反应详情

温度

80 °C

A mixture of 4-(4-chloro-2-fluoroanilino)-7-hydroxy-6-methoxyquinazoline 319.5 mg, 1 mmol), (prepared as described for the starting material in Example 24), potassium carbonate (414 mg, 3 mmol), potassium iodide (16 mg, 0.1 mmol) and 4-chloromethylpyrimidine (257 mg, 2 mmol) in DMF (20 ml) was heated at 80° C. for 2 hours. The solvent was removed by evaporation and the residue was triturated with water. The solid was collected by filtration and dried under vacuum. The solid was purified by column chromatography eluting with methylene chloride/methanol (95/5). The purified white solid was suspended in methanol (25 ml) and a solution of 7.5M hydrogen chloride in methanol (20 ml) was added. The resulting solid product was collected by filtration, washed with methanol and then pentane and dried under vacuum to give 4-(4-chloro-2-fluoroanilino)-6-methoxy-7-((pyrimidin-4-yl)methoxy)quinazoline hydrochloride (172 mg, 42%). m.p. 237-239° C. 1H NMR Spectrum: (DMSOd6; CF3COOD) 4.07(s, 3H); 5.53(s, 2H); 7.40(s, 1H); 7.46(dd, 1H); 7.65(t, 1H); 7.68-7.72(m, 2H); 8.26(s, 1H); 8.85(s, 1H); 8.91(d, 1H); 9.25(s, 1H) MS-ESI: 412 [MH]+

1. customprepared
2. customThe solvent was removed by evaporation
3. customthe residue was triturated with water
4. filtrationThe solid was collected by filtration
5. customdried under vacuum
6. customThe solid was purified by column chromatography
7. washeluting with methylene chloride/methanol (95/5)
8. additiona solution of 7.5M hydrogen chloride in methanol (20 ml) was added
9. filtrationThe resulting solid product was collected by filtration
10. washwashed with methanol
11. dry with materialpentane and dried under vacuum