Cesium carbonate → HCID 24944884, compound

Participants

Reaction Steps

A solution of 2-iodo adenosine (200 mg, 0.51 mmol), 3,5-difluorophenylboronic acid (150 mg, 0.95 mmol), cesium carbonate (364 mg, 1.12 mmol) and Pd(PPh3)4 (59 mg, 0.051 mmol) in toluene (1.2 mL) and ethanol (2.4 mL) was heated in a Biotage microwave (120° C., absorption high, pre-stirring 15 s) for 40 min. The solvents were then removed in vacuo and the residue dissolved in EtOAc (20 mL) and washed with sat. aq. NaHCO3 (20 mL×2) and brine (20 mL) and dried over MgSO4. Purification by reverse phase prep HPLC in 2 batches (Phenomenex Synergi, RP-Hydro 150×10 mm, 10%, 20 mL per min, gradient 5-100% acetonitrile in water over 10 min, product eluted in 35% acetonitrile) and (Phenomenex Synergi, RP-Hydro 150×10 mm, 10μ, 20 mL per min, gradient 5-100% acetonitrile in water over 10 min, product eluted in 40% acetonitrile), combination of the purer fractions from both columns, concentration in vacuo to ˜20 mL and filtration of the resulting white precipitate gave (2R,3R,4S,5R)-2-{6-amino-2-(3,5-difluorophenyl)-9H-purin-9-yl}-5-(hydroxymethyl)tetrahydrofuran-3,4-diol 10 as a white solid (16.8 mg, 9%).

Provenance & Evidence