Prepn and application of N-[2-(aryloxy)ethyl]-2-(arylthio) benzyl amine derivative

A technology of methoxyphenylsulfanyl and derivatives, applied in the direction of organic chemistry, etc., can solve problems such as hysteresis effect, nausea, anxiety, insomnia, urgent research, etc., and achieve the effect of no high temperature and high pressure operation and simple preparation process

Inactive Publication Date: 2005-12-14
TIANJIN UNIV
View PDF0 Cites 6 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] Tricyclic antidepressants (TCA, Anticholinergic) appeared in the 1950s, and 5-HT selective reuptake inhibitors SSRIs (Fluoxetine, Paroxetine, Sertaline, Citalopram, Fluvoxamine) appeared in the 1980s because of their good antidepressant properties, It has gradually replaced TCA and has become the leading product in the antidepressant market. However, because SSRI indirectly acts on all 5-HT receptors, it has side effects such as nausea, anxiety, insomnia, and sexual dysfunction. The weakness is the hysteresis effect, that is, the antidepressant effect usually appears after the first 2-6 weeks after starting to take the medicine. Therefore, in order to find antidepressants that are safe, fast-acting, and have few side effects, pharmacists have conducted various researches. try
[0004] Since the 1990s, some antidepressants with new mechanisms of action have appeared, such as NE / 5-HT reuptake inhibitor sNRI (Venlaxine, Milnacipran, Duloxetine, Nefazodone), selective monoamine oxidase inhibitor MAOI (Moclobe mide, Toloxatone), selective NE Reuptake inhibitor NARI (Reboxetine), NE energy and specific 5-HT energy antidepressant NaSSa (Mirtazapine), although these drugs have improved efficacy and rapid onset compared with SSRIs, but there are still 1 -2-week lag period, so research on faster-acting drugs is urgent

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
  • Prepn and application of N-[2-(aryloxy)ethyl]-2-(arylthio) benzyl amine derivative
  • Prepn and application of N-[2-(aryloxy)ethyl]-2-(arylthio) benzyl amine derivative
  • Prepn and application of N-[2-(aryloxy)ethyl]-2-(arylthio) benzyl amine derivative

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0027] Preparation of intermediates:

[0028] 2-(2-Methoxyphenylthio)benzoic acid

[0029] In the mixture of o-methoxythiophenol (48mmol, 6.72g) and DMF (120ml), add anhydrous potassium carbonate (144mmol, 19.9g), copper powder (12.6mmol, 0.8g), o-chlorobenzoic acid ( 40mmol, 6.26g), the reaction mixture was warmed up to 100°C and stirred vigorously for 24h, cooled, 600ml of distilled water was added to the mixture, filtered, the filtrate was decolorized with activated carbon for 30min, filtered, the filtrate was adjusted to pH 7.0 with 6mol / L hydrochloric acid, filtered, and the filtrate was adjusted to pH3 .0, white crystals were precipitated, filtered, washed with water (20ml×3), and vacuum-dried to obtain white crystals (7.85g, 75.5%).

[0030] mp: 198.0~200.0℃.MS m / z: 260.0(M + , 100), 200.0(18), 171.0(21), 137.0(40), 124.0(18), 82.9(20), 45.0(17).

[0031] 2-(2-Methoxyphenylthio)benzyl alcohol

[0032] Lithium aluminum hydride (0.044mol, 1.67g) was dissolved in tetra...

Embodiment 1

[0038] (1) 2-phenoxybromoethane

[0039] Add 5% sodium hydroxide solution (100ml), phenol (0.04mol, 3.76g) into the reaction flask, stir and dissolve, then add 1,2-dibromoethane (0.24mol, 19.8ml), tetrabutylammonium bromide (0.66g), heated to 80°C for 12h. Extracted with chloroform (50ml×3), washed with water (50ml×3), dried with chloroform (anhydrous sodium sulfate), and evaporated the solvent under reduced pressure to obtain light yellow oil (5.08g, 63.2%).

[0040] (2) 2-phenoxyethylamine

[0041] Dissolve 2-phenoxybromoethane (0.0249mol, 5.0g) in methanol (20ml) and add 10% CH 3 OH-NH 3 (110ml), reacted at 50°C for 36h, removed methanol under reduced pressure, dissolved the residue in chloroform (50ml), extracted with 2N hydrochloric acid (50ml×3), neutralized the hydrochloric acid solution to pH9 at room temperature with 2N sodium hydroxide solution, extracted with chloroform (50ml×3) 3), dried (anhydrous sodium sulfate), and evaporated the solvent under reduced press...

Embodiment 2

[0045] (1) 2-(4-trifluoromethylphenyl)bromoethane

[0046] 5% sodium hydroxide solution (100ml), 4-trifluoromethylphenol (0.04mol, 5.84g) was added to the reaction flask, stirred and dissolved, and 1,2-dibromoethane (0.24mol, 19.8ml) was added successively, Tetrabutylammonium bromide (0.66g) was heated to 80°C for 12h. Extracted with chloroform (50ml×3), washed with water (50ml×3), dried with chloroform (anhydrous sodium sulfate), evaporated the solvent under reduced pressure to obtain a light yellow oil (5.24g, 48.7%).

[0047] (2) 2-(4-trifluoromethylphenyl)ethylamine

[0048] Dissolve 2-(4-trifluoromethylphenyl)bromoethane (0.0335mol, 9.0g) in methanol (20ml) and add 10% CH 3 OH-NH 3 (120ml), reacted at 50°C for 48h, removed methanol under reduced pressure, dissolved the residue in chloroform (50ml), extracted with 2N hydrochloric acid (50ml×3), neutralized the hydrochloric acid solution to pH9 at room temperature with 2N sodium hydroxide solution, extracted with chlorof...

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 present invention relates to the structure, preparation process and application of N-[2-(acryloxy)ethyl]-2-(arylthio) benzyl amine derivative with depression resisting activity, and belongs to the field of medicine chemical technology. The structure is shown. The preparation process includes the reaction between aryl phenol and 1, 2-dibromo ethane to produce 2-aryloxy bromoethane, the reaction of 2-aryloxy bromoethane with methanol solution of ammonia to produce 2-aryloxy ethylamine; the Ullmann sulfidation reaction between one-methoxyphenyl thiophenol and one-chlorobenzoic acid to produce sulfide; the reduction and chlorination of sulfide to produce 2-(2-arylphenylthio) benzyl chloride; and final N-alkylation with 2-aryloxy ethylamine to produce the destination product. The compound in the form of free alkali or salt is used in preparing medicine for depression.

Description

technical field [0001] The present invention relates to the structure, preparation method and application of a N-[2-(aryloxy)ethyl]-2-(arylthio)benzylamine derivative with antidepressant activity, which belongs to the field of medicinal chemistry . Background technique [0002] Depression is a common mental illness, which is an emotional disorder. As the pace of life continues to accelerate, people's mental pressure is gradually increasing. Depression has become a common disease in modern society, with a high incidence, and its incidence is rising rapidly. : According to incomplete statistics, at present the world's depression patients have accounted for 3%-5% of the world's population, almost seen in all ages, and its prevalence is about 3% in the general population, and the patient population in general hospital health services In patients with chronic physical diseases (such as cardiovascular disease, diabetes), the rate of depressive disorder can be as high as 20%, but ...

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): C07C323/32
Inventor 李爱军刘东志周雪琴
Owner TIANJIN UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Try Eureka
PatSnap group products

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

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap