Novel method for preparing marbofloxacin

Abstract

The invention mainly discloses a novel method for preparing marbofloxacin, which comprises the following steps: under the protection of inert gases, 2,3,4,5-phenyl tetrafluoride formoxyl alkyl ester forms negative ions with alkali in an inert organic solvent, is condensed with imidic salt to obtain N-dimethyl substitutive enamine derivative, and reacts with N - methyl hydrazide in organic acid to obtain N-methyl-N-acyl substitutive enamine derivative; under the reflux state, the N-methyl-N-acyl substitutive enamine derivative is catalyzed by alkali to obtain quinoline carboxylic ether; the quinoline carboxylic ether takes water as a solvent, is catalyzed with alkali at proper temperature and is neutralized to obtain quinoline carboxylic acid; under the action of an acid-binding agent, the quinoline carboxylic acid is condensed with N-methyl piperazine to obtain a condensed piperazine substance; the condensed piperazine substance is heated to proper temperature in an alkalis hydroxid water solution, is kept at the temperature and is neutralized to obtain hydrolysate; and the hydrolysate takes water as a solvent and is reacted with dialkoxy methane or methylene halide to obtain the marbofloxacin under the catalysis of the catalyzer. The invention has high yield, thereby facilitating industrialized production at large scale.

Description

technical field [0001] The invention belongs to the field of chemistry, and specifically provides a new method for preparing marbofloxacin, which uses 2,3,4,5-tetrafluorobenzoyl ester as a raw material to obtain a target compound through a series of chemical reactions. Background technique [0002] Marbofloxacin (hereinafter referred to as compound I) is a new type of fluoroquinolone antibacterial drug for animals. It was first developed by Roche Company, and then further developed by Ve'toquinol Company. It was listed in Britain and France successively in 1995. Its structural formula is: [0003] [0004] Mabaofloxacin has the advantages of broad antibacterial spectrum, strong bactericidal power, fast absorption, wide distribution in the body, no cross-resistance with other antibacterial agents, convenient use, and small adverse reactions. Pharmacokinetic studies have shown that marbofloxacin has a long elimination half-life in animals, its bioavailability is close to ...

AI Technical Summary

Problems solved by technology

However, because the tetrabutylammonium fluoride used is expensive, and the reaction needs to be carried out under strict anhydrous conditions, there is no industrial value

[0025] In summary, there are various deficiencies in the existing synthetic route of marbofloxacin, such as harsh reaction conditions, expensive chemical reagents, too long reaction route, more impurities in individual reaction steps, etc.

Images