To a mixture of 5-bromo-4-(4-(cyclobutylmethyl)piperazin-1-yl)-3-nitropyridin-2-amine (0.036 g, 0.097 mmol) and EtOH (1 mL) was added p-anisaldehyde (0.015 g, 0.11 mmol) in EtOH (1.2 mL) followed by a freshly prepared aqueous solution of Na2S2O4 (1M; 0.29 mL, 0.29 mmol). The reaction mixture was heated at 85° C. for 24 h, then allowed to cool to room temperature and the solvents were removed in vacuo. The residue was absorbed on silica gel and purified by column chromatography on a Biotage SP1 system eluting with methanol (2-10%) in dichloromethane. The title compound was isolated as a pale yellow solid after trituration with diethyl ether (0.016 g, 37%); 1H-NMR (500 Mz, DMSO-d6): δ 1.63-1.73 (m, 2H), 1.77-1.93 (m, 2H), 2.00-2.10 (m, 2H), 2.42 (d, J=7.0 Hz, 2H, NCH2), 2.52-2.60 (m, 4H, piperazine N(CH2)2), 3.62 (m, 4H, piperazine N(CH2)2), 3.84 (s, 3H, OMe), 7.10 (d, J=9.0 Hz, 2H, ArH, C6H4—OMe), 8.13 (d, J=8.5 Hz, 2H, ArH, C6H4—OMe), 8.20 (s, 1H, imidazo[4,5-b]pyridine 5-H), 13.34 (br s, 1H, imidazo[4,5-b]pyridine N—H); LC (Method B)-MS (ESI, m/z) 3.29 min—456/458 [(M+H)+, Br isotopic pattern]. ESI-HRMS: Found: 456.1395, calculated for C22H27BrN5O (M+H)+: 456.1399.
