Reaction #1951038

Reaction equation

potassium hydroxide

hydroxylamine hydrochloride

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

MeOH CHCl3

→

hydroxylamine

4.140

Yield 41.0%

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

Yield 41.0%

Solvents

MeOH

hydroxylamine

MeOH

—

crude solution

MeOH

MeOH

MeOH

MeOH H2O

Conditions

Workup

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

Procedure

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.

Source