N-(1,3-dimethylpyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine → 2-[[2-[(1,3-dimethylpyrazol-4-yl)amino]-5-(trifluoromethyl)pyridin-4-yl]amino]-5-fluoro-N-methoxybenzamide

Participants

Reaction Conditions

Reaction Steps

2-amino-5-fluoro-N-methoxybenzamide (2.60 g, 14.13 mmol), N-(1,3-dimethyl-1H-pyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (3.6 g, 9.42 mmol) (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.545 g, 0.94 mmol) diacetoxypalladium (0.106 g, 0.47 mmol) and cesium carbonate (6.14 g, 18.84 mmol) were suspended in dioxane (40 mL). The reaction was degased, purged with argon (3 times) and heated to 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. The crude product was purified by flash chromatography on silica gel eluting with 0 to 15% methanol in ethyl acetate/DCM (1/1). Fractions containing the most part of pure product were evaporated. This residue was re-purified by trituration with DCM (with 5% MeOH), to give after filtration EN03299-42-01 (3.5 g, 7.98 mmol, 85 %) which contains trace of AcOEt and 30%mol DCM. The resulting solid was recrystallised from ethanol (35 ml) and the resulting crystalline solid was collected by filtration, washed with ethanol and dried to a constant weight in a vacuum oven to afford EN03299-42-02 (2.7 g, 5.54 mmol, 58.8 %) as a white crystalline solid. TSB 46.938

Provenance & Evidence