Phosphorus oxychloride → 6-[2-(2,5-Dimethoxyphenyl)ethyl]-4-chloroquinazoline

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Reaction Steps

150 mg of 6-[2-(2,5-dimethoxyphenyl)ethyl]-3H-quinazolin-4-one are heated together with 5 ml of phosphorus oxychloride and 100 mg of phosphorus pentachloride at reflux for 30 minutes. The mixture is concentrated in vacuo and then partitioned between ice-cold 2 M aqueous pH 7 buffer and ethyl acetate. The organic layer is separated, dried and evaporated in vacuo to yield crude 6-[2-(2,5-dimethoxyphenyl)ethyl]-4-chloroquinazoline, which can be directly used in the following step or purified by chromatography (silica gel, cyclohexane/ethyl acetate=1/1). The crude intermediate is added to a solution of sodium isopropoxide (prepared from 8.3 mg of sodium in 20 ml of isopropanol) in isopropanol. The mixture is refluxed for 1 hour, concentrated in vacuo and poured onto water. Extraction with ethyl acetate yields the crude title compound, which is purified by chromatography on silica gel (cyclohexane/ethyl acetate=2/1) to give a colourless oil.

Provenance & Evidence