反应详情

温度

80 °C

A mixture of 4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-ol (0.70 g), K2CO3 (0.61 g) and tert-butyl 2-(3-chloropropyl)hexahydro-1H-pyrrolo[3,4-c]pyridine-5(6H)-carboxylate (0.80 g) in 30 mL of DMF was stirred at 80° C. for 7 h, then poured into 50 mL of ice-water and extracted with CH2Cl2 (50 mL×3). The combined organic phases were dried over anhydrous Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was chromatographed with a silica gel column (eluting agent: 30:1 (v/v) DCM/MeOH) to give the title compound as colorless oil (0.48 g, 35.00%), HPLC: 95.00%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 587.2 (M+1); 1H NMR (400 MHz, d6-DMSO) δ: 1.45 (s, 9H), 1.99-2.06 (m, 4H), 2.32-2.38 (m, 2H), 2.46-2.50 (m, 4H), 2.67-2.71 (m, 2H), 3.40-3.45 (m, 2H), 4.17-4.19 (m, 2H), 4.19 (s, 3H), 4.20-2.26 (m, 2H), 7.21 (s, 1H), 7.42 (t, J=8.0 Hz, 1H), 7.44 (s, 2H), 7.78 (t, J=4.4 Hz, 1H), 8.50 (s, 1H) ppm.

1. extractionextracted with CH2Cl2 (50 mL×3)
2. dry with materialThe combined organic phases were 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: 30:1 (v/v) DCM/MeOH)