Water → HCID 54011039, compound

HRID 1769218Notes

Reaction equation

HRID 1769218 reaction equation
[CH3:1][C:2]1[C:8](=[O:9])[NH:7][C:5](=[O:6])[N:4]([C@@H:10]2[O:14][C@H:13]([CH2:15][OH:16])[C@@H:12]([N:17]=[N+:18]=[N-:19])[CH2:11]2)[CH:3]=1.C[O-].[Na+].BrC[C:25]([O:27][CH2:28][CH3:29])=[O:26].O>CN1C(=O)N(C)CCC1>[C:25]([N:7]1[C:8](=[O:9])[C:2]([CH3:1])=[CH:3][N:4]([C@@H:10]2[O:14][C@H:13]([CH2:15][OH:16])[C@@H:12]([N:17]=[N+:18]=[N-:19])[CH2:11]2)[C:5]1=[O:6])([O:27][CH2:28][CH3:29])=[O:26]

Participants

6

Reactant 4

HCID 962WaterHCID 7748Ethyl bromoacetate2×HCID 35370ZidovudineHCID 10942334Sodium Methoxide2×

Product 1

HCID 54011039HCID 54011039, compound

Reagents, catalysts & solvents 1

HCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Procedure

A solution of 267 mg AZT in 1 ml DMPU was treated with 500 ul of sodium methoxide solution (4.4 M NaOMe, in MeOH) and 250 ul of ethyl bromoacetate and stirred 30 minutes at room temperature. Another 500 ul NaOMe solution and 250 ul ethyl bromoacetate were added and the mixture was heated 1 hour at 60° C. in a water bath. The resulting suspension was diluted with 15 ml deionized water and extracted with EtOAc. The organic phase was washed, first with 5% NaHCO3 then saturated NaCl solution, concentrated under reduced pressure and chromatographed by preparative TLC on silica gel-F 2000 um using the solvent system CHCl3 /MeOH/HOAc (95+5+0.5). Three bands were visualized with UV (254 nm) and were eluted separately with MeOH. Fraction A (Rf =0.19) was identified as AZT by TLC and UV spectrum by comparison with an authentic AZT reference. It was also immunologically active in an AZT assay by FPIA. Fractions B (Rf =0.37) and C (Rf =0.57) had similar UV spectra, resembling that of 3-methylthymidine. Fraction B was immunologically active (approximately 110% "cross-reactivity" relative to AZT in an AZT assay by FPIA). Fraction C was immunologically inactive. Fraction B was therefore evaporated to dryness and saved.

Workup

  1. temperaturethe mixture was heated 1 hour at 60° C. in a water bath
  2. additionThe resulting suspension was diluted with 15 ml
  3. extractionextracted with EtOAc
  4. washThe organic phase was washed, first with 5% NaHCO3
  5. concentrationsaturated NaCl solution, concentrated under reduced pressure
  6. customchromatographed by preparative TLC on silica gel-F 2000 um
  7. washwere eluted separately with MeOH
  8. customFraction B was therefore evaporated to dryness

Sources & evidence

ORD record
ord-efe78c04606c43438cc29c6984dbcea5
Source dataset
uspto-grants-1995_01
Patent number
US05380825

Reaction notes

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