تفاعل #47493

ord-8241a16f825640cd9fc4385edf0b8ff8

ظروف التفاعل

درجة الحرارة
23°CELSIUS
الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    أخرىat room temperature
  2. 2
    غسيلwashed with a saturated aqueous ammonium chloride solution
  3. 3
    غسيلThe organic layer was then washed with a saturated aqueous sodium chloride solution
  4. 4
    أخرىseparated
  5. 5
    تجفيفdried over sodium sulfate
  6. 6
    تركيزconcentrated in vacuo
  7. 7
    أخرىto afford the crude product, which
  8. 8
    أخرىwas purified by flash column chromatography (silica gel (100-200 mesh)) which

الإجراء التجريبي

To a stirred solution of (S)-3-cyclohexyl-2-[4-(2-methylsulfanyl-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-propionic acid (200 mg, 0.53 mmol) in dichloromethane (12 mL) was gradually added 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (305 mg, 1.6 mmol) and N,N-diisopropylethylamine (387 mg, 3.0 mmol) at room temperature, under nitrogen. After 15 min, 1-hydroxybenzotriazole (245 mg, 1.7 mmol) and 1-(3-amino-pyrazol-1-yl)-2-methyl-propan-2-ol (prepared in U.S. Pat. Appl. US2008021032 Example 80, 82 mg, 0.53 mmol) were added to the reaction mixture. The reaction mixture was then stirred at 23° C. for 48 h. The reaction mixture was diluted with ethyl acetate and washed with a saturated aqueous ammonium chloride solution followed by a saturated aqueous sodium bicarbonate solution. The organic layer was then washed with a saturated aqueous sodium chloride solution, separated, dried over sodium sulfate and concentrated in vacuo to afford the crude product, which was purified by flash column chromatography (silica gel (100-200 mesh)) which afforded (S)-3-cyclohexyl-N-[1-(2-hydroxy-2-methyl-propyl)-1H-pyrazol-3-yl]-2-[4-(2-methylsulfanyl-phenoxy)-2-oxo-2,5-dihydro-pyrrol-1-yl]-propionamide (40 mg, 15%) as an light yellow solid.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US07741327B2uspto-grants-2010_06