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

Participants

Reaction Conditions

Reaction Steps

1-((2S,4R)-4-amino-2-methyl-6-(5-(morpholine-4-carbonyl)pyridin-2-yl)-3,4-dihydroquinolin-1(2H)-yl)ethanone hydrochloride (for a preparation see Intermediate 65) (120 mg, 0.278 mmol), 1-bromo-3-chlorobenzene (0.065 mL, 0.557 mmol), 2′-(dicyclohexylphosphino)-N,N-dimethyl-[1,1′-biphenyl]-2-amine (21.9 mg, 0.056 mmol), tris(dibenzylideneacetone)dipalladium(0) (25.5 mg, 0.028 mmol) and sodium tert-butoxide (37.5 mg, 0.390 mmol) were combined in 1,4-dioxane (2 mL) and the mixture degassed over a period of 15 mins, before being heated under microwave irradiation to 120° C. for 25 mins. The reaction mixture was partitioned between water (50 mL) and DCM (3×50 mL). The organics were combined, dried by passing through a hydrophobic frit and concentrated in vacuo to give a residue which was purified by MDAP (HpH) to give 1-((2S,4R)-4-((3-chlorophenyl)amino)-2-methyl-6-(5-(morpholine-4-carbonyl)pyridin-2-yl)-3,4-dihydroquinolin-1(2H)-yl)ethanone (13 mg, 0.026 mmol, 9.2% yield).

Provenance & Evidence