Method for synthesizing bromfenac sodium impurity standard substance

A synthesis method, the technology of bromfenac sodium, is applied in the field of medicine to achieve the effects of short synthesis period, low synthesis cost and quality control of preparations

Inactive Publication Date: 2017-01-04
HEFEI JIUNUO MEDICAL TECH
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In view of this impurity control is crucial to bromfenac sodium product quality, and it can be used as the preparation method and the quality detection method of the standard substance that those skilled in the art use as yet bibliographical information, so the obtaining of this impurity standard substance is very important for effectively controlling bromine. The quality of fenac sodium raw materials and its preparations is of great significance

Method used

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  • Method for synthesizing bromfenac sodium impurity standard substance
  • Method for synthesizing bromfenac sodium impurity standard substance
  • Method for synthesizing bromfenac sodium impurity standard substance

Examples

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Embodiment 1

[0046] The synthetic method of bromfenac sodium impurity standard substance in the present embodiment is as follows:

[0047] 1. Stir and dissolve 10 g (31.6 mmol) of 7-(4-bromobenzoyl) indolin-2-one in 280 ml of ethyl acetate, add 28.4 g (127.2 mmol) of copper bromide, and ℃, reflux and stir for 3 hours, lower the temperature to 20-30 ℃, wash the reaction solution with water equal to the volume of ethyl acetate and saturated aqueous sodium chloride solution, and concentrate the organic phase to dryness under reduced pressure at 50-60 ℃ to obtain the intermediate.

[0048] 2. Add 300ml of methanol / water mixed solution (volume ratio of methanol to water: 4:1) to the intermediate obtained in step 1, reflux and stir at 70-80°C for 2.5h, cool down to 20-30°C, filter, and filter cake Wash with water and methanol in turn, add 250ml of methanol to the filter cake, reflux at 65-70°C for 30 minutes, filter while hot, cool the filtrate to -5-0°C, stir and crystallize for 1 hour, filter,...

Embodiment 2

[0059] The synthetic method of bromfenac sodium impurity standard substance in the present embodiment is as follows:

[0060] 1. Stir and dissolve 10g (31.6mmol) of 7-(4-bromobenzoyl)indolin-2-one in 300ml of ethyl acetate, add 28.4g (127.2mmol) of copper bromide, and ℃ reflux and stir for 3 hours, lower the temperature to 20-30 ℃, wash the reaction solution with water equal to the volume of ethyl acetate and saturated aqueous sodium chloride solution, and concentrate the organic phase to dryness at 50-60 ℃ under reduced pressure to obtain the intermediate.

[0061] 2. Add 250ml of methanol / water mixed solution (volume ratio of methanol to water: 4:1) to the intermediate obtained in step 1, reflux and stir at 70-80°C for 2 hours, cool down to 20-30°C, filter, filter Wash the cake with appropriate amount of water and methanol in turn, add 200ml of methanol to the filter cake, reflux at 65-70°C for 30min, filter while hot, cool the filtrate to -5-0°C, stir and crystallize for 2h...

Embodiment 3

[0066] The synthetic method of bromfenac sodium impurity standard substance in the present embodiment is as follows:

[0067] 1. Stir and dissolve 25g (79mmol) of 7-(4-bromobenzoyl)indolin-2-one in 750ml of ethyl acetate, add 88.2g (395mmol) of copper bromide, and reflux at 78-85°C Stir the reaction for 4 hours, lower the temperature to 20-30°C, wash the reaction solution with water equal to the volume of ethyl acetate and saturated aqueous sodium chloride solution, and concentrate the organic phase to dryness at 50-60°C under reduced pressure to obtain the intermediate.

[0068] 2. Add 700ml of methanol / water mixed solution (volume ratio of methanol to water: 4:1) to the intermediate obtained in step 1, reflux and stir at 70-80°C for 3 hours, cool down to 20-30°C, filter, and filter cake in turn Wash with water and methanol, add 500ml of methanol to the solid, reflux at 65-70°C for 30min, filter while hot, cool the filtrate to -5-0°C, stir and crystallize for 2h, filter, dry ...

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Abstract

The invention discloses a method for synthesizing bromfenac sodium impurity standard substance. 7-(4-bromobenzoyl)-dihydro-2H-indol-2-one is used as the raw material, and subjected to brominating and hydrolyzing to obtain 7-(4-bromobenzoyl)-dihydro-2H-indol-2,3-one pure product. The content of the pure product is calibrated by adopting a conventional analysis way. The method is cheap and easily available in raw materials, simple in process and short in preparation period, and the content of the calibrated product is greater than 98.5%. The bromfenac sodium impurity provided by the invention can be used as an impurity standard substance and can be applied to qualitative and quantitative research and detection of the sodium bromate raw material and the preparation impurities thereof.

Description

[0001] 1. Technical field [0002] The invention relates to a preparation method of a drug impurity standard product, in particular to a synthesis method of a bromfenac sodium impurity standard product, and belongs to the technical field of medicine. [0003] 2. Background technology [0004] Bromfenac sodium sesquihydrate, the chemical name is 2-amino-3-(4-bromobenzoyl) phenylacetic acid sodium salt sesquihydrate, is a non-steroidal anti-inflammatory drug, produced by Japan Chishou Developed by Pharmaceutical Co., Ltd., it was approved by Japan PMDA in March 2000. The product name is "BRONUCK", and the specification is 0.1% bromfenac sodium eye drops of 5ml / bottle. Symptomatic treatment of diseases, including blepharitis, conjunctivitis, dynasticitis (including superior dynasticitis), postoperative inflammation, etc. [0005] The bromfenac sodium raw material and its preparations will produce degradation impurities during storage and transportation: 7-(4-bromobenzoyl)indoline...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D209/38
CPCC07D209/38
Inventor 吴标凌林佘文龙
Owner HEFEI JIUNUO MEDICAL TECH
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