Trifluoroacetic acid → 2-(6-fluoro-1-(3-(methylsulfonyl)propyl)-1H-indazol-3-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide

Participants

Reaction Steps

To a stirred solution of N-(1-(tert-butyldimethylsilyloxy)-2-methylpropan-2-yl)-2-(6-fluoro-1-(3-(methylsulfonyl)propyl)-1H-indazol-3-yl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (35 mg, 0.042 mmol) in DCM (2 mL) was added trifluoroacetic acid (1 mL) dropwise at room temperature. The reaction mixture was stirred at room temperature for 1 h, then concentrated in vacuo. The residue obtained was dissolved in DCM, washed with NaHCO3 (aq.), and then the organic layer was concentrated and purified by prep-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; 25% acetonitrile/75% water (doped with 0.1% TFA, v/v) to 42% acetonitrile/58% water (doped with 0.1% TFA, v/v) over 9 min) to give 2-(6-fluoro-1-(3-(methylsulfonyl)propyl)-1H-indazol-3-yl)-N-(1-hydroxy-2-methylpropan-2-yl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (10 mg, 50%) as a white solid. 1H NMR (300 MHz, DMSO): δ 12.81 (s, 1H), 9.10 (s, 1H), 8.63-8.58 (m, 1H), 8.37 (s, 1H), 7.90 (s, 1H), 7.71 (d, 1H, J=8.1 Hz), 7.16 (t, 1H, J=9.2 Hz), 5.08 (t, 1H, J=5.5 Hz), 4.62 (t, 2H, J=6.6 Hz), 3.60 (d, 2H, J=5.4 Hz), 3.18 (t, 2H, J=6.4 Hz), 2.96 (s, 3H), 2.32 (t, 2H, J=7.6 Hz), 1.43 (s, 6H). LC/MS: 489.2 [M+H]+, 487.0 [M−H]−.

Provenance & Evidence