Reacción #56632

Ecuación de reacción

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

DMF

hydroxylamine hydrochloride

potassium hydroxide

→

4.33

Rendimiento 70.4%

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

Rendimiento 70.4%

Disolventes

brine

water

MeOH

MeOH H2O

MeOH

Condiciones de reacción

Tratamiento posterior

1. 1
   Extracciónthe resulting aqueous suspension extracted with EtOAc (2×100 mL)
2. 2
   SecadoThe combined organic extracts were dried over MgSO4
3. 3
   Filtraciónfiltered
4. 4
   Otroevaporated
5. 5
   Otroto yield a clear oil which
6. 6
   workup.ADDITIONFractions containing product
7. 7
   Otroevaporated
8. 8
   Otroto yield a light tan solid which
9. 9
   Otrowas recrystallized from MeOH/H2O

Procedimiento

2,5,6-Trichloro-3-cyano-1-(β-D-ribofuranosyl)indole (4.4, 107 mg, 0.28 mmol) was dissolved in dry MeOH (5 mL) and dry DMF (1 mL) to which were added hydroxylamine hydrochloride (0.50 g, 7.2 mmol) and potassium hydroxide (0.39 g, 7.0 mmol). The resulting suspension was stirred at room temperature for 16 h, then poured into brine (25 mL) and water (25 mL), and the resulting aqueous suspension extracted with EtOAc (2×100 mL). The combined organic extracts were dried over MgSO4, filtered and evaporated to yield a clear oil which was dissolved in MeOH (1 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 a light tan solid which was recrystallized from MeOH/H2O to yield 81 mg (70%) of 4.33 as a light tan solid: mp dec >150 C; Rf 0.4 (20% MeOH/CHCl3); 1H-NMR (500 MHz, DMSO-d6): δ 9.71 (s, 1H, D2O exch.), 8.47 (s, 1H), 7.97 (s, 1H), 5.95 (d, 1H), 5.78 (s, 2H, D2O exch.), 5.36-5.33 (m, 2H, D2O exch.), 5.23 (d, 1H, D2O exch.), 4.44 (q, 1H), 4.14 (m, 1H), 3.96 (d, 1H), 3.71 (m, 2H). 13C-NMR (125 MHz, DMSO-d6): δ 145.92, 132.24, 125.86, 125.78, 125.10, 123.92, 121.27, 114.85, 107.15, 88.61, 85.77, 71.24, 69.59, 61.09. HRMS (EI) m/z calcd. for C14H14Cl3N3O5 408.9999, found 408.9999. Anal calcd for C14H14Cl3N3O5: C, 40.95; H, 3.44; N, 10.23. Found: C, 40.89; H, 3.61; N, 10.08.

Fuente