Diisopropylethylamine → 4-(4-Chloro-phenyl)-5-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid (3-methoxy-isoxazol-5-ylmethyl)-amide

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Reaction Steps

4-(4-Chloro-phenyl)-5-(2,2,2-trifluoro-ethoxy)-pyridine-2-carboxylic acid (100 mg, 0.3 mmol, example D) was dissolved in dimethylformamide (4 mL). To this stirred solution under argon was added in sequence 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate (107 mg, 0.3 mmol), N,N-diisopropyl ethyl amine (0.26 mL, 1.5 mmol) and 3-methoxy-5-isoxazolemethanamine hydrochloride (55 mg, 0.3 mmol). The mixture was shaken for 16 h at room temperature, solvent was removed in vacuo (45° C.) and the residue was digested with dichloromethane (5 mL) and 2N NaOH (1.5 mL) for 5 min. The mixture was absorbed onto 10 g ChemElut (Varian) and eluted with dichloromethane (70 mL). Solvent was evaporated and the brown, oily residue (160 mg) was purified by gradient chromatography on silica with ethyl acetate/n-heptane to give the title compound as a white solid (122 mg, 92%), LC-MS (UV peak area/ESI) 93%, 442.0769 (M+H)+.

Provenance & Evidence