Reaktion #718356

Reaktionsgleichung

3-chloro-5-((4-(methoxymethoxy)-2-methylphenyl)ethynyl)picolinonitrile

ethyl 3-(3-(tert-butoxycarbonylamino)-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl)propanoate

dicyclohexyl(2′,6′-dimethoxybiphenyl-2-yl)phosphine

sodium bicarbonate

n-butanol H2O

→

ethyl 3-(5-amino-2-((4-(methoxymethoxy)-2-methylphenyl)ethynyl)-benzo[f][1,7]naphthyridin-8-yl)propanoate

Lösungsmittel

ethyl acetate

water

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturAfter cooling to ambient temperature
2. 2
   SonstigeThe two phases were separated
3. 3
   Extraktionthe aqueous layer was extracted twice with ethyl acetate
4. 4
   WaschenThe combined organic layers were washed with brine
5. 5
   Trocknendried over anhydrous MgSO4
6. 6
   Einengenconcentrated in vacuo
7. 7
   SonstigeThe crude material was purified by flash chromatography on a COMBIFLASH® system (ISCO)
8. 8
   Sonstigeto remove the impurity

Vorschrift

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.

Quelle