[ClH:1].Cl[C:3]1[C:12]2[C:7](=[CH:8][C:9]([O:15][CH2:16][CH2:17][N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)=[C:10]([O:13][CH3:14])[CH:11]=2)[N:6]=[CH:5][N:4]=1.Br[C:26]1[C:32]([OH:33])=[CH:31][C:29]([NH2:30])=[C:28]([F:34])[CH:27]=1>C(O)(C)C.CC(C)=O>[Cl:1][C:26]1[C:32]([OH:33])=[CH:31][C:29]([NH:30][C:3]2[C:12]3[C:7](=[CH:8][C:9]([O:15][CH2:16][CH2:17][N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)=[C:10]([O:13][CH3:14])[CH:11]=3)[N:6]=[CH:5][N:4]=2)=[C:28]([F:34])[CH:27]=11M Ethereal hydrogen chloride (0.34 ml, 0.34 mmol) was added to 4-chloro-6-methoxy-7-(2-(4-methylpiperazin-1-yl)ethoxy)quinazoline (115 mg, 0.34 mmol) and 4-chloro-2-fluoro-5-hydroxyaniline (61 mg, 0.38 mmol), (as described in EP 61741 A2), in isopropanol (5 ml) and the mixture was heated at reflux for 90 minutes and then allowed to cool. The mixture was diluted with acetone, and the solid product collected by filtration. The impure solid was treated with methylene chloride/methanol/ammonia (100/8/1) (5 ml), and water was added. The reprecipitated product was collected by filtration and dried to give 4-(4-chloro-2-fluoro-5-hydroxyanilino)-6-methoxy-7-(2-(4-methylpiperazin-1-yl)ethoxy)quinazoline (32%).
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