Diisopropylethylamine → {3-(3-Ethoxy-1,2,4-oxadiazol-5-yl)-5-[3-fluoro-4-(2,2,2-trifluoroethyl)phenyl]piperidin-1-yl}-(thiomorpholin-4-yl)methanone

Participants

Reaction Steps

To a solution of 400 mg (0.783 mmol, purity 85%) of the carboxylic acid from Example 79A in 10.6 ml of N,N-dimethylformamide were added, at room temperature, 357 mg (0.939 mmol) of HATU and 0.30 ml (1.72 mmol) of N,N-diisopropylethylamine, and the mixture was stirred for 30 min. Subsequently, the mixture was admixed with 118 mg (1.02 mmol, purity 90%) of ethyl N′-hydroxyimidocarbamate [G. Zinner, G. Nebel, Arch. Pharm. 1970, 303, 385-390] and stirred at room temperature overnight. The reaction solution was diluted with 11 ml of N,N-dimethylformamide and then stirred at 140° C. for 3 h. The reaction solution was purified directly by means of preparative HPLC. Yield: 111 mg (28% of theory)

Provenance & Evidence