Tebipenem pivoxil intermediate and synthesis method and application thereof

Abstract

The invention belongs to the technical field of medicine, and particularly relates to a tebipenem pivoxil intermediate and a synthesis method and application thereof. The synthesis method comprises the following steps: with ethylamine and chloroacetamide as initial raw materials, successively carrying out multiple reactions; and carrying out rotary evaporation and concentration so as to obtain 3-acetylthio-1-(1,3-thiazol-2-yl)azetidine. According to the synthesis method, ethylamine and chloroacetamide are selected as the initial raw materials which are cheap and easily-available; the synthesisof the intermediate 1-azabicyclo[1.1.0]butane is avoided; reaction steps are few; reaction time is short; and industrial production of the method is facilitated. The chemical purity of the tebipenempivoxil intermediate can reach 90.44% or above, the yield can reach 79.13% or above, and the method has good industrial prospects.

Description

technical field [0001] The invention relates to the technical field of medicines, in particular to a tibipenem intermediate and its synthesis method and application. Background technique [0002] Carbapenem antibiotics are a class of broad-spectrum antibiotics developed in the 1970s. They have strong antibacterial activity and have good antibacterial effects on aerobic and anaerobic bacteria. They are stable to β-lactamase and are especially suitable for many A variety of bacteria, especially the mixed infection of aerobic bacteria and anaerobic bacteria, and it also has a killing effect on static bacteria. In addition, because this kind of drug has fewer adverse reactions, the application time is shorter, and the drug resistance has not been significantly strengthened, it is sometimes used as the last line of defense against bacteria and plays an important role in the treatment of severe hospital infections. Tibipenem is a carbapenem antibiotic developed by Pfizer of the U...

AI Technical Summary

Problems solved by technology

[0006] Isoda T, Yamamura I, Tamai S, et al.APractical and Facile Synthesis of Azetidine Derivatives for Oral Carbapenem, L-O84[J].Chem.Pharm.Bull,2006,54(10):1408-1411. Synthesize the side chain of tibipenem with epichlorohydrin as the starting material, avoiding the synthesis of the intermediate 121-azabicyclo[1.1.0]butane, the reaction conditions are not as harsh as route 1, but the next few steps of reaction operation Difficult to control, low yield, only 25-35%

Images