Trifluoroacetic acid → 5-Bromo-4-(4-((2-isopropylthiazol-4-yl)methyl)piperazin-1-yl)-3-nitropyridin-2-amine

Participants

Reaction Steps

tert-Butyl 4-((2-isopropylthiazol-4-yl)methyl)piperazine-1-carboxylate (0.380 g, 1.15 mmol, 1.0 eq) was dissolved in DCM (3.6 mL) and the mixture cooled in an ice-water bath before the dropwise addition of TFA (3.6 mL). Stirring was continued at this temperature for 1 h and the solvents were removed in vacuo. The resulting crude material was azeotroped with toluene and dried. The resulting 2-isopropyl-4-(piperazin-1-ylmethyl)thiazole (supposedly 0.260 g, 1.15 mmol, 1.1 eq) was suspended in iPrOH (3.5 mL) and DIPEA (0.9 mL). To this solution, 5-bromo-4-chloro-3-nitropyridin-2-amine (0.270 g, 1.05 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 (0.300 g, 59%); 1H-NMR (500 MHz, DMSO-d6): δ 1.31 (d, J=7.0 Hz, 6H, iPr—CH3), 2.53-2.65 (br s, 4H, piperazine N(CH2)2), 3.06 (m, 4H, piperazine N(CH2)2), 3.20-3.33 (m, 1H, iPr—CH), 3.61 (s, 2H, NCH2), 6.96 (s, 2H, NH2), 7.31 (s, 1H, thiazole 5-H), 8.15 (s, 1H, pyridine 6-H); LC (Method B)-MS (ESI, m/z): Rt=2.81 min—4411443 [(M+H+), Br isotopic pattern, 100%].

Provenance & Evidence