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

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(9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.303 g, 0.52 mmol), diacetoxypalladium (0.059 g, 0.26 mmol), 2-amino-N-methoxybenzamide (1.479 g, 8.90 mmol), N-(1,3-dimethyl-1H-pyrazol-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 let to bubble in the mixture for 10 minutes. The suspension was stirred at 100 °C overnight. The reaction mixture was allowed to cool to room temperature under stirring, diluted with dichloromethane and methanol, silicagel was added and the mixture was concentrated. The crude product was purified by flash chromatography on silica gel (150g) eluting with 0 to 5% methanol in ethyl acetate/DCM (1/1). The solvent was evaporated to dryness, giving a gummy foam. 35 mL of tBuOMe was added and the resulting solution was stirred at rt for 3 hours. The resulting precipitate was collected by filtration, washed with tBuOMe and dried to a constant weight to afford EN02430-89-01 (1.53 g, 3.64 mmol, 69.5 %) as a white solid, which was contained DCM and EtOAc. It was taken up into a minimum of MeCN, heated to 100°C and MeCN was added until complete solubilisation. The solution was filtered and left to cool to rt overnight. The crystallized product was collected by filtration and dried to constant weight under high vacuum (7.10-2mbar) at 50°C for 1h, to give EN02430-89-02 (1.2 g, 2.63 mmol, 50.2 %) as a crystalline white solid. The filtrate was concentrated, triturated in MeCN and the resulting solid was collected by filtration to give EN02430-89-03 (0.2 g, 0.476 mmol, 9.09 %) - a second crop - as a white solid. 1g of EN02430-89-02 (1.2 g, 2.63 mmol, 50.2 %), EN02430-89-03 (0.2 g, 0.476 mmol, 9.09 %) & EN02430-89-04 (48 mg, 0.114 mmol, 2.182 %) were combined, stirred in boiling water (100 mL) for 10 minutes, cooled down, collected by filtration and dried under vacuum (7.10-2mbar) at 50°C in presence of P2O5, to give EN02430-89-05 (1.1 g, 2.56 mmol, 49.0 %)

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