Trifluoroacetic acid → 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a pale yellow solution of 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-N-isopropyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (32.5 mg, 61.2 μmol) in dichloromethane (1.44 mL) was added TFA (426 mg, 288 μL, 3.73 mmol) and stirred at 25° C. for 15 h. The mixture was concentrated then re-dissolved in 5 mL of a solution of dichloromethane/MeOH/ammonium hydroxide (60:10:1) and stirred at 25° C. for 3 h, then evaporated to an off-white solid which was purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco, 0 to 5% MeOH containing 10% ammonium hydroxide in dichloromethane). The pure product was dissolved in dichloromethane/MeOH and dichloromethane evaporated to allow solid formation, then the solid was collected by filtration and dried to give 2-(5-(difluoromethoxy)-1-methyl-1H-indazol-3-yl)-N-isopropyl-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (23 mg, 57.4 μmol, 94%) as a light yellow solid. MS (M+H)+=401; 1H NMR (DMSO-d6) δ: 12.83 (br. s., 1H), 9.10 (s, 1H), 8.41 (s, 1H), 8.20 (d, J=2.3 Hz, 1H), 7.96 (d, J=7.9 Hz, 1H), 7.86 (d, J=9.4 Hz, 1H), 7.42 (dd, J=9.1, 1.9 Hz, 1H), 7.21 (t, J=74.4 Hz, 1H), 4.12-4.33 (m, 4H), 2.49 (s, 9H), 1.30 (d, J=6.4 Hz, 6H).

Provenance & Evidence