4774-14-5

Basic information

• Product Name: 2,6-Dichloropyrazine
• Synonyms: 2,6-dichloro-pyrazin;Pyrazine, 2,6-dichloro-;2,6-Dichloropyrazine,99%;2,6-Dichlor-pyrazin;2,6-Dichloropiperazine;6-Dichloropyrazine;M-Dichloropyrazine;2,6-Dichloro-1,4-diazine
• CAS NO: 4774-14-5
• Molecular Formula: C₄H₂Cl₂N₂
• Molecular Weight: 148.98
• EINECS: 225-316-8
• Product Categories: Halides;Pyrazines, Pyrimidines & Pyridazines;API intermediates;Heterocyclic Compounds;Pyrazines;Chloropyrazines, etc.;Heterocycles;Pyrazines, Pyrimidines & Pyridazines;Building Blocks;Halogenated Heterocycles;Heterocyclic Building Blocks;PyrazinesHeterocyclic Building Blocks;Building Blocks;Chemical Synthesis;Halogenated Heterocycles;Heterocyclic Building Blocks;alkyl chloride;Pesticides intermediate
• Mol File: 4774-14-5.mol
• Article Data: 4

Chemical Properties

• Melting Point: 55-58 °C(lit.)
• Boiling Point: 122 °C / 40mmHg
• Flash Point: >230 °F
• Appearance: White to beige/Crystals or Crystalline Powder
• Density: 1.6445 (rough estimate)
• Vapor Pressure: 0.867mmHg at 25°C
• Refractive Index: 1.6300 (estimate)
• Storage Temp.: Keep in dark place,Sealed in dry,Room Temperature
• Solubility: Soluble in ethanol and methanol.
• PKA: -3.11±0.10(Predicted)
• BRN: 2439
• CAS DataBase Reference: 2,6-Dichloropyrazine(CAS DataBase Reference)
• NIST Chemistry Reference: 2,6-Dichloropyrazine(4774-14-5)
• EPA Substance Registry System: 2,6-Dichloropyrazine(4774-14-5)

Safety Data

• Hazard Codes: Xi,Xn
• Statements: 36/37/38-20/21/22
• Safety Statements: 26-37/39-36/37/39-22-36
• WGK Germany: 3
• TSCA: T
• HazardClass: IRRITANT
• Hazardous Substances Data: 4774-14-5(Hazardous Substances Data)

Usage

Chemical Properties

White Powder

Uses

2,6-Dichloropyrazine is used in the preparation of pyrazine and pyridine compounds as ATR kinase inhibitors. It is also used in the synthesis of oxacalixarenes containing nitrogen heterocycles.

InChI:InChI=1/C4H2Cl2N2/c5-3-1-7-2-4(6)8-3/h1-2H

Synthetic route

2-chloropyrazin (14508-49-7) → 2,6-dichloropyrazine (4774-14-5)

Conditions	Yield
With pyridine; chlorine at 110℃; for 2h; Reagent/catalyst;	87.3%
With sulfuryl dichloride at 120℃;

Pyrazin-N.N'-dioxyd (2423-84-9) → 2,6-dichloropyrazine (4774-14-5)

Conditions	Yield
With trichlorophosphate for 6h; Heating;	84%

3-chloropyrazine 1-oxide (6863-76-9) → 2,5-dichloropyrazine (19745-07-4) + 2,3-dichloropyrazine (4858-85-9) + 2,6-dichloropyrazine (4774-14-5)

Conditions	Yield
With trichlorophosphate for 2h; Heating; Yield given. Yields of byproduct given;
With 1,8-diazabicyclo[5.4.0]undec-7-ene; trichlorophosphate for 2h; Heating; Yield given. Yields of byproduct given;

Pyrazin-N.N'-dioxyd (2423-84-9) → 2,3-dichloropyrazine (4858-85-9) + 2,6-dichloropyrazine (4774-14-5)

Conditions	Yield
With trichlorophosphate for 2h; Heating; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

3-chloropyrazine 1-oxide (6863-76-9) → 2-chloropyrazin (14508-49-7) + 2,5-dichloropyrazine (19745-07-4) + 2,3-dichloropyrazine (4858-85-9) + 2,6-dichloropyrazine (4774-14-5)

Conditions	Yield
With trichlorophosphate for 2h; Heating; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

2-chloropyrazine 1-oxide (16025-16-4) → 2-chloropyrazin (14508-49-7) + 2,3-dichloropyrazine (4858-85-9) + 2,6-dichloropyrazine (4774-14-5)

Conditions	Yield
With trichlorophosphate for 2h; Heating; Yield given. Yields of byproduct given. Title compound not separated from byproducts;

2-chloropyrazin (14508-49-7) + chlorine (7782-50-5) → 2,6-dichloropyrazine (4774-14-5)

Conditions	Yield
at 120℃;

1,4-pyrazine (290-37-9) + water (7732-18-5) + chlorine (7782-50-5) → 2-chloropyrazin (14508-49-7) + 2,5-dichloropyrazine (19745-07-4) + 2,3-dichloropyrazine (4858-85-9) + 2,6-dichloropyrazine (4774-14-5)

Conditions	Yield
at 350℃; Product distribution;

2-chloropyrazin (14508-49-7) → 2,6-dichloropyrazine (4774-14-5) + 2,3-dichloro-pyrazine, 2,5-dichloro-pyrazine

Conditions	Yield
With chlorine at 475℃;

1,4-pyrazine (290-37-9) → 2,6-dichloropyrazine (4774-14-5) + 2,3-dichloro-pyrazine, chloropyrazine 2,5-dichloro-pyrazine

Conditions	Yield
With water; chlorine at 350℃;

1,4-pyrazine (290-37-9) → 2,6-dichloropyrazine (4774-14-5) + 2,3-dichloro-pyrazine, chloropyrazine, 2,5-dichloro-pyrazine

Conditions	Yield
With water; chlorine at 400 - 500℃;
With water; chlorine at 400 - 500℃;

2,6-dichloropyrazine (4774-14-5) + 4-methoxyphenylboronic acid (5720-07-0) → 2,6-bis-(4-methoxy-phenyl)-pyrazine (135459-44-8)

Conditions	Yield
With sodium hydrogencarbonate; tetrakis(triphenylphosphine) palladium(0) In ethanol; toluene for 14h; Suzuki coupling; Heating;	100%
With tetrakis(triphenylphosphine) palladium(0); potassium carbonate In ethanol; toluene at 70℃; for 0.5h; Suzuki-Miyaura Coupling; Microwave irradiation;	97%

6-hydroxycoumarin (6093-68-1) + 2,6-dichloropyrazine (4774-14-5) → 2-chloro-6-(7-coumarinyloxy)-pyrazine (894416-91-2)

Conditions	Yield
With potassium tert-butylate In N,N-dimethyl-formamide at 90℃; for 5h;	100%

7-hydroxy-2H-chromen-2-one (93-35-6) + 2,6-dichloropyrazine (4774-14-5) → 2-chloro-6-(7-coumarinyloxy)-pyrazine (894416-91-2)

Conditions	Yield
With potassium tert-butylate In N,N-dimethyl-formamide at 90℃; for 5h; Inert atmosphere;	100%

5-hydroxy-2,3-dihydro-1H-indene-1-one (3470-49-3) + 2,6-dichloropyrazine (4774-14-5) → 2-chloro-6-(indanone-5-oxy)-pyrazine (894417-08-4)

Conditions	Yield
With potassium tert-butylate In N,N-dimethyl-formamide at 90℃; for 5h; Inert atmosphere;	100%

6-Hydroxy-1-tetralone (3470-50-6) + 2,6-dichloropyrazine (4774-14-5) → 2-chloro-6-(tetralon-1-yl-6-oxy)-pyrazine (894416-93-4)

Conditions	Yield
With potassium tert-butylate In N,N-dimethyl-formamide at 90℃; for 5h; Inert atmosphere;	100%

5-Hydroxy-1-tetralone (28315-93-7) + 2,6-dichloropyrazine (4774-14-5) → 2-chloro-6-(tetralon-1-yl-5-oxy)-pyrazine (894416-92-3)

Conditions	Yield
With potassium tert-butylate In N,N-dimethyl-formamide at 90℃; for 5h; Inert atmosphere;	100%

2,6-dichloropyrazine (4774-14-5) + N-(5-hydroxynaphthalen-2-yl)acetamide (86700-06-3) → 2-chloro-6-(6-acetamido-naphthyl-1-oxy)-pyrazine (894416-96-7)

Conditions	Yield
With potassium tert-butylate In N,N-dimethyl-formamide at 90℃; for 5h; Inert atmosphere;	100%

2,6-dichloropyrazine (4774-14-5) + tert-butyl (3R)-3-hydroxypiperidine-1-carboxylate (143900-43-0) → tert-butyl (3R)-3-[(6-chloropyrazin-2-yl)oxy]piperidine-1-carboxylate (1147998-31-9)

Conditions	Yield
Stage #1: tert-butyl (3R)-3-hydroxypiperidine-1-carboxylate With sodium hydride In tetrahydrofuran at 0 - 5℃; for 2h; Industry scale; Stage #2: 2,6-dichloropyrazine In tetrahydrofuran at 0 - 30℃; for 3.5h;	100%

2-(N,N-dimethylamino)ethanol (108-01-0) + 2,6-dichloropyrazine (4774-14-5) → 2-(6-chloropyrazin-2-yl)oxy-N,N-dimethylethanamine (1250740-85-2)

Conditions	Yield
With sodium hydride In tetrahydrofuran at 20℃;	100%
Stage #1: 2-(N,N-dimethylamino)ethanol With sodium hydride In tetrahydrofuran at 20℃; for 0.166667h; Stage #2: 2,6-dichloropyrazine In tetrahydrofuran at 50℃; for 0.166667h; Microwave irradiation;	99%
Stage #1: 2-(N,N-dimethylamino)ethanol With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 0.333333h; Inert atmosphere; Stage #2: 2,6-dichloropyrazine In N,N-dimethyl-formamide at 20℃; Inert atmosphere;	87%
Stage #1: 2-(N,N-dimethylamino)ethanol With sodium hydride In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere; Microwave irradiation; Stage #2: 2,6-dichloropyrazine In tetrahydrofuran for 0.166667h; Microwave irradiation;

3-Dimethylamino-1-propanol (3179-63-3) + 2,6-dichloropyrazine (4774-14-5) → 3-(6-chloropyrazin-2-yloxy)-N,N-diethylpropan-1-amine (1609955-47-6)

Conditions	Yield
With sodium hydride In tetrahydrofuran at 20℃;	100%

3-Dimethylamino-1-propanol (3179-63-3) + 2,6-dichloropyrazine (4774-14-5) → 3-(6-chloropyrazin-2-yl)oxy-N,N-dimethylpropan-1-amine (1247107-87-4)

Conditions	Yield
With sodium hydride In tetrahydrofuran at 20℃;	100%
Stage #1: 3-Dimethylamino-1-propanol With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 0.333333h; Inert atmosphere; Stage #2: 2,6-dichloropyrazine In N,N-dimethyl-formamide at 20℃; Inert atmosphere;	79%
Stage #1: 3-Dimethylamino-1-propanol With sodium hydride In tetrahydrofuran at 20℃; for 0.166667h; Stage #2: 2,6-dichloropyrazine In tetrahydrofuran at 50℃; for 0.166667h; Microwave irradiation;	77%
Stage #1: 3-Dimethylamino-1-propanol With sodium hydride In tetrahydrofuran at 20℃; for 0.5h; Inert atmosphere; Microwave irradiation; Stage #2: 2,6-dichloropyrazine In tetrahydrofuran for 0.166667h; Microwave irradiation;

Cyclopentanol (96-41-3) + 2,6-dichloropyrazine (4774-14-5) → 2-chloro-6-(cyclopentyloxy)pyrazine

Conditions	Yield
Stage #1: Cyclopentanol With sodium hydride In tetrahydrofuran at 20℃; for 0.166667h; Stage #2: 2,6-dichloropyrazine In tetrahydrofuran at 50℃; for 0.166667h; Microwave irradiation;	100%
Stage #1: Cyclopentanol With sodium hydride In tetrahydrofuran; mineral oil at 20℃; for 0.5h; Stage #2: 2,6-dichloropyrazine In tetrahydrofuran; mineral oil at 20℃; for 16h;	80%

2,6-dichloropyrazine (4774-14-5) + cyclohexanol (108-93-0) → 2-chloro-6-(cyclohexyloxy)pyrazine (1016681-36-9)

Conditions	Yield
Stage #1: cyclohexanol With sodium hydride In tetrahydrofuran at 20℃; for 0.166667h; Stage #2: 2,6-dichloropyrazine In tetrahydrofuran at 50℃; for 0.166667h; Microwave irradiation;	100%

N-methyl-4-hydroxypiperidine (106-52-5) + 2,6-dichloropyrazine (4774-14-5) → 2-chloro-6-((1-methylpiperidin-4-yl)oxy)pyrazine

Conditions	Yield
Stage #1: N-methyl-4-hydroxypiperidine With sodium hydride In tetrahydrofuran at 20℃; for 0.166667h; Stage #2: 2,6-dichloropyrazine In tetrahydrofuran at 50℃; for 0.166667h; Microwave irradiation;	100%

2,6-dichloropyrazine (4774-14-5) + sodium methylate (124-41-4) → 2,6-dimethoxypirazine (4774-15-6)

Conditions	Yield
In methanol for 18h; Reflux;	99%
In methanol Heating / reflux;	98%
In methanol at 80℃; for 18h; Reflux;	97%

2,6-dichloropyrazine (4774-14-5) + 4-Hydroxyacetophenone (99-93-4) → 2-chloro-6-(acetophenone-4-oxy)-pyrazine (894417-06-2)

Conditions	Yield
With potassium tert-butylate In N,N-dimethyl-formamide at 90℃; for 5h; Inert atmosphere;	99%

2,6-dichloropyrazine (4774-14-5) + meta-hydroxyacetanilide (621-42-1) → 2-chloro-6-(3-acetamidophenyl-oxy)-pyrazine (894417-03-9)

Conditions	Yield
With potassium tert-butylate In N,N-dimethyl-formamide at 90℃; for 5h; Inert atmosphere;	99%

2,6-dichloropyrazine (4774-14-5) + 2-(Diethylamino)ethanol (100-37-8) → 2-(6-chloropyrazin-2-yloxy)-N,N-diethylethanamine (1247497-41-1)

Conditions	Yield
With sodium hydride In tetrahydrofuran at 20℃;	99%
Stage #1: 2-(Diethylamino)ethanol With sodium hydride In tetrahydrofuran at 20℃; for 0.166667h; Stage #2: 2,6-dichloropyrazine In tetrahydrofuran at 50℃; for 0.166667h; Microwave irradiation;	95%

propylamine (107-10-8) + 2,6-dichloropyrazine (4774-14-5) → 6-Chloro-N-propylpyrazin-2-amine

Conditions	Yield
With triethylamine In ethanol for 1.5h; Reflux;	99%

tert-butyl [(2S)-1-aminopropan-2-yl]carbamate hydrochloride (959833-70-6) + 2,6-dichloropyrazine (4774-14-5) → tert-butyl (S)-(1-((6-chloropyrazin-2-yl)amino)propan-2-yl)carbamate

Conditions	Yield
With N-ethyl-N,N-diisopropylamine at 115℃; for 8h;	99%

4-methyl-3-(methyloxy)phenol (19217-50-6) + 2,6-dichloropyrazine (4774-14-5) → 2-chloro-6-(3-methoxy-4-methylphenoxy)pyrazine

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 80℃; for 3h;	99%

2-hydroxybromobenzene (95-56-7) + 2,6-dichloropyrazine (4774-14-5) → 2,6-bis(2-bromophenoxy)pyrazine

Conditions	Yield
With potassium carbonate In dimethyl sulfoxide at 160℃; for 16h; Inert atmosphere; Schlenk technique;	99%

furan-2-ylmethanamine (617-89-0) + 2,6-dichloropyrazine (4774-14-5) → 6-chloro-N-(2-furylmethyl)pyrazin-2-amine (629658-05-5)

Conditions	Yield
	98%

1-benzenesulfonyl-6-methoxy-2-tributylstannyl-1H-indole (722538-29-6) + 2,6-dichloropyrazine (4774-14-5) → 1-benzensulfonyl-2-(6-chloro-pyrazin-2-yl)-6-methoxy-1H-indole (1346163-38-9)

Conditions	Yield
With copper(l) iodide; tetrakis(triphenylphosphine) palladium(0) In tetrahydrofuran at 100℃; for 0.333333h; Stille cross-coupling; Inert atmosphere; Microwave irradiation;	98%

2,6-dichloropyrazine (4774-14-5) + 2-Methylphenylboronic acid (16419-60-6) → C18H16N2

Conditions	Yield
With C84H64Cl3N3Pd; potassium carbonate In ethanol at 80℃; for 2h; Suzuki-Miyaura Coupling;	98%

Thien-3-ylboronic acid (6165-69-1) + 2,6-dichloropyrazine (4774-14-5) → C12H8N2S2

Conditions	Yield
With C84H64Cl3N3Pd; potassium carbonate In ethanol at 80℃; for 2h; Suzuki-Miyaura Coupling;	98%

3-HYDROXYPYRIDINE (109-00-2) + 2,6-dichloropyrazine (4774-14-5) → 2,6-bis(3-pyridyloxy)pyrazine (477960-95-5)

Conditions	Yield
With CsCO3 In N,N-dimethyl-formamide at 110℃; for 20h;	97%

2,6-dichloropyrazine (4774-14-5) + phenylmethanethiol (100-53-8) → 2-(benzylthio)-6-chloropyrazine (33870-91-6)

Conditions	Yield
With potassium carbonate In N,N-dimethyl-formamide at 20℃; for 16h;	97%
With potassium carbonate In N,N-dimethyl-formamide at 30℃; for 13h;
With sodium hydroxide In ethanol at 20℃; for 6h;

2,6-dichloropyrazine (4774-14-5) + methylhydrazine (60-34-4) → 2,6-dimethylhydrazinopyrazine (1567389-01-8)

Conditions	Yield
for 1h; Reflux; Inert atmosphere;	97%
Reflux;

3-Hydroxyacetophenone (121-71-1) + 2,6-dichloropyrazine (4774-14-5) → 2-chloro-6-(acetophenone-3-oxy)-pyrazine (894417-05-1)

Conditions	Yield
With potassium tert-butylate In N,N-dimethyl-formamide at 90℃; for 5h; Inert atmosphere;	96%

Upstream product

• 14508-49-7 2-chloropyrazin 
• 2423-84-9 Pyrazin-N_.N'-dioxyd 
• 290-37-9 1,4-pyrazine 
• 7732-18-5 water 
• 7782-50-5 chlorine 
• 16025-16-4 2-chloropyrazine 1-oxide 
• 6863-76-9 3-chloropyrazine 1-oxide 

Downstream Products

• 4774-15-6 2,6-dimethoxypyrazine 
• 956006-14-7 C₂₀H₂₅ClN₄O₂ 
• 89284-38-8 3,5-dichloro-2-methyl-pyrazine 
• 641615-61-4 2-[(2-chloro)pyrazin-6-ylamino]-1-methyl-4-nitrobenzene 
• 63286-29-3 2-chloro-6-hydrazinopyridazine 
• 23229-25-6 2,6-dibromopyrazine 
• 642459-07-2 (6-chloro-pyrazin-2-yl )-(4-fluoro-phenyl)-amine 
• 860301-21-9 N-(tert-butyl)-6-chloropyrazin-2-amine 
• 853888-51-4 6-chloro-N-[(1S)-1-(4-fluorophenyl)ethyl]pyrazin-2-amine 
• 642459-04-9 6-(3-aminosulphonylphenylamino)-2-chloropyrazine 
• 426829-52-9 tert-Butyl 4-(6-Chloro-2-Pyrazinyl)-1-Piperazinecarboxylate 
• 312736-49-5 3,5-dichloropyrazine-2-carboxylic acid 
• 426830-12-8 2-[(4-Fluorobenzyl)Oxy]-6-(1-Piperazinyl)Pyrazine 
• 426829-59-6 2-Chloro-6-(3-Thienyl)Pyrazine 

Relevant articles and documents

Preparation method of 2, 6-dichloropyrazine

The invention discloses a preparation method of 2, 6-dichloropyrazine. The method comprises the following steps: taking glycine and glyoxal as raw materials, carrying out ammoniation and cyclization reactions to prepare 2-hydroxypyrazine sodium; and reacting 2-hydroxypyrazine sodium with thionyl chloride under the catalytic action of N,N-diisopropylethylamine to prepare 2-chloropyrazine; wherein pyridine is used as a solvent, and 2-chloropyrazine is subjected to chlorination of chlorine to obtain 2,6-dichloropyrazine. The method has the advantages that the raw material namely glycine is cheapand easily available, and phosphorus oxychloride is not used as a chlorination reagent, so that the generation of organic phosphorus-containing wastewater is greatly reduced, and an effective way is provided for efficient green industrial production of 2, 6-dichloropyrazine.

Studies on Pyrazines. 29. High Regioselective Synthesis of Chloropyrazines from 3-Substituted Pyrazine 1-Oxides

Reaction of 3-methoxy- or 3-chloropyrazine 1-oxides with refluxing phosphoryl chloride in the presence of amine led to a high regioselective formation of 3-substituted 2-chloropyrazines.In contrast, the use of chloroacetyl chloride instead of phosphoryl chloride enabled different regioselectivity to yield 6-substituted 2-chloropyrazines, particularly 3-methoxycarbonylpyrazine 1-oxide was almost exclusively converted into methyl 6-chloropyrazinecarboxylate under conditions without the amine.