Trifluoroacetic acid → 2-(6-fluoro-1-oxetan-3-yl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide

Participants

Reaction Steps

To a solution of 2-(6-fluoro-1-oxetan-3-yl-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide (98 mg, 0.18 mmol) in CH2Cl2 (1.5 mL) was added TFA (0.5 mL). The reaction mixture was stirred at room temperature for 3 h then concentrated. The residue was redissolved in 10:90:0.5 MeOH/CH2Cl2/NH4OH (3 mL) and stirred at room temperature for 3 h then concentrated. The residue was portioned between water and 10% MeOH/CH2Cl2. The aqueous layer was extracted with 10% MeOH/CH2Cl2 (3×). The combined organics were concentrated and the residue was purified by silica gel chromatography with 0% to 5% MeOH/CH2Cl2 (0.5% NH4OH) to afford 30 mg (41%) of 2-(6-fluoro-1-oxetan-3-yl-1H-indazol-3-yl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxylic acid isopropylamide as a white solid. MS (M+Na)+=417; 1H NMR (DMSO-d6, 300 MHz): δ (ppm) 12.87 (br. s., 1H), 9.20 (s, 1H), 8.45-8.51 (m, 1H), 8.44 (s, 1H), 8.04 (d, J=7.6 Hz, 1H), 7.73 (dd, J=9.8, 1.9 Hz, 1H), 7.22 (td, J=9.1, 1.9 Hz, 1H), 6.13 (quin, J=7.0 Hz, 1H), 5.11-5.20 (m, 2H), 4.99-5.10 (m, 2H), 4.21 (dq, J=13.5, 6.4 Hz, 1H), 1.30 (d, J=6.4 Hz, 6H).

Provenance & Evidence