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

HRID 427235Notes

Reaction equation

HRID 427235 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 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 produce 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. 145-152°.

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. customThe fractions with the main produce
  9. customevaporated
  10. customdried in vacuo
  11. stirringThe resultant foam is stirred with 150 ml of ether
  12. customto give crystalline product

Sources & evidence

ORD record
ord-85feaa8332e7463292c5a31712716730
Source dataset
uspto-grants-2001_11
Patent number
US06312953B1

Reaction notes

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