反应详情

Diethyl azodicarboxylate (378 μl, 2.4 mmol) was added dropwise to a mixture of 4-(4bromo-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (292 mg, 0.5 mmol), (prepared as described for the starting material in Example 48), triphenylphosphine (629 mg, 2.4 mmol) and 2-(2-morpholinoethoxy)ethanol (196 mg, 1.12 mmol), (pared as described for the staring material in Example 53), in methylene chloride (110 ml) under nitrogen. The mixture was stirred for 3.5 hours at ambient temperature and the mixture was purified by pouring it directly on to a column of silica and eluting with methylene chloride/acetonitrile/methanol (6/3/1). The purified product was dissolved in methylene chloride/methanol and the insolubles were removed by filtration. 2M Ethereal hydrogen chloride (1 ml) was added to the filtrate and the volatiles were removed by evaporation. The residue was triturated with ether, collected by filtration, washed with ether and dried under vacuum to give 4-(4bromo-2-fluoroanilino)-6-methoxy-7-(2-(2-morpholinoethoxy)ethoxy)quinazoline hydrochloride (232 mg, 490/o).

1. custom(prepared
2. customthe mixture was purified
3. additionby pouring it directly on to a column of silica
4. washeluting with methylene chloride/acetonitrile/methanol (6/3/1)
5. dissolutionThe purified product was dissolved in methylene chloride/methanol
6. customthe insolubles were removed by filtration
7. addition2M Ethereal hydrogen chloride (1 ml) was added to the filtrate
8. customthe volatiles were removed by evaporation
9. customThe residue was triturated with ether
10. filtrationcollected by filtration
11. washwashed with ether
12. customdried under vacuum