Potassium Phosphate, Tribasic → 3-Amino-4-(methylamino)-6-(4-(pyridin-4-ylmethoxy)-3-(trifluoromethyl)phenyl)picolinonitrile

Participants

Reaction Conditions

Reaction Steps

A suspension of 4-((4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-(trifluoromethyl)phenoxy)methyl)pyridine (1.39 g), 3-amino-6-chloro-4-(methylamino)-picolinonitrile (0.669 g), tris(dibenzylideneacetone)dipalladium (0) (173 mg), tricyclohexylphosphine (127 mg) and potassium phosphate (1.621 g) in 1,4-dioxane (15 ml) and water (7.5 ml) was stirred at 100° C. for 2 h. The reaction mixture was cooled, filtered to remove insoluble precipitate. The precipitate was dried in vacuum oven to give 430 mg light brown solid as 3-amino-4-(methylamino)-6-(4-(pyridin-4-ylmethoxy)-3-(trifluoromethyl)phenyl)picolinonitrile (29%). Filtrate was partitioned between water and ethyl acetate, washed with water, dried over sodium sulfate, filtered and concentrated. Purified by Biotage SNAP cartridge KP-Sil column (25 g, heptane:ethyl acetate=1:0, 1:1, 1:3 to 0:1 then ethyl acetate:methanol=25:1, 20:1 then dichloromethane:methanol=20:1) to give 568 mg of the title compound as a light brown solid (39%).

Provenance & Evidence