1,3-Dimethyl-1H-pyrazol-5-amine → 2-[[2-[(2,5-dimethylpyrazol-3-yl)amino]-5-(trifluoromethyl)-4-pyridyl]amino]-4-fluoro-N-methyl-benzamide

関与物質

反応条件

反応手順

2-(2-chloro-5-(trifluoromethyl)pyridin-4-ylamino)-4-fluoro-N-methylbenzamide (2 g, 5.75 mmol), 1,3-dimethyl-1H-pyrazol-5-amine (0.767 g, 6.90 mmol) diacetoxypalladium (0.103 g, 0.46 mmol) (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.533 g, 0.92 mmol) and cesium carbonate (2.249 g, 6.90 mmol) were suspended in dioxane (25 ml). The reaction was degased, purged with argon (3 times) and heated to at 90 °C for 4 hours. The reaction mixture was allowed to cool to room temperature, diluted with DCM (some drop of MeOH) and filtered. Silica gel was added and solvents were evaporated to afford the crude, which was purified by flash chromatography on silica gel eluting with 0 to 10% methanol in ethyl acetate/DCM (1/1) . The solvent was evaporated to dryness to give a residue which was triturated with DCM, filtered and dried to afford EN03299-48-01 (1.5 g, 3.55 mmol, 61.7 %) as a off-white solid. This sample EN03299-48-01 (1.5 g, 3.55 mmol, 61.7 %) and _EN03299-43-01_ were combined and triturated with hot tBuOMe, filtered and dried to afford EN03299-48-02 (2.1 g, 4.90 mmol, 85 %) as a white solid. Trituration filtrates were evaporated and the residue was taken with DCM, filtered and dried to afford EN03299-48-03 (0.5 g, 1.184 mmol, 20.58 %) as a white solid TSB 46.916

情報源と証拠