반응 #71512

반응 방정식

5-iodocytidine

bicarbonate

propargyltrifluoroacetamide

triethylamine

→

5-[3-(trifluoroacetamido)propynyl]cytidine

수율 67.0%

용매

DMF

methanol dichloromethane

반응 조건

후처리

1. 1
   workup.ADDITIONwere added to the reaction mixture under N2
2. 2
   workup.STIRRINGAfter stirring for about one h
3. 3
   여과the reaction mixture was filtered
4. 4
   세척the resin was washed with 1:1 methanol-dichloromethane
5. 5
   농축The combined filtrates were rapidly concentrated with a rotary evaporator
6. 6
   기타The residue was immediately purified by flash chromatography
7. 7
   기타Removal of solvent from the appropriate fractions

실험 절차

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.

출처