Trifluoroacetic acid → N-isopropyl-2-(1,6,6-trimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a solution of N-isopropyl-2-(1,6,6-trimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (90 mg, 181 μmol) in dichloromethane (3 mL) was added TFA (1.48 g, 1.00 mL, 13.0 mmol). The reaction mixture was stirred at 25° C. overnight then concentrated. The residue was re-dissolved in 5 mL of a mixture of dichloromethane/MeOH/ammonium hydroxide (60:10:1) and stirred at 25° C. for 3 h, then evaporated to a yellow solid, dissolved in dichloromethane (containing a few drops of MeOH) and purified by chromatography (40 g, 50 μm particle size, Analogix, 0 to 5% MeOH containing 10% ammonium hydroxide in dichloromethane). The pure product was suspended in dichloromethane and cyclohexane added to promote solid formation. The solid was separated by decanting the mother liquors and then dried to give N-isopropyl-2-(1,6,6-trimethyl-4,5,6,7-tetrahydro-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (54 mg, 147 μmol, 81%) as a white solid. MS (M+H)+=461; 1H NMR (DMSO-d6) δ: 9.11 (s, 1H), 8.37 (s, 1H), 8.17 (d, J=1.9 Hz, 1H), 7.90 (s, 1H), 7.87 (s, 1H), 7.27-7.38 (m, 2H), 7.06-7.15 (m, 1H), 6.91 (t, J=2.1 Hz, 1H), 6.80-6.89 (m, 1H), 4.20 (s, 3H), 4.11 (dq, J=13.9, 6.8 Hz, 1H), 1.06 (d, J=6.4 Hz, 6H).

Provenance & Evidence