The Preparation Of The Intermediate Of Rbx-7644

By now there are many drugs are resistant especially antibiotics. Oxazolidinone antibacterial drug is a new generation of synthetic antibacterial drugs and there are few reports on its dtug-resistant currently. Rbx-7644 is one of them and has been treaded to phaseâ…¡clinical experiment. The purpose of this paper is on the research how to preparation of the intermediate of it.Three synthetic routes to prepare the oxazolidinone ring in this paper, and the best route was determined to synthesis the intermediate of Rbx-7644 successfully, which isN-3-[3-fluoro-4-[N-1-(4-benzyloxycarbonyl)-piperazinyl]-phenyl]-2-oxo-5-oxazolealkyl ]-methyl azide,by a synthetic route. This paper determines to use 1,2-difluoro-4-nitroben--zene as the starting material and synthesis the intermediate, which is N-benzyloxycarbon-yl-3-fluoro-4-(N-benzyloxycarbonyl-piper-azine)aniline, through using substitution, nitration reduction and amine protection, and then it was used to get a reaction with racemic epichlorohydrin through substitution and azide. And the reaction condition of synthesizing intermediate is optimizes and the reaction was scaled up.In the process of synthesizing 3-fluoro-4-piperazinyl aniline, hydrazine hydrate and ferric chloride reduction system was using for nitro reduction. So that can reduce pollution and reduce the cost of synthesizing.In the process of synthesizing 3-fluoro-4-(piperazin-1-yl)benzene amine, this paper used benzyl carbonochloridate to replace of tert-butoxycar--bonyl group as an amine protection for simplifying the experimental conditions. So it was conducived to industrialization. The total yield of the two steps is 59%. The structures were confirmed through IR and NMR and MS.