Dichloromethane → 5-{2-[2-amino-6-(4-methylpiperazin-1-yl)pyrimidin-4-yl]-6-fluoro-1,2,3,4-tetrahydroisoquinolin-7-yl}-N-methylpyridine-2-carboxamide

Participants

Reaction Conditions

Reaction Steps

A mixture of 4-(7-bromo-6-fluoro-3,4-dihydroisoquinolin-2(1H)-yl)-6-(4-methylpiperazin-1-yl)pyrimidin-2-amine (0.025 g, 0.060 mmol), N-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine-2-carboxamide (0.0140 g, Frontier, Cat. No. M10074) in 1,4-dioxane (0.36 mL) was stirred at r.t. for 10 min. Potassium carbonate (37.8 mg, 0.274 mmol) in water (0.18 mL) was added. The mixture was degassed and refilled with nitrogen three times [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) complex with dichloromethane (1:1) (3.0 mg, 0.0036 mmol) was added and the mixture was degassed and refilled with nitrogen three times and then heated at 120° C.) (oil bath temperature) for 3 h. After cooling, the mixture was diluted with methanol, and filtered. The filtrate was purified on RP-HPLC (pH=10) to afford the desired product. LCMS (M+H)+: m/z=477.2.

Provenance & Evidence