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

Participants

Reaction Conditions

Reaction Steps

To a stirring solution of triphosgene (0.0205 g, 0.691 mmol) in 8 mL of CH2Cl2 at 0° C. was added dropwise a mixed solution of (S)-7-(trifluoromethyl)chroman-4-amine (44.91 mg, 0.2068 mmol) and N,N-diisopropylethylamine (0.108 mL, 0.620 mmol) in dichloromethane (2 mL). The reaction mixture was stirred at 0° C. for 30 minutes. Then to the mixture at 0° C. was slowly added a solution of the (R)-4-(4-chlorobenzyl)-3-(pyrrolidin-2-yl)-4H-1,2,4-triazole TFA salt (0.125 g, 0.2068 mmol) and N,N-diisopropylethylamine (0.108 mL, 0.620 mmol) in dichloromethane (2 mL). The resulting mixture was stirred 0° C. for 30 minutes, then at room temperature overnight. The reaction mixture was treated with sat. aqueous NaHCO3 (10 mL) and brine, dried over Na2SO4, and concentrated in vacuo. Flash chromatography purification (Hex/EtOAc gradient, 10-100% EtOAc with 10% of MeOH) afforded the desired product (55 mg, 52.6%).

Provenance & Evidence