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

Preparation method of vortioxetine

A technology of vortioxetine and preparation steps, which is applied in the field of preparation of vortioxetine, can solve problems such as unfavorable industrialization, cumbersome steps, and difficult purification, and achieve the effects of promoting development, simple process, and easy-to-obtain raw materials

Active Publication Date: 2014-05-14
优标易站(苏州)电子商务有限公司
View PDF14 Cites 30 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0015] Inspecting the above synthetic routes and preparation methods, although the process is constantly being optimized, there are still disadvantages such as rare raw materials, cumbersome steps, low yield and difficult purification, which are not conducive to industrialization

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
  • Preparation method of vortioxetine
  • Preparation method of vortioxetine
  • Preparation method of vortioxetine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] In a dry reaction flask under a nitrogen atmosphere, add 2-bromonitrobenzene (II) (10.0g, 0.05mol), 2,4-dimethylthiophenol (III) (7.59g, 1.1eq) and toluene 100mL, add tris(dibenzylideneacetone)dipalladium (0.46g, 0.01eq) and racemic 1,1'-binaphthyl-2,2'-diphenylphosphine (0.31g, 0.01eq) under stirring, room temperature React for 15 minutes. Potassium tert-butoxide (6.2 g, 1.1 eq) was added, the temperature was raised to reflux, and the reaction was stirred for 2 hours. The temperature was lowered to 0°C, and the reaction was continued for 2 hours. After filtration, the filtrate was distilled under reduced pressure to obtain 11.8 g of light yellow viscous liquid 2-(2,4-dimethylphenylsulfanyl)nitrobenzene with a yield of 91.1%.

Embodiment 2

[0040] In a dry glass tube reactor under a nitrogen atmosphere, add cuprous iodide (0.95g, 0.1eq), sodium tert-butoxide (4.8g, 1.0eq) and 30mL of acetonitrile, and add 2-bromonitrobenzene ( II) (10.0g, 0.05mol) and 2,4-dimethylthiophenol (III) (7.59g, 1.1eq), sealed and reacted at 0°C with a mercury lamp for 12-15 hours. Reduce to normal pressure, distill off the solvent under reduced pressure, dissolve the residue with ether, filter, and wash the filtrate with 5% dilute hydrochloric acid, saturated saline and pure water successively, and dry over anhydrous magnesium sulfate. The solvent was removed under reduced pressure to obtain 10.2 g of light yellow viscous liquid 2-(2,4-dimethylphenylsulfanyl)nitrobenzene (IV), with a yield of 78.8%.

Embodiment 3

[0042] Add 2-(2,4-dimethylphenylsulfanyl) nitrobenzene (IV) (2.59g, 10mmol), ferric chloride (0.27g, 1mmol), activated carbon 0.4g and ethanol in the reaction flask 50mL, add 80% hydrazine hydrate (1.25g, 20mmol) dropwise at room temperature, after the addition, raise the temperature to 50-60°C, react for 4-5 hours, filter, concentrate to remove the solvent ethanol, and recrystallize the residue with isopropyl ether to obtain Off-white solid 2-(2,4-dimethylphenylsulfanyl)aniline (V) 2.1 g, yield 91.7%.

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 discloses a preparation method of vortioxetine (I). The preparation method comprises the following steps: subjecting a compound shown in a formula (II) as a raw material and 2,4-dimethylthiophenol (III) to condensation to generate 2-(2,4-dimethylphenylthioalkyl)nitrobenzene (IV) or 2-(2,4-dimethylphenylthioalkyl)aniline (V) which is obtained by reducing the 2-(2,4-dimethylphenylthioalkyl)nitrobenzene (IV), and subjecting the 2-(2,4-dimethylphenylthioalkyl)aniline (V) and a compound shown in a formula (VI) to cyclization under alkaline conditions to obtain the vortioxetine (I). The preparation method is accessible in raw materials, is concise in process, is economical and environment-friendly and is suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis route design and preparation of raw materials and intermediates, and in particular relates to a preparation method of vortioxetine. Background technique [0002] Vortioxetine is a new antidepressant drug developed by Lundbeck of Denmark and Takeda Pharmaceutical of Japan. Because the compound does not have a standard Chinese translation name, the applicant hereby transliterates it as "vortioxetine". In September 2013, the drug was approved by the US Food and Drug Administration (FDA) under the trade name Brintellix. The drug is a 5-HT3, 5-HT7, 5-HT1D receptor antagonist, a 5-HT1B receptor partial agonist, a 5-HT1A receptor agonist, and a 5-HT transporter inhibitor. To antidepressant effect, for the treatment of major depressive disorder in adults. [0003] The chemical name of Vortioxetine is: 1-[2-(2,4-dimethylphenylsulfanyl)-phenyl]piperazine, and its structural formula is: [0004...

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 许学农
Owner 优标易站(苏州)电子商务有限公司
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