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

Preparation method of perampanel intermediate

A technology for intermediate and pyridine is applied in the field of preparation of perampanel intermediate 5--2-pyridone, which can solve the problems of unfavorable industrialized production, few preparation methods, complicated operation and the like, and achieves shortening of production cycle and process route. The effect of novel and simplified process operation

Active Publication Date: 2015-02-18
NANJING HUAWE MEDICINE TECH DEV
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Among the synthesis methods reported in the literature above, method 1 requires the use of butyllithium for the preparation of compound 13, requiring ultra-low temperature reaction (<-70°C), or the use of highly toxic tin reagents, which also lead to complicated operations and are not conducive to industrial production.
In the second method, highly toxic tin reagents are also used, and methyl protection and deprotection are required, which prolongs the preparation process and increases the production cycle, which is not conducive to industrial production
[0010]5-(pyridin-2-yl)-2(1H)-pyridone, as an important intermediate of perampanel, is not sold in the market, and the existing There are few preparation methods, and it is urgent to find a new process with low production cost, simple process and suitable for 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
  • Preparation method of perampanel intermediate
  • Preparation method of perampanel intermediate
  • Preparation method of perampanel intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0028] Example 1: Synthesis of 6-chloronicotinyl chloride (compound BL01)

[0029] Add 1.4kg of 6-chloronicotinic acid into 7L of toluene, stir and disperse. Then add 4.2Kg of thionyl chloride, heat to 80-90°C, and react for 10 hours. After the reaction was complete, it was concentrated to dryness under reduced pressure to obtain compound BL01, which was kept for future use.

Embodiment 2

[0030] Example 2: Synthesis of N-methoxy-N-methyl-6-chloronicotinamide (compound BL02)

[0031] 1.5 kg of dimethylhydroxylamine hydrochloride was dispersed in 10 L of dichloromethane, and the 6-nicotinoyl chloride obtained in Example 1 was slowly added dropwise into the reaction system, and reacted for 1 hour. After the reaction was completed, it was washed with water and saturated sodium chloride successively. It was dried over anhydrous sodium sulfate and concentrated under reduced pressure to obtain 1.65kg of compound BL02.

[0032] 1 H NMR (CDCl 3 , δ ppm): 3.39 (s, 3H), 3.73 (s, 3H), 7.32-7.37 (m, 1H), 7.73-7.80 (m, 1H), 8.59-8.61 (m, 1H); MS (ES+) m / z 210.6.

Embodiment 3

[0033] The synthesis of embodiment 3,2-chloro-5-acetylpyridine (compound BL03)

[0034] Disperse 1.6kg of compound (BL02) in 8L of tertiary methyl ether, and add 3L of methylmagnesium chloride solution dropwise. React for 1 hour. Stop the reaction, pour the reaction solution into 10L of water, and extract with dichloromethane. The organic phase was washed successively with water and saturated sodium chloride, dried over anhydrous sodium sulfate, and concentrated under reduced pressure to obtain 1.2kg of compound BL03.

[0035] 1 H NMR (CDCl 3 , δ ppm): 3.98 (s, 3H), 7.34-7.39 (m, 1H), 7.65-7.76 (m, 1H), 8.59-8.61 (m, 1H); MS (ES+) m / z 157.1.

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 relates to a preparation method of a perampanel intermediate 5-(pyridin-2-yl)-2(1H)-pyridinone which has the advantages of simplicity in operation, easily available raw materials, low production cost and good quality of the product and is suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical production, and in particular relates to a preparation method of a perampanel intermediate 5-(pyridin-2-yl)-2(1H)-pyridone. [0002] Background technique [0003] Perampanel, the chemical name is 3-(2-cyanophenyl)-5-(2-pyridyl)-1-phenyl-1, 2-dihydropyridin-2-one hydrate, It is an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (α-amino-3-hydroxy-5-methyl-4-isoxa-zolep-propionate acid, AMPA) receptor antagonist , which reduces neuronal hyperexcitation by inhibiting postsynaptic AMPA receptor glutamate activity. This is the first anti-epileptic drug with this mechanism of action approved by the FDA. It is clinically used as an adjuvant treatment for patients with partial seizures of epilepsy aged 12 and above. Food and Drug Administration (FDA) approved marketing, trade name Fycompa. [0004] The literature reports the following two synthetic methods of perampanel: [0005] Method 1: ...

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): C07D213/64
CPCC07D213/61C07D213/64
Inventor 包金远徐峰吴启光蒋玉伟张孝清
Owner NANJING HUAWE MEDICINE TECH DEV
Features
  • Generate Ideas
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

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

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com