Reaction Steps
A solution of (S)-2-methoxypropanoic acid (2.9 mg, 0.028 mmol), DIPEA (3.9 mg, 0.028 mmol), and HATU (10.6 mg, 0.028 mmol) in DMF (278 μL) was stirred at room temperature for 10 min then treated with N-(2,2-difluoroethyl)-2-(4-(2,4-difluorophenoxyl)piperidin-1-yl)-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-3-amine TFA salt (15 mg, 0.028 mmol). Stirring was continued overnight. The crude reaction mixture was diluted in DMF, filtered through a hydrophilic PTFE 0.45 μm filter (Millipore® Millex-LCR), and purified via HPLC Method A to give the title compound as a TFA salt (3 mg) as a clear oil. 1H NMR (400 MHz, methanol-d4, mixture of rotamers) δ ppm 1.32 (d, J=6.6 Hz, 1.3H), 1.38 (d, J=6.6 Hz, 1.7H), 1.91-2.04 (m, 2H), 2.09-2.19 (m, 2H), 2.76 (t, J=6.2 Hz, 0.9H), 2.84 (t, J=5.4 Hz, 1.1H), 2.95-3.05 (m, 2H), 3.33 (s, 3H), 3.35-3.43 (m, 2H), 3.78 (td, J=14.6, 4.3 Hz, 2H), 3.83-3.98 (m, 2H), 4.32-4.41 (m, 1H), 4.42-4.49 (m, 1H), 4.56 (m, 1.1H), 4.68 (m, 0.9H), 5.89-6.22 (m, 1H), 6.85-6.91 (m, 1H), 6.98 (ddd, J=11.2, 8.5, 3.0 Hz, 1H), 7.17 (td, J=9.2, 5.6 Hz, 1H); ESI-MS m/z [M+H]+ 512.4.
