Réaction #56632

Équation de réaction

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

DMF

hydroxylamine hydrochloride

potassium hydroxide

→

4.33

Rendement 70.4%

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

Rendement 70.4%

Solvants

brine

water

MeOH

MeOH H2O

MeOH

Conditions de réaction

Traitement

1. 1
   Extractionthe resulting aqueous suspension extracted with EtOAc (2×100 mL)
2. 2
   SéchageThe combined organic extracts were dried over MgSO4
3. 3
   Filtrationfiltered
4. 4
   Autreevaporated
5. 5
   Autreto yield a clear oil which
6. 6
   workup.ADDITIONFractions containing product
7. 7
   Autreevaporated
8. 8
   Autreto yield a light tan solid which
9. 9
   Autrewas recrystallized from MeOH/H2O

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 (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.

Source