Reaktion #1951038

Reaktionsgleichung

potassium hydroxide

hydroxylamine hydrochloride

5,6-Dichloro-2-bromo-3-cyano-1-(5-O-acetyl-β-D-ribofuranosyl)indole

MeOH CHCl3

→

hydroxylamine

4.140

Ausbeute 41.0%

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

Ausbeute 41.0%

Lösungsmittel

MeOH

hydroxylamine

MeOH

—

crude solution

MeOH

MeOH

MeOH

MeOH H2O

Reaktionsbedingungen

Aufarbeitung

1. 1
   FiltrationThe resulting solids were filtered
2. 2
   Waschenrinsed with cold absolute MeOH (10 mL)
3. 3
   Sonstigethe filtrate used without further purification
4. 4
   workup.STIRRINGstirred at room temperature for 4 days
5. 5
   SonstigeThe solvent was then removed under vacuum
6. 6
   workup.DISSOLUTIONthe residual solid dissolved in brine (40 mL)
7. 7
   ExtraktionThe aqueous suspension was extracted with EtOAc (2×50 mL)
8. 8
   Trocknenthe combined organic extracts dried over MgSO4
9. 9
   Filtrationfiltered
10. 10
    Sonstigeevaporated
11. 11
    Sonstigeto yield a pale yellow solid
12. 12
    workup.ADDITIONFractions containing product
13. 13
    Sonstigeevaporated
14. 14
    Sonstigeto yield a pale yellow solid
15. 15
    workup.ADDITIONFractions containing product
16. 16
    Sonstigeevaporated
17. 17
    Sonstigeto yield a pale yellow solid which
18. 18
    Sonstigewas recrystallized from MeOH/H2O

Vorschrift

A solution of hydroxylamine in absolute MeOH was prepared by adding potassium hydroxide (1.83 g, 33 mmol) to hydroxylamine hydrochloride (2.50 g, 36 mmol) dissolved in absolute MeOH (20 mL) and stirring for 10 min. The resulting solids were filtered and rinsed with cold absolute MeOH (10 mL), and the filtrate used without further purification. 5,6-Dichloro-2-bromo-3-cyano-1-(5-O-acetyl-β-D-ribofuranosyl)indole (4.139, 133 mg, 0.29 mmol) was dissolved in the crude solution of hydroxylamine in MeOH and stirred at room temperature for 4 days. The solvent was then removed under vacuum, and the residual solid dissolved in brine (40 mL). The aqueous suspension was extracted with EtOAc (2×50 mL), and the combined organic extracts dried over MgSO4, filtered and evaporated to yield a pale yellow solid. The solid was dissolved in MeOH (1 mL) and subjected to column chromatography (40×350 mm) on silica gel with 20% MeOH/CHCl3. Fractions containing product were pooled and evaporated to yield a pale yellow solid. The solid 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 pale yellow solid which was recrystallized from MeOH/H2O to yield 54 mg (41%) of 4.140 as a pale yellow powder: mp slow dec >170° C.; Rf0.5 (20% MeOH/CHCl3); 1H-NMR (500 MHz, DMSO-d6): δ 9.66 (s, 1H, D2O exch.), 8.48 (s, 1H), 7.89 (s, 1H), 5.99 (d, 1H), 5.76 (s, 2H, D2O exch.), 5.35 (t, 1H, D2O exch.), 5.31 (d, 1H, D2O exch.), 5.22 (d, 1H, D2O exch.), 4.45 (q, 1H), 4.15 (t, 1H), 3.96 (d, 1H), 3.72 (m, 2H). 13C-NMR (125 MHz, DMSO-d6): δ 146.18, 133.16, 127.04, 124.88, 123.77, 120.74, 115.72, 114.86, 110.61, 90.17, 85.68, 71.21, 69.55, 61.07. HRMS (ES) m/z calcd. for C14H14BrCl2N3O5+H 453.9572, found 453.9570. Anal calcd for C14H14BrCl2N3O5.¼MeOH: C, 36.96; H, 3.26; N, 9.07. Found: C, 37.11; H, 3.22; N, 8.85.

Quelle