2-chloro-4-iodopyrimidine Chemical Properties

Melting point:

111.3-112.4 °C

Boiling point:

317.8±15.0 °C(Predicted)

Density 

2.187±0.06 g/cm3(Predicted)

storage temp. 

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

pka

-2.88±0.20(Predicted)

Appearance

White to yellow Solid

InChI

InChI=1S/C4H2ClIN2/c5-4-7-2-1-3(6)8-4/h1-2H

InChIKey

LOPQDJJEZFCJMU-UHFFFAOYSA-N

SMILES

C1(Cl)=NC=CC(I)=N1

2-chloro-4-iodopyrimidine Usage And Synthesis

Description

2-Chloro-4-iodopyrimidine is an inhibitor of protein kinases. It binds to the ATP site of a kinase and inhibits its activity by forming a covalent bond with the serine or threonine residue of the active site. 2-Chloro-4-iodopyrimidine has been shown to inhibit tumor cell proliferation and induce apoptosis in vitro and in vivo. This compound has been shown to inhibit the activity of family kinases, including those involved in tumor growth and angiogenesis.

Preparation

The raw material and cuprous iodide are homogeneously mixed in acetonitrile. Add tert-butyl nitroso ester at -2 °C and stir for 5 min to heat the reaction to 73 °C. After 3h of the reaction, the raw material reaction was completed by TLC detection, cooled to room temperature, and water and saturated sodium carbonate solution were added to the reaction. Finally, the product is purified to obtain the product

Synthesis

General procedure for the synthesis of 2-chloro-4-iodopyrimidine from 2-chloropyrimidine: n-butyllithium (ca. 1.6 M hexane solution, 3.0 mmol) was sequentially added to a stirred solution of 2,2,6,6-tetramethylpiperidine (0.50 mL, 3.0 mmol) in tetrahydrofuran (THF, 6 mL) at 0 °C. After 5 min, ZnCl2-TMEDA ( 0.26 g, 1.0 mmol). The reaction mixture was continued to be stirred at 0 °C for 15 min, followed by the addition of 2-chloropyrimidine (0.11 g, 1.0 mmol). After 2 h of reaction at this temperature, a THF (10 mL) solution of iodine (I2, 0.76 g, 3.0 mmol) was added. The mixture was stirred overnight and upon completion of the reaction, the reaction was quenched by the addition of saturated sodium thiosulfate (Na2S2O3, 10 mL) solution and extracted with ethyl acetate (AcOEt, 3 x 20 mL). The organic layers were combined, dried with anhydrous magnesium sulfate (MgSO4), filtered and concentrated under reduced pressure. Purification by silica gel column chromatography (eluent: heptane/ethyl acetate, 95/5) afforded the target product 2-chloro-4-iodopyrimidine (4a) in 18% yield as a beige powder.

References

[1] Chemistry - A European Journal, 2009, vol. 15, # 6, p. 1468 - 1477
[2] Synlett, 2015, vol. 26, # 20, p. 2811 - 2816