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

tert-Butyl 4-((1-methyl-1H-imidazol-5-yl)methyl)piperazine-1-carboxylate (0.150 g, 0.54 mmol, 1.1 eq) was dissolved in DCM (1.7 mL) and the mixture cooled in a ice-water bath before the dropwise addition of TFA (1.7 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 1-((1-methyl-1H-imidazol-5-yl)methyl)piperazine (supposedly 0.097 g, 0.54 mmol, 1 eq) was suspended in iPrOH (1.6 mL) and DIPEA (0.42 mL). To this solution, 5-bromo-4-chloro-3-nitropyridin-2-amine (0.120 g, 0.49 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 (0.070 g, 33%); 1H-NMR (500 MHz, DMSO-d6): δ 3.03 (br s, 4H, piperazine N(CH2)2), 3.49 (s, 2H, NCH2), 3.62 (s, 3H, imidazole Me), 6.76 (s, 1H, imidazole H-4), 6.96 (s, 2H, NH2), 7.54 (s, 1H, imidazole H-2), 8.16 (s, 1H, pyridine 6-H); LC (Method B)-MS (ESI, m/z): Rt=1.56 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-Eintrag

ord-ed4703fa0f6b40c386c3805b7b2e7fd8

Quelldatensatz

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08088761B2