반응 #45730

ord-10b35e463ed443d2b0cd50bb67c59fcc

반응 조건

온도
90°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    온도After cooling to room temperature
  2. 2
    기타the reaction liquid
  3. 3
    추출The aqueous layer was further extracted twice with ethyl acetate
  4. 4
    세척washed with saturated brine
  5. 5
    건조dried over anhydrous sodium sulfate
  6. 6
    기타The insoluble matter was separated by filtration
  7. 7
    기타the solvent was evaporated away
  8. 8
    기타the resulting residue was purified by preparative TLC (eluent, chloroform:methanol=96:4)
  9. 9
    기타to obtain a roughly-purified product (211 mg, 74% for 2 steps) as a white solid
  10. 10
    기타This was recrystallized from ethyl acetate and diisopropyl ether

실험 절차

2-Cyclopropyl-6-(3,5-difluorophenyl)-7-fluoro-5-methyl-1,3-benzoxazole-4-carbonitrile (I-176) (including impurities, estimated as 0.68 mmol) was dissolved in dimethyl sulfoxide (5 ml), then at room temperature, triethylamine (142 μl, 1.02 mmol) and (3S)-3-(dimethylamino)pyrrolidine (112 μl, 0.88 mmol) were added, the solution was stirred under nitrogen atmosphere at 90° C. for 15 hours. After cooling to room temperature, the reaction liquid was fractionated with ethyl acetate and an aqueous saturated sodium hydrogencarbonate solution. The aqueous layer was further extracted twice with ethyl acetate. The organic layers were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The insoluble matter was separated by filtration, then the solvent was evaporated away, and the resulting residue was purified by preparative TLC (eluent, chloroform:methanol=96:4) to obtain a roughly-purified product (211 mg, 74% for 2 steps) as a white solid. This was recrystallized from ethyl acetate and diisopropyl ether to obtain the entitled compound (46 mg) as a white solid.

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US07737166B2uspto-grants-2010_06