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

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Reaction Steps

A solution of 4-chloro-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-2-ylamine (100 mg, 0.315 mmol, prepared as described in Example 1, Step B above) in THF (10 mL) was treated with NaH (37.8 mg, 0.944 mmol, 60% dispersion in oil), and the mixture was allowed to stir at room temperature for 1 h. Simultaneously, a solution of 3-tert-butyl-isoxazole-5-carboxylic acid (69.2 mg, 0.409 mmol, prepared as described in Example I above) in DCM (10 mL) was treated with oxalyl chloride (35.7 μL, 0.409 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 resulting mixture was stirred at room temperature for 15 min. The resulting mixture was then quenched with saturated aqueous NH4Cl (20 mL) and extracted twice with EtOAc (30 mL). The combined organic extracts were dried over MgSO4 and concentrated in vacuo. The residue was purified on a 25-g SEPRA Si 50 SPE column (Flow rate=20 mL/min; Eluent=EtOAc-hexanes, 1:99 for 10 min, then 1:99 to 1:3 over 40 min) to yield 3-tert-butyl-isoxazole-5-carboxylic acid [4-chloro-3-nitro-6-(2-trifluoromethyl-phenyl)-pyridin-2-yl]-amide as a yellow solid. Mass Spectrum (LCMS, ESI pos.): Calculated for C21H16N4O4ClF3: 469.1 (M+H); Measured: 469.1.

Provenance & Evidence