反应详情

温度

25 °C

Triethylsilane (0.075 mL, 0.468 mmol) and TFA (1.0 mL, 12.98 mmol) were sequentially added to a solution of (4R)-tert-butyl 4-(6-(5-cyano-1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-3-yl)pyrazin-2-yloxy)-6-azaspiro[2.5]octane-6-carboxylate (99.4 mg, 0.187 mmol) in CH2Cl2 (1.0 mL) and the resulting solution was stirred at 25° C. for 2.5 h. The mixture was concentrated in vacuo and the residue was taken up in DMSO (3.0 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)-1H-indazole-5-carbonitrile 2,2,2-trifluoroacetate (63.2 mg, 0.137 mmol, 73% yield) as a white solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 9.01 (1 H, s), 8.99 (1 H, d, J=11.2 Hz), 8.71 (1 H, s), 8.65 (1 H, d, J=8.2 Hz), 8.35 (1 H, s), 7.86 (1 H, d, J=8.7 Hz), 7.79 (1 H, dd, J=8.6, 1.4 Hz), 5.00 (1 H, s), 3.75 (1 H, d, J=12.9 Hz), 3.47 (1 H, t, J=12.0 Hz), 3.34 (1 H, d, J=12.7 Hz), 3.10-3.22 (1 H, m), 2.37-2.47 (1 H, m), 1.17 (1 H, d, J=14.5 Hz), 0.78-0.90 (2 H, m), 0.61-0.69 (1 H, m), 0.55 (1 H, dd, J=8.7, 4.2 Hz). 19F NMR (377 MHz, DMSO-d6) δ ppm −73.67 (3 F, s). MS (ESI, pos. ion) m/z: 347.1 (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)