2-Bromo-5-methylpyridine → 1-((2S,4R)-2-methyl-4-((5-methylpyridin-2-yl)amino)-6-(6-(morpholine-4-carbonyl)pyridin-3-yl)-3,4-dihydroquinolin-1(2H)-yl)ethanone

Participants

Reaction Conditions

Reaction Steps

1-((2S,4R)-4-amino-2-methyl-6-(6-(morpholine-4-carbonyl)pyridin-3-yl)-3,4-dihydroquinolin-1(2H)-yl)ethanone (for a preparation, see Intermediate 56) (80 mg, 0.203 mmol), 2-bromo-5-methylpyridine (69.8 mg, 0.406 mmol), 2′-(dicyclohexylphosphino)-N,N-dimethyl-[1,1′-biphenyl]-2-amine (16.0 mg, 0.041 mmol), tris(dibenzylideneacetone)dipalladium(0) (18.6 mg, 0.020 mmol) and sodium tert-butoxide (39.0 mg, 0.406 mmol) were combined in 1,4-dioxane (2 mL). The mixture was degassed over a period of 15 mins before being heated under microwave irradiation to 120° C. for 30 mins. The mixture was partitioned between saturated aq. sodium bicarbonate (50 mL) and DCM (3×50 mL). The organic layers were combined, dried by passing through a hydrophobic frit and concentrated in vacuo. The resulting residue was purified by MDAP (HpH) to give 1-((2S,4R)-2-methyl-4-((5-methylpyridin-2-yl)amino)-6-(6-(morpholine-4-carbonyl)pyridin-3-yl)-3,4-dihydroquinolin-1(2H)-yl)ethanone (13 mg, 0.027 mmol, 13% yield) as an off-white solid. LCMS: (Formate, 2 min), Rt=0.58 mins, MH+=486.

Provenance & Evidence