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

温度

90 °C

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

ORDレコード

ord-c8bd9a8a68d6433daf2fe8e0bf9a22b5

出典データセット

750 AstraZeneca ELN dataset

元リンク

出典を表示