2-Aminopyridine → (5-Fluoro-2-nitrophenyl)pyridin-2-yl-amine

Temperature

-78 °C

LiHMDS (1.0M in THF, 4.8 mL, 4.8 mmol) was added dropwise to a stirred solution of pyridin-2-ylamine (269 mg, 2.86 mmol) in anhydrous THF (10 mL) under a nitrogen atmosphere at −78° C. After 30 min stirring at −78° C., 2,4-difluoro-1-nitrobenzene (298 μL, 2.72 mmol) was added and stirring at −78° C. was continued for 30 min. The reaction mixture was slowly warmed to RT and after 30 min quenched by addition of an aqueous solution of NH4Cl (50 mL). The mixture was partitioned between EtOAc and water, then filtered through Celite®. The organic fraction was dried (Na2SO4), concentrated in vacuo and the resulting residue was purified by column chromatography (Si—PCC, gradient 0-40% EtOAc in cyclohexane) to afford the title compound as an orange solid (258 mg, 41%). 1H NMR (CDCl3, 400 MHz): δ 10.48 (1H, s), 8.82 (1H, dd, J=12.32, 2.77 Hz), 8.38 (1H, dd, J=5.03, 1.87 Hz), 8.34-8.25 (1H, m), 7.70-7.64 (1H, m), 7.03-6.94 (2H, m), 6.68-6.61 (1H, m).

1. stirringstirring at −78° C.
2. waitwas continued for 30 min
3. temperatureThe reaction mixture was slowly warmed to RT and after 30 min
4. customquenched by addition of an aqueous solution of NH4Cl (50 mL)
5. customThe mixture was partitioned between EtOAc and water
6. filtrationfiltered through Celite®
7. dry with materialThe organic fraction was dried (Na2SO4)
8. concentrationconcentrated in vacuo
9. customthe resulting residue was purified by column chromatography (Si—PCC, gradient 0-40% EtOAc in cyclohexane)

ORD record

ord-72f0e979836e4e2abdff64d38344d39c

Source dataset

uspto-grants-2014_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08653089B2