N,N-Dimethylaniline → 6-Bromo-4-chloro-2-(2-methoxyphenyl)quinazoline

Participants

Reaction Steps

6-Bromo-2-(2-methoxyphenyl)quinazolin-4(3H)-one (0.31 g, 0.94 mmol), POCl3 (86 μL, 0.94 mmol), and N,N-dimethylaniline (180 μL, 1.4 mmol) were refluxed in dry toluene for 3 h. Additional POCl3 (0.94 mmol) was added, and the reaction was refluxed for one additional hour. The reaction mixture was diluted with EtOAc and water. The aqueous layer was made basic with NaHCO3, and the layers were separated. After the organic phase was washed with water, dried over Na2SO4 and concentrated, purification via silica gel chromatography using 0-50% EtOAc in 1:1 hexanes:CH2Cl2 gave 6-bromo-4-chloro-2-(2-methoxyphenyl)quinazoline as a yellow solid (144 mg, 44%). 1H NMR (400 MHz, CDCl3) δ 8.45-8.45 (m, 1H), 8.04-7.99 (m, 2H), 7.82 (dd, J=7.6, 1.7 Hz, 1H), 7.49-7.45 (m, 1H), 7.12-7.08 (m, 1H), 7.06 (d, J=8.4 Hz, 1H), 3.90 (s, 3H); LC/MS: m/z 350.9 (M+H)+ at 3.56 min (10%-99% CH3CN (0.035% TFA)/H2O (0.05% TFA)).

Provenance & Evidence