반응 #662
ord-bdce974c72714a5996ad19d3b75acd9c
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2-chloro-5-fluoro-4-(4-fluoro-2-methoxyphenyl)pyrimidine (0.12 g, 0.47 mmol), 3-fluoro-5-((methylsulfonyl)methyl)aniline (0.095 g, 0.47 mmol), cesium carbonate (0.609 g, 1.87 mmol), (9,9-dimethyl-9H-xanthene-4,5-diyl)bis(diphenylphosphine) (0.068 g, 0.12 mmol)and Pd2(dba)3 (0.086 g, 0.09 mmol) were suspended in degassed 1,4-dioxane (3 mL) at ambient temperature. The resulting mixture was degassed, purged with nitrogen and heated at 100 °C for 3 hours after which time reaction was shown to be complete by LC-MS. The mixture was allowed to cool overnight. The reaction mixture was diluted with water (250 mL), and extracted with DCM (250 mL). The organic was dried over MgSO4, filtered and evaporated to afford crude product. The crude product was purified by flash silica chromatography, elution 50% ethyl acetate in Heptane. Fractions were evaporated to dryness to afford crude product. The crude product was purified by preparative HPLC (Waters XBridge Prep C18 OBD column, 5µ silica, 50 mm diameter, 150 mm length), using decreasingly polar mixtures of water (containing 1% NH3) and MeCN as eluents. Fractions containing the desired compound were evaporated to dryness to afford 5-fluoro-4-(4-fluoro-2-methoxyphenyl)-N-(3-fluoro-5-((methylsulfonyl)methyl)phenyl)pyrimidin-2-amine (0.120 g, 60.6 %) as a white solid.