Bicarbonate Ion → 5-[3-(Trifluoroacetamido)propynyl]cytidine

HRID 1501916Notes

Reaction equation

HRID 1501916 reaction equation
I[C:2]1[C:3]([NH2:18])=[N: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].[CH2:19]([NH:22][C:23](=[O:28])[C:24]([F:27])([F:26])[F:25])[C:20]#[CH:21].C(N(CC)CC)C.C(=O)(O)[O-]>CO.ClCCl.CN(C=O)C>[F:25][C:24]([F:27])([F:26])[C:23]([NH:22][CH2:19][C:20]#[C:21][C:2]1[C:3]([NH2:18])=[N: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:28]

Participants

7

Reactant 4

HCID 769Bicarbonate IonHCID 8471TriethylamineHCID 159359IodocytidineHCID 110948052,2,2-trifluoro-N-(prop-2-yn-1-yl)acetamide

Product 1

HCID 866586305-[3-(Trifluoroacetamido)propynyl]cytidineYield 67%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21226129Dichloromethane methanolSolvent

Procedure

A 100-mL three-necked flask was charged with 5-iodocytidine (2.66 g, 7.00 mmol, 1.00 equiv.), cuprous iodide (0.267 g, 1.40 mmol, 0.20 equiv.) and dry DMF (35 mL). After complete dissolution of the reaction mixture, propargyltrifluoroacetamide (3.17 g, 21.00 mmol, 3.00 equiv.), triethylamine (1.42 g, 14.00 mmol, 2.00 equiv.) and finally tetrakis (triphenylphosphine)palladium(0) (0.809 g, 0.70 mmol, 0.10 equiv.) were added to the reaction mixture under N2. The reaction was stirred at ambient temperature (around 19° C. to around 22° C.) under N2 for 18-24 h. The reaction was then diluted with 70 mL of 1:1 methanol-dichloromethane and the bicarbonate form of AGI X8 resin (12.00 g) was added. After stirring for about one h, the reaction mixture was filtered and the resin was washed with 1:1 methanol-dichloromethane. The combined filtrates were rapidly concentrated with a rotary evaporator. The residue was immediately purified by flash chromatography. Removal of solvent from the appropriate fractions afforded 1.84 g (67%) of 5-[3-(trifluoroacetamido)propynyl]cytidine as a light brown solid, which was confirmed by 1H-NMR.

Workup

  1. additionwere added to the reaction mixture under N2
  2. stirringAfter stirring for about one h
  3. filtrationthe reaction mixture was filtered
  4. washthe resin was washed with 1:1 methanol-dichloromethane
  5. concentrationThe combined filtrates were rapidly concentrated with a rotary evaporator
  6. customThe residue was immediately purified by flash chromatography
  7. customRemoval of solvent from the appropriate fractions

Sources & evidence

ORD record
ord-210f9aa84e544865a12459c2708c2c19
Source dataset
uspto-grants-2015_12
Patent number
US09206216B2

Reaction notes

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