Research On The Synthesis Of Moxifloxacin Hydrochloride And It's Impurity

Moxifloxacin hydrochloride,as a fourth-generation fluoroquinolone antibiotics,was developed by Bayer company.Compared with other fluoroquinolone structures,moxifloxacin not only has the common pharmacophore for inhibiting topoisomerase II,but also has 8-methoxy group for the inhibiting topoisomerase IV,which makes it has no fixed cross-resistance.with other quinolones.Moreover the special position of the C-7 cyclic structure of the product is introduced to inhibit bacterial efflux effect.Moxifloxacin almost has no photosensitivity reactions and excellent safety and high concerntration in the lung tissue,which makes it called the "nearly ideal treatment of respiratory infection drugs."In this paper,the synthesis of moxifloxacin hydrochloride was studied to determine an economic feasibility of a synthetic route.Using the 1-cyclopropyl-6,7-difluoro-8-methoxy-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid ethyl ester(referred to as quinolinecarboxylic acid ethyl ester),(S,S)-2,8-diazabicyclo[4.3.0]nonane(the chiral nonane)and boric acid ester as the starting material,a three-step reaction of moxifloxacin hydrochloride was investigated.The synthesizing process is simple,low cost,low environment contamination and suitable for industrialized production.Results of 3 batches products synthesized according to this technology show that the process has high repeatability and high yield(total molar yield:60.2%).In accordance with the above process for the synthesis of the aimed product,it's structure was confirmed by HPLC,IR,MS,NMR,DSC and other testing,and ultimately confirmed the synthetic product and the target compound moxifloxacin hydrochloride consistent structure.While using powder X-ray diffraction analysis method,the crystalline form of the product was determined and compared with the literature.Though the analysis of the synthesis process and reaction mechanism,the possible process impurities and degradation products were identified,including the enantiomers of moxifloxacin and five related substances.While using preparative HPLC extraction and separation of the product of an unknown impurity,a new structure moxifloxacin impurities,named moxifloxacin amino compounds,was confirmed by detailed structural and literature searches.Using HPLC method the moxifloxacin hydrochloride,related substances and enantiomers were analysed,with the impurities through the retention time comparison,detectable impurities of the product were qualitatived and quantified.Test results showed that the chromatographic purity of 99.9%.The study provided a detailed information on the quality study of moxifloxacin hydrochloride.