Idoxuridine → 5-Ethynyl-2'-deoxyuridine

Participants

Reaction Conditions

Reaction Steps

5-Iodo-2′-deoxyuridine (5, 1.0 g, 2.82 mmol) was dissolved in MeCN/Et3N (66 mL of 1:1, v/v) under argon atmosphere. Trimethylsilylacetylene (1.6 mL, 11.3 mmol), bis-(triphenylphosphine)-palladium(II) chloride (42.2 mg, 0.60 mmol), and CuI (28 mg, 0.15 mmol) were added, and the mixture was heated for 3.5 h in the flask immersed into a preheated oil bath (50° C.). The solvents were removed in vacuo to give a residue that was purified by silica gel flash column chromatography. Elution with CHCl3/MeOH (9:1, v/v) afforded trimethylsilyl intermediate as a solid (0.75 g, 82%). To the solution of this intermediate (0.7 g, 2.16 mmol) in anhydrous MeOH (16 mL) under argon atmosphere, a solution of NaOMe in MeOH (145 mL of 0.05 N) was added, and the reaction was stirred at 25° C. for 2 h. The pH of the solution was adjusted to 5-6 using Dowex 50 WX8-200 (H+), the mixture was filtered, and concentrated in vacuo to give a residue that was purified by silica gel column flash chromatography using CHCl3/MeOH (8:2, v/v) as eluent to yield 5-ethynyl-2′-deoxyuridine (EdU) as a white solid (395 mg, 73%); 1H NMR (DMSO-d6) δ 11.62 (s, 1H, NH), 8.29 (s, 1H, H-6), 6.10 (dd, J=6.56, 6.56 Hz, 1H, H-1′), 5.24 (d, J=4.31 Hz, 1H, C-3′ OH), 5.12 (t, J=4.91 Hz, 1H, C-5′ OH), 4.23 (m, 1H, H-3′), 4.10 (s, 1H, C≡CH), 3.79 (q, J=3.25, 3.25, 3.26 Hz, 1H, H-4′), 3.59 (m, 2H, H-5′, H-5″), 2.16 (m, 2H, H-2′, H-2″). HRMS calcd for C11H11N2O14 251.0673 (M−H)−. found 251.0683.

Provenance & Evidence