GENERAL STEPS: To a solution of 5-iodo-2'-deoxycytidine (2.2 g, 6.23 mmol) in anhydrous DMF (130 mL) was added imidazole (467 mg, 6.85 mmol). The reaction mixture was cooled to 0 °C and tert-butyldimethylsilyl chloride (TBDMSCl) (1.33 g, 6.85 mmol) was added slowly over 5 min. The reaction mixture was stirred at room temperature for 18 h and then concentrated under reduced pressure to remove volatiles. The residue was purified by fast column chromatography on silica gel with EtOAc:MeOH as eluent (95:5 to 90:10) to afford the target product 4-amino-1-((2R,4S,5R)-5-(((tert-butyldimethylsilyl)oxy)methyl)-4-hydroxytetrahydrofuran-2-yl)-5-iodopyrimidin-2(1H)-one (2.10 g, 72% yield) and unreacted feedstock (490 mg). The products were characterized as follows: 1H NMR (d6-DMSO) δ 0.11 (s, 3H, CH3), 0.12 (s, 3H, CH3), 0.89 (s, 9H, 3×CH3), 1.90 (ddd, J = 13.2, 7.7, 5.7 Hz, 1H, H-2'), 2.18 (ddd, J = 13.2, 5.7, 2.3 Hz, 1H, H-2'), 3.72 (ddd, J = 11.5, 3.6 Hz, 1H, H-5'), 3.80 (ddd, J = 11.5, 2.8 Hz, 1H, H-5'), 3.86-3.89 (m, 1H, H-4'), 4.14-4.18 (m, 1H, H-3'), 5.22 (ddd, J = 4.1 Hz, 1H, OH), 6.14-4.18 (m, 1H, H-3'), 5.22 (ddd, J = 4.1 Hz, 1H 1H, OH), 6.09 (dd, J = 7.8, 5.8 Hz, 1H, H-1'), 6.60 (br s, 1H, NH), 7.81 (br s, 1H, NH), 7.94 (s, 1H, H-6); MS (ES): m/z (%) (M + H)+ 468 (90%).
