Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Preparation method of favipiravir

A technology of favipiravir and reaction solution, which is applied in the field of drug synthesis, can solve the problems of cost, increased processing difficulty, heterogeneous reaction, etc., and achieve the effect of reducing post-processing steps, avoiding drug safety, and mild reaction conditions

Pending Publication Date: 2021-08-13
BEIJING SIHUAN PHARMA +2
View PDF3 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0006] This method has the following problems in the process of preparing 6-fluoro-3-hydroxyl-2-cyanopyrazine (compound II): one, heterogeneous reaction, stirring difficulty, increase processing difficulty; pH, extraction, washing, and drying and decompression to remove the solvent are cumbersome and costly; 3. Column chromatography is used for purification, which is not suitable for industrial production; 4. The yield of this step is only 45.6%, and the production cost has increased significantly
[0009] In this method, the intermediate 6-fluoro-3-hydroxyl-2-cyanopyrazine is made into an organic amine salt, and this step has the following problems: 1. After the reaction solution is filtered, it is necessary to adjust the pH and form a salt with ammonia water. It is cumbersome and complicated to handle; 2. In the salt-forming step, organic solvents acetone and toluene are introduced. The solvent itself is highly toxic, which increases the potential risk of solvent residue; 3. The introduced organic amine is difficult to remove from the product
In the step of preparing Favipiravir, there are the following problems: 1. Toluene is used as the reaction solvent, which is a carcinogenic solvent. It is used in large quantities in production, which affects the safety of operators, causes a large amount of waste liquid to affect environmental protection, and increases waste liquid treatment and environmental protection costs. , in addition, increase the solvent residue and increase the cost of quality control; 2. In the post-processing step, it is necessary to add seed crystals to precipitate solids.
[0012] This method has the following problems in the process of preparing 6-fluoro-3-hydroxyl-2-cyanopyrazine (compound II): one, the reaction solvent contains toluene, a carcinogenic solvent, two, concentrated hydrochloric acid is needed to adjust pH, extract, Washing requires drying and decompression to remove the solvent. The operation is cumbersome, costly, and inconvenient in production.
[0015] This method has the following problems in the process of preparing 6-fluoro-3-hydroxyl-2-cyanopyrazine: after the reaction, hydrochloric acid is required to adjust the pH, extract, wash, and also need to be dried and decompressed to remove the solvent, which is cumbersome and costly
In the step of preparing Favipiravir, one, using concentrated sulfuric acid as a solvent, which is very dangerous in itself, coupled with high temperature reaction, the risk factor increases, in addition, the equipment is severely corroded, and is not suitable for industrial production; two, concentrated sulfuric acid is dropped into water , a large amount of heat release, especially concentrated sulfuric acid solution at 50°C, the heat release is more serious, the risk factor increases, and it is very unsuitable for industrial production; 3. Water is used as a solvent, and there is a problem of difficulty in stirring; 4. Post-processing requires extraction and other operations, and it is also Need chromatographic column purification and separation, not suitable for suitability for suitability for industrialized production; Five, 3 embodiment two-step reaction average yields 64%

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Preparation method of favipiravir
  • Preparation method of favipiravir
  • Preparation method of favipiravir

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0049] The preparation of embodiment 1 Favipiravir

[0050]

[0051] Add 5.0 g of 3,6-difluoro-2-cyanopyrazine and 10 ml of dimethyl sulfoxide into the reaction flask, and add aqueous sodium acetate solution (5.1 g of anhydrous sodium acetate dissolved in 20 ml of water) under stirring conditions. Heat to 50-60°C and stir until the reaction is complete. The reaction solution was filtered, and the filter cake was rinsed with 20 ml of purified water. Add dropwise sodium hydroxide aqueous solution (4.1g sodium hydroxide dissolved in 20ml water) to the filtrate under stirring condition. After the dropwise addition, add 10ml water and 5ml hydrogen peroxide solution dropwise. React and stir until the reaction is complete. Cool down to 20-30°C, add concentrated hydrochloric acid dropwise to adjust the pH to 3.0. The temperature was lowered to crystallize, filtered, and the filter cake was rinsed with purified water and dried to obtain 4.73 g of favipiravir with a yield of 85.0%...

Embodiment 2

[0052] The preparation of embodiment 2 Favipiravir

[0053]

[0054] Add 10.0 g of 3,6-difluoro-2-cyanopyrazine and 15 ml of dimethyl sulfoxide into the reaction flask, and add aqueous sodium acetate solution (17.5 g of anhydrous sodium acetate dissolved in 30 ml of water) under stirring conditions. Heat to 65°C and stir until the reaction is complete. Add dropwise sodium hydroxide aqueous solution (5.7g sodium hydroxide dissolved in 15ml water) to the reaction solution under stirring. After the dropwise addition, add 50ml of water, and dropwise add 15ml of hydrogen peroxide aqueous solution at 65°C. After the dropwise addition, stir until the reaction is complete. Cool down to 20-30°C, add concentrated hydrochloric acid dropwise to adjust the pH to 4.0. The temperature was lowered to crystallize, filtered, and the filter cake was rinsed with purified water and dried to obtain 8.1 g of favipiravir with a yield of 82.3% and a purity of 99.55%.

Embodiment 3

[0055] The preparation of embodiment 3 Favipiravir

[0056]

[0057] Add 20.0 g of 3,6-difluoro-2-cyanopyrazine and 20 ml of dimethyl sulfoxide into the reaction flask, and add aqueous sodium acetate solution (23.1 g of anhydrous sodium acetate dissolved in 80 ml of water) under stirring conditions. Heat to 50-60°C and stir until the reaction is complete. The reaction solution was filtered, and the filter cake was rinsed with 20 ml of purified water. Add aqueous sodium hydroxide solution (16.5g sodium hydroxide dissolved in 80ml water) dropwise to the filtrate under stirring condition, after the dropwise addition, add 40ml water, add 25ml hydrogen peroxide aqueous solution dropwise at 50-60°C, after the dropwise addition , and stir until the reaction is complete. Cool down to 20-30°C, add concentrated hydrochloric acid dropwise to adjust the pH to 3.0. The temperature was lowered to crystallize, filtered, and the filter cake was rinsed with purified water and dried to ob...

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The invention relates to a preparation method of favipiravir, which comprises the following steps of: reacting 3,6-difluoro-2-cyanopyrazine under an alkaline condition at the temperature of between 40 and 70 DEG C to obtain 6-fluoro-3-hydroxy-2-cyanopyrazine, and then conducting a next-step reaction basically without treatment, and conducting reaction with inorganic alkali and hydrogen peroxide at 45-65 DEG C to obtain favipiravir. The preparation method avoids use of precursor control reagents or dangerous preparations, reduces dangerous factors in production, and has the advantages of simplicity and convenience in operation, high yield, high purity of the prepared product, safety, environmental protection, low cost, suitability for industrial production and the like.

Description

technical field [0001] The invention belongs to the field of drug synthesis, and in particular relates to a preparation method of Favipiravir. Background technique [0002] Favipiravir (trade name AVIGAN) is an RNA-dependent RNA polymerase (RdRp) inhibitor broad-spectrum antiviral drug developed by Japan Fukuyama Chemical Co., Ltd. Bioterrorism attacks have important practical significance. [0003] [0004] CN1418220A discloses the preparation method of Favipiravir, comprising the following steps: [0005] [0006] This method has the following problems in the process of preparing 6-fluoro-3-hydroxyl-2-cyanopyrazine (compound II): one, heterogeneous reaction, stirring difficulty, increase processing difficulty; pH, extraction, washing, and drying and decompression to remove the solvent are cumbersome and costly. Third, column chromatography is used for purification, which is not suitable for industrial production. Fourth, the yield of this step is only 45.6%, and th...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(China)
IPC IPC(8): C07D241/24
CPCC07D241/24
Inventor 邓声菊曾恩佑徐艳君王田园
Owner BEIJING SIHUAN PHARMA
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com