Reaktionsschritte
A mixture of (E)-ethyl 3-(4-((E)-2-(3-hydroxyphenyl)-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylate (300 mg, 0.57 mmol; Compound 346, Step 1), CuBr (3.6 mg, 0.025 mmol), Cs2CO3 (320 mg, 0.98 mmol), 2-iodopyridine (103 mg, 0.50 mmol), 1-(pyridin-2-yl)propan-2-one (15 mg, 0.11 mmol), and DMSO (1 mL) was degassed with three vacuum/N2 cycles, heated at 80° C. for 5 h, heated at 90° C. for 2 h, and then stirred at rt for 14 h. The reaction was diluted with EtOAc and filtered through Celite. The organic filtrate was washed with H2O (50 mL), washed with brine (40 mL), dried (MgSO4), filtered, concentrated, and purified by silica gel chromatography (10%-30% EtOAc in hexanes) to give 193 mg of (E)-ethyl 3-(4-((E)-2-(3-(pyridin-2-yloxy)phenyl)-1-(1-(tetrahydro-2H-pyran-2-yl)-1H-indazol-5-yl)but-1-en-1-yl)phenyl)acrylate as a white foam. 1H NMR (400 MHz, DMSO-d6): δ 8.13 (dd, 1H), 8.11 (s, 1H), 7.69-7.75 (m, 2H), 7.64 (s, 1H), 7.52 (d, 1H), 7.44 (d, 2H), 7.30 (t, 1H), 7.23 (dd, 1H), 7.06-7.10 (m, 2H), 6.90-6.95 (m, 3H), 6.85-6.88 (m, 1H), 6.65 (d, 1H), 6.52 (d, 1H), 5.85 (d, 1H), 4.16 (q, 2H), 3.87-3.92 (m, 1H), 3.70-3.78 (m, 1H), 2.38-2.48 (m, 3H), 1.95-2.08 (m, 2H), 1.70-1.81 (m, 1H), 1.56-1.62 (m, 2H), 1.25 (t, 3H), 0.94 (t, 3H); LCMS: 600 (M+H)+.
