6-Chloro-2-fluoropurine is a heterocyclic building block. It has been used in the synthesis of purine nucleosides that inhibit cyclin-dependent kinases (CDKs) in vitro. 6-Chloro-2-fluoropurine has also been used in the synthesis of purine nucleosides that are active against HIV-1 and hepatitis B virus (HBV) in vitro.
6-Chloro-2-fluoropurine is used as a reagent in the synthesis of several organic compounds including that of 2''-Fluoro-3''-Hydroxymethyl-5''-deoxythreosyl phosphonic acid nucleoside analogues which may potentially act as antiviral agents. It is also used in the synthesis of 2'',5'',5''-trifluoro-3''-hydroxy-apiosyl nucleoside phosphonic acid analogues which may possess potent anti-HCMV properties.
General procedure for the synthesis of 6-chloro-2-fluoro-9H-purine from 2-amino-6-chloropurine: 0.3 M NaNO2 aqueous solution (200 mL, 60 mmol) was slowly added dropwise to a vigorously stirred suspension of 2-amino-6-chloro-9H-purine (6.0 g, 35.4 mmol) at -15 °C. Subsequently, 120 mL of 48% HBF4 aqueous solution (0.92 mol) was added over 75 min. The reaction mixture was stirred at room temperature and kept in a light yellow reaction solution state for 20 min. After cooling again to -15 °C, it was neutralized with 50% NaOH aqueous solution to pH=6.0. The water was removed by vacuum and the orange solid obtained was purified by silica gel column chromatography (eluent ratio 90:10 dichloromethane to methanol, Rf value 0.50). 6-Chloro-2-fluoro-9H-purine was finally obtained as a white solid (3.0 g, 49.1% yield).
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