Triphenylphosphine → 4-(4-Chloro-2-fluoroanilino)-6-methoxyquinazoline

Participants

Reaction Steps

Diethyl azodicarboxylate (2.4 ml, 15 mmol) was added dropwise to a solution of 3-([N-(tert-butylcarbonyl)-N-methyl]amino)-1-propanol (1.77 g, 9.4 mmol), 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (2 g, 6.26 mmol), (prepared as described for the starting material in Example 2), and triphenylphosphine (4.1 g, 15 mmol) in methylene chloride (50 ml) under nitrogen. The mixture was stirred for 1 hour at ambient temperature, and further 3-([N-(tert-butylcarbonyl)-N-methyl]amino)-1-propanol (236 mg, 1.2 mmol), triphenylphosphine (820 mg, 3.1 mmol) and diethyl azodicarboxylate (492 μl, 3.1 mmol) were added. The solution was stirred for 1 hour at ambient temperature and concentrated by evaporation. The residue was purified on column chromatography eluting with acetonitrile. The purified product was triturated with ether, collected by filtration and repurified by column chromatography eluting with methylene chloride/methanol (97/3) to give 7-3-([N-(tert-butylcarbonyl)-N-methyl]amino)propoxy)-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline (2.2 g, 72%).

Provenance & Evidence