反应详情

A solution of (R)-2-methoxypropanoic acid (2.9 mg, 0.028 mmol), DIPEA (10.8 mg, 0.083 mmol), and HATU (10.6 mg, 0.028 mmol) in DMF (278 μL) was stirred at room temperature for 10 min followed by the addition of 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) and stirring 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=6.8 Hz, 1.3H), 1.38 (d, J=6.6 Hz, 1.6H), 1.90-2.04 (m, 2H), 2.09-2.18 (m, 2H), 2.76 (t, J=6.6 Hz, 0.9H), 2.84 (t, J=6.1 Hz, 1.1H), 3.00 (ddd, J=12.3, 8.6, 3.3 Hz, 2H), 3.33 (s, 3H), 3.34-3.43 (m, 2H), 3.72-3.84 (m, 2H), 3.84-3.98 (m, 2H), 4.32-4.41 (m, 1H), 4.42-4.50 (m, 1H), 4.51-4.55 (m, 0.6H), 4.62-4.69 (m, 1.4H), 5.89-6.22 (m, 1H), 6.84-6.91 (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.

1. customThe crude reaction mixture
2. filtrationfiltered through a hydrophilic PTFE 0.45 μm
3. filtrationfilter (Millipore® Millex-LCR)
4. custompurified via HPLC Method A