Piperidine → N-(7-(piperidin-1-yl)isoquinolin-3-yl)cyclopropanecarboxamide

Participants

Reaction Conditions

Reaction Steps

A solution was made of N-(7-bromoisoquinolin-3-yl)cyclopropanecarboxamide (66.6 mg, 0.229 mmol) and piperidine (46 uL, 0.46 mmol) in 1,4-dioxane (1.5 mL, 19 mmol). Nitrogen gas was bubbled through the mixture for 10 minutes, and then palladium (II) acetate (6.0 mg, 0.027 mmol), rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (15.2 mg, 0.0244 mmol), and cesium carbonate (231 mg, 0.709 mmol) were added. The reaction mixture was stirred in a sealed vial at 100° C. for 18 hours. The reaction mixture was then cooled to room temperature, diluted in ethyl acetate, filtered through celite, washed with saturated aqueous NaHCO3, dried over MgSO4, and evaporated in vacuo. The crude product was purified via reverse phase HPLC and lyophilized to yield 3.8 mg (6%) of N-(7-(piperidin-1-yl)isoquinolin-3-yl)cyclopropanecarboxamide. LCMS (ESI): RT=3.481, M+H=416.2, method=E; 1H NMR (400 MHz, DMSO-d6) δ 10.64 (s, 1H), 8.89 (s, 1H), 8.27 (s, 1H), 7.67 (d, J=9.1 Hz, 1H), 7.55 (dd, J=9.1, 2.4 Hz, 1H), 7.25 (d, J=2.1 Hz, 1H), 3.27-3.20 (m, 4H), 2.03 (m, 1H), 1.66 (d, J=4.6 Hz, 4H), 1.58 (d, J=4.7 Hz, 2H), 0.81 (m, 4H).

Provenance & Evidence