3,5-Dichloropyrazine-2-carboxyamide

3,5-Dichloropyrazine-2-carboxyamide Property

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

RIDADR 

UN2811

HS Code 

2933998090

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Warning

Hazard statements

H226Flammable liquid and vapour

H315Causes skin irritation

H319Causes serious eye irritation

Precautionary statements

P210Keep away from heat/sparks/open flames/hot surfaces. — No smoking.

P233Keep container tightly closed.

P240Ground/bond container and receiving equipment.

P241Use explosion-proof electrical/ventilating/lighting/…/equipment.

P242Use only non-sparking tools.

P243Take precautionary measures against static discharge.

P264Wash hands thoroughly after handling.

P264Wash skin thouroughly after handling.

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

P303+P361+P353IF ON SKIN (or hair): Remove/Take off Immediately all contaminated clothing. Rinse SKIN with water/shower.

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

P332+P313IF SKIN irritation occurs: Get medical advice/attention.

P337+P313IF eye irritation persists: Get medical advice/attention.

P370+P378In case of fire: Use … for extinction.

P403+P235Store in a well-ventilated place. Keep cool.

P501Dispose of contents/container to..…

3,5-Dichloropyrazine-2-carboxyamide Chemical Properties,Usage,Production

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