Trimethylsilyl triflate → 5,6-Difluoro-1-(2,3-di-o-acetyl-5-deoxy-beta-d-ribofuranosyl)-n-(1-methylethyl)1h-benzimidazol-2-amine

HRID 2227174Notes

Reaction equation

HRID 2227174 reaction equation
[F:1][C:2]1[C:14]([F:15])=[CH:13][C:5]2[NH:6][C:7]([NH:9][CH:10]([CH3:12])[CH3:11])=[N:8][C:4]=2[CH:3]=1.C/C(/O[Si](C)(C)C)=N\[Si](C)(C)C.O([Si](C)(C)C)S(C(F)(F)F)(=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>[F:15][C:14]1[C:2]([F:1])=[CH:3][C:4]2[N:8]([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:7]([NH:9][CH:10]([CH3:11])[CH3:12])=[N:6][C:5]=2[CH:13]=1

Participants

7

Reactant 5

HCID 65367Trimethylsilyl triflateHCID 516892Sodium BicarbonateHCID 6913588N,O-bis(trimethylsilyl)acetamideHCID 11196237Tri-O-acetyl-5-deoxy-D-ribofuranoseHCID 229954245,6-Difluoro-2-(isopropylamino)-1H-benzimidazole

Product 1

HCID 540999855,6-Difluoro-1-(2,3-di-o-acetyl-5-deoxy-beta-d-ribofuranosyl)-n-(1-methylethyl)1h-benzimidazol-2-amineYield 72.7%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent2×

Procedure

5,6-Difluoro-N-(1-methylethyl)1H-benzimidazol-2-amine (0.24 g, 1.1 mmol), N,O-bis(trimethylsilyl) acetamide (Aldrich, 0.30 mL, 1.2 mmol), and acetonitrile (Aldrich Sure Seal, 40 mL) were combined and refluxed under nitrogen for 15 min. The solution was cooled to room temperature and trimethylsilyl triflate (Aldrich, 0.13 mL, 0.7 mmol) was added. After 10 min, 1,2,3-tri-O-acetyl-5-deoxy-D-ribofuranose (0.38 g, 1.5 mmol) dissolved in acetonitrile (Aldrich Sure Seal, 15 mL) was added. The solution was stirred under nitrogen at rt for 4.5 h and then heated in an 80° C. oil bath for 2 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 (anhyd), filtered, and evaporated. The crude residue was purified on a silica gel column (2.5×20 cm, 230-400 mesh) with 95:5 dichloromethane-methanol to give the title compound (0.32 g, 0.8 mmol, 71%); 1H NMR (DMSO-d6) δ7.40-7.46 (m 1H, Ar—H), 7.21-7.28 (m, 1H, Ar—H), 6.74 (d, 1H, NH, J=7.5 Hz), 6.05 (d, 1H, H-1′, J=6.6 Hz), 5.55-5.59 (m, 1H, CH), 5.21-5.25 (m, 1H, CH), 4.00-4.24 (m, 2H, CH), 2.14 (s, 3H, OAc), 2.01 (s, 3H, OAc), 1.49 (d, 3H, 5′-CH3, J=6.3 Hz), 1.20-1.24 (m, 6H, CH3).

Workup

  1. temperaturerefluxed under nitrogen for 15 min
  2. additionwas added
  3. temperatureheated in an 80° C. oil bath for 2 h
  4. extractionextracted with ethyl acetate (3×100 mL)
  5. dry with materialThe organic layers were dried with magnesium sulfate (anhyd)
  6. filtrationfiltered
  7. customevaporated
  8. customThe crude residue was purified on a silica gel column (2.5×20 cm, 230-400 mesh) with 95:5 dichloromethane-methanol

Sources & evidence

ORD record
ord-114996d09f9b49b2af9135ab0fe57d8c
Source dataset
uspto-grants-2002_07
Patent number
US06413938B1

Reaction notes

Loading…