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

Lyrica preparation method

A technology of pregabalin and diethyl isobutylmalonate, which is applied in the field of preparation of pregabalin, can solve the problems of unfavorable product industrialization, low yield, high toxicity, etc., and achieve easy quality control and by-product The effect of fewer reaction steps

Active Publication Date: 2009-11-25
SHANGHAI CHENPON PHARMA TECH
View PDF5 Cites 11 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] Method one is to use toxic sodium azide in the process of synthesizing azide (formula A), which is not conducive to the industrialization of products
Method 2 is to synthesize racemate compound (formula B), then make pregabalin (formula i) after chiral resolution, the shortcoming of this method is that yield is lower during resolution

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
  • Lyrica preparation method
  • Lyrica preparation method
  • Lyrica preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0055] The preparation of embodiment 1 S-2-methyl-4-aminopentanol (formula viii)

[0056] Add 100ml of anhydrous tetrahydrofuran and 45.8g (0.35mol) of S-(+)-leucine into a 500ml three-neck flask, cool to 0°C in an ice bath under stirring, and slowly add 3.3g (0.087mol) of LiAlH 4 The mixture with 100ml of tetrahydrofuran was added dropwise, and the mixture was incubated and stirred for 3 hours. After the reaction is completed, dilute sulfuric acid is added dropwise to the reaction solution to adjust the pH value to neutral, then 300ml of water is added, extracted with 200ml×3 dichloromethane, the organic layer is separated, the organic layer is dried over anhydrous magnesium sulfate, and the organic layer is collected after filtration. layer, the organic solvent was recovered under reduced pressure, and the residue was subjected to column chromatography (petroleum ether: ethyl acetate = 20:1 v / v) to obtain 34.7 g of formula viii.

[0057] 1 H-NMR (CDCl 3 )

[0058] δ: 0.8...

Embodiment 2

[0059] The preparation of embodiment 2 S-2-bromo-4-methylpentanol (formula vii)

[0060] Dissolve 11.7g (0.1mol) of S-2-methyl-4-aminopentanol and 46.1g (0.32mol) of cuprous bromide in 80ml of water, and slowly add 24.6ml of 48% hydrogen bromide dropwise under stirring at room temperature ( 0.22 mol), the dropwise addition was completed, the reaction system was cooled to -15°C, and 8.56 g (0.12 mol) of sodium nitrite was slowly added to the reaction system in batches under nitrogen protection (about 5 g / 15 minutes). After the addition was complete, the temperature was maintained and the reaction was stirred for 2.5 hours. Then the temperature was raised to 0° C. and the reaction was stirred for 6 hours. After the reaction was complete, 100 ml of ethyl acetate × 6 was used to extract the combined organic phases. The organic layer was dried over anhydrous magnesium sulfate, filtered, and the organic solvent was recovered under reduced pressure. The residue was subjected to colum...

Embodiment 3

[0061] Example 3 Preparation of S-2-bromo-4-methylpentyloxy-tert-butyldimethylsilane (formula vi)

[0062] Under nitrogen protection, 9.8g (54mmol) of S-2-bromo-4-methylpentanol, 0.66g (5.4mmol) of dimethylaminopyridine, 20ml of triethylamine and 175ml of dichloromethane were added to a 500ml three-necked flask. Cool to 0° C. in an ice bath, and slowly add 10.24 g (68 mmol) of tert-butyldimethylsilyl chloride. After the addition was complete, the temperature was maintained and the reaction was stirred for 30 minutes, and then stirred and reacted at room temperature for 5 hours. Add 200ml of distilled water and stir for 30 minutes, extract with 100ml×3 dichloromethane, combine the organic phase, and use 100ml of saturated NaHCO for the organic phase 3 Extraction and washing, and extraction and washing with distilled water three times, the organic layer was dried over anhydrous magnesium sulfate, filtered, concentrated under reduced pressure, and the residue was subjected to co...

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 a lyrica preparation method. Lyrica is an analogue of a mammal neurotransmitter of Lambda-propalanine, is clinically used for curing diabetic peripheral neuralgia and post-herpetic neuralgia and adjunctively treating partial adult seizure. The Lyrica is synthesized through using S-(+)-leucine as a raw material by a chemical method without decomposition, and has the advantages of easily obtained raw materials, less reaction steps, mild reaction conditions, high reaction yield, and the like.

Description

technical field [0001] The present invention relates to pharmaceutical technology, in particular to a preparation method of pregabalin (formula i). Background technique [0002] As we all know, pregabalin (formula i) is an analogue of mammalian neurotransmitter λ-aminobutyric acid, and pregabalin can replace gabapentin. It was launched in 2004 and approved by the US FDA. It is currently clinically used for the treatment of neuralgia and adjuvant treatment of partial epilepsy in adults. [0003] Regarding the preparation of pregabalin, there are "Bioorg Med Lett, 1994, 4: 823-826", "Orgprocess Res Dev, 1997, 1: 26-28", "Med Res Dev, 1999, 19: 149-177", WO9640617, WO9638405 and other literature and patent reports. [0004] Based on the above-mentioned documents and patents, it can be seen that the synthesis of pregabalin involves a variety of preparation methods. In summary, there are mainly two methods. Method one is to synthesize azide (formula A) by asymmetric synthesis ...

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): C07C229/08C07C227/14A61P25/04A61P25/08
Inventor 吴波峰张挺杜狄峥
Owner SHANGHAI CHENPON PHARMA TECH
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