반응 #1951038

반응 방정식

potassium hydroxide

hydroxylamine hydrochloride

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

MeOH CHCl3

→

hydroxylamine

4.140

수율 41.0%

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

수율 41.0%

용매

MeOH

hydroxylamine

MeOH

—

crude solution

MeOH

MeOH

MeOH

MeOH H2O

반응 조건

후처리

1. 1
   여과The resulting solids were filtered
2. 2
   세척rinsed with cold absolute MeOH (10 mL)
3. 3
   기타the filtrate used without further purification
4. 4
   workup.STIRRINGstirred at room temperature for 4 days
5. 5
   기타The solvent was then removed under vacuum
6. 6
   workup.DISSOLUTIONthe residual solid dissolved in brine (40 mL)
7. 7
   추출The aqueous suspension was extracted with EtOAc (2×50 mL)
8. 8
   건조the combined organic extracts dried over MgSO4
9. 9
   여과filtered
10. 10
    기타evaporated
11. 11
    기타to yield a pale yellow solid
12. 12
    workup.ADDITIONFractions containing product
13. 13
    기타evaporated
14. 14
    기타to yield a pale yellow solid
15. 15
    workup.ADDITIONFractions containing product
16. 16
    기타evaporated
17. 17
    기타to yield a pale yellow solid which
18. 18
    기타was recrystallized from MeOH/H2O

실험 절차

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.

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