134628-42-5

Basic information

• Product Name: PIPERAZINE-2,2,3,3,5,5,6,6-D8
• Synonyms: PIPERAZINE-2,2,3,3,5,5,6,6-D8;Piperazine--d8
• CAS NO: 134628-42-5
• Molecular Formula: C₄H₁₀N₂
• Molecular Weight: 94.18
• Mol File: 134628-42-5.mol
• Article Data: 0

Chemical Properties

• Appearance: /
• CAS DataBase Reference: PIPERAZINE-2,2,3,3,5,5,6,6-D8(CAS DataBase Reference)
• NIST Chemistry Reference: PIPERAZINE-2,2,3,3,5,5,6,6-D8(134628-42-5)
• EPA Substance Registry System: PIPERAZINE-2,2,3,3,5,5,6,6-D8(134628-42-5)

Safety Data

• Hazardous Substances Data: 134628-42-5(Hazardous Substances Data)

Usage

Description

PIPERAZINE-2,2,3,3,5,5,6,6-D8, also known as Piperazine D8, is an isotopically labeled research compound derived from Piperazine. It is characterized by the presence of eight deuterium atoms, which replace hydrogen atoms in the Piperazine molecule. PIPERAZINE-2,2,3,3,5,5,6,6-D8 is commonly used as an internal standard in analytical chemistry, particularly for the quantification of Piperazine by gas chromatography (GC) or liquid chromatography (LC) mass spectrometry.

Uses

Used in Analytical Chemistry:
PIPERAZINE-2,2,3,3,5,5,6,6-D8 is used as an internal standard for the quantification of Piperazine by GCor LC-mass spectrometry. The incorporation of deuterium atoms in the Piperazine molecule allows for accurate and precise measurement of Piperazine levels in various samples, such as pharmaceuticals, environmental samples, and biological fluids. This application is particularly useful in ensuring the reliability and reproducibility of analytical results.
Used in Research and Development:
PIPERAZINE-2,2,3,3,5,5,6,6-D8 is also used as a valuable research compound in the development of new analytical methods, drug discovery, and understanding the metabolic pathways of Piperazine. The isotopically labeled nature of the compound allows researchers to differentiate between the native Piperazine and its labeled counterpart, providing insights into the compound's behavior and interactions within various systems.

Synthetic route

piperazine-2,2,3,3,5,5,6,6-d8 (134628-42-5) + 2-chloro-N-(2,6-di(d3-methyl)phenyl)-2,2-d2-acetamide (1054624-86-0) → N-(2,6-di(d3-methyl)phenyl)-2-(d8-piperazin-1-yl)-2,2-d2-acetamide (1054624-87-1)

Conditions	Yield
Stage #1: piperazine-2,2,3,3,5,5,6,6-d8; 2-chloro-N-(2,6-di(d3-methyl)phenyl)-2,2-d2-acetamide In ethyl [2]alcohol for 3h; Heating / reflux; Stage #2: With ammonia In ethyl [2]alcohol; water	99%

piperazine-2,2,3,3,5,5,6,6-d8 (134628-42-5) + 4-chlorobenzonitrile (100-00-5) → C10H5(2)H8N3O2

Conditions	Yield
In diethylene glycol dimethyl ether at 100℃; for 6h;	80%

tert-butyl 4-fluoro-2-nitrobenzoate (942271-60-5) + piperazine-2,2,3,3,5,5,6,6-d8 (134628-42-5) → C15H13(2)H8N3O4

Conditions	Yield
In water; N,N-dimethyl-formamide at 20℃; for 5h;	74.5%

piperazine-2,2,3,3,5,5,6,6-d8 (134628-42-5) + 1-[3-[(2-amino-6-fluoro-pyrazolo[1,5-a]pyrimidine-3-carbonyl)amino]-5-fluoro-4-pyridyl]piperidine-4-carboxylic acid hydrochloride (1613192-04-3) → 2-amino-6-fluoro-N-(5-fluoro-4-(4-(2,2,3,3,5,5,6,6-octadeutero-piperazine-1-carbonyl)piperidin-1-yl)-3-pyridyl)pyrazolo[1,5-a]pyrimidine-3-carboxamide

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 20℃; for 18h;	48%

ethyl 2-chloropyrimidine-5-carboxylate (89793-12-4) + piperazine-2,2,3,3,5,5,6,6-d8 (134628-42-5) + di-tert-butyl dicarbonate (24424-99-5) → C16H16(2)H8N4O4

Conditions	Yield
Stage #1: ethyl 2-chloropyrimidine-5-carboxylate; piperazine-2,2,3,3,5,5,6,6-d8 With N-ethyl-N,N-diisopropylamine In 1,4-dioxane at 20℃; for 3h; Cooling with ice; Inert atmosphere; Stage #2: di-tert-butyl dicarbonate In 1,4-dioxane for 1h; Inert atmosphere;	47.4%

methanesulfonic acid (75-75-2) + piperazine-2,2,3,3,5,5,6,6-d8 (134628-42-5) + 4-(chloromethyl-d2)-N-(4-(methyl-d3)-3-(4-(pyridin-3-yl)pyrimidin-2-ylamino)phenyl)benzamide → N-(4-(methyl-d3)-3-(4-(pyridin-3-yl)pyrimidin-2-ylamino)phenyl)-4-((piperazin-1-yl-d8)methyl-d2)benzamide bis-methanesulfonic acid salt

Conditions	Yield
Stage #1: piperazine-2,2,3,3,5,5,6,6-d8; 4-(chloromethyl-d2)-N-(4-(methyl-d3)-3-(4-(pyridin-3-yl)pyrimidin-2-ylamino)phenyl)benzamide In dichloromethane; acetonitrile Reflux; Stage #2: With [D]-sodium hydroxide In methanol; chloroform; water-d2 Stage #3: methanesulfonic acid In dichloromethane	43%

methanesulfonic acid (75-75-2) + piperazine-2,2,3,3,5,5,6,6-d8 (134628-42-5) + 4-(chloromethyl-d2)-N-(4-methyl-3-(4-(pyridin-3-yl)pyrimidin-2-ylamino)phenyl)benzamide (1207619-83-7) → N-(4-methyl-3-(4-(pyridin-3-yl)pyrimidin-2-ylamino)phenyl)-4-((piperazin-1-yl-d8)methyl-d2)benzamide bis-methanesulfonic acid salt

Conditions	Yield
Stage #1: piperazine-2,2,3,3,5,5,6,6-d8; 4-(chloromethyl-d2)-N-(4-methyl-3-(4-(pyridin-3-yl)pyrimidin-2-ylamino)phenyl)benzamide In dichloromethane; acetonitrile Reflux; Stage #2: With [D]-sodium hydroxide In methanol; chloroform; water-d2 Stage #3: methanesulfonic acid In acetone	33%

piperazine-2,2,3,3,5,5,6,6-d8 (134628-42-5) + 1-chloro-4-(chloro(phenyl)methyl)benzene (134-83-8) → 1-[(4-chlorophenyl)phenylmethyl]piperazine-2,2,3,3,5,5,6,6-d8

Conditions	Yield
With potassium carbonate In acetonitrile at 85℃; Sealed tube;	32.1%

piperazine-2,2,3,3,5,5,6,6-d8 (134628-42-5) + 1-(3-[D3]methoxy-4-nitrophenyl)piperidin-4-one → C16H13(2)H11N4O3

Conditions	Yield
With titanium(IV) isopropylate at 20℃;	25.4%

piperazine-2,2,3,3,5,5,6,6-d8 (134628-42-5) → d8-furan-2-yl-piperazin-1-yl-methanone (1006717-19-6)

Conditions	Yield
Stage #1: 2-furanoic acid With N-Bromosuccinimide; triphenylphosphine In dichloromethane at 0℃; for 0.25h; Stage #2: piperazine-2,2,3,3,5,5,6,6-d8 With pyridine In dichloromethane at 20℃;

piperazine-2,2,3,3,5,5,6,6-d8 (134628-42-5) + d12-2-(2-methoxyphenoxymethyl)oxirane (1092805-03-2) → d20-1-(2-methoxy-phenoxy)-3-piperazin-1-yl-propan-2-ol (1092805-04-3)

Conditions	Yield
In methanol at 0 - 5℃; for 3h;

5-Chloro-1-phenyltetrazole (14210-25-4) + piperazine-2,2,3,3,5,5,6,6-d8 (134628-42-5) → C11H6(2)H8N6 (1352806-46-2)

Conditions	Yield
With N-ethyl-N,N-diisopropylamine In tetrahydrofuran at 115℃; for 72h;

piperazine-2,2,3,3,5,5,6,6-d8 (134628-42-5) + benzoyl chloride-d5 (43019-90-5) → C11H(2)H13N2O (1352806-44-0)

Conditions	Yield
Stage #1: piperazine-2,2,3,3,5,5,6,6-d8 With n-butyllithium In tetrahydrofuran; hexane at 20℃; for 0.5h; Stage #2: benzoyl chloride-d5 In tetrahydrofuran; hexane for 0.0833333h;

piperazine-2,2,3,3,5,5,6,6-d8 (134628-42-5) + 3,4-Difluorobenzonitrile (64248-62-0) → 3-fluoro-4-(piperazin-1-yl-2,2,3,3,5,5,6,6-d8)benzonitrile

Conditions	Yield
at 110℃; for 16h;

piperazine-2,2,3,3,5,5,6,6-d8 (134628-42-5) + 2-((1H-pyrrolo[2,3-b]pyridin-5-yl)oxy)-4-fluorobenzoic acid methyl ester (1235865-75-4) → methyl 4-[(2,2,3,3,5,5,6,6-2H8)piperazin-1-yl]-2-(1H-pyrrolo[2,3-b]pyridin-5-yloxy)benzoate

Conditions	Yield
In dimethyl sulfoxide at 85℃; for 2.5h;

piperazine-2,2,3,3,5,5,6,6-d8 (134628-42-5) + di-tert-butyl dicarbonate (24424-99-5) → tert-butyl (2,2,3,3,5,5,6,6-(2H8))piperazine-1-carboxylate (1126621-86-0)

Conditions	Yield
Stage #1: piperazine-2,2,3,3,5,5,6,6-d8 With trifluoroacetic acid In methanol; water at 20 - 28℃; for 0.75h; Stage #2: di-tert-butyl dicarbonate With iodine In methanol; water at 20℃;	3.43 g

Downstream Products

• 1054624-87-1 N-(2,6-di(d3-methyl)phenyl)-2-(d8-piperazin-1-yl)-2,2-d2-acetamide 
• 1092805-04-3 d20-1-(2-methoxy-phenoxy)-3-piperazin-1-yl-propan-2-ol 
• 1352806-44-0 C₁₁H⁽²⁾H₁₃N₂O 
• 1189925-23-2 1-[(4-chlorophenyl)phenylmethyl]piperazine-2,2,3,3,5,5,6,6-d₈ 
• 1126621-86-0 tert-butyl (2,2,3,3,5,5,6,6-(²H₈))piperazine-1-carboxylate