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

tert-Butyl 4-((1-methyl-1H-imidazol-4-yl)methyl)piperazine-1-carboxylate (0.130 g, 0.46 mmol, 1.1 eq) was dissolved in DCM (1.45 mL) and the mixture cooled in a ice-water bath before the dropwise addition of TFA (1.45 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 1-((1-methyl-1H-imidazol-4-yl)methyl)piperazine (supposedly 0.083 g, 0.46 mmol, 1 eq) was suspended in iPrOH (1.4 mL) and DIPEA (0.35 mL). To this solution, 5-bromo-4-chloro-3-nitropyridin-2-amine (0.100 g, 0.42 mmol, 1 eq) was added and the mixture 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 (0.085 g, 47%); 1H-NMR (500 MHz, DMSO-d6): δ 2.50-2.58 (br s, 4H, piperazine N(CH2)2), 3.03 (m, 4H, piperazine N(CH2)2), 3.39 (s, 2H, NCH2), 3.60 (s, 3H, imidazole Me), 6.95 (s) and 6.97 (s), (3H, NH2 and 6-H), 7.46 (s, 1H), 8.14 (s, 1H, pyridine 6-H); LC (Method B)-MS (ESI, m/z): Rt=1.25 min—396/398 [(M+H+), Br isotopic pattern, 100%].

1. customThe solvents were removed in vacuo
2. customthe resulting crude material was azeotroped with toluene
3. customdried
4. temperaturethe mixture heated
5. stirringstirred for 17 h at 65° C
6. filtrationThe mixture was filtered
7. washwashed with iPrOH (3×3 mL), Et2O (2×3 mL)
8. customdried

ORD record

ord-9d7a7d8f848a4f5e8ac290516aac4d8d

Source dataset

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08088761B2