Trifluoroacetic acid → N-(1-methylcyclopropyl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide trifluoroacetate

Participants

Reaction Steps

To a solution of 2-(5-(difluoromethoxy)-1-(3-(dimethylamino)propyl)-1H-indazol-3-yl)-N-(1-methylcyclopropyl)-5-trityl-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide (200 mg, 0.3 mmol) in 3 mL of dichloromethane was added trifluoroacetic acid (3 mL). The reaction mixture was stirred at room temperature overnight. After solvent evaporation, the residue was purified by preparative-HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 mL/inj, flow rate: 20 mL/min; wavelength: 214 nm and 254 nm; the gradient conditions are: 40% acetonitrile/60% water (0.1% trifluoroacetic acid V/V) initially, and then proceed to 50% acetonitrile/50% water (0.1% trifluoroacetic acid V/V) in a linear fashion after just 9 min) to afford 245-(difluoromethoxy)-1-(3-(dimethylamino)propyl)-1H-indazol-3-yl)-N-(1-methylcyclopropyl)-5H-pyrrolo[3,2-b]pyrazine-7-carboxamide trifluoroacetate (20 mg, 7%) as a yellow solid. LCMS: (M+H)+=484; 1H NMR (300 MHz, CD3OD): δ 9.04 (s, 1H), 8.13 (s, 1H), 8.02 (s, 1H), 7.61 (d, 1H, J=9.0 Hz), 7.29 (dd, 1H, J1=9.0 Hz, J2=2.1 Hz), 6.78 (t, 1H, J=73.8 Hz), 4.56-4.52 (m, 2H), 3.19-3.12 (m, 2H), 2.79 (s, 6H), 2.39-2.33 (m, 2H), 1.47 (s, 3H), 0.93-0.89 (m, 2H), 0.76-0.72 (m, 2H).

Provenance & Evidence