Triethylamine → 5-methyl-1H-pyrazole-4-carboxylic acid [(S)-1-(3-trifluoromethyl-phenyl)-ethyl]-amide

To 5-methyl-1H-pyrazole-4-carboxylic acid (390 mg, 3.1 mmol) in DMF (10 mL) is added triethylamine (1.2 mL, 9.4 mmol) and benzotriazole-1-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate (PyBOP) (1.8 g, 3.5 mmol). After stirring for 5 min at room temperature, (S)-1-(3-trifluoromethyl-phenyl)-ethylamine (650 mg, 3.4 mmol) is added and the reaction is stirred at room temperature for 2 days. The mixture is then diluted with saturated ammonium chloride and extracted with EtOAc (4×15 mL). The combined organic layer is washed with saturated NaHCO3 solution (20 mL) followed by brine (20 mL), dried over sodium sulfate, filtered and concentrated in vacuo. The crude material is purified by flash chromatography on silica gel (eluted with 0 to 60% EtOAc/hexanes) followed by recrystallization from ether/hexanes to provide 5-methyl-1H-pyrazole-4-carboxylic acid [(S)-1-(3-trifluoromethyl-phenyl)-ethyl]-amide as a colorless solid (770 mg, 84%).

1. stirringthe reaction is stirred at room temperature for 2 days
2. extractionextracted with EtOAc (4×15 mL)
3. washThe combined organic layer is washed with saturated NaHCO3 solution (20 mL)
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. concentrationconcentrated in vacuo
7. customThe crude material is purified by flash chromatography on silica gel (eluted with 0 to 60% EtOAc/hexanes)
8. customfollowed by recrystallization from ether/hexanes

ORD-Eintrag

ord-085b5ed476c0431f8afa6a3c4abbbee7

Quelldatensatz

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08293917B2