Cl[C:2]1[N:7]=[C:6]([NH:8][C@@H:9]2[CH2:14][CH2:13][CH2:12][CH2:11][C@@H:10]2[NH:15]C(=O)[O-])[CH:5]=[N:4][C:3]=1[C:19]#[N:20].[N:21]1[CH:26]=[CH:25][CH:24]=[N:23][C:22]=1[C:27]1[CH:28]=[C:29]([NH2:33])[CH:30]=[N:31][CH:32]=1.C(=O)([O-])[O-:35].[Cs+].[Cs+].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.OS(O)(=O)=O>O1CCOCC1.C(O)(C(F)(F)F)=O.O.CC([O-])=O.CC([O-])=O.[Pd+2]>[NH2:15][C@H:10]1[CH2:11][CH2:12][CH2:13][CH2:14][C@H:9]1[NH:8][C:6]1[N:7]=[C:2]([NH:33][C:29]2[CH:30]=[N:31][CH:32]=[C:27]([C:22]3[N:23]=[CH:24][CH:25]=[CH:26][N:21]=3)[CH:28]=2)[C:3]([C:19]([NH2:20])=[O:35])=[N:4][CH:5]=1The mixture of tert-tutyl ((1S,2R)-2-((6-chloro-5-cyanopyrazin-2-yl)amino)cyclohexyl)carbamate (100 mg, 0.28 mmol), 5-(pyrimidin-2-yl)pyridin-3-amine (100 mg, 0.58 mmol), powder cesium carbonate (380 mg, 1.16 mmol), BINAP (37 mg, 0.06 mmol), Pd(OAc)2 (14 mg, 0.06 mmol) in 15 mL dioxane was degassed with argon stream. It was stirred in argon atmosphere at 110° C. for overnight. The mixture was cooled, diluted with 100 mL EtOAc, vigorously stirred, and filtered through celite. The filtrate was concentrated and subjected to silica flash column with 20-100% EtOAc in DCM to isolate the coupling product. It was then stirred in 5 mL TFA and 1 mL conc. H2SO4 at 80° C. for 30 m. It was cooled in ice bath, diluted with water, filtered, and subjected to reverse phase preparative HPLC to isolate the title compound (35 mg). MS found for C20H23N90 as (M+H)+ 406.5. UV: λ=259, 306 nm. 1H NMR: (CD3OD) δ 9.63 (1H, s), 9.24 (1H, s), 9.02 91H, s), 8.98 (2H, d, J=4.4 Hz), 7.70 (1H, s), 7.53 (1H, t, J=4.8 Hz), 4.74 (1H, m), 3.69 (1H, m), 1.92-1.56 (8H, m) ppm.
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