Under argon protection, 5-iodo-2'-deoxycytidine (10 g, 28.32 mmol) was dissolved in DMF (200 mL) in a light protected round bottom flask. CuI (1.08 g, 5.67 mmol), triethylamine (7.80 mL, 55.60 mmol), 2,2,2-trifluoro-N-(prop-2-yn-1-yl)acetamide (12.8 g, 84.76 mmol), and Pd(PPh3)4 (3.27 g, 2.83 mmol) were added sequentially. The reaction mixture was stirred at room temperature for 18 hours. Subsequently, sodium bicarbonate (20 mg) was added and stirring was continued for 1 hour. After completion of the reaction, the crude product was obtained by filtration under reduced pressure and concentration to remove the volatile solvent. Purification by silica gel fast column chromatography (elution gradient: CH2Cl2, CH2Cl2:EtOAc 1:1, EtOAc:MeOH 9:1) afforded the target compound N-(3-(4-amino-1-((2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)tetrahydrofuryl-2- yl)-2-oxo-1,2-dihydropyrimidin-5-yl)propane- 2-yn-1-yl)-2,2,2-trifluoroacetamide (7) as a beige solid in quantitative yield.1H NMR (D2O) δ 2.24-2.17 (m, 1H, H-2'), 2.41-2.37 (m, 1H, H-2'), 3.68 (dd, J = 12.5, 5.0 Hz, 1H, H-5'), 3.77 (dd, J = 12.5, 3.2 Hz, 1H, H-5'), 3.99 (m, 1H, H-4'), 4.27 (s, 2H, CH2N), 4.34 (m, 1H, H-3'), 6.11 (t, J = 6.3 Hz, 1H, H-1'), 8.1 (br s, 1H, NH); MS (ES): m/z (%) (M-H) 375 (100).
