Réaction #1951027

Équation de réaction

2,5,6-Trichloro-3-cyano-1-(β-D-ribofuranosyl)indole

MeOH H2O

→

4.34

Rendement 58.0%

Methyl 2,5,6-Trichloro-1-(β-D-ribofuranosyl)indole-3-formimidate

Rendement 58.0%

Solvants

DMF

MeOH

Conditions de réaction

Traitement

1. 1
   Températurewas cooled to 0 C in an ice bath
2. 2
   AutreHydrogen chloride gas was slowly bubbled through the solution for 2 h
3. 3
   Autrethe reaction vessel was tightly capped
4. 4
   workup.ADDITIONThe acidic solution was diluted with Et2O (20 mL)
5. 5
   Autreevaporated to dryness
6. 6
   Extractionextracted with EtOAc (3×100 mL, with vigorous shaking)
7. 7
   SéchageThe combined organic extracts were dried over MgSO4
8. 8
   Filtrationfiltered
9. 9
   Autreevaporated
10. 10
    Autreto yield a white solid which
11. 11
    workup.ADDITIONFractions containing product
12. 12
    Autreevaporated

Mode opératoire

2,5,6-Trichloro-3-cyano-1-(β-D-ribofuranosyl)indole (4.4, 107 mg, 0.28 mmol) was dissolved in dry MeOH (10 mL) which was cooled to 0 C in an ice bath. Hydrogen chloride gas was slowly bubbled through the solution for 2 h, then the reaction vessel was tightly capped, and the resulting solution was stirred at room temperature for 24 h. The acidic solution was diluted with Et2O (20 mL) and evaporated to dryness. The residual solid was suspended in 10% aqueous NaHCO3 (100 mL) and extracted with EtOAc (3×100 mL, with vigorous shaking). The combined organic extracts were dried over MgSO4, filtered and evaporated to yield a white solid which was dissolved in DMF (0.5 mL) and subjected to column chromatography (40×350 mm) on C18-reverse phase silica gel with 75% MeOH/H2O. Fractions containing product were pooled and evaporated to yield 64 mg (58%) of 4.34 as a white crystalline solid: mp 248-249 C; Rf0.6 (20% MeOH/CHCl3); 1H-NMR (500 MHz, DMSO-d6): δ 8.55 (s, 1H), 8.43 (s, 1H, D2O exch.), 7.96 (s, 1H), 5.98 (d, 1H), 5.39 (d, 1H, D2O exch.), 5.37 (t, 1H, D2O exch.), 5.24 (d, 1H, D2O exch.), 4.41 (q, 1H), 4.14 (s, 1H), 3.98 (d, 1H), 3.85 (s, 3H), 3.71 (m, 2H). 13C-NMR (125 MHz, DMSO-d6): δ 161.40, 132.01, 128.23, 125.67, 124.82, 124.50, 121.32, 115.19, 106.29, 88.73, 86.08, 71.40, 69.50, 60.99, 52.45. HRMS (EI) m/z calcd. for C15H15Cl3N2O5 408.0047, found 408.0043. Anal calcd for C15H15Cl3N2O5: C, 43.98; H, 3.69; N, 6.84. Found: C, 43.97; H, 3.81; N, 6.75.

Source