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Purification method of enzalutamide

A technology of enzalutamide and refining methods, applied in the direction of organic chemistry, can solve the problems of material precipitation and agglomeration, and can not be produced on a large scale, and achieve the effect of high product purity

Inactive Publication Date: 2015-05-13
JIANGSU HUIBO BIOTECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0009] Purpose: In order to solve the deficiencies of the prior art, the present invention provides a method for refining enzalutamide, which solves the problem that enzalutamide cannot be produced on a large scale by using silica gel column purification, and at the same time prevents the crude enzalutamide from being purified. During the recrystallization process, the material instantly precipitates and agglomerates

Method used

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  • Purification method of enzalutamide

Examples

Experimental program
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Effect test

Embodiment 1

[0024] In a 1000ml reaction flask, add 500ml of absolute ethanol, stir 50g of 95% crude enzalutamide, add 2.5g of activated carbon after stirring for 10 minutes, heat to reflux for 10 minutes, filter while hot, collect the filtrate, and set aside.

[0025] Add the above-mentioned 500ml enzalutamide filtrate into a 1500ml reaction flask, cool to 10°C, add 100ml cyclohexane dropwise for about 15 minutes while stirring, at a stirring speed of 50 rpm, continue stirring for 20 minutes, white crystals gradually precipitate out, After filtering and washing with cyclohexane, 37.2 g of refined enzalutamide was obtained. The product was analyzed by HPLC, the content was 99.5%, and the yield was 77.9%.

Embodiment 2

[0027] In a 1000ml reaction flask, add 600ml of isopropanol, add 50g of 95% enzalutamide crude product under stirring, add 5g of activated carbon after stirring for 10 minutes, heat to reflux for 15 minutes, filter while hot, collect the filtrate, and set aside.

[0028] Add the above-mentioned 600ml enzalutamide filtrate into a 1500ml reaction bottle, cool to 20°C, add 200ml of n-hexane dropwise for about 15 minutes while stirring, at a stirring speed of 200 rpm, continue stirring for 30 minutes, white crystals gradually precipitate, After filtering and washing with n-hexane, 35.8 g of refined enzalutamide was obtained. The product was analyzed by HPLC, the content was 99.6%, and the yield was 75.1%.

Embodiment 3

[0030] In a 1000ml reaction flask, add 500ml of n-butanol, add 50g of 95% enzalutamide crude product under stirring, add 4g of activated carbon after stirring for 10 minutes, heat to reflux for 20 minutes, filter while hot, collect the filtrate, and set aside.

[0031] Add the above-mentioned 500ml enzalutamide filtrate into a 1500ml reaction bottle, cool to 20°C, add 500ml of n-heptane dropwise for about 30 minutes while stirring at a stirring speed of 150 rpm, and continue stirring for 30 minutes, white crystals gradually precipitate out. After filtering and washing with n-heptane, 36.0 g of refined enzalutamide was obtained. The product was analyzed by HPLC, the content was 99.5%, and the yield was 75.5%.

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Abstract

The invention discloses a purification method of enzalutamide. According to the method, a coarse enzalutamide product is added to a recrystallization vessel and dissolved through an alcohol or amide organic solvent; a hydrocarbon solvent is dropwise added while agitating, wherein the dropwise adding speed is controlled and a crystal precipitate of materials in the system can be gradually separated out, and after the dropwise adding is done, the solid can be separated out; the solid can be filtered to obtain the fine enzalutamide product. By virtue of the method, the problems such as instantaneous caking and impurities occurring in recrystallization of enzalutamide can be solved; the method is suitable for industrial production; the enzalutamide product obtained by recrystallization has the purity more than 99.5%, and the recrystallization yield is more than 75%; an enzalutamide preparation is processed according to the requirements of standard on raw medicines in Chinese Pharmacopoeia, so that a patient can use safely.

Description

technical field [0001] The invention relates to a refining method of a novel anti-androgen receptor drug enzalutamide, in particular to a recrystallization refining method of adding a hydrocarbon organic solvent dropwise to an alcohol or amide organic solvent, and belongs to the technical field of medicine. Background technique [0002] Enzalutamide (enzalutamide 1), chemical name: 4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2- Thione-1-imidazolidinyl]-2-fluoro-N-methylbenzamide; trade names: MDV3100, Xtandi, Enzalutamide, enzalutamide, etc., the chemical structural formula is shown in formula 1, and it is manufactured by Medivation Company of the United States and Anzalutamide of Japan. Co-developed by Astellas, it was approved by the US Food and Drug Administration (FDA) on August 31, 2012, for the treatment of advanced (metastatic) male castration-resistant prostate cancer that has spread or recurred ( Castration-Resistant Prostate Cancer, CRPC), is a sec...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D233/86
CPCC07D233/86
Inventor 徐德锋
Owner JIANGSU HUIBO BIOTECH
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