GENERAL METHODS: A mixture of 5-bromo-2-nitropyridine (24.7 mmol), piperazine (29.2 mmol) and N,N-diisopropylethylamine (DIPEA, 37.1 mmol) in acetonitrile (100 mL) was refluxed for 8 hours. The reaction progress was monitored by thin layer chromatography (TLC), and after complete conversion of the feedstock, the reaction mixture was cooled to room temperature. The solvent was removed by evaporation and the residue was purified by column chromatography to afford 1-(6-nitropyridin-3-yl)piperazine (8c). The product was a yellow solid in 82% yield.1H NMR (DMSO-d6, 400 MHz) δ: 7.96 (d, J = 9.3 Hz, 1H, Pyr-H), 7.88 (d, J = 2.9 Hz, 1H, Pyr-H), 7.26 (dd, J = 9.3, 3.0 Hz, 1H, Pyr-H), 3.64 (t, 4H, Pyr -NCH2CH2N), 3.32 (t, 4H, Pyr-NCH2CH2N).13C NMR (DMSO-d6, 100 MHz): δ 151.7, 146.2, 136.6, 125.9, 118.4, 51.3, 45.8. High-resolution mass spectrometry (HRMS, ESI): the calculated value for C9H12N4O2 [M + H]+is 209.1039 and the measured value is 209.1030.
