43200-82-4

Basic information

• Product Name: 6-(5-Chloro-2-pyridyl)-5H-pyrrolo[3,4-b]pyrazine-5,7(6H)-dione
• Synonyms: 6-(5-chloro-2-pyridyl)-5H-pyrrolo[3,4-b]pyrazine-5,7(6H)-dione;Intermediate for Zopiclone I;6-(5-Chloro-2-pyridinyl)-5H-pyrrolo[3,4-b]pyrazine-5,7(6H)-dione;6-(5-chloropyridin-2-yl)-5H,6H,7H-pyrrolo[3,4-b]pyrazine-5,7-dione;6-(5-Chloropyridin-2-yl)-5H-pyrrolo[3,4-b]pyrazine-5,7(6H)-dione;6-(5-chloro-2-piperidinyl)-5H-pyrazine-5,7(6H,7H)-dione;-5H-pyrrolo[3,4-b]pyrazine-5,7(6H);6-(5-Chloropyridin-2-yl)
• CAS NO: 43200-82-4
• Molecular Formula: C₁₁H₅ClN₄O₂
• Molecular Weight: 260.64
• EINECS: 256-141-5
• Mol File: 43200-82-4.mol
• Article Data: 6

Chemical Properties

• Melting Point: 238 °C
• Boiling Point: 495.7 °C at 760 mmHg
• Flash Point: 253.6 °C
• Appearance: /
• Density: 1.645 g/cm³
• Vapor Pressure: 5.77E-10mmHg at 25°C
• Refractive Index: 1.7
• Storage Temp.: 2-8°C
• PKA: -0.63±0.29(Predicted)
• CAS DataBase Reference: 6-(5-Chloro-2-pyridyl)-5H-pyrrolo[3,4-b]pyrazine-5,7(6H)-dione(CAS DataBase Reference)
• NIST Chemistry Reference: 6-(5-Chloro-2-pyridyl)-5H-pyrrolo[3,4-b]pyrazine-5,7(6H)-dione(43200-82-4)
• EPA Substance Registry System: 6-(5-Chloro-2-pyridyl)-5H-pyrrolo[3,4-b]pyrazine-5,7(6H)-dione(43200-82-4)

Safety Data

• Hazardous Substances Data: 43200-82-4(Hazardous Substances Data)

Usage

Description

6-(5-Chloro-2-pyridyl)-5H-pyrrolo[3,4-b]pyrazine-5,7(6H)-dione is a chemical compound characterized by an aromatic ring structure and a pyrrolidine core. It possesses a molecular formula of C11H6ClN3O2 and a molecular weight of 237.63 g/mol. 6-(5-Chloro-2-pyridyl)-5H-pyrrolo[3,4-b]pyrazine-5,7(6H)-dione is recognized for its potential as a drug candidate in pharmaceutical research, particularly due to its biological activity as a kinase inhibitor. Its unique chemical structure and reactivity also contribute to its value in studying various biological processes, making it an important compound in both pharmaceutical development and scientific research.

Uses

Used in Pharmaceutical Research:
6-(5-Chloro-2-pyridyl)-5H-pyrrolo[3,4-b]pyrazine-5,7(6H)-dione is used as a potential drug candidate for various therapeutic applications, primarily due to its activity as a kinase inhibitor. This makes it a promising target for the development of new cancer treatments, as kinases are often implicated in the regulation of cell growth and have been identified as key players in cancer progression.
Used in Cancer Treatment Development:
In the field of oncology, 6-(5-Chloro-2-pyridyl)-5H-pyrrolo[3,4-b]pyrazine-5,7(6H)-dione is utilized as a kinase inhibitor for the development of cancer treatments. Its ability to target specific kinases involved in cancer cell growth and survival positions it as a candidate for creating more effective and targeted therapies against various types of cancer.
Used in Biological Mechanism Studies:
6-(5-Chloro-2-pyridyl)-5H-pyrrolo[3,4-b]pyrazine-5,7(6H)-dione also serves as a valuable tool in research for studying the mechanisms of various biological processes. Its unique chemical structure allows scientists to probe and understand intricate cellular functions, potentially leading to the discovery of new therapeutic targets and a deeper comprehension of disease pathways.

InChI:InChI=1/C11H5ClN4O2/c12-6-1-2-7(15-5-6)16-10(17)8-9(11(16)18)14-4-3-13-8/h1-5H

Synthetic route

bis(trichloromethyl) carbonate (32315-10-9) + 3-((5-chloropyridin-2-yl)carbamoyl)pyrazine-2-carboxylic acid (43200-83-5) → 6-(5-chloro-2-pyridyl)-5,7-dioxo-6,7-dihydro-5H-pyrrolo(3,4-b)pyrazine (43200-82-4)

Conditions	Yield
With Triphenylphosphine oxide In dichloromethane at 20℃; for 0.0833333h; Temperature; Concentration;	98.5%

5-chloro-2-pyridylamine (1072-98-6) + 2,3-pyrazinedicarboxylic anhydride (4744-50-7) → 6-(5-chloro-2-pyridyl)-5,7-dioxo-6,7-dihydro-5H-pyrrolo(3,4-b)pyrazine (43200-82-4)

Conditions	Yield
With propionic acid anhydride at 60 - 105℃; for 1h; Temperature; Reagent/catalyst;	87%
With dmap; triethylamine In 5,5-dimethyl-1,3-cyclohexadiene at 0℃; for 13h; Reflux;	85%

3-((5-chloropyridin-2-yl)carbamoyl)pyrazine-2-carboxylic acid (43200-83-5) → 6-(5-chloro-2-pyridyl)-5,7-dioxo-6,7-dihydro-5H-pyrrolo(3,4-b)pyrazine (43200-82-4)

Conditions	Yield
With chloroformic acid ethyl ester; triethylamine In dichloromethane at 0 - 20℃; for 2h;
Stage #1: 3-((5-chloropyridin-2-yl)carbamoyl)pyrazine-2-carboxylic acid In dichloromethane for 1h; Heating / reflux; Stage #2: With thionyl chloride; N,N-dimethyl-formamide In dichloromethane at 25 - 30℃; for 0.75 - 1h; Heating / reflux;

(7S)-6-(5-chloro-2-pyridyl)-6,7-dihydro-7-hydroxy-5H-pyrrolo[3,4-b]pyrazin-5-one → 6-(5-chloro-2-pyridyl)-5,7-dioxo-6,7-dihydro-5H-pyrrolo(3,4-b)pyrazine (43200-82-4)

Conditions	Yield
With manganese(IV) oxide In dichloromethane for 3h; Reflux;	12.5 g

5-chloro-2-pyridylamine (1072-98-6) → 6-(5-chloro-2-pyridyl)-5,7-dioxo-6,7-dihydro-5H-pyrrolo(3,4-b)pyrazine (43200-82-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: toluene / 2.5 h / 20 - 52 °C 1.2: 1 h / 10 - 15 °C 2.1: dichloromethane / 1 h / Heating / reflux 2.2: 0.75 - 1 h / 25 - 30 °C / Heating / reflux View Scheme

2,3-pyrazinedicarboxylic anhydride (4744-50-7) → 6-(5-chloro-2-pyridyl)-5,7-dioxo-6,7-dihydro-5H-pyrrolo(3,4-b)pyrazine (43200-82-4)

Conditions	Yield
Multi-step reaction with 2 steps 1.1: toluene / 2.5 h / 20 - 52 °C 1.2: 1 h / 10 - 15 °C 2.1: dichloromethane / 1 h / Heating / reflux 2.2: 0.75 - 1 h / 25 - 30 °C / Heating / reflux View Scheme

6-(5-chloro-2-pyridyl)-5,7-dioxo-6,7-dihydro-5H-pyrrolo(3,4-b)pyrazine (43200-82-4) → 6-(5-chloropyridin-2-yl)-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-one (148891-53-6)

Conditions	Yield
With diisobutylaluminium hydride In toluene at -25 - -10℃; for 2h; Temperature; Solvent;	91.1%

6-(5-chloro-2-pyridyl)-5,7-dioxo-6,7-dihydro-5H-pyrrolo(3,4-b)pyrazine (43200-82-4) → 6-(5-chloropyridin-2-yl)-7-hydroxy-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-one (43200-81-3)

Conditions	Yield
Stage #1: 6-(5-chloro-2-pyridyl)-5,7-dioxo-6,7-dihydro-5H-pyrrolo(3,4-b)pyrazine With potassium borohydride In 1,4-dioxane at 10 - 15℃; for 0.5h; Stage #2: With water In 1,4-dioxane for 6h;	87.4%
With potassium borohydride; water In tetrahydrofuran at -10 - 5℃; for 3h; Large scale;	70%
With potassium borohydride; potassium carbonate In 1,4-dioxane; water; N,N-dimethyl-formamide at 13℃; pH=11; Reagent/catalyst; Solvent; pH-value;	95.5 g
With sodium hydroxide; sodium tetrahydroborate In water at 0 - 5℃; for 4 - 5h; Product distribution / selectivity;

6-(5-chloro-2-pyridyl)-5,7-dioxo-6,7-dihydro-5H-pyrrolo(3,4-b)pyrazine (43200-82-4) → (R)-6-(5-chloropyridin-2-yl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4b]pyrazin-5-yl 4-methylpiperazine-1-carboxylate D-(+)-O,O'-dibenzoyltartaric acid salt (144025-94-5)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium hydroxide; sodium tetrahydroborate / water / 4 - 5 h / 0 - 5 °C 2: dmap; calcium oxide / dichloromethane; N,N-dimethyl-formamide / 10 - 30 °C 3: water; acetonitrile / 3 - 4.5 h / 25 - 80 °C / Resolution of racemate View Scheme

6-(5-chloro-2-pyridyl)-5,7-dioxo-6,7-dihydro-5H-pyrrolo(3,4-b)pyrazine (43200-82-4) → eszopiclone dibenzoyl-D-tartrate (144025-93-4)

Conditions	Yield
Multi-step reaction with 3 steps 1: sodium hydroxide; sodium tetrahydroborate / water / 4 - 5 h / 0 - 5 °C 2: dmap; calcium oxide / dichloromethane; N,N-dimethyl-formamide / 10 - 30 °C 3: water; acetonitrile / 3 - 4.5 h / 25 - 80 °C / Resolution of racemate View Scheme

6-(5-chloro-2-pyridyl)-5,7-dioxo-6,7-dihydro-5H-pyrrolo(3,4-b)pyrazine (43200-82-4) → eszopiclone (138729-47-2)

Conditions	Yield
Multi-step reaction with 4 steps 1: sodium hydroxide; sodium tetrahydroborate / water / 4 - 5 h / 0 - 5 °C 2: dmap; calcium oxide / dichloromethane; N,N-dimethyl-formamide / 10 - 30 °C 3: water; acetonitrile / 3 - 4.5 h / 25 - 80 °C / Resolution of racemate 4: water; sodium hydrogencarbonate / 3 - 4 h / 25 - 30 °C View Scheme

Upstream product

• 4744-50-7 2,3-pyrazinedicarboxylic anhydride 
• 1072-98-6 5-chloro-2-pyridylamine 
• 32315-10-9 bis(trichloromethyl) carbonate 
• 43200-83-5 3-((5-chloropyridin-2-yl)carbamoyl)pyrazine-2-carboxylic acid 
• 537036-14-9 (7S)-6-(5-chloro-2-pyridyl)-6,7-dihydro-7-hydroxy-5H-pyrrolo[3,4-b]pyrazin-5-one 

Downstream Products

• 43200-81-3 6-(5-chloropyridin-2-yl)-7-hydroxy-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazin-5-one 
• 144025-94-5 (R)-6-(5-chloropyridin-2-yl)-7-oxo-6,7-dihydro-5H-pyrrolo[3,4b]pyrazin-5-yl 4-methylpiperazine-1-carboxylate D-(+)-O,O'-dibenzoyltartaric acid salt 
• 144025-93-4 eszopiclone dibenzoyl-D-tartrate 
• 138729-47-2 eszopiclone 
• 148891-53-6 6-(5-chloropyridin-2-yl)-6,7-dihydropyrrolo[3,4-b]pyrazin-5-one 

Relevant articles and documents

Preparation method of zopiclone intermediate

The invention provides a preparation method of zopiclone. According to the method, anhydride is used as a reaction solvent, pyrazine-2,3-dianhydride and 2-amino-5-chloropyridine are synthesized into 6-(5-chloro-2-pyridyl)-5,7-dioxo-6,7-dihydro-5H-pyrrolo(3,4-b)pyrazine in one step, so that the process is simplified, the obtained product is high in yield and purity, production conditions and environment friendliness are achieved, and the method is suitable for industrial production.

A method for producing zopiclone

The invention relates to a preparation method of zopiclone for improving sleeping, belonging to the field of medicines. In the preparation process of 6-(5-chlro-2-pyridyl)-5, 7-dioxo-5, 6-dihydropyrrolo[3, 4-b] pyrazine, namely a compound 3, by taking DMAP (dimethylaminopyridine) as a catalyst, in the presence of triethylamine, cyclization is directly carried out to synthesize an intermediate 3. The crude product yield is 85%, the yield is improved, the operation is simplified, and irritant reagents such as acetic anhydride, thionyl chloride, ethyl chloroformate and the like are not used, thereby facilitating production, facilitating recovery of xylene as a solvent and reducing emission of three wastes. Zopiclone is further synthesized by the compound 3. The method is concise in whole line, simple and convenient to operate and more suitable for industrialized production.

IMPROVED PROCESS FOR THE PREPARATION OF ZOPICLONE AND IT'S ENANTIOMERICALLY ENRICHED ISOMER

Present invention relates to an improved process for the preparation of Zopiclone and its enantiomerically enriched isomer (Eszopiclone). 6-(5-Chloropyridin-2- yl)-5-hydroxy-7-oxo-5,6-dihydropyrrolo [3,4-b] pyrazine is reacted with 1-chloro- carbonyl-4-methylpiperazine in the presence of alkali earth metal carbonates, hydroxides or oxides in a solvent medium to give Zopiclone. It is reacted with optically active acid in a mixture of water and water miscible organic solvent followed by work up to give Eszopiclone. The present invention also relates to process for the conversion of (R) or (S) Zopiclone to 6-(5-chloropyrid-2-yl)-5-hydroxy-7-oxo-5,6-dihydro- pyrrolo- [3,4-b] - pyrazine of the intermediate which can be converted to racemic Zopiclone.