Cesium carbonate → 2-[[2-[(1,3-dimethylpyrazol-4-yl)amino]-5-(trifluoromethyl)-4-pyridyl]amino]-N-methoxy-benzamide

Participants

Reaction Conditions

Reaction Steps

9,9-dimethyl-4,5-bis(diphenylphosphino)xanthene (0.303 g, 0.52 mmol), palladium(II) acetate (0.059 g, 0.26 mmol), 2-amino-N-methoxybenzamide (1.479 g, 8.90 mmol), N-(1,3-dimethylpyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (2 g, 5.23 mmol) and cesium carbonate (3.41 g, 10.47 mmol) were weighed out in a round bottom flask. Dioxane (60 mL) was added and argon was bubbled through the mixture for 10 minutes. The suspension was stirred at 100° C. overnight. The reaction mixture was allowed to cool to room temperature with stirring, diluted with DCM and MeOH. Silica gel was added and the mixture was concentrated. The crude product was purified by flash chromatography on silica gel (150 g) eluting with 0 to 5% MeOH in EtOAc/DCM (1:1). The solvent was evaporated to dryness, giving. 35 mL of tBuOMe was added and the resulting solution was stirred at room temperature for 3 hours. The resulting precipitate was collected by filtration, washed with tBuOMe and dried to a constant weight to afford the title compound (1.53 g, 3.64 mmol, 69.5%) as a white solid. This solid was taken up into a minimum of acetonitrile, heated to 100° C. and more acetonitrile was added until complete solubilisation was achieved. The solution was filtered and left to cool to room temperature overnight. The resulting crystals were collected by filtration and dried to constant weight under high vacuum (7.10−2 mbar) at 50° C. for 1 hour, to give the title compound (1.2 g, 2.63 mmol, 50.2%) as a crystalline white solid.

Provenance & Evidence