Potassium Carbonate → N-tert-butyl-2-(5-(difluoromethoxy)-1-(2-(4-methylpiperazin-1-yl)-2-oxoethyl)-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-methylpiperazin-1-yl)ethanone (138.2 mg, 782 mmol) in DMF (32.0 mL) under Ar, potassium carbonate (328.5 mg, 2.38 mmol) was added at 25° C. After 1 h, N-tert-butyl-2-(5-(difluoromethoxy)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (80 mg, 151 μmol) in DMF (8.00 mL) was added and the reaction was stirred at 70° C. After 18 h, the reaction was cooled to 25° C. and quenched with water (350 mL). The product was extracted with ethyl acetate (2×250 mL). The organics were combined, dried over sodium sulfate, and the solvent removed to give a yellow oil. The solid was dried in vacuo (200 mTorr, 25° C.) to give a yellow solid. The solid was purified by chromatography (silica, 115 g Analogix column, 3-10% ethyl acetate in hexanes, gradient over 0.5 h) to give a yellow oil. The product was concentrated to a yellow oil and dried in vacuo to give N-tert-butyl-2-(5-(difluoromethoxy)-1-(2-(4-methylpiperazin-1-yl)-2-oxoethyl)-1H-indazol-3-yl)-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (41.7 mg, 62.2 μmol, 41.2%) as a yellow solid. MS (M)'=671; 1H NMR (DMSO-d6) δ: 9.09 (s, 1H), 8.60 (s, 1H), 8.22 (d, J=2.3 Hz, 1H), 7.88 (s, 1H), 7.78 (d, J=9.0 Hz, 1H), 7.40 (dd, J=2.3, 8.8 Hz, 1H), 7.21 (t, J=74.4 Hz, 1H), 5.73 (s, 2H), 5.67 (s 2H), 3.61 (br. s, 2H), 3.58 (t, J=8.0 Hz, 2H), 3.45 (br. s, 2H), 2.45 (br. s, 2H), 2.32 (m, 2H), 2.33 (s, 3H), 1.52 (s, 9H), 0.86 (t, J=8.0 Hz, 2H), −0.08 (s, 9H).

Provenance & Evidence