2-Hydrazinopyrazine

2-Hydrazinopyrazine Property

Melting point:

109-113℃

Boiling point:

246.3±23.0 °C(Predicted)

Density 

1.39±0.1 g/cm3(Predicted)

storage temp. 

Keep in dark place,Inert atmosphere,Store in freezer, under -20°C

pka

5.10±0.20(Predicted)

form 

Solid

color 

Yellow

Water Solubility 

Slightly soluble in water.

InChI

InChI=1S/C4H6N4/c5-8-4-3-6-1-2-7-4/h1-3H,5H2,(H,7,8)

InChIKey

IVRLZJDPKUSDCF-UHFFFAOYSA-N

SMILES

C1(NN)=NC=CN=C1

Safety

Hazard Codes 

Xn

Risk Statements 

22-41-36/37/38

Safety Statements 

26-39-36/37/39

HS Code 

29339900

Hazard and Precautionary Statements (GHS)

Symbol(GHS)

Signal word

Danger

Hazard statements

H302Harmful if swallowed

H315Causes skin irritation

H318Causes serious eye damage

H319Causes serious eye irritation

H335May cause respiratory irritation

Precautionary statements

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

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

P304+P340IF INHALED: Remove victim to fresh air and Keep at rest in a position comfortable for breathing.

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

P405Store locked up.

2-Hydrazinopyrazine Chemical Properties,Usage,Production

Chemical Properties

Pale yellow solid

Uses

Triazolo[4,3-a]pyrazine 7-oxide, 3-β-D-ribofuranosyl-1,2,4-triazolo[4,3-a]pyrazine, monohydrazones of pyridine, pyrazine, phenylglyoxal were synthesised from 2-Hydrazinopyrazine.

Application

2-Hydrazinopyrazine is used as a reagent in the synthesis of Sitagliptin (S491000, H3PO4) and its analogs. Sitagliptin is a trizolopyrazine dipeptidyl peptidase IV inhibitor that has recently been approved for the therapy of type II diabetes.

Synthesis

Step 1: Synthesis of pyrazine-2-hydrazine from 2-chloropyrazine. 2-Chloropyrazine (2.0 g, 17.5 mmol) was slowly added dropwise to 35% aqueous hydrazine hydrate (25.8 g, 97.8 mmol) at 63-65°C, and the rate of acceleration of the dropwise addition was strictly controlled so as to maintain the temperature of the reaction not exceeding 65°C. After the dropwise addition was completed, the reaction mixture was heated further up to 65°C and kept at this temperature. The reaction mixture was stirred overnight and cooled to room temperature. The solvent was removed by distillation under reduced pressure to give the product pyrazine-2-hydrazine (1.5 g, 75% yield) as a yellow powder. Mass spectrometry (ESI) analysis: calculated value C4H6N4[M]: 110.1; measured value: 111.4 [M+H]+.1H NMR (400 MHz, CD3OD) δ 8.10 (d, J=1.6 Hz, 1H), 8.00 (dd, J=3.2,1.6 Hz, 1H), 7.73 (d, J=3.2 Hz, 1H).

References

[1] Patent: WO2016/100349, 2016, A2. Location in patent: Paragraph 0204
[2] Letters in Organic Chemistry, 2013, vol. 10, # 5, p. 348 - 352
[3] Patent: WO2013/71697, 2013, A1. Location in patent: Paragraph 00198
[4] Patent: US2014/228361, 2014, A1. Location in patent: Paragraph 0279-0280
[5] Patent: CN106749262, 2017, A. Location in patent: Paragraph 0035