Diisopropylethylamine → N-{(1S)-1-[5-chloro-2-(1-{[(1R,2R,4R)-2-(2,4-difluorophenyl)-4-(dimethylamino)cyclopentyl]carbonyl}piperidin-4-yl)phenyl]ethyl}acetamide

Participants

Reaction Steps

N,N-diisopropylethylamine (82.4 μL, 0.473 mmol) was added to a stirred suspension of (1R,2R,4R)-2-(2,4-difluorophenyl)-4-(dimethylamino)cyclopentanecarboxylic acid hydrochloride (48.2 mg, 0.158 mmol, prepared essentially as described in EXAMPLE 44), N-[(1S)-1-(5-chloro-2-piperidin-4-ylphenyl)ethyl]acetamide hydrochloride (50 mg, 0.158 mmol), and O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (72.0 mg, 0.189 mmol) in N,N-dimethylformamide (1.5 mL) at ambient temperature. After approximately 18 h, the reaction mixture was poured into water and extracted three times with ethyl acetate. The combined organic extracts were washed with brine, dried (Na2SO4) and concentrated in vacuo. Purification of the crude residue by preparative reversed phase high pressure liquid chromatography on YMC Pack Pro C18 phase (gradient elution; 0–100% acetonitrile/water as eluent, 0.1% TFA modifier) afforded the title compound as a buff white solid (m/z (ES) 532 (MH+).

Provenance & Evidence