3-oxetanone (0.38 mL, 5.2 mmol) and 1-ethyl-3-(4-(8-methyl-4-morpholino-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-2-yl)phenyl)urea hydrochloride salt (451 mg, 1.04 mmol) were mixed in 1,2-Dichloroethane (6.2 mL) and N,N-Diisopropylethylamine (0.73 mL, 4.2 mmol). The reaction was stirred at 70° C. for 1 h and at 80° C. for 30 minutes. Sodium triacetoxyborohydride (0.71 g, 3.3 mmol) was added to the reaction, and the mixture was stirred at 80° C. for 30 minutes. The reaction mixture was quenched with NaHCO3 and water, which was extracted by CHCl3. The organic layers were combined, washed by water and brine (final pH ˜9), dried over Magnesium sulfate and evaporated. The residue was purified to give the desired product sk (269 mg, 57% yield) as white powder: 1H NMR (400 MHz, DMSO) δ 8.62 (s, 1H), 8.18 (d, J=8.8 Hz, 2H), 7.47 (d, J=8.8 Hz, 2H), 6.14 (t, J=5.5 Hz, 1H), 4.62 (m, 3H), 4.53 (t, J=6.2 Hz, 1H), 4.04 (p, J=6.7 Hz, 1H), 3.81-3.64 (m, 5H), 3.54-3.35 (m, 4H), 3.17-3.03 (m, 2H), 2.67 (m, 4H), 1.29 (d, J=6.8 Hz, 3H), 1.06 (t, J=7.2 Hz, 3H); LC-MS m/z=453 (M+H).
