33332-28-4

Basic information

• Product Name: 2-Chloro-6-aminopyrazine
• Synonyms: 2-AMINO-6-CHLOROPYRAZINE;6-CHLOROPYRAZIN-2-YLAMINE;TIMTEC-BB SBB005488;6-CHLOROPYRAZIN-2-AMINE;2-chloro-6-aminopyrazine;2-AMINO-6-CHLOROPYRAZINE 98%;2-PyrazinaMine, 6-chloro-;6-AMino-2-chloropyrazine
• CAS NO: 33332-28-4
• Molecular Formula: C₄H₄ClN₃
• Molecular Weight: 129.55
• EINECS: 206-027-6
• Product Categories: Nitrogen cyclic compounds;Amines;blocks;Pyrazines, Pyrimidines & Pyridazines;Pyrazine;Pyrazines;Pyrazines, Pyrimidines & Pyridazines;amine| alkyl chloride
• Mol File: 33332-28-4.mol
• Article Data: 15

Chemical Properties

• Melting Point: 150-152°C
• Boiling Point: 282.8 °C at 760 mmHg
• Flash Point: 124.8 °C
• Appearance: /Solid
• Density: 1.437 g/cm³
• Vapor Pressure: 0.00329mmHg at 25°C
• Refractive Index: 1.617
• Storage Temp.: under inert gas (nitrogen or Argon) at 2–8 °C
• Solubility: Soluble in dimethyl sulfoxide and methanol.
• PKA: 0.89±0.10(Predicted)
• CAS DataBase Reference: 2-Chloro-6-aminopyrazine(CAS DataBase Reference)
• NIST Chemistry Reference: 2-Chloro-6-aminopyrazine(33332-28-4)
• EPA Substance Registry System: 2-Chloro-6-aminopyrazine(33332-28-4)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 36/37/38-41-22
• Safety Statements: 26-36/37/39-60-37
• TSCA: Yes
• HazardClass: IRRITANT
• Hazardous Substances Data: 33332-28-4(Hazardous Substances Data)

Usage

Chemical Properties

2-Chloro-6-aminopyrazine is Purple Solid

Uses

Different sources of media describe the Uses of 33332-28-4 differently. You can refer to the following data:
1. 2-Chloro-6-aminopyrazine is a disubstituted pyrazine used in the preparation of A2B adenosine receptor antagonists and other biologically active compounds.
2. 2-Amino-6-chloropyrazine is used in the preparation of A2B adenosine receptor antagonists and other biologically active compounds.

InChI:InChI=1/C4H4ClN3/c5-3-1-7-2-4(6)8-3/h1-2H,(H2,6,8)

Synthetic route

2,6-dichloropyrazine (4774-14-5) → 2-amino-6-chloropyrazine (33332-28-4)

Conditions	Yield
With ammonia at 100℃; for 5h; Temperature;	95%
With ammonia In water at 100℃; Inert atmosphere; sealed tube;	91%
With ammonia In water at 100℃; for 18h; Sealed tube;	91%

6-chloro-N-(4-methoxybenzyl)pyrazin-2-amine (355836-31-6) → 2-amino-6-chloropyrazine (33332-28-4)

Conditions	Yield
In trifluoroacetic acid	77%

3-aminopyrazine 1-oxide (6863-77-0) → 3-chloropyrazin-2-amine (6863-73-6) + 2-amino-5-chloropyrazine (33332-29-5) + 2-amino-6-chloropyrazine (33332-28-4)

Conditions	Yield
With trichlorophosphate for 2h; Heating; Yield given. Yields of byproduct given. Title compound not separated from byproducts;
With trichlorophosphate for 2h; Product distribution; Mechanism; Heating; other substituted pyrazine-1-oxides and products, deoxygenation/chlorination competition; other time;

2-amino-6-chloropyrazine (33332-28-4) + phenylboronic acid (98-80-6) → 2-amino-6-phenylpyrazine (41270-69-3)

Conditions	Yield
With palladium diacetate; potassium carbonate; triphenylphosphine In ethanol; toluene at 100℃; Inert atmosphere;	100%
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In 1,4-dioxane; water at 20 - 90℃; for 16.1667h; Reagent/catalyst; Temperature; Solvent; Inert atmosphere;	83%
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In 1,4-dioxane; water at 90℃; for 16h; Inert atmosphere;	83%
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In 1,4-dioxane; water at 90℃; for 16h; Inert atmosphere;	83%
With potassium phosphate; 1,1'-bis(di-tertbutylphosphino)ferrocene; palladium diacetate In 1,4-dioxane at 100℃; for 5h; Suzuki coupling; Inert atmosphere; Sealed tube;	55%

4-fluoroboronic acid (1765-93-1) + 2-amino-6-chloropyrazine (33332-28-4) → 6-(4-fluoro-phenyl)-pyrazin-2ylamine (1159815-52-7)

Conditions	Yield
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; sodium carbonate In 1,4-dioxane; water at 20℃; for 20h; Reflux;	100%
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate In 1,4-dioxane; water at 90℃; for 16h; Inert atmosphere;	68%
With dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2; potassium carbonate In 1,4-dioxane; water at 90℃; for 16h; Inert atmosphere;	68%
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate In 1,4-dioxane; water at 95℃; for 12h; Inert atmosphere;

3-hydroxymethyl-3-methyloxethane (3143-02-0) + 2-amino-6-chloropyrazine (33332-28-4) → 6-((3-methyloxetan-3-yl)methoxy)pyrazin-2-amine (1431654-81-7)

Conditions	Yield
Stage #1: 3-hydroxymethyl-3-methyloxethane With sodium hydride In 1,4-dioxane; mineral oil at 20℃; for 2h; Stage #2: 2-amino-6-chloropyrazine for 16h; Reflux;	100%
Stage #1: 3-hydroxymethyl-3-methyloxethane With sodium hydride In 1,4-dioxane; mineral oil at 20℃; for 2h; Stage #2: 2-amino-6-chloropyrazine In 1,4-dioxane; mineral oil for 16h; Reflux;	100%

di-tert-butyl dicarbonate (24424-99-5) + 2-amino-6-chloropyrazine (33332-28-4) → N-(tert-butoxycarbonyl)-N-(6-chloropyrazin-2-yl) tert-butylcarbamate (815610-07-2)

Conditions	Yield
With dmap In tetrahydrofuran at 20℃; for 2h;	98%
With dmap In dichloromethane at 20℃; for 3h;	98%
With dmap In tetrahydrofuran at 20℃; for 8h;	88.4%

2-amino-6-chloropyrazine (33332-28-4) → 2-amino-5-bromo-3,6-dichloropyrazine (960510-36-5)

Conditions	Yield
Stage #1: 2-amino-6-chloropyrazine With N-Bromosuccinimide In methanol at 50℃; for 19h; Stage #2: With N-chloro-succinimide In methanol at 38 - 50℃; for 16h;	97%
Stage #1: 2-amino-6-chloropyrazine With N-Bromosuccinimide In methanol at 50℃; for 19h; Stage #2: With N-chloro-succinimide In methanol at 38 - 50℃; for 16h;	97%
Stage #1: 2-amino-6-chloropyrazine With N-Bromosuccinimide In methanol at 50℃; for 19h; Stage #2: With N-chloro-succinimide In methanol at 38 - 50℃; for 16h;	97%
Stage #1: 2-amino-6-chloropyrazine With N-Bromosuccinimide In methanol at 50℃; for 19h; Stage #2: With N-chloro-succinimide at 50℃; for 16h;	97%
Stage #1: 2-amino-6-chloropyrazine With N-Bromosuccinimide In methanol for 17h; Stage #2: With N-chloro-succinimide; N-Bromosuccinimide In methanol at 38 - 50℃; for 18h;	97%

2-amino-6-chloropyrazine (33332-28-4) + 3-Methylbenzoyl chloride (1711-06-4) → N-(6-chloropyrazin-2-yl)-3-methylbenzamide (1194688-06-6)

Conditions	Yield
With pyridine at 100℃; for 16h;	97%

2-amino-6-chloropyrazine (33332-28-4) → 6-chloro-5-iodo-pyrazin-2-ylamine (925678-00-8)

Conditions	Yield
With N-iodo-succinimide In dimethyl sulfoxide at 25℃;	88%
With N-iodo-succinimide In dimethyl sulfoxide at 20℃; for 72h;	80%
With N-iodo-succinimide In dimethyl sulfoxide at 20℃; for 72h;	80%

formamide (77287-34-4, 77287-35-5, 60100-09-6) + 2-amino-6-chloropyrazine (33332-28-4) → 7-chloropteridine (1125-84-4)

Conditions	Yield
With phosphorus tribromide at 50 - 60℃; Inert atmosphere;	87%

2-(tetrahydropyran-2-yloxy)ethanol (2162-31-4) + 2-amino-6-chloropyrazine (33332-28-4) → 6-(2-((tetrahydro-2H-pyran-2-yl)oxy)ethoxy)pyrazin-2-amine

Conditions	Yield
Stage #1: 2-(tetrahydropyran-2-yloxy)ethanol With sodium hydride In 1,4-dioxane at 0 - 20℃; for 0.5h; Stage #2: 2-amino-6-chloropyrazine In 1,4-dioxane at 0 - 80℃; for 16h;	87%

3-pyridylboronic acid (1692-25-7) + 2-amino-6-chloropyrazine (33332-28-4) → 6-pyridin-3-ylpyrazin-2-amine (925677-98-1)

Conditions	Yield
With caesium carbonate; dichloro(1,1'-bis(diphenylphosphanyl)ferrocene)palladium(II)*CH2Cl2 In 1,4-dioxane; water at 90℃; for 16h; Suzuki Coupling;	86%

N,N-dimethyl-formamide (68-12-2, 33513-42-7) + 2-amino-6-chloropyrazine (33332-28-4) → N'-(6-chloropyrazin-2-yl)-N,N-dimethylformamidine hydrochloride

Conditions	Yield
Stage #1: N,N-dimethyl-formamide With phenyl chloroformate at 20℃; for 0.0833333h; Stage #2: 2-amino-6-chloropyrazine for 0.0833333h; Mechanism; Reagent/catalyst; Concentration;	86%

N-formyldiethylamine (617-84-5) + 2-amino-6-chloropyrazine (33332-28-4) → N'-(6-chloropyrazin-2-yl)-N,N-diethylformamidine (1448017-68-2)

Conditions	Yield
Stage #1: N-formyldiethylamine With phenyl chloroformate at 20℃; for 0.166667h; Stage #2: 2-amino-6-chloropyrazine at 45℃; for 0.0833333h; Stage #3: With potassium carbonate	85%

2-isopropylphenylboronic acid (89787-12-2) + 2-amino-6-chloropyrazine (33332-28-4) → 6-(2-isopropylphenyl)pyrazin-2-amine

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate In water; N,N-dimethyl-formamide at 120℃; for 3h; Microwave irradiation;	84.6%

(S)-2-(2-methylpyrrolidin-1-yl)-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyrimidine (1421822-66-3) + 2-amino-6-chloropyrazine (33332-28-4) → (S)-6-(2-(2-methylpyrrolidin-1-yl)pyrimidin-5-yl)pyrazin-2-amine (1620136-71-1)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In 1,4-dioxane; water at 25 - 90℃; Inert atmosphere;	84%

1-methyl-2-N,N-dimethylaminoethanol (108-16-7) + 2-amino-6-chloropyrazine (33332-28-4) → 6-[1-(dimethylamino)propan-2-yloxy]pyrazin-2-amine (936004-96-5)

Conditions	Yield
Stage #1: 1-methyl-2-N,N-dimethylaminoethanol With sodium hydride In 1,4-dioxane for 0.5h; Stage #2: 2-amino-6-chloropyrazine In 1,4-dioxane at 100℃; Further stages.;	83%

(2-(3-azabicyclo[3.1.0]hexan-3-yl)pyrimidin-5-yl)boronic acid + 2-amino-6-chloropyrazine (33332-28-4) → 6-(2-(3-azabicyclo[3.1.0]hexan-3-yl)pyrimidin-5-yl)pyrazin-2-amine

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In 1,4-dioxane; water at 90℃; for 2h; Reagent/catalyst; Temperature; Inert atmosphere;	81.51%

2-amino-6-chloropyrazine (33332-28-4) + 1-(piperidin-1-yl)methanimine → 6-chloro-N-(piperidin-1-ylmethylene)pyrazin-2-amine (1448017-69-3)

Conditions	Yield
Stage #1: 1-(piperidin-1-yl)methanimine With phenyl chloroformate at 20℃; for 0.0833333h; Stage #2: 2-amino-6-chloropyrazine at 45℃; for 0.0833333h; Stage #3: With potassium carbonate	81%

2-amino-6-chloropyrazine (33332-28-4) → 6-Methoxy-pyrazin-2-ylamine (6905-47-1)

Conditions	Yield
With sodium methylate In methanol	80%
In 1,4-dioxane; methanol; ethyl acetate	11%

methanol (67-56-1) + palladium diacetate (3375-31-3) + 2-amino-6-chloropyrazine (33332-28-4) → methyl 6-amino-2-pyrazinecarboxylate (118853-60-4)

Conditions	Yield
With 1,1'-bis-(diphenylphosphino)ferrocene; triethylamine at 85℃; under 7600.51 Torr; for 5h; Large scale;	80%

fur-2-ylboronic acid (13331-23-2) + 2-amino-6-chloropyrazine (33332-28-4) → 6-(furan-2-yl)pyrazin-2-amine (925677-91-4)

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In ethanol; water; toluene at 100℃; for 18h; Inert atmosphere;	80%

4-Chlorophenylboronic acid (1679-18-1) + 2-amino-6-chloropyrazine (33332-28-4) → C10H8ClN3

Conditions	Yield
With tetrakis(triphenylphosphine) palladium(0); sodium carbonate In water; toluene at 100℃; for 18h; Inert atmosphere;	80%

Upstream product

• 4774-14-5 2,6-dichloropyrazine 
• 6863-77-0 3-aminopyrazine 1-oxide 
• 355836-31-6 6-chloro-N-(4-methoxybenzyl)pyrazin-2-amine 

Downstream Products

• 132453-63-5 N-(6-chloropyrazin-2-yl)acetamide 
• 190440-40-5 4-Phenyl-3,4,5,6-tetrahydro-2H-[1,2']bipyrazinyl-6'-ylamine 
• 190440-41-6 6-(4-Benzyl-piperidin-1-yl)-pyrazin-2-ylamine 
• 59489-29-1 2-Amino-5,6-dichlor-pyrazin 
• 173253-42-4 2-chloro-3-bromo-6-aminopyrazine 
• 212779-21-0 2-amino-3-bromo-6-chloropyrazine 
• 925677-89-0 6-(3-fluorophenyl)pyrazin-2-amine 
• 925677-96-9 6-(pyridin-2-yl)pyrazin-2-amine 
• 63744-41-2 5-chloro-imidazo[1,2-a]pyrazine 
• 1159815-68-5 6-(4-methoxyphenyl)pyrazinamine 
• 126993-72-4 2-amino-6-benzyloxypyrazine 
• 1620136-70-0 (S)-6-(2-(2-(trifluoromethyl)pyrrolidin-1-yl)pyrimidin-5-yl)pyrazin-2-amine 
• 1416420-86-4 C₁₂H₃Cl₄N₅ 
• 13484-51-0 3,5,6-trichloro-2-aminopyrazine 

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