تفاعل #45730

ord-10b35e463ed443d2b0cd50bb67c59fcc

ظروف التفاعل

درجة الحرارة
90°CELSIUS
الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

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

الإجراء التجريبي

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.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US07737166B2uspto-grants-2010_06