Potassium Carbonate → 1-(5-chloro-pyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxylic acid [(S)-1-(3-trifluoromethyl-phenyl)-ethyl]-amide

Participants

Reaction Conditions

Reaction Steps

5-Methyl-1H-pyrazole-4-carboxylic acid [(S)-1-(3-trifluoromethyl-phenyl)-ethyl]-amide (70 mg, 0.24 mmol), copper(I) iodide (10 mg, 0.05 mmol), 5-chloro-2-iodopyridine (75 mg, 0.31 mmol) and potassium carbonate (75 mg, 0.54 mmol) are added to a reaction vial with a septum top which is then evacuated and filled with argon for 3 cycles. DMF (2 mL, degassed) and racemic trans-N,N′-dimethylcyclohexane-1,2-diamine (15 μL, 0.10 mmol) are added and the reaction is heated at 120° C. for 17 hours. The resultant mixture is cooled to room temperature, diluted with saturated aqueous ammonium chloride (15 mL) and extracted with EtOAc (3×20 mL). The combined organic layers is washed with saturated aqueous sodium bicarbonate (15 mL) followed by brine (15 mL), dried over sodium sulfate, filtered and concentrated in vacuo to provide a crude solid. Recrystallization from ether/hexanes provides 1-(5-chloro-pyridin-2-yl)-5-methyl-1H-pyrazole-4-carboxylic acid [(S)-1-(3-trifluoromethyl-phenyl)-ethyl]-amide as a colorless solid (38 mg, 40%). (For references, see Buchwald, et al., J. Org. Chem. 2004, 69, 5578; Buchwald, et al., J. Am. Chem. Soc. 2002, 124, 11684).

Provenance & Evidence