Triethylamine → 5-[3-(Trifluoroacetyl)aminopropyn-1-yl]uridine

HRID 1168687Notes

Reaction equation

HRID 1168687 reaction equation
I[C:2]1[C:3](=[O:18])[NH:4][C:5](=[O:17])[N:6]([CH:16]=1)[C@@H:7]1[O:15][C@H:12]([CH2:13][OH:14])[C@@H:10]([OH:11])[C@H:8]1[OH:9].C(N(CC)CC)C.[CH2:26]([NH:29][C:30](=[O:35])[C:31]([F:34])([F:33])[F:32])[C:27]#[CH:28]>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[F:32][C:31]([F:34])([F:33])[C:30]([NH:29][CH2:26][C:27]#[C:28][C:2]1[C:3](=[O:18])[NH:4][C:5](=[O:17])[N:6]([CH:16]=1)[C@@H:7]1[O:15][C@H:12]([CH2:13][OH:14])[C@@H:10]([OH:11])[C@H:8]1[OH:9])=[O:35]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 12681085-IodouridineHCID 110948052,2,2-trifluoro-N-(prop-2-yn-1-yl)acetamide

Product 1

HCID 147685515-[3-(Trifluoroacetyl)aminopropyn-1-yl]uridineYield 95%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
45 °C

Procedure

This compound was prepared similarly. 5-Iodouridine (1.35 mmol, 500 mg) was dissolved in dry DMF (12 mL) and Ar was bubbled through the solution for 10 min. Then, (Ph3P)4Pd (0.1 equiv., 0.1351 mmol, 156 mg) was added and Ar was bubbled through the solution for another 5 min. Triethylamine (2.0 equiv., 2.703 mmol, 273 mg, 0.376 mL) was added via syringe followed by addition of N-propargyltrifluoroacetamide (2.5 equiv., 3.38 mmol, 510 mg and CuI (0.2 equiv., 0.27 mmol, 51.5 mg). The mixture was stirred at 45° C. for 3.5 h, then the solvent was evaporated, and the residue dissolved in MeOH/methylene chloride 1:1 (10 mL). Ion exchange resin (Bio-Rad AG1 X8, HCO3-form, 1.5 g) was added to remove Et3N.HI, and the mixture stirred at room temperature for 20 min. The mixture was then filtered through Celite, the solid washed with MeOH/methylene chloride 1:1 (10 mL) and the solvents removed by rotary evaporation. The residue was purified by column chromatography (chloroform/MeOH 8.25:1.75) to yield 5-(3-trifluoroacetamidopropyn-1-yl)-uridine (ca. 95%) as a yellow foam contaminated with some Et3N.HI. Rf:0.43 (chloroform/MeOH 8.25:1.75). 1H-NMR (DMSO-d6): 3.61 (m, 2H, 5′), 3.86 (m, 1H, 4′), 3.93-4.08 (m, 2H, 2′, 3′), 4.23 (m, 2H, H-9), 5.08 (d, 1H, OH), 5.19 (t, 1H, OH), 5.41 (d, 1H, OH), 5.75 (d, 1H, 1′), 8.48 (s, 1H, H-6), 10.10 (t, 1H, NH chain), 11.64 (s, 1H, NH cycl.). 13C-NMR (DMSO-d6): 29.5 (C-9), 60.5 (5′), 69.6 (3′), 73.8 (2′), 75.3 (C-8), 85.0 (4′), 87.6, (C-7), 88.3 (1′), 97.8 (C-5), 113.9, 117.7 (q, CF3, J=288.48 Hz), 144.4 (C-6), 149.7 (C-2), 155.9, 156.4 (q, COCF3, J=36.80 Hz), 161.6 (C-4).

Workup

  1. customThis compound was prepared similarly
  2. customAr was bubbled through the solution for 10 min
  3. customAr was bubbled through the solution for another 5 min
  4. customthe solvent was evaporated
  5. dissolutionthe residue dissolved in MeOH/methylene chloride 1:1 (10 mL)
  6. additionIon exchange resin (Bio-Rad AG1 X8, HCO3-form, 1.5 g) was added
  7. customto remove Et3N
  8. stirringHI, and the mixture stirred at room temperature for 20 min
  9. filtrationThe mixture was then filtered through Celite
  10. washthe solid washed with MeOH/methylene chloride 1:1 (10 mL)
  11. customthe solvents removed by rotary evaporation
  12. customThe residue was purified by column chromatography (chloroform/MeOH 8.25:1.75)

Sources & evidence

ORD record
ord-8cac19aef3fd410d95071d0b658a4d5b
Source dataset
uspto-grants-2003_09
Patent number
US06627456B1

Reaction notes

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