Unlock instant, AI-driven research and patent intelligence for your innovation.

Preparation method of chiral tetrahydroimidazo [1, 5-a] piperazine medical intermediate

A technology of tetrahydroimidazole and 5-a, applied in organic chemistry methods, chemical instruments and methods, organic racemization, etc., can solve the problem of no synthetic route suitable for scale-up, and achieve mild reaction conditions and convenient use

Active Publication Date: 2021-06-11
SHANGHAI TIANYE CHEM +1
View PDF1 Cites 1 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

At present, there are relatively few synthetic methods reported in the literature, and there is no synthetic route suitable for scale-up. Therefore, it is necessary to study it and develop a suitable preparation method to meet market demand.

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
  • Preparation method of chiral tetrahydroimidazo [1, 5-a] piperazine medical intermediate
  • Preparation method of chiral tetrahydroimidazo [1, 5-a] piperazine medical intermediate
  • Preparation method of chiral tetrahydroimidazo [1, 5-a] piperazine medical intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0026] The first step: the synthesis of 2,2,2-trifluoro-N-(3-methyl-pyrazin-2-ylmethyl)-acetamide.

[0027]

[0028] Add 123.6g (1.0mol) of 3-methyl-2-pyrazineethylamine and 1L of dichloromethane into the reaction flask, lower the temperature and control it at -2-2°C, add 231g (1.1mol) of trifluoroacetic anhydride, and At this temperature, 276.9 g (3.5 mol) of pyridine was added dropwise. After the drop was completed, the temperature was slowly raised to 20-25° C., and the reaction was carried out for 2 hours. HPLC detected 0.3% of the raw material, and 1 M hydrochloric acid was added to adjust the pH=4-5. Extract with dichloromethane, combine the organic phases, wash with potassium bicarbonate aqueous solution, wash with saturated brine, concentrate the organic phase, add n-heptane and filter to obtain 2,2,2-trifluoro-N-(3-methyl- Pyrazin-2-ylmethyl)-acetamide 200.5g, yield 91.5%, HPLC: 99.1%. 1 HNMR (400MHz, CDCl 3 )δ:8.20(m,2H),6.31(s,1H),4.55-4.46(m,2H),2.35(s,3H).

...

Embodiment 2

[0032] The second step: the synthesis of 8-methyl-3-trifluoromethylimidazo[1,5-a]pyrazine.

[0033]

[0034] Add 190 g (0.867 mol) of 2,2,2-trifluoro-N-(3-methyl-pyrazin-2-ylmethyl)-acetamide and 950 mL of phosphorus oxychloride into the reaction flask, and heat up to 60- At 70°C, add 135.4g (0.954mol) of phosphorus pentoxide, raise the temperature to 80-85°C, and react for 3-5 hours. TLC detects that the reaction of the raw materials is complete, concentrate under reduced pressure to remove phosphorus oxychloride, and cool down to -10°C. Add 300mL of water at 0°C dropwise, control the temperature by adding 1N aqueous sodium hydroxide solution to adjust the pH=7-7.5, add dichloromethane, raise the temperature to 20-25°C, separate layers, extract the aqueous phase with dichloromethane, and combine the organic phases , concentrated, added n-heptane to beat at room temperature, filtered to obtain 126.4 g of 8-methyl-3-trifluoromethylimidazo[1,5-a]pyrazine, yield 72.5%, HPLC: 9...

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 preparation method for synthesizing (R)-8-methyl-3-trifluoromethyl-5, 6, 7, 8-tetrahydroimidazo [1, 5-a] piperazine, and belongs to the technical field of medical intermediates. The preparation method comprises the following steps: reacting 3-methyl-2-pyrazine ethylamine serving as a raw material with trifluoroacetic anhydride under an alkaline condition to obtain 2, 2, 2-trifluoro-N-(3-methyl-pyrazine-2-ylmethyl)-acetamide, then carrying out cyclization under the catalysis of a condensing agent to obtain 8-methyl-3-trifluoromethyl imidazo [1, 5-a] pyrazine,then carrying out palladium-carbon hydrogenation to obtain 8-methyl-3-trifluoromethyl-5, 6, 7, 8- -tetrahydroimidazo [1, 5-a] piperazine, and then splitting by D-DBTA to obtain the (R)-8-methyl-3-trifluoromethyl-5, 6, 7, 8-tetrahydroimidazo [1, 5-a] piperazine; and the raw materials of the synthesis process are common raw materials in the market and are convenient to use, the reaction conditions are relatively mild, and process verification is carried out on hectogram scale verification.

Description

technical field [0001] The invention belongs to the technical field of pharmaceutical intermediates, in particular to (R)-8-methyl-3-trifluoromethyl-5,6,7,8-tetrahydroimidazo[1,5-a]piperazine method of preparation. Background technique [0002] Imidazopiperazine organic compounds widely exist in biologically active natural products, drugs and candidate drugs, and can be used as corticotropin releasing factors and melanocortin receptors, etc., and its derivatives have good bioactivity, It can often be used for the treatment of coronary artery dilation, nerve stability and neuropeptide drugs (such as orexin), and peptides synthesized with other amino acids for the treatment of diabetes. In addition, its biological activity also includes antibacterial, antifungal, antitumor and so on. Tetrahydroimidazopiperazine organic compounds are widely used in organic synthesis, especially in the synthesis of heterocyclic compounds and biologically active natural products. [0003] (R)-...

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): C07B57/00C07D487/04
CPCC07B57/00C07D487/04C07B2200/07
Inventor 薛峰刘洪强谢楠田贝贝
Owner SHANGHAI TIANYE CHEM
Features
  • R&D
  • Intellectual Property
  • Life Sciences
  • Materials
  • Tech Scout
Why Patsnap Eureka
  • Unparalleled Data Quality
  • Higher Quality Content
  • 60% Fewer Hallucinations
Social media
Patsnap Eureka Blog
Learn More

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

© 2025 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com