2-Bromo-5-cyclopropylpyridine - ≥97% , CAS No.1142197-14-5

CAS: 1142197-14-5 Cat. No.: B189780 Formula: C₈H₈BrN Peso molecolare: 198.06 Numero EC: 856-612-0

QUALITÀ & PUREZZA ≥97%

Synonyms

SY129681 | 1142197-14-5 | MFCD11869551 | Pyridine, 2-bromo-5-cyclopropyl- | EN300-1170000 | 2-bromo-5-cyclopropylpyridine | AKOS015945170 | MB10291 | FT-0750793 | SCHEMBL1655533 | WCHBRVOAPMMHIR-UHFFFAOYSA-N | DTXSID40671758 | A894234 | DS-6949 | J-508360

Storage

Room temperature

Shipped In

Normal

Specifiche

Sinonimi

SY129681 | 1142197-14-5 | MFCD11869551 | Pyridine, 2-bromo-5-cyclopropyl- | EN300-1170000 | 2-bromo-5-cyclopropylpyridine | AKOS015945170 | MB10291 | FT-0750793 | SCHEMBL1655533 | WCHBRVOAPMMHIR-UHFFFAOYSA-N | DTXSID40671758 | A894234 | DS-6949 | J-508360

Specifiche e purezza

≥97%

Condizioni di conservazione di stoccaggio

Room temperature

Spedito in

Normal

Purezza

≥97%

Nomi e identificatori

Pubchem Sid

504770626

Pubchem Sid Url

https://pubchem.ncbi.nlm.nih.gov/substance/504770626

Sorrisi canonici

C1CC1C2=CN=C(C=C2)Br

IUPAC Name

2-bromo-5-cyclopropylpyridine

InChIKey

WCHBRVOAPMMHIR-UHFFFAOYSA-N

INCHI

1S/C8H8BrN/c9-8-4-3-7(5-10-8)6-1-2-6/h3-6H,1-2H2

Isomeri SMILES

C1CC1C2=CN=C(C=C2)Br

Peso molecolare

198.06

Reaxy-Rn

22948611

Reaxys-RN_link_address

https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=22948611&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Classe Pyridines and derivatives
      • Subclass Halopyridines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Classe: Pyridines and derivatives
• Subclass: Halopyridines
• Intermediate Tree Nodes: Not available
• Direct Parent: 2-halopyridines
• Alternative Parents: Aryl bromides Heteroaromatic compounds Azacyclic compounds Organonitrogen compounds Organobromides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: 2-halopyridine - Aryl halide - Aryl bromide - Heteroaromatic compound - Azacycle - Organic nitrogen compound - Hydrocarbon derivative - Organonitrogen compound - Organobromide - Organohalogen compound - Aromatic heteromonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as 2-halopyridines. These are organic compounds containing a pyridine ring substituted at the 2-position by a halogen 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

Proprietà chimiche e fisiche

• Peso molecolare: 198.060 g/mol
• XLogP3: 2.800
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 1
• Rotatable Bond Count: 1
• Exact Mass: 196.984 Da
• Monoisotopic Mass: 196.984 Da
• Topological Polar Surface Area: 12.900 Ų
• Heavy Atom Count: 10
• Formal Charge: 0
• Complexity: 122.000
• 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

No assay-validated biological application protocols are provided for this item.

Synthetic usage examples (general guidance only)

• Stock solution prep: Dissolve to 0.1–1.0 M in dry solvent (e.g., THF, dioxane, toluene, DMF) under inert atmosphere for glovebox or Schlenk-line transfer.
• Cross-coupling setup: Charge aryl bromide (1.0 equiv), boronic acid/amine partner (1.2–1.5 equiv), base (2–3 equiv), Pd catalyst (1–3 mol%) and ligand (if separate). Add solvent to 0.1–0.5 M, heat to 80–100 °C with stirring. Monitor by LC/MS or GC.
• Workup: Dilute with EtOAc, wash with water/brine, dry (Na2SO4), filter, concentrate. Purify by silica chromatography; note brominated starting material elutes slower than coupled products.

These are generic methods for aryl bromides and must be optimized for specific substrates and partners.

Biological Roles

This product is a small heteroaromatic building block rather than a biological macromolecule or metabolite.

• Intrinsic biological role: None established. 2-bromo-5-cyclopropylpyridine is not known as a natural product, metabolite, or enzyme cofactor.
• Research context: The 5-cyclopropyl motif is frequently explored in medicinal chemistry as a compact, lipophilicity-enhancing substituent. The 2-pyridyl position allows modulation of basicity, metal-binding, and H-bond acceptor strength upon derivatization.
• Caution: Any biological activity of downstream derivatives is context-dependent and must be characterized empirically. No medical or clinical claims are made for this reagent.

For biochemists

• The parent compound’s pyridine nitrogen can coordinate to metals in vitro and may act as a weak base; however, this reagent is primarily intended for chemical synthesis, not for probing biological pathways directly.

Buffer Applications

Not typically applicable. 2-Bromo-5-cyclopropylpyridine is an organic synthetic building block and is not used as a buffering agent.

Practical note

• If used in biochemical assays as a small-molecule intermediate or control, prepare stock solutions in DMSO or MeCN and dilute into assay buffers keeping co-solvent content low (e.g., ≤1–2%). Validate solubility and non-specific binding to plastics/proteins.

Green Alternatives

Greener choices focus on solvent and methodology optimizations rather than altering the electrophile itself.

Greener solvent options (literature guidance)

• Replace dioxane/DMF with 2-MeTHF, CPME, or bio-derived alcohol/water mixtures where feasible.
• Employ aqueous micellar catalysis (e.g., TPGS-750-M) for Suzuki or Buchwald–Hartwig couplings to reduce organic solvent use.

Comparison (general)

• Dioxane (traditional) vs 2-MeTHF (greener): similar polarity; 2-MeTHF has renewable sourcing and better safety profile; may require ligand/base re-optimization.
• DMF/NMP (traditional) vs Cyrene/DMAc alternatives: Cyrene can substitute in some couplings; assess solubility and base stability.
• Toluene vs CPME: CPME offers wide liquid range, lower peroxide formation than ethers like THF; flammability still requires controls.

Methodological alternatives

• Direct C–H activation at C2 of 5-cyclopropylpyridine (where feasible) could avoid prefunctionalization with bromine; however, selectivity and catalyst cost are considerations.
• Photoredox/Ni dual catalysis for sp3–sp2 couplings under milder conditions and in water-rich media.

Trade-offs

• Greener solvents may reduce rate/solubility; tweak temperature, base, and ligand loadings.
• Aqueous systems can hydrolyze sensitive boronates or amines; select robust coupling partners (e.g., boronic acids vs pinacol esters) and bases accordingly.

Pharmaceutical Uses

No excipient or formulation roles are specified for this item. It is intended for research and laboratory synthesis only.

Industry context (general)

• Heteroaryl bromides like 2-bromo-5-cyclopropylpyridine are commonly employed as intermediates in the synthesis of drug candidates, enabling rapid diversification via cross-coupling and amination.
• Compliance: If materials made with this building block progress toward GMP manufacturing, resourcing under appropriate quality systems and full impurity profiling would be required. This catalog item is provided for research use only.

Physical Properties

Item-specific numerical specifications (e.g., mp, bp, density) are Not specified for this item; refer to CoA/Spec Sheet.

Literature/estimated physicochemical data for 2-bromo-5-cyclopropylpyridine (for planning only, not product specifications):

• Molecular formula: C8H8BrN (structure-derived)
• Molecular weight: ~198.06 g/mol (calculated)
• Expected phase at ambient conditions: low–moderate volatility organic compound; solid or high-boiling liquid depending on crystal packing (literature expectation for related 2-bromopyridines)
• LogP: anticipated low-to-moderate lipophilicity due to aryl bromide and ring N; cLogP likely in the 1–2 range (computed values in literature for similar analogs). Use your preferred calculator for exact needs.
• Solubility (qualitative, literature): miscible with most polar aprotic organic solvents (THF, DCM, EtOAc, MeCN); low aqueous solubility expected for neutral heteroaromatics.
• UV characteristics: pyridine chromophore; π→π* absorption in UV range. Quantitative cutoff Not specified for this item; refer to CoA/Spec Sheet.
• Refractive index, density, melting/boiling point: Not specified for this item; refer to CoA/Spec Sheet.

Notes

• Values above are general/literature guidance for this structure class and should not be used as acceptance criteria. Always verify with the item’s CoA/SDS before critical use.

Quality and Grades

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

Guidance on typical grades for heteroaryl building blocks (general)

• Research grade: Suitable for most synthetic applications; impurity profile may include trace isomers, residual solvents, or halide byproducts. Confirm by NMR/GC/LC prior to sensitive steps.

• 95–98% purity (common for catalog building blocks): Generally adequate for cross-couplings and library synthesis. For SAR or scale-up, consider additional purification to remove protodehalogenated impurities.

• Low-water/trace-metal considerations: For Pd-catalyzed couplings, trace metal content is typically not critical in the electrophile; catalyst quality dominates. Water content can affect base and boronate speciation; Karl Fischer as needed.
• Stabilizers: Not typically required for aryl bromides. If present, they are usually neutral and removable on workup. For this item, stabilizers are Not specified for this item; refer to CoA/Spec Sheet.

Quality control suggestions

• Identity: 1H/13C NMR (diagnostic pyridine pattern; cyclopropyl multiplets), HRMS (M/M+2 pattern for Br), and LC purity.
• Residual solvents and inorganic halides: Verify via GC-HS and ion chromatography if relevant.
• For chromatographic methods: Note two-isotope bromine pattern (1:1 M/M+2) aids mass-spectral confirmation.

Reaction and Applications

Role: 2-Bromo-5-cyclopropylpyridine is a versatile electrophile and heteroaryl building block. The C–Br bond at C2 enables many cross-coupling and metalation strategies, while the cyclopropyl at C5 offers a compact hydrophobic handle that can modulate sterics/electronics in target molecules.

Representative applications (literature/general)

• Suzuki–Miyaura coupling at C2 to install aryl/alkenyl/alkyl (via B-alkyl reagents) substituents, retaining the C5-cyclopropyl group. N-lone pair and ortho bromide can influence oxidative addition rates; typically reactive with Pd(0)/phosphine systems.
• Buchwald–Hartwig amination to access 2-aminated 5-cyclopropylpyridines; ligands such as BrettPhos/XPhos or BINAP often effective. Base: NaOtBu, Cs2CO3, or K3PO4.
• Negishi/Kumada/Stille couplings for more challenging sp2/sp3 transfer under milder or complementary conditions.
• Metal–halogen exchange (e.g., with nBuLi or iPrMgCl·LiCl) at low temperature to generate 2-pyridyl organometallics for electrophile trapping (formylation, carboxylation, acylation). The ring N can direct metalation and requires control to avoid over-lithiation at C3.
• Directed ortho functionalization: Temporary N-oxide formation can tune reactivity for further substitution on the ring in multistep sequences.
• Radical chemistry: Strained cyclopropyl group can undergo ring-opening under radical or cationic conditions; typically preserved under standard Pd-catalyzed couplings.

Use cases

• Scaffold elaboration in medicinal chemistry, fragment-to-lead programs, and SAR libraries where a 5-cyclopropyl motif improves metabolic stability and lipophilicity balance.

Reaction Conditions

General, literature-style guidance for elaborating 2-bromo-5-cyclopropylpyridine (not product specifications):

Suzuki–Miyaura coupling

• Catalyst: Pd(PPh3)4 (1–3 mol%) or Pd2(dba)3 (1 mol%) + XPhos/SPhos (2–5 mol%).
• Base: K3PO4 (2–3 equiv) or K2CO3; aqueous or solid-assisted.
• Solvent: 1,4-dioxane/H2O (3:1), THF/H2O, or MeCN/H2O.
• Temperature/time: 60–100 °C, 2–16 h. Typical isolated yields: 60–90% (substrate- and partner-dependent; literature range).

Buchwald–Hartwig amination

• Catalyst/ligand: Pd2(dba)3 (1–2 mol%) with BrettPhos or RuPhos (2–4 mol%) or Pd(OAc)2 with BINAP.
• Base: NaOtBu, Cs2CO3, or K3PO4 (2–3 equiv).
• Solvent: Toluene, dioxane, or tBuOH.
• Temperature/time: 80–110 °C, 4–18 h. Typical yields: 55–85% (literature range).

Halogen–metal exchange/electrophile trapping

• Reagent: nBuLi (1.1–1.5 equiv) in anhydrous THF or Et2O at −78 to −40 °C; or iPrMgCl·LiCl (Turbo Grignard) at −40 to 0 °C.
• Quenches: DMF (formylation), CO2 (carboxylation), B(OMe)3 (borylation), electrophilic halogen sources.

Practical tips

• Dry glassware/solvents; exclude air/moisture for organometallic steps.
• The pyridine N can coordinate catalysts; ligand selection and base choice help maintain activity.
• Monitor for protodebromination at high temperature; adjust catalyst/ligand loading and base strength to minimize side reactions.

Safety and Handling

Regulatory/GHS (item-specific)

• Signal word: Not specified for this item; refer to SDS.
• Hazard statements (H-): Not specified for this item; refer to SDS.
• GHS classification/pictograms: Not specified for this item; refer to SDS.

General laboratory safety guidance for aryl bromides/heteroarenes (informational only)

• Hazards: Many halopyridines are irritants and harmful if swallowed or inhaled. Avoid dust/vapor formation and skin/eye contact. Some may be combustible.
• PPE: Safety glasses, lab coat, appropriate chemical-resistant gloves (e.g., nitrile). Use in a chemical fume hood.
• Handling: Keep containers tightly closed. Avoid strong bases at elevated temperature unless intended for reaction (risk of dehydrohalogenation or ring lithiation protocols). Dry material prior to air/moisture-sensitive reactions.
• Incompatibilities: Strong oxidizers (general), very strong bases/nucleophiles may induce undesired substitution/elimination; organolithium reagents can effect metal–halogen exchange (intentional only under controlled conditions).
• First aid (overview; defer to SDS):
  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Skin/eyes: Rinse with water for several minutes; remove contaminated clothing; seek medical attention for persistent irritation.
  • Ingestion: Rinse mouth; do not induce vomiting; obtain medical attention.
• Spills: Absorb with inert material; collect for disposal per local regulations.
• Waste: Dispose as halogenated organic waste per institutional and regulatory requirements.

Always consult the product SDS for authoritative hazard, exposure limits, and response procedures.

Solvent Selection

Compound type: heteroaryl bromide (electrophilic coupling partner) with moderate hydrophobicity and one ring nitrogen.

Solubility/miscibility (general expectations)

• Good solubility in polar aprotic solvents (DMF, DMAc, NMP, DMSO, MeCN) and common organic solvents (THF, dioxane, toluene, EtOAc, DCM). Low solubility in water.

Choosing solvents by application

• Pd-catalyzed cross-coupling (Suzuki/Miyaura): 1,4-dioxane/H2O, THF/H2O, MeCN/H2O, or toluene/EtOH/H2O mixtures. Base-dependent; e.g., K3PO4, K2CO3.
• Buchwald–Hartwig amination: Toluene, dioxane, or tBuOH; for challenging amines, use polar solvents (DMAc, dioxane) with bulky ligands.
• Lithiation/metal–halogen exchange: Anhydrous ethers (THF, Et2O) at low temperature (−78 to −20 °C) under inert atmosphere.
• Nucleophilic aromatic substitution (SNAr): Less favored at C2 vs Br due to pyridine activation; requires strong nucleophiles/bases in DMSO/DMF at elevated temp if attempted.

Quick comparison (guidance)

• THF/dioxane: good for Suzuki and lithium-halogen exchange; peroxide monitoring required for ethers.
• Toluene: higher-temp couplings; good for Buchwald–Hartwig with bulky ligands.
• DMF/DMAc/NMP: dissolve polar substrates; withstand high temps; consider workup challenges and EHS profiles.
• MeCN: medium polarity, easy removal; useful in Suzuki with aqueous base.

Note: Select solvent with base/catalyst compatibility, substrate solubility, and EHS constraints in mind.

Storage and Reconstitution

Storage (from Product Data)

• Storage conditions: Room temperature.
• Shipped in: Normal.

General handling guidance

• Keep container tightly closed in a dry, well-ventilated place. Protect from prolonged light/heat.
• For air/moisture-sensitive transformations (e.g., metal–halogen exchange), pre-dry the material under vacuum and handle under inert gas.

Reconstitution/solution preparation

• Not applicable to biological reconstitution. For synthetic use, prepare stock solutions in dry organic solvents (e.g., THF, toluene, dioxane, DMF, DMSO) at 0.1–1.0 M. Filter if particulates are present.
• Avoid long-term storage of solutions, especially in peroxide-forming ethers. Prepare fresh or store short-term at 2–8 °C under inert atmosphere in amber vials.

Shelf-life considerations

• Item-specific stability data are Not specified for this item; refer to CoA/Spec Sheet. Under typical lab storage, aryl bromides are generally stable for extended periods when sealed and kept dry.

Research use note

• For research use only. Not for human or veterinary use.

Structure and Identity

Product identity (from Product Data)

• SKU: B189780
• Product name: 2-Bromo-5-cyclopropylpyridine
• CAS: 1142197-14-5
• CID: 45788476
• InChIKey: 394623 (as provided)

Structure (literature/structure-derived, non-spec item data)

• Core scaffold: substituted pyridine (six-membered aromatic ring with one ring nitrogen at position 1)
• Substituents and regiochemistry: bromo at C2 (adjacent to ring N) and cyclopropyl at C5 (meta to N)
• Functional groups: aromatic heteroarene (pyridine), aryl bromide (C–Br), cycloalkyl (cyclopropyl)
• Molecular formula (calculated from structure): C8H8BrN (literature/structure-derived)
• Molecular weight (calculated): ~198.06 g/mol (literature/structure-derived)
• Representative SMILES (literature): n1c(Br)ccc(c1)C2CC2
• Stereochemistry: none (achiral as drawn)

2D description in words

• A planar pyridine ring bearing a bromine atom ortho to the ring nitrogen and a small, strained three-membered cyclopropyl ring at the position para to the bromine across the ring (C5). The electron-withdrawing ring nitrogen and the aryl bromide activate C2 for cross-coupling and metal–halogen exchange, while the cyclopropyl group provides a compact hydrophobic appendage that can influence binding and sterics in advanced intermediates.

Synthetic Utility

Key reactive handle: the aryl C–Br at C2.

Transformations (literature/general)

• C–C bond formation: Suzuki–Miyaura (with boronic acids/esters), Negishi (with organozincs), Stille (with stannanes), Kumada (with Grignards under Ni/Pd).
• C–N bond formation: Buchwald–Hartwig amination delivering 2-aminopyridines; ligand choice (BrettPhos/XPhos/BINAP) tunes reactivity and scope.
• C–O/S bond formation: Ullmann-type or Pd-catalyzed etherification/thioetherification to give 2-alkoxy/2-thio derivatives.
• Lithiation/halogen–metal exchange: nBuLi or Turbo Grignard (iPrMgCl·LiCl) at −78 to −20 °C to generate 2-pyridyl organometallics; subsequent trapping with electrophiles (CO2, DMF, acyl chlorides, electrophilic fluorinating reagents).
• Directed strategies: N-oxide formation or temporary protection (e.g., pyridine N-oxide, N-oxide–borane complexes) can alter electronics and regioselectivity for further substitution at C3/C4.

Role of the cyclopropyl group

• Provides a sterically compact, conformationally restricted hydrophobe; typically inert under standard Pd catalysis, yet can participate in radical ring-opening if desired.

Retrosynthetic value

• Serves as a convergent node: electrophile at C2, preinstalled C5 substituent fixed, enabling late-stage diversification of the C2 position without perturbing the cyclopropyl motif.

Target Specificity

Not applicable. This product is a small-molecule chemical building block and does not have antigen/epitope or biological target specificity inherent to antibodies, enzymes, or probe molecules.