Diisopropylethylamine → (S)-4-Methyl-piperazine-1-carboxylic acid {1-[4,4-bis-(4-fluoro-phenyl)-butylcarbamoyl]-3-methyl-butyl)-amide

온도

0 °C

(S)-2-[(4-Methyl-piperazine-1-carbonyl)-amino]-4-methyl pentanoic acid (0.300 g, 1.23 mmol) 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 (0.644 mL, 3.70 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 4,4-bis-(4-fluoro-phenyl)-butylamine monohydrochloride (0.367 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 an viscous oil. The crude product was further purified by flash chromatography (20% MeOH in EtOAc) to afford 0.45 g (73%) of the pure titled compound as a white foam; mp 73-91° C. APCI-MS m/z 501.3 (MH+).

1. customThe resulting reaction mixture
2. stirringAfter stirring for, sequentially, 10 minutes at 0° C.
3. custom20 minutes at ambient temperature, reaction mixture
4. washthe resulting mixture was successively washed with saturated aqueous NaHCO3 solution (2×60 mL), brine (2×60 mL)
5. dry with materialwas dried over Na2SO4
6. concentrationThe solution was concentrated in vacuo
7. customaffording an viscous oil
8. customThe crude product was further purified by flash chromatography (20% MeOH in EtOAc)

ORD 기록

ord-69f96db623f04f6baf94a0478cb89db5

출처 데이터셋

uspto-grants-2002_10

DOI

10.6084/m9.figshare.5104873.v1

특허 번호

US06458781B1