反应详情

To the solution of 3-(8-(2,6-difluorophenyl)-2-{[2-(dimethylamino)ethyl]-amino}-7-oxo-5,6,7,8-tetrahydropyrimido[4,5-d]pyrimidin-4-yl)benzoic acid (23 mg, 0.05 mmol) in CH2Cl2 (3 mL) were added ammonia (2.0 M soln. in isopropanol, 0.0275 mL, 0.055 mmol), HATU (20 mg, 0.052 mmol) and diisopropyl ethyl amine (0.05 mL, 0.3 mmol). The reaction mixture was stirred over night. The reaction mixture was diluted with CH2Cl2 (5 mL) and water (5 mL) and shaked. The layers were separated and the organic layer was washed with brine (8 mL), dried over Na2SO4, filtered and concentrated. CombiFlash chromatography (mobile phase DCM/DCM[90]+MeOH[7]+NH4OH[3]) then provided the title compound as a white solid (6 mg, 26%). LC-MS m/z 468 (M+H)+; 1H-NMR (MeOD) δ 2.16 (s, 6H), 2.36 (m, 2H), 3.20 (m, 2H), 4.46 (s, 2H), 7.14 (m, 2H), 7.49 (m, 1H), 7.61 (m, 1H), 7.75 (m, 1H), 8.00 (d, 1H), 8.07 (s, 1H).

1. customThe layers were separated
2. washthe organic layer was washed with brine (8 mL)
3. dry with materialdried over Na2SO4
4. filtrationfiltered
5. concentrationconcentrated