2-Hydrazinopyrazine Chemical Properties

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 Information

Hazard Codes 

Xn

Risk Statements 

22-41-36/37/38

Safety Statements 

26-39-36/37/39

HS Code 

29339900

2-Hydrazinopyrazine Usage And Synthesis

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

2-Hydrazinopyrazine(54608-52-5)Related Product Information

• Methyl 3-Oxo-4-(2,4,5-trifluorophenyl)butanoate
• Sitagliptin
• Sitagliptin S-IsoMer
• 3-(tert-butoxycarbonyl aMino)-4-(2,4,5-trifluoro phenyl)butanoic acid
• 1-(2,4,5-trifluorophenyl)propan-2-one
• (S)-1-(2,4,5-trifluorophenyl)propan-2-amine hydrochloride
• Methyl 3-aMino-4-(2,4,5-trifluorophenyl)butanoate
• tert-butyl 4-oxo-4-(3-(trifluoroMethyl)-5,6-dihydro-[1,2,4]triazolo [4,3-a]pyrazin-7(8H)-yl)-1-(2,4,5-trifluorophenyl) butan-2-ylcarbaMate
• (S)-methyl 3-amino-4-(2,4,5-trifluoro phenyl) butanoate
• 1-(2,4,5-trifluorophenyl)propan-2-amine hydrochloride
• (S)-Sitagliptin Phosphate
• 3-Amino-4-(2,4,5-trifluorophenyl)butanoic acid
• 5-1-hydroxy-2-(2,4,5-trifluorophenyl)ethylidene-2,2-dimethyl-1,3-dioxane-4,6-dione
• Benzenebutanoicacid,b-aMino-2,4,5-trifluoro-,Methylester,(bR)-
• (R)-Methyl 3-aMino-4-(2,4,5-trifluorophenyl)butanoate hydrochloride
• (R)-Methyl 3-aMino-4-(2,4,5-trifluorophenyl) butanoate .(R)-2-hydroxy-2-phenylacetate
• 1-(2,4,5-trifluorophenyl)propan-2-amine
• (R)-1-(2,4,5-trifluorophenyl)propan-2-amine