反应详情

Diethyl azodicarboxylate (209 mg, 1.2 mmol) was added dropwise to a suspension of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (128 mg, 0.4 mmol), (prepared as described for the starting material in Example 24), triphenylphosphine (314 mg, 1.2 mmol) and 2-(N-methyl-N-(pyridazin-4-yl)amino)ethanol (80 mg, 0.52 mmol) in methylene chloride (5 ml) and the mixture stirred for 2 hours at ambient temperature. The solvent was removed by evaporation, the residue was triturated with ether and the resulting solid was collected by filtration. The solid was purified by column chromatography eluting with methylene chloride/methanol (9/1 followed by 8/2) to give a white solid. This solid was dissolved in methylene chloride/methanol and ethereal hydrogen chloride (0.5 ml of a 4M solution) was added. The volatiles were removed by evaporation, the residue was triturated with ether, collected by filtration and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-N-methyl-N-(pyridazin-4-yl)amino)ethoxy)quinazoline hydrochloride (110 mg, 60%).

1. custom(prepared
2. customThe solvent was removed by evaporation
3. customthe residue was triturated with ether
4. filtrationthe resulting solid was collected by filtration
5. customThe solid was purified by column chromatography
6. washeluting with methylene chloride/methanol (9/1 followed by 8/2)
7. customto give a white solid
8. customThe volatiles were removed by evaporation
9. customthe residue was triturated with ether
10. filtrationcollected by filtration
11. customdried under vacuum