Reaction Steps
To a suspension of 3-(4-(2,4-difluorophenoxyl)piperidin-1-yl)-N-isopropyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-2-amine TFA salt (50 mg, 0.080 mmol) and K2CO3 (44.4 mg, 0.322 mmol) in acetone (2.0 mL) was added 1-bromo-2-fluoroethane (5.4 μL, 0.072 mmol) at 23° C. The reaction mixture was stirred at 23° C. for 1 h and then at 50° C. for 3 days. The reaction mixture was cooled to 23° C., an additional portion of 1-bromo-2-fluoroethane (2.7 μL, 0.036 mmol) was added, and the reaction mixture was heated for an additional 1.5 hr at 50° C., cooled to 23° C., and concentrated via rotary evaporation. The resulting crude material was reconstituted in DMSO, filtered, rinsed with DMSO, and purified by HPLC Method B using a 30% to 70% ACN gradient to give the title compound as a TFA salt (10.7 mg, 23.6%) as a yellow film. 1H NMR (500 MHz, DMSO-d6, mixture of rotamers) δ ppm 1.19 (d, J=6.8 Hz, 6H), 1.83-1.92 (m, 2H), 2.02-2.13 (m, 2H), 2.79-2.96 (m, 3H), 2.96-3.11 (m, 0.9H), 3.24-3.36 (m, 2H), 3.38-3.55 (m, 1.1H) 3.65 (br s, 1.1H), 3.71 (m, 0.9H), 3.73-3.84 (m, 1H), 4.12-4.19 (m, 1H), 4.28 (br s, 0.9H), 4.30 (br s, 1.1H), 4.54 (ddd, J=11.7, 7.8, 3.9 Hz, 1H), 4.87 (t, J=4.4 Hz, 0.9H), 4.88-4.95 (m, 1H), 4.97 (t, J=4.4 Hz, 1.1H), 5.86 (d, J=8.3 Hz, 1H), 6.97-7.08 (m, 1H), 7.25-7.37 (m, 2H); ESI-MS m/z [M+H]+ 450.5.
