Potassium Phosphate, Tribasic → 3-Amino-6-(4-((2-methoxyethoxy)-methoxy)-3-(trifluoromethyl)phenyl)-4-(methylamino)picolinonitrile

Participants

Reaction Conditions

Reaction Steps

2-(4-((2-Methoxyethoxy)methoxy)-3-(trifluoromethyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3.83 g), 3-amino-6-chloro-4-(methylamino)-picolinonitrile (1.55 g), tris(dibenzylideneacetone)dipalladium (0) (0.389 g), tricyclohexylphosphine (0.286 g) and potassium phosphate (3.60 g) were charged to a 100 ml flask. Dioxane (30 ml) and water (12 ml) were added and the mixture placed under a nitrogen atmosphere. The reaction was heated to 110° C. for 3 hours and allowed to stand at room temperature for 2 hours. The mixture was diluted with EtOAc (200 ml) filtered through celite, washed with water (3×200 ml), dried over sodium sulphate and then solvent was evaporated under reduced pressure to yield crude product as a brown oil. DCM was added to the residue causing a pale brown solid to crash out of solution. The mixture was filtered and the solid washed with a small amount of DCM followed by ether to afford 3-amino-6-(4-((2-methoxyethoxy)-methoxy)-3-(trifluoromethyl)phenyl)-4-(methylamino)picolinonitrile (28% yield). The liquors were purified by flash chromatography (340 g silica column; 2:1, 1:1, 0:1 heptane/EtOAc mobile phase) to afford further 3-amino-6-(4-((2-methoxyethoxy)-methoxy)-3-(trifluoromethyl)phenyl)-4-(methylamino)picolinonitrile (49% yield).

Provenance & Evidence