2,6-Diaminopyridine → HCID 86066180, compound

Temperature

80 °C

2,6-Diaminopyridine (9.2 mmol, 1.0 g) and 2-fluoro-5-nitropyridine (4.6 mmol, 0.65 g) were dissolved in 6 mL of DMSO. The solution was heated to 80° C. for 18 h. The solution eventually turned dark red. The reaction mixture was cooled to room temperature and purified directly by flash column chromatography (silica, EtOAc:Hexanes=1:3) to give N2-(5-nitropyridin-2-yl)pyridine-2,6-diamine as a reddish crystalline solid (0.21 g, 20% yield): 1H NMR (500 MHz, CDCl3) δ 9.13 (d, 1H, J=3.0 Hz), 8.36 (dd, 1H, J=3.0 Hz, J2=9.5 Hz), 7.94 (d, 1H, J=9.5 Hz), 7.66 (s, 1H), 7.46 (t, 1H, J=8.0 Hz), 6.68 (d, 1H, J=8.0 Hz), 6.23 (d, 1H, J=8.0 Hz), 4.46 (s, 2H); Ms m/z (relative intensity) 232 (M+1, 100), 186 (57). The nitro compound (0.78 mmol, 0.18 g) and 10% Pd/C (20 mg) were added to a 20 mL test tube equipped with a stir bar, dry ice (0.5 g) was added to the mixture just before MeOH (7 mL) was added. The suspension was then put into a pressure vessel under 80 psi of H2. The reaction mixture was stirred for 2 hours. The solution turned from yellow to colorless. The reaction mixture was transferred into a 10 mL syringe and was then filtered through an Acrodisc syringe Filter into a 100 mL round bottom flask containing 37% aqueous HCl (4 mL). The solvent was then evaporated and azeotroped to dryness with toluene and absolute ethanol (3×30 mL of 1:1 mixture). The product was obtained as a grayish yellow powder in quantitative yield.

1. temperatureThe reaction mixture was cooled to room temperature
2. custompurified directly by flash column chromatography (silica, EtOAc:Hexanes=1:3)

ORD record

ord-dbc564b70ef04d54a97e42e1ad002f55

Source dataset

uspto-grants-2007_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07303592B2