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To a solution of 4-iodo-1-trityl-1H-imidazole (609 mg, 1.4 mmol) in dry THF (6 ml) was added EtMgBr (1M in THF, 1.5 ml, 1.5 mmol) and the mixture was stirred at RT for 10 min. Then a solution of ZnCl2 (1M in THF, 2.8 ml, 2.8 mmol) was dropwise added and the mixture was stirred for 2 h. Resulting thick slurry was transferred to an argon purged mixture of 2′,3′,5′-tri-O-TBS-7-iodotubericidine {compound 4 from Example 17, Step 1} (515 mg, 0.7 mmol) and Pd(PPh3)4 (40 mg, 0.035 mmol) and the mixture was stirred at 90° C. for 16 h. The mixture was diluted with CHCl3 (20 ml) and washed with aq EDTA (sat., 20 ml). Aqueous layer was re-extracted with CHCl3 (2×5 ml). Collected organic extracts were dried over MgSO4, evaporated and chromatographed on silica (hexanes/AcOEt, 4:1→3:1) affording crude TBS,Tr-protected product contaminated by N-tritylimidazole. Crude product was deprotected by stirring in aq TFA (90% v/v, 2 ml) at RT for 18 h. The volatiles were removed in vacuo and the residue was several times co-evaporated with MeOH and finally loaded on silica by co-evaporation from MeOH. Column chromatography on silica (0→10% MeOH in CHCl3) afforded title compound 2r as white powder (179 mg, 77%). Compound was recrystallized from MeOH/water. Mp 276-278° C. [α]D −61.4 (c 0.249, DMSO). 1H NMR (500.0 MHz, DMSO-d6): 3.53 (ddd, 1H, Jgem=12.0, J5′b,OH=6.5, J5′b,4′=4.2, H-5′b); 3.64 (dd, 1H, Jgem=12.0, J5′a,OH=4.8, J5′a,4′=4.2, H-5′a); 3.89 (td, 1H, J4′,5′=4.2, J4′,3′=3.4, H-4′); 4.09 (ddd, 1H, J3′,2′=5.0, J3′,OH=4.8, J3′,4′=3.4, H-3′); 4.41 (ddd, 1H, J2′,OH=6.5, =6.3, J2′,3′=5.0, H-2′); 5.14 (d, 1H, JOH,3′=4.8, OH-3′); 5.30 (dd, 1H, JOH,5′=6.5, 4.8, OH-5′); 5.34 (d, 1H, JOH,2′=6.5, OH-5′); 6.03 (d, 1H, J1′,2′=6.3, H-1′); 7.14 (bs, 1H, NHaHb); 7.50 (d, 1H, J5,NH=2.0, J5,2=0.8, H-5-imidazole); 7.68 (s, 1H, H-6); 7.81 (d, 1H, J2,5=0.8, H-2-imidazole); 8.01 (s, 1H, H-2); 9.99 (bs, 1H, NHaHb); 12.31 (bs, 1H, NH-imidazole). 13C NMR (125.7 MHz, DMSO-d6): δ2.11 (CH2-5′); 70.87 (CH-3′); 73.76 (CH-2′); 85.23 (CH-4′); 87.30 (CH-1′); 100.77 (C-4a); 110.84 (C-5); 111.81 (CH-5-imidazole); 117.90 (CH-6); 134.95 (CH-2-imidazole); 135.10 (C-4-imidazole); 150.56 (C-7a); 152.08 (CH-2); 158.59 (C-4). MS (ESI) m/z 333 (M+H), 355 (M+Na). HRMS (ESI) for C14H17N6O4 [M+H] calcd: 333.1306. found: 333.1306. Anal. Calcd for C14H16N6O4: C, 50.60; H, 4.85; N, 25.29. Found: C, 50.55; H, 5.01; N, 24.28.
