Water → HCID 54011039, compound

HRID 728759Notes

Reaction equation

HRID 728759 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 (4.4M 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 hourat 60° C. in a water bath. The resulting suspension was diluted with15 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 TLCon 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 P (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). FractionC was immunologically inactive. Fraction B was therefore evaporated to dryness and saved.

Workup

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

Sources & evidence

ORD record
ord-39474cd89e384597a6847d6d4bd9bb7d
Source dataset
uspto-grants-1991_09
Patent number
US05051361

Reaction notes

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