A kind of original research quality ceftazidime and pharmaceutical preparation thereof

Abstract

The invention discloses original development quality ceftazidime and a medicine preparation thereof. The third-generation cephalosporin antibiotics active ester midbody key technology and industrialization obtains the second prize of National Scientific and Technological Progress Award. The cephalosporin antibiotics active ester belongs to a key factor for influencing the internal quality of the cephalosporin. A preparation method comprises the following steps that (a) mixed solvents are added into ceftazidime side chain acid, dibenzothiazyl disulfide, aniline and 2-picoline; triethyl phosphate is dripped for reaction; (b) a coarse product is refined to obtain ceftazidime side chain acid active ester, and the first mother liquid is recovered; (c) the material is added into a mixed solvent for neutralizing 7-APCA; triethylamine is dripped; the temperature reduction is performed for crystal separation and filtering to obtain ceftazidime tert-butyl ester; the second mother liquid is recovered; (d) the ceftazidime tert-butyl ester is subjected to hydrolysis and purification, and then, the ceftazidime is obtained. The original development quality ceftazidime has the advantages that high-toxicity triphenylphosphine is not used; waste liquid and waste slag can be sufficiently recovered and reutilized; the method is safe; the cost is low; the yield is high; the industrial production is facilitated.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to ceftazidime and a pharmaceutical preparation thereof. Background technique [0002] Ceftazidime is an antibiotic with outstanding efficacy against Pseudomonas aeruginosa. It is one of the important third-generation semi-synthetic cephalosporin antibiotics. It has the characteristics of strong bactericidal power and wide antibacterial spectrum. It is widely used clinically. One of the newest and best-selling cephalosporins on the market. [0003] At present, the synthetic method of ceftazidime is mainly to use ceftazidime side chain acid as raw material, react with dibenzothiazole disulfide (DM) under the catalysis of organic base, generate ceftazidime side chain acid active ester; Then react with 7-amino-3 -(1-pyridylmethyl)cephemic acid (7-APCA) was prepared through a series of reactions to ceftazidime. [0004] Jincheng Pharmaceutical's "key technology of active ester inter...

AI Technical Summary

Problems solved by technology

The disadvantage of this method is that dichloromethane is used as the solvent, the solubility of the product is too large, the yield is low, the price of triphenylphosphine is expensive, and the production cost is high

[0008] Therefore, for the existing synthetic route of ceftazime, in the process of preparing ceftazidime side chain acid active ester and ceftazidime hydrochloride, the condensing agent triphenylphosphine that uses has high toxicity, and cost is high, and reaction by-product triphenoxyphos and DM cannot be effectively recovered, and the amount of waste water and residue is large and difficult to handle, which is not conducive to industrial production

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