Dichloromethane → 2-(3-((4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl)oxy)propyl) hexahydropyrano[3,4-c]pyrrol-4(2H)-one

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(3-chloropropyl)hexahydropyrano[3,4-c]pyrrol-4(2H)-one (0.19 g) in DMF (8 mL) was added K2CO3 (3.0 eq), 4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-ol (0.25 g) and tetrabutylammonium iodide (0.1 eq). The reaction mixture was heated at 90° C. for 20 h, and then treated with CH2Cl2 (100 mL). The mixture was washed with water (100 mL×3) and brine (100 mL), and dried over anhydrous Na2SO4. The mixture was filtered and the filtrate was concentrated in vacuo. The residue was chromatographed with a silica gel column (eluting agent: 20:1 (v/v) CH2Cl2/CH3OH) to give the title compound (113 mg, 19.62%), HPLC: 95.64%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 502.0 (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, 1H), 7.95-7.98 (m, 1H), 8.28 (s, 1H), 8.63 (s, 1H) ppm.

Provenance & Evidence