Isophthaloyl chloride → HCID 178476350, compound

HRID 703549Notes

Reaction equation

HRID 703549 reaction equation
[C:1]([O:4][CH2:5][C@H:6]1[O:10][C@@H:9]([N:11]2[CH:18]=[C:17]([F:19])[C:15](=[O:16])[NH:14][C:12]2=[O:13])[CH2:8][C@@H:7]1[O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)(=[O:3])[CH3:2].[C:28](Cl)(=[O:38])[C:29]1[CH:37]=[CH:36][CH:35]=[C:31]([C:32](Cl)=[O:33])[CH:30]=1.C(N(CC)CC)C.[OH:47][C:48]1[CH:53]=[CH:52][NH:51][C:50](=[O:54])[CH:49]=1>O1CCOCC1>[C:1]([O:4][CH2:5][C@H:6]1[O:10][C@@H:9]([N:11]2[CH:18]=[C:17]([F:19])[C:15](=[O:16])[N:14]([C:28](=[O:38])[C:29]3[CH:37]=[CH:36][CH:35]=[C:31]([C:32]([O:47][C:48]4[CH:53]=[CH:52][N:51]=[C:50]([OH:54])[CH:49]=4)=[O:33])[CH:30]=3)[C:12]2=[O:13])[CH2:8][C@@H:7]1[O:20][CH2:21][C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1)(=[O:3])[CH3:2]

Participants

6

Reactant 4

HCID 7451Isophthaloyl chlorideHCID 8471Triethylamine2×HCID 136874845'-O-acetyl-3'-O-benzyl-2'-deoxy-5-fluorouridineHCID 546960044-Hydroxy-2(1H)-pyridinone

Product 1

HCID 178476350HCID 178476350, compoundYield 30.1%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of 3.00 g of 5'-O-acetyl-3'--O--benzyl- 2'-deoxy-5-fluorouridine in 100 ml of dry dioxane were added 2.40 g of isophthaloyl chloride and 8.5 ml of triethylamine, and the mixture was refluxed for 2 hours. Then, to the reaction mixture were added a suspension of 1.77 g of 4-hydroxy-2(1H)-pyridone and 9.60 ml of triethylamine in 100 ml of dry dioxane, and the mixture was refluxed for 2 hours. The insolubles were removed by filtration and the filtrate was concentrated. The residue was dissolved in 100 ml of ethyl acetate, and the solution was washed twice with 30 ml of saturated aqueous solution of sodium chloride. The ethyl acetate layer was dried on anhydrous sodium, sulfate and concentrated. The residue was placed on a silica gel column to conduct a gradient elution using chloroform and mixtures of methanol (up to 2%) and chloroform. The fractions corresponding to the title compound were collected and concentrated to dryness, giving 1.48 g of the title compound as a powder in a yield of 30%.

Workup

  1. temperaturethe mixture was refluxed for 2 hours
  2. additionThen, to the reaction mixture were added
  3. temperaturethe mixture was refluxed for 2 hours
  4. customThe insolubles were removed by filtration
  5. concentrationthe filtrate was concentrated
  6. dissolutionThe residue was dissolved in 100 ml of ethyl acetate
  7. washthe solution was washed twice with 30 ml of saturated aqueous solution of sodium chloride
  8. dry with materialThe ethyl acetate layer was dried on anhydrous sodium, sulfate
  9. concentrationconcentrated
  10. washa gradient elution
  11. customThe fractions corresponding to the title compound were collected
  12. concentrationconcentrated to dryness

Sources & evidence

ORD record
ord-4b1fbd5698854f948801056f0d61c61f
Source dataset
uspto-grants-1991_01
Patent number
US04983609

Reaction notes

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