A stirred mixture of mostly 2,5-dicyclohexenylpyridin-3-amine (0.047 g, 0.19 mmol), 4-bromo-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinoline (0.085 g, 0.26 mmol), 2-dicyclohexylphosphino-2,4,6,-triisopropylbiphenyl (0.019 g, 0.039 mmol), tris(dibenzylideneacetone)dipalladium (0) (0.018 g, 0.019 mmol), and sodium tert-butoxide (0.056 g, 0.58 mmol) in dry toluene (2.0 mL) was purged three times with argon and placed under vacuum three times, then the mixture was heated to 100° C. After 2.5 h, the reaction was cooled to rt. After extracting twice with EtOAc, the organics were combined and dried over anhydrous magnesium sulfate. After filtration and concentration the residue was purified on silica gel (0-10% of 89:9:1 DCM:MeOH:ammonium hydroxide solution in DCM) to afford an impure light yellow film. The light yellow film was further purified with HPLC 10-90% of 0.1% TFA acetonitrile solution in 0.1% TFA water solution. The desired fractions (Prep. HPLC Retention time was −14.1 min) were concentrated then diluted with EtOAc. After washing twice with satd aq. sodium bicarbonate solution and once with brine, the solvent was removed under reduced pressure to yield a light yellow solid as N-(2,5-di-1-cyclohexen-1-yl-3-pyridinyl)-5,7-difluoro-3-methyl-2-(2-pyridinyl)-4-quinolinamine. 1H NMR (500 MHz, CDCl3) δ ppm 8.74 (1H, ddd, J=4.9, 1.7, 1.0 Hz), 8.23 (1H, d, J=2.0 Hz), 7.91 (1H, m), 7.85 (1H, m), 7.62 (1H, ddd, J=9.7, 2.4, 1.1 Hz), 7.38 (1H, ddd, J=7.4, 4.8, 1.2 Hz), 7.33 (1H, d, J=11.5 Hz), 7.00 (1H, ddd, J=13.6, 8.6, 2.6 Hz), 6.86 (1H, d, J=2.0 Hz), 6.18 (1H, m), 6.14 (1H, m), 2.48 (2H, br. s.), 2.33 (2H, br. s.), 2.29 (2H, m), 2.22 (2H, m), 2.14 (3H, s), 1.88 (2H, m), 1.79 (4H, m), 1.67 (2H, m). Mass Spectrum ESI (pos.) m/e: 509.2 (M+H)+.
