Product Overview

Ethyl 6-Amino-5-nitronicotinate (CAS 90765-07-4, molecular formula C₈H₉N₃O₄, MW 211.17) — also known as ethyl 6-amino-5-nitropyridine-3-carboxylate and 6-amino-5-nitropyridine-3-carboxylic acid ethyl ester — is a difunctional pyridine building block that combines an electron-donating 6-amino group with an electron-withdrawing 5-nitro group on the pyridine-3-carboxylate ester scaffold. This ortho-amino-nitro substitution pattern is synthetically strategic: the 6-amino group provides a nucleophilic handle for imine formation, acylation, diazotization, and N-arylation, while the 5-nitro group simultaneously activates the pyridine ring for nucleophilic aromatic substitution at positions 2 and 4 and serves as a reducible precursor to a second amino group via catalytic hydrogenation — yielding 5,6-diaminonicotinate, a versatile intermediate for fused heterocycle assembly. The ethyl ester at position 3 offers orthogonal reactivity: it can be hydrolyzed to the free carboxylic acid (for amide coupling or salt formation) or reduced to the alcohol (for further functionalization). This triple reactivity in a single molecule — amino nucleophile, nitro electrophile/reducible group, and ester — makes it a privileged scaffold for constructing imidazo[4,5-b]pyridines, pyrido[2,3-d]pyrimidines, triazolopyridines, and other nitrogen-rich fused heterocycles that map onto ATP-binding site pharmacophores in kinase drug discovery.

UPOR Biotech is a specialty research chemical supplier providing Ethyl 6-Amino-5-nitronicotinate at 95-98% HPLC purity in research-grade quantities from 100mg evaluation samples to bulk 5g+ production scales. Our product is supplied with full analytical documentation — ¹H-NMR, HPLC purity, and LC-MS — enabling direct integration into medicinal chemistry workflows, structure-activity relationship (SAR) libraries, and pharmaceutical intermediate synthesis. Custom synthesis, scale-up, and OEM/private label manufacturing are available for drug discovery programs requiring multi-gram to kilogram quantities. ISO 9001:2015 certified quality management system. Free sample evaluation available for qualified research groups.

Ortho-Amino-Nitro Pyridine vs Simple Nicotinate Esters — The Synthetic Efficiency Advantage

Starting from unsubstituted nicotinate esters, introducing both 6-amino and 5-nitro substituents requires 3-5 sequential synthetic steps — nitration (with regioselectivity challenges on pyridine), protection/deprotection, and amination — each with associated yield losses and purification overhead. Ethyl 6-Amino-5-nitronicotinate provides this difunctional scaffold pre-installed in a single building block, eliminating 2-3 synthetic steps, reducing time-to-first-SAR-data by weeks, and conserving valuable Advanced Intermediate inventory for your medicinal chemistry team. For programs exploring kinase hinge-binding motifs, nitroreductase-activated prodrugs, or ¹⁸F-PET tracer precursors — where the ortho-amino-nitro pyridine core is the key pharmacophore — this compound is the most direct synthetic entry point available.

Technical Specifications

PropertySpecification
Product NameEthyl 6-Amino-5-nitronicotinate — Research Grade
Common Name / SynonymsEthyl 6-amino-5-nitronicotinate; Ethyl 6-amino-5-nitropyridine-3-carboxylate; 6-Amino-5-nitropyridine-3-carboxylic acid ethyl ester; 3-Pyridinecarboxylic acid, 6-amino-5-nitro-, ethyl ester
CAS Number90765-07-4
Molecular FormulaC₈H₉N₃O₄
Molecular Weight211.17 g/mol
SMILESO=C(OCC)C1=CN=C(N)C([N+]([O-])=O)=C1
InChIKeySAOCMXIYAPVORO-UHFFFAOYSA-N
AppearanceYellow to orange crystalline powder
Assay (HPLC)≥95% (standard); ≥98% (high-purity grade)
Key Structural FeatureOrtho-amino-nitro difunctional pyridine — 6-NH₂ (nucleophile) + 5-NO₂ (electron-withdrawing / reducible) + 3-COOEt (ester)
XLogP3-AA1.1
Topological Polar Surface Area111 Ų
Hydrogen Bond Donors / Acceptors1 HBD / 6 HBA
Rotatable Bonds3
Heavy Atom Count15
SolubilitySoluble in DMF, DMSO, THF, dichloromethane, ethyl acetate; limited solubility in water
StabilityStable under inert atmosphere; protect from light and moisture. Ethyl ester stable under basic/neutral conditions; cleaved by strong acid.
Storage Conditions2-8°C, sealed under argon or nitrogen, protected from light and moisture
Heavy Metals≤20 ppm (as Pb)
Loss on Drying≤0.5%
Residue on Ignition≤0.1%
GradeResearch Grade (RUO) — not for human diagnostic or therapeutic use
CertificationsISO 9001:2015; COA with ¹H-NMR, HPLC, LC-MS per lot
Packaging100mg / 250mg / 1g / 5g — amber glass vials with PTFE-lined caps, argon-flushed
MOQ100mg (evaluation); bulk quantities 1g-5g+
Shelf Life24 months from date of manufacture under recommended storage conditions

Key Benefits for Medicinal Chemistry

Pre-Installed Ortho-Amino-Nitro Scaffold for Heterocycle Synthesis

The 6-NH₂ / 5-NO₂ difunctional arrangement eliminates 2-3 synthetic steps vs stepwise functionalization of unsubstituted nicotinate. The amino group undergoes imine formation and acylation; the nitro group activates the ring for SNAr and reduces to a second amine — enabling imidazopyridine, pyridopyrimidine, and triazolopyridine assembly in a single transformation sequence.

Synthetic Efficiency

Kinase Inhibitor Pharmacophore — ATP-Binding Site Mimicry

The 6-amino-5-nitropyridine core maps onto the adenine-recognition region of kinase ATP-binding pockets — the 6-NH₂ mimics the adenine 6-NH₂ hydrogen bond donor, while the 5-NO₂ / ester orients the scaffold for hinge-region interactions. This makes it a direct precursor for Type I kinase inhibitor lead optimization libraries targeting EGFR, VEGFR, and CDK families.

Drug Discovery

Nitroreductase-Activated Prodrug Precursor

The 5-nitro group is enzymatically reducible by bacterial and mammalian nitroreductases under hypoxic conditions — enabling the design of hypoxia-selective prodrugs and antibody-directed enzyme prodrug therapy (ADEPT) constructs. The 6-amino group provides a conjugation handle for antibody-linker attachment without blocking prodrug activation.

Prodrug Design

Triple Orthogonal Reactivity — Amino, Nitro, and Ester

Three functional groups with independent reactivity manifolds: the 6-NH₂ is a nucleophile (acylation, diazotization, reductive amination), the 5-NO₂ is both an electron-withdrawing activator and a reducible group (→ 5-NH₂ via H₂/Pd-C), and the 3-COOEt is an ester (hydrolysis → COOH, reduction → CH₂OH, aminolysis → CONHR). This orthogonal trifunctionality enables sequential derivatization without protecting group chemistry.

Chemical Versatility

Research Applications

Kinase Inhibitor Lead Optimization

Building block for Type I kinase inhibitors targeting EGFR, VEGFR, CDK, and Aurora kinase families. The amino-nitropyridine core is a privileged ATP-competitive pharmacophore for hinge-region binding.

Fused Heterocycle Construction

Direct precursor for imidazo[4,5-b]pyridines, pyrido[2,3-d]pyrimidines, triazolopyridines, and pyridopyrazines — nitrogen-rich scaffolds prevalent in antimicrobial and anticancer clinical candidates.

Nitroreductase Prodrug Development

5-NO₂ group enables enzymatic reduction under hypoxia for tumor-selective activation. 6-NH₂ provides a non-competing linker attachment site for antibody-drug conjugate (ADC) and gene-directed enzyme prodrug therapy (GDEPT) constructs.

Antibacterial Agent Synthesis

Nitroaromatic pyridine precursor for nitroimidazole and nitrofuran bioisosteres. The amino group enables further derivatization to Schiff bases and hydrazones with demonstrated Gram-positive and Gram-negative activity.

¹⁸F-PET Tracer Radiolabeling

The 5-nitro group is a leaving group for nucleophilic aromatic ¹⁸F-fluorination — enabling rapid access to ¹⁸F-labeled pyridine PET tracers for neuroinflammation and oncology imaging without multi-step precursor synthesis.

Metal-Organic Framework (MOF) Ligands

Pyridine-3-carboxylate ester with 6-NH₂ coordination site and 5-NO₂ hydrogen-bond acceptor — a ditopic linker for constructing functionalized MOFs with catalytic and gas-separation applications.

Frequently Asked Questions

Ethyl 6-Amino-5-nitronicotinate (CAS 90765-07-4) is a difunctional pyridine-3-carboxylate ester featuring both an electron-donating 6-amino group and an electron-withdrawing 5-nitro group on the same pyridine ring — a combination that enables regioselective derivatization at multiple positions. Unlike simple nicotinate esters, the ortho-amino-nitro substitution pattern provides a versatile scaffold for constructing fused heterocycles including imidazo[4,5-b]pyridines, pyrido[2,3-d]pyrimidines, and triazolopyridines — key pharmacophores in kinase inhibitor and antimicrobial drug discovery programs. The ethyl ester offers orthogonal reactivity for further diversification via hydrolysis, reduction, or aminolysis.

This compound serves as a privileged intermediate for: (1) Kinase inhibitor scaffolds — the 6-amino-5-nitropyridine core maps onto ATP-binding site pharmacophores; (2) Nitroreductase-activated prodrugs — the 5-nitro group is enzymatically reducible for hypoxia-selective activation; (3) Antibacterial agent synthesis — nitroaromatic pyridines are precursors to nitroimidazole and nitrofuran bioisosteres; (4) Fused heterocycle construction — the ortho-amino-nitro arrangement enables cyclization to imidazopyridines, pyridopyrimidines, and triazolopyridines; (5) PET tracer precursors — the nitro group is a leaving group for ¹⁸F-fluorination in radiochemistry. Typical usage at stoichiometric 1-2 equivalents in coupling, cyclization, and substitution reactions.

Usage rate: stoichiometric (1-2 equivalents) in coupling, cyclization, and substitution reactions. Soluble in DMF, DMSO, THF, and dichloromethane; limited aqueous solubility. The ethyl ester is stable under basic and neutral conditions; acidic hydrolysis cleaves the ester to the free carboxylic acid. The 6-amino group is reactive toward acylating agents and aldehydes; the 5-nitro group is stable under most reaction conditions but undergoes catalytic hydrogenation (H₂/Pd-C) to yield 5,6-diaminonicotinate. Storage: 2-8°C under inert atmosphere (argon or nitrogen), protected from light and moisture. Standard laboratory PPE recommended. COA with ¹H-NMR, HPLC purity, and LC-MS data provided with every order.

The ortho-amino-nitro arrangement on the pyridine ring is synthetically strategic: (1) the 6-amino group acts as a nucleophile for imine formation, acylation, and diazotization — enabling N-arylation and cyclization to imidazopyridines; (2) the 5-nitro group is a strong electron-withdrawing group that activates the pyridine ring for nucleophilic aromatic substitution at positions 2 and 4 while also serving as a reducible precursor to a second amino group (via catalytic hydrogenation to 5,6-diamino). This dual functionality in a single building block eliminates 2-3 synthetic steps compared to sequential functionalization of unsubstituted nicotinate — reducing time-to-first-SAR-data by weeks. For comparison, ethyl 6-aminonicotinate (no nitro) lacks the ring activation and reducible functionality; ethyl 5-nitronicotinate (no amino) lacks the nucleophilic handle for cyclization. Only the ortho-amino-nitro combination delivers both reactivities simultaneously.

UPOR Biotech provides: Certificate of Analysis (COA) with HPLC purity assay (≥95% or ≥98%, depending on grade ordered), ¹H-NMR spectrum with peak assignments, and LC-MS molecular ion confirmation; Material Safety Data Sheet (MSDS) with handling, storage, and disposal guidance; ISO 9001:2015 Certificate of Conformance. Our quality management system ensures full batch traceability with assigned batch numbers. For pharmaceutical development programs: Drug Master File (DMF) support, residual solvent analysis (per USP <467>), and elemental impurity testing (per ICH Q3D) are available upon request. MOQ starts at 100mg for initial evaluation; bulk quantities (1g, 5g, and larger) with competitive volume-based pricing. Free 100mg evaluation samples available for qualified academic and industry research groups. Contact our technical sales team at [email protected] with your purity, quantity, and documentation requirements.