Hydrazine hydrate (1:1) → 1-(3-Azido-2,3-dideoxy-beta-D-erythropentofuranosyl)-5-methyl-2(1H)-pyrimidinone

HRID 2248852Notes

Reaction equation

HRID 2248852 reaction equation
C([O:4][CH2:5][C@H:6]1[O:10][C@@H:9]([N:11]2[CH:16]=[C:15]([CH3:17])[C:14](N3C=NC=N3)=[N:13][C:12]2=[O:23])[CH2:8][C@@H:7]1[N:24]=[N+:25]=[N-:26])(=O)C.O.NN>CC#N.CCO.N>[N:24]([C@@H:7]1[C@@H:6]([CH2:5][OH:4])[O:10][C@@H:9]([N:11]2[CH:16]=[C:15]([CH3:17])[CH:14]=[N:13][C:12]2=[O:23])[CH2:8]1)=[N+:25]=[N-:26]

Participants

6

Reactant 2

HCID 24654Hydrazine hydrate (1:1)HCID 474354[(2s,3s,5r)-3-Azido-5-[5-methyl-2-oxo-4-(1,2,4-triazol-1-yl)pyrimidin-1-yl]tetrahydrofuran-2-yl]methyl acetate

Product 1

HCID 4515791-(3-Azido-2,3-dideoxy-beta-D-erythropentofuranosyl)-5-methyl-2(1H)-pyrimidinone

Reagents, catalysts & solvents 3

HCID 222AmmoniaSolventHCID 702EthanolSolventHCID 6342AcetonitrileSolvent

Procedure

1-(5-O-Acetyl-3-azido-2,3-dideoxy-β-D-erythro-pentofuranosyl)-5-methyl-4-(1,2,4-triazol-1-yl)-2-(1H)-pyrimidinone (0.5 g, 1.4 mMol) was dissolved in CH3CN (10 mL) and treated with 85% hydrazine hydrate (0.105 g, 2.1 mMol) for 30 minutes at ambient temperature, analogous to the procedure described in D. Cech and A. Holy, Coll. Czech. Chem. Comm. 42, 2246 (1977). The solvents were evaporated in vacuo and the residue chromatographed on silica gel with 9:1 CHCl3 /MeOH (v/v) as the eluting solvent. Collection and evaporation of appropriate fractions yielded a solid. The solid was dissolved in EtOH (50 mL) containing Ag2O (0.35 g, 1.5 mMol, 1.5 eq) and refluxed for 90 minutes. Filtration of the hot suspension through a bed of celite followed by removal of solvents in vacuo gave a solid. The solid was chromatographed on silica gel and eluted with 20:1 CHCl3 /MeOH (v/v). Combination and evaporation of appropriate fractions gave a solid which was dissolved in NH3 -saturated MeOH (50 mL) for 3 hours. Evaporation of the solvents in vacuo yielded an oil which was chromatographed on silica gel eluted with 20:1 CHCl3 /MeOH (v/v). The appropriate fractions were combined and solvents evaporated in vacuo to give an oil which slowly solidified upon standing: mp =62°-63° C.; UV (nm): at ph 1λmax =326, 212 (ε=7700, 13000), λmin =263(ε=200); at pH 13λmax 322,218(ε=22700, 10800), λmin =246 (ε=400); H'NMR: (DMSO-d6) δ8.46(d, 1H, H4, J=3.28 Hz), 8.28(d, 1H, H6, J=3.23 Hz), 6.00(t, 1H, H1', J=5.08 Hz), 5.31(t, 1H, 5'OH, J=5.12 Hz), 4.4-4.3(m, 1H, H3 '), 3.95-3.89(m, 1H, H4 '), 3.8-3.6(m, 2H, H5 '), 2.5-2.3(m, 2H, H2 '), 2.03(s, 3H, 5-CH3).

Workup

  1. customThe solvents were evaporated in vacuo
  2. customthe residue chromatographed on silica gel with 9:1 CHCl3 /MeOH (v/v) as the eluting solvent
  3. customCollection and evaporation of appropriate fractions
  4. customyielded a solid
  5. temperaturerefluxed for 90 minutes
  6. filtrationFiltration of the hot suspension through a bed of celite
  7. customfollowed by removal of solvents in vacuo
  8. customgave a solid
  9. customThe solid was chromatographed on silica gel
  10. washeluted with 20:1 CHCl3 /MeOH (v/v)
  11. customCombination and evaporation of appropriate fractions
  12. customgave a solid which
  13. customEvaporation of the solvents in vacuo
  14. customyielded an oil which
  15. customwas chromatographed on silica gel
  16. washeluted with 20:1 CHCl3 /MeOH (v/v)
  17. customsolvents evaporated in vacuo
  18. customto give an oil which
  19. custommp =62°-63° C.

Sources & evidence

ORD record
ord-9c70af81537c451fa3d32b68582da027
Source dataset
uspto-grants-1991_08
Patent number
US05041543

Reaction notes

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