Preparation of agomelatine midbody, 2-(7-anisyl-1-naphthyl) ethylamine

A methoxyl and naphthyl technology, applied in the field of medicine, can solve the problems of high equipment requirements, low total yield, difficult industrial scale, etc., and achieve the effect of reducing one-step reaction, high total yield and safe operation

Active Publication Date: 2010-05-19
TIANJIN INSTITUTE OF PHARMA RESEARCH +1
View PDF1 Cites 17 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] (1) With 7-methoxy tetralone (III) as the starting material, 7 steps of synthetic formula (II) compound have been used, with 2-(7-methoxy-1-naphthyl) acetamide (VII ) used 2 steps to synthesize (II) compound for the starting material, the steps are longer, and the total yield is low
[0010] (2) The reduction of 2-(7-methox

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 of agomelatine midbody, 2-(7-anisyl-1-naphthyl) ethylamine
  • Preparation of agomelatine midbody, 2-(7-anisyl-1-naphthyl) ethylamine
  • Preparation of agomelatine midbody, 2-(7-anisyl-1-naphthyl) ethylamine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Add 15g of 2-(7-methoxy-1-naphthyl)acetamide (VII), 5.3g of sodium borohydride, 20.2g of boron trifluoride ethyl ether (47% content), and 300ml of tetrahydrofuran into the reaction flask, and reflux the reaction until the substrate disappears. Pour into dilute hydrochloric acid, extract twice with ethyl acetate, basify the aqueous layer with 10% sodium hydroxide, extract twice with ethyl acetate, combine the oil layers, dry over anhydrous magnesium sulfate, filter, recover ethyl acetate, evaporate Dry to give 2-(7-methoxy-1-naphthyl)ethylamine. Hydrochloric acid-ethyl acetate was added to precipitate a solid, which was filtered to obtain 12 g of off-white solid. The yield was 72.2%. The product is tested with a YRT-3 melting point apparatus, and the melting point of the product is 213-215° C. after testing. Then weigh 10 mg of the resulting product and dissolve it in 0.5 ml of organic solvent (DMSO-d 6 ), using Bruker AV400 to carry out NMR analysis on the sample, t...

Embodiment 2

[0026] Add 15g of 2-(7-methoxy-1-naphthyl)acetamide (VII), 7.6g of potassium borohydride, 101.3g of boron trifluoride ether, and 300ml of tetrahydrofuran into the reaction flask, and reflux until the substrate disappears. Pour into dilute hydrochloric acid, extract twice with ethyl acetate, alkalinize the aqueous layer with 10% sodium hydroxide, extract twice with ethyl acetate, combine the oil layers, dry over anhydrous magnesium sulfate, filter, pass through hydrochloric acid gas, solid Precipitated and filtered to obtain 13 g of off-white solid. The melting point is 214-215°C.

Embodiment 3

[0028] Add 10.8g of 2-(7-methoxy-1-naphthyl)acetamide (VII), 4.8g of sodium borohydride, 22g of aluminum trichloride, and 150ml of tetrahydrofuran into the reaction flask, and reflux until the substrate disappears. Add dilute hydrochloric acid, extract twice with ethyl acetate, alkalinize the aqueous layer with 10% sodium hydroxide, extract twice with ethyl acetate, combine the oil layers, dry over anhydrous magnesium sulfate, filter, add hydrochloric acid-ethyl acetate, solid Precipitated and filtered to obtain 12.8 g of off-white solid. The melting point is 213-215°C.

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 aims at providing a preparation method of 2-(7-anisyl-1- naphthyl) ethylamine (II) which is an important midbody of agomelatine. The preparation method uses 2- (7-anisyl-1-naphthyl) acetamide (VII) as an initiative raw material, only needs one reaction step, has higher yield, abolishes high-voltage hydrogenation, has mild conditions and does not need special devices.

Description

technical field [0001] The invention belongs to the field of medicine. The invention relates to a preparation method of 2-(7-methoxy-1-naphthyl)ethylamine and its hydrochloride. Background technique [0002] Agomelatine (agomelatine), the chemical name is N-[2-(7-methoxy-1-naphthyl) ethyl] acetamide (I), and its trade name is Valdoxan / Thymanax , the structural formula is as follows: [0003] [0004] Agomelatine is a new type of antidepressant, which is not only a melatonin (MT) receptor agonist, but also a 5-hydroxytryptamine (5-HT) 2C receptor antagonist. Agomelatine can effectively treat depression in adults, especially for major depressive disorder (MMD), and can effectively improve sleep parameters and maintain sexual function. [0005] [0006] The compound represented by formula (II) is an important intermediate 2-(7-methoxy-1-naphthyl)ethylamine for the synthesis of agomelatine. European patent specification EP0447285 reports the preparation method of a...

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
IPC IPC(8): C07C217/60C07C213/08
Inventor 陈蔚潘毅陶勇
Owner TIANJIN INSTITUTE OF PHARMA RESEARCH
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