Method for preparing nitazoxanide

A technology for nitazoxanide and nitazoxanide crude products, applied in the direction of organic chemistry and the like, can solve the problems of large amount of tetrahydrofuran, poor operating environment, low solubility, etc., and achieve the effects of good crystallization, improved operating environment and high quality

Inactive Publication Date: 2007-03-28
HANGZHOU SHINYANG SAMWOO FINE CHEM CO LTD
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

[0006] The purpose of this invention is to provide a kind of preparation method of nitazoxanide, which mainly solves the solubility of 2-amino-5-nitrothiazole, o-acetylsalicyloyl chloride and nitazoxanide in tetrahydrofuran existing in the prior art Not high, resulting in a large amount of tetrahydrofuran, the technical problem that the cost is higher; the present invention also solves the problem that the acid-binding agent is selected from the organic base triethylamine, which has a fishy smell and is not good for the operating environment. Insoluble in water, after the system is diluted in water, a small amount of excess triethylamine turns into oil, agglomerates with materials, poor product quality and other technical problems

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  • Method for preparing nitazoxanide

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Effect test

Embodiment 1

[0047] Embodiment 1: The preparation method of the nitazoxanide of this example is used to produce the intermediate of nitazoxanide for the treatment of protozoan diarrhea, and its steps are:

[0048] a. Add N,N-dimethylformamide or DMF: 50ml into a 250ml flask, then add o-acetylsalicyloyl chloride: 60g, stir until completely dissolved, and put it in the dropping funnel for later use;

[0049] b. Add DMF: 70ml to a 250m flask, then add 2-amino-5-nitrothiazole: 29g, potassium carbonate: 42g, stir, and cool down to 0°C;

[0050] c. Slowly add the above-mentioned o-acetylsalicyloyl chloride DMF solution dropwise, control the temperature at 0-5°C, and add the dropwise time for about 2 hours;

[0051] d. After the dropwise addition, carry out the condensation reaction, raise the temperature to 25°C, keep warm at about 25°C for 2 hours, dilute in water, precipitate the product, and filter;

[0052] e. Wash once with methanol and dry to obtain crude nitazoxanide. The methanol mothe...

Embodiment 2

[0055] Embodiment 2: The preparation method of the nitazoxanide of this example is used to produce the intermediate of nitazoxanide for the treatment of protozoan diarrhea, and its steps are:

[0056]a. Add DMF: 80ml to a 250m flask, then add 2-amino-5-nitrothiazole: 29g, potassium carbonate: 36g, stir, and cool down to 0°C;

[0057] b. Slowly add 52 g of o-acetylsalicyloyl chloride solid in batches, control the temperature at 0-5°C, and add for about 2 hours;

[0058] c. After the addition, carry out condensation reaction, raise the temperature to 25°C, keep warm at about 25°C for 2 hours, dilute in water, precipitate the product, and filter;

[0059] d, wash once with methanol, dry to obtain the crude product nitazoxanide, and distill the methanol mother liquor for recycling;

[0060] e. Add DMF: 80ml to a 250ml flask, add dried crude nitazoxanide: 50g, activated carbon: 2.5g, and heat up to 55-60°C;

[0061] f. Keep warm at 55-60°C for 1.0 hour, heat filter, add methanol:...

Embodiment 3

[0062] Embodiment 3: the preparation method of the nitazoxanide of this example is used to produce the intermediate of nitazoxanide for the treatment of protozoan diarrhea, and its steps are:

[0063] a. Add DMF: 40ml to a 250ml flask, then add o-acetylsalicyloyl chloride: 48g, stir until completely dissolved, and then put it in the dropping funnel for later use;

[0064] b. Add DMF: 70ml to a 250m flask, then add 2-amino-5-nitrothiazole: 29g, potassium carbonate: 34g, stir, and cool down to 0°C;

[0065] c. Slowly add the above-mentioned o-acetylsalicyloyl chloride DMF solution dropwise, control the temperature at 0-5°C, and add the dropwise time for about 2 hours;

[0066] d. After the dropwise addition, carry out the condensation reaction, raise the temperature to 25°C, keep warm at about 25°C for 2 hours, dilute in water, precipitate the product, and filter;

[0067] e, wash once with methanol, dry to obtain the crude product nitazoxanide, and the methanol mother liquor i...

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Abstract

The invention relates to a nidazolenit preparing method, mainly solving the technical problems of large utilization of tetrahydrofuran and higher cost; and also resolving the technical problem of bad quality of product by selecting organic alkali triethylamine as acid binder. And it comprises the steps of: dissolving 2-amino-5-nitrothiazole in enough nitrogen-containing compound solvent, adding in enough acid binder and blending, and lowering the temperature; adding in ortho-acetyl salicyl chloride and making full condensation reaction; dissolving idazolenit crude in nitrogen-containing compound solvent, and adding in activated carbon to decolor; filtering and adding alcohol in mother solution for alcohol precipitation, filtering and drying.

Description

technical field [0001] The invention relates to a preparation method of a pharmaceutical intermediate, in particular to a preparation method of nitazoxanide for treating protozoan diarrhea. Background technique [0002] According to statistics, among diarrhea patients in developed countries, the infection rate of Cryptosporidium is 0.6% to 7.3%; in developing countries, it is 3% to 13%; in my country, the infection rate is 1.4% to 13.3%. Nitazoxanide, through repeated clinical trials abroad, has special effects on children with diarrhea caused by Cryptosporidium and Giardia lamblia. [0003] The chemical name of nitazoxanide is 2-acetoxy-N-(5-nitro-2-thiazolyl)benzamide, and its reaction formula is [0004] [0005] At present, most of the following methods are used to prepare nitazoxanide: after dissolving 2-amino-5-nitrothiazole with tetrahydrofuran, add o-acetylsalicyloyl chloride to react at low temperature, neutralize the generated HCl with triethylamine after the r...

Claims

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Application Information

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IPC IPC(8): C07D277/58
Inventor 梅天明沈少华袁忻
Owner HANGZHOU SHINYANG SAMWOO FINE CHEM CO LTD
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