Diisopropylethylamine → (R)-2-(2-(4-chlorobenzyl)-5-methyl-2H-1,2,4-triazol-3-yl)-N-((S)-7-(trifluoromethyl)-3,4-dihydro-2H-chromen-4-yl)pyrrolidine-1-carboxamide

Participants

Reaction Steps

To a stirring solution of triphosgene (18 mg, 0.06 mmol) in dichloromethane (3 ml) was slowly added dropwise via syringe a premixed solution of (S)-7-(trifluoromethyl)chroman-4-amine (39 mg, 0.18 mmol) and N,N-diisopropylethylamine (0.069 ml) dissolved in dichloromethane (3 ml). The reaction mixture was stirred at room temperature for 30 minutes. The isocyanate thereby generated was then treated dropwise with a solution of (R)-1-(4-chlorobenzyl)-3-methyl-5-(pyrrolidin-2-yl)-1H-1,2,4-triazole (52 mg, 0.18 mmol) and N,N-diisopropylethylamine (0.067 ml, 0.4 mmol) dissolved in dichloromethane (5 ml). The reaction mixture was stirred at room temperature for 16 h. The reaction mixture was evaporated to dryness, diluted with EtOAc, washed with 5% aqueous NaHCO3 and brine, dried (Na2SO4), filtered and concentrated. Purification by preparative HPLC yielded a clear oil (14 mg, 15%)

Provenance & Evidence