Preparation method of cefazedone sodium compound

Abstract

The invention discloses a preparation method of a cefazedone sodium compound. 7-ACA and a compound III react to prepare a compound IV, and the compound IV and a compound V have an amidation reaction,and are salified and refined to obtain a competitive product of cefazedone sodium (I). The process route of the reaction is simple, the total yield and the purity are high, and the method is suitablefor industrial production.

Description

technical field

[0001] The invention belongs to the technical field of medicine, in particular to a preparation method of an anti-infective drug cefazedone sodium compound. Background technique

[0002] Cefazedone (cefazedone) was developed by E Merck, Darmstadt laboratory in the late 1970s, and was the first generation of cephalosporin antibiotics. Cefozione is a semi-synthetic cephalosporin antibiotic, which mainly inhibits and kills bacteria by interfering with and preventing the synthesis of bacterial cell walls. It has good antibacterial activity against common clinical Gram-positive and some Gram-negative bacteria, and some anaerobic bacteria, and can be used for respiratory system, urinary system, gastrointestinal tract infection and gynecology, peritoneum, skin, soft tissue and plastic surgery, etc. Sensitivity to the treatment of both causes of infection.

[0003] The chemical name of cefazolone sodium is: (6R,7R)-3-(5-methyl-1,3,4-thiadiazolyl-2-mercaptomethyl)-7...

Examples

Embodiment 1

[0031] Preparation of compound Ⅳ

[0032] Add 27.23g of 7-ACA(II), 13.22g of compound III and 600ml of N,N-dimethylformamide in sequence in the reaction bottle, control the temperature at 40-50°C and stir the reaction for 3h, monitor the completion of the reaction by TLC, then evaporate to remove Solvent, 800ml of ethyl acetate and 800ml of saturated sodium bicarbonate were added to the obtained oil, and the layers were separated. The organic layer was dried over anhydrous sodium sulfate and filtered. After the filtrate was concentrated, it was recrystallized with ether to obtain a solid of 31.87g. The molar yield was 92.4%. , HPLC purity of 99.86%.

Embodiment 2

[0034] Preparation of compound Ⅳ

[0035] Add 27.23g of 7-ACA(II), 13.22g of compound III and 600ml of methylene chloride in sequence in the reaction flask, control the temperature at 40-50°C and stir the reaction for 3h, monitor the completion of the reaction by TLC, and then evaporate the solvent to obtain the oil Add 800ml of ethyl acetate and 800ml of saturated sodium bicarbonate, separate layers, dry the organic layer over anhydrous sodium sulfate, filter, concentrate the filtrate, and recrystallize with ether to obtain 31.34g of solid, with a molar yield of 90.8% and an HPLC purity of 99.78% .

Embodiment 3

[0037] Preparation of compound Ⅳ

[0038] Add 27.23g of 7-ACA(II), 14.54g of compound III and 600ml of N,N-dimethylformamide in sequence in the reaction bottle, control the temperature at 40-50°C and stir the reaction for 3h, monitor the completion of the reaction by TLC, and then remove it by evaporation Solvent, 800ml of ethyl acetate and 800ml of saturated sodium bicarbonate were added to the obtained oil, and the layers were separated. The organic layer was dried over anhydrous sodium sulfate and filtered. After the filtrate was concentrated, it was recrystallized with ether to obtain a solid of 32.29g. The molar yield was 93.6%. , HPLC purity of 99.85%.

technical field

[0001] The invention belongs to the technical field of medicine, in particular to a preparation method of an anti-infective drug cefazedone sodium compound. Background technique

[0002] Cefazedone (cefazedone) was developed by E Merck, Darmstadt laboratory in the late 1970s, and was the first generation of cephalosporin antibiotics. Cefozione is a semi-synthetic cephalosporin antibiotic, which mainly inhibits and kills bacteria by interfering with and preventing the synthesis of bacterial cell walls. It has good antibacterial activity against common clinical Gram-positive and some Gram-negative bacteria, and some anaerobic bacteria, and can be used for respiratory system, urinary system, gastrointestinal tract infection and gynecology, peritoneum, skin, soft tissue and plastic surgery, etc. Sensitivity to the treatment of both causes of infection.

[0003] The chemical name of cefazolone sodium is: (6R,7R)-3-(5-methyl-1,3,4-thiadiazolyl-2-mercaptomethyl)-7...

Examples

Embodiment 1

[0031] Preparation of compound Ⅳ

[0032] Add 27.23g of 7-ACA(II), 13.22g of compound III and 600ml of N,N-dimethylformamide in sequence in the reaction bottle, control the temperature at 40-50°C and stir the reaction for 3h, monitor the completion of the reaction by TLC, then evaporate to remove Solvent, 800ml of ethyl acetate and 800ml of saturated sodium bicarbonate were added to the obtained oil, and the layers were separated. The organic layer was dried over anhydrous sodium sulfate and filtered. After the filtrate was concentrated, it was recrystallized with ether to obtain a solid of 31.87g. The molar yield was 92.4%. , HPLC purity of 99.86%.

Embodiment 2

[0034] Preparation of compound Ⅳ

[0035] Add 27.23g of 7-ACA(II), 13.22g of compound III and 600ml of methylene chloride in sequence in the reaction flask, control the temperature at 40-50°C and stir the reaction for 3h, monitor the completion of the reaction by TLC, and then evaporate the solvent to obtain the oil Add 800ml of ethyl acetate and 800ml of saturated sodium bicarbonate, separate layers, dry the organic layer over anhydrous sodium sulfate, filter, concentrate the filtrate, and recrystallize with ether to obtain 31.34g of solid, with a molar yield of 90.8% and an HPLC purity of 99.78% .

Embodiment 3

[0037] Preparation of compound Ⅳ

[0038] Add 27.23g of 7-ACA(II), 14.54g of compound III and 600ml of N,N-dimethylformamide in sequence in the reaction bottle, control the temperature at 40-50°C and stir the reaction for 3h, monitor the completion of the reaction by TLC, and then remove it by evaporation Solvent, 800ml of ethyl acetate and 800ml of saturated sodium bicarbonate were added to the obtained oil, and the layers were separated. The organic layer was dried over anhydrous sodium sulfate and filtered. After the filtrate was concentrated, it was recrystallized with ether to obtain a solid of 32.29g. The molar yield was 93.6%. , HPLC purity of 99.85%.

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