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

온도

100 °C

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)+.

1. washThe organic layer was washed with water
2. customdried
3. concentrationconcentrated
4. dissolutionThe resulting material was dissolved in 8 mL of ethanol
5. addition0.22 mL of formaldehyde (37% in water), a few drops of 5% sodium hydroxide solution were added
6. temperatureThe mixture was heated at 90° C. for 1 d
7. stirringwith stirring
8. additiondiluted with 10 mL of water and 30 mL of ethyl acetate
9. washThe organic layer was washed with water
10. customdried
11. concentrationconcentrated
12. customThe resulting crude material was purified by silica gel column chromatography

ORD 기록

ord-ec19be825890422d85717bc66627dc0e

출처 데이터셋

uspto-grants-2012_11

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US08309562B2