反应详情

温度

90 °C

To a solution of 1,2-dichloroethane (20 mL) and tert-butylalcohol was added 4-chloro-6,7-bis-(2-methoxy-ethoxy)-quinazoline and 4-(4-amino-2-methyl-phenoxy)-piperidine-1-carboxylic acid tert-butyl ester. The reaction was heated at 90° C. for 1 hour. The reaction was cooled to room temperature then hydrogen chloride gas was bubbled in for 10 minutes. Ethyl acetate (30 mL) was added then cooled to 0° C. for 30 minutes. The solids were filtered and rinsed with ethyl acetate. Light yellow solids were further dried in a vacuum oven yielding the mono hydrochloride salt (1.91 g, 99%). 1H NMR (400 MHz, DMSO-d6) δ 11.42(s, 1H), 9.15(bs, 1H), 9.05(bs, 1H), 8.72(s, 1H), 8.40(s, 1H), 7.41(d, J=17.03 Hz, 2H), 7.40(d, J=2.49 Hz, 1H), 7.08(d, J=8.30 Hz, 1H), 4.67(m, 1H), 4.34(t, J=9.14, 4.98 Hz, 2H), 4.27(t, J=8.72, 4.56 Hz, 2H), 3.74(t, J=5.81, 3.32, 4H), 3.16(m, 2H), 3.07(m, 2H), 2.18(s, 3H), 2.10(m, 2H), LRMS (M+): 483.3, (M−): 481.3).

1. temperatureThe reaction was cooled to room temperature
2. customhydrogen chloride gas was bubbled in for 10 minutes
3. additionEthyl acetate (30 mL) was added
4. temperaturethen cooled to 0° C. for 30 minutes
5. filtrationThe solids were filtered
6. washrinsed with ethyl acetate
7. customLight yellow solids were further dried in a vacuum oven