反应详情

温度

100 °C

A solution of 3-chloro-5-((4-(methoxymethoxy)-2-methylphenyl)ethynyl)picolinonitrile (6-10) (1.0 equiv.), ethyl 3-(3-(tert-butoxycarbonylamino)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propanoate (6-5) (1.25 equiv.), tris(dibenzylideneacetone)dipalladium(0) (0.10 equiv.), dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine (0.20 equiv.), and sodium bicarbonate (3.0 equiv.) in n-butanol/H2O (5:1, 0.2 M) was degassed and stirred at 100° C. overnight. After cooling to ambient temperature, the reaction content was diluted with ethyl acetate and water. The two phases were separated, and the aqueous layer was extracted twice with ethyl acetate. The combined organic layers were washed with brine, dried over anhydrous MgSO4, and concentrated in vacuo. The crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO) using 0-40% ethyl acetate in DCM first to remove the impurity, then 0-4% MeOH in DCM to give ethyl 3-(5-amino-2-((4-(methoxymethoxy)-2-methylphenyl)ethynyl)-benzo[f][1,7]naphthyridin-8-yl)propanoate (6-11). Further purification was accomplished by precipitating and washing in hot ether.

1. temperatureAfter cooling to ambient temperature
2. customThe two phases were separated
3. extractionthe aqueous layer was extracted twice with ethyl acetate
4. washThe combined organic layers were washed with brine
5. dry with materialdried over anhydrous MgSO4
6. concentrationconcentrated in vacuo
7. customThe crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO)
8. customto remove the impurity