1H-Indole-1-carboxylic acid, 3-[2-(dimethylamino)ethyl]-, 1,1-dimethylethyl ester

1H-Indole-1-carboxylic acid, 3-[2-(dimethylamino)ethyl]-, 1,1-dimethylethyl ester (CAS: 2210243-51-7) is a versatile Boc-protected indole building block widely used in medicinal chemistry, organic synthesis, and drug discovery research. Featuring a unique molecular architecture that combines a tert-butyl carbamate (Boc)-protected indole nitrogen with a dimethylaminoethyl side chain at the C-3 position, it offers orthogonal protection strategies, tunable physicochemical properties, and diverse synthetic transformability compared to unprotected indole analogues. Its well-defined protecting group strategy, reliable synthetic accessibility, and established utility as a key intermediate for constructing drug-like scaffolds make it a dependable standard for medicinal chemistry, chemical biology, and pharmaceutical research. Its primary applications are outlined below:

1. Medicinal Chemistry & Drug Discovery

Kinase Inhibitor Development
This compound serves as a valuable precursor for the synthesis of indole-based kinase inhibitors targeting oncogenic pathways (e.g., EGFR, VEGFR, BTK, and CDK families). The Boc-protected indole nitrogen allows for selective deprotection and subsequent functionalization to introduce diverse pharmacophores, while the dimethylaminoethyl side chain enhances solubility and provides a handle for salt formation or further derivatization. Medicinal chemists employ this scaffold in SAR studies to optimize potency, selectivity, and pharmacokinetic properties against various cancer cell lines.

GPCR Modulator & CNS Agent Design
The indole scaffold is privileged in GPCR-targeted drug discovery, particularly for serotonin (5-HT), dopamine, and melatonin receptors. This compound is utilized as a key intermediate for synthesizing receptor agonists, antagonists, and allosteric modulators. Researchers leverage the Boc group for orthogonal protection during multi-step synthesis, enabling rapid exploration of substitution patterns at the indole nitrogen while maintaining the dimethylaminoethyl moiety for receptor recognition and blood-brain barrier penetration.

Antimicrobial & Antiviral Agent Synthesis
Indole derivatives bearing basic side chains have demonstrated activity against bacterial, fungal, and viral pathogens. This building block is employed in the synthesis of novel antimicrobial agents targeting DNA gyrase, topoisomerase IV, and HIV integrase. The Boc protection facilitates incorporation of the indole core into complex molecular architectures without interference from the N-H moiety during coupling reactions.

Anti-inflammatory & Immunomodulatory Compounds
The compound is used in the construction of indole-based anti-inflammatory agents, including COX-2 inhibitors, 5-LOX inhibitors, and nuclear receptor modulators (e.g., RORγt, AhR). Its dimethylaminoethyl group enhances aqueous solubility and can be further transformed into quaternary ammonium salts or N-oxides for improved bioavailability.

2. Organic Synthesis & Chemical Methodology

Boc Protection & Selective Deprotection
The tert-butyl carbamate group provides robust protection for the indole nitrogen during synthetic transformations (e.g., lithiation, alkylation, acylation, cross-coupling reactions). Researchers utilize this compound to demonstrate chemoselective deprotection under acidic conditions (e.g., TFA, HCl/dioxane) while preserving the dimethylaminoethyl side chain and other acid-labile functionalities. It serves as a model substrate in methodology development for N-protection/deprotection strategies.

Functionalization of the Indole C-2 & C-5 Positions
While the C-3 position bears the dimethylaminoethyl substituent, the remaining positions (C-2, C-4, C-5, C-6, C-7) are available for further functionalization via electrophilic aromatic substitution, palladium-catalyzed cross-couplings (Suzuki, Buchwald-Hartwig, Heck), or directed metalation. The Boc group directs electrophiles to specific positions, enabling controlled, regioselective derivatization.

Multicomponent & Cascade Reaction Scaffold
The compound serves as a substrate in multicomponent reactions (e.g., Mannich, Ugi, Pictet-Spengler) to rapidly generate diverse indole-based libraries. Its compatibility with microwave-assisted synthesis and flow chemistry enhances throughput in library generation for high-throughput screening campaigns.

Solid-Phase Peptide & Combinatorial Synthesis
As a Boc-protected indole derivative, it is amenable to solid-phase synthesis protocols, enabling the preparation of indole-containing peptides, peptidomimetics, and macrocycles. This application is particularly valuable in the discovery of constrained cyclic peptides with enhanced metabolic stability and target affinity.

3. Chemical Biology & Biochemical Probe Development

Fluorescent & Bioorthogonal Probe Synthesis
The indole core can be converted into fluorescent analogues (e.g., through extension of the π-system or incorporation of push-pull chromophores) or derivatized with clickable handles (azides, alkynes) for bioorthogonal labeling. Researchers use this building block to prepare chemical probes for imaging, target engagement studies, and cellular uptake tracking.

Affinity-Based Protein Profiling (AfBPP)
Derivatives of this compound bearing photoreactive groups (e.g., diazirine, benzophenone) or electrophilic warheads are synthesized to create activity-based probes for target identification. The Boc group allows late-stage diversification, ensuring that the photoaffinity label and reporter tags can be introduced without compromising the indole scaffold.

Metabolic Stability & Solubility Enhancement Studies
The dimethylaminoethyl side chain is employed as a solubilizing group in drug candidates. Medicinal chemists use this scaffold to systematically study the impact of N-alkylation and N-oxidation on metabolic stability, plasma protein binding, and oral bioavailability, guiding the optimization of lead compounds.

4. Material Science & Agrochemical Research

Organic Semiconductors & Optoelectronic Materials
Indole-based derivatives are explored as building blocks for organic field-effect transistors (OFETs), organic photovoltaics (OPVs), and light-emitting diodes (OLEDs). The Boc-protected intermediate enables controlled deposition and post-processing deprotection to tune electronic properties, surface wettability, and film morphology.

Synthesis of Indole Alkaloid Analogues
This compound is employed as a synthetic precursor to natural product-inspired libraries, particularly analogues of tryptamine, serotonin, and other indole alkaloids. Researchers utilize it in total synthesis campaigns and late-stage functionalization studies.

Agrochemical Lead Discovery
Indole-containing compounds are investigated for herbicidal, fungicidal, and insecticidal activities. The building block is used to prepare libraries of substituted indoles for screening against agricultural pests and pathogens, enabling the identification of novel crop protection leads with favorable environmental profiles.

5. Pharmacological Profiling & ADME Studies

Physicochemical Property Assessment
The compound serves as a model substrate for evaluating the impact of basic side chains on physicochemical properties, including pKa, logP/logD, and kinetic solubility. Researchers use it to benchmark computational predictions and to develop structure-property relationship models.

Metabolic Pathway Elucidation
In vitro metabolism studies employing liver microsomes, S9 fractions, or hepatocytes utilize this compound to investigate the metabolic fate of Boc-protected indole derivatives. Key metabolic pathways include Boc deprotection (to expose the indole N-H), oxidative N-dealkylation of the dimethylaminoethyl group, and aromatic hydroxylation. Identification of metabolites informs medicinal chemistry efforts to block metabolic soft spots.

Drug-Drug Interaction & CYP Inhibition Studies
The compound and its derivatives are evaluated for their potential to inhibit or induce cytochrome P450 enzymes (CYP1A2, CYP2D6, CYP3A4), providing data for early-stage drug-drug interaction risk assessment.

6. Handling & Storage

Storage Conditions
Store as supplied in tightly sealed, amber glass containers under inert atmosphere (N₂ or Ar) at 2–8 °C, protected from light, moisture, and strong oxidizing agents. The compound is stable under recommended storage conditions for extended periods. Desiccated storage is advised to prevent hydrolysis of the carbamate bond.

Solubility & Preparation
Soluble in common organic solvents including dimethyl sulfoxide (DMSO), dichloromethane (DCM), chloroform, ethyl acetate, tetrahydrofuran (THF), and methanol; poorly soluble in water. For biological assays, prepare stock solutions in DMSO (10–100 mM) and dilute with aqueous buffers (final DMSO concentration ≤0.1–1% v/v). The compound may form salts with acids, enhancing aqueous solubility.

Chemical Stability Considerations
The Boc group is susceptible to cleavage under acidic conditions (e.g., TFA, HCl, formic acid); neutral or slightly basic conditions (pH 7–9) are recommended for long-term storage in solution. The tertiary amine may react with strong electrophiles or oxidizing agents; avoid prolonged exposure to air to prevent N-oxide formation.

Intended Use
This product is intended for research, development, and laboratory use only. It is not for human therapeutic use, clinical diagnostics, veterinary treatment, or food applications. Standard laboratory safety practices (chemical fume hood, impermeable gloves, safety goggles) should be followed during handling. Avoid inhalation of dust and contact with skin or eyes.

Summary

The value of 1H-Indole-1-carboxylic acid, 3-[2-(dimethylamino)ethyl]-, 1,1-dimethylethyl ester (CAS: 2210243-51-7) lies in its strategic combination of a Boc-protected indole core with a synthetically versatile dimethylaminoethyl side chain, enabling diverse applications across medicinal chemistry, organic synthesis, and chemical biology. Its applications span from kinase inhibitor and GPCR modulator development (as a key intermediate) to organic synthesis (as a substrate for orthogonal functionalization), from chemical probe design (as a precursor for fluorescent and photoaffinity labels) to agrochemical lead discovery. The well-defined protecting group strategy, reliable synthetic accessibility, and proven utility as a versatile building block for constructing complex drug-like molecules make this compound a dependable standard for pharmaceutical research, chemical synthesis, and drug discovery worldwide.

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