Dichloromethane → N-(3-chloro-4-fluorophenyl)-6-(3-(5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)propoxy)-7-methoxyquinazolin-4-amine

Participants

Reaction Conditions

Reaction Steps

To a solution of 5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine (0.18 g) in DMF (8 mL) was added Ag2CO3 (1.12 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) at rt under stirring. The reaction mixture was heated at 80° C. for 36 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 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 title compound (80.00 mg, 17.62%), HPLC: 88.57%. The title compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 484.2 (M+1); and 1H NMR (400 MHz, CDCl3) δ: 22.02-2.08 (m, 2H), 2.75 (t, J=13.20 Hz, 2H), 2.89 (t, J=10.80 Hz, 2H), 3.73 (s, 2H), 3.94 (s, 3H), 4.01 (t, J=10.80 Hz, 2H), 4.12 (t, J=12.40 Hz, 2H), 7.10 (m, 1H), 7.24 (s, 1H), 7.27 (t, J=6.00 Hz, 1H), 7.43 (s, 1H), 7.54-7.58 (m, 1H), 7.82-7.84 (m, 1H), 8.05 (s, 1H), 8.44 (s, 1H), 8.64 (s, 1H) ppm.

Provenance & Evidence