p-Toluenesulfonic acid → 5,6-Dichloro-2-(2-fluoro-1-methylethylamino)-1-(2,3,5-tri-O-acetyl-beta-L-ribofuranosyl)-1H-benzimidazole

Participants

Reaction Steps

Fluoroacetone (5 g) and 5,6-dichloro-2-amino-1-(2,3,5-tri-O-acetyl-beta-L-ribofuranosyl)-1H-benzimidazole (0.38 g, 0.82 mmol) were combined with tosic acid (0.050 g, 0.26 mmol) and stirred at reflux in a flask fitted with a Dean Stark trap. After four hours sodium cyanoborohydride (0.16 g, 2.4 mmol) was added and reflux was continued for six hours. The solution was diluted with ethyl acetate (200 mL) and washed with sat'd NaCl (2×50 mL) and water (50 mL). The organics were dried (Na2SO4), decanted, and concentrated. The crude product was purified on a silica gel column (230-400 mesh, 2.5×18 cm) with 1:25 methanol:CH2Cl2 gave 0.19 g of crude product This material was further purified on a chromatotron (2 mm rotor) with 1:1 ethyl acetate hexanes to give a light yellow solid (0.10 g, 0.20 mmol, 24%); MS (API+; m/z (rel. intensity) 520 (62.63, M+); 1H NMR (DMSO-d6) d 7.66 (s, 1H, Ar—H), 7.51 (s, 1H, Ar—H), 7.30 (d, 1 H, NH, J=7.6 Hz), 6.25 (d, 1H, H-1′, J=7.5 Hz), 5.31-5.23 (m, 1H, H-2′), 5.48-5.44 (m, 1H, H-3′), 4.63-4.26 (m, 6H, 2F, CH, H-4′ and 5′), 2.21 (s, 3H, OAc), 2.19 (s, 3H, OAc), 2.02 (s,3H, OAc), 1.24 (d, 3H, CH(CH3), J=7.5 Hz).

Provenance & Evidence