Trimethylsilyl triflate → 1-(2,3,5-Tri-O-acetyl-beta-D-ribofuranosyl)-2,4,6-trichlorobenzimidazole

HRID 6348

Reaktionsgleichung

Reaktionsgleichung von HRID 6348
[Cl:1][C:2]1[NH:3][C:4]2[C:10]([Cl:11])=[CH:9][C:8]([Cl:12])=[CH:7][C:5]=2[N:6]=1.C(O[C@@H:17]1[O:29][C@H:28]([CH2:30][O:31][C:32](=[O:34])[CH3:33])[C@@H:23]([O:24][C:25](=[O:27])[CH3:26])[C@H:18]1[O:19][C:20](=[O:22])[CH3:21])(=O)C.[Si](OS(C(F)(F)F)(=O)=O)(C)(C)C>CC#N.CCOC(C)=O>[C:20]([O:19][C@@H:18]1[C@H:23]([O:24][C:25](=[O:27])[CH3:26])[C@@H:28]([CH2:30][O:31][C:32](=[O:34])[CH3:33])[O:29][C@H:17]1[N:6]1[C:5]2[CH:7]=[C:8]([Cl:12])[CH:9]=[C:10]([Cl:11])[C:4]=2[N:3]=[C:2]1[Cl:1])(=[O:22])[CH3:21]

Komponenten

6

Edukt 3

HCID 65367Trimethylsilyl triflateHCID 830641,2,3,5-Tetraacetyl-beta-D-ribofuranoseHCID 178418601HCID 178418601, Verbindung

Produkt 1

HCID 106960641-(2,3,5-Tri-O-acetyl-beta-D-ribofuranosyl)-2,4,6-trichlorobenzimidazoleAusbeute 71,3 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6342AcetonitrileLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

To a suspension of 1.362 g (6.15 mmol) of 2,4,6-trichlorobenzimidazole in 31 mL of MeCN, was added 1.52 mL (6.15 mmol) of BSA. The reaction mixture was stirred at 80° C. for 15 min to give a clear solution. This solution was treated with 2.153 g (6.675 mmol) of 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose and 1.426 mL (7.380 mmol) of TMSOTf at 80° C. for 1 h. The reaction mixture was cooled and diluted with EtOAc (150 mL). The EtOAc solution was washed with sat. NaHCO3 solution (150 mL×2), sat. NaCl solution (150 mL), dried (Na2SO4), and evaporated. The residue was coevaporated with MeOH and then suspended in 50 mL of hot MeOH. The suspension was cooled, filtered, and the solid product was washed with MeOH to give 2.103 g of 80 as white crystals (This product showed one spot on TLC). The mother liquor was evaporated and the residue was chromatographed on a silica column (2.5×20 cm, eluted with CHCl3 and 0.5% MeOH/CHCl3). Evaporation of fractions 20-24 (20 mL per fraction) and recrystallization from MeOH gave an additional 0.258 g of 80 as white crystals. The total yield of 80 was 2.361 g (80%). MP: 198°-200° C. MS: (El) m/e 480.0069 (4%, for C18H1735ClN237ClN2O7 : M+ =480.0072). 1 H NMR (DMSO-d6): δ7.89 (d, 1, 7-H, J7-5 =2.0 Hz), 7.58 (d, 1, 5-H), 6.26 (d, 1, 1'-H, J1'-2' =7.0 Hz), 5.54 (t, 1, 2'-H, J2'-3' =7.0 Hz), 5.44 (dd, 1, 3'-H, J3'-4' =4.5 Hz), 4.48, 4.38 (2×m, 3, 4'-H and 5'-H), 2.14, 2.02 (2×s, 9, 3×Ac). 13H NMR (DMSO-d6): δ169.84, 169.37, 169.09 (3×COCH3), 140.91 (C2), 137.39 (C3a), 134.14 (C7a), 128.47 (C6), 123.66 (C4), 123.25 (C5), 111.06 (C7), 86.91 (C1'), 79.58 (C4'), 70.54 (C2'), 68.55 (C3'), 62.47 (C5'), 20.48, 20.19, 19.90 (3×COCH3). Anal. Calcd. for C18H17Cl3N2O7 : C, 45.07; H, 3.57; N, 5.84. Found: C, 45.08; H, 3.62; N, 5.87.

Aufarbeitung

  1. additionwas added 1.52 mL (6.15 mmol) of BSA
  2. customto give a clear solution
  3. temperatureThe reaction mixture was cooled
  4. washThe EtOAc solution was washed with sat. NaHCO3 solution (150 mL×2), sat. NaCl solution (150 mL)
  5. dry with materialdried (Na2SO4)
  6. customevaporated
  7. temperatureThe suspension was cooled
  8. filtrationfiltered
  9. washthe solid product was washed with MeOH

Quellen und Nachweise

ORD-Eintrag
ord-9fe5815b9f6446a0bb918644fe3631c0
Quelldatensatz
uspto-grants-1993_09
Patentnummer
US05248672

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