane reacted in...

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): C07D215/22
CPCC07D215/22
Inventor 吴晓东
Owner DISHA PHARMA GRP
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