Trifluoroacetic acid → 5-Chloro-3-nitro-4-[4-(1,2,4-oxadiazol-3-ylmethyl)-1-piperazinyl]-2-pyridinamine

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Reaction Steps

To a solution of tert-butyl 4-((1,2,4-oxadiazol-3-yl)methyl)piperazine-1-carboxylate (213 mg, 0.790 mmol) in CH2Cl2 (18 mL) was added TFA (1.8 mL, 23.8 mmol) and the solution was stirred at room temperature for 1½ h. The reaction was concentrated in vacuo, azeotroping with toluene (×2) and dried in vacuum desiccator (containing KOH) overnight to give a yellow oil. The crude oil was dissolved in iPrOH (4.4 mL) and both 2-amino-3-nitro-4,5-dichloropyridine (190 mg, 0.752 mmol) and DIPEA (520 μl, 3.00 mmol) were added. The solution was stirred at 50° C. for 4 h. On cooling, a yellow precipitate dropped out which was filtered, washed with Et2O, dried in vacuo to yield the title compound as a yellow solid (165 mg, 0.486, 65%). The filtrate was concentrated in vacuo to give 715 mg oily yellow solid. Purification was accomplished by flash chromatography on silica gel (4×11) eluting with EtOAc/hexane (40-50%) to yield the title compound (42 mg, 16%) as a yellow solid.

Provenance & Evidence