Acetone → 2-methyl-2-((((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)amino)propanenitrile

Participants

Reaction Conditions

Reaction Steps

A 5-mL vial was charged with 2-(4-((2S)-2-(aminomethyl)-4-(2-thiophenylsulfonyl)-1-piperazinyl)phenyl)-1,1,1-trifluoro-2-propanol (0.0521 g, 0.116 mmol, Example 192, Step 2), acetone (10 μL, 0.14 mmol) and EtOH (1 mL). The reaction mixture was cooled to 0° C. and stirred for 35 min. Trimethylsilyl cyanide (46.3 μL, 0.348 mmol, Sigma-Aldrich, St. Louis, Mo.) was added drop wise at 0° C. The mixture was slowly allowed to warm up to room temperature and stirred for 12 h. The solvent was removed and the remaining white residue was dissolved into EtOAc and passed through a pad of silica gel rinsing with EtOAc as eluent. The solvent was removed and the crude product was purified by column chromatography (10 g of silica gel, 50 to 100% EtOAc in hexanes) to afford 2-methyl-2-((((2S)-4-(2-thiophenylsulfonyl)-1-(4-(2,2,2-trifluoro-1-hydroxy-1-methylethyl)phenyl)-2-piperazinyl)methyl)amino)propanenitrile (0.0312 g) as an off-white solid.

Provenance & Evidence