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

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Reaction Steps

tert-Butyl 4-(thiazol-5-ylmethyl)piperazine-1-carboxylate (0.350 g, 1.23 mmol, 1.1 eq) was dissolved in DCM (3.9 mL) and the mixture cooled in a ice-water bath before the dropwise addition of TFA (3.9 mL). Stirring was continued at this temperature for 1 h. Solvents were removed in vacuo and the resulting crude material was azeotroped with toluene and dried. The resulting 5-(piperazin-1-ylmethyl)thiazole (supposedly 0.230 g, 1.23 mmol, 1 eq) was suspended in iPrOH (2.4 mL) and DIPEA (0.70 mL). To this solution, 5-bromo-4-chloro-3-nitropyridin-2-amine (0.280 g, 1.12 mmol, 1 eq) was added and the 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 (0.330 g, 67%); 1H-NMR (500 MHz, DMSO-d6): δ 2.51-2.58 (br s, 4H, piperazine N(CH2)2), 3.01-3.10 (m, 4H, piperazine N(CH2)2), 3.82 (s, 2H, NCH2), 6.98 (s, 2H, NH2), 7.78 (s, 1H, thiazole 4-H), 8.16 (s, 1H, pyridine 6-H), 9.03 (s, 1H, thiazole 2-H); LC (Method B)-MS (ESI, m/z): Rt=2.17 min—399/401 [(M+H+), Br isotopic pattern, 100%].

Provenance & Evidence