Diisopropylethylamine → (s)-4-Methyl-piperazine-1-carboxylic acid (1-{4-[bis-(4-fluoro-phenyl)-methyl]-piperazine-1-carbonyl}-3-methyl-butyl)-amide

Participants

Reaction Conditions

Reaction Steps

(S)-2-[(4-Methyl-piperazine-1-carbonyl)-amino]-4-methyl pentanoic acid (0.300 g, 1.23 mmol, Example 29, Step B) was dissolved in dry DMF (4 mL) under nitrogen atmosphere and cooled to 0° C. in an ice-water bath. To this solution were added, in succession, N,N-diisopropylethylamine (0.129 mL, 2.47 mmol) and solid O-benzotriazol-1-yl-N,N,N′,N′-tetramethyluronium hexafluorophosphate (0.468 g, 1.23 mmol). The resulting reaction mixture was stirred at that temperature for 30 minutes; solid 1-bis(4-fluorophenyl)methyl piperazine (0.356 g, 1.23 mmol) was then added. After stirring for, sequentially, 10 minutes at 0° C. and 20 minutes at ambient temperature, reaction mixture was mixed with 60 mL of diethyl ether; the resulting mixture was successively washed with saturated aqueous NaHCO3 solution (2×60 mL), brine (2×60 mL), and was dried over Na2SO4. The solution was concentrated in vacuo affording a viscous oil. The crude product was further purified by flash chromatography (20% MeOH in EtOAc) to provide 0.53 g (78%) of the pure titled compound as a white foam: mp 65-78° C. APCI-MS m/z 528.4 (MH+).

Provenance & Evidence