3-Bromo-4-methyl-1,8-naphthyridine - ≥95% , CAS No.893566-54-6

CAS: 893566-54-6 Cat. No.: B972704 Summenformel: C9H7BrN2 PubChem CID: 68528911

GRADE & PURITY ≥95%

Storage

Room temperature

Specifications

Spezifikationen & Reinheit

≥95%

Storage

Room temperature

Reinheit

≥95%

Namen und Kennungen

Kanonisches Lächeln

CC1=C2C=CC=NC2=NC=C1Br

IUPAC Name

3-bromo-4-methyl-1,8-naphthyridine

InChIKey

DOZALCOKNIMKNG-UHFFFAOYSA-N

INCHI

1S/C9H7BrN2/c1-6-7-3-2-4-11-9(7)12-5-8(6)10/h2-5H,1H3

Isomere SMILES

CC1=C2C=CC=NC2=NC=C1Br

PubChem CID

68528911

Chemische und physikalische Eigenschaften

• Molekulargewicht: 223.070 g/mol
• XLogP3: 2.500
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 0
• Exact Mass: 221.979 Da
• Monoisotopic Mass: 221.979 Da
• Topological Polar Surface Area: 25.800 Ų
• Heavy Atom Count: 12
• Formal Charge: 0
• Complexity: 163.000
• 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 protocols are validated for this item. It is supplied as a research chemical building block. For general use:

• Prepare analytical samples in deuterated DMSO or CDCl3 for NMR; add a drop of TFA if peaks are broadened by basic nitrogens
• For biological screening, prepare sterile-filtered DMSO stock (e.g., 10–50 mM), store aliquots at −20 °C protected from light; verify solubility upon dilution into assay buffers All procedures should be adapted to your laboratory’s SOPs and safety practices.

Biological Roles

• Item-specific biological data: Not specified for this item; no biological assays are provided. For research use only.
• General context (literature, not product-specific):
  • 1,8‑Naphthyridines are bioisosteric to quinolines/pyridopyrimidines and frequently appear as heteroaromatic cores in discovery chemistry for enzyme and receptor ligands
  • The diazine nitrogens can act as hydrogen‑bond acceptors (e.g., hinge-binding motifs in kinase/ATP‑competitive scaffolds) and as metal‑binding sites in metalloenzyme probe design
  • Substitution at C3 enables projection into hydrophobic or polar subpockets; the C4‑methyl influences electronics and lipophilicity and can be leveraged for benzylic functionalization
• ADME-relevant features (general):
  • Moderate aromaticity and a single halogen often yield increased metabolic stability; weak basicity tends to reduce salt formation and aqueous solubility
  • Polar surface area is driven chiefly by ring nitrogens; further functionalization is typically required for solubility tuning No clinical or therapeutic claims are made; any biological use should be confined to non-clinical laboratory research.

Buffer Applications

This compound is a neutral/weakly basic heteroaromatic building block and is not used as a buffering agent. It lacks the acid/base conjugate pair characteristics and high aqueous solubility typical of laboratory buffers. For aqueous work, prepare DMSO or DMF stock solutions and dilute into compatible buffered media as needed, ensuring final organic content and precipitation risk are acceptable.

Green Alternatives

When developing routes that use 3‑Bromo‑4‑methyl‑1,8‑naphthyridine, greener choices often relate to solvent, base, and coupling partner selection.

• Prefer greener solvents where feasible:
  • Replace DMF/NMP with MeTHF, CPME, propylene carbonate, or water/ethanol cosolvent systems when compatible with the catalyst/boron reagent
  • Use 2‑MeTHF or CPME for Suzuki reactions in place of dioxane/THF; consider micellar catalysis (TPGS‑750‑M in water) for certain couplings
• Base and reagent considerations:
  • Swap inorganic bases with high EHS footprints (Cs2CO3) for K2CO3 or K3PO4; avoid stoichiometric tin reagents (Stille) in favor of boron or zinc chemistry
• Energy and catalyst loading:
  • Employ ligand-optimized Pd catalysts that allow lower temperatures and ppm‑level loadings; explore nickel catalysis for aryl bromides when applicable

Comparison (general, not product-specific):

• Conventional vs greener conditions for Suzuki couplings:
  • Conventional: Pd(PPh3)4 (2–5 mol%), dioxane/H2O, 80–100 °C
  • Greener: Pd-precatalyst with dialkylbiaryl ligand (0.1–0.5 mol%), 2‑MeTHF/H2O or aqueous micelles, 40–70 °C

Tradeoffs:

• Greener media may reduce substrate/catalyst solubility or rate; ligand and base tuning is often needed.
• Water‑rich systems can hydrolyze boronate esters—select robust MIDA/Neopentyl boronates or adjust pH.

Pharmaceutical Uses

• Item-specific pharmacopeial status: Not specified for this item; not listed as an excipient or compendial standard.
• Research/formulation context (general):
  • Employed as a heteroaromatic building block in medicinal chemistry for structure–activity relationship (SAR) exploration
  • Can be formulated into DMSO stock solutions for in vitro screening; for in vivo research formulations (non-clinical), additional solubilizers/co‑solvents may be required due to low aqueous solubility
  • No role as an approved active pharmaceutical ingredient or excipient is implied
• Process chemistry notes (general):
  • For scale‑up, attention to Pd removal after cross‑coupling may be necessary (activated carbon, metal scavengers)
  • Crystallization from ethyl acetate/hexanes or MeCN/ether systems is commonly effective for related heteroarenes; confirm polymorph/solvate forms by PXRD if relevant All uses are limited to research and laboratory development; not for human or veterinary use.

Physical Properties

• Item-specific specs: Not specified for this item; refer to CoA/Spec Sheet.
• Literature/general expectations for this heteroaryl bromide (informational, not product specifications):
  • Phase at ambient: typically a crystalline solid for comparable naphthyridine aryl bromides
  • Approximate molecular weight: ~223.02 g/mol (for C9H7BrN2; derived)
  • Solubility profile (general):
    • Good solubility in polar aprotic organics (DMSO, DMF, NMP) and chlorinated solvents (DCM, chloroform)
    • Moderate solubility in ethyl acetate, acetonitrile; low in hexanes
    • Very low aqueous solubility at neutral pH; increased in acidic media is limited since ring nitrogens are only weakly basic
  • Acid–base behavior (literature): ring nitrogens are pyridine-like (pKb in the range of substituted diazines); overall weakly basic character
  • LogP/logD: expected moderate lipophilicity for a mono-brominated bicyclic diazine bearing one methyl; exact values not determined here
  • UV characteristics: conjugated heteroaromatic; absorbs in the near‑UV; exact λmax not determined here
  • Melting/boiling points, density, refractive index: Not specified for this item; consult literature or CoA/SDS if needed. Notes: All values above (where given) are general/literature expectations for the scaffold and should not be treated as this item’s specification.

Quality and Grades

• Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet.
• What “research grade” typically implies (general):
  • Suitable for synthetic and discovery chemistry; may not include low‑UV or trace‑metal specifications required for analytical/HPLC or catalytic applications unless stated on the CoA
  • Actual assay, residual solvents, and impurity profile should be confirmed on the supplied Certificate of Analysis for each lot
• Stabilizers/inhibitors: None indicated for this item. If present on a specific lot, the CoA/Spec Sheet will note it and you should consider its impact on coupling or metal‑catalyzed chemistry.
• Trace metals/UV cutoff/water/peroxide limits: Not specified for this item; refer to CoA/Spec Sheet.
• Practical guidance for this scaffold:
  • For palladium‑catalyzed couplings, trace metal background in the substrate is usually not limiting; instead, ligand/catalyst choice dominates outcome for heteroaryl bromides
  • If low background absorbance is needed (photophysical work), request a CoA with UV‑Vis data
  • For medicinal chemistry, confirm identity and purity by 1H/13C NMR, HRMS, and HPLC prior to SAR use; heteroaryl regioisomers can occasionally contaminate commercial lots—verify NMR diagnostic signals for C3/C4 substitution.

Reaction and Applications

As a 3‑brominated 1,8‑naphthyridine, this compound is a versatile electrophile for heteroaryl cross‑couplings and late‑stage diversification.

• Cross‑coupling platforms (literature/general):
  • Suzuki–Miyaura C–C: couples with aryl/heteroaryl/alkenyl boronic acids/esters to access 3‑substituted 4‑methyl‑1,8‑naphthyridines
  • Buchwald–Hartwig C–N: amination with (hetero)arylamines, anilines, cyclic amines; dialkylbiaryl phosphines (XPhos, BrettPhos) often effective on heteroaryl bromides
  • Sonogashira: installation of alkynes under Pd/Cu or copper‑free conditions; useful for annulation or further cycloadditions
  • Negishi/Kumada/Stille: organozinc/magnesium/stannane partners for challenging couplings; consider compatibility with ring nitrogens
• Directed metalation/functionalization:
  • The 1,8‑diazine motif can direct lithiation or magnesiation adjacent to ring nitrogens under strong base at low temperature, enabling halogen–metal exchange or further elaboration (requires careful control to avoid ring reduction)
• Electrophilic modifications at C4‑methyl:
  • Benzylic oxidation to the corresponding aldehyde/acid (e.g., SeO2, MnO2, or metal‑catalyzed oxidations)
  • Benzylic bromination (NBS) enabling subsequent substitution or cross‑coupling via benzylic intermediates
• Heteroarene N‑oxide chemistry:
  • N‑oxidation (mCPBA, peracids) can tune electronics and direct regioselective substitution; subsequent deoxygenation (PCl3, Zn/AcOH) restores the parent ring
• Applications:
  • Scaffold for ligand discovery, kinase hinge binders, and fluorescent probe development (due to diazine electronics). Research use only.

Reaction Conditions

General literature guidance for heteroaryl bromide couplings (adapt as needed; not product specifications):

• Suzuki–Miyaura (C3–Csp2):
  • Catalyst: Pd2(dba)3 (1–2 mol%) + SPhos/XPhos (2–4 mol%) or precatalysts; Base: K3PO4 or K2CO3 (2–3 equiv)
  • Solvent: 1,4‑dioxane/H2O (4:1) or 2‑MeTHF/H2O; Temp: 60–90 °C; Time: 2–16 h
  • Notes: Heteroaryl boronates (MIDA/NEt) may give cleaner reactions; aqueous content aids transmetalation
• Buchwald–Hartwig amination (C3–N):
  • Catalyst: Pd2(dba)3 (1 mol%) + BrettPhos/XPhos (2–3 mol%); Base: NaOtBu or K3PO4
  • Solvent: toluene, tBuOH, or dioxane; Temp: 80–110 °C; Time: 4–18 h
  • Notes: For aliphatic amines, dialkylbiaryl phosphines excel; for anilines, biaryl/biaryl‑BrettPhos ligands often superior
• Sonogashira (C3–C≡C):
  • Catalyst: Pd(PPh3)2Cl2 (1–2 mol%) + CuI (5–10 mol%); Base: Et3N or iPr2NEt
  • Solvent: THF, MeCN, or DMAc; Temp: rt–70 °C; Time: 2–12 h; Copper‑free variants reduce Glaser coupling
• Halogen–metal exchange:
  • n‑BuLi at −78 to −40 °C in THF; subsequent quench with electrophiles. Competes with directed metalation near ring nitrogens—requires careful control
• Benzylic functionalization (C4‑methyl):
  • NBS, AIBN, CCl4 or photochemical bromination (0–25 °C); oxidations with MnO2 or SeO2 to aldehyde/acid Typical isolated yields for optimized couplings: 60–90% (substrate/partner dependent). Conduct small‑scale scouting to tune ligand/base/solvent.

Safety and Handling

• Item-specific GHS/SDS data: Not specified for this item; refer to the SDS for authoritative classification, pictograms, H‑statements, and first‑aid.
• General hazards for heteroaryl bromides (informational guidance):
  • May cause skin/eye irritation and respiratory irritation upon dust inhalation; avoid generating dust/aerosols
  • Harmful if swallowed; toxicological profile not fully characterized—handle as potentially harmful
  • Aquatic hazard is possible for halogenated aromatics; avoid environmental release
• PPE and engineering controls:
  • Wear lab coat, nitrile gloves, safety glasses; handle in a chemical fume hood
  • Use weighing boats and antistatic measures to minimize airborne particulate
• Handling incompatibilities and precautions:
  • Keep away from strong bases and nucleophiles that could promote undesired substitution or decomposition under forcing conditions
  • Avoid strong oxidizers and strong reducing agents
  • Dry conditions recommended for long-term integrity; moisture is not expected to hydrolyze aryl C–Br but can impact reactions/storage
• First-aid (general):
  • Skin/eye: Rinse with water for 15 minutes; remove contaminated clothing; seek medical attention if irritation persists
  • Inhalation: Move to fresh air; seek medical advice if symptoms develop
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical assistance
• Fire safety:
  • Organic solid; combustible. Use CO2, dry chemical, or foam. Thermal decomposition may release HBr/NOx; firefighters wear SCBA. Always consult the SDS for definitive safety information.

Solvent Selection

• Polarity and miscibility (general for this scaffold):
  • Moderately lipophilic heteroaromatic; dissolves well in DMSO, DMF, NMP, and chlorinated solvents; sparing in alcohols; poor in alkanes
  • Not water‑soluble under neutral conditions
• Choosing solvents by application:
  • Stock solutions for screening: DMSO (10–100 mM typical) with amber storage; can co‑dose with aqueous buffers by serial dilution
  • Cross‑couplings (Suzuki/Sonogashira/Buchwald): 1,4‑dioxane, toluene, DMAc, or mixed aqueous dioxane/THF; heteroarenes often benefit from polar aprotic media (DMAc, NMP) to accelerate oxidative addition
  • N‑oxidation or electrophilic functionalization: acetic acid, TFA/DCM, or MeCN depending on reagent
• Short comparison (general):
  • DMSO vs DMF: DMSO provides higher solubility and thermal stability but can coordinate metals; DMF is lower viscosity and easier workup
  • 1,4‑Dioxane vs toluene: dioxane improves solubility of bases and boron reagents; toluene better for air‑sensitive catalysts and high‑temp runs
• Drying/degassing:
  • For air‑sensitive couplings, use anhydrous, degassed solvents. Molecular sieves or solvent purification systems are recommended. Note: The above are general solvent selection principles for 3‑brominated heteroarenes and should be adapted to your specific method.

Storage and Reconstitution

• Item-specific storage: Room temperature (per Product Data). Store tightly closed in a dry, well‑ventilated place, protected from light.
• Shipping: Not specified for this item; refer to product label/logistics documents.
• Stability (general guidance):
  • Aromatic C–Br heteroarenes are typically shelf‑stable for years when kept dry and away from strong light/heat
  • Avoid prolonged exposure to strong bases, acids, or oxidants during storage
• Reconstitution and working solutions:
  • Prepare stock solutions in anhydrous DMSO, DMF, or NMP (typical concentrations 10–100 mM for discovery work)
  • Filter through 0.2 µm PTFE for particulate removal if needed
  • For coupling reactions, dissolve directly in the reaction solvent under inert atmosphere if air‑sensitive catalysts are used
• Freeze–thaw:
  • If preparing DMSO stocks, aliquot to minimize freeze–thaw cycles; store at −20 °C to −30 °C protected from moisture
• Specifications not provided:
  • Appearance, purity/assay, water content, residual solvents, and exact solubility: Not specified for this item; refer to CoA/Spec Sheet. Research Use Only: Not for human or veterinary use.

Structure and Identity

A fused diazine aromatic scaffold for heteroaryl coupling and SAR exploration on the 1,8‑naphthyridine core.

• Item-specific (from Product Data):
  • Product name: 3-Bromo-4-methyl-1,8-naphthyridine (CAS: 893566-54-6; CID: 68528911)
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Computed/literature identification (non-spec):
  • Core: 1,8‑naphthyridine (a naphthalene analog with N atoms at positions 1 and 8)
  • Substituents: bromo at C3, methyl at C4
  • Molecular formula (derived/literature): C9H7BrN2
  • Molecular weight (derived/literature): ~223.02 g/mol
• Structural features (general description):
  • Fused bicyclic aromatic system (two six‑membered rings) containing two ring nitrogens meta‑disposed across the fusion (positions 1 and 8)
  • One sp2‑carbon bearing bromine (C–Br aryl) at the 3‑position; adjacent sp2‑carbon bearing a methyl (benzylic C–H at C4)
  • Planar, conjugated π‑system; basic ring nitrogens (pyridine‑like) provide Lewis basicity and potential metal-binding
  • No stereocenters; molecule is achiral
• 2D depiction in words:
  • A quinoline-like framework where the ring nitrogen replaces the ring carbon at the “top-left” and “bottom-right” positions of the fused system (1,8). The bromine is on the ring carbon next to the N at position 1 (C3), and a methyl group sits adjacent at C4.

Synthetic Utility

Key functional elements enabling broad synthetic diversification:

• Aryl bromide at C3:
  • Serves as a robust electrophile for Pd/Ni‑catalyzed cross‑couplings (Suzuki, Buchwald–Hartwig, Sonogashira, Negishi). The heteroaryl nature typically facilitates oxidative addition relative to unactivated arenes.
• Benzylic C4‑methyl:
  • Vector for oxidation (to aldehyde/acid), halogenation (NBS), or formation of benzylic organometallics under strong base, enabling two‑site diversification on a common core
• Diazine nitrogens (N1, N8):
  • Modulate electronics; amenable to N‑oxidation to direct further substitution and then deoxygenation (Polonovski/Chichibabin manifolds)
  • Coordinate to metals—useful in assembling ligand libraries or metal‑templated constructions
• Retrosynthetic value:
  • Provides rapid access to 3‑substituted 1,8‑naphthyridines from a single handle (C–Br). Parallel synthesis with diverse boron/amine/alkyne partners builds SAR matrices efficiently.
• Downstream transformations:
  • Cycloadditions or annulations from alkynylated products to extend π‑systems (fluorophores/materials)
  • Late‑stage heteroatom installation (sulfurization, oxygenation) using cross‑coupled intermediates Overall, the scaffold balances reactivity and stability, making it a practical node in heteroarene libraries.

Target Specificity

Not applicable. This product is a small-molecule heteroaromatic building block, not a biological macromolecule or antibody. No antigen/epitope, species reactivity, clone, or isotype information applies.