Preparation method of ornidazole injection impurity 1-(3-chloro-propenyl)-2-methyl-5-nitroimidazole

A technology of ornidazole injection and nitroimidazole, which is applied in the field of drug synthesis, can solve problems such as difficulties in the preparation of impurities, and achieve the effects of high yield, good commercial value, and simple operation

Active Publication Date: 2016-01-20
SHANDONG QIDU PHARMA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0007] The purpose of this invention is to provide a kind of preparation method of ornidazole injection impurity 1-(3-chloro-propenyl)-2-methyl-5-nitroimidazole, solve the difficult problem of impurity preparation, have relatively high yield High, environment-friendly and easy to operate

Method used

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  • Preparation method of ornidazole injection impurity 1-(3-chloro-propenyl)-2-methyl-5-nitroimidazole
  • Preparation method of ornidazole injection impurity 1-(3-chloro-propenyl)-2-methyl-5-nitroimidazole
  • Preparation method of ornidazole injection impurity 1-(3-chloro-propenyl)-2-methyl-5-nitroimidazole

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Embodiment 1

[0026] Add 2-methylimidazole (20.0g, 0.24mol), 1,3-dichloropropene (26.4g, 0.24mol), potassium hydride (12.0g, 0.30mol), and 500ml tetrahydrofuran into a 1L three-necked flask, and heat. Raise the temperature to reflux, keep the temperature and react for 12 hours. After the reaction is completed, filter and spin dry to form an oily substance. Column chromatography (dichloromethane:methanol=50:1, filled with silica gel is 200-300 mesh) yields the intermediate product V-235.5g, Yield: 87.0%.

[0027] Measure 50ml of fuming nitric acid into a 250ml three-necked bottle, cool to 0°C, slowly add the intermediate product (20g, 0.12mol) in the previous step to the system, and control the temperature at 0-5°C. After the addition, 25 g of phosphorus pentoxide was added in batches to the system, and the temperature was controlled at 0-5° C. during the addition. Then keep the reaction at 0-5°C for 4h. After the reaction is complete, pour the reaction solution into purified water cooled ...

Embodiment 2

[0029] Add 2-methylimidazole (20.0g, 0.24mol), 1,3-dichloropropene (33.0g, 0.30mol), potassium carbonate (48.3g, 0.35mol), and 500ml of acetonitrile into a 1L three-necked flask, heat, Raise the temperature to reflux, and keep it warm for 16 hours. After the reaction is completed, filter and spin dry to form an oily substance. Column chromatography (dichloromethane:methanol=50:1, filled with silica gel is 200-300 mesh) yields the intermediate product Ⅴ-233.0g, Yield: 80.8%.

[0030] Measure 50ml of fuming nitric acid into a 250ml three-necked bottle, cool to 0°C, slowly add the intermediate product (20g, 0.12mol) in the previous step to the system, and control the temperature at 0-5°C. After the addition, 30 g of acetic anhydride was slowly added dropwise to the system, and the temperature was controlled at 0-5° C. during the addition. Then the reaction was incubated at 0-5°C for 5h. After the reaction is complete, pour the reaction solution into purified water cooled to 0°C...

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Abstract

The invention belongs to the technical field of drug synthesis, and particularly relates to a preparation method of ornidazole injection impurity 1-(3-chloro-propenyl)-2-methyl-5-nitroimidazole. The preparation method comprises the following steps: dissolving 2-methylimidazole, 1,3-dichloropropene and alkali into a solvent, heating to backflow for performing a reaction, and after the reaction, a product, namely the 1-(3-chloro-propenyl)-2-methylimidazole is obtained through post-treatment; adding the product into a reactor containing nitrosonitric acid for performing a nitration reaction, after adding, adding a dehydrating agent in batches into a system, and obtaining 1-(3-chloro-propenyl)-2-methyl-5-nitroimidazole through post-treatment. The preparation method provided by the invention has the advantages of being simple to operate, mild in reaction, relatively high in yield, high in product purity, suitable for quality research and the like, has excellent commercial value, and provides a guarantee for the quality of ornidazole.

Description

technical field [0001] The invention belongs to the technical field of medicine synthesis, and in particular relates to a preparation method of ornidazole injection impurity 1-(3-chloro-propenyl)-2-methyl-5-nitroimidazole. Background technique [0002] Ornidazole is the third generation of nitroimidazole derivatives. It is a powerful drug against anaerobic bacteria and antiprotozoal infection. Better and wider distribution of nitroimidazole derivatives in vivo. The antimicrobial effect of ornidazole is through the reduction of the nitro group in its molecule to an amino group in an oxygen-free environment, or through the interaction with cell components in the form of free radicals, resulting in the death of microorganisms. The plasma elimination half-life of ornidazole is 14 hours, the plasma protein binding rate is less than 15%, and it is widely distributed in tissues and body fluids, including cerebrospinal fluid. Ornidazole is metabolized in the liver and excreted mai...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D233/93
CPCC07D233/93
Inventor 杨学谦张涛王朋曹鹏刘文坤刘海萍
Owner SHANDONG QIDU PHARMA
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