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Preparation method of linezolid injection for degrading impurities

A technology for linezolid and injection, which is applied in the field of preparation of linezolid injection impurities, which can solve problems such as difficulty in refining and affecting the purity of the final product, and achieve the effects of stable quality, mild reaction conditions, and simple operation

Active Publication Date: 2018-07-24
CHONGQING CHANGJIE MEDICINE CHEM
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

They believe that intermediate 4 can be directly obtained by monoacetylation on the aniline of intermediate 2, but the formation of diacylated impurities (3) and hydroxyl monoacylated impurities cannot be avoided
Experiments have shown that these two impurities will seriously affect the purity of the final product, making it difficult to refine

Method used

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  • Preparation method of linezolid injection for degrading impurities
  • Preparation method of linezolid injection for degrading impurities

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] Example 1: Preparation of (2R)-1-chloro-3-{[3-fluoro-4-(morpholin-4-yl)phenyl]amino}-propan-2-ol (7)

[0020] Add 10g of intermediate (6) to a 250mL three-neck flask, then add 100mL of acetonitrile, dissolve at room temperature, then add 6.9g of (S)-epichlorohydrin, and heat up to 50°C for reaction. After 5 hours, the solvent was distilled off, 100 mL of dichloromethane was added, and washed with 3×50 mL of water. The organic layer was dried over anhydrous sodium sulfate and concentrated to obtain 10.4 g of oily intermediate (7) with a purity of 96.2% and a yield of 71%.

Embodiment 2

[0021] Example 2: Preparation of (2R)-1-{acetyl[3-fluoro-4-(morpholin-4-yl)phenyl]amino}-3-chloropropan-2-yl acetate (8)

[0022] Dissolve 10.4g of intermediate (7) in 42mL of dry dichloromethane, add it to a 100mL three-necked flask, then add 8.7g of triethylamine, cool to 0-5°C, add 6.8g of acetyl chloride dropwise, and finish dropping within half an hour. Then it was raised to 20-25°C for 2 hours, and the reaction solution was quenched by adding 40 mL of ice water. The organic layer was washed with 3×50 mL of water, dried over anhydrous sodium sulfate, and concentrated. 11.0 g of oil was obtained with a purity of 92.5% and a yield of 82%.

Embodiment 3

[0023] Example 3: Preparation of (2R)-1-{acetyl[3-fluoro-4-(morpholin-4-yl)phenyl]amino}-3-chloropropan-2-yl acetate (8)

[0024] Dissolve 10.4g of intermediate (7) in 42mL of dry dichloromethane, add it to a 100mL three-necked flask, add 6.8g of pyridine, cool to 5-10°C, add 6.8g of acetyl chloride dropwise, and finish dropping within half an hour. Then it was raised to 25-30°C for 2 hours, and the reaction solution was quenched by adding 40 mL of ice water. The organic layer was washed with 3×50 mL of water, dried over anhydrous sodium sulfate, and concentrated. 11.3 g of oil was obtained with a purity of 93.6% and a yield of 84%.

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Abstract

The invention discloses a preparation method of a linezolid injection degradation impurity. The method consists of: carrying out condensation reaction on N-carboxybenzyl-3-fluoro-4-morpholinoaniline and R-epichlorohydrin, then conducting acetylation, and finally carrying out hydrolysis aminolysis so as to obtain the linezolid injection degradation impurity N-[(2S)-3-amino-2-hydroxpropyl]-N-[3-fluoro-4-(4-morpholinyl)phenyl]-acetamide, the chemical structure of which is shown as the specification.

Description

technical field [0001] The invention relates to a method for preparing impurities in linezolid injection, which belongs to the field of medicine and chemical industry. Background technique [0002] Linezolid (Linezolid) is a new type of oxazolone antibacterial drug, which has high antibacterial activity against various Gram-positive bacteria that cause community and nosocomial infections, and can treat nosocomial pneumonia, skin and soft tissue Infection, community infectious pneumonia and other diseases, its curative effect has been widely clinically confirmed. In addition, the clinical efficacy of linezolid is better than or equal to that of conventional antibacterial drugs, and it is effective against infections caused by methicillin-resistant staphylococci (MRSA), glycopeptide-resistant enterococci, penicillin-resistant pneumococci (PRSP), etc. Also effective, and less toxic and side effects, safe to use. [0003] Linezolid injection is one of the main formulations of ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D295/135
CPCC07D295/135
Inventor 辛涛林江
Owner CHONGQING CHANGJIE MEDICINE CHEM
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