N-(3-methoxyphenyl)pivalamide → N-(2-{[5-chloro-3-(4-chloro-3-trifluoromethyl-benzenesulfonylamino)-pyridin-2-yl]-hydroxy-methyl}-3-methoxy-phenyl)-2,2-dimethyl-propionamide

Temperatur

-78 °C

To a stirred solution of N-(3-methoxy-phenyl)-2,2-dimethyl-propionamide (1.11 g, 4.8 mmol) in anhydrous THF at 0° C. was added a solution of n-BuLi (3.65 mL, 9.1 mmol) in hexanes. After 45 minutes, anhydrous MgBr2-Et2O (1.23 g, 4.8 mmol) was added in one portion and stirring was continued at the same temperature for 1 h. The mixture was then cooled to −78° C. and solid 4-chloro-N-(5-chloro-2-formyl-pyridin-3-yl)-3-trifluoromethyl-benzenesulfonamide (300 mg, 0.75 mmol) was added in one portion and slowly warmed to room temperature over 4 h. The mixture was then quenched with saturated aqueous NH4Cl (10 mL), and extracted with EtOAc (3×75 mL). The combined extracts were washed with brine, dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by chromatography on silica gel using ethyl acetate-hexane to provide N-(2-{[5-chloro-3-(4-chloro-3-trifluoromethyl-benzenesulfonylamino)-pyridin-2-yl]-hydroxy-methyl}-3-methoxy-phenyl)-2,2-dimethyl-propionamide: MS m/z 606.0 (M+H)+.

1. waitwas continued at the same temperature for 1 h
2. temperatureslowly warmed to room temperature over 4 h
3. customThe mixture was then quenched with saturated aqueous NH4Cl (10 mL)
4. extractionextracted with EtOAc (3×75 mL)
5. washThe combined extracts were washed with brine
6. dry with materialdried (Na2SO4)
7. filtrationfiltered
8. concentrationconcentrated under reduced pressure
9. customThe residue was purified by chromatography on silica gel

ORD-Eintrag

ord-8346c049ab6a40d989e0b627de78de2d

Quelldatensatz

uspto-grants-2012_01

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08093247B2