Reaction Steps
2,4,6-Triisopropyl benzenesulfonyl chloride (363 mg, 1.2 mmol) was added to a solution of compound 48 (170 mg, 0.24 mmol), DMAP (32 mg, 0.26 mmol), and triethylamine (0.34 mL, 2.4 mmol) in anhydrous CH2Cl2 (8.0 mL). The mixture was stirred at room temperature overnight under a nitrogen atmosphere, concentrated in vacuo, and the residue was dissolved in a solution of NH3 in 1,4-dioxane (0.5 M, 20 mL). The mixture was transferred into a sealed tube and was heated at 90° C. overnight. The mixture was cooled to room temperature, concentrated in vacuo, dissolved in CH2Cl2 (20 mL), and washed with brine (50 mL). The organic and aqueous phases were separated, and the aqueous phase was extracted with CH2Cl2 (30 mL) three times. The combined organic phase was dried over Na2SO4, concentrated in vacuo, and the residue was purified by silica gel column chromatography to yield 3′,5′-O-bis-(tert-butyldimethylsilyl)-5-[(S)-1-(5-methoxy-2-nitrophenyl)-2,2-dimethyl-propyloxy]methyl-2′-deoxycytidine 49 (110 mg, 65% for two steps). 1H NMR (400 MHz, DMSO-d6): δ 7.96 (d, J=8.8 Hz, 1H, Ph-H), 7.50 (br s, 1H, NH2), 7.38 (s, 1H, H-6), 7.08 (dd, 1H, J=2.8 and 8.8 Hz, Ph-H), 7.04 (d, 1H, J=2.8 Hz, Ph-H), 6.80 (br s, 1H, NH2), 6.13 (t, 1H, J=6.4 Hz, H-1′), 5.09 (s, 1H, Ph-CH), 4.31 (m, 1H, H-3′), 4.25 (d, 1H, J=12.8 Hz, 5-CH2a), 4.08 (d, 1H, J=12.8 Hz, 5-CH2b), 3.87 (s, 3H, OCH3), 3.76 (m, 1H, H-4′), 3.64 (m, 2H, H-5′), 3.76 (dd, 1H, J=2.8 Hz, H-5′b), 2.10 (m, 1H, H-2′a), 2.00 (m, 1H, H-2′b), 0.87 (s, 9H, C(CH3)3), 0.78 and 0.76 (2 s, 18H, SiC(CH3)3), 0.07, 0.06, −0.01, and −0.04 (4 s, 12H, SiCH3).
