Trimethylsilyl triflate → 2-Chloro-5,6-difluoro-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)benzimidazole

HRID 263877

Reaktionsgleichung

Reaktionsgleichung von HRID 263877
[Cl:1][C:2]1[NH:3][C:4]2[CH:10]=[C:9]([F:11])[C:8]([F: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>C(Cl)CCl.C(Cl)(Cl)Cl>[Cl:1][C:2]1[N:3]([C@@H:17]2[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]2[O:19][C:20](=[O:22])[CH3:21])[C:4]2[CH:10]=[C:9]([F:11])[C:8]([F:12])=[CH:7][C:5]=2[N:6]=1

Komponenten

6

Edukt 3

HCID 65367Trimethylsilyl triflateHCID 830641,2,3,5-Tetraacetyl-beta-D-ribofuranoseHCID 4694162-chloro-5,6-difluoro-1H-benzimidazole

Produkt 1

HCID 106232802-Chloro-5,6-difluoro-1-(2,3,5-tri-O-acetyl-beta-D-ribofuranosyl)benzimidazole

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 111,2-DichloroethaneLösungsmittelHCID 6212ChloroformLösungsmittel

Reaktionsbedingungen

Temperatur
75 °C

Versuchsvorschrift

To a suspension of 0.943 g (5 mmole) of 12 in 25 mL of ClCH2CH2Cl, was added 1.25 mL (5 mmole) of BSA at 75° C. The reaction mixture was stirred at 75° C. for 30 min. To this solution, was added 1.75 g (5.5 mmole) of 1,2,3,5-tetra-O-acetyl-β-D-ribofuranose and 1.07 mL (5.5 mmole) of TMSOTf. Stirring was continued at 75° C. for 30 min. The reaction mixture was cooled to room temperature, diluted with 100 mL of CHCl3, and extracted with sat. NaHCO3 solution (100 mL×2) and sat. NaCl solution (100 mL). The CHCl3 phase was dried (Na2SO4) and evaporated. The residue was chromatographed on a silica column (3×25 cm, eluted successively with 0.5%, 1% MeOH/CHCl3). Evaporation of the appropriate fractions and recrystallization of the residue from MeOH gave 1.257 g (3 crops, 56%) of 64 as crystalline needles. MP 90°-91° C.; MS m/e 446.0694 (5%, M+ =446.0692); 1H NMR (DMSO-d6) d 7.93 (dd, 1, 7-H, 3JF-H =10.5 Hz, 4JF-H =7.5 Hz), 7.82 (dd, 1, 4-H, 3JF-H =10.5 Hz, 4JF-H =7.5 Hz), 6.23 (d, 1, 1'-H, J1'-2' =7.0 Hz), 5.55 (t, 1, 2'-H, J2'-3' =7.0 Hz), 5.44 (m, 1, 3'-H, J3-4 =4.5 Hz), 4.45 (m, 3, 4'-H and 5'-H), 2.13, 2.10, 2.02 (3×s, 9, 3×Ac); 13C NMR (DMSO-d6) d 169.95, 169.50, 169.18 (3×OCOCH3), 148.76, 148.62, 146.10, 145.93 (C5 and C6, 1JF-C =242 Hz), 140.16 (C2), 137.01 (C3a, 3JF-C =12 Hz), 128.54 (C7a, 3JF-C =12 Hz), 107.31, 107.09 (C4, JF-C =20 Hz), 100.93, 100.66 (C7, JF-C =24 Hz), 86.89 (Cl'), 79.41 (C4'), 70.40 (C2'), 68.62 (C3'), 62.67 (C5'), 20.43, 20.28, 20.00 (3×OCOCH3).

Aufarbeitung

  1. additionwas added 1.25 mL (5 mmole) of BSA at 75° C
  2. stirringStirring
  3. waitwas continued at 75° C. for 30 min
  4. temperatureThe reaction mixture was cooled to room temperature
  5. extractionextracted with sat. NaHCO3 solution (100 mL×2) and sat. NaCl solution (100 mL)
  6. dry with materialThe CHCl3 phase was dried (Na2SO4)
  7. customevaporated
  8. customThe residue was chromatographed on a silica column (3×25 cm
  9. washeluted successively with 0.5%, 1% MeOH/CHCl3)
  10. customEvaporation of the appropriate fractions and recrystallization of the residue from MeOH

Quellen und Nachweise

ORD-Eintrag
ord-88da0c8a86ce4168ae82b3a174d62bec
Quelldatensatz
uspto-grants-1997_07
Patentnummer
US05646125

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