反应详情

温度

80 °C

To a solution of 3-ethyl-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine (0.12 g) in DMF (5 mL) was added Ag2CO3 (0.73 g, 5 eq). The mixture was then added into a solution of N-(3-chloro-4-fluorophenyl)-6-(3-chloropropoxy)-7-methoxyquinazolin-4-amine (0.21 g) in DMF (2 mL) with stirring. The reaction mixture was heated at 80° C. for 40 h under N2, and cooled to room temperature. To the reaction mixture was added CH2Cl2 (100 mL), and the reaction mixture was washed with brine (100 mL×3). The organic phase 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 (63.00 mg, 15.56%), HPLC: 90.54%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 512.1 (M+1); 1H NMR (400 MHz, CDCl3) δ: 1.29 (t, J=12.80 Hz, 3H), 2.61-2.69 (m, 2H), 2.70 (t, J=13.60 Hz, 2H), 2.86 (t, J=11.20 Hz, 3H), 3.49 (s, 2H), 3.65 (s, 2H), 3.81 (t, J=13.60 Hz, 2H), 3.91 (s, 1H), 4.08 (t, J=12.40 Hz, 2H), 7.09 (m, 1H), 7.23-7.27 (m, 1H), 7.55-7.59 (m, 2H), 7.76-7.78 (m, 1H), 8.64 (s, 1H), 8.76 (s, 1H) ppm.

1. temperaturecooled to room temperature
2. washthe reaction mixture was washed with brine (100 mL×3)
3. dry with materialThe organic phase 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)