Synthesis method of gatifloxacin cyclic ester

Abstract

The invention belongs to a production process of a pharmaceutical intermediate, and particularly discloses a synthesis method of gatifloxacin cyclic ester. The synthesis method comprises the followingsteps: performing hydrolysis, decarboxylation and methylation on 3, 4, 5, 6-tetrafluoro-N-methylphthalimide serving as a starting material to obtain 2,4,5-trifluoro-3-methoxybenzoyl chloride, coupling the 2,4,5-trifluoro-3-methoxybenzoyl chloride with N,N-ethyl dimethylaminoacrylate, then replacing with cyclopropylamine, and finally performing cyclization to produce the gatifloxacin cyclic esterunder the action of DMF and potassium fluoride. The reaction route is short, the raw materials are wide in source; furthermore, the reaction conditions are mild and easy to operate and control, whichreduces the consumption of the raw materials, facilitates the post-treatment and reduces the cost; potassium fluoride used instead of potassium carbonate in the reaction can not only reduce productionof exhaust gas, but also make the used potassium fluoride used continuously through adjustment by potassium hydroxide, and the cost is further reduced.

Description

technical field [0001] The invention belongs to the production process of pharmaceutical intermediates, in particular to a synthesis method of gatifloxacin cycloester. Background technique [0002] Quinolones, also known as pyruvate or pyridone, target the deoxyribonucleic acid of bacteria and have a broad antibacterial spectrum. Quinolones have developed rapidly since their inception, and have been written as one of the main drugs against bacterial infections. They are widely used to treat various infections, and have played an important role in improving the cure rate of infections caused by sensitive bacteria and reducing the fatality rate of critical infections. [0003] Gatifloxacin, whose English name is gatifloxacin, is a new 6-fluoro-8-methoxyquinolone compound created by Japan Kyorin Pharmaceutical Co., Ltd., which is effective against Gram-negative bacteria, Gram-positive bacteria, anaerobic bacteria, mycoplasma, and chlamydia Both mycobacteria and mycobacteria ha...

AI Technical Summary

Problems solved by technology

In the above-mentioned reactions, there are many by-products during decarboxylation and Grignard reaction, difficult product separation, large discharge of three wastes, need to use raw materials with great safety hazards such as triethyl orthoformate, and use 2,4,5-tetrafluoro-3-formazol Oxybenzoyl chloride is used as a starting material, which increases the cost of synthesis

[0006] In addition, 3,4,5,6-tetrafluorophthalic acid can also be used as a starting material. The patent document EP0352123A2 introduces that 3,4,5,6-tetrafluorophthalic acid undergoes hydrolysis, decarboxylation, and methylation in sequence. Kylation, acylation, condensation, hydrolysis, condensation, amination and cyclization to obtain the main structure of quinolones, but this synthetic route has long steps, low yield, poor atom economy in the reaction, and reduced utilization of raw materials

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