Hydrochloric Acid → 4-Amino-2-butyl-1-(2-hydroxy-2-methylpropyl)-7-methoxycarbonyl-1H-imidazo[4,5-c]quinoline

Participants

Reaction Conditions

Reaction Steps

To 5-(2-amino-4-methoxycarbonylphenyl)-2-butyl-1-(2-hydroxy-2-methylpropyl)-1H-imidazole-4-carbonitrile S6 (118 mg, ˜90% pure, 0.27 mmol, 1.0 equiv) was added 4 N HCl in dioxane (2.0 mL, 8.0 mmol, 30 equiv) at 25° C. The reaction was heated at reflux 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 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 420 (95 mg, 32% over 2 steps) as an off white solid: 1H NMR (CD3OD, 600 Hz) δ1.02 (t, J=6.6 Hz, 3H), 1.28 (br s, 6H), 1.51 (hex, J=7.8 Hz, 2H), 1.88 (pent, J=7.2 Hz, 2H), 3.13 (t, J=7.2 Hz, 2H), 3.95 (s, 3H), 7.86 (dd, J=8.4, 1.8 Hz, 1H), 8.33 (d, J=1.8 Hz, 1H), 8.37 (d, J=8.4 Hz, 1H); 13C NMR (CD3OD, 150 Hz) δ 12.8, 22.2, 27.2, 29.7, 48.1, 51.3, 54.8, 71.1, 117.9, 118.6, 121.0, 121.3, 127.2, 127.9, 134.0, 143.6, 152.1, 157.3, 167.2; MS (APCI+): calcd C20H27N4O3 [M+H]+ 371.5. found 371.5.

Provenance & Evidence