反应详情

1,1′-(azodicarbonyl)dipiperidine (840 mg, 3 mmol) was added in portions to a mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (315 mg, 1 mmol), ethyl 4-hydroxymethyl-2-pyridinecarboxylate (250 mg, 1.4 mmol), (J. Het. Chem. 1993, 30, 631-635) and tributylphosphine (800 μl, 3 mmol) in methylene chloride (50 ml) at 0° C. The mixture was allowed to warm to ambient temperature over 2 hours, the insolubles were removed by filtration and the filtrate was washed with water and brine, dried (Na2SO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (10:0 increasing to 9:1). The purified product was recrystallised from methylene chloride/hexane to give 4-(4-chloro-2-fluoroanilino)-7-(2-ethoxycarbonylpyrid-4-yl)methoxy-6-methoxyquinazoline (285 mg, 60%).

1. customthe insolubles were removed by filtration
2. washthe filtrate was washed with water and brine
3. dry with materialdried (Na2SO4)
4. customthe solvent removed by evaporation
5. customThe residue was purified by column chromatography
6. washeluting with methylene chloride/methanol (10:0 increasing to 9:1)
7. customThe purified product was recrystallised from methylene chloride/hexane