Preparation process for intermediate of doripenem

Abstract

The invention relates to the technical field of medicines and particularly provides a preparation process of the intermediate I of doripenem. In the process, a reagent which is environmentally-friendly and low in cost is used in place of a high-cost and high-toxicity reagent in the prior art, the synthesis route is optimized, the product purity is improved, and the preparation method is simple, reliable, easy to operate, high in yield and low in cost, reduces emission to the environment to the lowest degree and contributes to industrial production. The structure of the intermediate I of the doripenem is shown below.

Description

A kind of preparation technology of the intermediate of doripenem 1. Technical field The invention belongs to the technical field of medicine, and in particular relates to a preparation process of an important intermediate I of doripenem. 2. Background technology Carbapenem antibiotics have strong antibacterial activity and broad antibacterial spectrum, and because of their stability to β-lactamase, they have high clinical applicability. Doripenem is a carbapenem antibiotic for injection synthesized by Shionogi Pharmaceutical Co., Ltd. It has a pyrrolidinyl group substituted by a methyl group at the 4th position and an aminosulfonamide group at the 3rd position. The mechanism of action of doripenem is the same as that of other β-lactam antibacterial drugs. It mainly binds to the bacterial cell wall synthesis enzyme bacterial penicillin-binding protein (PBP) to inhibit the synthesis of bacterial cell walls. Doripenem has the characteristics of broad antibacterial spectru...

AI Technical Summary

Problems solved by technology

In the above-mentioned process, we can see that the two routes are roughly the same, and there are many defects: firstly, the intermediates in each step are not effectively separated and purified, resulting in low purity of the final product (90.5%), which is not suitable for refining, and does not meet the requirements. Market demand; secondly, the use of toxic solvents (such as toluene, etc.) and reagents (triphenylphosphine, etc.) that are more polluting to the environment in the reaction is not conducive to the protection of operators and the environment in the control and amplification of production; again, the production The use of expensive raw materials (triphenylphosphine, diisopropyl azodicarboxylate (DIAD), sodium borohydride, etc.) between), leading to higher product costs and poorer market competitiveness

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