3,5-Dichloropyrazine-2-carboxyamide Chemical Properties

Boiling point:

335.1±37.0 °C(Predicted)

Density 

1.718±0.06 g/cm3(Predicted)

storage temp. 

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

pka

1.21±0.28(Predicted)

form 

powder

color 

Yellow

InChI

InChI=1S/C5H2Cl2N2O2/c6-2-1-8-3(5(10)11)4(7)9-2/h1H,(H,10,11)

InChIKey

QRFOSHOPPFYNAH-UHFFFAOYSA-N

SMILES

C1(C(O)=O)=NC=C(Cl)N=C1Cl

Safety Information

RIDADR 

UN2811

HS Code 

2933998090

3,5-Dichloropyrazine-2-carboxyamide Usage And Synthesis

Uses

3,5-Dichloropyrazine-2-carboxylic acid is an organic intermediate used in the synthesis of perfluorinated cyclopropyl-fused 1,3-oxazine-2-amine compounds as 尾-secretase inhibitors.

Synthesis

The general procedure for the synthesis of 3,5-dichloropyrazine-2-carboxylic acid from carbon dioxide and 2,6-dichloropyrazine was as follows: n-butyllithium (1.6 M hexane solution, 104 mL, 166 mmol) was added slowly and dropwise to a solution of diisopropylamine (23.5 mL, 167.7 mmol) in tetrahydrofuran (THF, 400 mL) at -20 °C, followed by reaction of the mixture was stirred at 0 °C for 30 min. Next, the reaction system was cooled to -78 °C and a solution of 2,6-dichloropyrazine (10 g, 67 mmol) in THF (400 mL) was slowly added dropwise over 1.5 h. The reaction mixture was then stirred at 0 °C for 30 min. After the dropwise addition was completed, the reaction mixture was continued to be stirred at -78 °C for 1 hour. Subsequently, the reaction mixture was poured onto dry ice and allowed to warm slowly to room temperature over 16 hours. Upon completion of the reaction, the reaction mixture was treated with 1.5 N hydrochloric acid (200 mL) and extracted with ethyl acetate (EtOAc). The EtOAc layer was washed with saturated sodium bicarbonate solution and then the aqueous layer was acidified with 1.5N hydrochloric acid and extracted again with EtOAc. The organic phases were combined, washed with brine and concentrated to give a light yellow solid product. The resulting solid was used directly in the subsequent reaction without further purification. Yield: 9 g (yield 69.5%).1H NMR (300 MHz, DMSO-d6): δ 8.9 (s, 1H).

References

[1] Patent: US2011/105497, 2011, A1. Location in patent: Page/Page column 38
[2] Patent: WO2009/89042, 2009, A1. Location in patent: Page/Page column 112
[3] Bioorganic and Medicinal Chemistry Letters, 2014, vol. 24, # 19, p. 4714 - 4723
[4] Patent: WO2009/85983, 2009, A1. Location in patent: Page/Page column 74-75
[5] Patent: WO2014/138484, 2014, A1. Location in patent: Page/Page column 161

3,5-Dichloropyrazine-2-carboxyamide(312736-49-5)Related Product Information

• Isoniazid
• Ethambutol
• (5-CHLOROPYRAZIN-2-YL)METHANOL
• METHYL 3,5-DICHLOROPYRAZINE-2-CARBOXYLATE
• 5-CHLOROPYRAZINE-2-CARBALDEHYDE
• 2,6-Dichloropyrazine
• 3,5-Dichloropyrazine-2-carbaldehyde
• 3-CHLORO-2-PYRAZINE-CARBOXYLIC ACID
• 3-CHLORO-PYRAZINE-2-CARBALDEHYDE
• 3,5-Dichloropyrazine-2-carboxyamide
• 5-CHLORO-PYRAZINE-2-CARBOXYLIC ACID