2,6-Lutidine → N-[1-({2-Chloro-4-[(phenylmethyl)oxy]phenyl}methyl)-1H-pyrazol-3-yl]-2,6-difluorobenzamide

Temperatur

160 °C

To a solution of 2,6-difluoro-N-(1H-pyrazol-3-yl)benzamide (for a preparation see Intermediate 9)(0.961 g, 4.31 mmol) and 1-(bromomethyl)-2-chloro-4-[(phenylmethyl)oxy]benzene (1.21 g, 3.88 mmol) in anhydrous NMP (15 ml) was added 2,6-lutidine (0.5 ml, 4.29 mmol, Aldrich). The reaction vessel (20 ml) was sealed and heated in Biotage Initiator microwave to 160° C. for 30 min. After cooling the reaction mixture was partitioned between saturated aqueous sodium hydrogen carbonate (120 ml) and ethyl acetate (100 ml). The phases were separated and the aqueous phase extracted with ethyl acetate (50 ml). The combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate (50 ml), dried (MgSO4), filtered and the solvent removed in vacuo to leave a red oil (2.84 g). The residue was loaded in dichloromethane and purified on silica (100 g×2) using 0-100% ethyl acetate-cyclohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a white solid (0.778 g); LCMS: (System 4) MH+=454, tRET=3.35 min.

1. customThe reaction vessel (20 ml) was sealed
2. temperatureAfter cooling the reaction mixture
3. customwas partitioned between saturated aqueous sodium hydrogen carbonate (120 ml) and ethyl acetate (100 ml)
4. customThe phases were separated
5. extractionthe aqueous phase extracted with ethyl acetate (50 ml)
6. washThe combined organic extracts were washed with saturated aqueous sodium hydrogen carbonate (50 ml)
7. dry with materialdried (MgSO4)
8. filtrationfiltered
9. customthe solvent removed in vacuo

ORD-Eintrag

ord-f2fca628f23147f08d8fd95425e5dffc

Quelldatensatz

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08399436B2