Refining method for tedizolid phosphate

Abstract

The invention belongs to the field of medicine synthesis and relates to a refining method for tedizolid phosphate.The refining method for tedizolid phosphate includes the following steps that crude tedizolid phosphate is added into water, the pH value is adjusted with alkali liquor, tedizolid phosphate disodium salt is formed, activated carbon decoloration is conducted, acetone is slowly added into filtrate, a large number of solids are separated out, stirring crystallization is conducted, and tedizolid phosphate disodium salt is obtained after filtration; tedizolid phosphate disodium salt is dissolved in water and acidized, white solids are separated out, acetonitrile is added, stirring crystallization is conducted, and high-purity tedizolid phosphate is obtained after filtration.The purity of the product obtained through the method is 99.5% or above, the single impurity content is smaller than 0.1%, and the refining yield is not smaller than 85%; another remarkable advantage is that tedizolid phosphate A crystal form solids can be stably obtained, the particle size distribution D99 of the solids is smaller than 20 micrometers, no adhesion is caused in the pelleting process, and the solids are suitable for producing and processing preparations.

Description

technical field [0001] The invention belongs to the field of drug synthesis, and in particular relates to a method for refining tedizolid phosphate. Background technique [0002] Tedizolidphosphate, also known as tedizolid phosphate, tedizolid phosphate, tedizolid phosphate, the chemical name is [(5R)-3-{3-fluoro-4-[6-( 2-Methyl-2H-tetrazol-5-yl)pyridin-3-yl]phenyl}-2-oxooxazolidin-5-yl]methyl hydrogen phosphate, the molecular formula is C 17 h 16 FN 6 o 6 P, its structural formula is as follows: [0003] [0004] Tedizolidphosphate (Tedizolidphosphate) is a second-generation oxazolidinone antibiotic developed by Dong-APharmaceutical. Its phase III clinical trials have shown that its clinical effect is comparable to that of linezolid, in terms of gastrointestinal tract and thrombocytopenia There are fewer adverse reactions than linezolid, and the incidence of drug resistance is also lower. Trials have shown that tedizolid is also better tolerated than vancomycin. F...

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Problems solved by technology

[0008] In the above publications, the disodium salt is formed in CN1894242B and the pH is adjusted with trifluoroacetic acid. After concentration, the method of crystallization with ethanol and ether has weak impurity removal ability, and high-purity tedizolid phosphate cannot be obtained, and the flash point of ether is Low, not suitable for industrial production

In the patent application CN201080014363.0, the refining method of dimethyl sulfoxide or N-methylpyrrolidone is used, the yield is low and the high boiling point solvent dimethyl sulfoxide or N-methylpyrrolidone is difficult to remove, and the disclosed tedizolid phosphate Add acid to the disodium salt solution to adjust the pH, then add water or a mixture of tetrahydrofuran / water, crystallize to obtain tedizolid phosphate, which can obtain stable A crystal form, and has a suitable particle size distribution, but in the preparation of tedizolid phosphate In the process of tablet process development, it was found that tedizolid phosphate obtained from water or tetrahydrofuran-water system would produce gel and stickiness when encountering water, resulting in low tablet dissolution

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