反应详情

温度

40 °C

A mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline (250 mg, 0.78 mmol), (prepared as described for the starting material in Example 24), 2-acetamido-4-chloromethylthiazole (164 mg, 0.86 mmol) and potassium carbonate (216 mg, 1.5 mmol) in DMF (5 ml) was stirred at 40° C. for 7 hours. The mixture was partitioned between ethyl acetate and water and the aqueous layer was adjusted to pH7 with 2M hydrochloric acid. The organic phase was washed with water, brine, dried (MgSO4) and the solvent removed by evaporation. The residue was purified by column chromatography eluting with methylene chloride/methanol (95/5). The purified solid was dissolved in a mixture of methylene chloride and methanol and a 5M solution of hydrogen chloride in isopropanol (1.0 ml) was added. The volatiles were removed by evaporation to give a solid, which was triturated with ether, collected by filtration and dried under vacuum to give 7-((2-acetamidothiazol-4-yl)methoxy)-4-(4-chloro-2-fluoroanilino)-6-methoxyquinazoline hydrochloride (96 mg, 24%).

1. custom(prepared
2. customThe mixture was partitioned between ethyl acetate and water
3. washThe organic phase was washed with water, brine
4. dry with materialdried (MgSO4)
5. customthe solvent removed by evaporation
6. customThe residue was purified by column chromatography
7. washeluting with methylene chloride/methanol (95/5)
8. dissolutionThe purified solid was dissolved in a mixture of methylene chloride and methanol
9. additiona 5M solution of hydrogen chloride in isopropanol (1.0 ml) was added
10. customThe volatiles were removed by evaporation
11. customto give a solid, which
12. customwas triturated with ether
13. filtrationcollected by filtration
14. customdried under vacuum