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Chloroacetyl chloride (135 mg) was added to a solution of 4-(3-chloro-2-fluoroanilino)-6-(piperidin-4-yloxy)-7-methoxyquinazoline di-hydrochloride (500 mg) (Starting material for Example 16) and diisopropylethylamine (368 mg) in methylene chloride (15 ml) that was cooled at 0° C. and the mixture was stirred for 2 hours and allowed to warm to room temperature. The reaction mixture was adsorbed onto silica and the residue purified by column chromatography on silica eluting with increasingly polar mixtures of methylene chloride/methanol (100/0 to 94/6). The fractions containing the expected product were combined and were re-purified by column chromatography on silica eluting with increasingly polar mixtures of methylene chloride/methanol (100/0 to 96/4). The fractions containing the expected product were combined and evaporated under vacuum to give 4-(3-chloro-2-fluoroanilino)-6-[1-(chloroacetyl)piperidin-4-yloxy]-7-methoxyquinazoline as a crystalline solid (0.33 g); 1H NMR Spectrum: (DMSO d6) 1.60-1.83 (m, 2H), 1.94-2.10 (m, 2H), 3.36-3.46 (m, 2H), 3.67-3.86 (m, 2H), 3.94 (s, 3H), 4.40 (s, 2H), 4.77 (m, 1H), 7.22 (s, 1H), 7.27 (t, 1H), 7.46-7.55 (m, 2H), 7.89 (s, 1H), 8.38 (s, 1H), 9.60 (s, 1H); Mass Spectrum: (M+H)+ 479.

1. temperatureto warm to room temperature
2. customthe residue purified by column chromatography on silica eluting
3. temperaturewith increasingly polar mixtures of methylene chloride/methanol (100/0 to 94/6)
4. additionThe fractions containing the expected product
5. customwere re-purified by column chromatography on silica eluting
6. temperaturewith increasingly polar mixtures of methylene chloride/methanol (100/0 to 96/4)
7. additionThe fractions containing the expected product
8. customevaporated under vacuum