反应详情

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-(3-oxomorpholino)ethoxy)quinazoline hydrochloride (108 mg, 26%).

1. custom(prepared
2. customthe insolubles were removed by filtration
3. customThe filtrate was purified
4. additionby pouring it directly on to a column of silica
5. washeluting with methylene chloride/ethyl acetate/methanol (60/35/5)
6. customThe purified product was triturated with ether
7. filtrationcollected by filtration
8. dissolutionThe solid was dissolved in methylene chloride containing a few drops of methanol and 3.8M ethereal hydrogen chloride (0.5 ml)
9. additionwas added
10. customThe volatiles were removed by evaporation
11. customthe residue was triturated with ether
12. filtrationcollected by filtration
13. customdried under vacuum