Potassium Carbonate → N-tert-butyl-2-(5-(difluoromethoxy)-1-(2-oxo-2-(4-(2,2,2-trifluoroethyl)piperazin-1-yl)ethyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 2-chloro-1-(4-(2,2,2-trifluoroethyl)piperazin-1-yl)ethanone (115 mg, 471 μmol) in DMF (16 mL) under Ar, potassium carbonate (200 mg, 1.45 mmol) was added in a single portion at 25° C. After 1 h, a solution of N-tert-butyl-2-(5-(difluoromethoxy)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (50 mg, 94.2 μmol) in DMF (4.00 mL) was added in a single portion and the reaction was stirred at 60° C. After 18 h, the reaction was cooled to 25° C. and quenched with water (400 mL). The product was extracted with ethyl acetate (3×150 mL) and the organics were washed with brine (200 mL). The organics were dried over sodium sulfate and concentrated to give a yellow oil. The oil was dried in vacuo (300 mTorr, 25° C.) and purified by chromatography (silica, 12 g Analogix column, 5-80% ethyl acetate in hexanes, gradient over 1 h) to give N-tert-butyl-2-(5-(difluoromethoxy)-1-(2-oxo-2-(4-(2,2,2-trifluoroethyl)piperazin-1-yl)ethyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (69.0 mg, 93.3 mmol, 99%) as a yellow solid. MS (M)'=739; 1H NMR (DMSO-d6) δ: 9.09 (s, 1H), 8.60 (s, 1H), 8.22 (d, J=2.0 Hz, 1H), 7.88 (s, 1H), 7.78 (d, J=9.3 Hz, 1H), 7.40 (dd, J=2.0, 8.8 Hz, 1H), 7.21 (t, J=74.3 Hz, 1H), 5.74 (s, 2H), 5.67 (s, 2H), 3.64 (br. s, 2H), 3.58 (t, J=8.0 Hz, 2H), 3.46 (d, J=4.5 Hz, 2H), 2.77 (br. s, 2H), 2.61 (d, J=18.8 Hz, 4H), 1.52 (s, 9H), 0.86 (t, J=8.0 Hz, 2H), −0.08 (s, 9H).

Provenance & Evidence