Preparation method of cefathiamidine

Abstract

The invention relates to a preparation method of cefathiamidine, which comprises the following steps: (1) preparing cefathiamidine acid, performing silanization of 7-AC by BSA at room temperature, reacting with bromoacetyl bromide at zero DEG C, processing and separating out solid, filtering and drying to obtain high-purity cefathiamidine acid; (2) adding alkaline reagent to the cefathiamidine acid, reacting with N, N'-diisopropyl thiourea, adding slightly soluble solvent and separating out coarse cefathiamidine; and (3) dissolving the coarse cefathiamidine in a proper solvent, regulating the pH value of the solution to be between 4 and 5.5, adding the lightly soluble solvent until the solution is turbid, controlling the stirring speed, continuing slowly dripping the slightly soluble solvent, separating out the product, separating and drying to obtain the cefathiamidine. The method has the advantages of few steps, simple process, high purity and easy implementation.

Description

Technical field [0001] The invention relates to a preparation method of a chemical raw material medicine cefathiamidine, which belongs to the field of chemical medicine synthesis. Background technique [0002] Cefathiamidine (Cefathiamidine) is the first-generation cephalosporin, which is the first in my country and used clinically. [0003] [0004] Commonly known as: Pioneermycin 18, Cephalosporin 18. The antibacterial spectrum is similar to cephalothin. It has a strong effect on Staphylococcus aureus, Streptococcus viridans, and pneumococcus. It has unique antibacterial activity against Enterococcus. It is mainly used for respiratory tract infections caused by Staphylococcus aureus, pneumococcus and streptococcus. Biliary tract infection, urinary tract infection, gynecological infection, sepsis, pneumonia, meningitis and other infections. USP 3,646,025 and "Chinese Journal of Medicinal Chemistry", 2001, 10, No. 11, P293-294, and application number 200410102519.7 provide a meth...

AI Technical Summary

Problems solved by technology

However, when producing cefathiamic acid in large quantities, the solvent system used is water-acetone, and the ratio of water is relatively large (2:1), which will hydrolyze bromoacetyl bromide and increase its consumption (1.3eq)

When dissolving 7-ACA with sodium bicarbonate, a large amount of foam will be generated, and the tank will overflow. You must wait for the foam to disappear before continuing to add sodium bicarbonate slowly, prolonging the operation time

Moreover, 7-ACA is unstable in alkaline solution, and prolonged time will affect product quality, especially in production

From the dropwise addition of bromoacetyl bromide to the adjustment of pH value, the reaction must be carried out at low temperature, and the energy consumption is high

Moreover, the free cefathiamic acid has poor solubility in ethyl acetate and acetone, so a large volume of solvent must be added for extraction, which causes inconvenience in operation

Also, the 42% yield of this method is not ideal

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