7-Bromo-2-chloro-1,6-naphthyridine - ≥90% , CAS No.1578484-42-0

CAS: 1578484-42-0 Cat. No.: B980757 Formule: C₈H₄BrClN₂ Poids moléculaire: 243.490

GRADE & PURITY ≥90%

Storage

Room temperature

Specifications

Spécifications et pureté

≥90%

Conditions de stockage de stockage

Room temperature

Pureté

≥90%

Noms et identifiants

• Sourires canoniques: C1=CC(=NC2=CC(=NC=C21)Br)Cl
• IUPAC Name: 7-bromo-2-chloro-1,6-naphthyridine
• InChIKey: VJBBSXXUQOWEOI-UHFFFAOYSA-N
• INCHI: 1S/C8H4BrClN2/c9-7-3-6-5(4-11-7)1-2-8(10)12-6/h1-4H
• Poids moléculaire: 243.490

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Classe Diazanaphthalenes
      • Subclass Naphthyridines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Classe: Diazanaphthalenes
• Subclass: Naphthyridines
• Intermediate Tree Nodes: Not available
• Direct Parent: Naphthyridines
• Alternative Parents: 2-halopyridines Aryl chlorides Aryl bromides Heteroaromatic compounds Azacyclic compounds Organonitrogen compounds Organochlorides Organobromides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Naphthyridine - 2-halopyridine - Pyridine - Aryl halide - Aryl chloride - Aryl bromide - Heteroaromatic compound - Azacycle - Organic nitrogen compound - Hydrocarbon derivative - Organonitrogen compound - Organochloride - Organobromide - Organohalogen compound - Aromatic heteropolycyclic compound
• Description: This compound belongs to the class of organic compounds known as naphthyridines. These are compounds containing a naphthyridine moiety, a naphthalene in which a carbon atom has been replaced by a nitrogen in each of the two rings. The naphthyridine skeleton can also be described as an assembly two fused pyridine rings, which do not share their 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

Propriétés chimiques et physiques

• Poids moléculaire: 243.490 g/mol
• XLogP3: 3.100
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 0
• Exact Mass: 241.925 Da
• Monoisotopic Mass: 241.925 Da
• Topological Polar Surface Area: 25.800 Ų
• Heavy Atom Count: 12
• Formal Charge: 0
• Complexity: 167.000
• 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 or immunoapplication protocols are specified for this item. As a synthetic intermediate, typical "applications" are chemical transformations (see Reaction Conditions and Synthetic Utility tabs).

For compound handling in discovery workflows (general):

• Prepare 10–50 mM DMSO stock solutions for screening chemistry; store aliquots dry and minimize freeze–thaw.
• For parallel synthesis, consider microwave-assisted conditions (120–160 C) for SNAr/couplings with appropriate sealed vessels.
• Use automated LC-MS to verify identity and purity of intermediates.

Refer to your internal SOPs and the product’s CoA/SDS for any handling specifics.

Biological Roles

Item-specific: None specified in Product Data.

General context:

• 1,6-Naphthyridines are synthetic heteroaromatic scaffolds; 7-bromo-2-chloro substitution patterns are not known natural metabolites.
• Such scaffolds are frequently explored in chemical biology and medicinal chemistry as cores for small-molecule libraries due to their planarity, H-bond accepting nitrogens, and tunable electronics via halogen substitution. This enables structure–activity relationship (SAR) studies against diverse protein targets.
• The compound itself has no inherent biological role or established metabolic function; any activity arises from derivatives after functionalization and must be empirically determined.

Research use only note:

• As stated by the manufacturer: For research use only. No medical, diagnostic, or therapeutic use is implied.

Buffer Applications

Not typically applicable. 7-Bromo-2-chloro-1,6-naphthyridine is a neutral, sparingly ionizable heteroaromatic building block rather than a buffering agent. It does not form a defined conjugate acid/base pair with a practical buffering range in aqueous systems.

For aqueous work (e.g., biological assays of derivatives), select standard buffers (PBS, HEPES, MOPS, citrate) appropriate to your system, and dissolve this compound first in a suitable co-solvent (DMSO/MeCN) before dilution when needed.

Green Alternatives

Greener solvent and process considerations (literature/general):

• Replace DMF/DMAc/NMP with safer dipolar aprotics where feasible:
  • Cyrene (dihydrolevoglucosenone) or PolarClean can support some SNAr and Pd-couplings.
  • Propylene carbonate can be effective for SNAr and as a co-solvent.
• Swap 1,4-dioxane/THF with 2-MeTHF or CPME in Pd-catalyzed couplings; these often allow comparable rates with improved safety and lower peroxide risk compared to dioxane.
• Aqueous micellar catalysis (e.g., TPGS-750-M) can enable Suzuki/Buchwald couplings in water, reducing organic solvent usage.
• Ligand efficiency: Highly active catalysts (Buchwald biaryl phosphines, NHC–Pd precatalysts) operate at lower loadings and milder temps, reducing energy input and waste.
• Base and workup: Opt for inorganic bases with benign byproducts (K3PO4, K2CO3) and implement solvent recycling.

Illustrative comparison (general):

• Conventional: DMF or dioxane, 100–120 C, 2–5 mol% Pd.
• Greener: 2-MeTHF/H2O or micellar H2O, 60–90 C, 0.5–1 mol% Pd (with modern ligands), simplified workup.

Trade-offs:

• Solubility of heteroaryl substrates may limit water-rich systems; ligand/base screening is often required.
• Cyrene/propylene carbonate can change selectivity; preliminary DoE is recommended.

Pharmaceutical Uses

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

General context (non-clinical):

• This heteroaryl dihalide is used as a synthetic intermediate to prepare candidate drug-like molecules during discovery. It can be incorporated into APIs at the R&D stage via cross-coupling or SNAr to generate analog series for SAR profiling.
• Process and formulation roles are not applicable to the parent compound; any pharmaceutical relevance would be through derivatives synthesized from this scaffold.

Compliance note:

• For research use only, not for human or veterinary use. No therapeutic claims are made.

Physical Properties

Item-specific (from Product Data):

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet. (Calculated literature value: ~243.49 g/mol for C8H4BrClN2)
• Storage conditions: Room temperature (per Product Data).

Not specified for this item; refer to CoA/Spec Sheet:

• Melting point, boiling point, density, refractive index, UV cutoff, water content, residual metals, peroxide content, solubility data.

Literature/general expectations for this scaffold (non-specification):

• Physical state: typically a pale solid for halogenated naphthyridines.
• Solubility: generally sparingly soluble in nonpolar hydrocarbons; improved solubility in polar aprotic and halogenated solvents (e.g., DMSO, DMF, NMP, CHCl3).
• Acidity/basicity: ring nitrogens are weakly basic; overall molecule is neutral and moderately electron-deficient due to diaza core and aryl halides.

Practical notes (general):

• For weighing and transfer, minimize exposure to ambient moisture only as a good lab practice; use dry glassware when planning organometallic or cross-coupling reactions.
• Generate exact physico-chemical parameters from your lot-specific CoA when method development requires them.

Quality and Grades

Item-specific (from Product Data):

• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.

Guidance (general):

• For heteroaromatic coupling building blocks, purity and identity are often confirmed by HPLC/UPLC, NMR, and HRMS. If your application is sensitive (e.g., SAR studies, medicinal chemistry hit-to-lead), request chromatographic purity, residual solvent profile, and water content on the specific lot.
• If an inhibitor for catalysis is suspected, check for trace halides/acid and metal content on the CoA. Low residual protic/acidic impurities are preferred for air-/moisture-sensitive cross-couplings and lithiation chemistry.
• Stabilizers: None specified for this item. If your process is catalyst-sensitive, confirm absence of amine stabilizers or acid scavengers.

Best practices:

• Record lot number and retain a copy of the CoA/Spec Sheet for method development and regulatory documentation.
• For analytical method development (e.g., LC-UV), obtain the UV profile or use HPLC-grade solvents to minimize baseline artifacts.

Reaction and Applications

Role: 7-Bromo-2-chloro-1,6-naphthyridine is a bifunctional heteroaryl electrophile enabling orthogonal derivatization of a 1,6-naphthyridine core.

Typical transformations (literature/general):

• Cross-coupling at C7–Br: Suzuki–Miyaura (aryl/heteroaryl/alkenyl boronates), Stille, Negishi, Kumada; Buchwald–Hartwig amination to install anilines/alkylamines.
• SNAr at C2–Cl: Nucleophilic substitution with amines, alkoxides, thiolates, or aza-nucleophiles, promoted by the adjacent ring nitrogen(s) that activate the aryl chloride.
• Sequential selectivity: C7–Br generally reacts faster than C2–Cl under Pd-catalyzed conditions, allowing stepwise diversification (first couple at Br, then displace Cl by SNAr or a second coupling under more forcing conditions).
• N-oxidation/N-oxide chemistry: Temporary activation of the ring via N-oxide formation can further direct substitution or enable Minisci-type reactions (advanced applications).

Applications:

• Library synthesis and SAR exploration in medicinal chemistry, where diazanaphthalenes serve as kinase or GPCR-privileged scaffolds (no clinical claims implied).
• Probe and material precursors where electron-deficient heteroarenes are desired.

Practical tips:

• Dry solvents and degas for Pd-catalyzed couplings; monitor by LC-MS.
• Use inorganic bases (K2CO3, Cs2CO3, K3PO4) for Suzuki; stronger bases (NaOtBu) for C–N couplings.
• For SNAr, heat 80–140 C in polar aprotic media; add catalytic phase-transfer base if needed.
• Control halide order of reactivity by ligand choice and temperature to avoid undesired di-functionalization.

Reaction Conditions

General literature guidance (illustrative, not item specifications):

• Suzuki–Miyaura at C7–Br:

  • Catalyst: Pd(dppf)Cl2·DCM (1–2 mol%) or Pd-PEPPSI/NHC; Ligands: XPhos/SPhos.
  • Base: K2CO3 or K3PO4 (2–3 equiv).
  • Solvent: 1,4-dioxane/H2O (3:1), 2-MeTHF/H2O, or DMF/H2O.
  • Temp/time: 70–100 C, 2–16 h.

• Buchwald–Hartwig amination at C7–Br:

  • Catalyst: Pd2(dba)3 (1–2 mol%) with BrettPhos/XPhos; or RuPhos Pd G3 precatalyst.
  • Base: NaOtBu, KOtBu, or Cs2CO3.
  • Solvent: Toluene, dioxane, or CPME.
  • Temp: 80–110 C.

• SNAr at C2–Cl:

  • Nucleophiles: primary/secondary amines, alkoxides, thiolates.
  • Solvent: DMSO, DMF, or NMP.
  • Base: DIPEA, K2CO3, or NaH (for alkoxides).
  • Temp: 80–140 C; pressure-rated vessels recommended for high-boiling media.

• C–Cl activation (harder coupling):

  • Catalyst: Pd/XPhos or t-BuBrettPhos systems; or Ni(0)/bipyridine for certain partners.
  • Stronger conditions: higher temp (100–130 C), more electron-rich ligands, and/or additives (KF for Suzuki with boronates).

Monitoring and control:

• Follow by LC-MS or GC-MS; check for halide scrambling or di-coupled byproducts.
• Degas solvents; employ inert atmosphere to preserve catalyst activity.

Yields: Dependent on substrate/partner; 60–90% are typical literature ranges for optimized couplings on related heteroaryl dihalides.

Safety and Handling

Item-specific (from Product Data):

• GHS classification, pictograms, signal word, and H-statements: Not specified for this item; refer to SDS.
• Storage: Room temperature (per Product Data).

General safety guidance for halogenated aza-arenes (literature/typical; defer to SDS):

• Potential hazards: May cause skin/eye irritation; harmful if swallowed or inhaled. Aromatic halides and aza-heterocycles can be irritants; avoid dust formation.
• PPE: Lab coat, safety glasses or chemical splash goggles, and appropriate gloves (e.g., nitrile). Handle in a chemical fume hood.
• Incompatibilities: Strong oxidizing agents and strong bases/acids can cause decomposition; avoid sodium/alkali metals unless intended for synthesis. For metal-catalyzed couplings, handle catalysts and bases with care.
• First aid (overview): If inhaled—fresh air; if on skin—wash with soap/water; if in eyes—rinse cautiously with water for several minutes; if ingested—rinse mouth and seek medical attention. Always consult the SDS for definitive instructions.
• Fire-fighting: Use dry chemical, CO2, or alcohol-resistant foam. Combustion may produce HBr/HCl and nitrogen oxides.
• Spill response: Avoid dust, ventilate area, contain and collect with inert absorbent; dispose according to regulations.

Authoritative safety information is in the product SDS; follow institutional risk assessments.

Solvent Selection

Applicability: This compound is a halogenated diaza-PAH building block rather than a solvent; guidance below focuses on dissolving/processing it for synthesis and analysis.

General solvent compatibility (literature/experience):

• Likely good solubility: DMSO, DMF, DMAc, NMP; moderate in MeCN, CHCl3, CH2Cl2; lower in EtOAc, toluene; poor in alkanes.
• For cross-coupling: Common media include 1,4-dioxane, toluene, THF, Me-THF, CPME, DMF, DMAc, or mixed aqueous-organic systems (e.g., dioxane/H2O).
• Analytical: DMSO for stock solutions; MeCN/H2O or MeOH/H2O for LC.

Selection tips:

• To exploit differential reactivity (Ar–Br vs Ar–Cl), choose solvent/base that favors selective activation of the bromide first (e.g., dioxane or toluene mixtures with Pd catalysis). For SNAr at C2–Cl, polar aprotic solvents (DMSO/DMF) and elevated temperatures often help.
• When scaling up, prefer higher-boiling, lower-toxicity options (e.g., Me-THF, CPME) over dioxane/DMF if compatible with your catalyst and base.

Brief comparison (general):

• DMSO/DMF: maximize solubility and SNAr rates; harder workup.
• Me-THF/CPME: greener, easy separations; may require higher temps/ligand tuning.
• Toluene/dioxane: common for Pd-couplings; monitor worker exposure limits.

Always verify actual solubility with your lot under intended conditions.

Storage and Reconstitution

Item-specific (from Product Data):

• Storage conditions: Room temperature.
• Shipped in: Not specified for this item; refer to CoA/Spec Sheet.

General guidance (non-specification):

• Keep container tightly closed in a dry, well-ventilated place. Protect from excessive heat and direct light as a good laboratory practice for halogenated heteroarenes.
• If preparing solutions: Use anhydrous solvents (e.g., DMSO, DMF, MeCN) and store working solutions in sealed vials under inert gas at 2–8 C or −20 C depending on solvent stability. Avoid repeated freeze–thaw by aliquoting.
• For long-term solid storage: Consider desiccation to maintain consistency for moisture-sensitive reactions, although the compound itself is not known to be hygroscopic.

Always consult the lot-specific CoA and SDS for authoritative storage, stability, and handling instructions.

Structure and Identity

Item-specific (from Product Data):

• Product: 7-Bromo-2-chloro-1,6-naphthyridine (SKU B980757)
• CAS: 1578484-42-0
• CID: 89995603
• InChIKey: 380306 (as provided)
• SMILES: Not specified for this item; refer to CoA/Spec Sheet.

Literature/computed (non-specification, for context):

• Expected molecular formula (from name-derived structure): C8H4BrClN2
• Calculated molecular weight: ~243.49 g/mol (C8H4BrClN2)
• Structural class: dihalo diazanaphthalene (1,6-naphthyridine core) bearing bromine at C7 and chlorine at C2.
• Functional groups/features: two ring nitrogens (pyridine-like), one aryl bromide, one aryl chloride; planar, rigid, electron-deficient heteroaromatic system.
• 2D description: a fused bicyclic aromatic system (analogous to naphthalene) with nitrogens at positions 1 and 6 of the framework; a bromine substituent on the ring adjacent to one N (position 7) and a chlorine substituent on the ring adjacent to the other N (position 2). No stereocenters.

Notes:

• Identity confirmation should rely on orthogonal methods (HRMS, 1H/13C NMR, 2D NMR, and HPLC).

Synthetic Utility

Reactivity map (literature/general):

• Electrophilic handles: C7–Br (more reactive in Pd catalysis) and C2–Cl (amenable to SNAr and, under stronger conditions, Pd-coupling).
• Heteroaromatic activation: The 1,6-naphthyridine ring is electron-deficient; adjacent ring nitrogens facilitate addition–elimination in SNAr with amines, alkoxides, and thiolates.

Strategic applications:

• Orthogonal diversification: First modify the bromide via Suzuki/Negishi/Buchwald–Hartwig, then substitute the chloride by SNAr to introduce polar sidechains.
• Divergent synthesis: Invert sequence using bulky, strongly donating ligands at higher temperature to target C–Cl activation first, then address the bromide.
• Late-stage functionalization: Halide–metal exchange (e.g., Br–Mg, Br–Li) can be considered under carefully controlled, low-temperature conditions; quench with electrophiles to elaborate the scaffold (advanced users; manage lithiation near ring nitrogens).
• Directed transformations: Temporary N-oxide formation can steer regioselectivity or enable Minisci-type C–H functionalization on related systems.

Workup/purification:

• Heteroaryl salts can form during basic reactions; aqueous acidic washes may be useful to remove amines/bases, followed by basification and extraction if necessary.
• Silica gel chromatography with polar modifiers (1–5% Et3N) may prevent tailing of basic heteroarenes.

Target Specificity

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

Foire aux questions

How should this product be stored?

Store at room temperature.