2-Chloro-4-pivalamidonicotinic Acid: Properties & Lab Use Guide

2-Chloro-4-pivalamidonicotinic acid is a halogenated pyridinecarboxylic acid bearing a pivaloyl-protected amine at the 4-position, serving as a versatile heterocyclic building block in medicinal chemistry and pharmaceutical intermediate synthesis.

Chemical Name

2-Chloro-4-pivalamidonicotinic acid

SKU / Catalog Number

C165490

Molecular Formula

C₁₁H₁₃ClN₂O₃

Compound Class

Halogenated pyridinecarboxylic acid derivative with N-pivaloyl protecting group

Primary Application

Pharmaceutical intermediate and synthetic building block in heterocyclic chemistry

Key Functional Groups

Carboxylic acid, aromatic C–Cl bond, pivaloyl amide (protected amine)

Chemical Identity and Structural Features

2-Chloro-4-pivalamidonicotinic acid (Aladdin SKU: C165490) is a substituted pyridine-3-carboxylic acid (nicotinic acid) derivative. Its structure incorporates three key features: (1) a chloro substituent at the 2-position of the pyridine ring, providing a handle for nucleophilic aromatic substitution or transition-metal-catalysed cross-coupling; (2) a pivaloyl amide (pivalamide, –NHC(O)C(CH₃)₃) at the 4-position, which both masks the free amine for selective downstream deprotection and exerts electronic and steric directing effects on the ring; and (3) a free carboxylic acid at the 3-position, enabling amide coupling, esterification, or use as an acidic handle in salt formation.

The combination of an electron-withdrawing chlorine and an electron-donating protected amine on the pyridine ring creates a polarised aromatic system with differentiated reactivity at multiple positions, making this compound a multifunctional scaffold for medicinal chemistry programmes.

Handling, Storage, and Safety Guidelines

Personal Protective Equipment (PPE): Handle 2-Chloro-4-pivalamidonicotinic acid in a well-ventilated fume hood. Wear appropriate chemical-resistant gloves (nitrile recommended), safety goggles, and a laboratory coat. Avoid inhalation of dust or aerosols.

Storage: Store the compound in a tightly sealed container in a cool, dry, well-ventilated location away from incompatible materials such as strong oxidisers and strong bases. Refrigerated storage (2–8 °C) is generally recommended for long-term stability of solid organic acid intermediates of this class; consult the current product specification sheet for confirmed storage conditions.

Disposal: Dispose of waste material in accordance with local, regional, and national regulations governing halogenated organic waste. Do not pour down the drain without appropriate treatment.

First Aid: In case of skin or eye contact, flush immediately with copious water for at least 15 minutes and seek medical attention. If inhaled, remove to fresh air. Refer to the Safety Data Sheet (SDS) supplied with the product for complete hazard and first-aid information.

Note: Always consult the current SDS for C165490 before use, as regulatory classifications may be updated.

Synthetic Applications and Research Utility

2-Chloro-4-pivalamidonicotinic acid occupies a strategic role in multi-step pharmaceutical synthesis. Its utility arises from the orthogonal reactivity of its three functional groups, which can be addressed sequentially:

• Cross-coupling at C-2: The aryl chloride at the 2-position is amenable to palladium- or nickel-catalysed cross-coupling reactions (e.g., Suzuki–Miyaura, Buchwald–Hartwig), enabling C–C or C–N bond formation to elaborate the pyridine scaffold.
• Amide coupling or esterification at C-3: The carboxylic acid can be activated (e.g., via EDC/HOBt, SOCl₂, or mixed anhydride methods) to form amides or esters, facilitating introduction of pharmacophoric fragments.
• Amine deprotection at C-4: The pivaloyl group is a robust protecting group removable under acidic or basic hydrolysis conditions, revealing the free 4-aminopyridine motif for further functionalisation or as the final pharmacophore.

This compound is particularly valuable in the synthesis of kinase inhibitors, antiviral agents, and other nitrogen-heterocycle-based drug candidates where differentially functionalised pyridine cores are required. It is also used as a building block in fragment-based drug discovery (FBDD) libraries.

Quality, Purity, and Specification Considerations

For pharmaceutical research and process chemistry applications, the purity of 2-Chloro-4-pivalamidonicotinic acid is critical, as residual impurities can affect downstream reaction yields and product quality. Researchers should request and review the Certificate of Analysis (CoA) for each lot of C165490, paying particular attention to:

• Purity (HPLC): Typical specification for research-grade material; consult the current CoA for lot-specific data.
• Identity confirmation: Verified by ¹H NMR, ¹³C NMR, and/or high-resolution mass spectrometry (HRMS).
• Appearance: Expected as a solid powder; colour may range from white to off-white.
• Water content: Karl Fischer titration data may be relevant for moisture-sensitive applications.

If the compound is intended for use in regulated analytical methods or GMP-adjacent workflows, contact Aladdin Scientific's technical team to discuss available grades, lot-to-lot consistency data, and custom specification requirements.

Frequently asked questions

What is the primary use of 2-Chloro-4-pivalamidonicotinic acid in medicinal chemistry?

It serves as a multifunctional heterocyclic building block whose aryl chloride, protected amine, and carboxylic acid groups can be addressed orthogonally in multi-step synthesis. It is commonly employed in the preparation of kinase inhibitors, antiviral agents, and other nitrogen-heterocycle-based drug candidates.

How should 2-Chloro-4-pivalamidonicotinic acid be stored to maintain stability?

The compound should be stored in a tightly sealed container in a cool, dry, and well-ventilated environment, away from strong oxidisers and bases. Refrigerated storage at 2–8 °C is generally recommended for long-term preservation of solid organic acid intermediates of this class. Always refer to the current product specification sheet and SDS for lot-specific storage instructions.

Can the pivaloyl protecting group on the amine be selectively removed without affecting the carboxylic acid or aryl chloride?

Yes, the pivaloyl (trimethylacetyl) amide is a robust protecting group that can typically be cleaved under acidic hydrolysis (e.g., concentrated HCl or H₂SO₄ in water or an alcohol solvent) or under strongly basic aqueous conditions, conditions that leave the aryl chloride largely intact. However, specific reaction conditions should be optimised empirically, as the carboxylic acid may require protection depending on the synthetic route.

What cross-coupling reactions are compatible with the aryl chloride in this compound?

The aryl chloride at the 2-position of the pyridine ring is compatible with palladium-catalysed reactions such as Suzuki–Miyaura (C–C bond formation with boronic acids), Buchwald–Hartwig amination (C–N bond formation), and Negishi coupling, as well as nickel-catalysed cross-coupling protocols. Appropriate ligand selection is important to achieve good yields with aryl chloride substrates.

How do I request a Certificate of Analysis or Safety Data Sheet for C165490?

Certificates of Analysis (CoA) and Safety Data Sheets (SDS) for C165490 can be requested directly from Aladdin Scientific through the product page on the website or by contacting the customer service or technical support team. Always use the lot number from your shipment to obtain the correct lot-specific CoA.

References

1. March, J. Advanced Organic Chemistry: Reactions, Mechanisms, and Structure. Wiley-Interscience. General reference for nucleophilic aromatic substitution and amide coupling methodology.
2. Clayden, J.; Greeves, N.; Warren, S. Organic Chemistry. Oxford University Press. General reference for protecting group chemistry including pivaloyl amides.
3. Nicolaou, K. C.; Bulger, P. G.; Sarlah, D. Palladium-Catalyzed Cross-Coupling Reactions in Total Synthesis. Angewandte Chemie International Edition, 2005. General reference for cross-coupling methodology applicable to aryl chlorides.
4. Aladdin Scientific Product Page: 2-Chloro-4-pivalamidonicotinic acid, SKU C165490. For current specifications, CoA, and SDS.

Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.