5-Fluoropyrimidine-4,6-diol Chemical Properties

Density 

1.73±0.1 g/cm3(Predicted)

storage temp. 

2-8°C

pka

3.42±0.10(Predicted)

Appearance

Off-white to light brown Solid

Safety Information

HazardClass 

IRRITANT

HS Code 

29335990

5-Fluoropyrimidine-4,6-diol Usage And Synthesis

Uses

5-Fluoropyrimidine-4,6-diol is used in preparation of Phenylpyrimidine derivatives and analogs for use as Kynurenine-3-monooxygenase inhibitors.

Preparation

synthesis of 5-Fluoro-4,6-dihydroxypyrimidine: Formamidine acetate (2.06 g, 20 mmol) was added to the solution of sodium (1.38 g, 60 mmol) in anhydrous ethanol (40 mL) and the mixture was heated to reflux. Diethyl 2-fluoromalonate (3.20 g, 18 mmol) was added dropwise over 20 minutes and the mixture was heated at reflux for 6 h. After cooling to room temperature, the solution was evaporated to dryness, the residue was dissolved in water (20 mL), acidified with HCl (5 mL), the precipitate was filtered, washed with water (5 mL), ethanol (2 × 5 mL) and diethyl ether (2 × 5 mL). After drying in vacuo, 5-fluoro-4,6-dihydroxypyrimidine (1.50 g, 64%) was obtained as a brown powder.
m.p.: >300 °C; ([M + H]+ , 131.0244, C4H4FN2O2 requires: [M]+ , 131.0257); IR (neat, cm-1 ) 3053, 2639, 1633, 1547, 1388, 1213; δH (DMSO d6, 400 MHz) 7.90 (1H, s, C-H), 12.38 (2H, bs, OH); δF (DMSO d6, 376 MHz): -178.06 (s); δC (DMSO d6, 100 MHz) 132.79 (d, 1 JCF 235.6, C-F), 144.46 (d, 4 JCF 7.7, C-H), 155.83 (d, 2 JCF 15.0, C-OH); m/z (ASAP) 131 (100%, [M + H]+ ).21a

Synthesis

GENERAL STEPS: To a stirred solution of sodium ethanolate (2.7 g, 0.04 mol) in ethanol (40 mL) was added formamidine hydrochloride (4.2 g, 0.04 mol), followed by the slow dropwise addition of diethyl 2-fluoromalonate (dissolved in 10 mL of ethanol) at 0 °C. The reaction mixture was heated to 90 °C and stirred overnight. Upon completion of the reaction, ethanol was removed by distillation under reduced pressure and the residue was acidified with concentrated hydrochloric acid to pH < 2. The precipitated solid was collected by filtration and washed with a small amount of cold water, and finally dried under vacuum to afford 5-fluoro-4,6-dihydroxypyrimidine as crude product (750 mg, 52% yield). The structure of the product was confirmed by 1H-NMR (DMSO-d6, 200 MHz): δ 12.40 (broad peak, 2H, OH), 7.89 (single peak, 1H, pyrimidine ring H).

References

[1] Patent: US2009/36419, 2009, A1. Location in patent: Page/Page column 43; 44
[2] ACS Medicinal Chemistry Letters, 2018, vol. 9, # 5, p. 457 - 461

5-Fluoropyrimidine-4,6-diol(106615-61-6)Related Product Information

• NA
• 2,5-Diamino-4,6-dihydroxy-pyrimidine
• 4-Hydroxy-5-fluorpyrimidine
• 5-Fluoropyrimidine
• 6-Fluoro-pyrimidine-2,4-diol
• 2-[(4,6-DIMETHOXY-5-FLUOROPYRIMIDIN-2-YL)OXY]BENZOIC ACID, METHYL ESTER
• 5-Fluoropyrimidine-4,6-diol
• FLUOXASTROBIN