5-Benzyl-octahydro-1H-pyrrolo[3,4-c]pyridine: Properties & Uses
5-Benzyl-octahydro-1H-pyrrolo[3,4-c]pyridine: Properties & Uses
5-benzyl-octahydro-1H-pyrrolo[3,4-c]pyridine is a fully saturated bicyclic nitrogen heterocycle featuring fused pyrrolidine and piperidine rings with an N-benzyl protecting group, widely valued in medicinal chemistry and pharmaceutical research as a versatile amine building block.
- IUPAC Name
- 5-benzyl-octahydro-1H-pyrrolo[3,4-c]pyridine
- SKU
- B175293
- Core Scaffold
- Bicyclic pyrrolidine-piperidine (pyrrolo[3,4-c]pyridine), fully saturated
- Functional Groups
- Two secondary/tertiary amine nitrogens; N-benzyl (Cbz-compatible) protecting group
- Primary Application
- Pharmaceutical intermediate and medicinal chemistry building block
- Molecular Framework
- Fused 5-6 bicyclic saturated ring system with two nitrogen atoms
Chemical Structure and Physicochemical Properties
5-Benzyl-octahydro-1H-pyrrolo[3,4-c]pyridine belongs to the pyrrolopiperidine family of bicyclic saturated heterocycles. Its core framework consists of a five-membered pyrrolidine ring fused to a six-membered piperidine ring, sharing two adjacent carbon atoms at the ring junction. This cis- or trans-fused bicyclic skeleton provides a three-dimensional, conformationally constrained scaffold that is highly prized in drug discovery programs targeting enzyme active sites and G-protein-coupled receptors (GPCRs).
The benzyl group on the piperidine nitrogen (N-5 position) serves both as a protecting group and as a handle for selective deprotection via catalytic hydrogenolysis under mild conditions, liberating the free secondary amine for further functionalization. The pyrrolidine nitrogen remains available for acylation, alkylation, or sulfonylation reactions, granting significant synthetic flexibility.
As a fully saturated system, the compound exhibits sp³-rich character, contributing to favorable drug-likeness metrics such as fraction of sp³ carbons (Fsp³) and reduced aromatic ring count—properties increasingly associated with improved aqueous solubility and lower attrition rates in preclinical development. Specific physicochemical data (exact molecular weight, melting point, logP) should be verified against the certificate of analysis supplied with SKU B175293.
Synthesis and Key Synthetic Utility
The pyrrolo[3,4-c]pyridine bicyclic core is commonly accessed through intramolecular cyclization strategies applied to appropriately functionalized piperidine or pyrrolidine precursors. N-Benzylation of the piperidine nitrogen is typically introduced early in the synthetic sequence to differentiate the two amine sites and direct regioselective transformations at the pyrrolidine nitrogen.
As a building block, 5-benzyl-octahydro-1H-pyrrolo[3,4-c]pyridine participates in a broad range of chemical transformations:
• Acylation and sulfonylation of the pyrrolidine NH to install amide or sulfonamide linkers common in drug candidates.
• Reductive amination at the pyrrolidine nitrogen to introduce diversity elements.
• N-Debenzylation by catalytic hydrogenolysis (Pd/C, H₂) to unmask the piperidine NH for further elaboration or coupling reactions.
• Salt formation to improve crystallinity and handling of the free-base compound.
The conformational rigidity introduced by the bicyclic framework often translates to improved selectivity when the scaffold is incorporated into bioactive molecules, because the restricted geometry pre-organizes pharmacophoric elements for target engagement.
Applications in Medicinal Chemistry and Drug Discovery
Saturated bicyclic amine scaffolds such as the pyrrolo[3,4-c]piperidine framework have gained prominence as privileged structures in modern drug discovery. Their three-dimensional shape and dual nitrogen functionalities make them attractive for fragment-based drug design (FBDD), high-throughput screening (HTS) library construction, and lead optimization campaigns.
5-Benzyl-octahydro-1H-pyrrolo[3,4-c]pyridine is particularly useful in the preparation of:
• Protease inhibitors, where the bicyclic amine mimics transition-state geometry.
• Kinase inhibitor intermediates, exploiting the NH as a hinge-binding element after deprotection.
• CNS-active compounds, leveraging the lipophilicity balance and compact three-dimensional profile compatible with blood–brain barrier penetration.
• Diversified libraries via parallel synthesis, where the two orthogonally addressable nitrogens allow rapid generation of structural diversity.
The growing industry preference for Fsp³-enriched scaffolds to combat the high failure rate of flat, aromatic-heavy drug candidates underscores the continued relevance of compounds like 5-benzyl-octahydro-1H-pyrrolo[3,4-c]pyridine in contemporary pharmaceutical research.
Handling, Storage, and Safety Considerations
As with all secondary and tertiary amine-containing compounds, 5-benzyl-octahydro-1H-pyrrolo[3,4-c]pyridine should be handled with appropriate laboratory precautions. Researchers should consult the Safety Data Sheet (SDS) provided with SKU B175293 before use.
General guidelines:
• Handle in a well-ventilated fume hood using nitrile gloves, safety glasses, and a lab coat.
• Avoid inhalation of dust or vapors and contact with skin or eyes.
• Store according to the conditions specified on the product label and SDS—typically in a cool, dry environment away from oxidizing agents and strong acids.
• The compound should be kept in a tightly sealed container under an inert atmosphere (nitrogen or argon) if moisture-sensitive behavior is observed upon receipt.
• Dispose of waste in compliance with local institutional and regulatory guidelines for nitrogen-containing organic compounds.
Specific hazard classifications, GHS pictograms, flash point, and LD₅₀ data must be obtained from the official SDS for B175293; do not rely on generic amine hazard profiles without verification.
Frequently asked questions
What is 5-benzyl-octahydro-1H-pyrrolo[3,4-c]pyridine used for in research?
It is primarily used as a bicyclic amine building block in medicinal chemistry and pharmaceutical research. Its dual nitrogen functionalities and conformationally constrained scaffold make it valuable for synthesizing protease inhibitors, kinase inhibitor intermediates, CNS-active compounds, and diversified screening libraries.
How can the benzyl protecting group be removed from this compound?
The N-benzyl group on the piperidine nitrogen can be selectively removed by catalytic hydrogenolysis using palladium on carbon (Pd/C) under a hydrogen atmosphere at ambient or slightly elevated pressure. This mild deprotection liberates the free secondary piperidine amine for subsequent synthetic transformations.
What makes the pyrrolo[3,4-c]piperidine scaffold advantageous for drug discovery?
The fully saturated bicyclic framework provides a three-dimensional, sp³-rich architecture that improves drug-likeness metrics such as Fsp³ and reduces planarity compared to aromatic heterocycles. This is associated with better aqueous solubility, lower non-specific binding, and potentially reduced attrition in preclinical development, making such scaffolds increasingly preferred in modern lead optimization.
How should SKU B175293 be stored to maintain product integrity?
Store in a cool, dry location in a tightly sealed container, away from oxidizing agents and strong acids. If the compound shows sensitivity to moisture, storage under an inert atmosphere (nitrogen or argon) is recommended. Always refer to the SDS and product label supplied with B175293 for specific storage conditions.
Can 5-benzyl-octahydro-1H-pyrrolo[3,4-c]pyridine be used in parallel synthesis?
Yes. The two orthogonally addressable nitrogen atoms—one protected with a benzyl group and one available as a free amine—allow chemists to selectively functionalize each nitrogen under different conditions. This orthogonal reactivity is well-suited for automated parallel synthesis workflows used in the generation of compound libraries for high-throughput screening.
References
- Lovering, F.; Bikker, J.; Humblet, C. Escape from Flatland: Increasing Saturation as an Approach to Improving Clinical Success. J. Med. Chem. 2009, 52, 6752–6756. doi:10.1021/jm901241e
- Vitaku, E.; Smith, D. T.; Njardarson, J. T. Analysis of the Structural Diversity, Substitution Patterns, and Frequency of Nitrogen Heterocycles among U.S. FDA Approved Pharmaceuticals. J. Med. Chem. 2014, 57, 10257–10274. doi:10.1021/jm501100b
- Aladdin Scientific. Product Information: 5-benzyl-octahydro-1H-pyrrolo[3,4-c]pyridine, SKU B175293. Aladdin Scientific, Shanghai.
Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.
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