Inhibitory Activity Against West Nile Virus
1783
was allowed to stir at room temperature for 2 h. It was then filtered and
evaporated under reduced pressure. The residue was purified by flash
chromatography on a silica gel column using a mixture of dichloromethane:
methanol (99:1) as an eluant. Appropriate fractions were pooled and
evaporated under reduced pressure to obtain a gummy residue. Yield: 2.71
g, 46%; Rf 0.40 (chloroform:methanol, 50:2); IR 1716, 1611, 1446, 1267,
1
1177, 1096 cm−1; H NMR (CDCl3, 300 MHz) δ 7.93–7.87 (m, 4H, Ar-H),
7.81 (s, 1H, imidazole CH), 7.26–7.20 (m, 4H, Ar-H), 6.69 (dd, J = 5.4 and
5.7 Hz ,1H, 1ꢁ-H,), 6.37 (s, 1H, CH(OEt)2), 5.59 (m, 1H, 3ꢁ-H), 4.73 (m, 2H,
4ꢁ, 5ꢁ-H), 4.68 (m, 1H, 5ꢁꢁ-H), 4.36 (q, J = 7.2 Hz, 2H, ester CH2), 3.86–3.48
(m, 4H, 2 CH2, acetal CH2), 2.90–2.87 (m, 1H, 2ꢁ-H), 2.50–2.42 (m, 2 H,
2ꢁꢁ-H), 2.41 (s, 3H, Ar-CH3), 2.38 (s, 3H, Ar-CH3), 1.38 (t, 3H, ester CH3),
1.22–1.14 (m, 6H, 2 acetal CH3; Mass (FAB), m/z 595.60 (MH+); Anal. Calcd
for C32H38N2O9: C, 64.63; H, 6.44; N, 4.71. Found: C, 64.64, H, 6.22, N, 4.70.
Ethyl 5-Formyl-1-[(2 -deoxy-3 ,5 -di-O-p-toluoyl)-β-D-erythropentofura-
nosyl]imidazole-4-carboxylate (5). A solution of ester-acetal 4 (2.37 g, 4
mmol) in 80% aqueous acetic acid (10 mL) was stirred at room tempera-
ture for 22 h. The reaction mixture was poured into ice water and the pre-
cipitated solid was extracted with dichloromethane. The organic extract was
dried over anhydrous sodium sulfate. The residue obtained after removal of
the solvent was purified by silica gel flash chromatography using a mixture
of dichloromethane-methanol (98:2) as the eluant. Appropriate fractions
were pooled and evaporated under reduced pressure. The residue was trit-
urated with methanol to get pure ester-aldhehyde 5. Yield 1.15 g, 55%; mp
125–127◦C; Rf = 0.44 (dichloromethane:methanol, 99:1); IR 1723, 1651,
1
1611, 1537, 1485, 1265, 1084 cm−1; H NMR (CDCl3, 400 MHz) δ 10.42
(s, 1H, CHO), 8.03 (s, 1H, imidazole CH), 7.89 (d, J = 6.8 Hz, 2H, Ar-H),
7.76 (d, J = 6.68 Hz, 2H, Ar-H), 7.20 (d, J = 8.72 Hz, 2H, Ar-H), 7.14 (d,
J = 7.36 Hz, 2H, Ar-H), 6.67 (t, J = 6.4 Hz, 1H, 1ꢁ-H), 5.51 (s, 1H, 3ꢁ-H),
4.69–4.59 (m, 3H, 4ꢁ, 5ꢁ, and 5ꢁꢁ-H), 4.40 (q, J = 6.88 Hz, 2H, ester CH2),
3.01–2.96 (m, 1H, 2ꢁ-H), 2.36 (s, 3H, Ar-CH3), 2.32 (s, 3H, Ar-CH3), 2.28–
2.23 (m, 1 H, 2ꢁꢁ-H), 1.36 (t, J = 6.88 Hz, 3H, ester CH3); 13C NMR (CDCl3,
100 MHz) 182.84, 166.21, 166.07, 161.89, 144.68, 144.45, 141.98, 138.27,
131.45, 129.94, 129.68, 129.50, 129.40, 126.43, 126.33, 88.53, 83.91, 74.53,
63.81, 61.89, 40.97, 21.85, 21.78, 14.37. Mass Spectrum (FAB) m/z 521.50
(MH+); Anal. Calcd for C28H28N2O8: C, 64.61; H, 5.42; N, 5.38. Found: C,
64.50, H, 5.43, N, 5.35.
5-(4,6-Diamino-2,5-dihydro-1,3,5-triazin-2-yl)-1-(2 -deoxy-β-D-erythro-
pentofuranosyl)imidazole-4-carboxamide (7). Method A: Guanidine hydro-
chloride (0.38 g, 0.006 mol) was neutralized with a solution of sodium (0.32
g, 0.02 mol) in anhydrous ethanol (10 mL) at ice cold temperature. This
guanidine solution was added to the aldehyde 5 or 2 (0.0015 mol) in anhy-