Sodium hydride → 4-(1-(4-Nitronaphthalen-1-yloxy)ethyl)pyridin-2-amine

Temperature

0 °C

To a stirred solution of 1-(2-aminopyridin-4-yl)ethanol (37) (73 mg, 0.528 mmol) in DMF (1.5 mL), under nitrogen at 0° C., was added sodium hydride (32 mg, 0.793 mmol, 60 wt %). The resulting mixture was stirred at 0° C. for 40 min, and a solution of 1-fluoro-4-nitronaphthalene (14) (101 mg, 0.528 mmol) in DMF (1.5 mL) was added dropwise. The resulting dark-red mixture was stirred at 0° C. for 5 min and at RT for 40 min and was quenched by the addition of 1.0 mL of NH4Cl solution. Water (20 mL) and EtOAc (20 mL) were added, and the layers were separated. The aqueous layer was extracted with EtOAc (3×15 mL). The combined organic extracts were washed with brine, dried and the solvents removed in vacuo. The crude material was purified by column chromatography (SiO2, 12 g, 0-80% EtOAc in isohexane, gradient elution) to give the title compound (38) (94.6 mg, 57%) as an orange gum: m/z 310 (M+H)+ (ES+).

1. stirringThe resulting dark-red mixture was stirred at 0° C. for 5 min and at RT for 40 min
2. customwas quenched by the addition of 1.0 mL of NH4Cl solution
3. additionWater (20 mL) and EtOAc (20 mL) were added
4. customthe layers were separated
5. extractionThe aqueous layer was extracted with EtOAc (3×15 mL)
6. washThe combined organic extracts were washed with brine
7. customdried
8. customthe solvents removed in vacuo
9. customThe crude material was purified by column chromatography (SiO2, 12 g, 0-80% EtOAc in isohexane, gradient elution)

ORD record

ord-5d5c841b914d4dd6b168aa5f29736d91

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08299073B2