A kind of synthetic method of febuxostat

A febuxostat compound technology, applied in the field of febuxostat synthesis, can solve the problems of low industrialization feasibility, serious environmental pollution, and difficult wastewater treatment, so as to avoid the problem of unstable reaction, simple waste liquid treatment, harm reduction effect

Active Publication Date: 2015-08-26
CHONGQING KERUI PHARMA GRP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0014] 1) The process is cumbersome, and the acidic waste liquid produced in the synthesis process is more, which seriously pollutes the environment; and the yield of the final product is low, and the industrialization feasibility is low
[0015] 2) Potassium cyanide KCN is used to introduce cyano groups during the synthesis process. Potassium cyanide KCN is a highly toxic substance, and the wastewater in the process is difficult to treat
[0016] In summary, the current synthetic method of febuxostat has the disadvantages of complicated process, serious environmental pollution, low product yield, and low product purity.

Method used

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  • A kind of synthetic method of febuxostat
  • A kind of synthetic method of febuxostat
  • A kind of synthetic method of febuxostat

Examples

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preparation example Construction

[0050] A preparation method of febuxostat, comprising the steps of:

[0051]

example 1

[0053] 1) Preparation of ethyl 2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylate hydrochloride:

[0054] Inject 250L of absolute ethanol into a dry and clean 500L enamel reaction kettle equipped with a thermometer and agitator, start stirring, add 50kg of 4-hydroxythiobenzamide into the reaction kettle from the solid feeding port, continue stirring and turn on the external The bath is heated up. During the heating process, 59kg of ethyl 2-chloroacetoacetate is pumped into a 100L dry and clean high-level tank. When the system temperature rises to about 50°C, the system dissolves and continues to heat up to 70°C. Add 20kg of ethyl 2-chloroacetoacetate, when the system is turbid (the system is turbid because the reflux reaction is violent, and a large amount of solids are washed out, at this time, a constant stirring should be ensured) immediately stop the dropwise addition, and stop the external bath heating at the same time, until the reflux is stable (The process lasts about ...

example 2

[0070] 1) Preparation of ethyl 2-(4-hydroxyphenyl)-4-methylthiazole-5-carboxylate hydrochloride:

[0071] Inject 260L of absolute ethanol into a dry and clean 500L enamel reaction kettle equipped with a thermometer and agitator, start stirring, add 50kg of 4-hydroxythiobenzamide into the reaction kettle from the solid feeding port, continue stirring and turn on the external The temperature of the bath is raised. During the heating process, 60kg of ethyl 2-chloroacetoacetate is pumped into a 100L dry and clean high-level tank. When the system temperature rises to about 50°C, the system dissolves, and when the temperature continues to rise to 72°C, it begins to drip Add 20kg of ethyl 2-chloroacetoacetate, when the system is turbid (the system is turbid because the reflux reaction is violent, and a large amount of solids are washed out, at this time, a constant stirring should be ensured) immediately stop the dropwise addition, and stop the external bath heating at the same time, ...

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Abstract

The invention discloses a synthetic method of febuxostat. The synthetic method mainly comprises the following steps: (1) by taking a compound 4-hydroxythiobenzamide in a formula II as a raw material, preparing a compound in a formula III through cyclization reaction; (2) carrying out nucleophilic aromatic substitution reaction on the compound in the formula III to obtain a compound in a formula IV; (3) carrying out substitution reaction on the compound in the formula IV to obtain a compound in a formula V; (4) carrying out cyanation reaction on the compound in the formula V to obtain a compound in a formula VI; (5) carrying out hydrolysis reaction on the compound in the formula VI to obtain a compound febuxostat in a formula I. The preparation method disclosed by the invention has the advantages of being easy in process and suitable for industrial production, and the synthesized product febuxostat has the advantages of high purity and high yield.

Description

technical field [0001] The invention relates to the technical field of anti-gout drugs, in particular to a synthetic method of febuxostat. Background technique [0002] The occurrence of gout is due to the excessive production of uric acid in the body and the decline in the ability of the kidneys to clear it. The accumulation of uric acid in the body leads to the deposition of urate crystals in the joints and various organs. Therefore, the usual means of treatment for gout is to promote uric acid excretion and inhibit uric acid production, and take appropriate measures to improve related symptoms. [0003] The generation of uric acid in the body is related to purine metabolism. In the final step of purine metabolism, hypoxanthine generates xanthine under the action of xanthine oxidoreductase (XOR), and then further generates uric acid. Inhibiting the activity of this enzyme can effectively reduce Production of uric acid. Febuxostat is the latest XOR inhibitor developed in ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D277/56
CPCC07D277/56
Inventor 李强刘睿斌刘俊敏李荣程鹏王翔李飞
Owner CHONGQING KERUI PHARMA GRP
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