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

HRID 2227174ノート

反応式

HRID 2227174 の反応式
[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

参加物

7

反応物 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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6342Acetonitrile溶媒2 回

実験手順

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).

後処理

  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

出典と根拠

ORDレコード
ord-114996d09f9b49b2af9135ab0fe57d8c
出典データセット
uspto-grants-2002_07
特許番号
US06413938B1

反応ノート

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