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A kind of synthetic method of ceftizoxamic acid

A ceftizoxime acid and synthetic method technology, applied in the direction of organic chemistry, etc., can solve the problems of increased operating procedures and production costs, low product yield and purity, long reaction steps, etc., to improve the total product yield and purity , low production cost, high product yield and high purity

Active Publication Date: 2021-02-26
SHANDONG LUOXIN PHARMA GRP CO LTD +2
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This route removes the protecting group many times, resulting in long reaction steps, increasing the operating procedures and production costs
The other is to directly condense 7-amino-non-3-cephalosporin-4-carboxylic acid with aminothioxime acetic acid as a raw material, and then form a salt. The product of this route needs to be purified by column chromatography, and the operation is cumbersome
[0007] 2. Chinese patent CN102603771A reports that 7-ANCN and AE active ester are used as raw materials to react at 20-40°C to prepare ceftizoxamic acid, but the yield and purity of the product are still not high, and there are still carbonyl and amide bonds The problem of impurities such as by-products has not been solved

Method used

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Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0023] Preparation of ceftizoxamic acid

[0024] Add 20.01g (0.1mol) of 7-ANCA, 150ml of dichloromethane, and 0.2mol of triethylamine to the reactor in order to stir and dissolve, and control the condition of 5-10°C, add 35.02g (0.1mol) of AE active ester dropwise, Add 0.05 mol of 4-dimethylaminopyridine in 15 minutes, keep the temperature constant, and stir for 3-4 hours. After the reaction, add water at room temperature for layering, separate the organic phase, and keep the water phase , add dichloromethane to wash, then add activated carbon for decolorization, add hydrochloric acid to crystallize, centrifuge, and dry to obtain 32.64g of ceftizoxamic acid, the product yield is 85%, the purity is 99.5%, the maximum single impurity is 0.06%, and the total impurity is 0.36%. .

Embodiment 2

[0026] Preparation of ceftizoxamic acid

[0027] Add 20.02g (0.1mol) of 7-ANCA, 150ml of dichloromethane, and 0.2mol of 4-dimethylaminopyridine to the reactor in order to stir and dissolve. Controlled at -5-0°C, add 38.52g of AE active ester dropwise ( 0.11mol), after 15 minutes, add 0.05mol of 4-dimethylaminopyridine, keep the temperature and condition unchanged, stir for 3-4h, after the reaction, add water at room temperature for layering, and separate the organic phase , retain the water phase, add dichloromethane to wash, then add activated carbon for decolorization, add hydrochloric acid to crystallize, centrifuge, and dry to obtain 37.13 g of ceftizoxamic acid, with a yield of 97%, a purity of 99.8%, a maximum of 0.05% of impurities, and a total of 0.05% of impurities. 0.18%.

Embodiment 3

[0029] Preparation of ceftizoxamic acid

[0030] Add 20.02g (0.1mol) of 7-ANCA, 150ml of dichloromethane, and 0.2mol of N,N-diisopropylethylamine to the reactor in order to stir and dissolve, control the temperature at 0-5°C, and add AE active ester dropwise 42.01g (0.12mol), add in 15 minutes, keep the temperature condition unchanged, stir the reaction for 3-4h, after the reaction, add water at room temperature for layering, separate the organic phase, keep the water phase, add dichloro Wash with methane, then add active carbon for decolorization, add hydrochloric acid to crystallize, centrifuge, and dry to obtain 30.65 g of ceftizoxamic acid, with a yield of 80%, a purity of 99.7%, a maximum of 0.07% of impurities, and a total of 0.25% of impurities.

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Abstract

The invention discloses a method for synthesizing ceftizoxime acid, which belongs to the technical field of pharmaceutical synthesis. The present invention prepares ceftizoxime acid by reacting 7-ANCA with AE active ester. The invention has the advantages of simple synthesis method, easy reaction operation, high yield and purity, and few by-products, and is suitable for industrial production.

Description

technical field [0001] The invention belongs to the technical field of drug synthesis, in particular to a synthesis method of ceftizoxime acid. Background technique [0002] Ceftizoxamic acid, chemical name: (6R,7R)-7-[(Z)-2-(2-amino-4-thiazolyl)-2-methoxyiminoacetamido]-8-oxo -5-thia-1-aminobicyclo[4.2.0]oct-2-ene-2-carboxylic acid, the structural formula is: [0003] . [0004] Ceftizoxime is the third-generation cephalosporin antibiotic developed by Fujisawa Pharmaceutical Co., Ltd. in Japan. It was first listed in Japan in 1982 under the trade name Ceftizox. This product is a third-generation cephalosporin antibiotic. Its mechanism of action is to achieve bactericidal effect by inhibiting the biosynthesis of bacterial cell wall mucopeptides. It has the characteristics of broad-spectrum, high efficiency, enzyme resistance, low toxicity and can pass through the blood-brain barrier. It is stable against broad-spectrum β-lactamases (including penicillinase and cephalosp...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D501/06C07D501/20
CPCC07D501/06C07D501/20
Inventor 高红军徐之存张会
Owner SHANDONG LUOXIN PHARMA GRP CO LTD