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A kind of preparation method of bicalutamide intermediate

A technology of bicalutamide and intermediates, applied in the preparation of organic compounds, carboxylic acid nitrile preparation, chemical instruments and methods, etc., can solve the problems of poor safety, environmental pollution, high cost, etc.

Active Publication Date: 2021-08-20
SHANXI ZHENDONG PHARMA +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0020] Its purpose is to provide a new method for the preparation of bicathione intermediates applicable to large-scale production, so as to solve the problems of poor safety, environmental pollution and high cost in the existing synthesis technology of bicalutamide

Method used

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  • A kind of preparation method of bicalutamide intermediate
  • A kind of preparation method of bicalutamide intermediate
  • A kind of preparation method of bicalutamide intermediate

Examples

Experimental program
Comparison scheme
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Embodiment 1

[0038] N-(4-cyano-3-trifluoromethylphenyl)methacrylamide (1g) was dissolved in 15ml of acetone, cooled to 0~5°C, slowly added 0.58g of concentrated sulfuric acid, stirred, dropwise 5.86g of 10% sodium hypochlorite solution, after dropping, stir for 0.5h, add 20ml of ethyl acetate and 20ml of water to the reaction solution, separate the liquids, wash the organic phase successively with saturated sodium bicarbonate solution and saturated brine, and dry over anhydrous sodium sulfate , filtered, and precipitated to obtain 1.2 g of a yellow crude product, which was recrystallized with 10 ml of toluene to obtain 1 g of off-white crystals, with a yield of 83% and a purity of 98.02% by HPLC.

Embodiment 2

[0040] N-(4-cyano-3-trifluoromethylphenyl)methacrylamide (1g) was dissolved in 15ml of methanol, cooled to 0~5°C, slowly added 1.17g of concentrated hydrochloric acid, stirred, and added dropwise 5.86g of 10% sodium hypochlorite solution, after dropping, stir for 0.5h, add 20ml of dichloromethane and 20ml of water to the reaction solution, separate the liquids, wash the organic phase successively with saturated sodium bicarbonate solution and saturated brine, and dry over anhydrous sodium sulfate , filtered, and precipitated to obtain 1.1 g of a yellow crude product, which was recrystallized with 10 ml of toluene to obtain 0.95 g of off-white crystals, with a yield of 79% and a HPLC purity of 97.27%.

Embodiment 3

[0042] N-(4-cyano-3-trifluoromethylphenyl)methacrylamide (1g) was dissolved in 25ml of ethanol, cooled to 0~5°C, slowly added 0.58g of concentrated sulfuric acid, stirred, and added dropwise 5.86g of 10% sodium hypochlorite solution, after dropping, stir for 0.5h, add 20ml of ethyl acetate and 20ml of water to the reaction solution, separate the liquids, wash the organic phase successively with saturated sodium bicarbonate solution and saturated brine, and dry over anhydrous sodium sulfate , filtered, and precipitated to obtain 1.2 g of a yellow crude product, which was recrystallized with 10 ml of toluene to obtain 0.91 g of off-white crystals, with a yield of 76% and a purity of 97.95% by HPLC.

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Abstract

The invention provides a preparation method of a bicalutamide intermediate, specifically a method for preparing 3-chloro-N-methacrylamide with N-(4-cyano-3-trifluoromethylphenyl)methacrylamide (4-cyano-3-trifluoromethylphenyl)-2-hydroxy-2-methylpropanamide method: in solvent, N-(4-cyano-3-trifluoromethylphenyl ) methacrylamide as raw material, add acid, cool to 0~15°C, stir, dropwise add sodium hypochlorite solution for oxidation, keep the temperature of the reaction system at 0~15°C after dropping, carry out the reaction for 0.5~1 hour, and the obtained solution is separated and purified Can obtain high-purity 3-chloro-N-(4-cyano-3-trifluoromethylphenyl)-2-hydroxyl-2-methylpropionamide, the preparation method is safe and economical, and can be applied to large The picarthioether intermediate is prepared in large-scale production, and the raw material is cheap and easy to obtain, the production cycle is shortened, and no environmental pollution occurs.

Description

technical field [0001] The invention belongs to the synthesis of chemical drugs in the field of biomedicine, and in particular relates to a preparation method of an antiandrogen drug bicalutamide intermediate. Background technique [0002] Bicalutamide, chemical name N-[4-cyano-3-(trifluoromethyl)phenyl]-3-(4-fluorophenylsulfonyl)-2-methyl-2-hydroxyl Propanamide, the English name is N-[4-cyano-3-(trifluoromethyl)phenyl]-3-[(4-flurophenyl)sulfonyl]-2-hydroxy-2-methyl-propanamide, the chemical formula is as follows: [0003] [0004] It was first launched in the UK in 1995 under the trade name of Casodex, and my country approved the import of bicalutamide tablets in 1999. Bicalutamide is a non-steroidal antiandrogen drug recorded in the 32nd edition of the United States Pharmacopoeia with definite curative effect, strong specificity of action, effective oral administration, convenient administration, good tolerance, and a long half-life. It is currently the only one-time ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07C255/60C07C253/30
CPCC07C253/30C07C255/60
Inventor 李建军高志远熊继业余晓磊梁波乔玉峰周红军
Owner SHANXI ZHENDONG PHARMA