[NH2:1][C:2]1[C:3]([C:9]([NH:11][C:12]2[CH:13]=[N:14][CH:15]=[CH:16][C:17]=2[C:18]2[CH:23]=[C:22]([CH3:24])[N:21]=[C:20]([N:25](C(OC(C)(C)C)=O)C(OC(C)(C)C)=O)[CH:19]=2)=[O:10])=[N:4][C:5](Br)=[CH:6][CH:7]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.CC([O-])=O.[K+].Br[C:83]1[C:88]([F:89])=[CH:87][CH:86]=[CH:85][N:84]=1>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].C(Cl)Cl.CCOC(C)=O.O.O1CCOCC1>[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:83]2[C:88]([F:89])=[CH:87][CH:86]=[CH:85][N:84]=2)=[N:4][C:3]=1[C:9]([NH:11][C:12]1[CH:13]=[N:14][CH:15]=[CH:16][C:17]=1[C:18]1[CH:23]=[C:22]([CH3:24])[N:21]=[C:20]([NH2:25])[CH:19]=1)=[O:10]To a solution of degassed dioxane (0.03M) was added 3-amino-6-bromo-N-(2′-(di-BOC-amino)-6′-methyl-4,4′-bipyridin-3-yl)picolinamide (1.0 equiv.), bis(pinacolato)diboron (2.0 equiv.), Pd2(dba)3 (0.05 equiv.), PCy3 (0.075 equiv.), and KOAc (3.0 equiv.). The solution was heated to 90° C. for 16 hrs until all starting material was consumed. Filtered the reaction and concentrated the filtrate. The crude was dried under vacuo, then dissolved in DME/2M Na2CO3 (3:1, 0.05M), followed by addition of 2-bromo-3-fluoropyridine (2.0 equiv.) and Pd(dppf)Cl2-DCM (0.10 equiv.). The reaction was heated to 100° C. in an oil bath until consumption of the boronic ester. Cooled to room temperature, added H2O and EtOAc, the organic phase was washed with brine, then dried with Na2SO4, and concentrated. The crude material was purified via SiO2 column chromatography eluting with EtOAc and hexanes (1:1) and the pure product was concentrated and stirred in DCM/TFA (25%) until completion of the deprotection. The reaction was concentrated to dryness and purified via reverse phase HPLC to afford 5-amino-N-(2′-amino-6′-methyl-4,4′-bipyridin-3-yl)-3′-fluoro-2,2′-bipyridine-6-carboxamide. LCMS (m/z): 416.2 (MH+); LC Rt=1.77 min.
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