Reaction Steps
Combine bis(pinacolato)diboron (0.437 g, 1.72 mmol), potassium acetate (0.454 g, 4.62 mmol), 1,1′-bis(diphenylphosphino)ferrocene (0.0273 g, 0.0492 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (0.0377 g, 0.0461 mmol), flush with nitrogen, treat with a solution of trifluoro-methanesulfonic acid 1-benzyl-1,2,5,6-tetrahydro-pyridin-3-yl ester (See Zheng, Q.; Yang, Y.; Martin, A. R. Tetrahedron Lett. 1993, 34, 2235-2238) (0.503 g, 1.56 mmol) in dioxane (10 mL), stir and heat at 80° C. After 4 h, concentrate the reaction mixture and dry in vacuo. Combine crude boronate, potassium carbonate (0.650 g, 4.70 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (0.0777 g, 0.0951 mmol), treat with a solution of 6-(4-iodo-phenoxy)-nicotinamide (0.582 g, 1.71 mmol) in dimethylformamide (10 mL), stir and heat at 80° C. After 4.5 h, cool the reaction mixture to ambient temperature, dilute with water (30 mL), and extract with ethyl acetate (3×30 mL). Wash combined organic extracts with brine (1×), dry over anhydrous magnesium sulfate, filter, and concentrate. Purify the residue by silica gel chromatography (10:1 to 5:1 ethyl acetate:methanol), then reverse-phase HPLC to provide 0.175 g (29%) of the title compound as a white solid: mass spectrum (electrospray) m/z=386.2 (M+1); 1H NMR (methanol-d4): 8.66 (d, 1H, J=2.4 Hz), 8.32 (dd, 1H, J=2.4, 8.3 Hz), 7.65-7.52 (m, 5H), 7.52-7.48 (m, 2H), 7.22 (d, 1H, J=8.8 Hz), 7.10 (d, 1H, J=8.8 Hz), 6.41 (m, 1H), 4.61 (d, 1H, J=13.2 Hz), 4.52 (d, 1H, J=12.7 HZ), 4.22-4.20 (m, 2H), 3.72-3.67 (m, 1H), 3.36-3.31 (m, 1H), 2.75-2.65 (m, 1H).
