反应详情

温度

90 °C

To a solution of 2-(3-chloropropyl)hexahydropyrano[3,4-c]pyrrol-4(2H)-one (0.25 g) in DMF (8 mL) was added K2CO3 (3.0 eq), 4-((4-fluorophenyl)amino)-7-methoxyquinazolin-6-ol (0.38 g) and tetrabutylammonium iodide (0.1 eq). The reaction mixture was heated to 90° C. and stirred for 10 h. To the mixture was added CH2Cl2 (100 mL). The mixture was washed with water and brine. 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 product (0.20 g, 32.50%), HPLC: 97.35%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 467.2 (M+1); 1H NMR (400 MHz, CDCl3) δ: 2.06-2.12 (m, 4H), 2.35 (d, J=2.92 Hz, 1H), 2.51-2.58 (m, 3H), 2.76-2.79 (m, 2H), 2.97-3.02 (m, 1H), 3.49-3.50 (m, 1H), 3.52 (s, 1H), 4.00 (s, 3H), 4.18 (d, J=1.80 Hz, 1H), 4.21-4.24 (m, 1H), 4.35-4.40 (m, 1H), 7.13 (t, J=8.80 Hz, 1H), 7.24 (d, J=9.48 Hz, 1H), 7.41 (s, 1H), 7.68 (m, 2H), 7.95-7.98 (m, 1H), 8.28 (s, 1H), 8.63 (s, 1H) ppm.

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