Reaction Steps
Methyl 4-(4-morpholino-7-(pyrimidin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenylcarbamimidothioate (0.070 g, 0.00015 mol) in 1-Propanol (5.00 mL, 0.0669 mol) was added Ethanamine, 2,2-diethoxy- (0.0664 mL, 0.000454 mol) heated at 97° C. for 2 hours. At this time, an additional portion of Ethanamine, 2,2-diethoxy- (0.0222 mL, 0.000152 mol) was added to the reaction mixture and stirred for 1 hour at 97° C. After this time, an additional portion of Ethanamine, 2,2-diethoxy- (0.0222 mL, 0.000152 mol) was added to the reaction mixture and heated at 97° C. for 6 hours. The reaction mixture was concentrated and dried in vacuo overnight. The crude product was cooled at 0° C. and then added 10.0 M of Hydrogen chloride in Water (2.00 mL), allowed to warm slowly to room temperature, stirred for 6 hours, then poured into ice, and to the ice solution was added saturated NaHCO3 until the pH was approximately 9. The aqueous solution was extracted three times with 10% MeOH in dichloromethane, dried over Magnesium sulfate, filtered, and concentrated to provide the crude product which was chromatographed through silica gel (4 g, 0-10% MeOH in dichloromethane), and further purified by HPLC. 1-(4-(4-morpholino-7-(pyrimidin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)-1H-imidazol-2-amine (tz) 1H NMR (400 MHz, DMSO) δ 8.44 (t, J=6.7, 3H), 8.23 (s, 1H), 7.58 (d, J=8.7, 2H), 6.93 (d, J=1.5, 1H), 6.71 (t, J=4.7, 1H), 6.59 (d, J=1.5, 1H), 5.52 (s, 2H), 4.86 (s, 2H), 4.00 (t, J=5.1, 2H), 3.74 (d, J=4.5, 4H), 3.52 (d, J=4.4, 4H), 2.79 (s, 2H). LC/MS-m/z+456.2 (M+H)+; and N-(4-(4-morpholino-7-(pyrimidin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)-1H-imidazol-2-amine (ty) LC/MS-m/z+456.2 (M+H)+.
