5'-Deoxy-5-fluorocytidine Chemical Properties

Melting point:

196-198°C

Boiling point:

437.9±55.0 °C(Predicted)

Density 

1.84±0.1 g/cm3(Predicted)

storage temp. 

Keep in dark place,Sealed in dry,Room Temperature

solubility 

DMSO (Slightly), Methanol (Slightly)

form 

Solid

pka

13.65±0.70(Predicted)

color 

White to Light Beige

Stability:

HYGROSCOPIC

CAS DataBase Reference

66335-38-4(CAS DataBase Reference)

Safety Information

Hazard Codes 

Xn,Xi

Risk Statements 

20/21/22-36/37/38

Safety Statements 

26-36-37/39-24/25

HS Code 

29349990

5'-Deoxy-5-fluorocytidine Usage And Synthesis

Chemical Properties

White Solid

Uses

A metabolite of Capecitabine.

Definition

ChEBI: 5'-Deoxy-5-fluorocytidine is a N-glycosyl compound.

Synthesis

1. Pentyl (1-((2R,3R,4S,5R)-3,4-dihydroxy-5-methyltetrahydrofuran-2-yl)-5-fluoro-2-oxo-1,2-dihydropyrimidin-4-yl)carbamate (capecitabine, 4.5 g, 12.5 mmol) was suspended with potassium carbonate (8.8 g, 63.77 mmol) in methanol (250 mL) and N,N- dimethylformamide (DMF, 10 mL). The mixture was heated to reflux for 24 hours. Upon completion of the reaction, the reaction solution was cooled and concentrated to dryness under reduced pressure at below 45 °C. The residue was dissolved in hot methanol, filtered and washed with hot methanol. The filtrate was pre-adsorbed on silica gel and purified by fast column chromatography using 50% methanol/ethyl acetate as eluent to afford 1-[3,4-dihydroxy-5-methyltetrahydrofuran-2-yl]-4-amino-1H-pyrimidin-2-one (3.0 g, 90% yield). 2. The above product (3.0 g) was suspended in chloroform (125 mL) and heated to 50 °C. The product (3.0 g) was added to the mixture. Acetic acid (2 mL, 34 mmol) and acetyl chloride (20 mL, 206 mmol) were added sequentially and stirred at 50 °C for 7 hours, followed by continued stirring at 20 °C for 72 hours. At the end of the reaction, ether (100 mL) was added, the solid was collected by filtration and washed with ether to afford 1-[3,4-diacetoxy-5-methyltetrahydrofuran-2-yl]-4-amino-1H-pyrimidin-2-one hydrochloride (4.0 g, 90% yield). 3. The above hydrochloride (2.07 g, 5.7 mmol) was dissolved in pyridine (1.4 mL, 17.4 mmol) and dichloromethane (DCM, 15 mL) with 5-nitrothiophen-2-ylmethanol (1.47 g, 9.3 mmol). A 2M toluene solution of phosgene (3.6 mL, 7.2 mmol) was slowly added at 0 °C and stirred for 2.5 h. After 2.5 h, the same amount of phosgene solution was added again and stirring was continued for 2 h at 0 °C, followed by 18 h of refrigeration. The reaction solution was partitioned with ethyl acetate and brine, the aqueous phase was extracted with ethyl acetate, the organic phases were combined, dried and concentrated under reduced pressure. The residue was purified by silica gel column chromatography with 2% methanol/DCM as eluent to give an off-white foamy product (400 mg, 14% yield). Thin layer chromatography (TLC) showed Rf=0.45 (2% methanol/ethyl acetate as unfolding agent). Liquid chromatography-mass spectrometry (LC-MS) analysis showed a retention time of 4.68 min (TFA 20-50% gradient) and a mass m/z of 201/159/143. nuclear magnetic resonance hydrogen spectra (1H NMR, 500 MHz, DMSO-d6) δ 11.20 (1H, broad single peak, NH), 8.3 (1H, broad peak, NCH=CF). 8.05 (1H, single peak, HarH), 7.30 (1H, single peak, HarH), 5.80 (1H, single peak, NCHO), 5.42 (3H, multiple peaks, HarCH2OCONH, CHOAc), 5.15 (1H, single peak, CHOAc), 4.05 (1H, multiple peaks, OCHCH3), 3.45 (2H, multiple peak, 2×CHOAc), 2.48 (3H, single peak, OAc), 2.05 (3H, single peak, OAc), 1.37 (3H, single peak, OCHCH3) ppm.

References

[1] Patent: WO2006/32921, 2006, A1. Location in patent: Page/Page column 37-38

5'-Deoxy-5-fluorocytidine(66335-38-4)Related Product Information

• 5-Fluorocytidine
• 5-Azacytidine
• Chenodeoxycholic acid
• Cytidine-5'-triphosphate disodium salt dihydrate
• Cytarabine
• Fluorocytosine
• 1-beta-D-Arabinofuranosylcytosine hydrochloride
• 2',3'-Di-O-acetyl-5'-deoxy-5-fuluro-D-cytidine
• 5'-deoxy-5-fluore-N-[(pentoyloxy)carbonyl]cytidine 2',3'-diacetate
• Ursodeoxycholic acid
• Doxifluridine
• 1,2,3-Triacetyl-5-deoxy-D-ribose
• 2'-Deoxycytidine monohydrate
• 3'-O-(5'-Deoxy-α-D-ribofuranosyl) Capecitabine
• 2'-O-(5'-Deoxy-β-D-ribofuranosyl) Capecitabine
• CAPECITABINE related substance USP
• 5'-Deoxy-5-fluoro-N-[(2-methylbutoxy)carbonyl]cytidine
• 5'-Deoxy-5-fluoro-N4-(isopentyloxycarbonyl)cytidine