反应详情

To 7-(5-fluoro-2-methylphenyl)isoquinolin-3-amine (151.4 mg, 0.6001 mmol) and 2-bromo-6-methoxypyridine (110.0 uL, 0.8951 mmol) was added 1,4-dioxane (4.0 mL, 51 mmol). Nitrogen gas was bubbled through this mixture while stirring for 10 minutes, and then palladium (II) acetate (14.5 mg, 0.0646 mmol), 4,5-bis(diphenylphosphino)-9,9-dimethylxanthene (57.1 mg, 0.0987 mmol), and cesium carbonate (397.6 mg, 1.220 mmol) were added. The reaction mixture was stirred in a sealed vial at 100° C. for 90 minutes. The reaction mixture was diluted with dichloromethane, filtered through celite, and evaporated in vacuo. The crude residue was purified via flash chromatography on silica gel (12 g silica, solvent gradient: 0-80% ethyl acetate in dichloromethane) to yield 227.4 mg of the title compound as 80% pure material. 52.4 mg of this material was purified via reverse phase HPLC and lyophilized to yield 17.9 mg of 7-(5-fluoro-2-methylphenyl)-N-(6-methoxypyridin-2-yl)isoquinolin-3-amine. LCMS (ESI): RT (min)=5.057, M+H=360.1, method=E; 1H NMR (400 MHz, DMSO-d6) δ 9.80 (s, 1H), 9.11 (s, 1H), 8.58 (s, 1H), 7.97 (s, 1H), 7.84 (d, J=8.5 Hz, 1H), 7.64 (d, J=8.4 Hz, 1H), 7.56 (t, J=7.8 Hz, 1H), 7.38 (q, J=6.3 Hz, 1H), 7.15 (t, J=8.5 Hz, 2H), 6.82 (d, J=7.8 Hz, 1H), 6.28 (d, J=7.8 Hz, 1H), 4.01 (s, 3H), 2.26 (s, 3H).

1. customNitrogen gas was bubbled through this mixture
2. stirringThe reaction mixture was stirred in a sealed vial at 100° C. for 90 minutes
3. filtrationfiltered through celite
4. customevaporated in vacuo
5. customThe crude residue was purified via flash chromatography on silica gel (12 g silica, solvent gradient: 0-80% ethyl acetate in dichloromethane)