反应详情

温度

70 °C

[2-{4-[3-Chloro-4-(3-fluoro-benzyloxy)-phenylamino]-quinazolin-6-ylimino}-3-(2,2,2-trifluoro-ethyl)-oxazolidin-5-yl]-methanol is prepared from N4-[3-chloro-4-(3-fluoro-benzyloxy)-phenyl]-quinazoline-4,6-diamine. 1,1-Thiocarbonyldiimidazole (55 mg, 0.28 mmol) is added to a solution of N4-[3-chloro-4-(3-fluoro-benzyloxy)-phenyl]-quinazoline-4,6-diamine (100 mg, 0.253 mmol) in 1:1 THF:DCE (1 ml). After 30 min, a 1:1 THF:DCE (1 ml) solution of 3-(2,2,2-trifluoro-ethylamino)-propane-1,2-diol (88 mg, 0.51 mmol) is added. After 16 h, the reaction mixture is concentrated and the resulting solid is suspended in Et2O and filtered. EDCI (110 mg, 0.560 mmol) and catalytic DMAP is added to a suspension of the solid thiourea in 1:1 THF:DCE (4 ml). After 6 h, an additional 200 mg EDCI is added and the reaction mixture is heated to 70° C. After 16 h, the reaction mixture is cooled to room temperature and diluted with water. The aqueous layer is extracted with EtOAc. The combined organic extracts are dried (Na2SO4) and concentrated. Purification on a silica gel column (EtOAc) yields the desired product as a yellow solid (10 mg, 7%). MS ESI (+) m/z 576.2, 578.2 (M+1) detected; 1H NMR (400 MHz, DMSO-d6) δ 9.56 (s, 1H), 8.47 (s, 1H), 8.08 (d, 1H), 7.94 (s, 1H), 7.77 (m, 1H), 7.62 (m, 2H), 7.47 (m, 1H), 7.32 (m, 2H), 7.24 (d, 1H) 7.19 (m, 1H), 5.25 (s, 2H), 5.19 (t, 1H), 4.77 (br, 1H), 3.77 (m, 1H), 3.66 (m, 1H), 3.55 (m, 2H), 2.97 (m, 2H).

1. waitAfter 16 h
2. concentrationthe reaction mixture is concentrated
3. filtrationfiltered
4. waitAfter 6 h
5. waitAfter 16 h
6. temperaturethe reaction mixture is cooled to room temperature
7. extractionThe aqueous layer is extracted with EtOAc
8. dry with materialThe combined organic extracts are dried (Na2SO4)
9. concentrationconcentrated
10. customPurification on a silica gel column (EtOAc)