Idoxuridine → 5-Ethynyl-2′-deoxyuridine

HRID 1525519Notes

Reaction equation

HRID 1525519 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.C[Si]([C:22]#[CH:23])(C)C.C[O-].[Na+]>CC#N.CCN(CC)CC.CO.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu]I>[C:22]([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)#[CH:23]

Participants

8

Reactant 3

HCID 5905IdoxuridineHCID 66111TrimethylsilylacetyleneHCID 10942334Sodium Methoxide

Product 1

HCID 4721725-Ethynyl-2′-deoxyuridineYield 73%

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 887MethanolSolvent2×HCID 21895542Acetonitrile triethylamineSolvent

Conditions

Temperature
25 °C

Procedure

5-Iodo-2′-deoxyuridine (5, 1.0 g, 2.82 mmol) was dissolved in MeCN/Et3N (66 mL of 1:1, v/v) under argon atmosphere. Trimethylsilylacetylene (1.6 mL, 11.3 mmol), bis-(triphenylphosphine)-palladium(II) chloride (42.2 mg, 0.60 mmol), and CuI (28 mg, 0.15 mmol) were added, and the mixture was heated for 3.5 h in the flask immersed into a preheated oil bath (50° C.). The solvents were removed in vacuo to give a residue that was purified by silica gel flash column chromatography. Elution with CHCl3/MeOH (9:1, v/v) afforded trimethylsilyl intermediate as a solid (0.75 g, 82%). To the solution of this intermediate (0.7 g, 2.16 mmol) in anhydrous MeOH (16 mL) under argon atmosphere, a solution of NaOMe in MeOH (145 mL of 0.05 N) was added, and the reaction was stirred at 25° C. for 2 h. The pH of the solution was adjusted to 5-6 using Dowex 50 WX8-200 (H+), the mixture was filtered, and concentrated in vacuo to give a residue that was purified by silica gel column flash chromatography using CHCl3/MeOH (8:2, v/v) as eluent to yield 5-ethynyl-2′-deoxyuridine (EdU) as a white solid (395 mg, 73%); 1H NMR (DMSO-d6) δ 11.62 (s, 1H, NH), 8.29 (s, 1H, H-6), 6.10 (dd, J=6.56, 6.56 Hz, 1H, H-1′), 5.24 (d, J=4.31 Hz, 1H, C-3′ OH), 5.12 (t, J=4.91 Hz, 1H, C-5′ OH), 4.23 (m, 1H, H-3′), 4.10 (s, 1H, C≡CH), 3.79 (q, J=3.25, 3.25, 3.26 Hz, 1H, H-4′), 3.59 (m, 2H, H-5′, H-5″), 2.16 (m, 2H, H-2′, H-2″). HRMS calcd for C11H11N2O14 251.0673 (M−H)−. found 251.0683.

Workup

  1. temperaturethe mixture was heated for 3.5 h in the flask
  2. customimmersed into a preheated oil bath
  3. custom(50° C.)
  4. customThe solvents were removed in vacuo
  5. customto give a residue that
  6. customwas purified by silica gel flash column chromatography
  7. washElution with CHCl3/MeOH (9:1
  8. customv/v) afforded trimethylsilyl intermediate as a solid (0.75 g, 82%)
  9. filtrationthe mixture was filtered
  10. concentrationconcentrated in vacuo
  11. customto give a residue that
  12. customwas purified by silica gel column flash chromatography

Sources & evidence

ORD record
ord-dec4ea0e328f4553bc828fa9e3e329be
Source dataset
uspto-grants-2015_07
Patent number
US09080169B2

Reaction notes

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