Carbonic acid-guanidine (1:1) → 8-Isopropyl-7-methoxy-quinazolin-2-ylamine

Participants

Reaction Conditions

Reaction Steps

A mixture of 6-hydroxymethylene-2-isopropyl-3-methoxy-cyclohex-2-enone (3.5 g) and guanidine carbonate (7 g) in DMF (40 mL) was heated at 150° C. for 4 hours. The solvent was removed under reduced pressure, then ice-cold water was added to the residue. The product was extracted with ethyl acetate (3×50 mL). The combined organic layers were washed with water, then brine, and dried over anhydrous sodium sulfate. Solvent was removed under reduced pressure to give a crude mixture of dihydroquinazolines (4 g). The dihydroquinazolines were aromatized to the title compound by heating in nitrobenzene (70 mL) at 150° C. in the presence of 10% Pd-C (400 mg) for 3 days. The catalyst was removed by filtration, then the filtrate was concentrated, and the resulting product was purified on a column of silica gel (Hex:EtOAc) to give the title compound as an off-white solid (2.1 g, 54.2%). mp 112–113° C.; 1H NMR (CDCl3): δ 1.38 (d, 6H, 2×CH3), 3.95 (s, 3H, OCH3), 4.24 (m, 1H, CH), 5.0 (br s, 2H, NH2), 7.02 (d, 1H, Ar-H, J=9 Hz), 7.55 (d, 1H, Ar-H, J=9 Hz), 8.87 (s, 1H, Ar-H); MS m/z 218.05, C12H15N3O (M++1).

Provenance & Evidence