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

Saxagliptin and saxagliptin salt preparation method

A compound and reaction technology, applied in the field of preparing saxagliptin and its salts, can solve the problems of not being suitable for large-scale industrial production, serious environmental impact, complicated post-treatment, etc., and achieve cheap raw materials, simple post-reaction treatment, and high reaction efficiency. Mild and easy-to-control effects

Inactive Publication Date: 2015-12-09
SHANGHAI DESANO CHEM PHARMA +1
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

But this method needs to use excessive trifluoroacetic anhydride and pyridine, especially needs a large amount of pyridine, and aftertreatment is comparatively complicated, and has serious impact on environment, and utilizes the reaction of trifluoroacetic anhydride and pyridine dehydration to produce more By-products, including trifluoroacetic anhydride and hydroxyl to generate ester groups (amide groups are not converted to cyano groups), or products of tert-butoxycarbonyl removal
In U.S. Patent No. 7214702B2, a method for converting amides into cyano groups using phosphorus oxychloride is disclosed. In this method, phosphorus oxychloride is a dangerous reagent, and the reaction is violent and difficult to operate. Therefore, the current prior art is not suitable for industrialized large-scale production requirements.

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
  • Saxagliptin and saxagliptin salt preparation method
  • Saxagliptin and saxagliptin salt preparation method
  • Saxagliptin and saxagliptin salt preparation method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Embodiment 1: the preparation of formula II compound

[0024]

[0025] The compound of formula III (43.3g, 0.1mol) was dissolved in a mixed solvent formed by 100mL N,N-dimethylformamide and 330mL ethyl acetate, then lowered to 0-10°C, and cyanuric chloride (14.8g , 0.08mol), keep warm at 0-10°C and stir for 2-6 hours, add 400mL of water, stir for 2-3 hours, adjust the pH ≈ 8 in the reaction system with sodium hydroxide solution, separate the liquid, and use dichloromethane for the water layer Extract, combine the organic phases, and concentrate under reduced pressure to obtain 34.46 g of the compound of formula II with a molar yield of 83.3% and an HPLC purity of 96.8%.

Embodiment 2

[0026] Embodiment 2: the preparation of formula II compound

[0027] The compound of formula III (43.3g, 0.1mol) was dissolved in a mixed solvent formed by 100mL N,N-dimethylformamide and 330mL dichloromethane, then lowered to 0-10°C, and cyanuric chloride (14.8g, 0.08mol), keep warm at 0-10°C and stir for 2-6 hours, add 400mL water, stir for 2-3 hours, adjust the pH ≈ 8 in the reaction system with sodium hydroxide solution, separate the layers, and extract the water layer with dichloromethane , the organic phases were combined and concentrated under reduced pressure to obtain 35.9 g of the compound of formula II with a molar yield of 86.5% and an HPLC purity of 97.6%.

Embodiment 3

[0028] Embodiment 3: the preparation of formula I compound

[0029]

[0030] Dissolve the compound of formula II (34.5g, 0.1mol) in 100mL of dichloromethane, add hydrochloric acid-diethyl ether solution dropwise at 0-5°C, after dropping, keep warm at 0-5°C and stir for 1-2 hours, then concentrate under reduced pressure The reaction liquid obtained 34.9 g of saxagliptin hydrochloride, and the molar yield was 99.2%.

[0031] Dissolve the above-mentioned saxagliptin hydrochloride in 30 mL of water, add dropwise sodium hydroxide solution at 0-10°C to adjust the pH to ≈8.0, then extract with dichloromethane for 3 times, collect the organic phase, and concentrate under reduced pressure. 30.1 g of saxagliptin was obtained with a molar yield of 96.0% and an HPLC purity of 97.8%.

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 present invention discloses a saxagliptin and saxagliptin salt preparation method, which includes the following reaction shown in the specification, and is characterized in that: according reaction a, a compound of formula III is reacted with cyanuric chloride in an organic solvent to produce a compound of formula II. The method has the advantages of safe and easy operation, available and cheap raw materials, easy-control and mild reaction conditions, simple reaction post-processing, high yield, and the like, can achieve the requirements of low-cost, large-scale production of high purity saxagliptin, and has significant industrial value.

Description

technical field [0001] The invention relates to a method for preparing saxagliptin and a salt thereof, belonging to the technical field of medicinal chemistry. Background technique [0002] Saxagliptin is a highly efficient, selective and competitive dipeptidyl peptidase-IV (DPP-IV) inhibitor jointly developed by Bristol-Myers Squibb and AstraZeneca. Preclinical and clinical studies have confirmed its The curative effect is outstanding and the effect is long-lasting. In 2009, the FDA approved it for the treatment of type 2 diabetes. Its chemical structure is as follows: [0003] [0004] JournalofMedicinalChemistry, 2005,48(15), discloses the method for preparing saxagliptin in 5025-5037, and reaction scheme is as follows: [0005] [0006] It can be seen from the above route that converting amide into cyano is a relatively critical step. Among them, US2013012723 discloses the use of trifluoroacetic anhydride and pyridine for dehydration to convert amides into cyano...

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): C07D209/52
Inventor 李竟鹏赵楠曾振亚
Owner SHANGHAI DESANO CHEM PHARMA
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