259793-96-9 Usage
Description
Pyrazinecarboxamide, 6-fluoro-3,4-dihydro-3-oxo(9CI) is a chemical compound belonging to the class of pyrazines, specifically characterized by the presence of a carboxamide group, a fluoro substituent, and an oxo group at positions 3, 6, and 4, respectively. Pyrazinecarboxamide, 6-fluoro-3,4-dihydro-3-oxo(9CI) has potential applications in various industries due to its unique structural properties and reactivity.
Uses
Used in Pharmaceutical Industry:
Pyrazinecarboxamide, 6-fluoro-3,4-dihydro-3-oxo(9CI) is used as an intermediate compound for the synthesis of various pharmaceutical drugs. Its unique structure allows it to be a key component in the development of new medications targeting specific diseases and conditions.
Used in Antiviral Applications:
In the field of antiviral research, Pyrazinecarboxamide, 6-fluoro-3,4-dihydro-3-oxo(9CI) serves as a potential candidate for the development of new antiviral drugs. Its ability to inhibit RNA-dependent RNA polymerase (RdRp) makes it a promising agent against a variety of RNA viruses, including influenza A and B, Ebola virus, and COVID-19.
Used in Chemical Synthesis:
Pyrazinecarboxamide, 6-fluoro-3,4-dihydro-3-oxo(9CI) is used as a building block in the synthesis of various organic compounds and materials. Its reactivity and structural features make it a valuable component in the creation of new molecules with specific properties and applications.
Used in Research and Development:
Pyrazinecarboxamide, 6-fluoro-3,4-dihydro-3-oxo(9CI) is also utilized in research and development laboratories for studying its chemical properties, reactivity, and potential applications in various fields. Researchers can use Pyrazinecarboxamide, 6-fluoro-3,4-dihydro-3-oxo(9CI) to explore new reaction pathways and develop innovative synthetic methods.
History
Favipiravir was originally developed in the late 1990s by a company that was later purchased by the Japanese firm Fujifilm as part of its transition from the photo business to healthcare. After being tested against a range of viruses, the drug was approved in Japan in 2014 for emergency use against flu epidemics or to treat new strains of influenza.
Mechanism of action
Favipiravir is an antiviral drug that selectively inhibited the RdRP of influenza virus. It showed specific activity against all three influenza A, B, and C (Furuta et al., 2013). It also inhibited the RV replication in HeLa cells, with an EC50 of 29 μg/mL (Furuta et al., 2002). Analysis showed that the primary mechanism of action of favipiravir against the influenza virus was specific inhibition of vRNA polymerase (Furuta et al., 2005). It is predicted that a similar mechanism might occur with other viruses, such as PV and RV, inhibited by favipiravir, which may account for its broad-spectrum inhibition. Mechanistic studies show that the favipiravir and its form favipiravir-RMP (favipiravir-ribofuranosyl-50-monophosphate) do not inhibit influenza RNA polymerase activity, but it is the phosphoribosylated form, favipiravir-ribofuranosyl-50-triphosphate (RTP) that inhibits the enzyme.
Synthesis
Favipiravir was synthesized in only six steps from 3-aminopyrazine-2-carboxylic acid with an overall yield of about 22.3%. Key intermediates 3 and 6 were obtained in excellent purity via recrystallization from optimized solvents, which was beneficial to large-scale production. In the key synthetic reaction, 3,6-dichloropyrazine-2-carbonitrile (6) was reacted sequentially, in one pot, with KF and 30% H2O2 to give (after crystallization from 95% EtOH) favipiravir as colorless crystals, with a 60% yield for this final step of the synthesis. (DOI:10.1007/s11696-017-0208-6)645 grams of sodium hydroxide were dissolved in 9L of water, the temperature was lowered to 5°C, and 1.29 kg of 6-fluoro-3-hydroxy-2-cyanopyrazine was added in batches, stirred, and heated slightly, and the temperature of the reaction system was controlled to -10°C, it takes 3.5 hours to complete the addition, after holding for 1 hour, the temperature is raised to 40°C for 1 hour. Add 100g of activated carbon to the reaction solution, hot filter, cool the mother liquor to 5°C, adjust the pH to 3-4 with concentrated hydrochloric acid, precipitate a large amount of solids, filter and dry to obtain a crude off-white powder, beaten with 2.8 liters of 15% methanol aqueous solution and filter After drying, 1.34 kg of white powder favipiravir was obtained. 1H-NMR (DMSO, 600MHz): δ 13.38 (s, 1H), 8.73 (1s, 1H), 8.51-8.49 (d, J=12, 2H) (yield 91%).
References
1) Furuta?et al.?(2002),?In Vitro and In Vivo Activities of Anti-Influenza Virus Compound T-705; Antimicrob. Agents Chemother.,?46?977
2) Takahashi?et al.?(2003)?In Vitro and In Vivo Activities of T-705 and Oseltamivir Against Influenza Virus; Antivir. Chem. Chemother.,?14?235
3) Sleeman?et al.?(2010)?In Vitro Antiviral Activity of Favipiravir (T-705) against Drug-Resistant Influenza and 2009 A(H1N1) Viruses; Antimicrob. Agents Chemother.,?54?2517
4) Furuta?et al.?(2005)?Mechanism of action of T-705 against influenza virus; Antimicrob. Agents Chemother.,?49?981
5) Furuta?et al.?(2013)?), Favipiravir (T-705), a Novel Viral RNA Polymerase Inhibitor; Antiviral Res.,?100?446
6) Dong?et al.?(2020)?Discovering Drugs to Treat Coronavirus Disease 2019 (COVID-19); Drug Discov. Ther.,?14?58
7) Tu?et al.?(2020)?A Review of SARS-CoV-2 and the Ongoing Clinical Trials; Int. J. Mol. Sci., 21?E2657
Check Digit Verification of cas no
The CAS Registry Mumber 259793-96-9 includes 9 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 6 digits, 2,5,9,7,9 and 3 respectively; the second part has 2 digits, 9 and 6 respectively.
Calculate Digit Verification of CAS Registry Number 259793-96:
(8*2)+(7*5)+(6*9)+(5*7)+(4*9)+(3*3)+(2*9)+(1*6)=209
209 % 10 = 9
So 259793-96-9 is a valid CAS Registry Number.
259793-96-9Relevant articles and documents
PROCESS FOR PREPARATION OF FAVIPIRAVIR
-
Paragraph 0266, (2021/12/08)
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.
Scalable synthesis of favipiravir: Via conventional and continuous flow chemistry
Charoensetakul, Netnapa,Khamkhenshorngphanuch, Thitiphong,Srikun, Onsiri,Srimongkolpithak, Nitipol,Thongpanchang, Chawanee,Tiyasakulchai, Thanat,Yuthavong, Yongyuth
, p. 38691 - 38693 (2021/12/20)
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
Preparation method of favipiravir
-
Paragraph 0045-0057, (2021/08/14)
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.