Trifluoroacetic acid → 5-Bromo-3-nitro-4-(4-(thiazol-4-ylmethyl)piperazin-1-yl)pyridin-2-amine

Participants

Reaction Steps

tert-Butyl 4-(thiazol-4-ylmethyl)piperazine-1-carboxylate (0.160 g, 0.56 mmol, 1.0 eq) was dissolved in DCM (1.8 mL) and the reaction mixture cooled in a ice-water bath before the dropwise addition of TFA (1.8 mL). Stirring was continued at this temperature for 1 h, the solvents were removed in vacuo. The resulting crude material was azeotroped with toluene and dried. The resulting 4-(piperazin-1-ylmethyl)thiazole (supposedly 0.10 g, 0.56 mmol, 1.1 eq) was suspended in iPrOH (0.55 mL) and DIPEA (0.22 mL). To this solution, 5-bromo-4-chloro-3-nitropyridin-2-amine (0.130 g, 0.51 mmol, 1 eq) was added and the reaction mixture was heated and stirred for 17 h at 65° C. The mixture was filtered, washed with iPrOH (3×3 mL), Et2O (2×3 mL) and dried to give the title compound as a bright yellow powder (0.120 g, 55%); 1H-NMR (500 MHz, DMSO-d6): δ 2.58 (br s, 4H, piperazine N(CH2)2), 3.06 (m, 4H, piperazine N(CH2)2), 3.72 (s, 2H, NCH2), 6.96 (s, 2H, NH2), 7.54 (br d, 1H, J=1.2 Hz, thiazole 5-H), 8.15 (s, 1H, pyridine 6-H), 9.04 (d, 1H, J=1.7 Hz, thiazole 2-H); LC (Method B)-MS (ESI, m/z): Rt=1.83 min—398/400 [(M+H)+, Br isotopic pattern, 100%].

Provenance & Evidence