Process for preparing high-purity cefathiamidine

A cefathiamidine, high-purity technology, applied in the field of chemical drug synthesis, can solve the problem of high residual impurities, achieve the effects of high reaction yield, avoid side reactions, and simple and easy operation

Active Publication Date: 2016-03-30
山西振东泰盛制药有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0012] The present invention provides a kind of effectively reducing bromoacetyl-7ACA and high molecular Preparation method of high-purity cefathiamidine with residual impurities

Method used

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  • Process for preparing high-purity cefathiamidine
  • Process for preparing high-purity cefathiamidine
  • Process for preparing high-purity cefathiamidine

Examples

Experimental program
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Effect test

Embodiment 2

[0040]In a 10L reaction kettle, add DCM5320g (4L), TEA (200mL), bromoacetyl-7ACA500g in sequence, stir to dissolve, add co-solvent pure water 50mL, then add N,N-diisopropylthiourea 225g, stir to dissolve After clearing, heat the reaction solution to reflux. After 2-3 hours of reaction, stop the reaction and lower the internal temperature to 0°C to 15°C. Add 2L of acetone dropwise, stir and crystallize. After the dropwise addition, keep stirring at 8-12°C and filter with suction. After the filter cake is drained, add 1L of acetone to rinse the filter cake. After draining, add the filter cake to 10L Then add 600mL of pure water and stir to dissolve, then add 1080g (1.2L) of ethyl acetate, stir for 10 minutes, extract impurities, after standing for stratification, filter the water layer into the crystallization reaction kettle, wash with dilute hydrochloric acid Adjust the pH of the solution to 5.0, cool the obtained clear mixed solution to 0-5°C, add 5.6L of acetone dropwise, af...

Embodiment 3

[0042] Add 400mL of DCM, 18mL of TEA, and 50g of bromoacetyl-7ACA to a 1L reaction bottle in turn, stir to dissolve, add 10mL of co-solvent pure water, then add 22.5g of N,N-diisopropylthiourea, stir to dissolve, then heat the reaction solution Return to reflux, react for 2-3 hours, stop the reaction, add 10 mL of pure water as a co-solvent, and lower the internal temperature to 10°C to 15°C. Add 200mL of acetone dropwise, stir and crystallize. After the dropwise addition, keep stirring at 8-12°C and filter with suction. After the filter cake is drained, add 100mL of acetone to rinse the filter cake. In the reaction flask, add 60mL of pure water and stir to dissolve, then add 108g (120mL) of ethyl acetate, stir for ten minutes, extract impurities, stand and separate the layers, filter the water layer into the crystallization reaction flask, adjust with dilute hydrochloric acid Solution pH=4.5, the obtained clear mixed solution was cooled to 0-5°C, and 560mL of acetone was adde...

Embodiment 4

[0044] Add 400mL of DCM, 20mL of TEA, and 50g of bromoacetyl-7ACA to a 1L reaction flask in sequence, stir to dissolve, then add 22.5g of N,N-diisopropylthiourea, stir to dissolve, then heat the reaction solution to reflux, Reaction 2-3 After one hour, the reaction was stopped, and the internal temperature was lowered to 10°C to 15°C. Add 200mL of acetone dropwise, stir and crystallize. After the dropwise addition, keep stirring at 8-12°C and filter with suction. After the filter cake is drained, add 100mL of acetone to rinse the filter cake. In the reaction flask, add 60mL of pure water and stir to dissolve, then add 108g (120mL) of ethyl acetate, stir for ten minutes, extract impurities, stand and separate the layers, filter the water layer into the crystallization reaction flask, adjust with dilute hydrochloric acid Solution pH=5.0, the obtained clear mixed solution was cooled to 0-5°C, and 560mL of acetone was added dropwise. cake. After the filter cake was drained, the ...

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Abstract

The present invention relates to a process for preparing cefathiamidine, in particular a process for preparing high-purity cefathiamidine. The preparation method comprises the following steps of: adding water or an aqueous inorganic salt solution as an auxiliary solvent in or after a reaction on acetyl bromide-7ACA and N,N'-diisopropylthiourea; after the reaction, cooling the mixture, and dropwise adding a crystallization solvent into the mixture, and performing suction filtration to obtain a crude product of cefathiamidine; and purifying the crude product again,and drying the crude product in vacuum to obtain the high-purity cefathiamidine. According to the preparation method provided by the present invention, residues of impurities in the cefathiamidine can be effectively reduced, the content of acetyl bromide-7ACA and the macromolecular compound impurities can be reduced to 0.1% or less or can be completely eliminated, and other residues of impurities in the cefathiamidine can be reduced to be less than 0.2%.

Description

technical field [0001] The invention belongs to the field of chemical drug synthesis, and relates to a preparation method of high-purity cefathiamidine, in particular to a method for preparing high-purity cefathiamidine which utilizes bromoacetyl-7ACA and a polymer compound to reduce the impurity content of high-purity cefathiamidine Amidine process. Background technique [0002] Cefathiamidine is a β-lactam antibiotic independently developed by Shanghai Pharmaceutical Industry Research Institute and Guangzhou Baiyunshan Pharmaceutical Co., Ltd. It has strong antibacterial effect on most Gram-positive bacteria and some Gram-negative bacteria. role, especially for enterococci have a unique effect. It is widely used clinically, mainly for respiratory tract infection and biliary tract infection caused by Staphylococcus aureus, pneumococcus and streptococcus. [0003] The structural formula is as follows: [0004] [0005] At present, the intermediate bromoacetyl-7ACA prod...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D501/28C07D501/04
CPCC07D501/04C07D501/28
Inventor 高治华赵永军张涛沈达梁波李建军
Owner 山西振东泰盛制药有限公司
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