3,5-Dibromo-2-chloropyrazine Chemical Properties

Boiling point:

261℃

Density 

2.265

Flash point:

112℃

storage temp. 

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

pka

-6.65±0.10(Predicted)

Appearance

White to off-white Solid

Safety Information

HS Code 

2933998090

3,5-Dibromo-2-chloropyrazine Usage And Synthesis

Uses

An intermediate used for the 1) preparation of a number of salts of fused pyrazine derivative for treatment of degenerative and inflammatory diseases, 2) preparation of a number of pyridine and pyrazine derivatives as protein kinase modulators for the treatment of CDK9-mediated diseases.

Uses

3,5-Dibromo-2-chloropyrazine is an intermediate used for the 1) preparation of a number of salts of fused pyrazine derivative for treatment of degenerative and inflammatory diseases, 2) preparation of a number of pyridine and pyrazi ne derivatives as protein kinase modulators for the treatment of CDK9-mediated diseases.

Synthesis

General procedure for the synthesis of 3,5-dibromo-2-chloropyrazine from 2-amino-3,5-dibromopyrazine: titanium(IV) chloride (174 g, 926 mmol) was added to a solution of 2-amino-3,5-dibromopyrazine (234 g, 932 mmol) in dichloromethane (DCM, 700 mL), followed by slow addition of tert-butyl nitrite (572 g, 5.55 mol). The reaction mixture was stirred at room temperature for 2 h and then the reaction was quenched with water (500 mL). The reaction mixture was extracted with dichloromethane (3 × 500 mL). The organic layers were combined and concentrated under reduced pressure. Purification of the residue by rapid column chromatography on silica gel (eluent: ethyl acetate/petroleum ether, 1:50 v/v) afforded 3,5-dibromo-2-chloropyrazine (90d) as a colorless oil (210 g, 83% yield). Mass spectrum (LCMS, ESI positive ion mode): calculated value C4HBr2ClN2 [M+H]+: 272.8, measured value: 272.6.

References

[1] Patent: US2014/364414, 2014, A1. Location in patent: Paragraph 0945; 0952-0953
[2] Patent: US2009/286798, 2009, A1. Location in patent: Page/Page column 26-27
[3] Patent: US2011/118269, 2011, A1. Location in patent: Page/Page column 14
[4] Patent: WO2014/1377, 2014, A1. Location in patent: Page/Page column 153; 154