6966-01-4

Basic information

• Product Name: Methyl 3-amino-6-bromopyrazine-2-carboxylate
• Synonyms: METHYL 3-AMINO-6-BROMOPYRAZINE-2-CARBOXYLATE;5-AMINO-2-BROMO-6-PYRAZINECARBOXYLIC ACIDMETHYL ESTER;3-Amino-6-bromopyrazine-2-carboxylic acid methyl ester;Methyl 6-Bromo-3-aminopyrazine-2-carboxylic ester;5-amino-2-bromo-6-pyrazinecarboxylicacid methyl es;5-Bromo-3-(methoxycarbonyl)pyrazin-2-amine, 2-Amino-5-bromo-3-(methoxycarbonyl)pyrazine;3-AMino-6-broMo-2-pyrazinecarboxylic acid Methyl Ester;NSC 18700
• CAS NO: 6966-01-4
• Molecular Formula: C₆H₆BrN₃O₂
• Molecular Weight: 232.03
• EINECS: 1308068-626-2
• Product Categories: Bases & Related Reagents;Heterocycles;Nucleotides
• Mol File: 6966-01-4.mol
• Article Data: 22

Chemical Properties

• Melting Point: 164-166?C
• Boiling Point: 322.422 °C at 760 mmHg
• Flash Point: 148.796 °C
• Appearance: Off-white to yellow/Solid
• Density: 1.755 g/cm³
• Vapor Pressure: 0mmHg at 25°C
• Refractive Index: 1.615
• Storage Temp.: Refrigerator, Under Inert Atmosphere
• PKA: -1.74±0.10(Predicted)
• CAS DataBase Reference: Methyl 3-amino-6-bromopyrazine-2-carboxylate(CAS DataBase Reference)
• NIST Chemistry Reference: Methyl 3-amino-6-bromopyrazine-2-carboxylate(6966-01-4)
• EPA Substance Registry System: Methyl 3-amino-6-bromopyrazine-2-carboxylate(6966-01-4)

Safety Data

• Hazard Codes: Xi
• Statements: 43
• Safety Statements: 37
• Hazardous Substances Data: 6966-01-4(Hazardous Substances Data)

Usage

Chemical Properties

Orange Solid

Uses

Pyrazine derivatives as Axl and C-Met receptor enzyme inhibitors.

InChI:InChI=1/C6H6BrN3O2/c1-12-6(11)4-5(8)9-2-3(7)10-4/h2H,1H3,(H2,8,9)

Synthetic route

Methyl 3-amino-2-pyrazinecarboxylate (16298-03-6) → methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4)

Conditions	Yield
With N-Bromosuccinimide In acetonitrile for 2h; Heating / reflux;	100%
With bromine; acetic acid In water	94%
Stage #1: Methyl 3-amino-2-pyrazinecarboxylate With bromine; acetic acid at 45℃; for 0.833333h; Stage #2: With water at 20℃; for 0.5h;	94%

methanol (67-56-1) + 3-amino-6-bromo-pyrazine-2-carboxylic acid (486424-37-7) → methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4)

Conditions	Yield
With sulfuric acid at 0 - 40℃; for 48h;	80.1%
With sulfuric acid In water

3-aminopyrazinoic acid (5424-01-1) → methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4)

Conditions	Yield
Multi-step reaction with 2 steps 1: sulfuric acid 2: bromine; acetic acid View Scheme
Multi-step reaction with 2 steps 1: sulfuric acid / 20 °C / Cooling with ice 2: N-Bromosuccinimide / acetonitrile / 20 °C View Scheme
Multi-step reaction with 2 steps 1: sulfuric acid / 48 h / Cooling with ice 2: N-Bromosuccinimide / acetonitrile / 24 h / 20 °C / Inert atmosphere View Scheme

methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) → 3-amino-6-bromopyrazine-2-carbohydrazide (1225062-23-6)

Conditions	Yield
With hydrazine hydrate In ethanol at 50℃; for 40h; Inert atmosphere;	100%
With hydrazine hydrate In ethanol at 50℃; for 40h; Inert atmosphere;	100%
With hydrazine hydrate In ethanol at 50℃; for 40h; Inert atmosphere;	100%

methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) → 3-amino-6-bromopyrazine-2-carboxylic acid sodium salt

Conditions	Yield
With sodium hydroxide In water Reflux;	100%

methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) → 3-amino-6-bromo-pyrazine-2-carboxylic acid (486424-37-7)

Conditions	Yield
Stage #1: methyl 3-amino-6-bromopyrazine-2-carboxylate With water; lithium hydroxide In methanol at 90℃; for 5h; Stage #2: With hydrogenchloride In methanol; water	99%
With sodium hydroxide In ethanol	90%
With lithium hydroxide In methanol; water for 2h; Reflux;	83%

methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) + 2-Methoxyphenylboronic acid (5720-06-9) → methyl 3-amino-6-(2-methoxyphenyl)pyrazine-2-carboxylate

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; caesium carbonate In 1,4-dioxane; water at 100℃; Inert atmosphere;	99%

methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) + aniline (62-53-3) → 3-amino-6-bromo-N-phenyl-pyrazine-2-carboxamide (36204-92-9)

Conditions	Yield
at 115℃; for 4h; Microwave irradiation;	98%

4-(isopropylsulfonyl)phenylboronic acid + methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) → methyl 3-amino-6-(4-(isopropylsulfonyl)phenyl)pyrazine-2-carboxylate

Conditions	Yield
With potassium phosphate; bis(tri-t-butylphosphine)palladium(0) In water; acetonitrile at 20 - 60℃; for 2h; Suzuki Coupling;	97%

methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) + 4-methoxyphenylboronic acid (5720-07-0) → 3-Amino-6-(4-methoxy-phenyl)-pyrazine-2-carboxylic acid methyl ester (113892-84-5)

Conditions	Yield
With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; triethylamine In N,N-dimethyl-formamide at 90℃; for 12h;	94%

methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) + di-tert-butyl dicarbonate (24424-99-5) → methyl 3-(bis(tert-butoxycarbonyl)amino)-6-bromopyrazine-2-carboxylate (1225064-15-2)

Conditions	Yield
With dmap In 1,2-dichloro-ethane at 20 - 75℃; for 18.5h; Product distribution / selectivity; Inert atmosphere;	94%
dmap In 1,2-dichloro-ethane at 20 - 75℃; Product distribution / selectivity; Inert atmosphere;	94%

methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) + Cyclopentamine (1003-03-8) → 3-amino-6-bromo-N-cyclopentylpyrazine-2-carboxamide

Conditions	Yield
at 180℃; for 4h; Microwave irradiation;	93%

methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) → 3-hydroxy-6-bromopyrazine-2-carboxylic acid methyl ester (21874-61-3)

Conditions	Yield
Stage #1: methyl 3-amino-6-bromopyrazine-2-carboxylate With sulfuric acid; sodium nitrite at -5 - 25℃; for 2h; Stage #2: With water for 1.5h;	92.7%
With sulfuric acid; sodium nitrite at -5 - 20℃; for 2h;	90%
With sulfuric acid; sodium nitrite at 0 - 60℃; for 0.5h; Reagent/catalyst;	85%

methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) + benzylamine (100-46-9) → 3-amino-6-bromo-N-benzylpyrazine-2-carboxamide

Conditions	Yield
at 115℃; for 4h; Microwave irradiation;	92%

methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) + 4-methanesulphonylphenylboronic acid (149104-88-1) → 3-amino-6-(4-(methylsulfonyl)phenyl)pyrazine-2-carboxylic acid (1232423-29-8)

Conditions	Yield
Stage #1: methyl 3-amino-6-bromopyrazine-2-carboxylate; 4-methanesulphonylphenylboronic acid With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In 1,2-dimethoxyethane at 90℃; for 9h; Stage #2: With hydrogenchloride In water pH=1;	91%

methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) + 2,6-difluorophenylboronic acid (162101-25-9) → methyl 3-amino-6-(2,6-difluorophenyl)pyrazine-2-carboxylate (1620013-45-7)

Conditions	Yield
With bis(tri-t-butylphosphine)palladium(0); N-ethyl-N,N-diisopropylamine In 1,4-dioxane; water at 100℃; for 14h; Inert atmosphere; Sealed tube;	91%

methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) + ethanolamine (141-43-5) → 3-amino-6-bromo-N-(2-hydroxyethyl)pyrazine-2-carboxamide

Conditions	Yield
at 115℃; for 4h; Microwave irradiation;	91%

methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) + tert-butyl 3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]sulfonylpiperidine-1-carboxylate (1427750-91-1) → methyl 3-amino-6-[4-[(1-tert-butoxycarbonyl-3-piperidyl)sulfonyl]phenyl]pyrazine-2-carboxylate (1432755-73-1)

Conditions	Yield
With potassium phosphate; bis(tri-t-butylphosphine)palladium(0) at 60℃; for 2h; Inert atmosphere;	90.02%

methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) + methylamine (74-89-5) → 3-amino-6-bromo-N-methylpyrazine-2-carboxamide (146940-37-6)

Conditions	Yield
In water at 20℃;	90%
In water at 20℃; for 7h;	90%
In water at 20℃; for 4h;	90%
at 115℃; for 4h; Microwave irradiation;	53%
In water for 1.5h; Ambient temperature;

(2-ethoxypyridin-3-yl)boronic acid (854373-97-0) + methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) → 3-amino-6-(2-ethoxy-pyridin-3-yl)-pyrazine-2-carboxylic acid methyl ester

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In 1,4-dioxane; water at 20℃; for 16h; Suzuki cross-coupling;	90%

methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) + bis(pinacol)diborane (73183-34-3) → methyl 3-amino-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2-pyrazinecarboxylate

Conditions	Yield
With (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride; potassium acetate In 1,4-dioxane at 80℃; for 18h; Time; Inert atmosphere;	90%

methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) + furan-3-boronic acid (55552-70-0) → 3-amino-6-(furan-3-yl)-pyrazine-2-carboxylic acid methyl ester (113892-86-7)

Conditions	Yield
With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; triethylamine In N,N-dimethyl-formamide at 90℃; for 12h;	89%
Stage #1: methyl 3-amino-6-bromopyrazine-2-carboxylate With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate In N,N-dimethyl-formamide at 20 - 50℃; for 0.25h; Stage #2: furan-3-boronic acid With triethylamine In N,N-dimethyl-formamide at 90℃; for 16h;	61.8%
With triethylamine; 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate In N,N-dimethyl-formamide at 90℃; for 16h; Inert atmosphere;	61.8%
With potassium acetate; tetrakis(triphenylphosphine) palladium(0) In 1,4-dioxane at 170℃; for 0.333333h; Microwave irradiation;

pyrrolidine (123-75-1) + methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) → (3-amino-6-bromopyrazin-2-yl)(pyrrolidin-1-yl)methanone

Conditions	Yield
at 115℃; for 4h; Microwave irradiation;	89%

methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) + benzo[b]thiophen-3-yl-3-boronic acid (113893-08-6) → 3-Amino-6-benzo[b]thiophen-3-yl-pyrazine-2-carboxylic acid methyl ester (113892-85-6)

Conditions	Yield
With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; triethylamine In N,N-dimethyl-formamide at 90℃; for 12h;	87%

SEC-BUTYLAMINE (33966-50-6) + methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) → 3-amino-6-bromo-N-(sec-butyl)-pyrazine-2-carboxamide

Conditions	Yield
at 100℃; for 6h; Microwave irradiation;	87%

methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) + Trimethylboroxine (823-96-1) → methyl 3-amino-6-methylpyrazine-2-carboxylate (2032-84-0)

Conditions	Yield
With [1,1'-bis(diphenylphosphino)ferrocene]dichloropalladium(II); potassium carbonate In 1,2-dimethoxyethane at 100℃; for 16h; Inert atmosphere; Sealed tube;	87%

methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) + (2,3-dimethoxypyridin-4-yl)boronic acid (1031438-93-3) → methyl 3-amino-6-(2,3-dimethoxypyridin-4-yl)pyrazine-2-carboxylate (1031439-07-2)

Conditions	Yield
With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In 1,4-dioxane; water for 0.25h; Suzuki-Miyaura cross-coupling; Reflux;	86%

methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) → lithium 3-amino-6-bromopyrazine-2-carboxylate

Conditions	Yield
With water; lithium hydroxide In methanol at 20 - 50℃; for 3.08333h;	85%

methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) + 3-Diethylboranylpyridine (89878-14-8) → 3-amino-6-(pyridin-3-yl)pyrazine-2-carboxylic acid (1232423-31-2)

Conditions	Yield
Stage #1: methyl 3-amino-6-bromopyrazine-2-carboxylate; 3-Diethylboranylpyridine With bis-triphenylphosphine-palladium(II) chloride; sodium carbonate In 1,2-dimethoxyethane; water at 80℃; Suzuki coupling; Stage #2: With acetic acid In water pH=5;	84%

methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) + methyl 3-amino-5-<(ethoxycarbonyl)methyl>-6-chloropyrazinoate (113892-80-1) → 3-Amino-5-ethoxycarbonylmethyl-6-phenyl-pyrazine-2-carboxylic acid methyl ester (113892-87-8)

Conditions	Yield
With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; triethylamine In N,N-dimethyl-formamide at 90℃; for 12h;	82%

methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) + phenylboronic acid (98-80-6) → methyl 3-amino-6-phenyl-2-pyrazine carboxylate (1503-42-0)

Conditions	Yield
With 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate; triethylamine In N,N-dimethyl-formamide at 90℃; for 12h;	82%
Stage #1: 1,1'-bis-(diphenylphosphino)ferrocene; palladium diacetate In DMF (N,N-dimethyl-formamide) at 50℃; for 0.333333h; Stage #2: methyl 3-amino-6-bromopyrazine-2-carboxylate; phenylboronic acid With triethylamine In ISOPROPYLAMIDE at 20 - 90℃; for 12h;
With sodium carbonate; tetrakis(triphenylphosphine) palladium(0) In methanol; water; toluene at 85℃; for 4h; Inert atmosphere;

(4-(pyrrolidin-1-ylsulfonyl)phenyl)boronic acid (486422-57-5) + methyl 3-amino-6-bromopyrazine-2-carboxylate (6966-01-4) → methyl 3-amino-6-[4-(pyrrolidin-1-ylsulfonyl)phenyl]pyrazine-2-carboxylate (486423-09-0)

Conditions	Yield
With potassium phosphate tribasic; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride In 1,2-dimethoxyethane; water at 160℃; for 0.5h; heating in a microwave oven;	82%
With potassium phosphate tribasic; (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride In 1,2-dimethoxyethane; water at 160℃; for 0.166667h; microwave oven;	82%

Upstream product

• 67-56-1 methanol 
• 486424-37-7 3-amino-6-bromo-pyrazine-2-carboxylic acid 
• 16298-03-6 Methyl 3-amino-2-pyrazinecarboxylate 
• 5424-01-1 3-aminopyrazinoic acid 

Downstream Products

• 486424-37-7 3-amino-6-bromo-pyrazine-2-carboxylic acid 
• 938439-10-2 6-bromo-3-(3-chlorophenyl)pteridine-2,4(1H,3H)-dione 
• 1225062-23-6 3-amino-6-bromopyrazine-2-carbohydrazide 
• 767282-89-3 C₂₃H₂₆N₆O₂ 
• 486423-10-3 3-amino-N-(pyridin-3-yl)-6-[4-(pyrrolidin-1-ylsulfonyl)phenyl]pyrazine-2-carboxamide 
• 486423-11-4 3-amino-6-[4-(piperidin-1-ylsulfonyl)phenyl]-N-(pyridin-3-yl)pyrazine-2-carboxamide 
• 486423-23-8 3-amino-6-[4-(morpholin-4-ylsulfonyl)phenyl]-N-(pyridin-3-yl)pyrazine-2-carboxamide 
• 486424-33-3 C₂₂H₂₅N₇O₂ 
• 486424-20-8 AZD₂₈₅₈ 
• 1243644-13-4 3-amino-6-[4-[[(2-methoxyethyl)amino]sulfonyl]phenyl]-N-3-pyridinyl-2-pyrazinecarboxamide 
• 486424-26-4 C₂₁H₂₃N₇O₃S 
• 486424-25-3 C₂₁H₂₃N₇O₃S 
• 1432755-73-1 methyl 3-amino-6-[4-[(1-tert-butoxycarbonyl-3-piperidyl)sulfonyl]phenyl]pyrazine-2-carboxylate 

Relevant articles and documents

First synthesis of piperazine-derived [1,2,4]triazolo[1,5-a]pyrazine as an adenosine A2a receptor antagonist

Synthesis of piperazine-derived 2-furan-2-yl-[1,2,4]triazolo[1,5-a] pyrazines was achieved using methyl 3-amino-2-pyrazinecarboxylate. Introduction of the piperazine to the pyrazine template was achieved through a pteridin-4-one intermediate (7). Cyclization of the [1,2,4]triazolo[1,5-a]pyrazine ring was accomplished by amination of pyrazine (8) followed by condensation with 2-furaldehyde. Curtius rearrangement installed the amine to afford template (11). As one example of derivatizing 11, 6N-(4-(2,4,6-trifluorobenzyl)piperazin-1-yl)-2-(furan-2-yl)-[1,2,4]triazolo-[1,5-a]pyrazin-8-amine (12) showed moderate adenosine A2a receptor binding affinity and selectivity over the A1 receptor.{A figure is presented}.

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