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Preparation method for febuxostat intermediate

A technology of febuxostat and intermediates, applied in the field of medicinal chemistry, can solve problems such as large corrosion of equipment, and achieve the effects of simple operation and mild reaction conditions

Active Publication Date: 2013-07-03
NANJING HEALTHNICE MEDICAL TECH +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0008] In this process, trifluoroacetic acid is used to prepare ethyl 2-(3-formyl-4-hydroxyphenyl)-4-methyl-thiazole-5-carboxylate, which has great corrosion on equipment

Method used

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  • Preparation method for febuxostat intermediate
  • Preparation method for febuxostat intermediate
  • Preparation method for febuxostat intermediate

Examples

Experimental program
Comparison scheme
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Embodiment Construction

[0018] 1. Synthesis of 3-methyl-4-hydroxybenzonitrile

[0019] Dissolve 13.6 g of 3-methyl-4-hydroxybenzaldehyde in an appropriate amount of formic acid, add 9.6 g of hydroxylamine hydrochloride and 21.1 g of sodium formate dihydrate at room temperature, then heat up to formic acid reflux for 5 to 6 hours to complete the reaction, and the reaction solution Cool down to room temperature, filter the solid, wash the filter cake with water, and filter to obtain 8.7 g of the product 3-methyl-4-hydroxybenzonitrile, with a yield of 65%.

[0020] 2. Synthesis of 3-methyl-4-isobutoxybenzonitrile

[0021] Add 7g of 3-methyl-4-hydroxybenzonitrile into a 500mL flask, stir and dissolve in 150mL DMF, add 14.5g of potassium carbonate and 14.8g of potassium iodide, stir and react at 50°C for 10 minutes, slowly add 13.6g of bromoisobutane into The reaction solution was stirred and reacted at 50° C. for 10 hours. The reaction solution was cooled to room temperature, added with 250 mL of water...

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Abstract

The invention relates to the field of medicinal chemistry, in particular to a preparation method for an intermediate 2-(3-formoxyl-4-hydroxy phenyl)-4-methyl-thiazole-5-carboxylic acid ethyl ester of a febuxostat medicine for treating gout. The preparation method is characterized by comprising the following steps of: with 3-methyl-4-hydroxy benzaldehyde as an original raw material and carrying out cyanation, etherification, carbonylation, sulfo-amidation and cyclization on the raw material to obtain the fidarestat intermediate. The preparation method disclosed by the invention has the advantages of avoiding the using of highly toxic reagents such as sodium cyanide and strong corrosive reagents such as trifluoroacetic acid and urotropine, mild reaction conditions and simpleness and convenience for operation.

Description

technical field [0001] The invention relates to the field of medicinal chemistry, in particular to the preparation of an important intermediate 2-(3-formyl-4-hydroxyphenyl)-4-methyl-thiazole-5-carboxylic acid ethyl ester of febuxostat for the treatment of gout method. Background technique [0002] Febuxostat is a non-purine xanthine oxidase inhibitor developed by Teijin Corporation, which can effectively block the formation of uric acid. It is mainly used clinically for the prevention and treatment of hyperuricemia and the gout caused by it. Febuxostat was approved by the European Union for marketing in France in 2008. No, compared with the original allopurinol, a commonly used drug for the treatment of gout, the drug has a more significant therapeutic effect. The main related synthetic methods at home and abroad: [0003] 1. The synthesis process of the patent US5614520 febuxostat is as follows: [0004] [0005] This process route uses highly toxic potassium cyanide ...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D277/56
Inventor 邹巧根
Owner NANJING HEALTHNICE MEDICAL TECH