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

HRID 2227174노트

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HRID 2227174 반응식
[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

참가 물질

7

반응물 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

생성물 1

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

시약·촉매·용매 1

HCID 6342Acetonitrile용매2회

실험 절차

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).

후처리

  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

출처 및 근거

ORD 기록
ord-114996d09f9b49b2af9135ab0fe57d8c
출처 데이터셋
uspto-grants-2002_07
특허 번호
US06413938B1

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