Chemical Structure and Key Properties

(5-Chloro-1H-indol-3-yl)methanamine (SKU C189752) belongs to the indolylmethanamine family, structurally analogous to tryptamine but lacking the ethylene spacer between the indole C-3 position and the amine group. The compound features a bicyclic indole core—a benzene ring fused to a pyrrole ring—with a chlorine atom at the 5-position and a primary aminomethyl (–CH₂NH₂) group directly attached at C-3.

The 5-chloro substituent exerts both electronic and steric influences: it withdraws electron density from the aromatic system via an inductive effect while donating through resonance, modulating the nucleophilicity of the indole nitrogen and the reactivity of the primary amine. The unprotected NH of the indole and the primary amine provide two distinct sites for further functionalization, making this molecule highly versatile for multi-step synthesis.

Physicochemical highlights (verify all values against current CoA):

• Molecular formula: C₉H₉ClN₂
• Molecular weight: 180.63 g/mol
• The primary amine (pKa ~9–10, estimated) renders the compound basic and water-soluble under acidic conditions.
• Storage: typically recommended at 2–8 °C under inert atmosphere to prevent oxidation of the indole moiety.

Synthesis and Functionalization Strategies

(5-Chloro-1H-indol-3-yl)methanamine can be accessed via several synthetic routes commonly used for indole-3-methanamines. A classical approach involves the reduction of the corresponding indole-3-carbaldehyde or indole-3-carbonitrile. Reductive amination of 5-chloro-1H-indole-3-carbaldehyde with ammonia equivalents, followed by reduction, or direct reduction of 5-chloroindole-3-carbonitrile using lithium aluminium hydride (LiAlH₄) or diisobutylaluminium hydride (DIBAL-H) are reported strategies for related substrates.

Once in hand, the primary amine is amenable to a broad range of transformations:

• Acylation and sulfonylation: reaction with acid chlorides, anhydrides, or sulfonyl chlorides to generate amide or sulfonamide derivatives.
• Reductive amination: condensation with aldehydes or ketones followed by reduction to furnish secondary and tertiary amines.
• Urea and carbamate formation: coupling with isocyanates or chloroformates for pharmacophore diversification.
• N-Alkylation: reaction with alkyl halides under basic conditions.
• Indole N-functionalization: protection or alkylation of the pyrrolic NH enables orthogonal chemistry at the two nitrogen centers.

The chlorine at C-5 additionally enables transition-metal-catalyzed cross-coupling reactions (e.g., Suzuki–Miyaura, Buchwald–Hartwig) to introduce aryl, heteroaryl, or amino groups, dramatically expanding the accessible chemical space from this single precursor.

Research and Medicinal Chemistry Applications

Indole-containing amines constitute one of the most privileged scaffolds in drug discovery, reflected in numerous marketed pharmaceuticals targeting serotonin receptors, kinases, and other biological targets. (5-Chloro-1H-indol-3-yl)methanamine occupies an important niche within this chemical space owing to the combination of a reactive primary amine handle and a halogenated indole core.

Key application areas include:

• CNS pharmacology probes: The structural resemblance to tryptamine and serotonin metabolites makes chloroindolylmethylamines useful as starting materials for synthesizing receptor ligands targeting 5-HT receptor subtypes.
• Kinase inhibitor scaffolds: Halogenated indoles are frequently incorporated into ATP-competitive kinase inhibitors; the primary amine enables linker attachment or direct hydrogen-bond donor interactions with hinge-region residues.
• Antimicrobial and antifungal research: Chlorinated indole derivatives have been investigated for activity against bacterial and fungal strains; this compound may serve as a precursor for such studies.
• Fragment-based drug discovery (FBDD): The compact, bifunctional structure (MW ~181 Da, two H-bond donors, one H-bond acceptor) satisfies typical fragment library criteria (MW <300, clogP moderate).
• Fluorescent probe synthesis: Indolylmethylamines can be incorporated into fluorophore architectures for biological imaging applications.

Researchers should conduct independent biological evaluation of any derivatives prepared from this building block; Aladdin Scientific supplies C189752 for research purposes only.

Handling, Storage, and Safety Considerations

As with all primary arylalkylamines, (5-Chloro-1H-indol-3-yl)methanamine should be handled with appropriate laboratory precautions. Users must consult the current Safety Data Sheet (SDS) provided with the product before use.

General handling guidelines:

• Use personal protective equipment (PPE): nitrile gloves, laboratory coat, and safety goggles.
• Handle in a well-ventilated fume hood to avoid inhalation of dust or vapors.
• The indole ring is susceptible to oxidative degradation; minimize exposure to air, light, and moisture during weighing and transfer operations.

Storage recommendations (confirm with product label and CoA):

• Store at 2–8 °C in a tightly sealed container under an inert atmosphere (nitrogen or argon).
• Keep away from strong oxidizers, strong acids, and strong bases.
• Desiccant packaging is advisable to prevent moisture uptake.

Disposal: Dispose of according to local, regional, and national regulations for chemical waste. Do not discharge into drains or the environment.

All safety information is provided for general guidance only; the official SDS supersedes any information presented here.