Reaction Steps
and 1-(4-(7-(2-chloro-6-methylpyrimidin-4-yl)-4-morpholino-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)-3-ethylurea (vz2): 1-Ethyl-3-(4-(4-morpholino-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea (0.0506 g, 0.132 mmol) and 2,4-Dichloro-6-methylpyrimidine (0.0360 g, 0.221 mmol) were combined then added dry N,N-Dimethylformamide (0.910 mL, 11.8 mmol) followed by N,N-Diisopropylethylamine (0.0456 mL, 0.262 mmol). The reaction was microwaved on 200 watts, 120° C. for 30 minutes on a CEM microwave. The reaction mixture was concentrated, chromatographed through silica gel (4 g, 0-100% EtOAc in heptane), and then purified by HPLC. 1-(4-(7-(4-chloro-6-methylpyrimidin-2-yl)-4-morpholino-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)-3-ethylurea (vz1): 1H NMR (500 MHz, DMSO) δ 8.62 (s, 1H), 8.21 (d, J=8.8, 2H), 7.49 (d, J=8.8, 2H), 6.71 (s, 1H), 6.15 (t, J=5.6, 1H), 4.81 (s, 2H), 3.96 (s, 2H), 3.78-3.68 (m, 4H), 3.53-3.41 (m, 4H), 3.17-3.05 (m, 2H), 2.75 (t, J=5.2, 2H), 2.34 (s, 3H), 1.07 (t, J=7.2, 3H). LC/MS-m/z+509.2 (M+H)+; 1-(4-(7-(2-chloro-6-methylpyrimidin-4-yl)-4-morpholino-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)-3-ethylurea (vz2): 1H NMR (500 MHz, DMSO) δ 8.63 (s, 1H), 8.21 (d, J=8.8, 2H), 7.49 (d, J=8.8, 2H), 6.88 (s, 1H), 6.16 (t, J=5.6, 1H), 4.69 (s, 2H), 3.86 (s, 2H), 3.78-3.69 (m, 4H), 3.56-3.43 (m, 4H), 3.18-3.04 (m, 2H), 2.77 (d, J=4.6, 2H), 2.29 (s, 3H), 1.06 (t, J=7.2, 3H). LC/MS-m/z+509.2 (M+H)+
