Trifluoroacetic acid → 3-(7-(isopropylcarbamoyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1-methyl-4,5,6,7-tetrahydro-1H-indazole 2-oxide

Participants

Reaction Conditions

Reaction Steps

To a pale yellow solution of 3-(7-(isopropylcarbamoyl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1-methyl-4,5,6,7-tetrahydro-1H-indazole 2-oxide (45 mg, 92.8 μmol) in dichloromethane (2.00 mL) was added TFA (1.48 g, 1.00 mL, 13.0 mmo140), the reaction mixture turned dark red and was stirred at 25° C. overnight then concentrated. 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 3 h, then evaporated to a light yellow solid, dissolved in dichloromethane (added few drops MeOH and heating) and purified by chromatography (spherical silica 20-45 μm, 23 g, Versaflash Supelco) eluting with 0 to 10% over 15 min (MeOH containing 10% ammonium hydroxide)/dichloromethane. Pure white solid product was sonicated with hexanes. The solid was separated by decantation and dried under high vacuum to give 3-(7-(isopropylcarbamoyl)-5H-pyrrolo[2,3-b]pyrazin-2-yl)-1-methyl-4,5,6,7-tetrahydro-1H-indazole 2-oxide (27 mg, 76.2 mmol, 82.1%) as a white solid. MS (M+H)+=377 (100% purity); 1H NMR (DMSO-d6) δ: 12.93 (br. s., 1H), 8.93 (s, 1H), 8.45 (s, 1H), 7.45 (d, J=8.1 Hz, 1H), 4.13-4.33 (m, 1H), 3.35 (s, 3H), 2.37-2.46 (m, 2H), 1.83-2.18 (m, 6H), 1.22 (d, J=6.6 Hz, 6H).

Provenance & Evidence