Hydrochloric Acid → 4-Amino-1-isobutyl-7-methoxycarbonyl-1H-imidazo[4,5-c]-quinoline

Participants

Reaction Conditions

Reaction Steps

To 5-(2-amino-4-methoxycarbonylphenyl)-1-isobutyl-1H-imidazole-4-carbonitrile S12 (150 mg, 0.50 mmol, 1.0 equiv) was added 4 N HCl in dioxane (2.0 mL, 8.0 mmol, 16 equiv). The reaction was heated at reflux condition for 15 h then cooled to 25° C. The reaction was concentrated in vacuo and partitioned between 1:9 MeOH/EtOAc (50 mL) and saturated aqueous NaHCO3 solution (10 mL). The aqueous layer was extracted with 1:9 MeOH/EtOAc (3×10 mL). The combined organic layers were washed with saturated aqueous NaCl, dried (MgSO4), and concentrated in vacuo. Purification by flash column chromatography on silica gel (CH2Cl2-1/9 MeOH/CH2Cl2, gradient) afforded the title compound 412 (132 mg, 88%) as an off white solid: 1H NMR (CD3OD, 600 Hz) δ 1.01 (d, J=6.6 Hz, 6H), 2.26 (non, J=7.2 Hz, 1H), 3.96 (s, 3H), 4.43 (d, J=7.8 Hz, 2H), 7.89 (dd, J=7.8, 1.8 Hz, 1H), 8.05 (d, J=7.8 Hz, 1H), 8.19 (s, 1H), 8.32 (d, J=1.8 Hz, 1H); 13C NMR (CD3OD, 150 Hz) δ 18.4, 28.7, 51.4, 54.2, 117.9, 120.5, 121.8, 127.1, 128.6, 128.8, 132.1, 143.6, 144.3, 152.5, 167.0; MS (APCI+): calcd C16H19N4O2 [M+H]+ 299.2. found 299.2.

Provenance & Evidence