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

tert-Butyl 4-((2-isopropyloxazol-4-yl)methyl)piperazine-1-carboxylate (0.400 g, 1.29 mmol, 1.1 eq) was dissolved in DCM (5 mL) and the mixture cooled in a ice-water bath before the dropwise addition of TFA (5 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)oxazole (supposedly 0.270 g, 1.29 mmol, 1 eq) was suspended in iPrOH (2.5 mL) and DIPEA (1.0 mL). To this solution, the 5-bromo-4-chloro-3-nitropyridin-2-amine (0.300 g, 1.17 mmol, 0.91 eq) was added, and the mixture heated and stirred for 17 h at 60° C. The mixture was filtered, washed with iPrOH (3×3 mL), cold H2O (3×3 mL), Et2O (2×3 mL) and dried to give the title compound as a bright yellow solid (0.290 g, 53%); 1H-NMR (500 MHz, DMSO-d6): δ 1.26 (d, J=7.0 Hz, 6H, iPr—CH3), 2.52-2.64 (br s, 4H, piperazine N(CH2)2), 2.98-3.12 (m, 5H, piperazine N(CH2)2 and iPr—CH), 3.40 (s, 2H, NCH2), 6.98 (s, 2H, NH2), 7.84 (s, 1H, oxazole 5-H), 8.16 (s, 1H, pyridine 6-H); LC (Method B)-MS (ESI, m/z): R=2.46 min—425/427 [(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 60° C
6. filtrationThe mixture was filtered
7. washwashed with iPrOH (3×3 mL), cold H2O (3×3 mL), Et2O (2×3 mL)
8. customdried

ORDレコード

ord-74a51977a95a41eea5a42fecc884654f

出典データセット

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

特許番号

US08088761B2