The preparation method of dp-iv inhibitor alogliptin intermediate

A technology of intermediates and raw materials, which is applied in the field of preparation of alogliptin intermediates, can solve the problems of time-consuming and low process yield, and achieve the effect of good purity and simple post-treatment

Active Publication Date: 2021-10-15
HENAN MEDICAL COLLEGE
View PDF5 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Some responses are particularly time-consuming
[0004] CN105392772B discloses a variety of alogliptin intermediates and processes for further synthesizing downstream products, but some processes have problems such as low yields

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 1

[0017] To an ice-cold solution of benzyl 2-(2,5-difluorophenyl)-2-oxoethylcarbamate (0.1 mmol) in dimethylformamide (DMF) was added NaH (0.14 mmol), and the solution was Leave it in the ice bath for 20 minutes; continue to add propargyl ethanesulfonate (0.11 mmol) to the solution, and stir the mixture in the ice bath for 2 h. Add 10ml of water and wash with Et 2 O (3×5ml) extraction, the obtained organic phase was concentrated, and then purified by silica gel chromatography (eluent: cyclohexane / ether) to obtain 31.3 mg of a white solid product, 1-(2,5-difluorophenyl) The molar yield of benzyl-1-oxopent-4-yn-2-ylcarbamate was 91%. 1 H-NMR (CDCl 3 ),δ:

[0018] 7.55-7.59(m,1H),7.23-7.39(m,6H),7.12-7.18(m,1H),6.03(d,1H),5.28-5.34(m,1H),5.14(s,2H), 3.00(dm,1H), 2.71(dm,,1H), 2.00(t,1H).

Embodiment 2

[0020] To an ice-cold solution of benzyl 2-(2,5-difluorophenyl)-2-oxoethylcarbamate (0.1 mmol) in dimethylformamide (DMF) was added NaH (0.14 mmol), and the solution was It was left in the ice bath for 20 minutes; propargyl mesylate (0.11 mmol) was continued to be added to the solution, and the mixture was stirred in the ice bath for 2 h. Add 10ml of water and wash with Et 2 O (3×5ml) extraction, the obtained organic phase was concentrated, and then purified by silica gel chromatography (eluent: cyclohexane / ether) to obtain 27.9 mg of a white solid product, 1-(2,5-difluorophenyl) The molar yield of benzyl-1-oxopent-4-yn-2-ylcarbamate was 81%.

Embodiment 3

[0022] To an ice-cold solution of benzyl 2-(2,5-difluorophenyl)-2-oxoethylcarbamate (0.1 mmol) in dimethylformamide (DMF) was added NaH (0.14 mmol), and the solution was Leave it in the ice bath for 20 minutes; continue to add propargyl ethanesulfonate (0.12 mmol) to the solution, and stir the mixture in the ice bath for 2 h. Add 10ml of water and wash with Et 2 O (3×5ml) extraction, the obtained organic phase was concentrated, and then purified by silica gel chromatography (eluent: cyclohexane / ether) to obtain 33.0 mg of a white solid product, 1-(2,5-difluorophenyl) The molar yield of benzyl-1-oxopent-4-yn-2-ylcarbamate was 96%.

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 preparation method of an alogliptin intermediate, comprising, raw material A 2-(2,5-difluorophenyl)-2-oxoethylcarbamate alkyl ester, and raw material B alkyl sulfonate Acid propargyl ester reaction, obtains product C 1-(2,5-difluorophenyl)-1-oxopent-4-yn-2-ylcarbamate alkyl ester. The present invention has a unique approach, selects a specific alogliptin intermediate as a research direction, provides an efficient process, and the one-step reaction yield can be as high as 96%.

Description

technical field [0001] The invention relates to a preparation method of an alogliptin intermediate. Background technique [0002] Alogliptin is a novel dipeptidyl peptidase-IV (DP-IV) inhibitor that can be used in the treatment of type 2 diabetes, obesity and hypertension. [0003] Since Merck disclosed the drug, after a comprehensive search, dozens of families of patents around the world have disclosed its synthesis process, some of which require many synthesis steps and use quite expensive starting materials such as 2,5-difluorobenzaldehyde or 2- Bromo-1,4-difluorobenzene, preparation of Weinreb amides and use of carbonyldiimidazole (CDI). Some responses are particularly time-consuming. [0004] CN105392772B discloses a variety of alogliptin intermediates and processes for further synthesizing downstream products, but some processes have problems such as low yields. Contents of the invention [0005] The present invention has a unique approach, selects a specific alog...

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): C07C269/06C07C271/18
CPCC07C269/06C07C271/18
Inventor 刘岩李苏颖梁金英安硕黄丽珍
Owner HENAN MEDICAL COLLEGE
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