Water → HCID 54362158, compound

HRID 728760Notes

Reaction equation

HRID 728760 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.Br[CH2:21][CH2:22][CH2:23][N:24]1[C:28](=[O:29])[C:27]2=[CH:30][CH:31]=[CH:32][CH:33]=[C:26]2[C:25]1=[O:34].C[O-].[Na+].O>CN1C(=O)N(C)CCC1.CC(O)=O>[C:25]1(=[O:34])[N:24]([CH2:23][CH2:22][CH2:21][N:7]2[C:8](=[O:9])[C:2]([CH3:1])=[CH:3][N:4]([C@@H:10]3[O:14][C@H:13]([CH2:15][OH:16])[C@@H:12]([N:17]=[N+:18]=[N-:19])[CH2:11]3)[C:5]2=[O:6])[C:28](=[O:29])[C:27]2=[CH:30][CH:31]=[CH:32][CH:33]=[C:26]12

Participants

7

Reactant 4

HCID 962WaterHCID 21611N-3-Bromopropylphthalimide3×HCID 35370ZidovudineHCID 10942334Sodium Methoxide2×

Product 1

HCID 54362158HCID 54362158, compound

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 816462(1H)-Pyrimidinone, tetrahydro-1,3-dimethyl-Solvent

Conditions

Temperature
70 °C

Procedure

A solution of 280 mg AZT, 310 mg N-(3-bromopropyl)-phthalimide (BPP) and 300 ul of sodium methoxide solution (4.4M NaOMe in MeOH) in 1 ml DMPU was heated at 70° C. for one hour, then 145 mg BPP and 300 ul NaOMe solution was added and the mixture heated for another hour at 70° C. Another 175 mg BPP was added and heating was continued for a total of 4hours at 70° C. The reaction mixture was diluted with 10 volumes deionized water, acidified with 200 ul HOAc and extracted into EtOAc. The organic phase was washed with 5% NaHCO3, deionized water, 0.1M HOAc and saturated NaCl, then concentrated and chromatographed by preparative TLC on silica gel-F 2000 um using the solvent system CHCl3 /MeOH/HOAc(96.7+3.3+0.33). The product (Rf =0.35) was eluted with MeOH. It was immunologically active in an AZT assay by FPIA.

Workup

  1. temperatureheating
  2. customwas continued for a total of 4hours at 70° C
  3. additionThe reaction mixture was diluted with 10 volumes
  4. extractionextracted into EtOAc
  5. washThe organic phase was washed with 5% NaHCO3
  6. concentrationconcentrated
  7. customchromatographed by preparative TLC on silica gel-F 2000 um
  8. washThe product (Rf =0.35) was eluted with MeOH

Sources & evidence

ORD record
ord-739552566fbd47cd972e7c2e4af004b1
Source dataset
uspto-grants-1991_09
Patent number
US05051361

Reaction notes

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