cis-3-Methoxycyclobutanamine HCl: Properties & Lab FAQ

cis-3-methoxycyclobutanamine hydrochloride is a stereodefined, saturated cyclobutane-based primary amine salt widely employed as a synthetic building block in medicinal chemistry and drug discovery programs.

Chemical Name

cis-3-methoxycyclobutanamine hydrochloride

SKU / Catalog Number

C173975

Molecular Formula

C5H11NO · HCl

Stereochemistry

cis configuration (relative stereochemistry at C1 and C3 of cyclobutane ring)

Functional Class

Primary aliphatic amine, hydrochloride salt, saturated heterocyclic building block

Typical Applications

Medicinal chemistry synthesis, SAR studies, amide/urea coupling, bioisostere design

Overview and Chemical Identity

cis-3-Methoxycyclobutanamine hydrochloride (Aladdin SKU: C173975) is a small-molecule primary amine supplied as its stable hydrochloride salt. The compound features a four-membered carbocyclic ring bearing an amine group at C1 and a methoxy substituent at C3 in the cis (syn) relative configuration. The cyclobutane scaffold has gained significant attention in modern drug discovery as a bioisostere for gem-dimethyl groups, tert-butyl groups, and phenyl rings, offering improved aqueous solubility and reduced lipophilicity compared with many aromatic analogues.

The hydrochloride salt form enhances solid-state stability, facilitates accurate weighing, and improves shelf life relative to the free base, making it the preferred form for storage and distribution as a research reagent.

Physical and Chemical Properties

As a cyclobutane primary amine hydrochloride, this compound is expected to be a crystalline or amorphous solid at room temperature. The free-base molecular formula is C₅H₁₁NO, giving a free-base molecular weight of approximately 101.15 g/mol; with the HCl counterion the salt molecular weight is approximately 137.61 g/mol. The compound is anticipated to show good solubility in polar protic solvents such as water, methanol, and DMSO, consistent with the ionic nature of the hydrochloride salt and the presence of a hydrogen-bond-accepting methoxy ether.

The cis stereochemical designation refers to the relative orientation of the amine and methoxy groups on the same face of the cyclobutane ring. This defined geometry influences conformational dynamics and binding interactions in target-engagement studies, differentiating it from the trans isomer.

Storage, Handling, and Safety

Storage: Store cis-3-methoxycyclobutanamine hydrochloride in a tightly sealed container under cool, dry conditions, away from direct light, heat, and moisture. A temperature of 2–8 °C or room temperature (as specified on the product Certificate of Analysis) is typically recommended for long-term stability. Keep the container sealed when not in use to prevent hygroscopic uptake.

Handling: As a primary aliphatic amine, this compound may be irritating to skin, eyes, and the respiratory tract. Handle in a well-ventilated laboratory fume hood, wear appropriate personal protective equipment (gloves, safety glasses, lab coat), and avoid inhalation of dust. Consult the product Safety Data Sheet (SDS) for comprehensive hazard and first-aid information before use.

Disposal: Dispose of unused material and containers in accordance with local, national, and institutional regulations for chemical waste.

Research Applications and Synthetic Utility

cis-3-Methoxycyclobutanamine hydrochloride is primarily used as a versatile amine building block in synthetic and medicinal chemistry. Common synthetic transformations include:

• Amide bond formation: Coupling with carboxylic acids or activated esters (e.g., acid chlorides, NHS esters) using standard amide coupling reagents (EDC, HATU, DCC) to install the cyclobutylamine motif into lead compounds.
• Reductive amination: Reaction with aldehydes or ketones in the presence of a reducing agent (e.g., NaBH₃CN, NaBH(OAc)₃) to furnish secondary amines.
• Urea and sulfonamide synthesis: Condensation with isocyanates or sulfonyl chlorides for the preparation of ureas and sulfonamides relevant to kinase inhibitor and GPCR ligand programs.
• Scaffold decoration in SAR campaigns: Incorporation into compound libraries to explore how the cis-methoxy and amine geometry modulates potency, selectivity, and ADMET properties.

The cyclobutane ring is valued for its ability to rigidify a pharmacophore, reduce conformational entropy upon target binding, and replace planar aromatic rings to improve metabolic stability and reduce hERG liability in drug candidates.

Quality, Purity, and Ordering Information

Aladdin Scientific supplies cis-3-methoxycyclobutanamine hydrochloride under catalog number C173975. Each lot is accompanied by a Certificate of Analysis (CoA) documenting identity confirmation (typically by NMR and/or LC-MS), purity (commonly assessed by HPLC), and physical appearance. Researchers are encouraged to request or download the CoA for their specific lot number to verify that the material meets the requirements of their application.

For bulk quantities, custom packaging, or questions regarding specific purity grades and analytical data, contact Aladdin Scientific technical support or your regional sales representative. Product availability, pack sizes, and pricing are listed on the Aladdin Scientific website product page.

Frequently asked questions

What is cis-3-methoxycyclobutanamine hydrochloride used for in research?

It is primarily used as an amine building block in medicinal chemistry for the synthesis of drug candidates and compound libraries. Researchers employ it in amide couplings, reductive aminations, urea formations, and structure–activity relationship (SAR) studies where the stereodefined cyclobutane scaffold provides conformational rigidity and favorable physicochemical properties relative to flat aromatic rings.

What is the difference between the cis and trans isomers of 3-methoxycyclobutanamine?

In the cis isomer, the amine (–NH2) and methoxy (–OCH3) substituents are on the same face of the cyclobutane ring, whereas in the trans isomer they are on opposite faces. This difference in relative stereochemistry alters the three-dimensional shape of the molecule and can significantly influence binding affinity, selectivity, and pharmacokinetic properties when the compound is incorporated into a drug candidate, making the selection of the correct isomer critical in SAR studies.

How should cis-3-methoxycyclobutanamine hydrochloride be stored to maintain stability?

Store the compound in a tightly sealed container under cool, dry, and dark conditions. The hydrochloride salt form is inherently more stable than the free base; however, the material may be hygroscopic, so the container should be resealed promptly after each use. Always refer to the specific storage conditions stated on the product label and Certificate of Analysis for your lot.

How do I convert the hydrochloride salt to the free base for reactions requiring a neutral amine?

The free base can be generated in situ by adding a suitable base—commonly an organic base such as triethylamine (TEA), N,N-diisopropylethylamine (DIPEA/Hünig's base), or an inorganic base such as K2CO3—to the reaction mixture in approximately 1–2 equivalents relative to the HCl salt. Alternatively, the salt can be treated with aqueous base, and the free amine extracted into an organic solvent prior to use. Ensure the chosen base is compatible with other functional groups present in the reaction.

Is a Certificate of Analysis available for this product, and what analytical methods are used?

Yes, a Certificate of Analysis (CoA) is available for each production lot of C173975. The CoA typically documents structural identity confirmation by NMR spectroscopy and/or mass spectrometry (LC-MS), purity assessment by HPLC, and physical description. You may request the CoA for your specific lot number from Aladdin Scientific customer service or download it directly from the product page on the Aladdin Scientific website.

References

1. Stepan, A. F. et al. Application of the cyclobutyl bioisostere in drug discovery. Journal of Medicinal Chemistry, 2012.
2. Mykhailiuk, P. K. Saturated bioisosteres of benzene: where to go next? Organic & Biomolecular Chemistry, 2019.
3. Aladdin Scientific. Product page: cis-3-methoxycyclobutanamine hydrochloride, SKU C173975. Aladdin Scientific website.

Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.