Method for preparing nitazoxanide

A technology of nitazoxanide and nitrothiazole, which is applied in the field of preparation of nitazoxanide, can solve the problems of difficult handling, high production cost, and high cost, and achieve the effects of easy control, reduced production cost, and simple preparation process

Inactive Publication Date: 2013-06-19
ANHUI ZHONGSHENG PHARMA
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  • Abstract
  • Description
  • Claims
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Problems solved by technology

[0005] The disadvantage of this method is that: using DCC as a condensing agent, 1,3-dicyclohexylurea (DCU), which is difficult to handle, will be produced in the reaction, and DCU will still exist in the organic phase after extraction with ethyl acetate. It will also exist in the finished product during crystallization, affecting the purity of the finished product
[0008] The disadvantage of this method is that simply using o-acetylsalicyloyl chloride will cause high cost, and at the same time, the solubility of 2-amino-5-nitrothiazole in acetone is not high, and it cannot be completely dissolved with only 3-3.5 times the mass ratio of acetone 2-Amino-5-nitrothiazole, even if the triethylamine used to absorb hydrogen chloride is added dropwise in the later stage, the reaction will not be complete
[0011] The shortcoming of this method is: raw material o-acetylsalicyloyl chloride, solvent tetrahydrofuran are expensive, and production cost is higher

Method used

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  • Method for preparing nitazoxanide
  • Method for preparing nitazoxanide
  • Method for preparing nitazoxanide

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Embodiment 1

[0028] The preparation process of nitazoxanide comprises the following two steps:

[0029] (1) Synthesis of o-acetylsalicyloyl chloride:

[0030] In a 50L reaction kettle, add 8KG of acetylsalicylic acid and 6.34KG of thionyl chloride, mechanically stir, control the reaction temperature between 50°C and 60°C, and stir for 2 hours to obtain o-acetylsalicylic acid chloride. Concentrate under reduced pressure to remove excess thionyl chloride, and then add anhydrous 1,4-dioxane 16KG to prepare a solution of o-acetylsalicyloyl chloride for future use.

[0031] (2) Synthesis of nitazoxanide:

[0032] In a 100L reaction kettle, add 45L of anhydrous 1,4-dioxane, 5.37KG of 2-amino-5-nitrothiazole, and 3.74KG of triethylamine, cool down to -2°C, and control the temperature at -2°C~ Add the o-acetylsalicyloyl chloride solution obtained in step (1) dropwise at 2°C, raise the temperature to 20°C-25°C after the dropwise addition, stir for 30 minutes, then filter, and wash the filtrate wi...

Embodiment 2

[0034] The preparation process of nitazoxanide comprises the following two steps:

[0035] (1) Synthesis of o-acetylsalicyloyl chloride:

[0036] In a 100L reaction kettle, add 16KG of acetylsalicylic acid and 10.6KG of thionyl chloride, stir mechanically, control the reaction temperature at 65°C to 70°C, and stir for 2.5h to obtain o-acetylsalicylic acid chloride. Concentrate the excess chlorine sulfoxide, and then add N,N-dimethylformamide (DMF) 32KG to prepare a solution of o-acetylsalicyloyl chloride for later use.

[0037] (2) Synthesis of nitazoxanide:

[0038] In a 200L reactor, add 46L of N,N-dimethylformamide (DMF), 9.02KG of 2-amino-5-nitrothiazole and 6.29KG of triethylamine, cool down to -2°C, and control the temperature at -2 ℃~2℃, add the o-acetylsalicyloyl chloride solution obtained in step (1) dropwise, raise the temperature to 20℃~25℃ after the dropwise addition, stir for 60min and then filter, and wash the filtrate with 40KG water to obtain the crude produc...

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Abstract

The invention discloses a method for preparing nitazoxanide. The method comprises the following steps of: reacting acetylsalicylic acid with thionyl chloride at 50 DEG C-70 DEG C so as to generate O-acetylsalicylryl chloride, then preparing an O-acetylsalicylryl chloride solution by utilizing 1, 4-dioxane or N, N-dimethyl formamide (DMF), dripping the O-acetylsalicylryl chloride solution into a mixed liquid of 2-amino-5-nitrothiazole, triethylamine, 1, 4-dioxane or N, N-dimethyl formamide, continuously stirring for 20-60 minutes at room temperature after the dripping is ended, thus obtaining the nitazoxanide. The method has the advantages of moderate reaction conditions, low cost and simple post-processing method and is convenient for mass industrial production.

Description

technical field [0001] The invention relates to a preparation method of nitazoxanide. Background technique [0002] Nitazoxanide is a derivative of nitrothiasalicylic acid amide, which is active against Cryptosporidium, Giardia intestinalis, and intestinal parasites, and has a wide range of applications. Regarding the preparation of nitazoxanide, the preparation methods reported in the literature mainly contain the following three kinds: [0003] 1. Patent CN101007792A discloses a method for synthesizing nitrothiazole benzamide compounds, specifically: adding acetylsalicylic acid and 2-amino-5-nitrothiazole, -2 Stir at -3°C. Then add the condensing agent N,N-dicyclohexylcarbodiimide (DCC) and triethylamine in sequence. After the reaction is completed, filter the reactant with a Buchner funnel, and extract the filtrate with ethyl acetate and water, and ethyl acetate The layer was dried over anhydrous sodium sulfate and decolorized with activated carbon. Concentrate under ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D277/58
Inventor 王勇王建董泽新余贵菊程雪娇焦小军
Owner ANHUI ZHONGSHENG PHARMA
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