反应详情

温度

120 °C

4-(Piperidin-4-ylamino)benzoic acid tert-butyl ester (49) (0.15 g, 0.54 mmol), was added to a solution of 2-chloro-6,7-dimethoxy-quinazoline (0.07 g, 0.31 mmol) in n-pentanol (5 mL) at 25° C. The mixture was stirred at 120° C. for 12 h. The reaction mixture was then cooled to room temperature and concentrated to a brown solid residue. Purification of the residue by flash column chromatography (gradient elution 30 to 40% EtOAc/hexanes) provided the title compound (0.03 g, 18%): TLC (Rf =0.50; 50% EtOAc/hexanes); 1H NMR (DMSO) δ 8.93 (s, 1H), 7.62 (d, 2H, J=8.7), 7.20 (s, 1H), 6.91 (s, 1H), 6.61 (d, 2H, J=8.8), 6.37 (d, 1H, J=7.9), 4.67 (d, 2H, J=13.2), 3.89 (s, 3H), 3.82 (s, 3H), 3.65 (m, 1H), 3.16 (t, 2H, J=11.5), 1.97 (d, 2H, J=10.4), 1.48 (s, 9H), 1.36 (m, 2H); 13C NMR (DMSO) δ 165.3, 158.6, 158.4, 156.1, 151.5, 149.3, 146.5, 130.9, 117.5, 113.9, 111.1, 105.4, 104.4, 78.9, 55.8, 55.6, 48.9, 42.5, 31.2, 28.0; HRMS (FAB) m/z 465.2503 (M+H)+ (C26H32N4O4 requires 465.2494); Anal. (C26H32N4O4 ·1/4HCl·1/4H2O) C, H, N.

1. temperatureThe reaction mixture was then cooled to room temperature
2. concentrationconcentrated to a brown solid residue
3. customPurification of the residue
4. washby flash column chromatography (gradient elution 30 to 40% EtOAc/hexanes)