The preparation method of ceftezole sodium

Abstract

The invention discloses a preparation method of ceftizole sodium, which belongs to the field of medicinal chemistry. The method uses 1H-tetrazolium acetic acid and 2-mercapto-1,3,4-thiadiazole as raw materials, and generates 1H-tetrazolium acetic acid-1 under the catalysis of p-toluenesulfonic acid or dicyclohexylcarbodiimide ,3,4-thiadiazole-2-thioester (active ester), and then the active ester and 7-aminocephalosporanic acid are "one-pot" synthesis of ceftizole acid under the action of quaternary ammonium salt phase transfer catalyst, and then Sodium salt is generated, and further recrystallization and purification can obtain high-purity ceftiazole sodium. The preparation process is simple and feasible, the atom utilization rate is high, the product quality is good, and the industrial production requirements are met.

Description

technical field [0001] The invention belongs to the field of medicinal chemistry and relates to a method for synthesizing ceftizole sodium medicine. Background technique [0002] Ceftezole Sodium, English name Ceftezole Sodium, molecular weight is 461.9963, molecular formula is C 13 H 11 N 8 NaO 4 S 3 , the chemical name is (6R, 7R)-3-{[(1,3,4-thiadiazol-2-yl)thio]methyl}-7-[(1H-tetrazol-1-yl)acetyl Amino]-8-oxo-5-thia-1-azabicyclo[4,2,0]oct-2-ene-2-carboxylate, sodium salt. Its structural formula is as follows: [0003] [0004] Ceftizole sodium is the first generation of semi-synthetic cephalosporin antibiotics for injection. Its mechanism of action is to exert antibacterial activity by inhibiting the synthesis of bacterial cell walls. It is sensitive to gram-positive bacteria, especially Staphylococcus aureus, Streptococcus pyogenes, Pneumococcus, Hemolytic Streptococcus, Streptococcus viridans, Staphylococcus epidermidis, Bacillus diphtheriae, Bacillus anthraci...

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Problems solved by technology

[0010] Patent application CN101544659A discloses a method for preparing ceftezole, using boric acid as a catalyst, and reacting 7-ACA with 2-mercapto-1,3,4-thiadiazole in water to obtain 3 - position intermediate, but a large amount of 2-mercapto-1,3,4-thiadiazole and boric acid are used, and then reacted with 1H-tetrazolium acetyl chloride to prepare ceftezole acid, the acylation yield is low, and the total The yield is 38%

[0011] Patent application CN101735250A discloses a method for preparing ceftezole sodium, that is, tetrazoleacetic acid and 2-mercapto-1,3,4-thiadiazole are condensed to form tetrazoleacetic acid-1,3,4-thiadiazole -2-thioester reacts with 7-aminocephalosporanic acid to generate ceftezole sodium, which uses expensive reagent chlorine in the synthesis of tetrazoleacetic acid-1,3,4-thiadiazole-2-thioester Isopropyl formate and N-methylpiperidine used nitrogen in the reaction of 7-aminocephalosporanic acid to generate ceftezole sodium, which increased production costs

[0012] The method for synthesizing ceftezole sodium in the prior art generally has the disadvantages of low yield, poor product color grade and high industrial production cost

The difficulty of the process has resulted in the high price of the hospital preparations, causing economic burdens to the drug users, and the use of highly polluting chemical reagents in the synthesis process has caused great damage to the environment

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