Synthesis method of flunixin meglumine

A technology of flunixin meglumine and a synthesis method, applied in the field of drug synthesis, can solve problems such as increased production cost, high difficulty in purification and utilization, and achieve the effects of improved product yield, convenient industrial operation, and simple synthesis operation.

Active Publication Date: 2014-12-10
济南久隆医药科技有限公司 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the main raw material of this patent is 2-methyl-3-trifluoromethylaniline, and it is difficult to recover, purify and utilize it by using 2 times the amount of feed, which will inevitably lead to an increase in the entire production cost.

Method used

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  • Synthesis method of flunixin meglumine
  • Synthesis method of flunixin meglumine
  • Synthesis method of flunixin meglumine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0018] (1) Dissolve 4g of sodium hydroxide in 95ml of water. After the sodium hydroxide is completely dissolved and cooled, add 18.4g of 2-methyl-3-trifluoromethylaniline and 15.7g of 2-chloronicotinic acid into the sodium hydroxide solution After stirring and dissolving, add 95ml toluene and 0.157gTEBAC, control the temperature and stir at 40°C for 4 hours; adjust the pH to 10 with 3mol / L NaOH solution after the reaction solution drops to room temperature, stir for 10min, and remove the upper organic layer after standing for 20min. phase, and then adjust the obtained water phase to pH to 5 with 4mol / L sulfuric acid, after stirring for 1 hour, the filter cake was washed with purified water after suction filtration, and dried. 28.4 g of the product was obtained with a yield of 95.9%.

[0019] (2) Add 20.0 g of the product flunixin and 14.5 g of N-methylglucamine to 120 ml of isopropanol, heat to reflux for 1 hour, filter while hot to obtain the filtrate, and let the filtrate co...

Embodiment 2

[0033] (1) Dissolve 4g of sodium hydroxide in 95ml of water. After the sodium hydroxide is completely dissolved and cooled, add 18.5g of 2-methyl-3-trifluoromethylaniline and 15.7g of 2-chloronicotinic acid into the sodium hydroxide solution After stirring and dissolving, add 95ml toluene and 0.157g TEBAC, control the temperature at 45°C and stir for 4 hours; after the reaction solution drops to normal temperature, use 3mol / L NaOH solution to adjust the pH to 10, stir for 10min, and remove the upper organic layer after standing for 20min. phase, and then adjust the resulting aqueous phase to pH 6 with 4mol / L sulfuric acid, and after stirring for 1 hour, the filter cake was washed with purified water after suction filtration, and dried. Obtain product 28.2g, yield 95.3%

[0034] (2) Add 20.0 g of the product flunixin and 14.5 g of N-methylglucamine to 120 ml of isopropanol, heat to reflux for 1 hour, filter while hot to obtain the filtrate, and let the filtrate cool to 50 Stir...

Embodiment 3

[0036] (1) Dissolve 4g of sodium hydroxide in 106ml of water. After the sodium hydroxide is completely dissolved and cooled, add 18.4g of 2-methyl-3-trifluoromethylaniline and 15.7g of 2-chloronicotinic acid into the sodium hydroxide solution After stirring and dissolving, add 106ml toluene and 0.157g TEBAC, control the temperature and stir at 40°C for 4 hours; adjust the pH to 11 with 3mol / L NaOH solution after the reaction solution drops to room temperature, stir for 10min, and remove the upper organic layer after standing for 20min. layer, and then the resulting water layer was adjusted to pH to 5 with 4mol / L sulfuric acid, and after stirring for 1 hour, the filter cake was washed with purified water after suction filtration, and dried. 27.9 g of the product was obtained with a yield of 94.3%.

[0037](2) Add 20.0 g of the product flunixin and 14.5 g of N-methylglucamine to 130 ml of isopropanol, heat to reflux for 1 hour, filter while hot to obtain the filtrate, and let th...

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Abstract

The invention discloses a synthesis method of flunixin meglumine, which comprises the following steps: adding 2-chloronicotinic acid and 2-methyl-3-trifluoromethyl aniline into a sodium hydroxide water solution, stirring, adding toluene and a phase-transfer catalyst, reacting at controlled temperature of 40-45 DEG C for 4-5 hours, regulating the pH value of the solution to 10-11, stirring, standing to stratify, regulating the pH value of the water layer to 5-6, stirring, filtering, washing the filter cake, and drying to obtain flunixin, reacting flunixin and N-methylglucosylamine in isopropanol, heating under reflux for 0.5-1.5 hours, filtering, cooling to 50-60 DEG C, and stirring to crystallize; and when the system temperature drops to 25 DEG C below, continuing stirring for 1 hour, carrying out vacuum filtration on the crystal, and washing with isopropanol to obtain the flunixin meglumine. The method lowers the reaction temperature, saves the energy, shortens the reaction time, and is simple for synthesis operation, low in facility requests and convenient for industrialized operation.

Description

technical field [0001] The invention belongs to the technical field of medicine synthesis, and in particular relates to a synthesis method of flunixin meglumine. technical background [0002] Flunixin meglumine is a new type of non-steroidal animal-specific antipyretic and analgesic drug, which belongs to the derivative of nicotinic acid and is a cyclooxygenase inhibitor. Developed by Schering-Plough in the 1990s, it has been widely used in the United States, France, Switzerland, Germany, the United Kingdom and many other countries. At present, the Ministry of Agriculture of my country has approved some veterinary drug factories to produce flunixin meglumine. In veterinary clinical practice, the drug is used in horses to relieve inflammation and pain caused by muscle abnormalities, relieve horses' visceral colic, and treat foals' diarrhea, tremors, colitis, etc.; it is used in cattle to treat respiratory diseases, endotoxin-induced mastitis; for dogs to treat arthritis, fe...

Claims

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Application Information

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IPC IPC(8): C07D213/80C07D213/803C07C215/10C07C213/08
CPCC07D213/80C07D213/803
Inventor 周金华樊亚丽李志远李秀俊
Owner 济南久隆医药科技有限公司
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