700-49-2

Usage

Uses

Used in Anticancer Applications:
2-Fluoroadenine is used as an antineoplastic agent for its potential role in suicide gene therapy for human malignancy. It has been investigated for its ability to inhibit tumor growth and progression by modulating various oncological signaling pathways.
Used in Pharmaceutical Industry:
2-Fluoroadenine is used as an intermediate for the synthesis of antineoplastic drugs such as fludarabine, which is a chemotherapy drug used in the treatment of chronic lymphocytic leukemia. It serves as a crucial component in the development of novel cancer therapies.
Used in Drug Synthesis:
2-Fluoroadenine is used as a key compound in the synthesis of heat shock protein 90 (Hsp90) inhibitors, which have demonstrated anticancer activity in vitro. These inhibitors target specific proteins involved in cancer cell survival and proliferation, making them a promising avenue for cancer treatment.
Used in Research and Development:
2-Fluoroadenine is utilized in research and development for the exploration of its potential applications in cancer therapy. Its unique chemical properties and interactions with various biological targets make it an interesting candidate for further investigation and potential drug development.

InChI:InChI=1/C5H4FN5/c6-5-10-3(7)2-4(11-5)9-1-8-2/h1-2H,(H2,7,8,9,10,11)

Upstream product

• 37076-78-1 5'-deoxy-2-fluoroadenosine 
• 146-78-1 Fludarabine 
• 21679-12-9 2-fluoro-2'-deoxyadenosine 
• 146-78-1 2-fluoroadenosine 
• 134217-15-5 2-fluoro-9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-9H-purin-6-amine 
• 109-80-8 1.3-propanedithiol 
• 143482-58-0 6-azido-2-fluoropurine 
• 1904-98-9 2,6-diaminopurine 
• 1904-98-9 2,6-diaminopurine 
• 7306-68-5 6-chloro-9-(tetrahydro-2H-pyran-2-yl)-9H-purine 
• 1651-29-2 6-chloro-2-fluoro-7H-purine 
• 1651-29-2 6-chloro-2-fluoropurine 
• 875-70-7 2-flouroadenine hydrochloride 
• 845795-77-9 6-chloro-2-fluoro-9-(tetrahydro-2H-pyran-2-yl)-9H-purine 

Downstream Products

• 86626-06-4 9-(2,3-dihydroxypropyl)-2-fluoroadenine 
• 1492-62-2 2-fluoroadenosine 5'-triphosphate 
• 24649-69-2 2-fluoro-9-(2,3,5-tri-o-benzyl-beta-D-arabinofuranosyl)adenine 
• 518028-23-4 2-Fluoro-9-(2,3,5-tri-O-benzoyl-α-L-lyxofuranosyl)-9H-purin-6-amine 
• 21679-12-9 2-fluoro-2'-deoxyadenosine 
• 1093278-52-4 2-methoxy-2'-deoxy-2'-fluoroadenosine 
• 134217-15-5 2-fluoro-9-(2-deoxy-2-fluoro-β-D-arabinofuranosyl)-9H-purin-6-amine 
• 146-78-1 2-fluoroadenosine 
• 146-78-1 Fludarabine 
• 1341075-12-4 9-((1R,3R,4R,7S)-7-(benzyloxy)-1-((tert-butyldiphenylsilyloxy)methyl)-2,5-dioxabicyclo[2.2.1]heptan-3-yl)-2-fluoro-9H-purin-6-amine 
• 1341074-25-6 ((1S,3R,4R,7S)-3-(6-amino-2-fluoro-9H-purin-9-yl)-7-(benzyloxy)-2,5-dioxabicyclo[2.2.1]heptan-1-yl)methanol 
• 1341074-28-9 ((1S,3R,4R,7S)-3-(6-amino-2-morpholino-9H-purin-9-yl)-7-(benzyloxy)-2,5-dioxabicyclo[2.2.1]heptan-1-yl)methanol 
• 1341075-09-9 (2R,3R,4S,5S)-2-(6-amino-2-fluoro-9H-purin-9-yl)-4-(benzyloxy)-5-((tert-butyldiphenylsilyloxy)methyl)-5-(tosyloxymethyl)tetrahydrofuran-3-yl acetate 
• 1332623-00-3 (2R,3S,5S)-5-(6-amino-2-fluoropurin-9-yl)-2-[(tert-butyldiphenylsilyloxy)-methyl]-2-ethynyltetrahydrofuran-3-yl acetate 

Relevant academic research and scientific papers

Development of a Commercial Manufacturing Route to 2-Fluoroadenine, the Key Unnatural Nucleobase of Islatravir

We report the practical synthesis of a key fragment of islatravir (MK-8591), a novel nucleoside reverse transcriptase translocation inhibitor (NRTTI) currently under investigation for treatment and pre-exposure prophylaxis (PrEP) against HIV infection. The fragment, the unnatural nucleobase 2-fluoroadenine, is incorporated into MK-8591 via a biocatalytic aldol-glycosylation cascade, which imposes stringent requirements for its synthesis and isolation. Presented herein is the development work leading to a practical, scalable route from guanine, featuring a dual fluorination approach to a novel 9-THP-2,6-difluoropurine intermediate that enables a mild, highly selective, direct amination. This one-pot fluorination/amination sequence utilizes a direct isolation to deliver high purity 9-THP-2-fluoroadenine, which features ideal properties with respect to reactivity, solubility, and crystallinity. An acid-catalyzed liberation of 2-fluoroadenine in aqueous buffer delivers the appropriate purity profile to facilitate the enzymatic cascade to access MK-8591.

Preparation method of fludarabine antitumor drug intermediate

The invention relates to the field of preparation of fludarabine antitumor drug intermediates, and discloses a preparation method of a fludarabine antitumor drug intermediate. The method comprises the following steps: (1) mixing pyridine and triethylamine, adding a compound 1 and trifluoroacetic anhydride, reacting for 3-4 hours, and carrying out aftertreatment to obtain a compound 2; (2) mixing dichloromethane, dichloroethane and tetrahydrofuran, adding tetrabutylammonium nitrate and trifluoroacetic anhydride, adding the compound 2, reacting for 6-7 hours, and carrying out aftertreatment to obtain a compound 3; (3) mixing the compound 3, NaF, KF, tetrabutylammonium fluoride and DMF, reacting at 40-50 DEG C for 3-3.5 hours, and carrying out aftertreatment to obtain a compound 4; and (4) adding a compound 4 into methanol/water of KOH and LiOH, reacting for 2-3 hours, and carrying out post-treatment to obtain a compound 5, namely 2-fluorine-6-aminopurine. According to the method, the total yield of the fludarabine antitumor drug intermediate is increased.

Thermodynamic Reaction Control of Nucleoside Phosphorolysis

Nucleoside analogs represent a class of important drugs for cancer and antiviral treatments. Nucleoside phosphorylases (NPases) catalyze the phosphorolysis of nucleosides and are widely employed for the synthesis of pentose-1-phosphates and nucleoside analogs, which are difficult to access via conventional synthetic methods. However, for the vast majority of nucleosides, it has been observed that either no or incomplete conversion of the starting materials is achieved in NPase-catalyzed reactions. For some substrates, it has been shown that these reactions are reversible equilibrium reactions that adhere to the law of mass action. In this contribution, we broadly demonstrate that nucleoside phosphorolysis is a thermodynamically controlled endothermic reaction that proceeds to a reaction equilibrium dictated by the substrate-specific equilibrium constant of phosphorolysis, irrespective of the type or amount of NPase used, as shown by several examples. Furthermore, we explored the temperature-dependency of nucleoside phosphorolysis equilibrium states and provide the apparent transformed reaction enthalpy and apparent transformed reaction entropy for 24 nucleosides, confirming that these conversions are thermodynamically controlled endothermic reactions. This data allows calculation of the Gibbs free energy and, consequently, the equilibrium constant of phosphorolysis at any given reaction temperature. Overall, our investigations revealed that pyrimidine nucleosides are generally more susceptible to phosphorolysis than purine nucleosides. The data disclosed in this work allow the accurate prediction of phosphorolysis or transglycosylation yields for a range of pyrimidine and purine nucleosides and thus serve to empower further research in the field of nucleoside biocatalysis. (Figure presented.).

PROCESS FOR THE PREPARATION OF 2-FLUOROADENINE

The present invention provides processes for the preparation of 2-fluoroadenine, as well as certain intermediates useful in the preparation of 2'-deoxy-4'-C-ethynyl-2-fluoroadenosine (EFdA): EFdA.

One-Step Synthesis of 2-Fluoroadenine Using Hydrogen Fluoride Pyridine in a Continuous Flow Operation

We report the development of a one-pot synthesis of 2-fluoroadenine from an inexpensive 2,6-diaminopurine starting material using diazonium chemistry in a continuous fashion. Given the sensitivity of this transformation to temperature, we conducted critical experiments to study the exothermicity of the reaction and the heat removal, which were critical for the development of the process. Our goal was to improve the yield and purity of this pharmaceutical intermediate (2-fluoroadenine) and develop a more robust process.

The Method For Adenine Derivative

The present invention provides a method for manufacturing 2-fluoroadenine, comprising: a first step of amidating 6-chloro-2-fluoropurine (CFP) compound to synthesize a first intermediate product, which is N-(2-fluoropurin-6-yl)triphenylphosphine amide represented by chemical formula 2; a second step of acidifying the first intermediate product to synthesize a second intermediate product, which is 2-flouroadenine hydrochloride (2-FA HCl) represented by chemical formula 3; and a third step of neutralizing the second intermediate product to synthesize 2-fluorodadenine (2-FA) represented by chemical formula 4.COPYRIGHT KIPO 2019

The Method For Adenine Derivative

The purpose of the present invention is to provide a method for manufacturing adenine derivatives with high purity which can be easily manufactured. Provided is a method for manufacturing adenine derivatives to manufacture 2-fluoroadenine represented by chemical formula 3 by reacting 6-azido-2-fluoropurine compounds represented by chemical formula 1 with triphenylphosphine represented by chemical formula 2 in the presence of a solvent of tetrahydrofuran (THF) and hydrogenchloride (HCl).COPYRIGHT KIPO 2018

A 2 - fluoro adenine synthesis method (by machine translation)

The invention discloses a 2 - fluoro adenine synthesis method. Cheap 6 - chloropurine as raw materials, to the 9 bit NH to tetrahydropyranyl protection, then and trifluoromethanesulfonic anhydride reaction, in 2 introduces nitro, then and NH4 F reaction, nitro into atomic fluorine will at the same time, getting rid of the tetrahydro-pyranyl, finally being ammonia saturated methanol solution, the 6 position chlorine atom is converted into amino, to obtain 2 - fluoro adenine, total yield of 58%. The method easily obtained and cheap materials, to avoid the use of expensive and harmful toxic reagent, avoid the use of dangerous and corrosivity of the operation steps, and the reaction scale expanded to 200 g of the scale, the yield is not obviously dropped. The invention application for 2 - fluoro adenine synthesis provides a new synthetic pathway, has potential application prospect. (by machine translation)

PROCESS FOR THE PREPARATION OF 2-FLUOROADENINE

A process for the preparation of 2-fluoroadenine with a purity of at least 98% (HPLC Area) is presented. Such very high purity degree of at least 98% (HPLC Area) is obtained directly on the crude product after washing and filtration, without recrystallization and/or any further purification steps.

Process for the preparation of 2-fluoroadenine

The invention relates to a process for the preparation of 2-fluoroadenine with a purity of at least 98% (HPLC Area) characterised in that this very high purity degree of at least 98% (HPLC Area) is obtained directly on the crude product after washing and filtration, without recrystallization and/or any further purification steps.