8-amino-2-methyl-3,4-dihydroisoquinolin-1(2H)-one → 8-[(2,5-Dichloropyridin-4-yl)amino]-2-methyl-3,4-dihydroisoquinolin-1-one

Participants

Reaction Conditions

Reaction Steps

diacetoxypalladium (0.152 g, 0.68 mmol) was added to a stirred suspension of 2,5-dichloro-4-iodopyridine (3.71 g, 13.56 mmol), 8-amino-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (2.39 g, 13.56 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.785 g, 1.36 mmol) and cesium carbonate (6.63 g, 20.34 mmol) in 1,4-dioxane (70 mL). The resulting suspension was degassed with nitrogen and was stirred at 100 °C for 18 hours. Reaction was allowed to cool to room temperature, quenched with water (100 mL) and extracted with EtOAc*. Combined organic phases were washed with water, brine, dried over MgSO4 and concentrated to dryness. The crude product was purified by flash chromatography* on silica gel eluting with 0 to 10% ethyl acetate in dichloromethane. The solvent was evaporated to dryness to afford 8-(2,5-dichloropyridin-4-ylamino)-2-methyl-3,4-dihydroisoquinolin-1(2H)-one (2.160 g, 49.4 %) as a yellow crystalline solid.

Provenance & Evidence