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Novel synthesis method for key intermediate of tedizolid

A kind of technology of tedizolid and intermediate, which is applied in the field of raw medicine preparation, and achieves the effects of reducing the production of debrominated impurities, high yield and improved yield

Active Publication Date: 2017-12-19
CHONGQING SHENGHUAXI PHARMA CO LTD +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0014] The purpose of the present invention is to provide a method for preparing tedizolid key intermediate I with high yield and easy industrialization of reaction temperature for the defects of low temperature reaction and low yield in the existing key intermediate I preparation method

Method used

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  • Novel synthesis method for key intermediate of tedizolid
  • Novel synthesis method for key intermediate of tedizolid
  • Novel synthesis method for key intermediate of tedizolid

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0036] Dissolve the starting material SM (50g, 0.155mol) in 500ml of anhydrous tetrahydrofuran, cool the reaction solution to -10°C, add isopropylmagnesium bromide (0.156mol) in tetrahydrofuran solution dropwise, and stir the reaction at -10°C 3h, add n-butyl lithium n-hexane solution (0.158mol) dropwise, stir at -10°C for 1h, add trimethyl borate (19.3g, 0.186mol) dropwise, stir at -10°C for 2h, thin-layer chromatography After detecting the reaction of the raw materials, add 250ml of water dropwise, stir and separate the layers, extract the water layer with ethyl acetate until there is no product in the water layer, combine the organic layers, wash with saturated brine, dry and concentrate to dryness to obtain 40.3g of white powdery intermediate I , the yield is 90%, and the purity is 99%.

Embodiment 2

[0038] The starting material SM (200g, 0.62mol) was dissolved in 2000ml of anhydrous tetrahydrofuran, the reaction solution was cooled to -10°C, a solution of isopropylmagnesium chloride (1.24mol) in tetrahydrofuran was added dropwise, and the reaction was stirred at -10°C for 5h. Add n-butyllithium n-hexane solution (0.93mol) dropwise, stir and react at -10°C for 1h, add trimethyl borate (1.24mol) dropwise, stir and react at -10°C for 2h, the reaction of raw materials is detected by thin layer chromatography, Add 1000ml of water dropwise, stir and separate the layers, extract the aqueous layer with dichloromethane until there is no product in the aqueous layer, combine the organic layers, wash with saturated brine, dry and concentrate to dryness to obtain 170.2g of white powdery intermediate I, yield 95% , with a purity of 98.9%.

Embodiment 3-7

[0040] According to the general method described in Example 1, the yield and purity of the tedizolid key intermediate I obtained by changing the technical conditions of each reaction are summarized in the following table:

[0041] .

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Abstract

The invention relates to a novel synthesis method for a key intermediate of tedizolid. The method is characterized in that a starting material SM is dissolved in an anhydrous solvent; then a Grignard reagent isopropyl magnesium halide is added to prepare a Grignard reagent of SM; then n-butyllithium is added to prepare a SM magnesium-lithium complex; and then the SM magnesium-lithium complex is reacted with borate to prepare the target intermediate. The method provided by the invention overcomes the problem of extremely low reaction temperature in the prior art, greatly improves reaction yield, and is easy to realize industrialized production.

Description

technical field [0001] The present invention belongs to the technical field of raw material preparation, and in particular relates to a new preparation method of a key intermediate of oxazolidinone antibiotic tedizolid phosphate. Background technique [0002] Tedizolid phosphate is a new type of oxazolidinone antibiotic developed by Dong-APharm. Co. in Korea. It was approved by the US FDA in June 2014 for marketing in the US. The trade name is for sivextro. As a second-generation oxazolidinone antibiotic, compared with the first-generation linezolid, tedizolid phosphate showed higher resistance to Staphylococcus aureus, methicillin-resistant bacteria, and methicillin-sensitivity in clinical trials. Bacteria and streptococcal activity, which is 2-4 times that of linezolid. And compared with linezolid, tedizolid phosphate has other advantages: in clinical trials, tedizolid phosphate gastrointestinal side effects Fewer; no drug interactions similar to linezolid. [0003] The...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07F5/02
CPCC07F5/02
Inventor 曾秀秀白江燕
Owner CHONGQING SHENGHUAXI PHARMA CO LTD
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