Ammonia → Sonedenoson

HRID 966385Notes

Reaction equation

HRID 966385 reaction equation
Cl[C:2]1[N:10]=[C:9]([O:11][CH2:12][CH2:13][C:14]2[CH:19]=[CH:18][C:17]([Cl:20])=[CH:16][CH:15]=2)[N:8]=[C:7]2[C:3]=1[N:4]=[CH:5][N:6]2[C@@H:21]1[O:33][C@H:32]([CH2:34][O:35]C(=O)C)[C@@H:27]([O:28]C(=O)C)[C@H:22]1[O:23]C(=O)C.[NH3:39]>C(O)C>[Cl:20][C:17]1[CH:18]=[CH:19][C:14]([CH2:13][CH2:12][O:11][C:9]2[N:10]=[C:2]([NH2:39])[C:3]3[N:4]=[CH:5][N:6]([C:7]=3[N:8]=2)[C@@H:21]2[O:33][C@H:32]([CH2:34][OH:35])[C@@H:27]([OH:28])[C@H:22]2[OH:23])=[CH:15][CH:16]=1

Participants

4

Reactant 2

HCID 222AmmoniaHCID 591072566-Chloro-2-[2-(4-chlorophenyl)-ethoxy]-9-(2,3,5-tri-o-acetyl-beta-d-ribofuranosyl)purine

Product 1

HCID 9910098Sonedenoson

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
-50 °C

Procedure

A 2 liter stainless steel autoclave is charged with 6-chloro-2-[2-(4-chlorophenyl)-ethoxy]-9-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)purine (22.4 g, 39.4 mmoles) and anhydrous ethanol (800 mL) and chilled to −50° C. Liquid ammonia (200 mL) is condensed, added to the autoclave, the autoclave sealed, and the mixture heated to 105±5° C. for 24 hours. The autoclave is then cooled in an ice bath and vented when the pressure drops below 100 psi. After evaporating to approximately 250 mL, activated charcoal (2 g) is added, the mixture heated to reflux for 30 minutes, filtered through Celite®, and evaporated to dryness. The residue is extracted with boiling ethyl acetate (3×250 mL), then partitioned between ethyl acetate (200 mL) and water (250 mL). The final ethyl acetate extraction is washed once with water (100 mL), dried (Na2SO4), filtered, and added to the original ethyl acetate extracts. The combined organic extracts are evaporated to dryness and the solid recrystallized from ethanol (100 mL). The crystalline product is collected by filtration, washed with cold ethanol, and dried at 75° C./2 Torr for 24 hours. A second crop is obtained by concentrating the mother liquor and a third crop may be collected by chromatography of the mother liquor.

Workup

  1. customcondensed
  2. additionadded to the autoclave
  3. customthe autoclave sealed
  4. temperaturethe mixture heated to 105±5° C. for 24 hours
  5. temperatureThe autoclave is then cooled in an ice bath
  6. customAfter evaporating to approximately 250 mL, activated charcoal (2 g)
  7. additionis added
  8. temperaturethe mixture heated
  9. temperatureto reflux for 30 minutes
  10. filtrationfiltered through Celite®
  11. customevaporated to dryness
  12. extractionThe residue is extracted with boiling ethyl acetate (3×250 mL)
  13. custompartitioned between ethyl acetate (200 mL) and water (250 mL)
  14. extractionThe final ethyl acetate extraction
  15. washis washed once with water (100 mL)
  16. dry with materialdried (Na2SO4)
  17. filtrationfiltered
  18. additionadded to the original ethyl acetate extracts
  19. customThe combined organic extracts are evaporated to dryness
  20. customthe solid recrystallized from ethanol (100 mL)
  21. filtrationThe crystalline product is collected by filtration
  22. washwashed with cold ethanol
  23. customdried at 75° C./2 Torr for 24 hours
  24. customA second crop is obtained
  25. concentrationby concentrating the mother liquor
  26. customa third crop may be collected by chromatography of the mother liquor

Sources & evidence

ORD record
ord-9257984ae98744dcbd1029ff10f11081
Source dataset
uspto-grants-2005_10
Patent number
US06951932B2

Reaction notes

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