The preparation method of ceftezole sodium

A technology of ceftezole sodium and ceftezole acid, which is applied in the field of synthesis of ceftezole sodium, can solve the problems of expensive hospital preparations, strong pollution, and economic burden, and meet the needs of industrial production and simplify operation steps , The effect of simple and easy process

Inactive Publication Date: 2011-12-21
ZHENGZHOU UNIV
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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 c...

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  • The preparation method of ceftezole sodium
  • The preparation method of ceftezole sodium
  • The preparation method of ceftezole sodium

Examples

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Embodiment 1

[0028] 1. Synthesis of 1H-tetrazolium acetate-1,3,4-thiadiazole-2-thioester

[0029] 134.4 g (1.05 mol) of 1H-tetrazolium acetic acid and 118.0 g (1.00 mol) of 2-mercapto-1,3,4-thiadiazole were dissolved in 1000 mL of tetrahydrofuran, cooled to 0°C to 4°C, and then added A solution of 17.2g (0.10mol) of p-toluenesulfonic acid in 50mL of tetrahydrofuran was kept at the temperature for 2h, the solvent was recovered by distillation under reduced pressure, cooled to 0°C to 4°C, and filtered to obtain 220.8g of 1H-tetrazolium acetic acid-1 , 3,4-thiadiazole-2-thioester, yield 96.8%.

[0030] 2. Synthesis of ceftizole acid

[0031] Add 227.0 g (0.83 mol) of 7-aminocephalosporanic acid (7-ACA) and 112.9 g (0.83 mol) of crystalline sodium acetate to 1500 mL of water and 1500 mL of ethanol, stir to dissolve, and cool down to 0°C to 4°C in an ice bath. Then, 1H-tetrazolium acetate-1,3,4-thiadiazole-2-thioester prepared above was added in a molar ratio of 1.0:1.2, and the reaction w...

Embodiment 2

[0035] 1. Synthesis of 1H-tetrazolium acetate-1,3,4-thiadiazole-2-thioester

[0036]134.4 g (1.05 mol) of 1H-tetrazolium acetic acid and 118.0 g (1.00 mol) of 2-mercapto-1,3,4-thiadiazole were dissolved in 1200 mL of ethyl acetate, cooled to 0°C to 4°C, and then Then add 226.6g (1.10mol) of dicyclohexylcarbodiimide (DCC) and 500mL of ethyl acetate solution, keep the temperature for reaction for 2h, recover the solvent by vacuum distillation, cool down to 0℃~4℃, filter to obtain 213.8g of 1H-tetrazolium acetate-1,3,4-thiadiazole-2-thioester, yield 93.7%.

[0037] 2. Synthesis of ceftizole acid

[0038] As in Example 1, the phase transfer catalyst adopts tetrabutylammonium bromide; the organic solvent used is toluene.

[0039] 3. Synthesis and purification of ceftizole sodium

[0040] Same as Example 1. 135.6g of ceftizole sodium was obtained, the yield was 86.1%.

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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...

Claims

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Application Information

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IPC IPC(8): C07D501/36C07D501/04C07D501/06
Inventor 张秋荣可钰刘宏民季聪慧蒋腾飞杨志华
Owner ZHENGZHOU UNIV
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