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Synthesis process of cefazedone sodium

A synthesis process and technology of cephalosporins, which are applied in the field of pharmaceutical synthesis, can solve the problems of being unsuitable for industrialized large-scale production, difficult to find purification methods, and high industrial production costs, and achieve the advantages of reducing the occurrence of by-products, reducing product costs, and reducing side reactions. Effect

Inactive Publication Date: 2020-05-22
陶志泽
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0011] In the above-mentioned three kinds of processing routes, the synthesis of route one mainly starts from the 7-position of 7-ACA, and route two starts from the 3-position of 7-ACA. ) is slightly higher than route one (60%), but the disadvantage of route two is that the by-product of the reaction between 1-methylthiadiazole-5-thiol and 7-ACA is always accompanied in the final product, and it is difficult to find Appropriate purification method, such that its synthesis cost will increase accordingly, is not suitable for industrialized large-scale production, and the process of route three is basically mature. The present invention makes improvements to route three to increase the yield
[0012] In the prior art, the method for synthesizing cefazedone sodium generally has the disadvantages of low yield, poor product color grade and high industrial production cost.
The difficulty of the process makes the price of the preparation expensive, causing an economic burden to the drug users, and the use of highly polluting chemical reagents in the synthesis process causes great damage to the environment

Method used

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  • Synthesis process of cefazedone sodium
  • Synthesis process of cefazedone sodium

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0030] (1) Preparation of Thioester Compounds

[0031] In a dry reaction flask, add 200ml of dichloromethane, 22.2g (0.1mol) of 3,5-dichloro-4-pyridone-1-acetic acid and 2-mercapto-5-methyl-1,3,4 -Thiadiazole 14.55g (0.11mol), stirred, then added triethylamine 10.1g (0.1mol), DMF 1.83g (0.025mmol) stirred at room temperature for 1 hour, then slowly added dropwise the catalyst triphenyl phosphite Dichloromethane solution (31g of triphenyl phosphite dissolved in 50ml of dichloromethane, 0.1mol), dripped within 1 hour, controlled the temperature at 20-25°C, stirred and reacted for 1 hour, cooled to below 10°C, filtered, and the filtrate Spin dry, and vacuum dry below 40°C to obtain 33.5 g (0.099 mol) of the thioester compound, with a yield of 99.7% and an HPLC purity of 99.5%.

[0032] (2) Preparation of Cefazedone Sodium:

[0033] Under the protection of nitrogen, add 24.5g (0.09mol) of 7-ACA and 3.6g (0.09mol) of sodium hydroxide into the mixed solvent of water and acetonitri...

Embodiment 2

[0035] (1) Preparation of Thioester Compounds

[0036]In a dry reaction flask, add 200ml of dichloromethane, 22.2g (0.1mol) of 3,5-dichloro-4-pyridone-1-acetic acid and 2-mercapto-5-methyl-1,3,4 -Thiadiazole 14.55g (0.11mol), stirred, then added triethylamine 10.1g (0.1mol), DMF 0.73g (0.01mmol) stirred at room temperature for 1 hour, then slowly added dropwise the catalyst triphenyl phosphite Dichloromethane solution (31g of triphenyl phosphite dissolved in 50ml of dichloromethane, 0.1mol), dripped within 1 hour, stirred and reacted at 20-25°C for 2 hours, cooled to below 10°C, filtered, The filtrate was spin-dried and vacuum-dried below 40°C to obtain 32.3 g (0.096 mol) of the thioester compound with a yield of 96% and an HPLC purity of 99.5%.

[0037] (2) Preparation of Cefazedone Sodium:

[0038] Under the protection of nitrogen, add 24.5g (0.09mol) of 7-ACA and 3.6g (0.09mol) of sodium hydroxide into the mixed solvent of water and acetonitrile (100ml of water and 200ml ...

Embodiment 3

[0040] (1) Preparation of Thioester Compounds

[0041] In a dry reaction flask, add 200ml of dichloromethane, 22.2g (0.1mol) of 3,5-dichloro-4-pyridone-1-acetic acid and 2-mercapto-5-methyl-1,3,4 -Thiadiazole 14.55g (0.11mol), stirred, then added triethylamine 10.1g (0.1mol), DMF 3.65g (0.05mmol) stirred at room temperature for 1 hour, then slowly added dropwise the catalyst triphenyl phosphite Dichloromethane solution (31g of triphenyl phosphite dissolved in 50ml of dichloromethane, 0.1mol), dripped within 1 hour, controlled the temperature at 20-25°C, stirred and reacted for 1 hour, cooled to below 10°C, filtered, and the filtrate Spin dry, and vacuum dry below 40°C to obtain 31.9 g (0.095 mol) of the thioester compound, with a yield of 95% and an HPLC purity of 99.5%.

[0042] (2) Preparation of Cefazedone Sodium:

[0043] Under the protection of nitrogen, add 24.5g (0.09mol) of 7-ACA and 3.6g (0.09mol) of sodium hydroxide into the mixed solvent of water and acetonitrile ...

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Abstract

The invention relates to a synthesis process of cefazedone sodium, which is characterized in that a thioester compound synthesized by taking 3,5-dichloro-4-pyridone-1-acetic acid and 2-sulfydryl-5-methyl-1,3,4-thiadiazole as raw materials is directly subjected to a one-step reaction with 7-ACA to prepare the cefazedone sodium. The process has the advantages of simplified operation steps, mild production conditions, reduced generation of byproducts, simple production process, improved product yield and purity, reduced cost, small environmental pollution and better environmental friendliness, and enables the process to meet the requirements of industrialization.

Description

technical field [0001] The invention relates to the field of drug synthesis, in particular to a synthesis process of a novel cephalosporin anti-infective drug cefzidone sodium. Background technique [0002] Cefazedone sodium (Cefazedone) belongs to the first generation of injectable cephalosporin antibiotics, and its curative effect on various Gram-positive bacteria and Gram-negative bacteria, including Staphylococcus aureus, Streptococcus, and Enterococcus, is superior to similar drugs— The drug resistance of cefazolin and cephalothin is obviously better than that of the latter. They are classic broad-spectrum antibiotics with broad antibacterial spectrum and wide clinical application. A total of 732 patients in 7 foreign countries and 35 hospitals participated in the clinical research results showed that cefzidome was effective against urinary system infection, respiratory tract infection, surgical-skin infection and gynecological infection caused by gram-positive and nega...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D501/36C07D501/04C07D417/12
CPCC07D417/12C07D501/04C07D501/36
Inventor 陶志泽
Owner 陶志泽
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