反应详情

温度

20 °C

A stirred mixture of ethyl 3-(4-acryloyl-1-{[3-methoxy-4-(3-o-tolyl-ureido)-phenyl]-acetyl}-1,2,3,4-tetrahydro-quinoxalin-6-yl)-propanoate (283 mg, Reference Example 22) and methylamine (115 μl) in ethanol (5 ml) was heated at reflux for 8 hours, then treated with a further aliquot of methylamine (50 μl) and then heated at reflux for a further 2 hours. The reaction mixture was cooled to 20° C., then diluted with ethyl acetate, then treated with hydrochloric acid (50 ml, 0.1M) and separated. The ethyl acetate phase was washed with saturated aqueous sodium bicarbonate (10 ml), then washed three times with water (10 ml), then dried over magnesium sulfate and then evaporated under reduced pressure. The aqueous phase from above was extracted three times with dichloromethane (50 ml). The dichloromethane extracts were combined with the above ethyl acetate residue, dried over magnesium sulfate and then evaporated under reduced pressure. The crude residue (331 mg) was subjected to flash chromatography on silica (30 g, 0.040-0.063 mm particle size) eluting with a mixture of dichloromethane and methanol (99:1 to 96:4, v/v) to give the title compound as a white foam (275 mg). 1H NMR 400 MHz, (CD3)2SO, at a temperature of 383° K.]: δ1.20 (t, J=7 Hz, 3H); 2.19 (s, 6H); 2.28 (s, 3H); from 2.55 to 2.70 (m, 6H); from 2.75 to 3.00 (m, 2H); from 3.80 to 3.90 (m, 2H); 3.83 (s, 2H); 3.86 (s, 3H); 3.90 (m, 2H); 4.11(q, J=7 Hz, 2H); 6.67 (broad d, J=8 Hz, 1H); 6.81 (broad s, 1H); 6.99 (broad t, J=7.5 Hz, 1H); from 7.05 to 7.25 (m, 3H); 7.42 (broad s, 1H); 7.56 (d, J=8.5 Hz, 1H); 7.69 (broad d, J=8 Hz, 1H); 7.98 (d, J=8.5 Hz, 1H); 8.17 (broad s, 1H); 8.25 (broad s, 1H). MS (CI): 630 (MH+).

1. temperaturewas heated
2. temperatureat reflux for 8 hours
3. temperatureheated
4. temperatureat reflux for a further 2 hours
5. customseparated
6. washThe ethyl acetate phase was washed with saturated aqueous sodium bicarbonate (10 ml)
7. washwashed three times with water (10 ml)
8. dry with materialdried over magnesium sulfate
9. customevaporated under reduced pressure
10. extractionThe aqueous phase from above was extracted three times with dichloromethane (50 ml)
11. dry with materialdried over magnesium sulfate
12. customevaporated under reduced pressure
13. washeluting with a mixture of dichloromethane and methanol (99:1 to 96:4, v/v)