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

Method for synthesizing indiplon

A synthetic method, the technology of indiplon, is applied in the new synthetic field of indiplon, which can solve the problems of harsh reaction conditions, long reaction time, expensive reagents, etc., and achieve short reaction time, low synthesis cost and excellent yield Effect

Inactive Publication Date: 2009-12-02
ARMY MEDICAL UNIV
View PDF6 Cites 8 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0039] In summary, in the known synthetic methods of indiplon, there are some deficiencies in the synthetic route and synthetic process, such as long reaction time, harsh reaction conditions, expensive reagents, highly toxic, unsafe and environmental pollution, etc.

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
  • Method for synthesizing indiplon
  • Method for synthesizing indiplon
  • Method for synthesizing indiplon

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[0067] The method of the present invention is the preparation of indiplon:

[0068] (1) 3-aminoacetophenone at 0~room temperature, slowly add acetyl anhydride dropwise, react for 2~5 hours to convert into 3-acetamidoacetophenone, remove unreacted acetic acid with a large amount of water, use ethanol or acetic acid The pure product was obtained by recrystallization of ethyl ester; the yield was 90-99%.

[0069] (2) 3-Acetamidoacetophenone is dissolved in tetrahydrofuran or toluene, first reacted with powdered potassium hydroxide, and then reacted with methyl iodide for 5 to 12 hours to transform N-methyl-N-(3-acetylbenzene base) acetamide, filter off the inorganic salt, wash with water, and remove traces with toluene to obtain the product with a yield of 85-95%. The product can be directly used in the next reaction without further purification.

[0070] (3) N-methyl-N-(3-acetylphenyl)acetamide is dissolved in alcohol, first reacted with sodium ethoxide, and then reacted with ...

Embodiment 1

[0087] Example 1 Preparation of 3-acetamidoacetophenone

[0088]

[0089] Add 318g of m-aminoacetophenone (2.356mol) in a 1000ml Erlenmeyer flask, slowly add 166ml of acetic anhydride (2.452mol) dropwise within 2 hours under ice-cooling and stirring, and a large amount of solids precipitate out. TLC showed that the starting material disappeared, and the reaction mixture was poured into 2500 ml of ice water, filtered with suction, washed with distilled water until neutral, and dried to obtain 381.6 g of light yellow solid. Melting point: 125.6.~127.3°C; heat to dissolve with 2000ml ethyl acetate, filter out impurities while hot, and the filtrate naturally cools down to room temperature. A large amount of solid was precipitated, filtered with suction, washed with ice ethyl acetate, and dried to obtain 3-acetamidoacetophenone 351.9 as colorless granular crystals, with a yield of 96%. Melting point: 127.0.~128.4°C.

[0090] The product is detected by nuclear magnetic resonan...

Embodiment 2

[0091] Example 2 Preparation of N-methyl-N-(3-acetylphenyl)acetamide

[0092]

[0093] In a 250ml round-bottomed flask, add a magnet, dry it with a vacuum flame, cool to room temperature, and pass through N 2 , 11.128 grams of powdered KOH (0.199 mol) were added rapidly, 160 ml of a tetrahydrofuran solution containing 17.295 grams of 3-acetamidoacetophenone (0.098 mol) and 15 ml of methyl iodide (0.244 mol) were added, and stirred overnight at room temperature. Inorganic salts were filtered off, washed with 3×30ml of water, and concentrated. A small amount of water was removed from 40 ml of toluene to obtain 17.593 g of N-methyl-N-(3-acetylphenyl)acetamide as a colorless oil, with a yield of 94%.

[0094] The product is detected by nuclear magnetic resonance, and the data are as follows: 1 HNMR (400MHz, CDCl 3 )δ ppm : 1.872(s, 3H, COC H 3 ), 2.625 (s, 3H, NCOCH 3 ), 3.280 (s, 3H, NCH 3 ), 7.402(d, 2H, J=7.6Hz, 2'-H), 7534(t, 1H, J=7.6Hz, 3'-H), 7.7.791(s, H, 6'-H...

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

PropertyMeasurementUnit
Melting pointaaaaaaaaaa
Login to View More

Abstract

The invention relates to a method for synthesizing indiplon, which comprises the following steps: using low-cost available 3-aminoacetophenone as a starting raw material; reacting the 3-aminoacetophenone with acetic anhydride to convert the 3-aminoacetophenone into 3-acetamido-acetophenone; reacting the obtained 3-acetamido-acetophenone with powdered potassium hydrate first and then with iodomethane to convert the 3-acetamido-acetophenone into N-methyl-N-(3-acetyl-phenyl)-acetamide; reacting the obtained N-methyl-N-(3-acetyl-phenyl)-acetamide with ethyl formate under the action of sodium ethylate to obtain an alkali metal 3-(N-methyl-N-acetyl)amino-beta-ketone-phenyl-propionaldehyde enol salt; and synthesizing the indiplon by condensing the obtained alkali metal 3-(N-methyl-N-acetyl) amino-beta-ketone-phenyl-propionaldehyde enol salt and (3-amino-1H-pyrazole-4-yl)-2-thiophene ketone. The method has the advantages of low cost, mild reaction condition, safety and environmental protection, and easy industrialized production, and the obtained indiplon can be used as hypnagogue for treating anhypnosis.

Description

technical field [0001] The present invention relates to a new synthetic method of indiplon, specifically, a kind of 3-aminoacetophenone as raw material, through alkali metal 3-(N-methyl-N-acetyl)amino-β- A method for efficiently synthesizing indiplon by condensation of ketophenyl propionaldehyde enolate and (3-amino-1H-pyrazol-4-yl)-2-thiophenemethanone. technical background [0002] "Insomnia" refers to a patient's lack of sleep or any disturbed state associated with the sensation of sleep. Insomnia is a common disorder. The most direct consequence of insomnia is the disorder of the body's metabolism, reduced productivity, and changes in mood, behavior, and psychomotor functions. In addition, insomnia is associated with other diseases, including depression, anxiety, gastrointestinal tract, and cardiovascular disease. System obstacles, etc. The continuous experiment at the University of Chicago in the 1990s fully illustrated this point: the people who underwent the experi...

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): C07D487/04
Inventor 周向东徐长荣苏敏
Owner ARMY MEDICAL UNIV
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