4,5,6-TRIFLUOROPYRIMIDINE

4,5,6-TRIFLUOROPYRIMIDINE Property

Boiling point:

83-85°C

Density 

1.4609

refractive index 

1.4087

Flash point:

83-85°C

storage temp. 

under inert gas (nitrogen or Argon) at 2-8°C

solubility 

Acetone, Chloroform, Methanol (Slightly)

form 

Oil

pka

-6.10±0.26(Predicted)

color 

Clear Colourless to Light Yellow

CAS DataBase Reference

17573-78-3

Safety

Hazard Codes 

Xi

Risk Statements 

36/37/38

Safety Statements 

26-36

HazardClass 

IRRITANT

HazardClass 

8

PackingGroup 

III

HS Code 

29335990

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H314Causes severe skin burns and eye damage

H315Causes skin irritation

H318Causes serious eye damage

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

P261Avoid breathing dust/fume/gas/mist/vapours/spray.

P280Wear protective gloves/protective clothing/eye protection/face protection.

P303+P361+P353IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.

P305+P351+P338IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses, if present and easy to do. Continuerinsing.

P310Immediately call a POISON CENTER or doctor/physician.

4,5,6-TRIFLUOROPYRIMIDINE Chemical Properties,Usage,Production

Uses

4,5,6-Trifluoropyrimidine is a starting material for the preparation of O-linked pyrimidinamine-based compounds as deoxycytidine kinase inhibitors. These inhibitors are useful for treatment of cancer.

Synthesis

The general procedure for the synthesis of 4,5,6-trifluoropyrimidine from 4,5,6-trichloropyrimidine was as follows: first, 7160 mL of cyclobutanesulfone and 3876 g of potassium fluoride (KF) were added to an autoclave and stirred for 1 hour at 150 °C. Subsequently, 700 mL of the cyclobutanesulfone was removed by reduced pressure distillation to dry the mixture. The mixture was cooled to 90 °C and the air in the kettle was replaced with nitrogen. Next, a solution of 3122 g of 4,5,6-trichloropyrimidine and 2386 g of dried cyclobutanesulfone preheated to 45 °C was added. The reaction vessel was sealed after the rapid addition of 10 g of CNC catalyst and 20.5 g of nitrobenzene. The mixture was heated to 200 °C and the reaction was stirred for 5 hours, then warmed to 220 °C to continue the reaction for 11 hours. The maximum total pressure was controlled at 6.5 bar during the reaction. Upon completion of the reaction, the mixture was cooled to 40 °C with stirring and the product was slowly depressurized and transferred to an ice-cold receiver. Subsequently, the internal temperature was slowly raised to 150 °C and the product was distilled first at atmospheric pressure and then at reduced pressure. Redistillation of the crude product gave 1540 g of 4,5,6-trifluoropyrimidine (66% of theoretical yield) as a colorless liquid.

References

[1] Patent: US2006/9643, 2006, A1. Location in patent: Page/Page column 5