反应详情

According to Example 1, the reaction of 2-chloro-N-(6-methoxypyridin-3-yl)-6-morpholinopyrimidin-4-amine (40 mg, 0.124 mmol) with 4-methoxy-5-(4,4,5,5-tetramethyl(1,3,2-dioxaborolan-2-yl))pyrimidine-2-ylamine (94 mg, 0.372 mmol) gave 4′-methoxy-N4-(6-methoxypyridin-3-yl)-6-morpholino-2,5′-bipyrimidine-2′,4-diamine. A mixture of crude 4′-methoxy-N4-(6-methoxypyridin-3-yl)-6-morpholino-2,5′-bipyrimidine-2′,4-diamine and morpholine (0.108 mL, 1.24 mmol) in N-methylpyrrolidinone (2 mL) was heated under microwave irradiation (high absorption, fixed hold time) for 20 minutes at 200° C. Additional morpholine (0.108 mL, 1.24 mmol) was added and the solution heated at 200° C. under microwave irradiation for another 50 minutes. Another portion of morpholine (0.108 mL, 1.24 mmol) was added and the mixture heated at 200° C. under microwave irradiation for 90 minutes. Upon cooling the material was directly purified by reverse-phase HPLC. After lyophilization, the bis-TFA salt of 2-amino-5-(4-(6-methoxypyridin-3-ylamino)-6-morpholinopyrimidin-2-yl)pyrimidin-4(3H)-one was isolated as an off white solid (24.6 mg, 50%): LCMS (m/z): 397.1 (MH+). Rt: 1.92 min.