反应详情

Acetic anhydride (14.1 μL, 0.149 mmol) and formic acid (38.1 μL, 0.994 mmol) were combined in THF (99 μL) and stirred at room temperature for 10 min. This solution was cooled to 0° C. and was added to a stirring solution of (R)-2-(4-((2,4-difluorophenyl)fluoromethyl)piperidin-1-yl)-N-isopropyl-5,6,7,8-tetrahydropyrido[3,4-b]pyrazin-3-amine (41.7 mg, 0.099 mmol) in THF (895 μL) at 0° C. After 10 min, UPLC-MS showed conversion not to the formylated product, but to the acetylated product. The reaction mixture was treated with MeOH, concentrated under reduced pressure, taken up in MeOH, filtered, and purified by HPLC Method B to give the title compound, as a TFA salt, as a pale yellow solid (17.5 mg, 30.6%). 1H NMR (500 MHz, methanol-d4, mixture of rotamers) δ ppm 1.28 (m, 6H), 1.45 (d, J=12.7 Hz, 1H), 1.65 (m, 2H), 2.01 (m, 1H), 2.09 (m, 1H), 2.18 (s, 1.1H), 2.20 (s, 1.9H), 2.76 (m, 4H), 3.49 (m, 2H), 3.81 (t, J=6.1 Hz, 1.3H), 3.85 (t, J=5.9 Hz, 0.7H), 4.13 (m, 1H), 4.57 (s, 0.7H), 4.61 (s, 1.3H), 5.52 (m, 1H), 7.02 (m, 2H), 7.50 (m, 1H); ESI-MS m/z [M+H]+ 462.4.

1. temperatureThis solution was cooled to 0° C.
2. waitAfter 10 min
3. concentrationconcentrated under reduced pressure
4. filtrationfiltered
5. custompurified by HPLC Method B