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

Synthetic method for vortioxetine hydrobromide

A technology for the synthesis of vortioxetine hydrobromide and its synthesis method, which is applied in the field of synthesis of vortioxetine hydrobromide, can solve the problems of harsh reaction conditions, low product purity, and high price, and achieve mild reaction conditions and high purity , the effect of easy access to raw materials

Active Publication Date: 2016-02-24
山东川成医药有限公司
View PDF7 Cites 4 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0017] Patent WO2013102573 reports a synthetic route of vortioxetine, which adopts a one-pot cooking method with high yield and only one step of reaction, but the product has low purity and is not easy to purify
[0018] Based on the above several synthetic routes, expensive palladium catalysts and phosphine ligands are used in the synthetic method, and the reaction conditions are relatively harsh, which is not conducive to industrial production

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
  • Synthetic method for vortioxetine hydrobromide
  • Synthetic method for vortioxetine hydrobromide
  • Synthetic method for vortioxetine hydrobromide

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0037] The synthesis of embodiment 12-(2,4-dimethylphenylsulfanyl) nitrobenzene

[0038] Add o-nitrothiophenol (14.5g, 0.1mol), 2,4-dimethyliodobenzene (25.5g, 1.1eq) and 145mL tetrahydrofuran into a dry 250mL four-necked reaction flask, and add sodium hydride ( 3.6g, 1.5eq), react at room temperature for 2 hours. After the reaction was completed, the solvent was removed by rotary evaporation, 145 mL of toluene and 145 mL of water were added, the liquid was extracted and separated, the toluene layer was dried by adding anhydrous sodium sulfate, decolorized by activated carbon, and then the solvent was evaporated to obtain a yellow-brown oily substance 2-(2,4-dimethyl phenylthio) nitrobenzene 23.2g, yield 89.6%, purity 99.5%. MS(m / z):260[M+H] + ; 1 HNMR (400MHz, CDCl 3 )δ: 8.24(dd, J=8.2, 1.3Hz, 1H), 7.47(d, J=7.8Hz, 1H), 7.33~7.28(m, 1H), 7.22~7.15(m, 2H), 7.11(d ,J=7.8Hz,1H),6.72(dd,J=8.2,1.1Hz,1H),2.40(s,3H),2.31(s,3H).

Embodiment 2

[0039] The synthesis of embodiment 22-(2,4-dimethylphenylsulfanyl) nitrobenzene

[0040] Add o-nitrothiophenol (14.5g, 0.1mol), 2,4-dimethylbromobenzene (20.4g, 1.1eq) and tetrahydrofuran 145mL into a dry 250mL four-necked reaction flask, and add sodium hydride ( 3.6g, 1.5eq), react at room temperature for 2 hours. After the reaction was completed, the solvent was removed by rotary evaporation, 145 mL of toluene and 145 mL of water were added, the liquid was extracted and separated, the toluene layer was dried by adding anhydrous sodium sulfate, decolorized by activated carbon, and then the solvent was evaporated to obtain a yellow-brown oily substance 2-(2,4-dimethyl phenylthio) nitrobenzene 20.8g, yield 80.3%, purity 99.4%.

Embodiment 3

[0041] Synthesis of Example 32-(2,4-dimethylphenylthio)nitrobenzene

[0042] Add o-nitrothiophenol (14.5g, 0.1mol), 2,4-dimethyliodobenzene (25.5g, 1.1eq) and tetrahydrofuran 145mL into a dry 250mL four-necked reaction flask, and add calcium hydride ( 6.15g, 1.5eq), react at room temperature for 2 hours. After the reaction was completed, the solvent was removed by rotary evaporation, 145 mL of toluene and 145 mL of water were added, the liquid was extracted and separated, the toluene layer was dried by adding anhydrous sodium sulfate, decolorized by activated carbon, and then the solvent was evaporated to obtain a yellow-brown oily substance 2-(2,4-dimethyl phenylthio) nitrobenzene 21.3g, yield 82.1%, purity 99.0%.

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 synthetic method for vortioxetine hydrobromide. Firstly, 2-nitro thiophenol and 2,4-dimethyl iodobenzene are reacted, an intermediate 2-(2,4-dimethyl phenyl sulfenyl) nitrobenzene, the intermediate is subjected to reduction, 2-(2,4-dimethyl phenyl sulfenyl) phenylamine is prepared, then 2-(2,4-dimethyl phenyl sulfenyl) phenylamine and bis(2-chloroethyl)amine hydrochloride are subjected to a cyclization reaction, vortioxetine is prepared, finally, vortioxetine is reacted with hydrobromic acid and is salified, and vortioxetine hydrobromide is prepared. The total yield of vortioxetine hydrobromide can reach 65%, the method has advantages of cheap and easily available initial raw materials and simple synthetic technology, and meets requirements of large-scale industrial production.

Description

technical field [0001] The invention belongs to the field of organic drug synthesis, in particular to a method for synthesizing vortioxetine hydrobromide. Background technique [0002] Vortioxetine, the English name is Vortioxetine, the chemical name is: 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine, which is produced by the Danish Lundbeck Pharmaceutical Company (Lundbeck) and A new type of antidepressant drug jointly developed by Japan's Takeda Pharmaceutical Company (Takeda). In September 2013, the drug was approved by the FDA for marketing. The trade name is Brintellix. In December 2013, the drug was approved for marketing in the European Union. Its chemical structural formula is as follows: [0003] . [0004] The drug works through a combination of 2 mechanisms of action: modulation of receptor activity and inhibition of reuptake. In vitro studies have shown that vortioxetine is a 5-HT3 and 5-HT7 receptor antagonist, a 5-HT1B receptor partial agonist, a 5-HT...

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): C07D295/096
CPCC07D295/096
Inventor 孟庆亮闫海英韩立霞李国庆郭明刘怀振
Owner 山东川成医药有限公司
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