Sodium hydride → 2-N-Methyl-2-N-phenyl-6-(5-{6-[(2,2,2-trifluoroethoxy)methyl]pyridin-3-yl}-1,2,4-oxadiazol-3-yl)-1,3,5-triazine-2,4-diamine

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Reaction Steps

To a solution of [5-(3-{4-amino-6-[methyl(phenyl)amino]-1,3,5-triazin-2-yl}-1,2,4-oxadiazol-5-yl)pyridin-2-yl]methanol (Example 295, 30 mg, 79 μmol) in anhydrous THF (10 mL) was added trifluoromethanesulfonic acid 2,2,2-trifluoro-ethyl ester (56 mg, 239 μmol). The solution was cooled to 0 C and sodium hydride (60% dispersion in mineral oil, 7 mg, 159 μmol) was added under an inert atmosphere and the mixture was stirred at room temperature for 24 h. The reaction mixture was then re-treated with trifluoromethanesulfonic acid 2,2,2-trifluoro-ethyl ester (56 mg, 239 μmol) and sodium hydride (60% dispersion in mineral oil, 7 mg, 159 μmol) and stirred for an additional 48 h at room temperature. The reaction mixture was quenched with water (20 mL) and extracted into EtOAc (3×25 mL). Combined organics were dried over magnesium sulfate and evaporated to dryness. The crude product was purified by silica chromatography (3% MeOH in DCM) and then re-purified by preparative HPLC-MS (Method B) to afford the title compound as an off white solid (5.6 mg, 15%).

Provenance & Evidence