反应详情

4-[({4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]-1-methylpiperidine-4-carboxylic acid (50 mg, 0.1 mmol) was dissolved in N,N-dimethylformamide (2 ml) and O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (59 mg, 0.15 mmol) and N,N-diisopropylethylamine (89 μl, 0.51 mmol) were added. After a few minutes methylamine hydrochloride (10 mg, 0.15 mmol) was added and the mixture stirred for 1 hour at room temperature. The mixture was absorbed onto an Isolute SCX column, washed with methanol and eluted with ammonia in methanol. Appropriate fractions were combined and concentrated. The residue was purified by column chromatography on silica, eluting with 5% 7N ammonia in methanol/dichloromethane, to give the title product (40 mg, 77%) as a white solid; 1H NMR Spectrum: (DMSO d6) 1.82 (m, 2H); 2.02 (m, 2H); 2.13 (m, 8H); 2.65 (m, 5H); 3.60 (s, 2H); 3.94 (s, 3H); 7.18 (s, 1H); 7.30 (t, 1H); 7.50 (m, 1H); 7.58 (m, 2H); 8.32 (s, 1H); 8.73 (s, 1H); 9.68 (s, 1H). Mass Spectrum: (M+H)+ 501.

1. customThe mixture was absorbed onto an Isolute SCX column
2. washwashed with methanol
3. washeluted with ammonia in methanol
4. concentrationconcentrated
5. customThe residue was purified by column chromatography on silica
6. washeluting with 5% 7N ammonia in methanol/dichloromethane