反应详情

Dimethylcarbamyl chloride (38 μl, 0.42 mmol) was added to a solution of 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-methylaminoethoxy)quinazoline (150 mg, 0.4 mmol), (prepared as described for the starting material in Example 60), and triethylamine (61 μl, 0.44 mmol) in methylene chloride (4 ml). The mixture was stirred for 2.5 hours at ambient temperature, the resulting precipitate was collected by filtration and washed with ether. The solid was purified by column chromatography, eluting with methylene chloride/methanol (92/8). The purified product was dissolved in methylene chloride/methanol (1/1), 2.9M ethereal hydrogen chloride (1 ml) was added and the volatiles were removed by evaporation. The residue was triturated with ether and the solid product collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-N′,N′,N′-trimethylureido)ethoxy)quinazoline hydrochloride (80 mg, 41%).

1. custom(prepared
2. filtrationthe resulting precipitate was collected by filtration
3. washwashed with ether
4. customThe solid was purified by column chromatography
5. washeluting with methylene chloride/methanol (92/8)
6. dissolutionThe purified product was dissolved in methylene chloride/methanol (1/1)
7. addition2.9M ethereal hydrogen chloride (1 ml) was added
8. customthe volatiles were removed by evaporation
9. customThe residue was triturated with ether
10. filtrationthe solid product collected by filtration
11. washwashed with ether
12. customdried under vacuum