Novel preparation method and use of bisedaravone and medicinal salts of bisedaravone

A technology of solvent and molar ratio, which is applied in the direction of drug combination, cardiovascular system diseases, antitoxic agents, etc., can solve the problems of long synthetic route, low yield and purity, and achieve the effect of preventing and treating cerebral infarction

Inactive Publication Date: 2012-05-02
SHENYANG PHARMA UNIVERSITY +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

But these methods all need multi-step reaction to prepare diedaravone, and synthetic route is long, and yield and purity are on the low side

Method used

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  • Novel preparation method and use of bisedaravone and medicinal salts of bisedaravone
  • Novel preparation method and use of bisedaravone and medicinal salts of bisedaravone
  • Novel preparation method and use of bisedaravone and medicinal salts of bisedaravone

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Experimental program
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Effect test

Embodiment 1

[0024] A kind of preparation method of diedaravone is in oxygen atmosphere, under reflux state, ethyl acetoacetate 130.1 g (1.00 mol) is added dropwise rapidly to phenylhydrazine 113.5 g (1.05 mol) and absolute ethanol 150 mL of the mixed solution, pay attention to stirring while adding dropwise, and the solid will precipitate out soon. After the addition, continue to stir and reflux for 6 h. Suction filtration while hot, wash with absolute ethanol (50 mL×3), and dry the filter cake to obtain a light yellow powdery solid, which is the crude product of diedaravone. Recrystallized with 1500 mL of absolute ethanol and decolorized with activated carbon to obtain 229.7 g of white powdery solid with a yield of 66.3%.

Embodiment 2

[0026] A kind of preparation method of diedaravone is in oxygen atmosphere, under reflux state, methyl acetoacetate 116.1 g (1.00 mol) is added dropwise rapidly to phenylhydrazine 113.5 g (1.05 mol) and absolute ethanol 150 mL of the mixed solution, pay attention to stirring while adding dropwise, and the solid will precipitate out soon. After the addition, continue to stir and reflux for 6 h. Suction filtration while hot, wash with absolute ethanol (50 mL×3), and dry the filter cake to obtain a light yellow powdery solid, which is the crude product of diedaravone. Recrystallized with 1500 mL of absolute ethanol and decolorized with activated carbon to obtain 215.1 g of white powdery solid with a yield of 62.1%.

Embodiment 3

[0028] A kind of preparation method of diedaravone, is in oxygen atmosphere, under reflux state, ethyl acetoacetate 130.1 g (1.00 mol) is added dropwise rapidly to phenylhydrazine 113.5 g (1.05 mol) and anhydrous methanol 150 mL of the mixed solution, pay attention to stirring while adding dropwise, and the solid will precipitate out soon. After the addition, continue to stir and reflux for 8 h. Suction filtration while hot, wash with anhydrous methanol (50 mL×3), and dry the filter cake to obtain a light yellow powdery solid, which is the crude product of diedaravone. Recrystallized with 1500 mL of absolute ethanol and decolorized with activated carbon to obtain 203.0 g of white powdery solid with a yield of 58.6%.

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Abstract

The invention belongs to the technical field of medicine synthesis and relates to a novel preparation method and a use of bisedaravone and medicinal salts of bisedaravone. The preparation method comprises the fo0llowing steps that hydrazinobenzene and acetoacetic ester undergo a reaction in the air or oxygen atmosphere to produce edaravone; and the obtained edaravone undergoes an oxidation dimerization reaction to produce bisedaravone. The novel preparation method has a high yield. Through the novel preparation method, bisedaravone solubility is improved. The medicinal salts of bisedaravone comprise monosodium salts, disodium salts, monopotassium salts, dipotassium salts, monolithium salts and dilithium salts, have free radical scavenger effects, and can be utilized for clinical treatment on cerebral infarction.

Description

technical field [0001] The invention belongs to the technical field of drug synthesis, and relates to a new method for preparing diedaravone: in an air or oxygen atmosphere, phenylhydrazine reacts with acetoacetate to generate edaravone, and then oxidizes and dimersizes to generate diedaravone. Edaravone, the yield of this method is high, and the product is easier to purify; in order to increase the solubility of diedaravone, the present invention also provides its soluble medicinal salt and its preparation; It can be used to prevent and treat cerebral infarction. Background technique [0002] Edaravone (Edaravone, 1), the chemical name is 3-methyl-1-phenyl-2-pyrazolin-5-one, which is developed and produced by Mitsubishi–Tokyo Pharmaceuticals Inc., Japan. A new type of special free radical scavenger developed. In April 2001, the Japanese Ministry of Health and Welfare approved the drug for the treatment of acute cerebral infarction. At present, Edaravone is mainly used fo...

Claims

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Application Information

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IPC IPC(8): C07D231/26A61P39/06A61P9/10
Inventor 许佑君马占芝闫浩李志强李红亮刘宇卜平张磊
Owner SHENYANG PHARMA UNIVERSITY
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