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

Preparation method of cefozopran hydrochloride

A technology of ceftozolam hydrochloride and cefozopran hydrochloride, which is applied in the field of preparation of cefazolam hydrochloride, can solve the problems of reducing moisture content, reducing solvent residue, difficult moisture content, etc., to reduce the difficulty of reaction purification and facilitate industrial production , The effect of improving the utilization rate of raw materials

Active Publication Date: 2012-05-09
北京抗创联生物制药技术研究有限公司
View PDF7 Cites 5 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Experiments have proved that acetone cannot be washed away with low-boiling solvents such as ether. If the solvent is removed with high-humidity air, the water content will be too high
Experiments have proved that it is difficult to reduce the moisture content to less than 2.5% by ordinary vacuum drying methods (Japanese Pharmacopoeia JP15 standard)
[0013] In summary, the synthesis and preparation of cefozopran hydrochloride has problems such as difficult access to starting materials, low yield, low purity, difficulty in purification, difficulty in reducing solvent residues, and difficulty in reducing moisture content.

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 cefozopran hydrochloride
  • Preparation method of cefozopran hydrochloride
  • Preparation method of cefozopran hydrochloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0040] Embodiment 1: the preparation of cefozopran hydrochloride

[0041] (1) Under the protection of nitrogen, add 10L of dichloromethane and 1kg of 7-ACA into a 20L reaction kettle, under stirring at 25°C, add 0.89kg of hexamethyldisilazane, add 25g of methanesulfonic acid dropwise, and then heat to 55 ℃ reaction for 3 hours, and the reaction solution was set aside;

[0042] (2) Under the protection of nitrogen, add 8L of dichloromethane and 0.88kg of imidazo[1,2-b]pyridazine in a 30L reaction kettle, and add 1.47kg of iodotrimethylsilane under stirring at 20°C, and heat up to React at 30°C for 5 hours, and the reaction solution is set aside;

[0043] (3) Add the reaction solution in step (1) to the reaction solution in step (2), and keep it at about 30°C for 3 hours. After the reaction was completed, the reaction solution was cooled to about 0°C, and 1.5L of methanol was added dropwise, then stirred for 1 hour, filtered, and the filter cake was washed twice with pre-coole...

Embodiment 2

[0046] Embodiment 2: the preparation of cefozopran hydrochloride

[0047] (1) Under the protection of nitrogen, add 10L of dichloromethane and 1Kg of 7-ACA into a 20L reaction kettle, under stirring at 25°C, add 1.12kg of N,O-bistrimethylsilylacetamide (BSA), and react at 25°C for 1 hour, the reaction solution is standby;

[0048] (2) Under nitrogen protection, add 8L of dichloromethane and 1.05kg of imidazo[1,2-b]pyridazine into a 30L reaction kettle, add 1.47Kg of iodotrimethylsilane under stirring at room temperature, and heat up to 35°C React for 4 hours, and the reaction solution is ready for use;

[0049] (3) Add the reaction solution in step (1) to the reaction solution in step (2), and keep it at about 35°C for 3 hours. After the reaction was completed, the reaction liquid was cooled to about 0°C, and 1.5L of methanol was added dropwise, stirred for 1 hour, filtered, and the filter cake was washed twice with pre-cooled 1L of methanol, drained, and vacuum-dried to obt...

Embodiment 3

[0052] Embodiment 3: the preparation of cefozopran hydrochloride

[0053] (1) Add 10L of dichloromethane and 1kg of 7-ACA into a 20L reaction kettle under nitrogen protection, add 1.47kg of iodotrimethylsilane under stirring at 25°C, then react at 25°C for 2 hours, and the reaction solution is set aside;

[0054] (2) Add 8L of dichloromethane and 1.31kg of imidazo[1,2-b]pyridazine into a 30L reaction kettle under nitrogen protection, add 1.47kg of iodotrimethylsilane under stirring at room temperature, and heat up to 40°C for reaction 3 hours, the reaction solution is ready for use;

[0055] (3) Add the reaction solution in step (1) to the reaction solution in step (2), and keep it at about 40°C for 3 hours. After the reaction was completed, the reaction liquid bath was cooled to about 0°C, and 1.5L of methanol was added dropwise, stirred for 1 hour, filtered, and the filter cake was washed twice with pre-cooled 1L of methanol, drained, and vacuum-dried to obtain 1-[[ (6R,7R...

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 relates to a preparation method of cefozopran hydrochloride. The method comprises the following steps: 1, carrying out a silanization reaction on 7-ACA which is a raw material, and reacting the obtained substance with a compound of formula IIIa to obtain an intermediate of formula IV; and 2, carrying out a condensation reaction on the intermediate of the formula IV and an active ester to obtain a new substance, and reacting the new substance with hydrochloric acid to obtain a hydrochloride cefozopran hydrochloride of the formula I. According to the invention, the compound of the formula IIIa is firstly introduced into synthetic methods of cefozopran hydrochloride and the intermediate thereof, so reaction conditions for the preparation of the intermediate of the formula IV are mild, and the industrial production is easy; the cefozopran hydrochloride purity, the residual solvent amount and the water content accord with pharmacopeia standards, so cefozopran hydrochloride can be directly applied to medicinal preparations. R2 in the formula IIIa is defined in claim 1.

Description

technical field [0001] The invention relates to a preparation method of cephalosporins, in particular to a preparation method of cefozopran hydrochloride. Background technique [0002] Cefazolan hydrochloride is the fourth generation injection cephalosporin researched and developed by Takeda Corporation of Japan. + Bacteria, G - Bacteria and anaerobic bacteria show broad-spectrum antibacterial activity. It was first listed in Japan in 1995 under the trade name of Firstcin. [0003] The chemical name of cefazolam hydrochloride is 1-[[(6R,7R)-7-[(Z)-2-(5-amino-1,2,4-thiadiazol-3-yl)-2-methanol Oxyiminoacetamido]-2-carboxy-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-en-3-yl]methyl]imidazo[1, 2-b] pyridazinium hydroxide inner salt, the structural formula is as shown in formula I: [0004] [0005] EP0203271 discloses a preparation method of the 3-position quaternary ammonium methyl structure of cefazolam, which is a cephalosporin intermediate whose 3-position is a hydroxymethyl...

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): C07D519/06
Inventor 龚登凰马玉秀吕健武仙英高利郝盼杰孙会谦
Owner 北京抗创联生物制药技术研究有限公司
Features
  • Generate Ideas
  • 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