Trimethylsilyl triflate → 4,5-Dichloro-1-(2,3-di-O-acetyl-5-deoxy-beta-D-ribofuranosyl)-N-(1-methylethyl)-1H-benzimidazol-2-amine

HRID 2227178Notes

Reaction equation

HRID 2227178 reaction equation
[Cl:1][C:2]1[C:10]2[N:9]=[C:8]([NH:11][CH:12]([CH3:14])[CH3:13])[NH:7][C:6]=2[CH:5]=[CH:4][C:3]=1[Cl:15].C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.FC(F)(F)S(O[Si](C)(C)C)(=O)=O.C(O[CH:44]1[O:56][C@H:55]([CH3:57])[C@@H:50]([O:51][C:52](=[O:54])[CH3:53])[C@H:45]1[O:46][C:47](=[O:49])[CH3:48])(=O)C.C(=O)(O)[O-].[Na+]>C(#N)C>[Cl:1][C:2]1[C:10]2[N:9]=[C:8]([NH:11][CH:12]([CH3:13])[CH3:14])[N:7]([C@@H:44]3[O:56][C@H:55]([CH3:57])[C@@H:50]([O:51][C:52](=[O:54])[CH3:53])[C@H:45]3[O:46][C:47](=[O:49])[CH3:48])[C:6]=2[CH:5]=[CH:4][C:3]=1[Cl:15]

Participants

7

Reactant 5

HCID 65367Trimethylsilyl triflateHCID 516892Sodium BicarbonateHCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 11196237Tri-O-acetyl-5-deoxy-D-ribofuranoseHCID 184219284,5-Dichloro-N-(1-methylethyl)-1H-benzimidazol-2-amine

Product 1

HCID 570527734,5-Dichloro-1-(2,3-di-O-acetyl-5-deoxy-beta-D-ribofuranosyl)-N-(1-methylethyl)-1H-benzimidazol-2-amineYield 90%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

4,5-Dichloro-N-(1-methylethyl)-1H-benzimidazol-2-amine (0.50 g, 2.0 mmol), N,O-bis(trimethylsilyl) acetamide (Aldrich, 0.55 mL, 2.2 mmol), and acetonitrile (Aldrich Sure Seal, 70 mL) were combined and refluxed under nitrogen for 15 min. The solution was cooled to rt and trimethylsilyl trifluoromethanesulfonate (Aldrich, 0.24 mL, 1.2 mmol) was added. After 10 min, 1,2,3-tri-O-acetyl-5-deoxy-D-ribofuranose (0.69 g, 2.6 mmol) dissolved in acetonitrile (Aldrich Sure Seal, 10 mL) was added. The solution was stirred under nitrogen at rt for 12 h and then heated in an 80° C. oil bath for 2.5 h. The solution was then poured into 5% aqueous sodium bicarbonate (50 mL) and extracted with ethyl acetate (3×100 mL). The organic layers were dried with magnesium sulfate, filtered, and evaporated. The crude residue was purified on a silica gel column (2.5×20 cm, 230-400 mesh) with 97:3 dichloromethane-methanol to give the title compound (0.82 g, 1.8 mmol, 90%); 1H NMR (DMSO-d6) δ: 7.29 (s, 1H, Ar—H, J=8.4 Hz), 7.10 (s, 1H, Ar—H, J=8.4 Hz), 6.98 (d, 1H, NH, J=7.5 Hz), 6.10 (d, 1H, H-1′, J=6.3 Hz), 5.50-5.55 (m, 1H, CH), 5.15 (t, 1H, CH, J=6.0 Hz), 4.04-4.17 (m, 2H, CH), 2.14 (s, 3H, OAc), 2.01 (s, 3H, OAc), 1.48 (d, 3H, 5′-CH3, J=6.3 Hz), 1.24 (t, 6H, CH3, J=6.2 Hz).

Workup

  1. temperaturerefluxed under nitrogen for 15 min
  2. additionwas added
  3. temperatureheated in an 80° C. oil bath for 2.5 h
  4. extractionextracted with ethyl acetate (3×100 mL)
  5. dry with materialThe organic layers were dried with magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude residue was purified on a silica gel column (2.5×20 cm, 230-400 mesh) with 97:3 dichloromethane-methanol

Sources & evidence

ORD record
ord-205a0cdac3334cee9212788e51bc6ab0
Source dataset
uspto-grants-2002_07
Patent number
US06413938B1

Reaction notes

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