Methylamine → N2-Ethoxymethyl-N4-(4-methoxy-phenyl)-N2,N4-dimethyl-quinazoline-2,4-diamine

Participants

Reaction Conditions

Reaction Steps

To a solution of (2-chloroquinazolin-4-yl)-(4-methoxyphenyl)-methylamine hydrochloride (0.50 g, 1.50 mmol) in 10 mL of 2-propanol was added 2.0 M solution of methylamine (3.0 mL). The mixture was heated at 100° C. overnight with stirring. The solution was diluted with 20 mL of water and 50 mL of ethyl acetate. The organic layer was washed with water, then dried and concentrated. The resulting material was dissolved in 8 mL of ethanol and then 0.22 mL of formaldehyde (37% in water), a few drops of 5% sodium hydroxide solution were added. The mixture was heated at 90° C. for 1 d with stirring, and then diluted with 10 mL of water and 30 mL of ethyl acetate. The organic layer was washed with water, then dried and concentrated. The resulting crude material was purified by silica gel column chromatography to give the title compound (0.38 mg, 72%). 1H NMR (CDCl3, 400 MHz) δ 7.22 (d, 1H, J=8.4 Hz), 7.18 (t, 1H, J=6.8 Hz), 7.09 (d, 2H, J=8.8 Hz), 6.98 (d, 2H, J=8.8 Hz), 6.92 (d, 1H, J=8.4 Hz), 6.67 (t, 1H, J=6.8 Hz), 5.30 (s, 2H), 3.90 (s, 3H), 3.57 (q, 2H, J=6.8 Hz), 3.49 (s, 3H), 3.22 (s, 3H), 1.17 (t, 3H, J=6.8 Hz); ESI-MS m/z 353 (M+H)+.

Provenance & Evidence