2-amino-N,6-dimethoxybenzamide → 2-[[2-[(2,5-dimethylpyrazol-3-yl)amino]-5-(trifluoromethyl)pyridin-4-yl]amino]-N,6-dimethoxybenzamide

참여 물질

반응 조건

반응 단계

N-(1,3-dimethyl-1H-pyrazol-5-yl)-4-iodo-5-(trifluoromethyl)pyridin-2-amine (351 mg, 0.92 mmol), 2-amino-N,6-dimethoxybenzamide (270 mg, 1.38 mmol) and Cesium carbonate (598 mg, 1.83 mmol) in degassed dioxane (8 mL) under nitrogen at room temperature were allowed to stir, degassing (nitrogen) for a further 5 minutes before adding Palladium(II) acetate (10.30 mg, 0.05 mmol) and 4,5-Bis(diphenylphosphino)-9,9-dimethylxanthene (53.1 mg, 0.09 mmol). The reaction mixture was then stirred at 90 °C for 4 hours and cooled to RT. LCMS analysis showed a new peak for product but both SM's still remained. The RM was then heated at 100 °C for a further 4 hours, after this time LCMS analysis showed none of the pyridine SM remaining and a bigger peak for product. The RM was concentrated and then dissolved in methanol and dry loaded onto silica. The crude was purified on a 12g Si column eluting with 0-10 % methanol in DCM. Fractions 3-8 and 18-28 contained product and were combined. LCMS analysis/TLC showed that the product was still not pure. Diethyl ether trituration gave 2-(2-(1,3-dimethyl-1H-pyrazol-5-ylamino)-5-(trifluoromethyl)pyridin-4-ylamino)-N,6-dimethoxybenzamide (235 mg, 56.9 %) as a pure product.

출처 및 근거