Potassium Carbonate → N-(3-chloro-4-fluorophenyl)-7-methoxy-6-(3-(3-(trifluoromethyl)-5,6-dihydro-[1,2,4]triazolo[4,3-a]pyrazin-7(8H)-yl)propoxy)quinazolin-4-amine

Participants

Reaction Conditions

Reaction Steps

To a mixture of 4-((3-chloro-4-fluorophenyl)amino)-7-methoxyquinazolin-6-yl acetate (0.62 g) and K2CO3 (0.35 g) in 10 mL of DMF was added 7-(3-chloropropyl)-3-(trifluoromethyl)-5,6,7,8-tetrahydro-[1,2,4]triazolo[4,3-a]pyrazine (0.68 g) at rt. The reaction mixture was heated at 80° C. for 6 h, diluted with water and extracted with CH2Cl2. The combined organic phases were dried over anhydrous Na2SO4 for 1 h, 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 a white solid (0.43 g, 40.00%), HPLC: 95.00%. The compound was characterized by the following spectroscopic data: MS (ESI, pos. ion) m/z: 552.2 (M+1); 1H NMR (400 MHz, CDCl3) δ: 1.80 (m, 2H), 2.46 (t, J=4.2 Hz, 2H), 2.78 (t, J=3.6 Hz, 2H), 3.58 (s, 2H), 4.03 (s, 3H), 4.10 (t, J=4.2 Hz, 2H), 4.15 (t, J=3.6 Hz, 2H), 7.16 (s, 1H), 7.26 (s, 1H), 7.45 (s, 1H), 7.57 (m, 1H), 7.91 (m, 1H), 8.64 (s, 1H) ppm.

Provenance & Evidence