Dichloromethane → N-(3-chloro-4-fluorophenyl)-6-(3-(hexahydrocyclopenta[c]pyrrol-2(1H)-yl)propoxy)-7-methoxyquinazolin-4-amine

Participants

Reaction Conditions

Reaction Steps

To a solution of 2-(3-chloropropyl)octahydrocyclopenta[c]pyrrole (2.00 g, 1.2 eq) in DMF (15 mL) was added K2CO3 (2.46 g, 2.0 eq), 4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-ol (2.84 g, 1.0 eq) and tetrabutylammonium iodide (0.1 eq). The reaction mixture was stirred at 90° C. for 12 h under N2, and 100 mL of CH2Cl2 was added. The mixture was washed with water followed by brine. The mixture was dried over anhydrous Na2SO4 and concentrated in vacuo. The residue was chromatographed with a silica gel column (eluting agent: 20:1 (v/v) CH2Cl2/CH3OH) to afford the title compound (2.23 g, 75.59%), HPLC: 94.23%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 472.0 (M+1); 1H NMR (400 MHz, CDCl3) δ: 1.40-1.43 (m, 2H), 1.58-1.65 (m, 4H), 2.01 (t, J=8.92 Hz, 2H), 2.10 (t, J=13.48 Hz, 2H), 2.57-2.60 (m, 4H), 2.90 (t, J=16.32 Hz, 2H), 3.49 (s, 2H), 4.00 (s, 3H), 4.21 (t, J=12.00 Hz, 2H), 7.13-7.20 (m, 2H), 7.57 (d, J=1.28 Hz, 2H), 7.59-7.60 (m, 1H), 7.91 (m, 1H), 7.93 (m, 1H), 8.65 (s, 1H) ppm.

Provenance & Evidence