2-Bromo-5-chloropyridine → 1-((2S,4R)-4-((5-chloropyridin-2-yl)amino)-2-methyl-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-chloropyridine (78 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 (27.3 mg, 0.284 mmol) were combined in 1,4-dioxane (1 mL). The mixture was degassed over a period of 15 mins before being heated under microwave irradiation to 120° C. for 15 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)-4-((5-chloropyridin-2-yl)amino)-2-methyl-6-(6-(morpholine-4-carbonyl)pyridin-3-yl)-3,4-dihydroquinolin-1(2H)-yl)ethanone (54 mg, 0.107 mmol, 53% yield). LCMS: (Formate, 2 min), Rt=0.86 mins, MH+=506.

Provenance & Evidence