Sodium hydride → 5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid (6-bromo-3-nitro-pyridin-2-yl)-amide

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A solution of 6-bromo-3-nitro-pyridin-2-ylamine (750 mg, 3.44 mmol) in THF (20 mL) was treated with NaH (413 mg, 10.3 mmol) at room temperature for 1 h. Simultaneously a solution of 5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid (969 mg, 4.47 mmol, prepared as described in Example B) in DCM (20 mL) was treated with oxalyl chloride (390 μL, 4.47 mmol) and DMF (4 drops) at room temperature for 1 h. The acid chloride solution was concentrated to dryness in vacuo, taken up in THF (10 mL), and added to the sodium anilide solution. The resulting mixture was stirred at room temperature for 15 min, quenched with saturated aqueous NH4Cl (50 mL), and extracted twice with EtOAc (60 mL, 20 mL). The combined extracts were dried over MgSO4 and concentrated in vacuo. The residue was purified on a 40-g SEPRA Si 50 SPE column (Isco system: Flow rate=25 mL/min; Eluent=EtOAc/hexanes, 1:99 v/v for 1 min, then 1:99 to 3:17 v/v over 40 min) to yield 5-tert-butyl-4-chloro-2-methyl-2H-pyrazole-3-carboxylic acid (6-bromo-3-nitro-pyridin-2-yl)-amide as a pale yellow solid. 1H-NMR (400 MHz, CDCl3) δ: 10.48 (br. s., 1H), 8.31 (d, J=8.6 Hz, 1H), 7.46 (d, J=8.6 Hz, 1H), 4.12 (s, 3H), 1.42 (s, 9H). Mass Spectrum (LCMS, APCI pos.): Calculated for C14H15BrClN5O3: 416.0 (M+H); Measured: 416.1.

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