反应详情

温度

25 °C

TFA (1.7 mL, 22.07 mmol) was added to a solution of (4R)-tert-butyl 4-(6-(5-(1-methylcyclopropyl)-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)-6-azaspiro[2.5]octane-6-carboxylate (96.3 mg, 0.172 mmol) in DCM (1.7 mL) and the resulting solution was stirred at 25° C. for 2 h. The mixture was concentrated in vacuo and the residue was taken up in DMSO (2.0 mL) and purified by rpHPLC (Phenomenex Gemini C18 column (150×30 mm, 10 μm), 35 mL/min, 5-100% CH3CN/H2O+0.1% TFA, 15 min, 254 nm) to provide 3-(6-((4R)-6-azaspiro[2.5]oct-4-yloxy)-2-pyrazinyl)-5-(1-methylcyclopropyl)-1H-indazole 2,2,2-trifluoroacetate (64.6 mg, 0.132 mmol, 77% yield) as a yellow solid: 1H NMR (400 MHz, MeOH) δ ppm 9.02 (1 H, s), 8.26-8.33 (1H, m), 8.17-8.22 (1 H, m), 7.54 (1 H, d, J=8.8 Hz), 7.43 (1 H, dd, J=8.7, 1.5 Hz), 5.09 (1H, s), 3.90 (1 H, d, J=13.1 Hz), 3.60 (1 H, d, J=12.3 Hz), 3.47-3.55 (1 H, m), 3.33-3.39 (1 H, m), 2.65-2.77 (1 H, m), 1.49 (3 H, s), 1.23 (1 H, d, J=14.7 Hz), 1.01 (1 H, dt, J=9.7, 5.1 Hz), 0.90-0.95 (2 H, m), 0.82-0.90 (3 H, m), 0.75-0.81 (1 H, m), 0.64-0.73 (1 H, m). 19F NMR (377 MHz, MeOH) δ ppm −77.48 (3 F, s). MS (ESI, pos. ion) m/z: 376.3 (M+1).

1. concentrationThe mixture was concentrated in vacuo
2. custompurified by rpHPLC (Phenomenex Gemini C18 column (150×30 mm, 10 μm), 35 mL/min, 5-100% CH3CN/H2O+0.1% TFA, 15 min, 254 nm)