356783-31-8

Usage

Uses

Used in Pharmaceutical Industry:
2-Pyrazinecarbonitrile, 6-fluoro-3,4-dihydro-3-oxois used as a key intermediate in the synthesis of Favipiravir (F103350), an antiviral medication. Its chemical structure allows it to serve as a building block for the development of this drug, which is particularly effective against certain viral infections.

Melting Point

126 - 129℃

Upstream product

• 356783-28-3 3,6-difluoropyrazine-2-carbonitrile 
• 98-96-4 pyrazinamide 
• 18960-19-5 1,4-dioxopyrazinamide 
• 356783-16-9 3,6-dichloropyrazine-2-carbonitrile 
• 1023813-21-9 3,6-dichloropyrazine-2-carboxamide 
• 98142-97-3 3,6-dioxopiperazine-2-carboxamide 
• 41394-71-2 2-(chloroacetylamino)propanedioic acid diethyl ester 
• 1374986-06-7 C₇H₄FN₃O₃ 
• 1374986-05-6 methyl-5-chloroisoxazolo[4,5-b]pyrazine-3-carboxylate 
• 1374986-04-5 C₇H₅N₃O₄ 
• 1374986-03-4 C₁₁H₁₇N₃O₆ 
• 1374986-37-4 C₈H₉N₃O₅ 
• 1374986-35-2 C₈H₁₀N₂O₄ 
• 1374986-21-6 C₁₀H₁₀FN₃O₃ 

Downstream Products

• 259793-96-9 favipiravir 

Relevant academic research and scientific papers

Refining method of favipiravir

The invention provides a refining method of favipiravir. The method specifically comprises the following steps: 6-fluoro-3-hydroxy-2-cyanopyrazine reacts with hydrogen peroxide under an alkaline condition to obtain 6-fluoro-3-hydroxy-2-pyrazinamide; the 6-fluoro-3-hydroxy-2-pyrazinamide is prepared into an organic alkali salt in an anhydrous organic solvent, and then the pH value in water is adjusted to prepare high-purity 6-fluoro-3-hydroxy-2-pyrazinamide; and 6-fluoro-3-hydroxy-2-pyrazinamide and organic alkali are salified in an organic solvent, the salt has excellent crystallinity, high-purity favipiravir can be prepared with high yield through simple operation, the yield can reach 90% or above, and the HPLC purity reaches 99.9% or above.

Scalable synthesis of favipiravir: Via conventional and continuous flow chemistry

Decagram scale synthesis of favipiravir was performed in 9 steps using diethyl malonate as cheap starting material. Hydrogenation and bromination steps were achieved by employing a continuous flow reactor. The synthetic process provided a total of 16% yield and it is suitable for larger-scale synthesis and production. This journal is

PROCESS FOR PREPARATION OF FAVIPIRAVIR

The present invention relates to a process for the preparation of favipiravir and salts thereof. The present invention also relates to salts of 6-fluoro-3-hydroxy-2-pyrazinecarbonitrile with inorganic base, process for their preparation and conversion thereof to favipiravir. The present invention also relates to salts of 6-bromo-3-hydroxypyrazine-2-carboxamide with organic and inorganic base and their use in the preparation of favipiravir.

Preparation method of 6 -fluoro -3 -hydroxypyrazine -2 - formamide

The invention provides a preparation method of a pyrazine compound represented by the formula (I). To the invention, 6 -fluoro -3 -hydroxypyrazine -2 - methyl cyanide is used as a starting material, dimethyl sulfoxide is added under the conditions of hydrogen peroxide and sodium hydroxide, so that generation of oxygen in the system is avoided, and the production safety is greatly improved. The method provided by the invention is safe and suitable for industrial amplification, and has great help for industrial mass production of laprevir API.

PROCESS FOR THE PREPARATION OF 3,6-DICHLOROCYANO PYRAZINE, 3,6-DIOXOPIPERAZINE DERIVATIVES AND PRODUCTION OF FAVIPIRAVIR THEREOF

The present invention relates to a method of preparing derivatives of 3,6-dichlorocyano pyrazine, 3,6-dioxopiperizin and the production of favipiravir by cyclization and chlorination mediated by ammonia or amine using POCl3 in the presence of pyridine or PCl5. [Formula] In derivatives of 3,6-dioxopiperazine (III), X represents CN, CONH2 or COOR2', R1, R 2 and R2' are individually selected from H, alkyl C1-C12, COOR3 and SO2R3, R 3 being a linear or branched lower alkyl substituted or unsubstituted.

Preparation method of favipiravir

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.

Favipiravir intermediate and synthesis method of favipiravir

The invention discloses a favipiravir intermediate and a synthesis method of favipiravir. The synthesis method comprises the following steps: taking 2,5-dihalopyrazine as an initial raw material, reacting 2,5-dihalopyrazine with formamide under the action of an oxide and a catalyst to generate 6-halo-3-chloro-2-amide pyrazine; carrying out a reaction on 6-halo-3-chloro-2-amide pyrazine under the action of a dehydration chlorinating agent and an acid-binding agent to generate a favipiravir intermediate 3,6-dichloro-3-cyanopyrazine; carrying out an aromatic ring fluorination reaction on the obtained favipiravir intermediate and potassium fluoride in dimethyl sulfoxide to generate 3,6-difluoro-3-cyanopyrazine; adding the 3,6-difluoro-3-cyanopyrazine into a water solution containing sodium acetate, and carrying out hydrolysis to obtain 6-fluoro-3-hydroxyl-2-cyanopyrazine; and finally, carrying out a cyano hydrolysis reaction to obtain favipiravir. A mixture of 2,5-dichloropyrazine and 2-chloro-5-bromopyrazine are used as raw materials to synthesize the favipiravir intermediate, the raw material cost is remarkably reduced, and the provided synthesis method has the technical advantages of high yield and low cost.

Favipiravir synthesis process

The invention relates to a favipiravir synthesis process, which comprises: 1) dissolving a pyrazine compound in an organic reagent I, adding an oxidizing agent M, and carrying out a nitrogen oxidation reaction to obtain a white solid; 2) adding the obtained white solid to an organic reagent II, and carrying out a chlorination reaction to obtain a pale yellow solid; 3) uniformly mixing the obtained pale yellow solid, a dried aprotic polar solvent, a dried fluorine ion donor reagent and tetrabutylammonium bromide, and carrying out a stirring reaction to obtain a pale yellow solid; 4) adding the obtained pale yellow solid to water, and carrying out a reaction with 1,4-dioxane and sodium acetate to obtain a yellow oily matter; and 5) uniformly mixing the obtained yellow oily matter and concentrated sulfuric acid to obtain the target product favipiravir. According to the present invention, the method has advantages of simple and easily available raw materials, simple synthesis process and mild conditions, nitrogen oxidation, chlorination, fluorization and hydrolysis are performed to finally prepare the 6-fluoro-3-hydroxypyrazine-2-formamide, and the good industrial value is provided.

PYRAZINO[2,3-D]ISOXAZOLE DERIVATIVE

The object of the present invention is to provide a compound which is useful as a production intermediate of pyrazine carboxamide derivative such as 6-fluoro-3-hydroxy-2-pyrazine carboxamide. The present invention provides a pyrazino[2,3-d]isoxazole derivative represented by the formula (I): wherein X represents a halogen atom, a hydroxyl group or a sulfamoyloxy group, and Y represents —C(═O)R or —CN; wherein R represents a hydrogen atom, an alkoxy group an aryloxy group, an alkyl group, an aryl group or an amino group.

METHOD FOR PRODUCING DICHLOROPYRAZINE DERIVATIVE

A method for producing a hydroxypyrazine derivative represented by formula (I) (wherein R1 represents a halogen atom), the method including reacting a pyrazine derivative represented by formula (III) (wherein R2 represents a nitrile group, an N-unsubstituted or N-substituted carbamoyl group, an ester group or a carboxyl group, M represents a cation capable of forming a salt, and n represents a number corresponding with the valence of M) with a halogenating agent. Also, a method for producing a dichloropyrazine derivative represented by formula (II) (wherein R21 represents a nitrile group, an N-unsubstituted or N-substituted carbamoyl group, an ester group, a carboxyl group, or a group formed as a result of a change in the functional group of R2 during chlorination), the method including reacting the hydroxypyrazine derivative (I) with a chlorinating agent. According to the present invention, a dichloropyrazine derivative can be produced efficiently at low cost, and a hydroxypyrazine derivative that functions as a production intermediate for the dichloropyrazine derivative can be produced efficiently at low cost.