4-(3-Bromophenoxy)pyrimidine - ≥98% , CAS No.315189-72-1

CAS: 315189-72-1 Cat. No.: B944733 Formule: C₁₀H₇BrN₂O Poids moléculaire: 251.080

GRADE & PURITY ≥98%

Storage

Room temperature

Specifications

Spécifications et pureté

≥98%

Conditions de stockage de stockage

Room temperature

Pureté

≥98%

Noms et identifiants

• Sourires canoniques: C1=CC(=CC(=C1)Br)OC2=NC=NC=C2
• IUPAC Name: 4-(3-bromophenoxy)pyrimidine
• InChIKey: YEYYAGSOCKEGER-UHFFFAOYSA-N
• INCHI: 1S/C10H7BrN2O/c11-8-2-1-3-9(6-8)14-10-4-5-12-7-13-10/h1-7H
• Poids moléculaire: 251.080

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Classe Phenol ethers

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Classe: Phenol ethers
• Subclass: Not available
• Intermediate Tree Nodes: Not available
• Direct Parent: Phenol ethers
• Alternative Parents: Bromobenzenes Pyrimidines and pyrimidine derivatives Heteroaromatic compounds Ethers Azacyclic compounds Organopnictogen compounds Organonitrogen compounds Organobromides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Phenol ether - Halobenzene - Bromobenzene - Pyrimidine - Monocyclic benzene moiety - Heteroaromatic compound - Azacycle - Organoheterocyclic compound - Ether - Organic nitrogen compound - Organic oxygen compound - Organopnictogen compound - Hydrocarbon derivative - Organooxygen compound - Organonitrogen compound - Organobromide - Organohalogen compound - Aromatic heteromonocyclic compound
• Description: This compound belongs to the class of organic compounds known as phenol ethers. These are aromatic compounds containing an ether group substituted with a benzene ring.
• 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: 251.080 g/mol
• XLogP3: 2.800
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 2
• Exact Mass: 249.974 Da
• Monoisotopic Mass: 249.974 Da
• Topological Polar Surface Area: 35.000 Ų
• Heavy Atom Count: 14
• Formal Charge: 0
• Complexity: 180.000
• 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 validated bioassay or analytical application protocols are specified for this item. For compound handling in screening contexts (general guidance):

• Prepare a DMSO stock (e.g., 10–50 mM) using anhydrous solvent; vortex and, if needed, warm gently to aid dissolution.
• Filter (0.22 µm PTFE) for particulate removal if required.
• Aliquot to minimize freeze–thaw; store under inert headspace to limit oxidative degradation.
• Dilute into assay buffers ensuring final DMSO content is compatible with the system (commonly 0.1–1% v/v).
• Confirm concentration by UV–Vis or quantitative NMR where feasible.

Consult your internal SOPs for method-specific conditions.

Biological Roles

This product is a synthetic heteroaryl building block rather than a biomolecule.

• Not a natural metabolite or cofactor; no inherent biological role is established.
• Pyrimidine cores are common in nucleobases and medicinal chemistry; 4-aryloxypyrimidines frequently appear in research ligands (e.g., kinase-focused scaffolds), but any biological activity would derive from derivatives synthesized from this building block and must be determined empirically.
• No biological targets or pathways are assigned to this SKU. For biological testing, prepare appropriate solutions (typically in DMSO) and assess solubility/cytotoxicity independently.

Note: For research use only; not for diagnostic, therapeutic, or clinical applications.

Buffer Applications

Not typically applicable. 4-(3-Bromophenoxy)pyrimidine is a neutral organic building block and is not used as a buffering agent. For aqueous handling, dissolve in a miscible organic cosolvent (e.g., DMSO) before dilution into buffers if required for assays.

Green Alternatives

• Greener processing considerations relate mainly to solvent/catalyst choice during couplings rather than the substrate itself.

• Options (literature/general guidance):

  • Use bio-based ethers (2-MeTHF) or cyclopentyl methyl ether (CPME) in place of THF/toluene where solubility allows.
  • Employ water/ethanol co-solvent systems for Suzuki–Miyaura couplings with micellar catalysis (e.g., TPGS-750-M) to reduce organic solvent load.
  • Choose less toxic bases (K2CO3, K3PO4) over strong alkoxides.
  • Apply ligand-efficient Pd catalysis (ppm-level) or Ni catalysis to minimize precious metal usage and facilitate metal scavenging.

• Comparison (general):

  • Traditional vs greener
    • THF/toluene/dioxane vs 2-MeTHF/CPME/MeCN/water–micellar media
    • High Pd load (1–5 mol%) vs low/ppm Pd or Ni catalysis
    • Chlorinated solvent workups vs ester/alcohol media enabling easier solvent recovery

• Tradeoffs:

  • Solubility of heteroaryl ethers may limit use of greener solvents; modest heating or co-solvents often resolve this.
  • Micellar conditions can be sensitive to substrate hydrophobicity; optimization of surfactant loading and temperature is required.

Pharmaceutical Uses

• This item is not an excipient and has no pharmacopeial monograph specified. It serves as a research intermediate/building block.
• Potential roles in pharmaceutical R&D (general):
  • Scaffold for library synthesis in hit-to-lead campaigns, especially where pyrimidinyl ethers are desired.
  • Intermediate toward candidate compounds via cross-coupling on the aryl bromide.
• No clinical or therapeutic claims are made. Any use is restricted to research and development under appropriate quality systems.

Physical Properties

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

• General/literature expectations for 4-aryloxypyrimidines with aryl bromide:

  • Physical state: typically an off-white to pale solid (literature trend for analogous aryl–O–pyrimidines)
  • Polarity: moderately polar due to ring nitrogens and ether oxygen; overall neutral
  • Solubility profile (qualitative):
    • Organic: soluble in polar aprotic solvents (DMSO, DMF, NMP, acetone, acetonitrile); variable solubility in EtOAc and chlorinated solvents (DCM/CHCl3).
    • Aqueous: expected very low intrinsic solubility at neutral pH (no ionizable basic center strong enough to protonate under neutral conditions).
  • Hydrogen-bonding: good H-bond acceptor (pyrimidine N atoms, ether O); no donors.
  • Volatility: low (aromatic heteroaryl ether, brominated).

• If precise BP/MP, density, refractive index, pKa, logP, or UV cutoffs are needed, consult CoA/Spec Sheet or determine experimentally (DSC/MP, potentiometry, shake-flask, UV–Vis). Avoid assuming numeric values for process design without verification.

Quality and Grades

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

• Guidance on interpreting grade (general):

  • Research-grade heteroaryl building blocks are typically specified by assay (HPLC/GC area%), identity (NMR/HRMS), and impurity limits (residual solvents, inorganic residues).
  • For structure–activity studies or library synthesis, low UV background and single, well-resolved HPLC peak are preferred.
  • If a stabilizer is present (not indicated here), it would be declared on the CoA; absence of such a note generally implies neat material.

• Recommended quality checks prior to critical use:

  • Verify identity and purity by 1H/13C NMR and LC–MS.
  • Assess water content by Karl Fischer if using in moisture-sensitive couplings (e.g., phosphoramidite or Grignard-incompatible steps).
  • For medicinal chemistry, record exact batch MW and isotopic pattern (Br) to aid HRMS confirmation.

• Documentation: Request the CoA/Spec Sheet for this SKU (B944733) for definitive assay, residual solvent profile, and chromatographic conditions.

Reaction and Applications

• Functional group handles:

  • Aryl bromide (meta-bromophenyl) enables cross-couplings (Suzuki–Miyaura, Sonogashira, Stille, Negishi, Buchwald–Hartwig amination after halide activation).
  • Ether-linked pyrimidine ring offers an electron-deficient heteroaryl core prevalent in kinase-focused heterocycles and SAR exploration.

• Typical applications (literature/general):

  • Diversification at the bromide site to build libraries of 4-aryloxypyrimidines via Pd-catalyzed C–C/C–N bond formation.
  • Late-stage modification where the pyrimidin-4-oxy linkage serves as a stable handle under many coupling conditions.
  • SNAr onto activated pyrimidines is common, but here C4 is substituted; further substitution may occur at C2/C5 only if additional activation is introduced elsewhere in the route.

• Practical tips:

  • Cross-coupling: use Pd(0/II) complexes (e.g., Pd(PPh3)4, Pd2(dba)3/XPhos); bases such as K2CO3, Cs2CO3, or K3PO4; solvents 1,4-dioxane, toluene, THF, or MeCN; 50–110 °C depending on partner reactivity.
  • Sonogashira: Pd/Cu co-catalysis (Pd(PPh3)2Cl2, CuI), amine base (Et3N/DIPEA), toluene/THF/DMF, 25–80 °C. Copper-free variants reduce homocoupling.
  • Oxidative additions at aryl bromide are generally smooth; sterics are modest (meta-bromo), enabling high conversions with modern ligands.
  • The ether and diazine nitrogens can coordinate catalysts; ligand choice (bulky, electron-rich phosphines) can mitigate deactivation.

• Downstream transformations:

  • Bromide → boronate (Miayura borylation) for iterative coupling.
  • Bromide → amine (Buchwald–Hartwig) to install anilines para to O-link.
  • Bromide → CN (Rosenmund–von Braun or Pd-catalyzed cyanation; handle cyanides with appropriate safety controls).

Reaction Conditions

General literature guidance for aryl bromide couplings and derivatizations of 4-(3-bromophenoxy)pyrimidine (not item-specific; optimize per substrate and scale):

• Suzuki–Miyaura (Ar–Br → Ar–Ar'):

  • Catalyst: Pd(PPh3)4 (1–3 mol%) or Pd2(dba)3 (1 mol%) + XPhos/SPhos (2–4 mol%).
  • Base: K3PO4 (2–3 eq) or Cs2CO3 (2–3 eq).
  • Solvent: 1,4-dioxane/H2O (4:1), toluene/H2O, or MeCN/H2O.
  • Temp: 60–100 °C; time: 2–16 h.
  • Notes: Micellar aqueous media can work with appropriate surfactant.

• Buchwald–Hartwig amination (Ar–Br → Ar–NR2):

  • Catalyst: Pd2(dba)3 (1–2 mol%) + BrettPhos/XPhos (2–4 mol%).
  • Base: NaOtBu or K3PO4.
  • Solvent: toluene, dioxane, or t-AmOH.
  • Temp: 80–110 °C.

• Sonogashira (Ar–Br → Ar–C≡CR):

  • Catalyst: Pd(PPh3)2Cl2 (1–2 mol%) + CuI (5–10 mol%) or copper-free with bulky phosphines.
  • Base: Et3N, DIPEA, or K2CO3.
  • Solvent: THF, DMF, or MeCN.
  • Temp: rt–80 °C.

• Miyaura borylation (Ar–Br → Ar–B(pin)):

  • Catalyst: Pd(dppf)Cl2 (1–2 mol%).
  • Base: KOAc.
  • Solvent: 1,4-dioxane.
  • Temp: ~80 °C.

• Workup/purification:

  • Quench with water/brine, extract with EtOAc or DCM, charcoal if needed (Br-containing byproducts), and purify by silica gel or preparative HPLC.
  • Monitor by LC–MS exploiting the characteristic 79/81Br isotopic pattern.

Safety and Handling

• Item-specific GHS classification, pictograms, signal word, and H-statements: Not specified for this item; refer to SDS for authoritative safety data.

• General hazards for aromatic heteroaryl ethers bearing aryl bromide (literature-based):

  • May cause skin/eye irritation and respiratory tract irritation as dust/particles.
  • Combustible organic solid; fine dust may form explosive mixtures with air.
  • Aryl bromides are generally of low acute toxicity but should be handled to minimize exposure.

• Recommended PPE and controls:

  • Use in a fume hood; avoid inhalation of dust.
  • Wear lab coat, safety glasses, and suitable gloves (e.g., nitrile).
  • Employ dust control and local exhaust when weighing.
  • Wash thoroughly after handling; avoid contact with strong oxidizers.

• Incompatibilities and reactivity:

  • Strong oxidizing agents; strong bases at high temperature may cleave aryl–O bonds or promote side reactions.
  • Avoid prolonged exposure to strong acids or bases if maintaining integrity of the ether is critical.

• First-aid overview (consult SDS for full instructions):

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

• Fire-fighting: use CO2, dry chemical, or foam. Combustion may produce CO/CO2, HBr/Br-containing fumes.

Solvent Selection

This compound is a neutral, moderately polar aromatic ether with an aryl bromide, favoring polar aprotic media.

• Miscibility/solubility guidance (general):

  • Preferred: DMSO, DMF, NMP, DMAc, acetonitrile, acetone.
  • Often suitable: ethyl acetate, dichloromethane, chloroform, toluene (warm).
  • Poor: water and nonpolar alkanes (hexanes) unless aided by cosolvents or surfactants.

• Use-case driven selection:

  • Stock solutions for screening: anhydrous DMSO (e.g., 10–50 mM) with aliquots stored under inert gas; dilute into assay buffers with appropriate cosolvent percentage.
  • Cross-coupling (Suzuki/Sonogashira): toluene, 1,4-dioxane, THF, or mixtures with water/EtOH under Pd catalysis.
  • Nucleophilic substitutions on other fragments in the route: DMF/DMSO/NMP to stabilize anions.

• Comparison notes:

  • DMSO vs DMF: DMSO offers higher solubility but is harder to remove; DMF is common for coupling yet may require azeotropic co-evaporation.
  • Chlorinated solvents aid workup and TLC visualization but consider environmental and safety profiles.

• Drying: For moisture-sensitive steps, dry solvents over molecular sieves (3Å/4Å) or purchase anhydrous grades.

Storage and Reconstitution

• Item-specific storage: Room temperature (per Product Data).

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

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

• General storage advice for heteroaryl ethers:

  • Keep tightly closed in original container, protected from moisture and direct light.
  • Store under ambient, dry conditions; for long-term storage, consider desiccation or inert atmosphere.
  • Avoid prolonged exposure to strong acids/bases.

• Reconstitution/dissolution (general guidance):

  • For stock solutions, use dry DMSO, DMF, or acetonitrile; typical concentrations 10–50 mM for medicinal chemistry screening.
  • Warm gently (≤40 °C) and sonicate if necessary to achieve full dissolution.
  • Filter through PTFE syringe filter if particulates persist.
  • Record solvent, concentration, and date; aliquot to minimize freeze–thaw cycling.

• Stability: Item-specific stability data are not provided; verify by LC–MS/HPLC after storage as needed. Always refer to the CoA/SDS for definitive handling guidance.

Structure and Identity

Brief description: 4-(3-Bromophenoxy)pyrimidine is a heteroaryl aryl ether comprising a pyrimidine (1,3-diazine) core O-linked at C4 to a 3-bromophenyl ring. The molecule combines an electron-deficient pyrimidine with a cross-couplable aryl bromide.

• Item-specific (Product Data):

  • CAS: 315189-72-1
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
  • Storage conditions: Room temperature
  • Research use: For research use only

• Computed/literature (general reference values; not item-specific):

  • Molecular formula (derived from name): C10H7BrN2O
  • Molecular weight (calculated from formula): ~251.08 g/mol
  • Core structural features:
    • Aromatic heterocycle: pyrimidine (two ring nitrogens at positions 1 and 3)
    • Aryl–O–heteroaryl ether linkage at pyrimidine C4
    • Peripheral aryl bromide at the meta (3-) position on the phenyl ring
    • No stereocenters; fully aromatic, planar conjugated system
  • 2D structure in words: a six-membered benzene ring bearing Br at the 3-position is connected via an oxygen atom (phenoxy) to the 4-position of a six-membered 1,3-diazine (pyrimidine) ring.

• Notes: Where exact identifiers (e.g., canonical SMILES, full InChI/InChIKey) are required for informatics, generate from the verified structure or consult the CoA/SDS.

Synthetic Utility

• Retrosynthetic value:

  • Disconnection at the Ar–O bond suggests formation from pyrimidin-4-ol (or 4-halo-pyrimidine → 4-oxide) and 3-bromophenol via nucleophilic substitution (SNAr on activated 4-chloropyrimidine) or via Mitsunobu-like or Ullmann/Chan–Lam etherification strategies.
  • The aryl bromide enables late-stage diversification by cross-coupling, allowing rapid SAR generation without perturbing the pyrimidinyl ether linkage.

• Transformations enabled:

  • C(sp2)–C(sp2) formation (Suzuki, Stille, Negishi).
  • C(sp2)–N formation (Buchwald–Hartwig) at the bromide site.
  • C(sp2)–C(sp) formation (Sonogashira).
  • Borylation/silylation to versatile linchpins.
  • Electrophilic aromatic substitution on the phenyl ring is deactivated by the bromide and ether; cross-coupling routes are preferred.

• Protection/compatibility:

  • The ether linkage is generally stable to bases used in cross-couplings; avoid strong nucleophiles at elevated temperature that could induce ether cleavage.
  • Pyrimidine nitrogens may coordinate metals; select ligands/additives accordingly.

Target Specificity

Not applicable. This product is a small-molecule building block and not an antibody, enzyme, or affinity reagent. No target specificity information is provided for this SKU.