N-bromobutanimide → HCID 54473820, compound

HRID 1281703Notes

Reaction equation

HRID 1281703 reaction equation
[Cl:1][C:2]1[C:28]([S:29][CH3:30])=[CH:27][C:5]2[N:6]([C@@H:9]3[O:26][CH2:25][C@@H:20]([O:21][C:22](=[O:24])[CH3:23])[C@@H:15]([O:16][C:17](=[O:19])[CH3:18])[C@H:10]3[O:11][C:12](=[O:14])[CH3:13])[CH:7]=[N:8][C:4]=2[CH:3]=1.ClC1C(SC)=CC2N=CN([C@@H]3OC[C@@H](OC(=O)C)[C@@H](OC(=O)C)[C@H]3OC(=O)C)C=2C=1.[Br:61]N1C(=O)CCC1=O>O1CCCC1>[Br:61][C:7]1[N:6]([C@@H:9]2[O:26][CH2:25][C@@H:20]([O:21][C:22](=[O:24])[CH3:23])[C@@H:15]([O:16][C:17](=[O:19])[CH3:18])[C@H:10]2[O:11][C:12](=[O:14])[CH3:13])[C:5]2[CH:27]=[C:28]([S:29][CH3:30])[C:2]([Cl:1])=[CH:3][C:4]=2[N:8]=1

Participants

5

Reactant 3

HCID 67184N-bromobutanimideHCID 23383161HCID 23383161, compoundHCID 53840149HCID 53840149, compound

Product 1

HCID 54473820HCID 54473820, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

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).

Workup

  1. customThe product from work-up by General Procedure IV was purified on a silica gel column with dichloromethane
  2. customThe regioisomers were separated by SFC on a semi-preparative Chiralcel OD lot No
  3. washS017OD00CJ-HC001 eluting with a mobile phase of 90% carbon dioxide and 10% methanol at a flow rate of 2.0 ml/min
  4. customat a temperature of 40° C.

Sources & evidence

ORD record
ord-9bc4ee15bada468c8b7c90cfcd413e50
Source dataset
uspto-grants-2002_09
Patent number
US06455507B1

Reaction notes

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