反应详情

温度

90 °C

In a flask containing of 2-{1-[4-(4-Methoxy-benzenesulfonyl)-piperazin-1-yl]-ethyl}-3H-quinazolin-4-one (50.0 mg, 0.12 mmol) in DMF was added I-Iodo-2-methylpropane (42.0 mg, 0.24 mmol), K2CO3 (80.0 mg, 0.6 mmol). The mixture was heated at 90° C. for 2 hours with stirring. After cooling down to room temperature, the excess K2CO3 was filtrated; the solution was treated with TFA (0.5 ml) and water (0.1 ml) with stirring at 90° C. for 2 hrs. Purification by HPLC (Gilson-215, 0.035% TFA in acetonitrile and 0.05% water as mobile phase) yielded 3-Isobutyl-2-{1-[4-(4-methoxy-benzenesulfonyl)-piperazin-1-yl]-ethyl}-3H-quinazolin-4-one (Yield 21.0 mg, 37.0%) that was dried under reduced pressure. 1H NMR (400 MHz, DMSO-6): δ 0.98 (d, 3H, J=6.82 Hz), 1.01 (d, 3H, J=6.82 Hz), 1.76 (d, 3H, J=6.82 Hz), 2.08-1.99 (m, 1H), 3.51-3.19 (m, 6H), 3.86-3.75 (m, 2H), 3.93 (s. 3H), 4.16-3.93 (m, 2H), 4.84 (q, 1H, J=12.88, 7.07 Hz), 7.03 (dd, 2H, J=6.82, 2.27 Hz), 7.57 (dt, 1H, J=8.08, 1.01 Hz), 7.67 (dd, 2H, J=6.82, 2.27 Hz), 7.71 (d, 1H, J=8.08, Hz), 7.82 (dt, 1H, 8.59, 1.52 Hz), 8.39 (dd, 1H, J=8.08, 1.52 Hz). MS m/z calc. 484.21, found (ESI); 485.3 (M+1)+. Retention time 2.83 minutes.

1. temperatureAfter cooling down to room temperature
2. filtrationthe excess K2CO3 was filtrated
3. additionthe solution was treated with TFA (0.5 ml) and water (0.1 ml)
4. stirringwith stirring at 90° C. for 2 hrs
5. customPurification by HPLC (Gilson-215, 0.035% TFA in acetonitrile and 0.05% water as mobile phase)