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

Asymmetrical synthesis method of lyrica

A technique of isobutylcarba and its synthesis method, which is applied in the field of chemistry and medicine, can solve the problems that chiral catalysts are expensive and not suitable for large-scale production, and achieve the effect of cheap raw materials, few reaction steps, and easy-to-obtain raw materials

Inactive Publication Date: 2018-05-25
SYNCOZYMES SHANGHAI
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The chiral catalyst used in this method is expensive, and the post-treatment needs to be purified by column chromatography, which only stays in the laboratory stage and is not suitable for scale-up 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
  • Asymmetrical synthesis method of lyrica
  • Asymmetrical synthesis method of lyrica
  • Asymmetrical synthesis method of lyrica

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] The synthesis of embodiment 1 ibugaba

[0031] (1) Preparation of compound 2

[0032] Add 3-isobutylglutaric acid (1kg) and acetic anhydride (0.66kg) into a 1.5L round-bottomed flask, reflux the reaction mixture at 135-145°C for 2.5-3 hours, and evaporate unreacted acetic anhydride under vacuum , and cooled to obtain 0.91kg of compound 2, which was directly carried out to the next step without purification.

[0033] (2) Preparation of compound 3

[0034] Add toluene (3L), (R)-(+)-1-phenethylamine (0.97kg) and DMAP (6.5g) in 6L round-bottomed flask, compound 2 (0.91kg) at -20~-10 ℃ ) in toluene (1.5L) was slowly added into the flask (1-1.5h was added), and the reaction was stirred at -20~-10°C for 3-5 hours. The reaction solution was extracted with NaOH aqueous solution, the aqueous phase was washed with toluene, the pH value was adjusted to 2 by adding hydrochloric acid (2N) aqueous solution, the aqueous phase was extracted with ethyl acetate, dried, concentrated und...

Embodiment 2

[0039] The synthesis of embodiment 2 Ibugaba

[0040] (1) Preparation of Compound 2

[0041] Add 3-isobutylglutaric acid (10kg) and acetic anhydride (6.6kg) into a 15L reactor, and the reaction mixture is refluxed at 135-145°C for 4-6 hours, and the unreacted acetic anhydride is evaporated under vacuum, cooled 9.0kg of compound 2 was obtained, which was directly carried out to the next step without purification.

[0042] (2) Preparation of Compound 3

[0043] Add toluene (30L), (R)-(+)-1-phenethylamine (9.7kg) and DMAP (65g) in 60L reaction kettle, under -20~-10 ℃, compound 2 (9.0kg) The toluene solution (15L) was slowly added into the flask (3-3.5h to complete the addition), and the reaction was stirred at -20~-10°C for 5-6 hours. The reaction solution was extracted with NaOH aqueous solution, the aqueous phase was washed with toluene, the pH value was adjusted to 2 by adding hydrochloric acid (2N) aqueous solution, the aqueous phase was extracted with ethyl acetate, dried...

Embodiment 3

[0048] The synthesis of embodiment 3 Ibugaba

[0049] (1) Preparation of Compound 2

[0050] Add 3-isobutylglutaric acid (1kg) and acetic anhydride (0.75kg) in the 1.5L round-bottomed flask, the reaction mixture was refluxed for 2 hours at 51°C, evaporate unreacted acetic anhydride under vacuum, and cool to obtain 0.85 kg of compound 2 was directly carried out to the next step without purification.

[0051] (2) Preparation of Compound 3

[0052] Toluene (3L), (R)-(+)-1-phenethylamine (0.92kg) and DMAP (6.2g) were added in a 6L round bottom flask, and compound 2 (0.85kg ) in toluene (1.5L) was slowly added into the flask (1-1.5h was added), and the reaction was stirred at -20~-10°C for 3-5 hours. The reaction solution was extracted with NaOH aqueous solution, the aqueous phase was washed with toluene, the pH value was adjusted to 2 by adding hydrochloric acid (2N) aqueous solution, the aqueous phase was extracted with ethyl acetate, dried, concentrated under reduced pressure, ...

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 an asymmetrical synthesis method of lyrica, wherein the synthesis steps comprise: carrying out a cyclic anhydridization reaction by using 3-isobutylglutaric acid as a raw material, carrying out an asymmetric ring-opening reaction with (R)-(+)-1-phenylethylamine, and sequentially carrying out a hydrogenation reaction and Huffman rearrangement to obtain lyrica. Compared to the synthesis method in the prior art, the synthesis method of the present invention has advantages of inexpensive and easily-available raw materials and less reaction steps, has the total yield of up to 60%, the purity of the product lyrica of more than 99% and the ee value of more than 99%, and has good application prospect in industrial scale up production.

Description

technical field [0001] The invention belongs to the field of chemical medicine, and in particular relates to an asymmetric synthesis method of ibugaba. Background technique [0002] Ibugaba, developed by Pfizer, is an aminobutyric acid (GABA) receptor antagonist for the treatment of peripheral neuralgia and partial seizures, with the chemical name (S)-3-aminomethyl-5-methyl caproic acid. In July 2004, it was approved by the European Union and launched in the UK for the first time. In December 2004, it was approved by the FDA for marketing, and the trade name was Lyrica. Ibugaba works mainly by regulating the pressure-dependent calcium channel in the central nervous system. After oral administration, it is absorbed through the intestinal transport mechanism mediated by the carrier of neutral amino acids, and has high bioavailability. Compared with the clinically used gabapentin, ibugaba has stronger anticonvulsant effect, fewer adverse reactions, low dosage, less frequent 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
Patent Type & Authority Applications(China)
IPC IPC(8): C07C227/04C07C229/08C07B53/00
CPCC07B53/00C07C227/04C07C231/02C07C231/08C07D309/32C07C229/08C07C233/05
Inventor 竺伟王波李兵豪
Owner SYNCOZYMES SHANGHAI
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