Cesium carbonate → 7-(5-fluoro-2-methylphenyl)-N-(1,1,1-trifluoropropan-2-yl)isoquinolin-3-amine

Participants

Reaction Conditions

Reaction Steps

A mixture of 3-chloro-7-(5-fluoro-2-methylphenyl)isoquinoline (41 mg, 0.15 mmol), 1-methyl-2,2,2-trifluoroethylamine, hydrochloride (36.5 mg, 0.244 mmol), 2-(dicyclohexylphosphino)-3,6-dimethoxy-2′-4′-6′-tri-1-propyl-1,1′-biphenyl (8.4 mg, 0.016 mmol), chloro[2-(dicyclohexylphosphino)-3-,6-dimethoxy-2-4′-6′-tri-1-pr-1,1′-biphenyl)][2-(2-aminoethyl)Ph]Pd(II) (13.7 mg, 0.0172 mmol), and cesium carbonate (148 mg, 0.454 mmol) in 1,4-dioxane (1.5 mL, 19 mmol) was purged with nitrogen and then heated at 90° C., for 2 hours. Sodium-tert-butoxide (49.2 mg, 0.512 mmol) was then added and the reaction mixture heated at 90° C. overnight. The mixture was then partitioned between ethyl acetate and water, and the organic layer was washed with water and brine, dried over MgSO4, filtered, and evaporated in vacuo. The crude product was purified via reverse phase HPLC and lyophilized to yield 19.7 mg (37%) of 7-(5-fluoro-2-methylphenyl)-N-(1,1,1-trifluoropropan-2-yl)isoquinolin-3-amine. LCMS (ESI): RT (min)=5.716, M+H=349.1, method=E; 1H NMR (400 MHz, DMSO-d6) δ 8.96 (s, 1H), 7.84 (s, 1H), 7.66 (d, J=8.6 Hz, 1H), 7.53 (d, J=8.6 Hz, 1H), 7.36 (dd, J=9.3, 5.9 Hz, 1H), 7.13 (dd, J=7.8, 5.1 Hz, 2H), 7.01 (d, J=9.1 Hz, 1H), 6.88 (s, 1H), 5.11-4.91 (m, 1H), 2.25 (s, 3H), 1.37 (d, J=6.9 Hz, 3H).

Provenance & Evidence