Nitrogen → 3'-O-Azidomethyl-5-[3-(2,2,2-trifluoroacetamido)-prop-1-ynyl]-2'-deoxyuridine

Participants

Reaction Steps

To a solution of (3) (348 mg, 0.63 mmol) and cyclohexene (0.32 ml, 3.2 mmol) in dry CH2Cl2 (5 ml) at 4° C., sulfurylchloride (1M in CH2Cl2, 0.76 ml, 0.76 mmol) was added drop wise under N2. After 10 min TLC indicated the full consumption of the nucleoside (3). The solvent was evaporated and the residue was subjected to high vacuum for 20 min. It was then redissolved in dry DMF (3 ml) and treated with NaN3 (205 mg, 3.15 mmol). The resulting suspension was stirred under room temperature for 2 h. The reaction was quenched with CH2Cl2 and the organic layers were washed with sat aq. NaCl solution. After removing the solvent, the resulting yellow gum was redissolved in THF (2 ml) and treated with TBAF (1 M in THF, 0.5 ml) at room temperature for 30 min. The solvent was removed and the reaction worked up with CH2Cl2 and sat. aq. NaHCO3 solution. The aqueous layer was extracted three times with CH2Cl2. Purification by chromatography on silica (EtOAc:petroleum ether 1:1 to EtOAc) gave (4) (100 mg, 37%) as a pale yellow foam. 1H NMR (d6 DMSO) δ 2.15-2.26 (m, 2H, H-2′), 3.47-3.57 (m, 2H, H-5′), 3.88-3.90 (m, 1H, H-4′), 4.14 (d, J=4.7 Hz, 2H, CH2NH), 4.24-4.27 (m, 1H, H-3′), 4.75 (s, 2H, CH2N3), 5.14 (t, J=5.2 Hz, 1H, OH), 5.96-6.00 (m, 1H, H-1′), 8.10 (s, 1H, H-6), 10.00 (s, 1H, NHCOCF3)), 11.26 (s, 1H, NH).

Provenance & Evidence