P-Anisidine → 5,7-Dimethoxy-3-(4-methoxyphenyl)quinazoline-4-one

Participants

Reaction Conditions

Reaction Steps

A mixture of 50 g (0.224 mol) of the isatoic anhydride as prepared in Example 5, 68.9 g (0.560 mol) of p-anisidine, 2.73 g (0.022 mol) of N,N-dimethylamino pyridine, and 500 mL of anhydrous dimethylacetamide, was warmed to 110° C. A clear brown solution formed at 80-90° C. and bubbling was observed (CO2 loss). After 24 hr, the reaction was cooled to room temperature, diluted with water (1L), and extracted with EtOAc (3×500 mL). The combined organic layers were washed with brine (1×250 mL), dried over MgSO4, filtered, and concentrated to give a brown residue weighing 85.2 g. The brown residue was dissolved in anhydrous triethylorthoformate (720 mL) and warmed to reflux for 4 hr. Upon cooling to room temperature, an off-white solid precipitated. Filtration, washing with triethylorthoformate (1×1 L), air drying, and drying under high vacuum gave 55.1 g (79%) of 5,7-dimethoxy-3-(4-methoxyphenyl)quinazoline-4-one, as an off-white solid.

Provenance & Evidence