Preparation method of favipiravir

A technology of favipiravir and hydroxyl, applied in the new preparation field of favipiravir, can solve the problems of unsafe operation, unfriendly environment, large amount of waste water, etc. Effect

Inactive Publication Date: 2020-09-18
HANGZHOU HUANGSEN BIOLOGICAL TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0007] In summary, there are still many technical problems in the existing synthetic methods, such as low yield in industrialization, unsafe operation, large amount of waste water, and unfriendly to the environment

Method used

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  • Preparation method of favipiravir
  • Preparation method of favipiravir

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0022] Add 30 grams of 6-fluoro-3-hydroxy-2-cyanopyrazine dicyclohexylamine salt to 100 grams of anhydrous tert-butanol, and then add 22.4 grams of potassium hydroxide. The temperature was raised to 60° C., and the reaction was carried out for 8 hours. TLC detected that the reaction of the raw materials was complete. Evaporate tert-butanol, add 150 ml of water, 100 ml of ethyl acetate, adjust the pH of the water phase to 5-6 with hydrochloric acid, stir, let stand to separate layers, separate the ethyl acetate layer, wash once with 100 ml of saturated saline, and wash with Dry over anhydrous magnesium sulfate, concentrate under reduced pressure to obtain 14.13 grams of product, nuclear magnetic pattern is as follows figure 2 , it can be determined that it is Favipiravir. The molar yield is 96%, and the purity is 99.9%.

Embodiment 2

[0024] Add 27.8 grams of 6-fluoro-3-hydroxy-2-cyanopyrazine to 150 grams of anhydrous isopropanol, and then add 32 grams of sodium hydroxide. The temperature was raised to 60° C., and the reaction was carried out for 8 hours. TLC detected that the reaction of the raw materials was complete. Evaporate tert-butanol, add 150 ml of water, 150 ml of ethyl acetate, adjust the pH of the water phase to 5-6 with hydrochloric acid, stir, let stand to separate layers, separate the ethyl acetate layer, wash once with 150 ml of saturated saline, and wash with Dried over anhydrous magnesium sulfate, concentrated under reduced pressure to obtain 29.85 g of the product, the NMR results were the same as in Example 1, and it could be determined that it was favipiravir; the molar yield was 95%, and the purity was 99.9%.

Embodiment 3

[0026] Add 30 grams of 6-fluoro-3-hydroxy-2-cyanopyrazine dicyclohexylamine salt to 360 grams of anhydrous tert-butanol, and then add 180 grams of potassium hydroxide. The temperature was raised to 30° C., and the reaction was carried out for 8 hours. TLC detected that the reaction of the raw materials was complete. Evaporate tert-butanol, add 150 ml of water, 100 ml of ethyl acetate, adjust the pH of the water phase to 5-6 with hydrochloric acid, stir, let stand to separate layers, separate the ethyl acetate layer, wash once with 100 ml of saturated saline, and wash with Drying over anhydrous magnesium sulfate, concentrating under reduced pressure, the NMR results of the product obtained are the same as in Example 1, and it can be determined that it is favipiravir; the molar yield is 98%, and the purity is 99.9%.

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Abstract

The invention provides a preparation method of favipiravir, which comprises the following step: by using one or two of 6-fluoro-3-hydroxyl-2-cyanopyrazine and 6-fluoro-3-hydroxyl-2-cyanopyrazine organic amine salt as raw materials, carrying out high-yield preparation in an anhydrous organic solvent under alkaline conditions to obtain favipiravir. Compared with the existing concentrated sulfuric acid hydrolysis process and hydrogen peroxide hydrolysis process, a large amount of acidic wastewater generated in the concentrated sulfuric acid hydrolysis process is avoided, explosion hazards possibly caused by use of hydrogen peroxide are also avoided, meanwhile, hydrolysis and oxygenolysis phenomena of products in the concentrated sulfuric acid hydrolysis process and the hydrogen peroxide hydrolysis process are avoided, and the preparation method is environmentally friendly, simple and safe to operate and relatively high in yield.

Description

technical field [0001] The invention relates to a new preparation method of Favipiravir. Background technique [0002] Favipiravir (favipiravir, T-705, trade name Avigan, 1), the chemical name is 6-fluoro-3-hydroxy-2-pyrazine carboxamide, is a target RNA-dependent drug developed by Japan Toyama Chemical Pharmaceutical Co., Ltd. A new broad-spectrum antiviral drug based on RNA polymerase (RdRp), which was approved for marketing in Japan in March 2014, for the treatment of new and recurrent influenza. At present, phase III clinical research on anti-influenza A has been completed in the United States. Favipiravir has a good therapeutic effect on patients infected with Ebola virus, and phase II clinical research on anti-Ebola virus is being conducted in the United States. The mechanism of action of favipiravir is mainly that after entering the body, under the action of a series of cellular phosphokinases, it generates the form of its nucleoside analog triphosphate, thereby inte...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D241/24A61P31/12
CPCA61P31/12C07D241/24
Inventor 姚红罗瑾张广勤郑杰葛皓月
Owner HANGZHOU HUANGSEN BIOLOGICAL TECH CO LTD
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