Reaction #1951018

Reaction equation

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

ethylamine

MeOH CHCl3

MeOH H2O

→

4.18

Yield 43.0%

5,6-Dichloro-2-methylamino-3-formyl-1-(β-D-ribofuranosyl)indole

Yield 43.0%

Solvents

MeOH

MeOH

ethanol

Conditions

Workup

1. 1
   OtherThe solvent was then evaporated to approx 1 mL
2. 2
   workup.ADDITIONdiluted with EtOAc (50 mL)
3. 3
   WashThe suspension was washed with H2O (20 mL) and brine (50 mL)
4. 4
   Dryingdried over MgSO4
5. 5
   Filtrationfiltered
6. 6
   Otherevaporated
7. 7
   Otherto yield a yellow residue
8. 8
   workup.ADDITIONFractions containing product
9. 9
   Otherevaporated
10. 10
    Otherto yield a clear viscous residue which
11. 11
    workup.ADDITIONFractions containing product
12. 12
    Otherevaporated
13. 13
    Otherto yield a white solid which
14. 14
    Otherwas recrystallized from MeOH/H2O

Procedure

2,5,6-Trichloro-3-formyl-1-(β-D-ribofuranosyl)indole (4.3, 125 mg, 0.33 mmol) was dissolved in 33% ethylamine solution in ethanol (10 mL), and the resulting solution was stirred at room temperature for 30 min. The solvent was then evaporated to approx 1 mL, and diluted with EtOAc (50 mL). The suspension was washed with H2O (20 mL) and brine (50 mL), then dried over MgSO4, filtered and evaporated to yield a yellow residue. The residue 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 clear viscous residue 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 white solid which was recrystallized from MeOH/H2O to yield 56 mg (43%) of 4.18 as a white microcrystalline solid: mp 241-242 C; Rf0.5 (20% MeOH/CHCl3); 1H-NMR (500 MHz, DMSO-d6): δ 9.98 (s, 1H), 8.24 (s, 1H), 7.97 (q, 1H, D2O exch.), 7.69 (s, 1H), 5.93 (t, 1H, D2O exch.), 5.91 (d, 1H), 5.34 (d, 1H, D2O exch.), 5.32 (d, 1H, D2O exch.), 4.34 (q, 1H), 4.09 (t, 1H), 4.05 (s, 1H), 3.76-3.67 (m, 2H), 3.12 (d, 3H). 13C-NMR (125 MHz, DMSO-d6): δ 181.72, 154.48, 133.66, 127.05, 123.71, 122.72, 119.70, 110.91, 100.20, 88.56, 86.10, 70.78, 70.30, 60.80, 33.45. HRMS (ES) m/z calcd. for C15H16Cl2N2O5+H 375.0514, found 375.0511. Anal calcd for C15H16Cl2N2O5 ¼H2O: C, 47.45; H, 4.38; N, 7.38. Found: C, 47.53; H, 4.59; N, 7.26.

Source