2-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenyl → N-(5-(3,6-dihydro-2H-pyran-4-yl)pyridin-3-yl)-5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinolin-4-amine

Participants

Reaction Conditions

Reaction Steps

A mixture of 5-(3,6-dihydro-2H-pyran-4-yl)pyridin-3-amine (38.8 mg, 0.22 mmol), 4-chloro-5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinoline (52.8 mg, 0.17 mmol), 2-dicyclohexylphosphino-2,4,6,-triisopropylbiphenyl, (X-Phos) (14.4 mg, 0.03 mmol), tris(dibenzylideneacetone)dipalladium (0) (7.2 mg, 7.9 μmol), and sodium tert-butoxide (45.1 mg, 0.47 mmol) in dry toluene (1.5 mL) was degassed by nitrogen. The resulting reaction was heated to 100° C. and monitored with TLC and LC-MS. After 18 h, the reaction was cooled to rt then poured into water. After extracting twice with EtOAc and twice with DCM, the combined organic extractions were dried over anhydrous magnesium sulfate. After filtration and concentration, the residue was purified on basic alumina (0-30% EtOAc in hexanes) to afford an orange film as N-(5-(3,6-dihydro-2H-pyran-4-yl)pyridin-3-yl)-5,7-difluoro-3-methyl-2-(4-methylpyridin-2-yl)quinolin-4-amine. 1H NMR (400 MHz, CDCl3) δ ppm 8.63 (1H, m), 8.28 (1H, d, J=2.0 Hz), 8.17 (1H, d, J=2.5 Hz), 7.66 (2H, m), 7.20 (1H, ddd, J=5.0, 1.7, 0.8 Hz), 7.14 (1H, d, J=11.9 Hz), 7.10 (2H, m), 6.20 (1H, tt, J=3.0, 1.5 Hz), 4.32 (2H, q, J=2.7 Hz), 3.93 (2H, t, J=5.4 Hz), 2.55 (5H, m), 2.14 (3H, s). Mass Spectrum (pos.) m/e: 445.1 (M+1).

Provenance & Evidence