5,6-Dichloro-1H-benzimidazole → HCID 70177974, compound

Participants

Reaction Conditions

Reaction Steps

2′,5′-Dideoxy-2′-fluorouridine (1.1 g, 4.8 mmoles) was dissolved in 950 mL of 50 mmoler pH 6.0 citrate buffer. 5,6-Dichlorobenzimidazole (Townsend and Revankar, Chem. Rev. 1970, 70:389) (0.53 g, 2.9 mmoles) was added followed by 71,250 units of N-deoxyribofuranosyl transferase (Freeman, et.al, Bioorg. & Med. Chem. 1995, 3(4):447-58). The reaction was placed in a 50° C. water bath and gently shaken for 27 days. The enzyme was precipitated by heating to 80° C. then cooling to room temperature. Celite (50-60 g) was added and the reaction filtered. The product was extracted with ethyl acetate (3×). The ethyl acetate was removed in vacuo and the residue purified by chromatography on 75 g of silica gel eluted with ethyl acetate. The product containing fractions were combined and the solvents removed in vacuo. The yield was 0.5 g, 56%. MS (APCl(+)): m/z, 305; 1H NMR (DMSO-d6) δ8.51 (s, 1H, H-2), 8.03 (s,1H, Ar—H), 7.98 (s,1H, Ar—H), 6.32 (d,1H, H-1′, J=18 Hz), 5.72 (d, 1H, OH-3′, J=6 Hz), 5.34 (d, 1H, H-2′, J=53 Hz), 4.0 (m, 2H,), 1.32 (d, 3H, H-5′, J=4 Hz).

Provenance & Evidence