2,4-Dichloro-5-fluoropyrimidine Chemical Properties

Melting point:

37-41 °C (lit.)

Boiling point:

80 °C / 16mmHg

Density 

1.605±0.06 g/cm3(Predicted)

Flash point:

223 °F

storage temp. 

Inert atmosphere,2-8°C

solubility 

soluble in Chloroform, Methanol

pka

-3.96±0.29(Predicted)

form 

Powder or Crystalline Powder or Low Melting Solid

color 

White to pale brown

Sensitive 

Moisture Sensitive

InChI

InChI=1S/C4HCl2FN2/c5-3-2(7)1-8-4(6)9-3/h1H

InChIKey

WHPFEQUEHBULBW-UHFFFAOYSA-N

SMILES

C1(Cl)=NC=C(F)C(Cl)=N1

CAS DataBase Reference

2927-71-1(CAS DataBase Reference)

Safety Information

Hazard Codes 

Xi,C

Risk Statements 

36/37/38-34-22

Safety Statements 

26-36-37/39-45-36/37/39

RIDADR 

3261

WGK Germany 

3

Hazard Note 

Irritant

HazardClass 

8

PackingGroup 

Ⅲ

HS Code 

29335990

MSDS

• Language:English Provider:SigmaAldrich

2,4-Dichloro-5-fluoropyrimidine Usage And Synthesis

Chemical Properties

2,4-Dichloro-5-fluoropyrimidine is Yellow to Orange Crystalline Solid

Uses

2,4-Dichloro-5-fluoropyrimidine is used in the synthesis of two glucuronic derivatives of 5-fluorouracil as neoplasm inhibitors. It is used in the synthesis of two glucuronic derivatives of 5-fluorouracil as neoplasm inhibitors.

Uses

2,4-Dichloro-5-fluoropyrimidine can be used as a starting material to synthesize:

• 5-fluoropyrimidine-2-carboxamides and 5-fluoropyrimidine-4-carboxamides as potential kinase inhibitors.
• A series of 2,4-diamino-5-fluoropyrimidine derivatives as potential protein kinase Cθ inhibitors.
• 2,4-Bisanilinopyrimidine derivatives as potential aurora kinases inhibitors.
• 5-fluoro-N,N-bis(4-methoxyphenyl)-2,4-pyrimidinediamine by reacting with p-methoxy aniline in the presence of DIPEA.
• 2-chloro-5-fluoro-4-(4-fluorophenyl)pyrimidine by Suzuki coupling reaction in the presence of (4-fluorophenyl)boronic acid triphenylphosphine, and palladium(II) acetate catalyst.
• 5-fluoro-2-(piperidin-4-yloxy)pyrimidin-4-amine, a scaffold, which is used in the preparation of potent deoxycytidine kinase inhibitors.

Flammability and Explosibility

Not classified

Synthesis

The general procedure for the synthesis of 2,4-dichloro-5-fluoropyrimidine using 5-fluoropyrimidine-2,4(1H,3H)-dione as a starting material is as follows: 5-fluoropyrimidine-2,4-diol (525 kg, 1.00 mole equivalents) was mixed with phosphorus trichloride (1545 kg, 2.50 mole equivalents) under nitrogen protection and heated to about 100 °C with stirring. Subsequently, N,N-dimethylaniline (980 kg, 2.00 mole equivalents) was slowly added over a period of about 9 hours and the reaction mixture was continued to be stirred at about 100°C for no more than 4 hours. Upon completion of the reaction, the mixture was cooled to about 20°C over about 2 hours and then the reaction was quenched by slowly pouring into a mixture of water (3150 kg) and dichloromethane (1915 kg), ensuring that the temperature was controlled below 40°C. The mixture was stirred at about 20°C for at least 3 hours and then left to stratify. The aqueous phase was washed with dichloromethane (1915 kg) and the layers were separated again. The organic phase was combined and washed at least once with concentrated aqueous hydrochloric acid (525 kg), repeated if necessary, and then with 5% w/w aqueous sodium bicarbonate (2625 kg). The washed organic solution was concentrated by distillation at atmospheric pressure to about 1310 kg to give a dichloromethane solution of 2,4-dichloro-5-fluoropyrimidine with a typical concentration of about 50% w/w and a yield of about 95%. The solution can be used directly in subsequent reactions.

References

[1] Patent: US2015/175639, 2015, A1. Location in patent: Paragraph 0145
[2] Journal of Organic Chemistry, 2011, vol. 76, # 10, p. 4149 - 4153
[3] Patent: KR2016/69892, 2016, A. Location in patent: Paragraph 0090-0093
[4] Chemical and Pharmaceutical Bulletin, 1991, vol. 39, # 9, p. 2288 - 2300
[5] Patent: US2005/234046, 2005, A1. Location in patent: Page/Page column 64

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