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

Preparation method of rifamycin-nitroiminazole coupled molecule

A technology of nitroimidazole coupling and rifamycin is applied in the field of preparation of rifamycin-nitroimidazole coupling molecules, which can solve the problems of low product yield and the like, and achieve the effect of improving product yield

Active Publication Date: 2015-11-11
TENNOR THERAPEUTICS (SUZHOU) LTD
View PDF4 Cites 7 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] Because the disadvantage of the above preparation method is that not only the reaction conditions must be controlled at low temperature, but also the yield of the final product is low, so it is very important to study the preparation method with normal temperature and high yield.

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 rifamycin-nitroiminazole coupled molecule
  • Preparation method of rifamycin-nitroiminazole coupled molecule
  • Preparation method of rifamycin-nitroiminazole coupled molecule

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0025] Embodiment 1 A kind of preparation method of rifamycin-nitroimidazole coupling molecule

[0026] Step 1: Synthesis of 2-(2-methyl-5-nitro-1hydro-imidazol-1-yl)ethyl methanesulfonate

[0027]

[0028] Add dry dichloromethane (500mL) into a 1L three-necked flask, add metronidazole (98.6g, 0.576mol), then add 4-dimethylaminopyridine (3.5g, 0.03mol) and triethylamine (120mL) . After cooling down to 0°C, methanesulfonyl chloride (54 mL, 0.692 mol) was slowly added dropwise to the reaction solution. After the dropwise addition, the reaction was slowly raised to room temperature and stirred overnight. After the reaction was complete, the solid was filtered out, and the solid was dried in vacuo to further remove residual solvent. The resulting crude product was added to 500 mL of water, stirred, filtered, and the filter cake was vacuum-dried to obtain 2-(2-methyl-5-nitro-1 hydrogen-imidazol-1-yl) ethyl methanesulfonate (139 g , yield 97.5%). Mass Spectrum (ESI, M+1): The...

Embodiment 2

[0038] Embodiment 2 A kind of preparation method of rifamycin-nitroimidazole coupling molecule

[0039] Step 1: Synthesis of 2-(2-methyl-5-nitro-1hydro-imidazol-1-yl)ethyl trifluoromethylsulfonate

[0040]

[0041] Add dry dichloromethane (500mL) into a 1L three-necked flask, add metronidazole (98.6g, 0.576mol), then add 4-dimethylaminopyridine (3.5g, 0.03mol) and triethylamine (120mL) . After cooling to -10°C, trifluoromethanesulfonic anhydride (195 g, 0.692 mol) was slowly added dropwise. After the dropwise addition, the temperature was slowly raised to room temperature and stirred overnight. After the reaction was complete, the solid was filtered out, and the filter cake was vacuum-dried. The resulting crude product was added to 500 mL of water, stirred, filtered, and the filter cake was vacuum-dried to obtain 2-(2-methyl-5-nitro-1 hydrogen-imidazol-1-yl)ethyl trifluoromethylsulfonium Ester (173 g, yield 99.1%). Mass Spectrum (ESI, M+1): theoretical 304.0, found 304....

Embodiment 3

[0050] Embodiment 3 A kind of preparation method of rifamycin-nitroimidazole coupling molecule

[0051] Step 1: Synthesis of 2-(2-methyl-5-nitro-1hydro-imidazol-1-yl)ethyl p-toluenesulfonate

[0052]

[0053] Add dry dichloromethane (500mL) into a 1L three-necked flask, add metronidazole (98.6g, 0.576mol), then add 4-dimethylaminopyridine (3.5g, 0.03mol) and triethylamine (120mL) . After cooling to 10°C, p-toluenesulfonyl chloride (132 g, 0.692 mol) was slowly added dropwise to the reaction liquid. After the dropwise addition, the temperature was slowly raised to room temperature, and stirred overnight. After the reaction was complete, the solid was filtered out, and the filter cake was vacuum-dried. The obtained crude product was added into 500 mL of water, stirred, filtered, and the filter cake was vacuum-dried to obtain the title compound (158.3 g, yield 84.5%). Mass spectrum (ESI, M+1): theoretical 326.1, found 326.1.

[0054] Step 2: Synthesis of 9-(2-(2-methyl-5-ni...

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 of a rifamycin-nitroiminazole coupled molecule. By using metronidazole as the raw material and changing the synthesis route, the preparation method overcomes the defect that the reaction condition must be controlled at low temperature, and enhances the yield of the target product.

Description

technical field [0001] The invention relates to the technical field of chemical synthesis, in particular to a preparation method of a rifamycin-nitroimidazole coupling molecule. Background technique [0002] Rifamycin is a class of antibiotics produced by Streptococcus mediterranei. It has a broad-spectrum antibacterial effect against Gram-positive bacteria such as Mycobacterium tuberculosis, Leprosy, Streptococcus, and pneumococcus, especially drug-resistant Staphylococcus aureus. Bacteria are very powerful. [0003] A rifamycin-nitroimidazole conjugate molecule is a derivative of rifamycin, named 4-deoxy-3,4-[2-spirocycle-[1-[2-(2-methyl- 5-nitro-imidazol-1-yl)ethyl]-piperidin-4-yl]]-(1hydrogen)-imidazo-(2,5-dihydro)rifamycin S, its structural formula is as follows I: [0004] [0005] U.S. Patent No. 7,678,791B2 reports the method for preparing the above-mentioned compound, and the synthetic route is as follows: [0006] [0007] Since the disadvantage of the ab...

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): C07D498/22
CPCC07D498/22
Inventor 马振坤张天元丁俊
Owner TENNOR THERAPEUTICS (SUZHOU) LTD
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