Morpholine → 5,7-difluoro-N-(6'-methoxymorpholino-2,3'-bipyridin-3-yl)-3-methyl-2-(pyridin-2-yl)quinolin-4-amine

Participants

Reaction Conditions

Reaction Steps

A mixture of N-(5-bromo-6′-methoxy-2,3′-bipyridin-3-yl)-5,7-difluoro-3-methyl-2-(pyridin-2-yl)quinolin-4-amine (142.1 mg, 0.27 mmol), 2-dicyclohexylphosphino-2,4,6,-triisopropylbiphenyl, (X-Phos) (25.8 mg, 0.054 mmol), tris(dibenzylideneacetone)dipalladium (0) (25.1 mg, 0.027 mmol), morpholine (0.05 mL, 0.57 mmol), and sodium tert-butoxide (74.9 mg, 0.78 mmol) in dry toluene (5 mL) was degassed by nitrogen. The mixture was heated to 100° C. After 23 h, the reaction was cooled to rt then treated with water. After extracting twice with EtOAc, the organic layer was combined and dried over anhydrous magnesium sulfate. After filtration and concentration, the residue was purified on basic alumina (5-20% EtOAc in hexanes) to afford an impure orange residue that was further purified with SFC chromatography to afford a yellow solid as 5,7-difluoro-N-(6′-methoxymorpholino-2,3′-bipyridin-3-yl)-3-methyl-2-(pyridin-2-yl)quinolin-4-amine. 1H NMR (400 MHz, CDCl3) δ ppm 8.74 (2H, m), 8.10 (2H, m), 7.95 (2H, m), 7.61 (1H, d, J=9.6 Hz), 7.39 (1H, ddd, J=6.7, 4.8, 2.0 Hz), 7.01 (3H, m), 6.53 (1H, d, J=2.3 Hz), 4.07 (3H, m), 3.91 (4H, m), 3.24 (4H, m), 2.23 (3H, s). Mass Spectrum (pos.) m/e: 541.2 (M+1).

Provenance & Evidence