反応 #381
ord-f57bbfadfec74fbbad7d399cf7b15368
溶媒
反応条件
実験手順
N-(1,3-dimethyl-1H-pyrazol-4-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (113 mg, 0.30 mmol), 2-amino-5-fluoro-N-methoxybenzamide (60 mg, 0.33 mmol) and Cesium carbonate (193 mg, 0.59 mmol) in degassed dioxane (4 mL) under nitrogen at room temperature were degassed (nitrogen) for a further 5 minutes before adding Palladium(II) acetate (3.32 mg, 0.01 mmol) and 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (17.14 mg, 0.03 mmol) the reaction mixture then being allowed to stir at 95 °C for 6 hours and cooled to RT. LCMS analysis showed a new peak for product (9%) but both SM's still remained (pyridine 71%, benzamide 13 %). Another 1.1 eq of benzamide (60 mg in 2ml dioxane) was added and the RM was then heated at 95 °C overnight. Lcms after this time showed no further progression with the reaction. Therefore a further portion of palladium acetate (0.05 eq. 3.32 mg) and the xanthene ligand (0.1 eq. 17.14 mg) were added and the RM stirred o/n at 95°C. Analysis after this time showed a majority peak for product and no pyridine SM remaining. The RM was concentrated and dry loaded onto silica. It was then purified on a 12g isco column using initially 0-100 % ethyl acetate in DCM followed by 0-10 % methanol in ethyl acetate to give 2-(2-(1,3-dimethyl-1H-pyrazol-4-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-5-fluoro- N-methoxybenzamide (60.0 mg, 46.2 %) which was not very pure Trituration with diethyl ether did not produce a purer product.