反应详情

Acetyl chloride (27 mg) was added to a solution of 4-(3-chloro-2-fluoroanilino)-6-(piperidin-3-yloxy)-7-methoxyquinazoline (starting material described in Example 22; 134 mg) and diisopropylethylamine (65 mg) in methylene chloride (5 ml) and the reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was adsorbed onto silica and purified by column chromatography eluting with increasingly polar mixtures of methylene chloride/methanol (100/0 to 95/5). The fractions containing the required product were combined and evaporated to give the title product (0.07 g); 1H NMR Spectrum: (DMSO d6 at 373K) 1.52-1.62 (m, 1H), 1.80-1.94 (m, 2H), 2.00 (s, 3H), 2.06-2.15 (m, 1H), 3.43-3.64 (m, 3H), 3.82-4.04 (m, 4H), 4.58 (m, 1H), 7.20-7.29 (m, 2H), 7.42 (t, 1H), 7.59 (t, 1H), 7.93 (s, 1H), 8.40 (s, 1H), 9.30 (s, 1H); Mass Spectrum: (M+H)+ 445.

1. custompurified by column chromatography
2. washeluting
3. temperaturewith increasingly polar mixtures of methylene chloride/methanol (100/0 to 95/5)
4. additionThe fractions containing the required product
5. customevaporated