Reaction Steps
2-Bromo-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (244 mg, 571 μmol) and 1-(2-(1,3-dioxan-2-yl)ethyl)-5-(difluoromethoxy)-3-(tributylstannyl)-1H-indazole (335 mg, 571 μmol) were dissolved in DMF (3.00 mL) under argon, tetrakis(triphenylphosphine)palladium (0) (33.0 mg, 28.6 μmol) and CuI (21.7 mg, 114 mmol, Eq: 0.20) were added and the mixture sonicated for 5 min with bubbling argon. The reaction mixture was stirred at 90° C. (oil bath temperature) for 4 h. The reaction mixture was concentrated under high vacuum and the residue (dark solid) was purified by chromatography (80 g column, 50 μm from Analogix, 0-50% EtOAc in hexanes over 30 min) to give 2-(1-(2-(1,3-dioxan-2-yl)ethyl)-5-(difluoromethoxy)-1H-indazol-3-yl)-N-tert-butyl-5-((2-(trimethylsilyl)ethoxy)methyl)-5H-pyrrolo[2,3-b]pyrazine-7-carboxamide (230 mg, 357 μmol, 62.5%) as an off-white solid. MS (M+Na)+=667.1; 1H NMR (CDCl3) δ: 9.25 (s, 1H), 8.37 (s, 1H), 8.32 (d, J=2.0 Hz, 1H), 8.06 (s, 1H), 7.56 (dd, J=9.1, 0.5 Hz, 1H), 7.35 (dd, J=9.1, 2.3 Hz, 1H), 6.55 (t, J=74.3 Hz, 1H), 5.75 (s, 2H), 4.65 (t, J=6.9 Hz, 2H), 4.55 (t, J=4.9 Hz, 1H), 4.12-4.21 (m, 2H), 3.74 (td, J=12.3, 2.5 Hz, 2H), 3.56-3.65 (m, 2H), 2.34 (td, J=6.8, 5.3 Hz, 2H), 2.05-2.23 (m, 1H), 1.65 (s, 9H), 1.39 (dt, J=13.4, 1.3 Hz, 1H), 0.94-1.04 (m, 2H), −0.06-0.05 (m, 9H).
