A mixture of 2-(5-Bromo-pyridin-3-yl)-2-hydroxy-N,N-dimethyl-acetamide (160 mg, 0.62 mmol), bis(pinacol)diborane (173 mg, 0.68 mmol), potassium acetate (182 mg, 1.85 mmol), and 1,1′-bis(diphenylphosphino)ferrocenepalladium(II)-dichloride dichlormethane adduct (10 mg, 0.012 mmol) in dimethylacetamide (1 mL) was irradiated in a Personal Chemistry Optimizer at 120° C. for 30 min. 5-Bromo-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine-4-carbonitrile (159 mg, 0.42 mmol), sodium carbonate solution (2M in water, 1 mL, 2 mmol), dimethylacetamide (2 mL) and additional 1,1′-bis(diphenylphosphino)ferrocenepalladium(II)-dichloride dichlormethane adduct (10 mg, 0.012 mmol) was added and the mixture was irradiated for an additional 30 min at 120° C. Sodium sulfate was added to the crude reaction mixture and the solids were filtered over Celite. The solids were rinsed with ethyl acetate and acetonitrile and the combined filtrate was concentrated. The resulting residue was purified by flash silica gel chromatography using a gradient of ethyl acetate in hexanes to afford 2-[5-(4-Cyano-1H-pyrrolo[2,3-b]pyridin-5-yl)-pyridin-3-yl]-2-hydroxy-N,N-dimethyl-acetamide (35 mg). The material was dissolved in acetone (5 mL), and N-iodosuccinimide (27 mg, 0.12 mmol) was added. The mixture was stirred at 23° C. for 3d. The reaction was quenched with sodium thiosulfate solution (1N, 1 mL) and water (1 mL). The mixture was concentrated suspended in ethyl acetate and loaded onto silica. Purification by flash silica gel chromatography using a gradient of (dichloromethane, methanol, and conc. ammonium hydroxide 80:20:1) in dichloromethane afforded 2-[5-(3-Iodo-4-cyano-1H-pyrrolo[2,3-b]pyridin-5-yl)-pyridin-3-yl]-2-hydroxy-N,N-dimethyl-acetamide (46 mg, MS: m/z 447.9 (M+H+)). The material was dissolved in dimethylformamide (1.5 mL), and cooled to 0° C. Sodium hydride (60% suspension in mineral oil, 40 mg, 1 mmol) was added. The mixture was cooled to −42° C. and 2-trimethylsilanyl-ethoxymethylchloride (180 μL) was added slowly over 10 min. The mixture was stirred at −42° C. for 2 h and quenched with 2 mL saturated ammonium chloride solution and 2 mL water. The aqueous mixture was applied to a Varian chemelut cartridge and eluted with ethyl acetate. The crude product was purified by flash silica gel chromatography using a gradient of (ethyl acetate and methanol 9:1) in hexanes to afford 2-{5-[4-Cyano-3-iodo-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-pyridin-3-yl}-N,N-dimethyl-2-(2-trimethylsilanyl-ethoxymethoxy)-acetamide (49 mg). The material was loaded into a 5 mL Personal Chemistry microwave reaction vial and 2-methoxyphenylboronic acid (16 mg, 0.10 mmol), 1,1′-bis(diphenylphosphino)ferrocenepalladium(II)-dichloride dichloromethane adduct (3 mg, 0.003 mmol), acetonitrile (1 mL) and aqueous Na2CO3 solution (2M, 71 μL) were added. The vial was purged with nitrogen, sealed, and irradiated in a Personal Chemistry Optimizer at 120° C. for 30 min. Sodium sulfate was added to the reaction mixture and the slurry was filtered over Celite and concentrated. The crude product was dissolved in trifluoroacetic acid and shaken at 23° C. for 1 h. The mixture was concentrated and dissolved in dimethylsulfoxide and ethylenediamine. Purification by mass triggered reverse phase HPLC afforded 2-{5-[4-Cyano-3-(2-methoxy-phenyl)-1H-pyrrolo[2,3-b]pyridin-5-yl]-pyridin-3-yl}-2-hydroxy-N,N-dimethyl-acetamide as a white solid (2.3 mg, 0.005 mmol). 1H NMR (500 MHz, MeOH-d4) δ 8.75 (d, J=2 Hz, 1H), 8.72 (d, J=2 Hz, 1H), 8.46 (s, 1H), 8.06 (t, J=2 Hz, 1H), 7.68 (s, 1H), 7.37 (m, 2H), 7.05 (d, J=8 Hz, 1H), 7.03 (t, J=8 Hz, 1H), 5.67 (s, 1H), 3.8 (s, 3H), 2.99 (s, 6H). MS: m/z 428.4 (M+H+).
