The Differentiated Quinoxalinone Scaffold for Kinase Inhibitors, HDAC Modulators, and ALDH-Targeted Therapeutics: Methyl 3-Oxo-3,4-dihydro-6-quinoxalinecarboxylate CAS# 357637-38-8

Methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate (CAS# 357637-38-8), also known as methyl 3-oxo-3,4-dihydroquinoxaline-6-carboxylate, 3,4-dihydro-3-oxo-6-quinoxalinecarboxylic acid methyl ester, or methyl 3-oxo-4H-quinoxaline-6-carboxylate, is a heterobicyclic quinoxalinone ester with the molecular formula C₁₀H₈N₂O₃ and a molecular weight of 204.18 g/mol. Its molecular structure features a fused benzene–pyrazine (quinoxaline) ring system bearing a 3-oxo carbonyl group on the pyrazine ring and a 6-carboxylate methyl ester on the benzene ring. This specific substitution pattern—a quinoxalinone core with a methyl ester handle at the 6-position—confers a unique combination of physicochemical properties and synthetic utility that distinguishes it from its closest structural analogs, making it an indispensable building block in modern medicinal chemistry and pharmaceutical development.

The compound occupies a distinct physicochemical space relative to its structural analogs. With a calculated LogP of 1.13, it is approximately 0.5 log units more lipophilic than the corresponding free carboxylic acid (LogP ~0.62) and slightly less lipophilic than the non-oxo methyl quinoxaline-6-carboxylate (LogP ~1.27). The presence of the 3-oxo carbonyl introduces an additional hydrogen-bonding pharmacophore that is absent in the non-oxo analog, while the methyl ester enables chemoselective N-functionalization without requiring additional protection steps. This unique combination of moderate lipophilicity, dual carbonyl functionality, and a single hydrogen-bond donor (N–H) positions methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate as a versatile intermediate for constructing kinase-targeted, HDAC-inhibitory, and ALDH-modulating compound libraries, as evidenced by its specific citation in multiple therapeutic patent families.

The compound typically appears as a crystalline solid with a density of 1.4 ± 0.1 g/cm³ and a refractive index of 1.63. It is soluble in moderately polar organic solvents such as ethyl acetate and chloroform, but has limited solubility in water. The compound is typically supplied at ≥95% to ≥98% purity (HPLC) and should be stored in a cool, dry place protected from light and moisture. Under GHS, it is not classified as hazardous material for transport purposes, and is intended for research and development use only.

Market demand for methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate (CAS# 357637-38-8) is concentrated in three primary sectors: pharmaceutical R&D and drug discovery (approximately 55–60% of global consumption), medicinal chemistry and chemical probe development (approximately 25–30%), and specialty chemical synthesis and materials science (approximately 10–15%). Its differentiated quinoxalinone scaffold and versatile dual-carbonyl functionality serve as the core drivers of sustained demand growth.

In pharmaceutical R&D and drug discovery, methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate is a key building block for the synthesis of therapeutic agents targeting a range of diseases. The compound has been specifically cited as a synthetic intermediate or scaffold component in at least three distinct patent families targeting unrelated therapeutic proteins, including heterocyclic compounds as aldehyde dehydrogenase (ALDH) inhibitors for cancer, type 2 diabetes, and pulmonary arterial hypertension. The quinoxalinone scaffold is a privileged structure in medicinal chemistry, and its derivatives have demonstrated antiproliferative IC₅₀ values of 0.126 μM against HeLa cells, underscoring the scaffold's potential in oncology drug discovery. The compound's dual carbonyl functionality and single hydrogen-bond donor position it as a versatile intermediate for constructing kinase-targeted, HDAC-inhibitory, and ALDH-modulating compound libraries. The quinoxalinone core has been investigated as a novel inhibitor scaffold for EGFR (L858R/T790M/C797S) tyrosine kinase, VEGFR-2 kinase inhibitors, and JAK2/3 inhibitors, with demonstrated IC₅₀ values in the low-nanomolar range for JAK2 (13.00 ± 1.31 nM) and JAK3 (14.86 ± 1.29 nM). The methyl ester at the 6-position enables chemoselective N-functionalization without extra protection steps, a critical advantage for efficient analog synthesis and structure-activity relationship (SAR) studies.

In medicinal chemistry and chemical probe development, methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate serves as a differentiated quinoxalinone scaffold for constructing focused libraries of bioactive molecules. The compound's unique physicochemical profile—moderate lipophilicity (LogP 1.13) and a single hydrogen-bond donor—supports drug-like property profiling, making it valuable for lead optimization and pharmacokinetic predictability. The quinoxaline ring system is known for its diverse biological activities, including antimicrobial, antiviral, anticancer, and anti-inflammatory properties, making the compound a versatile starting point for developing therapeutic agents against cancer, tuberculosis, and malaria. The compound is used as a biochemical probe to study quinoxalinone-related biological pathways, and its rigid bicyclic core offers excellent target binding affinity and pharmacokinetic properties.

In specialty chemical synthesis and materials science, methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate is employed as a key intermediate for the synthesis of functional materials. The compound's quinoxaline core provides a conjugated aromatic system that can be used to synthesize organic materials with optoelectronic properties, making it valuable for developing novel functional materials for organic electronics and sensor applications. The methyl ester handle enables further derivatization through hydrolysis to the corresponding carboxylic acid, which can then be used to construct more complex quinoxaline-containing compounds.

Methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate (CAS# 357637-38-8) is a differentiated quinoxalinone ester whose value derives from the orthogonal reactivity of its 3-oxo carbonyl, 6-methyl ester, and N–H functionalities.

Key physicochemical parameters include:

The compound's reactivity is defined by its three orthogonal handles: the 3-oxo carbonyl group on the pyrazine ring enables nucleophilic addition, condensation, and cyclization reactions; the 6-methyl ester group enables hydrolysis to the corresponding carboxylic acid, transesterification, and amidation; and the N–H group at the 4-position enables N-alkylation, N-acylation, and N-functionalization. The 3-oxo group introduces an additional hydrogen-bonding pharmacophore that facilitates interactions with biological targets, while the methyl ester enhances solubility and reactivity for subsequent derivatization. The compound can undergo various chemical reactions including oxidation, reduction (of the keto group to yield alcohol derivatives using sodium borohydride), and electrophilic substitution at various positions on the quinoxaline ring.

The synthesis of methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate can be accomplished through several synthetic routes. A common method involves the reaction of o-phenylenediamine with diethyl oxalate or similar reagents to form the quinoxaline ring, followed by subsequent reactions to introduce the keto group at the 3-position and the carboxylate group at the 6-position. Alternative routes include hydrazinolysis of ethyl 4-methyl-3-oxo-3,4-dihydroquinoxaline-2-carboxylate to yield 4-methyl-3-oxo-3,4-dihydroquinoxaline-2-carbohydrazide as an intermediate, followed by condensation with methyl esters or aldehydes to introduce the 6-carboxylate group. Typical reaction conditions include reflux in solvents such as ethanol or acetic acid, with catalysts such as sulfuric acid used to facilitate cyclization.

The global supply system for methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate (CAS# 357637-38-8) features a pattern of “specialized heterocyclic building block manufacturers, multinational research chemical distributors, and Chinese producers serving distinct market segments.” As a specialized quinoxalinone scaffold rather than a bulk commodity, the market is characterized by a moderate number of suppliers catering to pharmaceutical R&D, medicinal chemistry, and academic research.

In the global research and high-purity segment, key international suppliers include AK Scientific (AKSci), offering the compound at 95% purity under product code 8913DT, with long-term storage in a cool, dry place, DOT/IATA classification as non-hazardous material, and all products stocked and shipped from the SF Bay Area, California, USA. ChemScene offers the compound at ≥98% purity under catalog number CS-0620904. BenchChem offers the compound under catalog number B13113600 with standard pack sizes of 10 mg, 50 mg, 100 mg, and bulk custom, with in-stock availability and custom synthesis available on request. EvitaChem offers the compound under catalog number EVT-13247924 for non-human research use only. VulcanChem offers the compound under catalog number VC17572026. CalpacLab offers the compound at 95% purity under CAS 357637-38-8 with 250 mg packaging. CymitQuimica offers the compound under CAS 357637-38-8. These suppliers serve the pharmaceutical, biotechnology, and academic research communities with products that meet rigorous quality specifications.

In the industrial and large-scale production segment, XinChem is a reliable manufacturer and supplier of high-purity methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate from China, offering the compound with stringent quality standards for use in pharmaceutical R&D, kinase inhibitor discovery, and medicinal chemistry applications. XinChem provides the compound with comprehensive quality documentation, batch-specific Certificates of Analysis (COA), customizable packaging, and globally compliant REACH, ISO 9001, and GMP-aligned manufacturing. The company emphasizes that methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate is an important intermediate in pharmaceutical chemical synthesis and a key raw material for constructing quinoxaline derivatives with potential biological activity, of great significance for the development of new drugs for the treatment of certain diseases. XinChem offers the compound at various purity grades (typically 95–99%) and packaging options—from 100 mg to multi-gram quantities—serving both domestic and export markets.

The global methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate market exhibits distinct regional characteristics, with production concentrated in Asia-Pacific (particularly China) and consumption distributed across North America, Europe, and the Asia-Pacific region, aligned with the pharmaceutical, biotechnology, and academic research industries in these regions.

The Asia-Pacific region has emerged as a significant production hub for methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate, with China hosting numerous manufacturers and suppliers including XinChem. The region’s competitive advantages include lower production costs, established chemical infrastructure, and proximity to rapidly growing pharmaceutical and biotechnology industries. XinChem offers the compound at various purity grades (typically 95–99%) and packaging options, serving both domestic and export markets. The growing pharmaceutical R&D, kinase inhibitor discovery, and medicinal chemistry sectors in China, India, Japan, and South Korea continue to drive regional consumption growth. The compound is classified as a pharmaceutical intermediate and organic synthesis intermediate in the Chinese market, with multiple suppliers offering the product in packaging sizes ranging from 100 mg to 5 g.

North America remains a key market for high-purity and research-grade methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate, driven by demand from the pharmaceutical industry, biotechnology companies, and academic research institutions. The United States hosts numerous research organizations, pharmaceutical companies, and contract research organizations that require high-quality quinoxalinone scaffolds for kinase inhibitor discovery, HDAC modulator development, and ALDH-targeted therapeutics. AK Scientific, BenchChem, ChemScene, and EvitaChem serve the North American market with extensive distribution networks. The region's well-established regulatory framework, including FDA oversight of pharmaceutical R&D, supports demand for high-grade research chemicals and pharmaceutical intermediates.

Europe is characterized by stringent regulatory requirements, including REACH registration, and a strong focus on quality and sustainability in pharmaceutical and chemical research. European pharmaceutical companies, medicinal chemistry laboratories, and research institutions demand high-purity heterocyclic building blocks with comprehensive documentation. CymitQuimica serves the European market with in-stock availability. The compound is intended for research and development use only, not for therapeutic or veterinary use.

As a heterocyclic ester and pharmaceutical intermediate, methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate (CAS# 357637-38-8) is subject to regulatory oversight in major global economies. Compliance with relevant regulations is essential for market access and trade.

Methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate is not classified as hazardous material for DOT/IATA transport purposes. The compound is intended for research and development use only and is not intended for therapeutic, food, cosmetic, or consumer applications unless explicitly stated otherwise. Standard laboratory safety practices should be followed during handling, including the use of appropriate personal protective equipment such as lab gloves, safety glasses, and a lab coat. Operations should be conducted in a well-ventilated environment.

Methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate should be stored long-term in a cool, dry place, protected from light and moisture. The compound is stable under recommended storage conditions but should be kept away from strong oxidizing agents and bases.

In the European Union, the compound must comply with REACH registration requirements for import and use. Manufacturers and suppliers must provide comprehensive Safety Data Sheets (SDS) and maintain appropriate documentation. In the United States, methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate is intended for research and development use only and is not intended for therapeutic, food, cosmetic, or consumer applications unless explicitly stated otherwise. For pharmaceutical intermediate applications, manufacturers must comply with relevant FDA regulations and quality standards. The compound is not a controlled substance.

Methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate is not classified as hazardous material for DOT/IATA transport purposes. Proper packaging, labeling, and documentation are nevertheless required for international shipping. The HS code for the compound is 2933990090 (heterocyclic compounds with nitrogen hetero-atoms only).

The market outlook for methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate is positive, supported by several key growth drivers across its major application segments. While the compound remains a relatively specialized quinoxalinone scaffold, its differentiated physicochemical profile and essential role in kinase inhibitor, HDAC modulator, and ALDH-targeted therapeutic development position it for steady growth in the coming years.

Key growth drivers include:

The continued development of kinase inhibitors for oncology, inflammation, and autoimmune diseases drives demand for privileged quinoxalinone scaffolds that enable rapid analog synthesis and SAR exploration. The compound's demonstrated utility in EGFR, VEGFR-2, and JAK2/3 inhibitor development supports sustained demand from oncology and immunology drug discovery programs.

The increasing interest in ALDH inhibitors for cancer, type 2 diabetes, and pulmonary arterial hypertension drives demand for methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate as a key intermediate for heterocyclic ALDH inhibitors. The compound's specific citation in ALDH inhibitor patent families positions it at the forefront of this emerging therapeutic area.

The growing emphasis on epigenetic therapeutics and HDAC inhibitors drives demand for quinoxalinone-based scaffolds that can be efficiently functionalized for HDAC-targeted compound libraries.

The growing recognition of the quinoxalinone scaffold as a privileged structure in medicinal chemistry drives demand for methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate as a differentiated building block that cannot be substituted by the free acid or non-oxo analog without introducing quantifiable liabilities in pharmacokinetic predictivity and synthetic utility.

The increasing investment in drug discovery and API manufacturing in China and India supports demand for high-quality heterocyclic building blocks and pharmaceutical intermediates.

Challenges and considerations:

As a specialized quinoxalinone scaffold, the market for methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate is smaller than that of commodity chemicals.

The market faces competition from other quinoxalinone derivatives and heterocyclic building blocks with similar reactivity profiles.

Some suppliers have listed the compound as discontinued, which may create supply chain challenges for research and development programs.

Increasingly stringent pharmaceutical and chemical regulations may require ongoing investment in quality systems and documentation.

To succeed in this evolving market landscape, suppliers must focus on product quality (particularly purity and batch-to-batch consistency), supply chain reliability, regulatory compliance, and responsive customer service. Companies that can offer high-purity products, flexible packaging options, and technical support for pharmaceutical, medicinal chemistry, and drug discovery applications will be well-positioned to capture growing demand.

Shanghai XinChem Co., Ltd. (XinChem) is a world-leading supplier of organic chemicals and heterocyclic building blocks. The company is dedicated to meeting the innovative needs of the pharmaceutical, biotechnology, and fine chemical industries. Leveraging extensive experience and advanced manufacturing capabilities, XinChem provides high-quality Methyl 3-Oxo-3,4-dihydro-6-quinoxalinecarboxylate (CAS# 357637-38-8) to customers worldwide.

As a trusted manufacturer and supplier based in China, XinChem combines competitive pricing, reliable supply, and exceptional service to establish itself as a preferred partner for pharmaceutical companies, medicinal chemistry researchers, and drug discovery institutions seeking this versatile differentiated quinoxalinone scaffold.

XinChem utilizes state-of-the-art manufacturing facilities and rigorous quality control measures to ensure the purity, consistency, and safety of its methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate products. The production process incorporates established synthetic routes—including the reaction of o-phenylenediamine with diethyl oxalate followed by cyclization and subsequent functionalization—enabling the delivery of products with purity ≥95% (HPLC) and ≥98% (HPLC) to meet diverse application requirements. Strict process control ensures consistent product quality, minimal impurities, and batch-to-batch reproducibility, providing customers with reliable performance in kinase inhibitor discovery, HDAC modulator development, and ALDH-targeted therapeutic synthesis.

The production process strictly adheres to international quality standards, with comprehensive quality control covering raw material sourcing, in-process monitoring, and finished product testing. Each batch is accompanied by a detailed Certificate of Analysis (COA) documenting physical and chemical properties, purity data (HPLC), density (1.4 g/cm³), refractive index (1.63), LogP (1.13), and impurity profiles. XinChem offers batch-specific COA, customizable packaging, and globally compliant REACH, ISO 9001, and GMP-aligned manufacturing.

XinChem offers methyl 3-oxo-3,4-dihydro-6-quinoxalinecarboxylate with purity ≥95% (HPLC) and ≥98% (HPLC) available, ensuring optimal performance in pharmaceutical R&D, kinase inhibitor discovery, and medicinal chemistry applications. The product’s high purity minimizes the risk of unwanted side reactions and impurities, making it suitable for demanding applications in drug discovery, SAR studies, and chemical probe development. The compound is supplied as a crystalline solid with consistent appearance and defined physicochemical properties.

Key specifications include:

XinChem provides a range of packaging options to accommodate diverse customer needs, from laboratory-scale quantities (10 mg, 50 mg, 100 mg, 250 mg) to industrial-scale packaging (1 g, 5 g, 10 g, 25 g, 100 g) and bulk shipments. Customized packaging solutions are available upon request, ensuring safe handling, storage, and transportation with appropriate protection from light and moisture.

As a differentiated quinoxalinone scaffold, Methyl 3-Oxo-3,4-dihydro-6-quinoxalinecarboxylate (CAS# 357637-38-8) exhibits wide application value across multiple industries:

XinChem’s team of experienced chemists and application engineers provides full technical support throughout the customer journey—from product selection and specification development to application guidance and troubleshooting. Whether customers require optimization of synthetic routes, guidance on derivatization strategies for kinase inhibitor discovery, or assistance with regulatory documentation, XinChem’s technical experts are ready to help. Custom synthesis and contract manufacturing with flexible scaling from R&D to commercial quantities are available upon request.

With established supply chains serving markets across Europe, North America, Asia-Pacific, and beyond, XinChem ensures timely delivery and consistent product availability. The company’s logistics team manages all aspects of international shipping, including customs clearance and documentation, with appropriate protection from light and moisture for product stability.

XinChem provides comprehensive documentation to support regulatory compliance, including Safety Data Sheets (SDS), Certificates of Analysis (COA), and other required certificates. The company stays current with evolving regulatory requirements in major markets, including REACH, TSCA, and other regional regulations, helping customers navigate the complexities of global trade.

Extensive experience and deep expertise in heterocyclic building block synthesis and supply.

Rigorous quality control, high purity (≥95% to ≥98%), and adherence to international standards.

Stable supply, competitive pricing, and timely delivery.

Customized solutions to meet diverse customer needs, including custom synthesis and packaging.

Responsive technical support and comprehensive documentation including batch-specific COA.

Contact us today to start your partnership with XinChem!

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