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) (1.817 g, 3.14 mmol), diacetoxypalladium (0.353 g, 1.57 mmol), 2-amino-N-methoxybenzamide (8.87 g, 53.39 mmol), N-(1,3-dimethyl-1H-pyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (12 g, 31.40 mmol) and cesium carbonate (20.46 g, 62.81 mmol) were weighed out in a round bottom flask. dioxane (130 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 ethyl acetate and the insolubles were removed by filtration, washed with EtOAc and the filtrate was concentrated. (Insolubles~19g). The crude product (30g) was purified by flash chromatography on silica gel eluting with 0 to 5% methanol in ethyl acetate. The solvent was evaporated to dryness, giving a gummy foam EN02972-52-01 (15 g, 35.7 mmol, 114 %): not pure. It was repurified by flash chromatography on silica gel eluting with 0 to 5% methanol in ethyl acetate. The solvent was evaporated to dryness to give to batches: one pure EN02972-52-02 (12 g, 28.5 mmol, 91 %), one less pure EN02972-52-03 (0.8 g, 1.903 mmol, 6.06 %). The foam EN02972-52-02 (12 g, 28.5 mmol, 91 %) was dissolved in hot EtOH (12mL). Crystallisation occurred. The resulting crystalline solid was collected by filtration and dried to a constant weight to afford EN02972-52-04 (8.7 g, 19.04 mmol, 60.6 %) as a white crystalline solid. Its filtrate was combined with EN02972-52-03 (0.8 g, 1.903 mmol, 6.06 %) and vacced down. The solid was taken up into EtOH, collected by filtration to give a second crop as a white solid EN02972-52-05 (1.88 g, 4.47 mmol, 14.24 %).

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