Refining method for tedizolid phosphate

A technology of tedizolid phosphate and tedizolid phosphate disodium salt, which is applied in the field of refining tedizolid phosphate, and can solve problems such as low flash point and difficult removal of gel and ether

Active Publication Date: 2016-07-13
NANJING GRITPHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

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

Method used

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  • Refining method for tedizolid phosphate
  • Refining method for tedizolid phosphate
  • Refining method for tedizolid phosphate

Examples

Experimental program
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Effect test

Embodiment 1

[0060] Dissolve 45g of tedizolid phosphate in purified water (185ml), add dropwise 8% sodium hydroxide solution at an internal temperature of 15-25°C, adjust the pH to 7.5, add activated carbon (2.25g), and control the internal temperature at 15-25°C. Stir at 25°C for 2 hours, filter, transfer the filtrate to a reaction flask, slowly add acetone (1.73L), stir and analyze for 2 hours, a large amount of solid precipitates, filter, wash the filter cake with a small amount of acetone, and drain to obtain tedizolid phosphate sodium salt .

[0061] The tedizolid phosphate sodium salt obtained above was transferred to a reaction flask, and purified water (185 ml) was added to dissolve it. 3% hydrochloric acid solution (365ml) was added dropwise at an internal temperature of 15-25°C. After the dropwise addition was complete, the mixture was stirred at the same temperature for 1h, and then acetonitrile (890ml) was slowly added. Stir and crystallize at 15-25°C for 3h, stirring at 200r....

Embodiment 2

[0063] Dissolve 30g of tedizolid phosphate in purified water (180ml), add 10% sodium hydroxide solution dropwise at an internal temperature of 5-10°C, adjust the pH to 7.2, add activated carbon (3.0g), and control the internal temperature at 20-10°C. Stir at 25°C for 1 hour, filter, transfer the filtrate to a reaction flask, add acetone (760ml) slowly, stir and analyze for 3 hours, a large amount of solid precipitates, filter, wash the filter cake with a small amount of acetone, and drain to obtain tedizolid phosphate sodium salt.

[0064] The tedizolid phosphate sodium salt obtained above was transferred to a reaction flask, and purified water (180 ml) was added to dissolve it. 5% hydrochloric acid solution (365ml) was added dropwise at an internal temperature controlled at 5-10°C. After the dropwise addition was complete, the mixture was stirred at the same temperature for 1h, and acetonitrile (380ml) was slowly added. Stir and crystallize at 15-25°C for 5h, stirring at 230r...

Embodiment 3

[0066] Dissolve 30g of tedizolid phosphate in purified water (150ml), add 5% sodium hydroxide solution dropwise at an internal temperature of 10-15°C, adjust the pH to 7.4, add activated carbon (2.5g), and control the internal temperature at 15-15°C. Stir at 20°C for 1.5h, filter, transfer the filtrate to a reaction flask, slowly add acetone (950ml), stir and analyze for 2h, a large amount of solid precipitates, filter, wash the filter cake with a small amount of acetone, and drain to obtain tedizolid phosphate sodium salt .

[0067] The tedizolid phosphate sodium salt obtained above was transferred to a reaction flask, and purified water (150 ml) was added to dissolve it. Add 8% hydrochloric acid solution (300ml) dropwise at an internal temperature of 5-10°C. After the dropwise addition, stir at the same temperature for 2h at a stirring speed of 215r.p.m, and slowly add acetonitrile (760ml). Stir and crystallize at 5-10°C for 4 hours, filter, wash with a small amount of puri...

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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...

Claims

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Application Information

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IPC IPC(8): C07F9/6558
CPCC07F9/65583
Inventor 杨建楠李营刘二军陆滢炎赵卿霍立茹李战
Owner NANJING GRITPHARMA CO LTD
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