反应详情

To a solution of 4,6-dichloro-pyrimidine-5-carbaldehyde (177 mg, 1.0 mmol) and (R)-1-amino-3-(2,4-dimethyl-phenoxy)-propan-2-ol (195.3 mg, 1.0 mmol) in chloroform (8 mL) was added Et3N (348 μL, 2.5 mmol). After it was stirred at the room temperature for 8 h, the reaction mixture was evaporated under reduced pressure thoroughly. The remaining residue was mixed with 5,6-diamino-2-(1-methyl-piperidin-4-yl)-isoindole-1,3-dione (274 mg, 1.0 mmol) in DMA (10 mL). After it was heated at 110° C. for 14 h, the reaction mixture was cooled to the room temperature and mixed with aqueous HCl solution (12 N, 1 mL). The resulting mixture was heated in a sealed vial at 110° C. for 3 h and evaporated to dryness. The residue was basified with NH3 in EtOH (2 M) and concentrated. Chromatography of the crude afforded the title compound (93 mg, 17% yield for 3 steps). 1H NMR (DMSO-d6) δ 1.62 (m, 2H), 1.97 (m, 2H), 2.14 (s, 3H, CH3), 2.17 (s, 3H, CH3), 2.17 (s, 3H, CH3), 2.38 (m, 2H), 2.89 (m, 2H), 3.80 (m, 1H), 3.90-4.02 (4H), 4.11 (m, 1H), 5.47 (br s, 1H, NH), 6.82 (d, J=6 Hz, 1H), 6.93 (d, J=6 Hz, 1H), 6.97 (s, 1H), 8.06 (s, 1H), 8.12 (s, 1H), 10.83 (br s, 1H, NH); ESI-MS m/z 572.3 (MH+).

1. customthe reaction mixture was evaporated under reduced pressure thoroughly
2. temperatureAfter it was heated at 110° C. for 14 h
3. temperaturethe reaction mixture was cooled to the room temperature
4. temperatureThe resulting mixture was heated in a sealed vial at 110° C. for 3 h
5. customevaporated to dryness
6. concentrationconcentrated