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

Participants

Reaction Steps

To a solution of 150 mg (0.376 mmol, 2:1 cis/trans isomer mixture) of the carboxylic acid from Example 73A in 5.2 ml of N,N-dimethylformamide were added, at RT, 172 mg (0.452 mmol) of HATU and 0.14 ml (0.83 mmol) of N,N-diisopropylethylamine, and the mixture was stirred for 30 min. Subsequently, the mixture was admixed with 43.1 mg (0.414 mmol) of ethyl N′-hydroxyimidocarbamate [G. Zinner, G. Nebel, Arch. Pharm. 1970, 303, 385-390] and then stirred at room temperature for 2 h. The reaction solution was purified directly by means of preparative HPLC. The resulting intermediate (118 mg) was taken up in toluene (24 ml), admixed with 4 Å molecular sieve and stirred under reflux overnight. The reaction solution was filtered, the filtrate was concentrated under reduced pressure and the residue was purified by means of preparative HPLC. Yield: 55.4 mg (32% of theory)

Provenance & Evidence