2-Bromo-5-methylpyridine → 1-((2S,4R)-2-methyl-4-((5-methylpyridin-2-yl)amino)-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) (80 mg, 0.186 mmol), 2-bromo-5-methylpyridine (63.9 mg, 0.371 mmol), 2′-(dicyclohexylphosphino)-N,N-dimethyl-[1,1′-biphenyl]-2-amine (14.6 mg, 0.037 mmol), tris(dibenzylideneacetone)dipalladium(0) (17 mg, 0.019 mmol) and sodium tert-butoxide (53.5 mg, 0.557 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 130° C. for 50 mins. A further portion of 2-bromo-5-methylpyridine (63.9 mg, 0.371 mmol), 2′-(dicyclohexylphosphino)-N,N-dimethyl-[1,1′-biphenyl]-2-amine (14.6 mg, 0.037 mmol), tris(dibenzylideneacetone)dipalladium(0) (17 mg, 0.019 mmol), sodium tert-butoxide (53.5 mg, 0.557 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 130° 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)-2-methyl-4-((5-methylpyridin-2-yl)amino)-6-(5-(morpholine-4-carbonyl)pyridin-2-yl)-3,4-dihydroquinolin-1(2H)-yl)ethanone (38 mg, 0.078 mmol, 42% yield). LCMS: (Formate, 2 min), Rt=0.58 mins, MH+486.

Provenance & Evidence