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

To a stirred solution of 2-(2-aminopyridin-4-yl)propan-2-ol (40) (1.55 g, 10.0 mmol) in DMF (30 mL), under nitrogen at 0° C., was added sodium hydride (60% wt, 0.61 g, 15.0 mmol) and the resulting mixture was stirred at 0° C. for 5 min. A solution of 1-fluoro-4-nitronaphthalene (14) (1.95 g, 10 mmol) in DMF (30 mL) was added dropwise and the resulting dark-red mixture was stirred at 0° C. for a further 5 min and then at RT for 2 hr. The reaction mixture was quenched by the addition of saturated aq NH4Cl solution (10 mL). Water (150 mL) and EtOAc (150 mL) were added, and the layers were separated. The aqueous layer was extracted with EtOAc (3×100 mL) and the combined organic extracts were washed with brine, dried (MgSO4) and evaporated in vacuo. The crude residue was purified by flash column chromatography (SiO2, 80 g, 0-60% EtOAc in isohexane, gradient elution) to afford the title compound (41) (282 mg, 8%) as a red oil: m/z 324 (M+H)+ (ES+).

1. stirringthe resulting dark-red mixture was stirred at 0° C. for a further 5 min
2. waitat RT for 2 hr
3. customThe reaction mixture was quenched by the addition of saturated aq NH4Cl solution (10 mL)
4. additionWater (150 mL) and EtOAc (150 mL) were added
5. customthe layers were separated
6. extractionThe aqueous layer was extracted with EtOAc (3×100 mL)
7. washthe combined organic extracts were washed with brine
8. dry with materialdried (MgSO4)
9. customevaporated in vacuo
10. customThe crude residue was purified by flash column chromatography (SiO2, 80 g, 0-60% EtOAc in isohexane, gradient elution)

ORD record

ord-88ccbba5a2ec444b892e92a800b2f444

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08299073B2