Unlock instant, AI-driven research and patent intelligence for your innovation.

A kind of preparation method of antidepressant vortioxetine

A technology of vortioxetine and antidepressant, which is applied in the field of preparation of antidepressant vortioxetine, can solve the problems of low yield, high production cost, and high industrialization cost, and achieve simple and safe operation, low production cost, The effect of high yield

Active Publication Date: 2021-03-12
ANHUI THERAPY PHARMA CO LTD
View PDF12 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] There are following problems in this technique: 1, use 2,4-dimethyliodobenzene and o-bromothiophenol as starting raw materials, the starting materials are expensive, the source is unstable, the production cost is high, and o-bromothiophenol Has a strong foul smell and is not environmentally friendly
2. Use bis(dibenzylideneacetone) palladium and binaphthyl diphenylphosphine as catalysts, the price is more expensive, the industrialization cost is too high, and using palladium acetate as catalyst will easily cause the heavy metal content of the final product to exceed the standard
3. Severe side effects of piperazinyl
[0011] There are following problems in this technique: 1, use 2,4-dimethylthiophenol and o-bromoiodobenzene as starting raw materials, the starting raw materials are expensive, the source is unstable, the production cost is high, and 2,4-bis Methylthiophenol has a strong foul smell and is not environmentally friendly
2. Use bis(dibenzylideneacetone) palladium and binaphthyl diphenylphosphine as catalysts, the price is more expensive, the industrialization cost is too high, and using palladium acetate as catalyst will easily cause the heavy metal content of the final product to exceed the standard
3. Severe side effects of piperazinyl
Among them, compound 2 needs to be refluxed in tetrahydrofuran for 60 hours from compound 3 and 4, the reaction time is long, and the yield is also low, and the final product needs to be de-BOC later, and the operation route is long, 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
  • A kind of preparation method of antidepressant vortioxetine
  • A kind of preparation method of antidepressant vortioxetine
  • A kind of preparation method of antidepressant vortioxetine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0033] Weigh 42.7g (0.316mol, 1.0eq) of benzothiazole and place it in a 1.0L reactor, add 57.5g (0.411mol, 1.3eq.) of 2,4-dimethylchlorobenzene, 206.0g (0.632mol , 2eq.) cesium carbonate, 4.5g (31.6mmol, 10mol%) cuprous bromide, 500mL polyethylene glycol 200, stirred and reacted at 140°C for 22h under nitrogen protection. Cool down to room temperature, add 200mL of ethyl acetate and 300mL of water, stir well to make it uniform, then filter with diatomaceous earth, separate the liquid, and remove the solvent by rotary evaporation under reduced pressure to obtain a black viscous liquid with a purity of 95.3% by HPLC and a yield of 94.2%.

Embodiment 2

[0035] Weigh 41.1g (0.309mol) of iminodiacetic acid and place it in a 500ml reaction flask, add 205ml of acetic anhydride, heat to 150°C under nitrogen protection and reflux for 2h, cool down to obtain the product 2,6-dicarbonylmorpholine, the yield 96.2%.

Embodiment 3

[0037] The product 2-(2,4-dimethylphenylsulfanyl)aniline (IV) 68.2g (0.297mol, 1.0eq) obtained in Example 1 was added to the 2,6-dicarbonylmorpholine obtained in Example 2 34.2g (0.297mol, 1.0eq) of the mixed solution was heated to 150°C and refluxed for 3h, concentrated to remove the solvent, added 400ml of ethyl acetate, extracted with 200ml of water, and concentrated the organic layer to obtain 97.9g of a solid product with an HPLC purity of 94.6%. The rate is 95.5%.

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 antidepressant vortioxetine, which relates to the technical field related to raw materials; it comprises the following steps: taking formula benzothiazole as raw material, coupling with 2,4-dimethylchlorobenzene (III) Synthesis of 2-(2,4-dimethylphenylsulfanyl) aniline (IV), iminodiacetic acid (V) self-condensation synthesis 2,6-dicarbonyl morpholine (VI), compound IV2-(2 , 4-dimethylphenylsulfanyl) aniline and compound (VI) 2,6-dicarbonylmorpholine are condensed to obtain 4-[2-(2,4-dimethylphenylsulfanyl) phenyl]- 3,5-dioxopiperazine (VII), VII obtains vortioxetine through reduction again; The preparation method of vortioxetine of the present invention no longer uses volatile thiophenol derivatives with stench, Environmentally friendly, and the preparation method does not use precious metals and phosphorus ligand catalytic coupling, low production cost, simple and safe operation, high yield, high purity of the prepared vortioxetine, can meet the requirements of raw materials, and is suitable for industrialization 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 antidepressant vortioxetine. Background technique: [0002] Vortioxetine was jointly developed by Lundbeck and Takeda, the chemical name is 1-[2-(2,4-dimethylphenylthio)phenyl]piperazine, and its bisaryl sulfide amine The structure of the class is a new chemical structure class in depression drugs, which was approved by the US Food and Drug Administration (FDA) on September 30, 2013, for the treatment of adult depression (MDD). [0003] Serotonin is a messenger of pleasure that affects nearly every aspect of brain activity: from regulating mood, experience, and memory to shaping outlook on life. People with lower serotonin levels are more likely to experience depression, impulsive behavior, alcoholism, suicide, aggression, and violence. In addition, 5-hydroxytryptamine...

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 Patents(China)
IPC IPC(8): C07D295/096
Inventor 彭兵兵任磊孙玉行张红夺何斌马恩源
Owner ANHUI THERAPY PHARMA CO LTD