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

Participants

Reaction Conditions

Reaction Steps

LiHMDS (1.0M in THF, 62 mL, 6.2 mmol) was added dropwise to a stirred solution of pyridin-2-ylamine (3.1 g, 33 mmol) in anhydrous THF (50 mL) under a nitrogen atmosphere at −78° C. After 30 min stirring at −78° C., 2,4-difluoro-1-nitrobenzene (3.4 mL, 31 mmol) was added and stirring at −78° C. continued for 30 min. The reaction mixture was slowly warmed to RT and after 5 h quenched by addition of a saturated aqueous solution of NH4Cl (150 mL). The mixture was partitioned between EtOAc and water, then filtered through Celite®. The organic fraction was dried (MgSO4), concentrated in vacuo and the resulting residue purified by column chromatography (Si—PCC, gradient 0-50% DCM in cyclohexane) to afford the title compound as an orange solid (3.9 g, 54%). 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).

Provenance & Evidence