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

HRID 1876151Notes

Reaction equation

HRID 1876151 reaction equation
Cl.Cl[C:3]1[N:12]=[C:11]([N:13]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)[CH3:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1.[CH3:23][NH2:24].[C:25]([O:28][CH2:29]C)(=O)[CH3:26]>CC(O)C.O>[CH2:25]([O:28][CH2:29][N:24]([CH3:23])[C:3]1[N:12]=[C:11]([N:13]([C:15]2[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=2)[CH3:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[N:4]=1)[CH3:26]

Participants

6

Reactant 3

HCID 6329MethylamineHCID 8857Ethyl AcetateHCID 86639964(2-Chloroquinazolin-4-yl)-(4-methoxyphenyl)-methylamine hydrochloride

Product 1

HCID 59242060N2-Ethoxymethyl-N4-(4-methoxy-phenyl)-N2,N4-dimethyl-quinazoline-2,4-diamineYield 72%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 3776IsopropanolSolvent

Conditions

Temperature
100 °C

Procedure

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)+.

Workup

  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

Sources & evidence

ORD record
ord-ec19be825890422d85717bc66627dc0e
Source dataset
uspto-grants-2012_11
Patent number
US08309562B2

Reaction notes

Loading…