Thionyl Chloride → 3-[6-(4-ethylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]-N-isoxazol-3-yl-4-methylbenzamide

Participants

Reaction Conditions

Reaction Steps

To a stirred slurry of 4-methyl-3-[6-(4-ethylpiperazin-1-yl)-4-oxoquinazolin-3(4H)-yl]benzoic acid (0.19 g) and DMF (0.05 ml) in methylene chloride (4 ml) at 35° C. was added thionyl chloride (0.18 ml). The resultant green solution was stirred at 35° C. for 1.5 hours. The reaction mixture was concentrated to give yellow foam. The solid was stirred in methylene chloride (4 ml) at room temperature and 3-aminoisoxazole (0.15 ml) and N,N-diisopropylethylamine (0.25 ml) was added, stirred for 1.5 hours and concentrated. The resultant oil was partitioned between ethyl acetate and a saturated NaHCO3 solution. The aqueous layer was separated and the organic layer washed with brine (5 ml). The organic phase concentrated to give an off-white solid. The solid was triturated with ethyl acetate and collected by filtration to give the title compound as an off-white solid (85 mg); NMR Spectrum: (DMSOd6) 1.05 (3H, t), 2.18 (3H, s), 2.41 (2H, m), 2.55 (4H, m), 3.29 (4H, m), 7.05 (1H, s), 7.50 (1H, s), 7.62 (3H, m), 8.07 (2H, m), 8.13 (1H, s), 8.87 (1H, s), 11.47 (1H, s); Mass Spectrum: M+H+ 459.

Provenance & Evidence