Cyanoacetic acid (0.0300 g, 0.000353 mol) in dry N,N-Dimethylformamide (1.60 mL, 0.0207 mol) was added 1-Hydroxybenzotriazole (0.0488 g, 0.000361 mol) followed by N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride (0.0721 g, 0.000376 mol) then followed by N,N-Diisopropylethylamine (0.161 mL, 0.000924 mol) and then (S)-1-ethyl-3-(4-(4-(3-methylmorpholino)-5,6,7,8-tetrahydropyrido[4,3-d]pyrimidin-2-yl)phenyl)urea hydrochloride (0.1000 g, 0.0002310 mol). The reaction mixture heated at 40° C. and was stirred for 4 days. The reaction mixture was concentrated, chromatographed through silica gel again (12 g, 0-10% MeOH in dichloromethane), and purified by HPLC. 1H NMR (500 MHz, DMSO) δ 8.69 (s, 1H), 8.18 (d, J=8.8, 2H), 7.48 (d, J=8.8, 2H), 6.18 (t, J=5.6, 1H), 4.65 (d, J=15.7, 1H), 4.51-4.38 (m, 1H), 4.26-4.14 (m, 2H), 3.96-3.84 (m, 2H), 3.80-3.56 (m, 5H), 3.44 (dd, J=19.8, 12.6, 2H), 3.15-3.07 (m, 2H), 3.02-2.94 (m, 1H), 2.84 (s, 1H), 1.25 (t, J=5.4, 3H), 1.06 (t, J=7.2, 3H). LC/MS-m/z+464.2 (M+H)+.
