Reacción #1951027

Ecuación de reacción

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

MeOH H2O

→

4.34

Rendimiento 58.0%

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

Rendimiento 58.0%

Disolventes

DMF

MeOH

Condiciones de reacción

Tratamiento posterior

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

Procedimiento

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.

Fuente