5-BroMo-6-chloropicolinonitrile

5-BroMo-6-chloropicolinonitrile Property

Boiling point:

284.8±35.0 °C(Predicted)

Density 

1.85±0.1 g/cm3(Predicted)

storage temp. 

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

pka

-6.54±0.10(Predicted)

Appearance

Off-white to light brown Solid

InChI

InChI=1S/C6H2BrClN2/c7-5-2-1-4(3-9)10-6(5)8/h1-2H

InChIKey

GKCQPDVYUJLEIJ-UHFFFAOYSA-N

SMILES

C1(C#N)=NC(Cl)=C(Br)C=C1

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H302Harmful if swallowed

Precautionary statements

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

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

5-BroMo-6-chloropicolinonitrile Chemical Properties,Usage,Production

Application

5-Bromo-6-chloropicolinonitrile can be used as a pharmaceutical synthesis intermediate, and can be used in laboratory research and development as well as in chemical and pharmaceutical synthesis processes.

Synthesis

Step 2. Synthesis of 5-bromo-6-chloropyridine-2-carbonitrile (C28): Trimethylmethylsilyl cyanide (19 mL, 0.15 mol) was slowly added with stirring to a solution of acetonitrile (400 mL) containing 3-bromo-2-chloropyridine 1-oxide (C27) (31.6 g, 0.152 mol) and triethylamine (63.4 mL, 0.46 mol). . The reaction mixture was heated to 50°C and maintained for 2 hours. Subsequently cooled to room temperature, trimethylmethylsilyl cyanide (19 mL) was added again and the reaction mixture was continued to be heated at 50°C for 1.5 hours. Finally, a third portion of trimethylsilyl cyanide (28.5 mL, 0.23 mol) was added and the reaction mixture was heated to reflux for 3 days. After completion of the reaction, the reaction mixture was diluted with dichloromethane (2 L), washed sequentially with saturated aqueous sodium bicarbonate (800 mL) and water (1 L), and the organic phase was dried with magnesium sulfate and concentrated under reduced pressure. Purification by silica gel column chromatography (elution gradient: 20% to 25% ethyl acetate/heptane) afforded 5-bromo-6-chloro-2-pyridinecarbonitrile as a yellow solid in 14.92 g (68.6 mmol, 45%) yield. The reaction was carried out using the acylating agent dimethylcarbamoyl chloride: a solution of dimethylcarbamoyl chloride (12.9 mL, 0.14 mol) in dichloromethane (23 mL) was slowly added dropwise to a stirred solution of 3-bromo-2-chloropyridine 1-oxide (C27) (11.23 g, 53.9 mmol) and trimethylsilyl cyanide (17.5 mL, 0.14 mol) in in a solution of dichloromethane (200 mL). The reaction mixture was heated and refluxed for 3 days, and after completion of the reaction, it was diluted with dichloromethane (450 mL), washed sequentially with saturated aqueous sodium bicarbonate (2×200 mL) and water (200 mL), and the organic phase was dried with magnesium sulfate and concentrated under reduced pressure. Purification by silica gel column chromatography (elution gradient: 15% to 20% ethyl acetate/heptane) afforded 5-bromo-6-chloropyridine-2-carbonitrile as an off-white solid containing dimethylcarbamoyl cyanide (12.73 g, 100%) as impurity.

References

[1] Bioorganic and Medicinal Chemistry Letters, 2012, vol. 22, # 8, p. 2906 - 2911
[2] Patent: US2012/252758, 2012, A1. Location in patent: Page/Page column 28