Trifluoroacetic acid → HCID 71279625, compound

Participants

Reaction Conditions

Reaction Steps

To a pale yellow solution of N-tert-butyl-2-(5-(difluoromethoxy)-1-(3-hydroxypropyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (17 mg, 28.9 μmol) in dichloromethane (4.00 mL) was added TFA (1480 mg, 1.0 mL, Eq 450), the reaction mixture turned orange and was stirred at 25° C. for 24 h, mixture concentrated and the residue was re-dissolved in 5 mL of a solution of (dichloromethane/MeOH/ammonium hydroxide; 60:10:1) and stirred at 25° C. for 1 h, then evaporated to an off-white solid, which was dissolved in dichloromethane and purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco) eluting with 0 to 5% over 20 min (MeOH containing 10% ammonium hydroxide)/dichloromethane. The pure product dissolved in dichloromethane and cyclohexane added to allow solid formation, light yellow solid was separated by filtration and dried under high vacuum to give N-tert-butyl-2-(5-(difluoromethoxy)-1-(3-hydroxypropyl)-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (12 mg, 26.2 μmol, 90.6%). MS (M+H)+=459; 1H NMR (DMSO-d6) δ: 9.05 (s, 1H), 8.37 (s, 1H), 8.19 (s, 1H), 7.79-7.94 (m, 2H), 7.38 (d, J=8.7 Hz, 1H), 7.18 (t, J=74.4 Hz, 1H), 4.62-4.68 (m, 1H), 4.59 (t, J=6.8 Hz, 2H), 3.40-3.51 (m, 2H), 2.06 (t, J=6.2 Hz, 1H), 1.49 (s, 9H).

Provenance & Evidence