Reaction Steps
5-Iodouridine-5′-phosphoromorpholidate (107 mg, 0.21 mmol) was co-evaporated (3×) with dry pyridine (5 mL). Galactose-1-phosphate (tributylamine salt, 326 mg, 0.55 mmol) was 17 added, and the mixture was further co-evaporated (3×) with pyridine (5 mL). Under a nitrogen atmosphere, the dry residue was dissolved in dry DMF (2 mL) and a 0.05M solution of tetrazole (80 mg, 1.14 mmol) in dry acetonitrile was added. The reaction was stirred at room temperature for 5 h, by which time the reaction had reached completion. All solvents were removed under reduced pressure, and the crude residue was purified sequentially by purification methods 1 and 2. The title compound 2 was obtained in its triethylammonium salt form as a colourless, glassy solid in 42% yield (60 mg). δH (400 MHz, D2O) 3.70-3.76 (2H, m, H-6″), 3.77-3.82 (1H, m, H-2″), 3.92 (1H, dd, J=3.3 and 10.1 Hz, H-3″), 4.01 (1H, d, J=3.7 Hz, H-4″), 4.16-4.19 (1H, m, H-5″), 4.20-4.23 (2H, m, H-5′), 4.25-4.28 (1H, m, H-4′), 4.33-4.39 (2H, m, H-2′, H-3′), 5.64 (1H, dd, J=3.6 and 6.6 Hz, H-1″), 5.93 (1H, d, J=5.9 Hz, H-1′), 8.25 (1H, s, H-6); δC (75.5 MHz, D2O) 59.6, 61.8, 65.8 (d, J=3.0 Hz), 69.3, 69.8, 70.0, 70.4, 72.7, 74.6, 84.2 (d, J=5.3 Hz), 89.3, 96.6 (d, J=3.8 Hz), 146.6, 152.4, 164.1; δP (121.5 MHz, D2O) −9.21 (d, J=21.2 Hz), −7.71 (d, J=21.2 Hz). m/z (ESI) 709.9863 [M+NH4]+, C15H27N3O17P2I requires 709.9855.
