Synthesizing method of omarigliptin

A synthesis method and compound technology, applied in the field of pharmaceutical synthesis, can solve the problems of low product yield, high cost, poor quality and the like, and achieve the effects of simple and easy synthesis method, good product quality and low cost

Inactive Publication Date: 2017-10-10
SUZHOU XINEN PHARMA
View PDF3 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] In the prior art, the synthesis process of alogliptin is often more complicated, the cost is higher, and there are still 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

Examples

Experimental program
Comparison scheme
Effect test

Embodiment

[0021] Preparation of compound (3)

[0022] Under the protection of nitrogen, add 3.7 kg (10 mol) of compound (2), 271 g (1 mol) of mercuric chloride and 216 g (1 mol) of mercuric oxide into 20L ethanol (containing 5% water). After the completion of the reaction monitored by TLC, slowly add 25L of water, rise to room temperature, stir and crystallize, filter, wash the filter cake with 10L of water, and dry to obtain the crude product of compound (1), which is recrystallized from ethanol\water to obtain the refined product of compound (1). The product is 2.61 kg (9.2 mol), and the yield is 92.0%. HPLC detection purity: 98.1%.

[0023] 1 H NMR (400 MHz, DMSO- d 6 ) δ 7.51 – 7.09 (m, 3H), 5.20 (m, 1H), 4.74(d, J = 17.6 Hz, 1H), 4.56 – 4.35 (m, 2H), 3.90 (m, 1H), 3.30 – 2.57 (m, 3H), 1.17 (t, J = 6.0 Hz, 3H).

[0024] ESI+ [M+H] + =285.

[0025] Preparation of compound (5)

[0026] Under nitrogen protection, 2.56 kg (9.0 mol) of compound (3) and 1.85 kg (9.9 mol) of c...

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 provides a synthesizing method of an omarigliptin compound shown in a formula (1). The synthesizing method comprises the following steps: by using a compound shown in a formula (2) as an initial raw material, performing a series of following reaction, so as to finally obtain the compound shown in the formula (1), namely omarigliptin, wherein reaction formulae are shown in the description. Compared with the prior art with multiple synthesizing steps and complicated synthesizing technology for synthesizing the omarigliptin, the synthesizing method has the advantages that the method is simple, the implementing is easy, the cost is lower, the yield rate is higher, the product quality is higher, and the synthesizing method is suitable for large-scale industrialized production.

Description

technical field [0001] The invention relates to a synthesis method of alogliptin, which belongs to the technical field of medicine synthesis. Background technique [0002] Ologliptin (common name: Omarigliptin, trade name Marizev), chemical name ((2R,3S,5R)-2-(2,5-difluorophenyl)-5-(2-(methylsulfonyl) )pyrrolo[3,4-c]pyrazolyl-5(2H,4H,6H)-yl)tetrahydro-2H-pyran-3-amine). The molecular weight of alogliptin: 398.43; CAS registration number: 1226781-44-7; the structural formula is shown in formula 1: [0003] [0004] Formula 1 [0005] Alogliptin was developed by Merck & Co. Omarigliptin, a drug for the treatment of type 2 diabetes approved in Japan on September 30, 2015, is a type of DPP-4 inhibitor, which can be achieved by taking it only once a week. [0006] prior art literature [0007] Non-patent literature: 1: Org. Lett., 2014, vol.16, pp5422-5425; Non-patent literature 2: J. Med.Chem., 2014, vol.57, pp3205-3212 [0008] Patent documents: WO 2013 / 003249 and US20...

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): C07D487/04
CPCC07D487/04
Inventor 佘阳
Owner SUZHOU XINEN PHARMA
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
Try Eureka
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap