Dichloromethane → 4-(4-Bromo-2-fluoroanilino)-6-methoxy-7-(2-(3-oxomorpholino)ethoxy)quinazoline hydrochloride

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Reaction Steps

Diethyl azodicarboxylate (368 μl, 2.34 mmol) was added dropwise to a mixture of 4-(4-bromo-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (284 mg, 0.78 mmol), (prepared as described for the starting material in Example 48), triphenylphosphine (613 mg, 2.34 mmol) and 4-(2-hydroxyethyl)-3-morpholinone (170 mg, 1.17 mmol), (EP580402A2), in methylene chloride (10 ml) under nitrogen. The mixture was stirred for 2.5 hours at ambient temperature, the insolubles were removed by filtration. The filtrate was purified by pouring it directly on to a column of silica and eluting with methylene chloride/ethyl acetate/methanol (60/35/5). The purified product was triturated with ether and collected by filtration. The solid was dissolved in methylene chloride containing a few drops of methanol and 3.8M ethereal hydrogen chloride (0.5 ml) was added. The volatiles were removed by evaporation and the residue was triturated with ether, collected by filtration and dried under vacuum to give of 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(2-(3oxomorpholino)ethoxy)quinazoline hydrochloride (108 mg, 26%).

Provenance & Evidence