Idoxuridine → 5-[3-(2-Trifluoroacetamidoethoxy)propynyl]-2'-deoxyuridine

HRID 1416387Notes

Reaction equation

HRID 1416387 reaction equation
I[C:2]1[C:3](=[O:17])[NH:4][C:5](=[O:16])[N:6]([CH:15]=1)[C@@H:7]1[O:14][C@H:11]([CH2:12][OH:13])[C@@H:9]([OH:10])[CH2:8]1.[I-].C(N(CC)CC)C.[F:26][C:27]([F:38])([F:37])[C:28]([NH:30][CH2:31][CH2:32][O:33][CH2:34][C:35]#[CH:36])=[O:29]>[Cu].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Pd].C(O)(=O)C>[F:26][C:27]([F:37])([F:38])[C:28]([NH:30][CH2:31][CH2:32][O:33][CH2:34][C:35]#[C:36][C:2]1[C:3](=[O:17])[NH:4][C:5](=[O:16])[N:6]([CH:15]=1)[C@@H:7]1[O:14][C@H:11]([CH2:12][OH:13])[C@@H:9]([OH:10])[CH2:8]1)=[O:29]

Participants

8

Reactant 4

HCID 5905IdoxuridineHCID 8471TriethylamineHCID 30165Iodide IonHCID 167426213-(2-Trifluoroacetamidoethoxy)propyne

Product 1

HCID 213095685-[3-(2-Trifluoroacetamidoethoxy)propynyl]-2'-deoxyuridine

Reagents, catalysts & solvents 3

HCID 23978CopperCatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 176Acetic AcidSolvent

Procedure

A mixture of 5-iodo-2'-deoxyuridine (3.54 g, 10 mmol), copper(l) iodide (0.19 g, 1 mmol) and tetrakis(triphenylphosphine)palladium(O) (0.58 g, 0.5 mmol) is dried in vacuo at 60° for 3 hours and placed under argon. A suspension of the mixture in dry DMF (20 ml) is stirred under argon and treated with dry triethylamine (1.7 ml, 12 mmol) followed by 3-(2-Trifluoroacetamidoethoxy)propyne (3.17 g, 16 mmol). The mixture is cooled at room temperature in a water bath and stirred for 17 hours. The mixture is treated with 2% acetic acid (100 ml), the catalyst is removed by filtration and washed with 50% methanol. The filtrates are combined and passed onto a LiChroprep RP-18 column (5×25 cm), the column is washed, then eluted with 1% acetic acid in 50% (v/v) methanol. The fractions with the main product are combined, evaporated, and dried in vacuo. The resultant foam is stirred with 150 ml of ether to give crystalline product; yield 3.6 g (85%); m.p. 145-1520.

Workup

  1. customis dried in vacuo at 60° for 3 hours
  2. additionA suspension of the mixture in dry DMF (20 ml)
  3. stirringstirred for 17 hours
  4. customthe catalyst is removed by filtration
  5. washwashed with 50% methanol
  6. washthe column is washed
  7. washeluted with 1% acetic acid in 50% (v/v) methanol
  8. customevaporated
  9. customdried in vacuo
  10. stirringThe resultant foam is stirred with 150 ml of ether
  11. customto give crystalline product

Sources & evidence

ORD record
ord-97edc8428f5841a28cb292a09f352f2d
Source dataset
uspto-grants-1999_06
Patent number
US05912340

Reaction notes

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