2-Chloro-3-cyano-4,6-dimethylpyridine

2-Chloro-3-cyano-4,6-dimethylpyridine Property

Melting point:

98-99°C

Boiling point:

305.3±37.0 °C(Predicted)

Density 

1.22±0.1 g/cm3(Predicted)

storage temp. 

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

form 

powder to crystal

pka

-0.41±0.10(Predicted)

color 

White to Almost white

BRN 

131348

InChI

InChI=1S/C8H7ClN2/c1-5-3-6(2)11-8(9)7(5)4-10/h3H,1-2H3

InChIKey

RETJKTAVEQPNMH-UHFFFAOYSA-N

SMILES

C1(Cl)=NC(C)=CC(C)=C1C#N

CAS DataBase Reference

14237-71-9(CAS DataBase Reference)

Safety

Hazard Codes 

Xi,T

Risk Statements 

36/37/38-41-37/38-25

Safety Statements 

26-36/37/39-45

RIDADR 

3276

WGK Germany 

3

Hazard Note 

Irritant

HazardClass 

6.1

PackingGroup 

III

HS Code 

29333990

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H301Toxic if swalloed

H315Causes skin irritation

H318Causes serious eye damage

H335May cause respiratory irritation

Precautionary statements

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

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

P301+P310IF SWALLOWED: Immediately call a POISON CENTER or doctor/physician.

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

2-Chloro-3-cyano-4,6-dimethylpyridine Chemical Properties,Usage,Production

Uses

2-Chloro-3-cyano-4,6-dimethylpyridine is mainly used as an organic synthesis intermediate and can be used to prepare polysubstituted pyridine bioactive molecules. For example, there are patent reports that this substance can be used to synthesize protein kinase (CDK) inhibitors.

Chemical Properties

White to brown solid

Synthesis

Example 6 Synthesis of 3-(5-phenyl-2,4-dimethyl-6-oxo-1,6-dihydropyrimidin-3-yl)benzonitrile Step 1: Preparation of 2-chloro-3-cyano-4,6-dimethylpyridine: In a reaction flask, 3-cyano-4,6-dimethyl-2-hydroxypyridine (4.35 g, 29.39 mmol) was mixed with phosphorus pentachloride (6.92 g, 33.21 mmol) were mixed and heated to 120 °C with continuous stirring. The reaction mixture gradually changed to a clarified solution and stirring was continued for 1 hour to ensure complete reaction. Subsequently, the reaction mixture was slowly poured into a pre-prepared ice/water mixture (250 mL) and allowed to stand for 30 minutes to complete hydrolysis. The aqueous phase was adjusted to pH 6 with sodium bicarbonate and then extracted with dichloromethane (400 mL). The organic layers were combined, dried with anhydrous sodium sulfate, filtered and concentrated under reduced pressure to afford the crude product 2-chloro-3-cyano-4,6-dimethylpyridine (4.60 g, 94% yield) as a brown solid, which was analyzed to contain about 15% impurities. The product was characterized by LC/MS and NMR: LC/MS showed m/e = 167/169 (M + H) with a retention time of 2.98 min; 1H NMR (CDCl3, 400 MHz) δ 7.08 (s, 1H), 2.57 (s, 3H), 2.55 (s, 3H).

References

[1] Journal of Medicinal Chemistry, 1992, vol. 35, # 10, p. 1887 - 1897
[2] Patent: WO2005/97750, 2005, A1. Location in patent: Page/Page column 75
[3] Chemistry of Heterocyclic Compounds, 2009, vol. 45, # 1, p. 35 - 41
[4] Journal of Heterocyclic Chemistry, 2013, vol. 50, # SUPPL.1, p. E12-E17
[5] Journal of the American Chemical Society, 1949, vol. 71, p. 331