反应详情

温度

80 °C

Morpholine (196 mg, 2.25 mmol) was added to Acetic acid (1 mL) and the mixture vigorously shaken for 5 min. The resulting mixture was treated with 37% aq formaldehyde (67 mg, 2.24 mmol) and stirred until homogeneous. The resulting solution was treated with a solution of 1-[4-(4-amino-6-methylpyrrolo[2,1-f][1,2,4]triazin-5-yl)-2-fluorophenyl]-3-[4-(trifluoromethyl)pyridin-2-yl]urea in 2 mL AcOH and the mixture heated at 80° C. for 14 h. The reaction was diluted with EtOAc (50 mL) and washed with sodium carbonate solution. The organic layer was dried with sodium sulfate and concentrated under vacuum. The resulting solid was taken up in 1 mL MeOH with the aid of TFA (50 uL). Purification by preparative RP-HPLC provided the desired product (41.1 mg, 34%) as a white solid. 1H-NMR (DMSO-d6) δ 10.25 (s, 1H), 10.19 (bs, 1H), 9.98 (bs, 1H), 8.63 (d, 1H, J=5 Hz), 8.36-8.44 (m, 1H), 8.11 (s, 1H), 8.09 (s, 1 H), 7.43-7.50 (m, 1H), 7.38 (dd, 1H, J=12, 2 Hz), 7.24 (dd, 1H, J=8, 1 Hz), 4.78 (s, 2H), 3.97-4.08 (m, 2H), 3.68-3.81 (m, 1H), 3.40-3.55 (m, 2H), 3.23-3.45 (m, 2H), 2.27 (s, 3H); MS [M+H]+=545.1; LCMS RT=2.56 min.

1. stirringstirred until homogeneous
2. washwashed with sodium carbonate solution
3. dry with materialThe organic layer was dried with sodium sulfate
4. concentrationconcentrated under vacuum
5. customPurification by preparative RP-HPLC