反应详情

温度

50 °C

(S)-4-(4-(3-methylmorpholino)-7-(pyrimidin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)aniline (0.0501 g, 0.000124 mol) in dry 1,4-Dioxane (2.00 mL, 0.0256 mol) was added Triethylamine (0.0190 mL, 0.000136 mol) followed by 20% Phosgene in toluene (1:4, Phosgene:Toluene, 0.080 mL). The reaction mixture was heated at 50° C. for 1 hour. The reaction mixture was cooled to room temperature and then added 2,2-difluoroethylamine (0.0604 mL, 0.000876 mol). The reaction mixture was stirred for 3 days. The reaction mixture was concentrated and purified by HPLC. 1H NMR (400 MHz, DMSO) δ 8.94 (s, 1H), 8.44 (d, J=4.7, 2H), 8.23 (d, J=8.8, 2H), 7.51 (d, J=8.8, 2H), 6.69 (t, J=4.7, 1H), 6.57 (t, J=6.0, 1H), 6.07 (tt, J=56.1, 3.8, 1H), 4.90 (d, J=18.7, 1H), 4.73 (d, J=18.7, 1H), 4.18-4.04 (m, 3H), 3.91-3.78 (m, 2H), 3.70 (dd, J=11.3, 2.5, 1H), 3.65-3.48 (m, 5H), 3.41 (dd, J=17.7, 8.1, 1H), 3.17 (d, J=3.4, 2H), 2.74 (s, 2H), 1.25 (d, J=6.6, 3H). LC/MS-m/z+511.2 (M+H)+

1. temperatureThe reaction mixture was cooled to room temperature
2. concentrationThe reaction mixture was concentrated
3. custompurified by HPLC