2-Bromopyridine → 1-((2S,4R)-2-methyl-6-(5-(morpholine-4-carbonyl)pyridin-2-yl)-4-(pyridin-2-ylamino)-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-bromopyridine (0.044 mL, 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 (66.9 mg, 0.696 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 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 dissolved in acetonitrile (20 mL) and 0.1M aq. ammonium bicarbonate (20 mL). The mixture was filtered, and the filtrate concentrated in vacuo to give a residue which was purified by MDAP (HpH) to give 1-((2S,4R)-2-methyl-6-(5-(morpholine-4-carbonyl)pyridin-2-yl)-4-(pyridin-2-ylamino)-3,4-dihydroquinolin-1(2H)-yl)ethanone (41 mg, 0.087 mmol, 38% yield). LCMS: (Formate, 2 min), Rt=0.55 mins, MH+472

Provenance & Evidence