Reaction #1951019

Reaction equation

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

MeOH CHCl3

MeOH H2O

→

4.19

Yield 83.8%

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

Yield 83.8%

Solvents

MeOH

isopropylamine

MeOH

Conditions

Workup

1. 1
   OtherThe solvent was then evaporated
2. 2
   workup.DISSOLUTIONthe residue dissolved in 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 syrup
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, 171 mg, 0.45 mmol) was dissolved in isopropylamine (10 mL), and the resulting solution was stirred at room temperature for 16 h. The solvent was then evaporated and the residue dissolved in 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 syrup. 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 76 mg (42%) of 4.19 as a white microcrystalline solid: mp 143-145 C; Rf0.6 (20% MeOH/CHCl3); 1H-NMR (500 MHz, DMSO-d6): δ 9.90 (s, 1H), 8.19 (s, 1H), 7.73 (s, 1H), 7.26 (d, 1H, D2O exch.), 5.87 (d, 1H, D2O exch.), 5.68 (s, 1H, D2O exch.), 5.37 (d, 1H, D2O exch.), 5.29 (d, 1H), 4.35 (q, 1H), 4.10 (s, 1H), 4.07 (m, 1H), 4.00 (s, 1H), 3.70 (m, 2H), 1.28 (s, 6H). 13C-NMR (125 MHz, DMSO-d6): δ 181.55, 153.38, 133.43, 127.15, 123.96, 122.70, 119.37, 111.47, 99.04, 88.51, 85.88, 70.76, 69.80, 60.69, 48.99, 22.77, 22.55. HRMS (ES) m/z calcd. for C17H20Cl2N2O5.Na.CH3OH 457.0909, found 457.0912. Anal calcd for C17H20Cl2N2O5.¼H2O: C, 49.53; H, 5.13; N, 6.80. Found: C, 49.83; H, 5.04; N, 6.51.

Source