Reaction #718356
ord-5f3dcea1c0e04df28f31a6d535ad1474
Reaction equation
Reactants
Solvents
Conditions
Workup
- 1TemperatureAfter cooling to ambient temperature
- 2OtherThe two phases were separated
- 3Extractionthe aqueous layer was extracted twice with ethyl acetate
- 4WashThe combined organic layers were washed with brine
- 5Dryingdried over anhydrous MgSO4
- 6Concentrationconcentrated in vacuo
- 7OtherThe crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO)
- 8Otherto remove the impurity
Procedure
A solution of 3-chloro-5-((4-(methoxymethoxy)-2-methylphenyl)ethynyl)picolinonitrile (10) (1.0 equiv.), ethyl 3-(3-(tert-butoxycarbonylamino)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propanoate (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, 0.2M) 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 (11). Further purification was accomplished by precipitating and washing in hot ether.