[B-](F)(F)(F)F.N#[O+].[NH2:8][C:9]1[C:14]([F:15])=[C:13]([C:16]2[CH:21]=[CH:20][C:19](N)=[CH:18][CH:17]=2)[N:12]=[C:11]([C:23]([O:25][CH3:26])=[O:24])[C:10]=1[CH:27]=[CH2:28].[Br-:29].[K+].C1OCCOCCOCCOCCOCCOC1.N1C2C(=CC=C3C=2N=CC=C3)C=CC=1>C(Cl)Cl.CCOCC.[Cu](Br)Br.[Cu]Br.CC#N>[NH2:8][C:9]1[C:14]([F:15])=[C:13]([C:16]2[CH:21]=[CH:20][C:19]([Br:29])=[CH:18][CH:17]=2)[N:12]=[C:11]([C:23]([O:25][CH3:26])=[O:24])[C:10]=1[CH:27]=[CH2:28]To a 0° C. suspension of nitrosyl tetrafluoroborate (0.122 g, 1.044 mmol) in CH2Cl2 (2 mL) was added a solution of methyl 4-amino-6-(4-aminophenyl)-5-fluoro-3-vinylpicolinate (0.3 g, 1.044 mmol) in a 1:1 mixture of CH2Cl2 and CH3CN (10 mL). The reaction mixture was stirred at 0° C. for 30 min, then was added dropwise to a suspension of potassium bromide (0.497 g, 4.18 mmol), 18-crown-6 (0.028 g, 0.104 mmol), copper(II) bromide (0.023 g, 0.104 mmol), copper(I) bromide (0.015 g, 0.104 mmol), and 1,10-phenanthroline (0.019 g, 0.104 mmol). The mixture was stirred at 20° C. for 1 h. Additional copper (I) bromide (0.749 g, 5 equiv) was added and the reaction was stirred at 20° C. for an additional 1 h. The reaction mixture was diluted with Et2O and filtered on a short pad of Celite™. The supernatant was concentrated and purified by flash column chromatography (SiO2, hexanes/EtOAc gradient) followed by preparative reverse phase HPLC (water/acetonitrile gradient) to afford the title compound as a light brown solid (130 mg, 0.370 mmol, 35.5%).
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