N-bromobutanimide → HCID 54473820, compound

Participants

Reaction Steps

The title compound was prepared according to General Procedure IV using 5-chloro-6-methylthio-1-(2,3,4-tri-O-acetyl-beta-D-ribopyranosyl)-1H-benzimidazole and 6-chloro-5-methylthio-1-(2,3,4-tri-O-acetyl-beta-D-ribopyranosyl)-1H-benzimidazole as a mixture of regioisomers (0.36 g, 0.79 mmol), 30 ml tetrahydrofuran (Aldrich Sure Seal, Milwaukee), and a total of 1.68 g (9.4 mmol) of N-bromosuccinimide that was added over 2 h. The product from work-up by General Procedure IV was purified on a silica gel column with dichloromethane and a step gradient from 0-0.5% methanol. This provided 0.18 g (0.34 mmol) of the title compounds as a mix of regioisomers. The regioisomers were separated by SFC on a semi-preparative Chiralcel OD lot No. S017OD00CJ-HC001 eluting with a mobile phase of 90% carbon dioxide and 10% methanol at a flow rate of 2.0 ml/min and a pressure of 3000 psi at a temperature of 40° C. with signal detection at 254 nm. 2-Bromo-5-chloro-6-methylthio-1-(2,3,4-tri-O-acetyl-beta-D-ribopyranosyl)-1H-benzimidazole eluted first (RT=5.78 min) and 0.047 g was obtained after evaporation of the solvent. 1H NMR (DMSO-d6) δ7.79 (s, 1H), 7.68 (s, 1H), 6.03-6.00 (d, 1H), 5.78-5.74 (m, 2H), 5.57 (m, 1H), 4.23-4.17 (m, 1H), 4.09-4.01 (t, 1H), 2.64 (s, 3H), 2.26 (s, 3H), 2.04 (s, 3H), 1.80 (s, 3H). 2-Bromo-6-chloro-5-methylthio-1-(2,3,4-tri-O-acetyl-beta-D-ribopyranosyl)-1H-benzimidazole eluted from the chiral column last (RT=7.22 min) and 0.057 g was obtained after evaporation of the solvent. 1H NMR (DMSO-d6) δ8.27 (s, 1H), 7.51 (s, 1H), 5.98-5.95 (d, 1H), 5.78-5.72 (m, 3H), 4.17-4.16 (m, 1H) 4.06-3.98 (t, 1H), 2.26 (3, 3H), 2.04 (s, 3H), 1.79 (s, 3H).

Provenance & Evidence