Trimethylsilyl triflate → 2,4-Dibromo-5,6-dichloro-1-(2,3-di-O-acetyl-5-deoxy-beta-D-ribofuranosyl)-1H-benzimidazole

HRID 2227219Notes

Reaction equation

HRID 2227219 reaction equation
[Br:1][C:2]1[NH:6][C:5]2[CH:7]=[C:8]([Cl:13])[C:9]([Cl:12])=[C:10]([Br:11])[C:4]=2[N:3]=1.C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.C(O[CH:30]1[O:42][C@H:41]([CH3:43])[C@@H:36]([O:37][C:38](=[O:40])[CH3:39])[C@H:31]1[O:32][C:33](=[O:35])[CH3:34])(=O)C.C[Si](OS(C(F)(F)F)(=O)=O)(C)C>C(#N)C.C(OCC)(=O)C>[Br:1][C:2]1[N:6]([C@@H:30]2[O:42][C@H:41]([CH3:43])[C@@H:36]([O:37][C:38](=[O:40])[CH3:39])[C@H:31]2[O:32][C:33](=[O:35])[CH3:34])[C:5]2[CH:7]=[C:8]([Cl:13])[C:9]([Cl:12])=[C:10]([Br:11])[C:4]=2[N:3]=1

Participants

7

Reactant 4

HCID 65367Trimethylsilyl triflateHCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 11196237Tri-O-acetyl-5-deoxy-D-ribofuranoseHCID 184721252,4-dibromo-5,6-dichloro-1H-benzimidazole

Product 1

HCID 538921832,4-Dibromo-5,6-dichloro-1-(2,3-di-O-acetyl-5-deoxy-beta-D-ribofuranosyl)-1H-benzimidazoleYield 64.2%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
70 °C

Procedure

To a suspension of 2,4-dibromo-5,6-dichloro-1H-benzimidazole (0.35 g, 1 mmol), in acetonitrile (5 mL) was added N,O-bis(trimethylsilyl)acetamide (0.25 mL, 1 mmol). The resulting mixture was allowed to stir at 70° C. for 15 min, followed by the addition of 1,2,3-tri-O-acetyl-5-deoxyribofuranose (0.31 g, 1.2 mmol) in acetonitrile (5 mL) and trimethylsilyltrifluoromethane sulfonate (0.25 mL, 1.3 mmol). The mixture was allowed to stir at 70° C. for 30 min and was then allowed to cool to RT. The mixture was diluted with ethyl acetate, washed with a saturated aqueous NaHCO3 solution, dried over NaSO4 and the solvents were removed by rotary evaporation. The product was purified by flash chromatography using methylene chloride then 1:1 methylene chloride/chloroform followed by recrystallization from methanol to provide 0.35 g (63%) of the title compound as white crystals: m.p. 152-154° C.; 1H NMR (DMSO-d6) δ: 8.16 (s, 1H), 6.15 (d, 1H), 5.63 (t, 1H), 5.27 (dd, 1H), 4.26 (m, 1H), 2.13 (s, 3H), 2.02 (s, 3H), 1.51 (d, 3H).

Workup

  1. stirringto stir at 70° C. for 30 min
  2. temperatureto cool to RT
  3. washwashed with a saturated aqueous NaHCO3 solution
  4. dry with materialdried over NaSO4
  5. customthe solvents were removed by rotary evaporation
  6. customThe product was purified by flash chromatography
  7. custom1:1 methylene chloride/chloroform followed by recrystallization from methanol

Sources & evidence

ORD record
ord-f59a87f4ff4a4a20a955265a883795b1
Source dataset
uspto-grants-2002_07
Patent number
US06413938B1

Reaction notes

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