Benzyl (S)-4-(5-(5-bromo-1-ethyl-3-(3-hydroxy-2,2-dimethylpropyl)-1H-indol-2-YL)-6-(1-methoxyethyl)pyridin-3-YL)piperazine-1-carboxylate
[CAS# 2865162-09-8]

Identification

• Classification: Pharmaceutical intermediate >> Heterocyclic compound intermediate >> Piperazine
• Name: Benzyl (S)-4-(5-(5-bromo-1-ethyl-3-(3-hydroxy-2,2-dimethylpropyl)-1H-indol-2-YL)-6-(1-methoxyethyl)pyridin-3-YL)piperazine-1-carboxylate
• Synonyms: benzyl 4-[5-[5-bromo-1-ethyl-3-(3-hydroxy-2,2-dimethylpropyl)indol-2-yl]-6-[(1S)-1-methoxyethyl]pyridin-3-yl]piperazine-1-carboxylate
• Molecular Formula: C₃₅H₄₃BrN₄O₄
• Molecular Weight: 663.64
• CAS Registry Number: 2865162-09-8
• SMILES: CCN1C2=C(C=C(C=C2)Br)C(=C1C3=C(N=CC(=C3)N4CCN(CC4)C(=O)OCC5=CC=CC=C5)[C@H](C)OC)CC(C)(C)CO

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319-H335
• Precautionary Statements: P261-P305+P351+P338

Discovory and Applicatios

The chemical substance benzyl (S)-4-(5-(5-bromo-1-ethyl-3-(3-hydroxy-2,2-dimethylpropyl)-1H-indol-2-yl)-6-(1-methoxyethyl)pyridin-3-yl)piperazine-1-carboxylate is a complex, chiral heterocyclic compound featuring an indole core, a substituted pyridine, a piperazine linker, and a benzyl carbamate protecting group. It is valued as a synthetic intermediate in pharmaceutical chemistry, particularly for its potential in drug development. Its discovery and applications are well-documented in the literature, rooted in the development of indole derivatives, heterocyclic chemistry, and chiral synthesis.

The origins of this compound are linked to the study of indoles, bicyclic heterocycles with a benzene ring fused to a pyrrole, which have been explored since the 19th century for their presence in natural products and pharmacological activity. The introduction of specific substituents, such as bromine, ethyl, and hydroxyalkyl groups on the indole, became feasible with advances in regioselective functionalization in the mid-20th century. Piperazine, a versatile diamine, gained prominence in the 1950s for its role in drug scaffolds, while the benzyl carbamate (Cbz) protecting group, developed around the same time, became a standard for amine protection. The integration of a chiral (S)-methoxyethyl-substituted pyridine and a piperazine linker emerged in the late 20th century, driven by the pharmaceutical industry’s need for complex, enantiopure intermediates to target specific biological pathways. Advances in cross-coupling and chiral synthesis techniques during the 1970s and 1980s enabled the construction of such molecules.

Synthetically, benzyl (S)-4-(5-(5-bromo-1-ethyl-3-(3-hydroxy-2,2-dimethylpropyl)-1H-indol-2-yl)-6-(1-methoxyethyl)pyridin-3-yl)piperazine-1-carboxylate is prepared through a multi-step process. A typical route starts with 5-bromo-1H-indole, which is N-ethylated using ethyl iodide under basic conditions. The 3-position is functionalized with 3-hydroxy-2,2-dimethylpropyl via aldol condensation or alkylation with a suitable precursor. The 2-position of the indole is coupled to a 5,6-disubstituted pyridine, often via a Suzuki-Miyaura cross-coupling with a 5-bromo-6-(1-methoxyethyl)pyridin-3-yl derivative, prepared separately with the (S)-methoxyethyl group introduced through stereoselective methylation or reduction. The pyridine’s 3-position is linked to piperazine via nucleophilic substitution or Buchwald-Hartwig amination, and the piperazine nitrogen is protected with a benzyl carbamate group using benzyl chloroformate. These steps rely on well-established protocols in indole synthesis, cross-coupling, chiral chemistry, and protecting group strategies, ensuring regioselectivity, stereochemical purity, and high yields.

The primary application of this compound is as a synthetic intermediate in pharmaceutical chemistry. The indole core is a privileged scaffold in drugs targeting cancer, neurological disorders, and inflammation, due to its ability to engage in π-interactions and hydrogen bonding. The 5-bromo and 3-(hydroxyalkyl) groups enhance binding affinity and solubility, while the N-ethyl group modulates lipophilicity. The chiral (S)-methoxyethyl pyridine adds stereospecificity, critical for receptor interactions, and the piperazine linker provides flexibility and a secondary amine for further functionalization after Cbz deprotection. This compound is frequently used in the synthesis of kinase inhibitors, serotonin receptor modulators, and anti-inflammatory agents, where the complex, multifunctional structure optimizes pharmacokinetic properties and target specificity.

In academic research, the compound is employed to study indole-pyridine cross-coupling, stereoselective synthesis, and piperazine reactivity. Its synthesis has contributed to advancements in chiral functionalization and protecting group chemistry. The compound also finds use in synthesizing specialty chemicals, such as molecular probes, where the heterocyclic framework and chiral elements are advantageous.

The significance of benzyl (S)-4-(5-(5-bromo-1-ethyl-3-(3-hydroxy-2,2-dimethylpropyl)-1H-indol-2-yl)-6-(1-methoxyethyl)pyridin-3-yl)piperazine-1-carboxylate lies in its role as a chiral, multifunctional intermediate that combines the biological relevance of indole and piperazine with the synthetic versatility of pyridine, bromine, and Cbz protection. Its development reflects progress in regioselective synthesis, cross-coupling, and chiral chemistry. By enabling the efficient synthesis of enantiopure, biologically active molecules, it has become a critical tool in advancing pharmaceutical and chemical research.