反应详情

温度

80 °C

To a solution of 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine (0.16 g) in DMF (8 mL) was added Ag2CO3 (0.98 g) and a solution of 6-(3-chloropropoxy)-N-(4-fluorophenyl)-7-methoxyquinazolin-4-amine (0.32 g) in DMF (2 mL) at room temperature under stirring. The mixture was heated at 80° C. for 36 h under N2, and cooled to room temperature. To this, CH2Cl2 (100 mL) was added. The mixture was washed with brine (100 mL×3). The organic layer was dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was chromatographed with a silica gel column (eluting agent: 20:1 (v/v) CH2Cl2/CH3OH) to give the title compound as a white solid (87.70 mg, 20.41%), HPLC: 90.53%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 450.2 (M+1); 1H NMR (400 MHz, CDCl3) δ: 2.02-2.10 (m, 2H), 2.68 (t, J=13.20 Hz, 2H), 3.03 (t, J=10.80 Hz, 2H), 3.75 (s, 2H), 3.89 (s, 3H), 4.03 (t, J=10.80 Hz, 2H), 4.08 (t, J=12.40 Hz, 2H), 7.12 (m, 1H), 7.26 (s, 1H), 7.29 (t, J=6.00 Hz, 1H), 7.38 (s, 1H), 7.54-7.58 (m, 2H), 7.81-7.84 (m, 1H), 8.07 (s, 1H), 8.46 (s, 1H), 8.70 (s, 1H) ppm.

1. temperaturecooled to room temperature
2. washThe mixture was washed with brine (100 mL×3)
3. dry with materialThe organic layer was dried over anhydrous Na2SO4
4. filtrationfiltered
5. concentrationThe filtrate was concentrated in vacuo
6. customthe residue was chromatographed with a silica gel column (eluting agent: 20:1 (v/v) CH2Cl2/CH3OH)