Réaction #1840361

ord-48c8af35f7a74a9c998c3bcd09aa4318

Conditions de réaction

Température
0°CELSIUS
Conditions détaillées
See reaction.notes.procedure_details.

Traitement

  1. 1
    Autreallowed at room temperature
  2. 2
    workup.STIRRINGstirred overnight
  3. 3
    ExtractionThe mixture was then extracted with EtOAc (4×10 mL)
  4. 4
    LavageThe combined organic layers were washed with brine
  5. 5
    Séchagedried (Na2SO4)
  6. 6
    Filtrationfiltrated
  7. 7
    Concentrationconcentrated in vacuo
  8. 8
    Autreto give a residue that
  9. 9
    Autrewas purified by flash chromatography (Biotage SP4, gradient EtOAc 5 CV, 0%-10% MeOH in EtOAc 9 CV, hold 10% 3 CV and 10-30% 3 CV)

Mode opératoire

7-amino-10a-(4-methoxyphenyl)-1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one (190 mg, 0.47 mmol) was mixed with concentrated HCl (0.4 mL) and water (0.4 mL) and the mixture cooled down at 0° C. Aqueous NaNO2 solution (49 mg, 0.70 mmol) in water (0.4 mL) was added dropwise at such rate that the temperature didn't exceed 0-5° C. The mixture was stirred at that temperature for 30 minutes. A solution of sodium azide (44 mg, 0.68 mmol) and sodium acetate (565 mg, 6.9 mmol) in water (2 mL) was then added dropwise at 0-5° C. and the mixture allowed at room temperature and stirred overnight. The mixture was then extracted with EtOAc (4×10 mL). The combined organic layers were washed with brine, dried (Na2SO4), filtrated and concentrated in vacuo to give a residue that was purified by flash chromatography (Biotage SP4, gradient EtOAc 5 CV, 0%-10% MeOH in EtOAc 9 CV, hold 10% 3 CV and 10-30% 3 CV) to give 7-azido-10a-(4-methoxyphenyl)-1-[(3-methyl-1,2-oxazol-4-yl)carbonyl]-2,3,10,10a-tetrahydro-1H,5H-imidazo[1,2-a]pyrrolo[1,2-d]pyrazin-5-one (57 mg, yield: 28%).

Source

DOI: 10.6084/m9.figshare.5104873.v1Brevet: US09163029B2uspto-grants-2015_10