Sodium hydride → 3-Tert-butyl-isoxazole-5-carboxylic acid [3-nitro-4-trifluoromethyl-6-(2-trifluoromethyl-phenyl)-pyridin-2-yl]-amide

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Reaction Steps

A solution of 3-nitro-4-trifluoromethyl-6-(2-trifluoromethyl-phenyl)-pyridin-2-ylamine (64.0 mg, 0.182 mmol, prepared as described in STEP D above) in THF (10 mL) was treated with NaH (21.9 mg, 0.547 mmol, 60% dispersion in oil), and the resulting mixture was allowed to stir at room temperature for 1 h. Simultaneously, a solution of 3-tert-butyl-isoxazole-5-carboxylic acid (40.1 mg, 0.237 mmol, prepared as described in Example I above) in anhydrous DCM (10 mL) was treated with oxalyl chloride (20.7 μL, 0.237 mmol) and DMF (2 drops), and the resulting mixture was stirred at room temperature for 1 h. Volatile components were removed in vacuo, and the residue was taken up in anhydrous THF (6 mL). The above-prepared acid chloride solution was added to the sodium anilide solution above, and the mixture was stirred at room temperature for 1 h. The mixture was quenched with saturated aqueous NH4Cl (20 mL) and extracted twice with EtOAc (25 mL). The residue was purified on a 12-g SEPRA Si 50 SPE column (Flow rate=15 mL/min; Eluent=EtOAc-hexanes, 1:99 for 10 min, then 1:99 to 1:4 over 40 min) to yield 3-tert-butyl-isoxazole-5-carboxylic acid [3-nitro-4-trifluoromethyl-6-(2-trifluoromethyl-phenyl)-pyridin-2-yl]-amide as an off-white solid. Mass Spectrum (LCMS, APCI pos.): Calculated for C21H16N4O4F6: 503.1 (M+H); Measured: 503.2.

Provenance & Evidence