cis-5-Amino-2-Boc-Hexahydro-Cyclopenta[c]pyrrole HCl FAQ
cis-5-Amino-2-Boc-Hexahydro-Cyclopenta[c]pyrrole HCl FAQ
cis-5-amino-2-boc-hexahydro-cyclopenta[c]pyrrole hydrochloride is a Boc-protected bicyclic pyrrolidine scaffold bearing a free primary amine, widely used as a conformationally constrained building block in medicinal chemistry and pharmaceutical synthesis.
- Product SKU
- C174710
- Chemical Class
- Boc-protected bicyclic pyrrolidine hydrochloride salt
- Sterochemistry
- cis configuration at the ring junction
- Key Functional Groups
- tert-butyloxycarbonyl (Boc) protected nitrogen, primary amine (as HCl salt)
- Primary Application
- Conformationally constrained scaffold for drug discovery and medicinal chemistry
- Storage Recommendation
- Store in a cool, dry place away from light and moisture; follow supplier label instructions
What Is cis-5-Amino-2-Boc-Hexahydro-Cyclopenta[c]pyrrole Hydrochloride?
cis-5-amino-2-boc-hexahydro-cyclopenta[c]pyrrole hydrochloride is a bicyclic heterocyclic compound featuring a fused cyclopentane–pyrrolidine (cyclopenta[c]pyrrole) ring system. The nitrogen of the pyrrolidine ring is protected with a tert-butyloxycarbonyl (Boc) group, while the amine at the 5-position is present as a hydrochloride salt, rendering it stable and easy to handle. The cis designation specifies the relative stereochemistry at the ring junction, which constrains the three-dimensional shape of the molecule and distinguishes it from its trans isomer.
This compound belongs to the broader family of conformationally restricted amine building blocks that have gained significant importance in modern drug discovery programs, where rigidity can improve target selectivity, metabolic stability, and pharmacokinetic profiles relative to more flexible acyclic analogues.
Key Chemical Properties and Structure
The hexahydro-cyclopenta[c]pyrrole core is a bicyclic system in which a five-membered carbocyclic ring (cyclopentane) is fused to a five-membered nitrogen-containing ring (pyrrolidine). In the fully saturated (hexahydro) form, the system is sp³-rich, contributing to improved aqueous solubility and three-dimensionality compared with aromatic heterocycles.
The Boc group on the pyrrolidine nitrogen serves as an orthogonal protecting group readily removed under mild acidic conditions (e.g., trifluoroacetic acid or HCl in dioxane) without affecting most other functional groups. The primary amine at C-5 is isolated as its hydrochloride salt to improve stability and shelf life. The cis relative configuration locks the amine and the Boc-nitrogen substituents on the same face of the bicyclic scaffold, providing a defined vector for pharmacophore presentation.
Applications in Medicinal Chemistry and Drug Discovery
cis-5-amino-2-boc-hexahydro-cyclopenta[c]pyrrole hydrochloride is primarily employed as a synthetic building block in fragment-based and lead-optimization drug discovery campaigns. Its two differentially protected nitrogen atoms allow orthogonal elaboration: the Boc-protected pyrrolidine nitrogen can be deprotected and functionalized independently from the primary amine, enabling the construction of complex amine-containing architectures via amide coupling, reductive amination, sulfonamide formation, or urea synthesis.
The rigid bicyclic scaffold is particularly valued for replacing flexible piperazine or piperidine motifs in drug candidates, as the enforced cis geometry can project substituents in well-defined directions, improving binding affinity and selectivity toward biological targets such as kinases, GPCRs, and protease active sites.
The compound is also used in the synthesis of peptidomimetics and macrocyclic precursors, where conformational control is critical to activity.
Handling, Storage, and Safety Considerations
As with most hydrochloride salts of primary amines, cis-5-amino-2-boc-hexahydro-cyclopenta[c]pyrrole hydrochloride should be handled using standard laboratory precautions: wear appropriate personal protective equipment (PPE) including gloves, safety glasses, and a lab coat. Work in a well-ventilated area or fume hood when weighing or dissolving the compound.
For storage, keep the material tightly sealed in its original container in a cool, dry location away from light and moisture. Hygroscopic behavior is common for amine hydrochloride salts, so exposure to air should be minimized. Always consult the product-specific Safety Data Sheet (SDS) supplied by Aladdin Scientific for detailed hazard classifications, first-aid measures, and disposal guidelines before use.
The Boc group is sensitive to strong acids and prolonged exposure to elevated temperatures; avoid storing or dissolving the compound under strongly acidic conditions unless Boc removal is intended.
Ordering and Quality Information
cis-5-amino-2-boc-hexahydro-cyclopenta[c]pyrrole hydrochloride is available from Aladdin Scientific under SKU C174710. Researchers are encouraged to confirm current stock availability, purity specifications, certificate of analysis (CoA), and pricing by contacting Aladdin Scientific directly or visiting the product page on the Aladdin website.
When placing an order, please verify that the required purity grade, pack size, and stereochemical specification (cis) match your experimental requirements. For bulk quantities or custom specifications, contact Aladdin Scientific's sales team for a tailored quotation.
Frequently asked questions
What is the difference between the cis and trans isomers of 5-amino-2-boc-hexahydro-cyclopenta[c]pyrrole hydrochloride?
The cis and trans designations refer to the relative stereochemistry at the ring junction of the bicyclic scaffold. In the cis isomer, the amine substituent and the Boc-nitrogen are oriented on the same face of the ring system, providing a specific three-dimensional geometry that influences how the molecule interacts with biological targets. The trans isomer places these groups on opposite faces, resulting in a distinct spatial arrangement and potentially different binding profiles. In medicinal chemistry applications, the choice of isomer is critical and must match the target's binding site geometry.
How do I remove the Boc protecting group from cis-5-amino-2-boc-hexahydro-cyclopenta[c]pyrrole hydrochloride?
The Boc group is routinely removed under mild acidic conditions. Common methods include treatment with trifluoroacetic acid (TFA) in dichloromethane (typically 20–50% v/v) at room temperature, or with 4 M HCl in dioxane. These conditions cleave the Boc carbamate to release the free amine (as its TFA or HCl salt) and isobutylene gas. The reaction is generally complete within 30–60 minutes at room temperature. The primary amine at C-5, already present as an HCl salt, is unaffected by these deprotection conditions. Always optimize reaction conditions for your specific substrate and downstream synthetic steps.
In what solvents is cis-5-amino-2-boc-hexahydro-cyclopenta[c]pyrrole hydrochloride soluble?
As a hydrochloride salt of a bicyclic amine bearing a Boc group, this compound is generally expected to show good solubility in polar protic solvents such as water and methanol, as well as in polar aprotic solvents such as dimethyl sulfoxide (DMSO) and dimethylformamide (DMF). Solubility in less polar solvents such as dichloromethane may be moderate. Specific solubility data should be confirmed against the product's certificate of analysis or by conducting solubility tests under your experimental conditions, as solubility can vary with concentration, temperature, and pH.
How should I store cis-5-amino-2-boc-hexahydro-cyclopenta[c]pyrrole hydrochloride to maximize shelf life?
Store the compound tightly sealed in its original container in a cool, dry, dark location. Amine hydrochloride salts are often hygroscopic; minimize exposure to atmospheric moisture by using appropriate techniques such as storing under inert gas (nitrogen or argon) or with desiccant. Avoid storage under acidic conditions or elevated temperatures to prevent unintentional Boc deprotection. Always refer to the SDS and CoA provided by Aladdin Scientific for product-specific storage conditions and recommended shelf life.
Can cis-5-amino-2-boc-hexahydro-cyclopenta[c]pyrrole hydrochloride be used directly in amide coupling reactions?
Yes, the primary amine at C-5 (present as the hydrochloride salt) can participate in amide coupling reactions after neutralization of the salt with a suitable base (e.g., triethylamine or diisopropylethylamine, DIPEA) in the reaction mixture. Standard amide coupling reagents such as HATU, EDC/HOBt, or DIC/HOBt can then be employed with a carboxylic acid partner. The Boc group on the pyrrolidine nitrogen remains intact under these mild conditions, allowing selective functionalization of the primary amine while preserving the Boc handle for subsequent synthetic steps.
References
- Greene, T. W.; Wuts, P. G. M. Protective Groups in Organic Synthesis, 4th ed.; Wiley-Interscience: New York, 2007. (General reference for Boc protecting group chemistry.)
- 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. (Conceptual basis for sp³-rich bicyclic scaffolds in drug discovery.) doi:10.1021/jm901241e
- Aladdin Scientific. Product Page: cis-5-amino-2-boc-hexahydro-cyclopenta[c]pyrrole hydrochloride, SKU C174710. (Supplier product information.)
Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.
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