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Method for preparing lesinurad intermediate

A technology for lesanolide and intermediates, which is applied in the field of preparation of lesinolide intermediates, can solve the problems of many reaction steps, achieve simple preparation, avoid the use of toxic reagents such as thiophosgene, and have low cost Effect

Active Publication Date: 2016-08-31
CHENGDU BAIYU PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0010] The purpose of the present invention is to provide a preparation method of Lesanolide intermediates, to solve the problem of using toxic reagents such as thiophosgene and many reaction steps in the existing synthetic routes

Method used

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  • Method for preparing lesinurad intermediate
  • Method for preparing lesinurad intermediate
  • Method for preparing lesinurad intermediate

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0062] Example 1 Synthetic route of lesanolide of the present invention

[0063]

[0064] step one:

[0065]In a 100ml three-necked flask equipped with a stirring bar and a thermometer, add 50ml of ethanol and 2.23g of 4-bromonaphthol, stir at room temperature, add 1.01g of 3-mercapto-1,2,4-triazole until it dissolves with stirring, and control Add 0.4g of sodium hydroxide at 30°C, keep stirring for 3 hours, concentrate to remove ethanol, add 25ml of purified water and 25ml of dichloromethane for extraction and separation, concentrate the organic layer to remove dichloromethane, add 25ml of acetone to the residue, stir and crystallize to obtain 2.34g product, ie intermediate (I), yield 96.30%.

[0066] Step two:

[0067] In a 100ml three-necked flask equipped with a stirrer and a thermometer, add 50ml of dichloromethane, 2.43g of intermediate (I), drop 3 drops of DMF, and slowly add 1.8g of thionyl chloride; after the addition, heat up to reflux and maintain reflux After...

Embodiment 2

[0076] Embodiment 2 Synthetic method of lesinolide of the present invention

[0077] step one:

[0078] In a 100ml three-neck flask equipped with a stirring bar and a thermometer, add 50ml of ethanol and 2.23g of 4-bromonaphthol, stir at room temperature, add 1.01g of 3-mercapto-1,2,4-triazole until it dissolves with stirring, and control Add 0.4g of triethylamine at 30°C, keep stirring for 3 hours, concentrate to remove ethanol, add 25ml of purified water and 25ml of dichloromethane for extraction and separation, concentrate the organic layer to remove dichloromethane, add 25ml of acetone to the residue, stir and crystallize to obtain 2.30g product, ie intermediate (I), yield 94.65%.

[0079] Step two:

[0080] In a 100ml three-necked flask equipped with a stirrer and a thermometer, add 50ml of dichloromethane, 2.43g of intermediate (I), drop 3 drops of DMF, and slowly add 1.8g of thionyl chloride; after the addition, heat up to reflux and maintain reflux After 4 hours, it...

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Abstract

The invention discloses a method for preparing a lesinurad intermediate shown in the formula (I). By means of the method, triazole functional groups can be directly introduced, the reaction yield is as high as 96.30%, and use of thiophosgene and other toxic reagents is avoided. Besides, a cyclization step is not needed in the synthetic route, the final product can be obtained through six-step reaction, preparation is easy, cost is low, and the method is suitable for industrial production. Please see the structural formula in the description.

Description

technical field [0001] The invention relates to a preparation method of a lesanolide intermediate, which belongs to the field of medicine. Background technique [0002] Lesinurad (lesinurad, RDEA594) is a new type of gout drug developed by Ardea Biosciences, with a chemical name of 2-[(5-bromo-4-(4-cyclopropylnaphthalen-1-yl)-4H -1,2,4-triazol-3-yl)thio]acetic acid, through inhibiting urate transporter 1 (uric acid salt transport protein 1, URAT1), promoting uric acid excretion and reducing uric acid levels. Clinical studies have shown that lesinurad can reduce the level of uric acid in plasma in a dose-dependent manner, can effectively accelerate the elimination of uric acid in patients with gout, and has high safety. The development prospect of the drug is good, and the research on its synthesis process has also attracted widespread attention. [0003] At present, the construction of the triazole functional group is still the key point and technical difficulty in the pre...

Claims

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Application Information

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IPC IPC(8): C07D249/12
CPCC07D249/12
Inventor 雷朗李善伟熊波
Owner CHENGDU BAIYU PHARMA CO LTD
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