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A kind of allopurinol impurity C and preparation method thereof

A technology for allopurinol and impurities, which is applied in the field of compound preparation, can solve the problems of low content, low yield, and low purity, and achieve the effects of simple operation, simple preparation route, and increased electrophilicity

Active Publication Date: 2022-05-20
无锡紫杉药业股份有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0009] The purity of the official USP reference substance is more than 99%, and the content of the label is 88%. Therefore, the impurity C obtained in CN201410117885 is not only low in purity, but also far lower in content than the reference substance, and cannot completely replace the official USP in the quality research of allopurinol. Use as a reference
In addition, it can also be inferred that the yield of this patent is actually much lower, about 40%.

Method used

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  • A kind of allopurinol impurity C and preparation method thereof
  • A kind of allopurinol impurity C and preparation method thereof
  • A kind of allopurinol impurity C and preparation method thereof

Examples

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Effect test

Embodiment 1

[0030] An allopurinol impurity C and a preparation method thereof, comprising the following steps:

[0031] S1: Weigh 5.0g 3-aminopyrazole-4-carboxamide hemisulfate, add 20g formamide to a 100ml reaction flask, add 1.2g hydrazine hydrate (80wt%) and 4g concentrated sulfuric acid (98wt%), Raise the temperature to 110°C and react for 8 hours;

[0032] S2: After the reaction of S1 is completed, cool the reaction liquid to room temperature, add 1mol / L sodium hydroxide solution to adjust the pH value to alkaline (pH value is about 14), add 50ml water and 50ml ethyl acetate, extract and separate the liquid, and collect the water phase ;

[0033] S3: Add 50ml of n-butanol to the water phase, extract and separate the liquid, collect the n-butanol phase, concentrate the n-butanol phase until a large amount of solids are precipitated, filter with suction, and vacuum-dry the filter cake at 60°C for 14 hours to obtain 4.41g of allopurinol impurity C, the yield is 86.7%, the purity is 99...

Embodiment 2

[0040] S1: Take 20.0g of 3-aminopyrazole-4-carboxamide hemisulfate, add it to a 500ml reaction flask containing 120g of formamide, add 5.2g of hydrazine hydrate (80wt%) and 18g of concentrated sulfuric acid (98wt%), and heat up To 120°C, react for 5h;

[0041] S2: After the reaction of S1 is completed, cool the reaction solution to room temperature, add 1mol / L sodium hydroxide solution to adjust to alkaline (pH value is 14), add 250ml of water and 250ml of ethyl acetate, extract and separate the liquid, and collect the water phase;

[0042] S3: Add 250ml of n-butanol to the water phase, extract and separate the liquid, collect the n-butanol phase, concentrate the n-butanol phase until a large amount of solids precipitate, filter with suction, and vacuum-dry the filter cake at 60°C for 13 hours to obtain 16.4g of allopurinol impurities C, the yield is 80.6%, and the purity is 99.839%.

Embodiment 3

[0044] S1: Get 1.0g 3-aminopyrazole-4-carboxamide hemisulfate, add in the 100ml reaction flask that 5g formamide is housed, add 0.25g hydrazine hydrate (80wt%) and 0.9g concentrated sulfuric acid (98wt%), Raise the temperature to 120°C and react for 6 hours;

[0045] S2: After the reaction of S1 is completed, cool the reaction solution to room temperature, add 1 mol / L sodium hydroxide solution to adjust to alkaline (pH about 14), add 50 ml of water and 50 ml of ethyl acetate, extract and separate the liquid, and collect the aqueous phase;

[0046] S3: Add 50ml of n-butanol to the water phase, extract and separate the liquid, collect the n-butanol phase, concentrate the n-butanol phase until a large amount of solids are precipitated, filter with suction, and dry the filter cake in vacuum at 60°C for 14 hours to obtain 0.86g of allopurinol Impurity C, the yield is 84.5%, and the purity is 99.841%.

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Abstract

The invention discloses an allopurinol impurity C and its preparation method, which belongs to the field of compound synthesis. The key point of the technical scheme is that S1: 3-aminopyrazole-4-formamide hemisulfate is dissolved in formamide, and 80wt% Hydrazine hydrate and 98wt% concentrated sulfuric acid are heated up to react; S2: After the reaction of S1 is completed, cool to room temperature, add sodium hydroxide solution to adjust the pH value of the solution to alkaline, add water and ethyl acetate, extract and separate the liquid, and collect the water phase; S3: Add n-butanol to the water phase in S2, extract and separate the liquids, collect the n-butanol phase, concentrate the n-butanol phase until solids are precipitated, filter with suction, and dry to obtain the product. The invention has mild reaction conditions, is easy to operate, has high product purity, can replace the official reference substance, and the obtained product has great significance for the quality research of allopurinol.

Description

technical field [0001] The invention relates to the field of compound preparation, in particular to an allopurinol impurity C and a preparation method thereof. Background technique [0002] Allopurinol and its metabolite oxypurinol can inhibit xanthine oxidase, prevent the metabolism of hypoxanthine and xanthine into uric acid, thereby reducing the production of uric acid, reducing the uric acid content in blood and urine to a level below the solubility, preventing Uric acid forms crystals and deposits in joints and other tissues, which also helps to redissolve uric acid crystals in the tissues of gout patients. [0003] There are many impurities involved in the impurity research of allopurinol, among which USP contains impurity C, whose structural formula is as follows: [0004] [0005] The Chinese patent with the publication number CN103910715B provides a method for synthesizing the allopurinol impurity C, which is as follows: in the presence of an organic solvent, 3-...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D403/04
CPCC07D403/04Y02P20/582
Inventor 王莉佳黄春王旭阳
Owner 无锡紫杉药业股份有限公司
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