2-Bromo-5-chloropyridine → 1-((2S,4R)-4-((5-chloropyridin-2-yl)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) (100 mg, 0.232 mmol), 2-bromo-5-chloropyridine (89 mg, 0.464 mmol), 2′-(dicyclohexylphosphino)-N,N-dimethyl-[1,1′-biphenyl]-2-amine (18.3 mg, 0.046 mmol), tris(dibenzylideneacetone)dipalladium(0) (21.3 mg, 0.023 mmol) and sodium tert-butoxide (44.6 mg, 0.464 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. A further portion of 2-bromo-5-chloropyridine (89 mg, 0.464 mmol), 2′-(dicyclohexylphosphino)-N,N-dimethyl-[1,1′-biphenyl]-2-amine (18.3 mg, 0.046 mmol), tris(dibenzylideneacetone)dipalladium(0) (21.3 mg, 0.023 mmol), sodium tert-butoxide (44.6 mg, 0.464 mmol) and 1,4-dioxane (1 mL) were added 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 saturated aqueous sodium bicarbonate (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-((5-chloropyridin-2-yl)amino)-2-methyl-6-(5-(morpholine-4-carbonyl)pyridin-2-yl)-3,4-dihydroquinolin-1(2H)-yl)ethanone (34 mg, 0.067 mmol, 29% yield) LCMS: (Formate, 2 min), Rt=0.83 mins, MH+506.

Provenance & Evidence