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

Application of asymmetric hydrogenation in synthesis of Trelagliptin intermediate

An intermediate and asymmetric technology, applied in the field of drug synthesis, can solve problems such as low product yield, high cost, and complexity, and achieve the effect of simple synthesis method, good product quality, and high yield

Inactive Publication Date: 2017-12-08
SUZHOU XINEN PHARMA
View PDF2 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] In the prior art, the synthesis process of trexagliptin intermediates is often more complicated, the cost is higher, and there are also defects of low product yield and poor quality, which cannot be suitable for industrialized large-scale 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
  • Application of asymmetric hydrogenation in synthesis of Trelagliptin intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0028] Preparation of compound (3)

[0029] Add 20 L of absolute ethanol and 2 kg (10 mol) of compound (2) as the reaction solvent into a 50 L reactor at room temperature, then add 848 g (11 mol) of ammonium acetate, and heat the reaction solution to reflux after the addition. The reaction was tracked by TLC. After 7 hours, the reaction was completed. The temperature was lowered to about 25°C, 20L of water was added, stirred and crystallized for 2 hours, filtered, the filter cake was washed with 10L of water, and dried to obtain 1.86 kg (9.37 mol) of compound (3). The rate is 93.7%. HPLC detection purity: 97.7%.

[0030] 1 H NMR (400 MHz, DMSO- d 6 ) δ 6.92 (s, 2H), 5.97 – 5.70 (m, 1H), 3.10 –2.83 (m, 2H), 2.05 – 1.80 (m, 4H), 1.43 (s, 9H).

[0031] ESI+ [M-Boc] + =97.

[0032] Preparation of compound (4)

[0033] Add 1.78 kg (9 mol) of compound (3) in 25L of anhydrous dichloromethane to a 50L autoclave at room temperature, add [Rh(cod) 2 ] BF 4 36 g (0.09 mol) and ...

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 provides a method for synthesizing an intermediate of compound trexagliptin of formula (1). The compound of formula (2) is used as the starting material, and the compound of formula (1) is finally obtained through the following series of reactions, that is, the Trexagliptin intermediate: Compared with the prior art, there are many synthesis steps and complicated synthesis process for the trexagliptin intermediate. The synthesis method of the present invention is simple and easy, with low cost, high yield and good product quality, suitable for large-scale industrial production.

Description

technical field [0001] The invention relates to a synthesis method of a trexagliptin intermediate, which belongs to the technical field of medicine synthesis. Background technique [0002] Trelagliptin (common name: Trelagliptin succinate, trade name Zafatek), chemical name: (R)-2-((6-(3-aminopyridin-1-yl)-3-methyl-2,4 -Dioxy-3,4-dihydropyrimidin-1(2H)-yl)methyl)-4-fluorobenzonitrile succinate. The molecular weight of trelagliptin succinate: 475.47; CAS registration number: 1029877-94-8 (Trelagliptin Succinate), 865759-25-7 (Trelagliptin); the structural formula is shown in formula 1: [0003] [0004] Formula 1 [0005] Trexagliptin was developed by Takeda Pharmaceutical Company of Japan. On March 26, 2015, it was approved by PMDA in Japan for the treatment of type 2 diabetes. Trexagliptin is a DPP-4 inhibitor drug. It is a long-acting selective dipeptidyl peptidase-4 (DPP- 4) Inhibitor, which can effectively inhibit the activity of DPP-4, prevent the glucagon-like p...

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): C07D211/56C07B53/00
CPCC07D211/56C07B53/00C07B2200/07
Inventor 王爱玉
Owner SUZHOU XINEN 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