NSC45721

NSC45721 Property

Melting point:

157 °C

Density 

1.76±0.1 g/cm3(Predicted)

storage temp. 

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

pka

4.97±0.10(Predicted)

Appearance

White to off-white Solid

Safety

HS Code 

2933599590

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

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

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

NSC45721 Chemical Properties,Usage,Production

Uses

4,6-Dichloro-2-hydroxypyrimidine is a useful building block used in the preparation of diaminopyrimidinone IRAK4 inhibitors. An isomer of 5-Chlorouracil (C423775).

Synthesis

The general procedure for the synthesis of 4,6-dichloro-1H-pyrimidin-2-one from 2,4,6-trichloropyrimidine was carried out as follows: an aqueous 3.8 M sodium hydroxide solution (10 mL, 38.7 mmol) was slowly added to a vigorously stirred solution of 2,4,6-trichloropyrimidine (4.74 g, 25.8 mmol) in tetrahydrofuran (THF, 80 mL). The reaction progression was monitored by liquid chromatography-mass spectrometry (LC-MS) and the product peak (m/z 165, retention time 4.08 min) and residual 2,4,6-trichloropyrimidine (retention time 5.28 min) were observed. After 48 hours of reaction, the reaction mixture was concentrated under reduced pressure and filtered, retaining the filtrate. The resulting precipitate was dissolved in hot water (120 mL) and the pH of the solution was subsequently adjusted to 2 with 3.6 M hydrochloric acid and cooled at 0 °C. The precipitate was collected by filtration, washed with water and dried under reduced pressure to give the first batch of 4,6-dichloro-1H-pyrimidin-2-one (1.17 g, 27% yield) as a white solid. The retained filtrate was concentrated to near dryness and the above purification steps were repeated to afford the second batch of 4,6-dichloro-1H-pyrimidin-2-one (2.03 g, 48% yield) as a white solid. The total yield of the two batches of product was 3.2 g with an overall yield of 75%.

References

[1] Patent: WO2014/188193, 2014, A1. Location in patent: Page/Page column 84-85
[2] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 21, p. 6671 - 6676,6