6-Azaspiro[4.5]decane - ≥95% , CAS No.177-17-3

CAS: 177-17-3 Cat. No.: A1067956 Summenformel: C₉H₁₇N Molekulargewicht: 139.240 EG-Nummer: 961-318-1

GRADE & PURITY ≥95%

Storage

Room temperature

Specifications

Spezifikationen & Reinheit

≥95%

Storage

Room temperature

Reinheit

≥95%

Namen und Kennungen

• Kanonisches Lächeln: C1CCC2(C1)CCCCN2
• IUPAC Name: 6-azaspiro[4.5]decane
• InChIKey: FIEQFLLZBBTQHY-UHFFFAOYSA-N
• INCHI: 1S/C9H17N/c1-2-6-9(5-1)7-3-4-8-10-9/h10H,1-8H2
• Molekulargewicht: 139.240

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Klasse Azaspirodecane derivatives

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Klasse: Azaspirodecane derivatives
• Subclass: Not available
• Intermediate Tree Nodes: Not available
• Direct Parent: Azaspirodecane derivatives
• Alternative Parents: Piperidines Dialkylamines Azacyclic compounds Hydrocarbon derivatives
• Molecular Framework: Aliphatic heteropolycyclic compounds
• Substituents: Azaspirodecane - Piperidine - Azacycle - Secondary amine - Secondary aliphatic amine - Organic nitrogen compound - Hydrocarbon derivative - Organonitrogen compound - Amine - Aliphatic heteropolycyclic compound
• Beschreibung: This compound belongs to the class of organic compounds known as azaspirodecane derivatives. These are organic compounds containing a spirodecane moiety with at least one nitrogen atom.
• External Descriptors: Not available

Data sources

1. Djoumbou Feunang Y, Eisner R, Knox C, Chepelev L, Hastings J, Owen G, Fahy E, Steinbeck C, Subramanian S, Bolton E, Greiner R, and Wishart DS. ClassyFire: Automated Chemical Classification With A Comprehensive, Computable Taxonomy. Journal of Cheminformatics, 2016, 8:61.

DOI: 10.1186/s13321-016-0174-y

Chemische und physikalische Eigenschaften

• Molekulargewicht: 139.240 g/mol
• XLogP3: 1.700
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 1
• Rotatable Bond Count: 0
• Exact Mass: 139.136 Da
• Monoisotopic Mass: 139.136 Da
• Topological Polar Surface Area: 12.000 Ų
• Heavy Atom Count: 10
• Formal Charge: 0
• Complexity: 114.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 0
• Undefined Atom Stereocenter Count: 0
• Defined Bond Stereocenter Count: 0
• Undefined Bond Stereocenter Count: 0
• The total count of all stereochemical bonds: 0
• Covalently-Bonded Unit Count: 1

Application Protocols

Not applicable. No assay protocols (e.g., WB, IHC, IF, FC) are associated with this small-molecule building block. For synthetic usage, refer to the Reaction Conditions and Synthetic Utility sections for general guidance.

Biological Roles

Item-specific biological activity data are not provided for this product. As a saturated spirocyclic secondary amine, 6-azaspiro[4.5]decane is primarily a synthetic scaffold used in chemical biology and medicinal chemistry campaigns rather than a molecule with a defined intrinsic biological role.

General/literature context:

• Physicochemical profile: spirocyclic, basic, and conformationally constrained, often used to modulate ligand 3D character (increase Fsp3), basicity, and solubility when incorporated into larger molecules.
• Derivatization: amide, urea, and carbamate derivatives of spirocyclic amines are frequently explored as fragments or substructures in probe and lead design.
• Protonation: at physiological pH, secondary aliphatic amines are largely protonated, which can affect membrane permeability and target engagement depending on the broader pharmacophore.

No claims are made regarding pharmacology or therapeutic effects. For all biological experiments, users should establish safety, off-target profiles, and suitability of derivatives through their own validation.

Buffer Applications

This compound is not a conventional buffering reagent. As a basic amine, it will accept a proton, but it lacks a defined pKa window and salt system optimized for buffering over a narrow pH range.

• If protonated forms are needed (e.g., to improve solubility), prepare the desired salt (e.g., HCl salt) separately; do not rely on it as a buffer component.
• For buffer needs, select established systems (phosphate, HEPES, MOPS, acetate) with defined buffering ranges.

Green Alternatives

While 6-azaspiro[4.5]decane is a building block rather than a solvent, many of its common transformations are traditionally conducted in less sustainable media. Consider the following greener choices (literature/general):

• Replace chlorinated solvents:
  • Use 2-MeTHF or EtOAc instead of DCM/CHCl3 for acylations and workups when reactivity and selectivity permit.
• Favor bio-based ether/esters:
  • 2-MeTHF (from hemicellulose) often matches THF performance and tolerates water; EtOAc is readily biodegradable and has favorable safety.
• Aqueous and alcohol media:
  • Reductive aminations can proceed efficiently in EtOH or i-PrOH; catalytic hydrogenations in EtOH/water blends reduce VOC impact.
• Safer bases and reagents:
  • Swap DIPEA with aqueous NaHCO3 where possible for acylations using activated esters; use T3P (in EtOAc) rather than DCC/HOBt to reduce sensitization waste.
• Energy considerations:
  • Utilize micellar catalysis (aqueous surfactant media) for certain couplings or alkylations at ambient temperature to lower energy input.

Comparison (general):

• Conventional: DCM or DMF for couplings; NaBH3CN for reductive amination.
• Greener: 2-MeTHF/EtOAc for couplings; NaBH(OAc)3 or catalytic H2 (Pd/C) in EtOH for reductive amination.

Trade-offs:

• Solubility of salts in greener solvents may differ; salt switches or co-solvents may be required.
• Reaction rates/selectivity may vary; small-scale scouting is recommended.

Pharmaceutical Uses

No pharmacopoeial/excipient status or formulation role is specified for this item; refer to CoA/Spec Sheet.

General/literature context (non-clinical, research only):

• Synthetic intermediate: commonly used as a scaffold in the preparation of candidate molecules and chemical probes to tune 3D shape and basicity.
• Salt formation: hydrochloride or mesylate salts of derived compounds may aid in crystallinity, stability, and dosage-form development during preclinical research.
• Process considerations: spirocyclic amines can influence solid-state properties (polymorphism) of their derivatives; early salt/polymorph screening is recommended in development workflows.

No therapeutic or clinical claims are implied. All uses are confined to research and development.

Physical Properties

• Item-specific specifications: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/general properties for 6-azaspiro[4.5]decane (for planning only; not product specifications):

  • State at ambient conditions: typically a colorless to pale liquid or low-melting solid depending on purity and salt/base form (literature/general)
  • Basicity: secondary aliphatic amine; conjugate-acid pKa typically ~10–11 for related saturated secondary amines (literature/general)
  • Solubility profile:
    • Miscible with many polar organic solvents (alcohols, acetone, acetonitrile) and chlorinated solvents (DCM, CHCl3) (literature/general)
    • Sparingly soluble to moderate in nonpolar alkanes; readily soluble in dilute mineral acids as ammonium salts (literature/general)
  • Volatility: expected moderate; can distill under reduced pressure if free base (literature/general)
  • LogP/logD: secondary cycloalkyl amines of similar size often show logP ~1–2 as free bases; protonation markedly increases aqueous solubility (literature/general)

Practical notes (general):

• Forms stable crystalline salts (e.g., HCl, p-TsOH) that are often easier to handle and purify than the free base.
• Free base can absorb CO2 and moisture from air; tight closure is recommended.

Always verify lot-specific BP/MP, density, refractive index, water content, and residual solvent limits on the CoA/Spec Sheet for your batch.

Quality and Grades

• Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet.

Guidance on grades for amine building blocks (general):

• Research/technical grade: suitable for discovery chemistry, scaffold synthesis, library generation; may have broader impurity profile.

• 95–98% assay (common for building blocks): typically adequate for SAR work; residual solvents and secondary amines/oligomers should be monitored by GC/HPLC and 1H NMR.

• High-purity/HPLC grade for sensitive applications: low UV background and tight specs for nonvolatile residues and water; helpful for photoredox or catalyst-sensitive transformations.

Stabilizers/inhibitors:

• Secondary aliphatic amines are usually supplied neat without stabilizers. If supplied as a salt (e.g., HCl), stability, handling, and weighing precision often improve.

What to check on the CoA for this item:

• Assay method (GC vs. HPLC), identity confirmation (1H/13C NMR, MS), residual solvents, water (Karl Fischer), and color.
• Salt form vs. free base; if salt, confirm counterion stoichiometry.
• If you intend to use it in catalytic couplings or late-stage functionalization, review residual metal content (if any) and peroxide tests (typically not applicable to saturated amines).

Note: In the absence of a stated grade here, set internal specifications appropriate to your application and qualify the lot with small-scale trials.

Reaction and Applications

6-Azaspiro[4.5]decane serves as a compact, conformationally restricted, saturated amine scaffold widely used in discovery and process chemistry. Its spiro topology imparts three-dimensionality and basicity similar to other secondary aliphatic amines, enabling diverse transformations.

Typical applications (literature/general):

• Amide and carbamate synthesis:
  • Acylation with acid chlorides/anhydrides or coupling of acids via EDCI/HOBt, HATU, T3P to give amides; reaction typically fast at 0–25 C in DCM/DMF with tertiary base (TEA/DIPEA).
  • Chloroformates (e.g., Boc2O) or alkyl chloroformates form carbamates under mild conditions.
• Ureas and thioureas:
  • Reaction with isocyanates/isothiocyanates; useful for introducing hydrogen-bonding donors/acceptors while retaining the spiro core.
• N-alkylation/arylation:
  • Alkyl halides or sulfonates under SN2 conditions (K2CO3/MeCN or DMF) afford tertiary amines.
  • Chan–Lam N-arylation (Cu/O2, arylboronic acids) or Buchwald–Hartwig amination (after protecting as amide/carbamate and subsequent steps) to access arylated derivatives.
• Reductive amination:
  • Condense with aldehydes/ketones followed by NaBH(OAc)3 or catalytic hydrogenation to furnish tertiary amines with good stereocontrol around newly formed centers.
• Salt formation/crystallization:
  • HCl, HBr, or p-toluenesulfonic acid salts improve handling and often enable polymorph screening in development.

Use cases:

• MedChem scaffold hopping to increase Fsp3 and modulate physicochemical properties.
• Ligand design (e.g., chelating to metals after further functionalization) and as a masked diamine upon appropriate functional-group interconversions.

Practical tips:

• Dry the amine (molecular sieves or azeotrope) before moisture-sensitive couplings.
• Avoid nitrosating conditions; exclude strong oxidants during storage and reactions.

Reaction Conditions

The following conditions are general literature guidance for secondary aliphatic amines like 6-azaspiro[4.5]decane and should be optimized experimentally. They are not product specifications.

• Amide formation (acid chloride):
  • Solvent: DCM or 2-MeTHF; Base: DIPEA or TEA (2–3 equiv).
  • Temperature: 0–25 C; Time: 0.5–3 h; Typical outcomes: rapid, high conversion with minimal overacylation.
• Amide formation (carbodiimide or uronium coupling):
  • Solvent: DMF, MeCN, or EtOAc; Reagents: EDCI/HOBt, HATU, or T3P.
  • Base: DIPEA (2–3 equiv); 20–40 C; 1–12 h.
• Carbamate formation (Boc protection):
  • Reagents: Boc2O (1.1–1.5 equiv), catalytic DMAP; Base: NaHCO3 or DIPEA.
  • Solvent: DCM, THF, or MeCN; 0–25 C; 1–4 h.
• Urea/thiourea formation:
  • Reagents: isocyanates/isothiocyanates (1.0–1.2 equiv); Solvent: DCM or toluene.
  • 0–25 C; 0.5–3 h.
• Reductive amination:
  • Step 1: Carbonyl (1.0 equiv) + amine (1.1–1.5 equiv) with AcOH (0.1–0.5 equiv) in MeOH/MeCN.
  • Step 2: NaBH(OAc)3 (2–3 equiv) at rt; 2–16 h. Alternative: H2 (1–5 bar), Pd/C in EtOH at rt–40 C.
• N-Alkylation (SN2):
  • Electrophile: primary alkyl bromides/iodides or tosylates; Base: K2CO3 or Cs2CO3 (2–3 equiv).
  • Solvent: MeCN, acetone, or 2-MeTHF; 25–60 C; 4–24 h; monitor to minimize dialkylation.
• Chan–Lam N-arylation (tertiary derivatives often via protection):
  • Cu(OAc)2 (10–20 mol%), arylboronic acid (1.5–2.0 equiv), pyridine or MeOH as solvent, O2/air, rt–40 C; 6–24 h.

Workup/purification tips:

• Quench acylations with saturated NH4Cl; extract, then form HCl salt for crystallization if needed.
• For volatile free base, distill under reduced pressure or convert to a crystalline salt for isolation.

Safety and Handling

• GHS/CLP item-specific data: Not specified for this item; refer to the SDS for authoritative classification, pictograms, and H/P statements.

General hazards for aliphatic secondary amines (literature/general):

• Can cause skin and eye irritation; vapors may irritate the respiratory tract.
• Flammable/combustible depending on BP and flash point; keep away from ignition sources until specific data are confirmed on SDS.
• Amines are reactive toward acylating agents, strong oxidizers, and nitrosating agents (risk of N-nitrosamine formation in presence of nitrite under acidic conditions).

PPE and engineering controls (general best practice):

• Wear lab coat, nitrile gloves, and splash goggles. Handle in a fume hood to control vapors and odors.
• Avoid breathing mists/vapors; use closed transfers where practical.

Incompatibilities and storage notes:

• Separate from strong oxidizers, acyl halides, acid anhydrides, and strong acids/bases when not in use.
• Amines can attack certain plastics and coatings; verify compatibility.
• Per Product Data: store at room temperature. Keep container tightly closed under inert headspace if possible to minimize CO2 uptake.

First aid (overview; defer to SDS):

• Skin/eye contact: rinse with water for at least 15 minutes; remove contaminated clothing. Seek medical advice.
• Inhalation: move to fresh air; obtain medical attention if symptoms persist.
• Ingestion: rinse mouth; do not induce vomiting; seek medical attention.

Solvent Selection

This product is a spirocyclic secondary amine building block, not a process solvent. Solvent choice should be optimized for its use in reactions, extractions, and purifications.

• Polarity and dissolution (literature/general):
  • Freely soluble in polar organics (MeOH, EtOH, i-PrOH, acetone, MeCN) and chlorinated solvents (DCM, CHCl3).
  • Limited solubility in aliphatic hydrocarbons; solubility improves upon protonation (work in aqueous acids for salt formation/extraction).
• Acid–base handling:
  • Convert to the hydrochloride or p-toluenesulfonate salt for crystallization and improved handling; back-free-base with aqueous alkali as needed.
• When to choose which solvent (general guidance):
  • Acylation/urea/carbamate formation: use DCM, THF, 2-MeTHF, MeCN, or toluene depending on reagent; add a non-nucleophilic base (DIPEA, TEA).
  • Reductive amination: MeOH, EtOH, i-PrOH, or EtOH/THF mixtures; for hydride reagents (NaBH(OAc)3, NaBH3CN), use MeOH/MeCN or DCE.
  • N-alkylation: polar aprotic solvents (DMF, DMSO, MeCN) with suitable bases; consider green alternatives (MeCN, 2-MeTHF) when feasible.
  • Salt formation and workup: EtOAc/hexanes for organic phase; aqueous HCl for protonation and extraction; switch back to free base with NaHCO3/NaOH.

Note: Verify solvent compatibility with your reagents and desired crystallization behavior for the salt form you target.

Storage and Reconstitution

• Storage conditions (item-specific): Room temperature (per Product Data). Store tightly capped in a dry, well-ventilated area away from incompatible materials.
• Container considerations: Use amber glass if long-term storage is anticipated to minimize potential light exposure; include inert headspace (N2/Ar) to reduce CO2/moisture uptake of the free base.
• Form selection:
  • Free base: convenient for reactions but may absorb CO2/H2O. If viscosity/volatility impedes handling, convert to a salt.
  • Salts (e.g., HCl): improved stability and weighability; store desiccated to prevent deliquescence if hygroscopic.
• Reconstitution/preparation:
  • If supplied as a salt and the free base is required, basify an aqueous solution with NaHCO3 or NaOH and extract with an appropriate organic solvent (e.g., DCM or EtOAc). Dry over MgSO4/Na2SO4 and concentrate under reduced pressure.
  • For moisture-sensitive couplings, dry the free base over molecular sieves (3 Å or 4 Å) or by azeotropic removal of water with toluene or MeCN.
• Stability: Avoid strong oxidizers and nitrosating agents. No freeze–thaw concerns for neat liquids/solids; if preparing solutions, make fresh or store short-term at 2–8 C in sealed vials.
• Shipped in: Not specified for this item; refer to CoA/Spec Sheet.
• Research use only (per Product Data).

Structure and Identity

6-Azaspiro[4.5]decane is a saturated spirocyclic secondary amine featuring a single spiro junction that connects two rings.

• Item-specific identifiers (from Product Data):
  • CAS: 177-17-3
  • SKU: A1067956
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet. (Provided string “83419” is not a standard InChIKey.)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Literature/computed identifiers and features (general information):
  • Structural class: spirocyclic aliphatic amine (one five-membered ring and one six-membered ring joined at a quaternary spiro center)
  • Functional groups: secondary amine (basic, nucleophilic), saturated carbocycles
  • Stereochemistry: spiro center is tetrahedral but the molecule is achiral in the absence of substituents that break symmetry (literature/general)
  • Molecular formula (literature/computed): C9H17N
  • Molecular weight (literature/computed): ~139.24 g/mol
• 2D structure in words:
  • A central spiro carbon is shared by two rings. One ring contains a nitrogen atom within a saturated ring system; the other is an all-carbon saturated ring. The nitrogen is secondary (one N–H) and exocyclic substituents are absent; no aromaticity or additional heteroatoms are present.

Note: Confirm all structure identifiers for your lot on the CoA/Spec Sheet if regulatory documentation is required.

Synthetic Utility

Key functional element: a secondary aliphatic amine embedded in a rigid spirocyclic framework (five- and six-membered saturated rings). This imparts nucleophilicity/basicity and conformational control valuable in structure–activity relationship (SAR) studies.

Transformations (literature/general):

• Electrophile capture at nitrogen:
  • Acylation to amides/carbamates; sulfonylation to sulfonamides; phosphorylation (less common) for probe synthesis.
• Reductive amination:
  • Formation of tertiary spirocyclic amines with aldehydes/ketones under NaBH(OAc)3 or catalytic H2.
• N-Alkylation/arylation:
  • SN2 with alkyl halides/tosylates; Chan–Lam N-arylation with aryl boronic acids (Cu catalysts, O2) to furnish anilide-type N-aryl amines.
• Protection/deprotection:
  • Boc, Cbz, or Fmoc protection to direct chemoselectivity; deprotections under standard acidic (Boc) or hydrogenolysis (Cbz) conditions.
• Isocyanate chemistry:
  • Reaction with isocyanates to ureas; with chloroformates to carbamates—useful for linker installation.

Strategic roles:

• Spirocore insertion: replacing linear dialkyl amines with this spiro motif elevates Fsp3 and can reduce planarity-driven liabilities.
• Exit-vector control: N-functionalization sets vector geometry orthogonal to each ring plane, aiding optimization of binding interactions in ligand design.

Handling notes:

• Free base vs. salt: choose form to balance reactivity (free base) and handling/purification (salt). Dry before moisture-sensitive couplings.

Target Specificity

Not applicable. This product is a small-molecule amine building block and is not an antibody, enzyme, or targeted affinity reagent. No target, epitope, clone, or isotype information applies.