反应详情

According to Example 1 the reaction of 2-chloro-4-morpholino-6-(tetrahydro-2H-pyran-4-yloxy)pyrimidine (20 mg, 0.067 mmol) with 4-methoxy-5-(4,4,5,5-tetramethyl(1,3,2-dioxaborolan-2-yl))pyrimidine-2-ylamine (50 mg, 0.200 mmol) afforded 4′-methoxy-4-morpholino-6-(tetrahydro-2H-pyran-4-yloxy)-2,5′-bipyrimidin-2′-amine. The crude product was treated with morpholine (0.058 mL, 0.667 mmol) in NMP (2 mL) and heated under microwave irradiation (high absorption, fixed hold time) for 60 minutes at 200° C. Additional morpholine (0.058 mL, 0.667 mmol) was added and the solution heated at 200° C. under microwave irradiation for another 30 minutes, then another 60 minutes at 210° C. Upon cooling the material was directly purified by reverse-phase HPLC. After lyophilization, the TFA salt of 2-amino-5-(4-morpholino-6-(tetrahydro-2H-pyran-4-yloxy)pyrimidin-2-yl)pyrimidin-4(3H)-one was isolated as an off white solid (17.1 mg, 68%), LCMS (m/z): 375.1 (MH+). Rt: 1.74 min.