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

Tazobactam synthesis method

A technology of tazobactam and a synthesis method, applied in the field of synthesis of tazobactam, can solve the problems of lowering product yield, less demanding operation requirements, etc., and achieves the effects of high yield and low impurity content

Active Publication Date: 2012-08-22
山东安信制药有限公司 +1
View PDF3 Cites 20 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0020] Comparing the three different routes of 6-APA, each has advantages and disadvantages, but in comparison, route 1 has simple raw materials, less demanding operation requirements, and is easier for industrial production, but its disadvantages are: in the process of azidation In the process, some five-membered ring products are converted into six-membered ring by-products (the molar ratio of compound 7 and compound 7' generated by the azidation reaction is about 1: 1), thereby reducing the yield of the product

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
  • Tazobactam synthesis method
  • Tazobactam synthesis method
  • Tazobactam synthesis method

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Embodiment 1: the preparation of benzhydryl β-chloromethyl penicillanic acid

[0037] With 6,6-dihydropenicillane sulfoxide benzhydryl as raw material, with reference to the preparation method of literature (Synthesis, 1986, (4), 292), obtain quantitative brownish yellow oil (according to 6,6-diphenyl Hydropenicillane sulfoxide benzhydryl 20g (52.2mmol) feeds intake, and 100% conversion rate calculates);

Embodiment 2

[0038] Embodiment 2: Preparation of 2β-chloromethylpenicillanic acid benzhydryl ester-1β-oxide (compound 6')

[0039] Add 240ml of dichloromethane to the oil obtained in Example 1, stir to dissolve, cool down to 0-5°C, start to slowly add 10.5g (67.8mmol) sodium perborate tetrahydrate in batches, and slowly heat up to 20°C after adding. Insulate at -25°C for 3-5 hours, slowly add 200ml of water, stir for 30 minutes, let stand to separate layers, distill the organic phase under reduced pressure to obtain an oily substance, separate by column chromatography, and obtain 2β-chloromethylpenicillanic acid diphenyl Methyl ester-1β-oxide, melting point: 55-60°C, ESI (m / z): 417; 1 HNMR (CDCl 3 )δ (ppm): 1.42 (3H, S), 3.04 (1H, dd), 3.25 (1H, dd), 3.52 (1H, d), 3.77 (1H, d), 4.25 (1H, m), 4.4 ( 1H, s), 6.53 (1H, s), 7.19 (4H, dd), 7.27 (4H, dd), 7.37 (2H, dd).

Embodiment 3

[0040] Example 3: Preparation of 2β-azidomethylpenicillanic acid diphenylmethyl ester-1β-oxide (compound 7”)

[0041]Add 240ml of N,N-dimethylformamide to the oil obtained in Example 2, stir to dissolve, keep the temperature at -5-5°C, add 5.08g (78.4mmol) sodium azide, and heat up to Incubate at 20-30°C for 20-30 hours, add 360ml of water, add 250ml of dichloromethane for extraction, let stand to separate layers, distill the organic phase under reduced pressure to obtain an oily substance, and separate it by column chromatography to obtain 2β-azidomethylpenicillane Acid benzhydryl-1β-oxide, melting point: 70-75°C, ESI (m / z): 426; 1 HNMR (CDCl 3 )δ (ppm): 1.41 (3H, S), 1.53 (1H, d), 1.74 (1H, d), 2.99 (1H, dd), 3.24 (1H, dd), 4.22 (1H, m), 4.35 ( 1H, s), 6.54 (1H, S), 7.19 (4H, dd), 7.27 (4H, dd), 7.37 (2H, dd).

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 tazobactam synthesis method, which belongs to the technical field of medicines, and includes the steps: firstly, enabling 6,6-dihydropenam sulfoxide acid diphenylmethyl ester serving as raw materials to undergo thermal cracking and chloromethylation reaction to obtain 2beta-chloromethyl penicillanic acid diphenylmethyl ester; secondly, adding oxidizing agent to oxidize the 2beta-chloromethyl penicillanic acid diphenylmethyl ester-1beta-oxide, enabling the oxidized 2beta-chloromethyl penicillanic acid diphenylmethyl ester-1beta-oxide to react with sodium azide to generate 2beta-hydrazoic methyl penicillanic acid diphenylmethyl ester-1beta- oxide, and then generating 2beta-hydrazoic methyl penicillanic acid diphenylmethyl ester-1,1- dioxide by means of oxidization under the action of potassium permanganate and acetic acid; and finally, preparing the tazobactam by means of deprotection under the action of acetylene cyclization and metacresol. Compared with a past 6-APA (aminopenicillanic acid) route, the tazobactam synthesis method has the advantages that the step of sulfur atom single oxidization is added, so that possibility of ring expansion due to affinity of lone pair electrons on a sulfur atom is blocked, and transformation of five-membered ring products to six-membered ring by-products during hydrazoic reaction can be effectively controlled.

Description

technical field [0001] The invention relates to a method for synthesizing tazobactam, which belongs to the technical field of medicine. Background technique [0002] The chemical name of tazobactam is: [2S-(2a,3b,5a)]-3-methyl-7-oxo-3-(1H-1,2,3-triazol-1-ylmethyl )-4-thio-1-azabicyclo[3,2,0]heptane-2-carboxylic acid 4,4-dioxide. [0003] Molecular weight: 322.27 [0004] Molecular formula: C 10 h 12 N 4 o 5 S [0005] The structural formula is: [0006] [0007] Tazobactam is a new type of penicillane sulfone β-lactamase inhibitor developed by Dapeng Pharmaceutical Company in Japan. It is one of the best β-lactamase inhibitors in clinical application at present, with high stability and high activity Low toxicity, strong enzyme inhibitory activity and so on. In 1992, the compound drug tazobactam / piperacillin (1:8) of tazobactam was first launched in France for the treatment of various bacterial infections. [0008] The synthesis of tazobactam mainly has three syn...

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): C07D499/87
Inventor 杨庆坤孙政军张小勇樊长莹吴柯李保勇
Owner 山东安信制药有限公司
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