[CH3:1][NH:2][C:3]([C:5]1[C:10]([NH2:11])=[N:9][CH:8]=[C:7](Br)[N:6]=1)=[O:4].ClCCl.O.[NH2:17][C:18]1[CH:19]=[C:20](B(O)O)[CH:21]=[CH:22][CH:23]=1.C(N(CC)CC)C>CN(C)C=O.CCOC(C)=O>[NH2:11][C:10]1[C:5]([C:3]([NH:2][CH3:1])=[O:4])=[N:6][C:7]([C:22]2[CH:21]=[CH:20][CH:19]=[C:18]([NH2:17])[CH:23]=2)=[CH:8][N:9]=1
To a solution of 3-amino-6-bromo-pyrazine-2-carboxylic acid methylamide (1.234 g, 5.30 mmol, 1.00 equiv.) in N,N-dimethylformamide (DMF, 30 mL) was added [1,1′-bis(diphenylphosphino)-ferrocene]dichloropalladium(II) complex with dichloromethane (1:1), (Aldrich Chemical Company, 433 mg, 0.530 mmol, 0.100 equiv.), 3-aminophenylboronic acid monohydrate (Aldrich Chemical Company, 1.149 g, 7.41 mmol, 1.40 equiv.), and triethylamine (TEA, 1.073 g, 10.6 mmol, 2.00 equiv.). Nitrogen was passed through the solution for 3-5 min. The reaction mixture was heated at 85-90° C. for 15 h with stirring. The reaction was allowed to cool to room temperature and diluted with 400 mL of EtOAc. The mixture was washed with saturated aqueous NaHCO3 (2×50.0 mL), saturated aqueous NaCl (1×50.0 mL), dried over magnesium sulfate (MgSO4), and filtered. The filtrate was concentrated on a rotary evaporator under reduced pressure. To the crude product was added 30 mL of a 4.0M solution of anhydrous HCl in dioxane. The resulting solid was filtered and rinsed with 20% methanol in diethyl ether to remove impurities. The solid was dissolved in methanol and neutralized with sufficient AG 1-X8 Resin (hydroxide form) that the pH of the solution became basic. The mixture was filtered, and the filtrate was concentrated on a rotary evaporator at reduced pressure to afford the title compound (0.695 g, 54% yield).
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