反应详情

Isonicotinoyl chloride (36 mg, 0.2 mmol) was added to a suspension of 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(methylamino)ethoxy)quinazoline hydrochloride hydrate (90 mg, 0.1 mmol), (prepared as described for the starting material in Example 54), in methylene chloride (3 ml) and triethylamine (80 mg, 0.8 mmol) was then added dropwise. The mixture was stirred for 30 minutes at ambient temperature and the solvent was then removed by evaporation. The residue was partitioned between ethyl acetate and water, the organic layer was separated, washed with brine, dried (MgSO4) and the solvent removed by evaporation. The residue was dissolved in methylene chloride/methanol and 3M ethereal hydrogen chloride (0.5 ml) was added. The suspension was diluted with ether, the precipitate was collected by filtration, washed with ether and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-(2-(N-methyl-N-(4-pyridylcarbonyl)amino)ethoxy)quinazoline hydrochloride (75 mg, 67%).

1. custom(prepared
2. customthe solvent was then removed by evaporation
3. customThe residue was partitioned between ethyl acetate and water
4. customthe organic layer was separated
5. washwashed with brine
6. dry with materialdried (MgSO4)
7. customthe solvent removed by evaporation
8. dissolutionThe residue was dissolved in methylene chloride/methanol
9. addition3M ethereal hydrogen chloride (0.5 ml) was added
10. additionThe suspension was diluted with ether
11. filtrationthe precipitate was collected by filtration
12. washwashed with ether
13. customdried under vacuum