Dimethylformamide → N-isoxazol-5-yl-4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]benzamide

Participants

Reaction Conditions

Reaction Steps

To a stirred slurry of 4-methyl-3-[6-(4-methylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]benzoic acid (0.3 g) and DMF (0.05 ml) in methylene chloride (30 ml) at 35° C. was added thionyl chloride (0.3 ml). The resultant yellow solution was stirred at 45° C. for 1.5 hours. The reaction mixture was concentrated to give a yellow/orange solid. The solid was stirred in methylene chloride (30 ml) at room temperature with 5-aminoisoxazole (0.11 g) and pyridine (0.2 ml) for 18 hours. The reaction mixture was washed with saturated NaHCO3 solution, brine and concentrated. The residue was purified by column chromatography on a silica column using initially methylene chloride and then a 9:1 mixture of methylene chloride and methanol as eluent. There was thus obtained the title compound (70 mg); NMR Spectrum: (DMSOd6) 2.19 (s, 3H), 2.25 (s, 3H), 2.49 (m, 4H), 3.30 (m, 4H), 6.43 (d, 1H), 7.50 (d, 1H), 7.62 (s, 1H), 7.65 (m, 2H), 8.08 (s, 1H), 8.10 (m, 1H), 8.13 (s, 1H), 8.50 (d, 1H), 12.04 (s, 1H); Mass Spectrum: M+H+ 444.

Provenance & Evidence