Ethylenediamine → 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(S)-1-(5-trifluoromethyl-1H-imidazol-2-yl)ethyl]-amide

Participants

Reaction Steps

To a stirred solution of 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(S)-1-(5-trifluoromethyl-1H-imidazol-2-yl)-ethyl]-amide (34 mg, 56.4 μmol) in dichloromethane (0.5 mL) was added trifluoroacetic acid (174 μL, 2.26 mmol) at 20° C. After 3 h, the mixture was concentrated in vacuo. The residue was diluted with dichloromethane and concentrated again. The residue was then suspended in dichloromethane (1 mL) and ethylenediamine (229 μL, 3.39 mmol) added. The mixture was stirred for 1 h, then diluted with ethyl acetate and water. The organic layer was washed with brine, then dried (sodium sulfate), filtered and concentrated in vacuo. The residue was purified by chromatography (silica, 12 g Analogix column, 0-10% methanol in dichloromethane, gradient over 30 min) to give 2-(6-fluoro-1-methyl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid [(S)-1-(5-trifluoromethyl-1H-imidazol-2-yl)ethyl]-amide (16 mg, 60%) as a light yellow solid. MS (M+H)+=473; 1H NMR (DMSO-d6) δ: 12.94 (d, J=3.0 Hz, 1H), 12.80 (br. s., 1H), 9.12 (s, 1H), 8.63 (d, J=8.5 Hz, 1H), 8.50 (d, J=3.3 Hz, 1H), 8.42-8.49 (m, 1H), 7.72 (s, 1H), 7.67 (dd, J=9.8, 2.0 Hz, 1H), 7.00 (td, J=9.2, 2.3 Hz, 1H), 5.32-5.59 (m, 1H), 4.14 (s, 3H), 1.64 (d, J=6.8 Hz, 3H).

Provenance & Evidence