Dichloromethane → N-(4-bromo-2-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 (0.15 g) in DMF (8 mL) was added Ag2CO3 (1.00 g) and a solution of N-(4-bromo-2-fluorophenyl)-6-(3-chloropropoxy)-7-methoxy quinazolin-4-amine (0.40 g) in DMF (2 mL) at room temperature under stirring. The mixture was stirred at 80° C. for 36 h under N2 and cooled to room temperature. To this, CH2Cl2 (100 mL) was added. The mixture was washed with brine (100 mL×3), 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 (89 mg, 18.50%), HPLC: 91.13%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 528.1 (M+1); 1H NMR (400 MHz, CDCl3) δ: 2.03-2.10 (m, 2H), 2.68 (t, J=13.20 Hz, 2H), 3.03 (t, J=10.80 Hz, 2H), 3.75 (s, 2H), 3.89 (s, 3H), 4.03 (t, J=10.80 Hz, 2H), 4.08 (t, J=12.40 Hz, 2H), 7.03 (m, 1H), 7.24 (s, 1H), 7.32 (m, 1H), 7.38 (s, 1H), 7.81-7.84 (m, 2H), 8.46 (s, 1H), 8.70 (s, 1H) ppm.

Provenance & Evidence