Eureka AIR delivers breakthrough ideas for toughest innovation challenges, trusted by R&D personnel around the world.

A kind of preparation method of Trexagliptin

A compound, methyl technology, applied in the field of preparation of trexagliptin, can solve the problem of low purity of trexagliptin, and achieve the effects of high conversion rate, mild reaction conditions and high total yield

Active Publication Date: 2018-07-13
山东四环药业股份有限公司
View PDF4 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

In this reaction, since the structure of R-3-aminopiperidine bishydrochloride contains both primary amine and secondary amine, two nucleophilic substitution products at different positions are generated in the reaction, resulting in poor purity of the target product trexagliptin. High, multiple refining and purification treatments are required to obtain high-purity trexagliptin

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
  • A kind of preparation method of Trexagliptin
  • A kind of preparation method of Trexagliptin
  • A kind of preparation method of Trexagliptin

Examples

Experimental program
Comparison scheme
Effect test

example 1

[0048] Example 1: Preparation of compound shown in formula 4

[0049] The compound shown in formula 6 (100g, 340.5mmol), the compound shown in formula 5 (49.0g, 375mmol) and potassium carbonate (94.0g, 682.0mmol) were added in N,N-dimethylformamide (600ml), Raise the temperature to 70°C and react for 2 hours. After the reaction, cool down to 20°C. Add 1800ml of water and 2M / L dilute hydrochloric acid to adjust the pH of the feed solution to ≤ 6. A large amount of solids are precipitated. After stirring for 30 minutes, filter, rinse with 100ml of ethanol, and dry to obtain Off-white compound 130.2g, purity 99.7%, maximum single impurity 0.1%. The yield was 98.9%.

[0050] ESI-MS: m / z([M+H] + ) is 387.4.

example 2

[0051] Example 2: step2-1, the preparation of compound (X is Cl) shown in formula 3-1

[0052] The compound shown in formula 4 (5g, 12.94mmol) was added in 50ml of dichloromethane, and the temperature was lowered to 0°C, and thionyl chloride (1.8g, 15mmol) was added dropwise. Concentrate under reduced pressure to dryness to obtain 4.9 g of a light yellow solid, with a yield of 93.5%, a purity of 98.7%, and a maximum single impurity of 0.1%.

[0053] ESI-MS: m / z([M+H] + ) is 405.8.

example 3

[0054] Example 3: step2-1, the preparation of compound (X is Br) shown in formula 3-1

[0055] Add the compound shown in Formula 4 (5g, 12.94mmol) into 50ml of dichloromethane, drop the temperature to 0°C, and add a solution of phosphorus oxybromide (4.3g, 15.0mmol) dropwise in dichloromethane, and continue the reaction for 1 hour after dropping , heated to 30° C. and concentrated under reduced pressure to dryness to obtain 5.5 g of a light yellow solid with a yield of 94.6%, a purity of 98.4%, and a maximum single impurity of 0.13%.

[0056] ESI-MS: m / z([M+H] + ) is 450.3.

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 Trelagliptin preparation method. The method comprises that a compound shown in the formula 6 and a compound shown in the formula 5 undergo a condensation reaction in the presence of an organic solvent and an alkali to produce a compound shown in the formula 4, a compound shown in the formula 2 is prepared through halogenations and azidation, or acid anhydride formation and azidation, or direct azidation, or esterification, hydrazide formation and azidation, or esterification and azidation, and Trelagliptin is prepared through a rearrangement hydrolysis reaction. The method has the advantages of mild reaction conditions, high conversion rate, less impurities, low cost and high finished product purity and is suitable for industrial production.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to a preparation method of trexagliptin. Background technique [0002] Trexagliptin is a once-weekly dipeptidyl peptidase IV (DPP-4) inhibitor that controls blood glucose levels through selective and sustained inhibition of DPP-4. DPP-4 is an enzyme that triggers the inactivation of incretin (glucagon-like peptide-1) and diabetes-dependent insulinotropic polypeptide (GIP), two incretins that play a role in blood glucose regulation important role. Inhibition of DPP-4 can increase blood glucose level-dependent insulin secretion, thereby controlling blood glucose levels. [0003] Trexagliptin, chemical name: 2-{[6-[(3R)-3-amino-1-piperidinyl]-3,4-dihydro-3-methyl-2,4-dioxo -1(2H)-pyrimidinyl]methyl}-4-fluoro-benzonitrile. Its structural formula is as follows: [0004] [0005] Chinese patent CN102675221 discloses a method for preparing trexagliptin, and its synthetic route is...

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 Patents(China)
IPC IPC(8): C07D401/04
CPCC07D401/04
Inventor 李刚孙崇国郭建军刘慧敏徐春海
Owner 山东四环药业股份有限公司
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
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