7-Methylquinazoline - ≥97% , CAS No.7556-98-1

CAS: 7556-98-1 Cat. No.: M1008511 Formula: C₉H₈N₂ Peso molecolare: 144.170

GRADE & PURITY ≥97%

Storage

Room temperature

Specifications

Specifiche e purezza

≥97%

Condizioni di conservazione di stoccaggio

Room temperature

Purezza

≥97%

Nomi e identificatori

• Sorrisi canonici: CC1=CC2=NC=NC=C2C=C1
• IUPAC Name: 7-methylquinazoline
• InChIKey: WUQQKWIILPEEKY-UHFFFAOYSA-N
• INCHI: 1S/C9H8N2/c1-7-2-3-8-5-10-6-11-9(8)4-7/h2-6H,1H3
• Peso molecolare: 144.170

Taxonomic Classification

Taxonomy Tree

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

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Classe: Diazanaphthalenes
• Subclass: Benzodiazines
• Intermediate Tree Nodes: Not available
• Direct Parent: Quinazolines
• Alternative Parents: Pyrimidines and pyrimidine derivatives Benzenoids Heteroaromatic compounds Azacyclic compounds Organonitrogen compounds Hydrocarbon derivatives
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Quinazoline - Benzenoid - Pyrimidine - Heteroaromatic compound - Azacycle - Organic nitrogen compound - Hydrocarbon derivative - Organonitrogen compound - Aromatic heteropolycyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as quinazolines. These are compounds containing a quinazoline moiety, which is made up of two fused six-member aromatic rings, a benzene ring and a pyrimidine 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

Proprietà chimiche e fisiche

• Peso molecolare: 144.170 g/mol
• XLogP3: 1.400
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 0
• Exact Mass: 144.069 Da
• Monoisotopic Mass: 144.069 Da
• Topological Polar Surface Area: 25.800 Ų
• Heavy Atom Count: 11
• Formal Charge: 0
• Complexity: 136.000
• 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 standardized bioassay protocols (e.g., WB, IHC, IF, FC) are associated with this small-molecule building block. For synthetic or analytical uses, develop method-specific procedures (e.g., reaction setups, chromatographic methods) tailored to your laboratory and verify performance with small-scale pilots.

Biological Roles

This product is a small-molecule heteroaromatic building block and is provided for research use only.

• General context (literature; not product-specific and not a medical claim)

  • Quinazoline scaffolds are prevalent in chemical biology and medicinal chemistry as privileged structures for ligand development due to their planarity, hydrogen-bond acceptors, and tunable electronics via ring substitution.
  • Methyl substitution at the benzenoid ring modulates hydrophobicity and π-stacking propensity, which can influence binding in fragment-based screening campaigns.
  • The diazine nitrogens can serve as weak hydrogen-bond acceptors; N-oxide formation offers additional polarity handles for probe optimization.

• Practical notes for research users

  • As a fragment or intermediate, 7-methylquinazoline can be elaborated to more polar or functionalized derivatives suitable for target engagement studies.
  • For biochemical assays, ensure thorough characterization of purity and residual solvent content to avoid assay interference. Use matched negative controls where possible.

No biological activity or target specificity is claimed or implied for this catalog item. Always perform your own target validation and toxicity assessments appropriate to your research setting.

Buffer Applications

7-Methylquinazoline is a neutral, weakly basic heteroaromatic and is not typically used as a buffer component.

• Applicability
  • It lacks the requisite conjugate acid/base pair with a practical pKa in the physiological buffering range and is not used in standard biochemical buffer systems.

For solution-phase work involving this compound, select an appropriate buffer based on your biological assay needs (e.g., phosphate, HEPES, MOPS) and confirm the compound’s solubility and stability in that system.

Green Alternatives

Although 7-methylquinazoline is a target/building block rather than a solvent, greener choices can be made in its synthesis, derivatization, and processing.

• Process solvent choices (general guidance)

  • Prefer bio-derived ethers/esters (2-MeTHF, CPME, EtOAc, propylene carbonate) over chlorinated solvents when compatible with the transformation and workup.
  • Replace DMF/DMAc/NMP with safer polar aprotics (DMSO, propylene carbonate, PC/EtOH mixtures) when catalyst system tolerates them.
  • For extractions and chromatography, EtOAc/MeOH/hexanes systems are greener than DCM/MeOH; heptane often substitutes for hexane.

• Oxidations and halogenations

  • Benzylic oxidations: Consider O2 or H2O2 with appropriate catalysts (e.g., TEMPO/O2, Mn or Co catalysts) over Cr(VI)/Mn(VII) reagents.
  • Electrophilic halogenation: Use NBS/NCS in safer solvents (EtOAc, MeCN) instead of Br2/Cl2 in chlorinated media.

• Energy and workup

  • Continuous flow for exothermic EAS or oxidations can reduce solvent/energy usage and improve safety.
  • Use aqueous micellar catalysis (TPGS-750-M or similar) for certain cross-couplings on pre-halogenated quinazolines to minimize organic solvent load (literature).

• Comparison snapshot (illustrative)

  • THF vs 2-MeTHF: Similar reactivity in lithiation; 2-MeTHF is renewable and offers improved safety profile.
  • DCM vs EtOAc: EtOAc is biodegradable and less toxic; DCM sometimes necessary for solubility—evaluate on a case-by-case basis.

Adopt green metrics (E-factor, PMI) and solvent selection guides (ACS, GSK) to benchmark improvements.

Pharmaceutical Uses

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

• General context (no therapeutic claims)

  • Quinazoline cores are commonly used as intermediates in the synthesis of API leads during discovery and process development. 7-Methyl substitution can serve as a handle for benzylic oxidations or cross-couplings after halogenation, allowing rapid exploration of SAR.
  • When used in process R&D as an intermediate, attention should be paid to residual solvents, elemental impurities, and polymorphic form where relevant; these considerations are governed by ICH Q3C/Q3D and related guidance in later development.

• Formulation/analytical considerations (if used as a standard or impurity benchmark)

  • Ensure high chemical purity and defined water content for accurate assay standards.
  • The strong UV chromophore aids HPLC/UPLC detection; confirm wavelength and extinction coefficients experimentally for quantitative use.

This product is supplied strictly for research use only and is not for human or veterinary use.

Physical Properties

• Item-specific specifications

  • Appearance: Not specified for this item; refer to CoA/Spec Sheet.
  • Density, melting/boiling point, refractive index, UV cutoff: Not specified for this item; refer to CoA/Spec Sheet.
  • Water, peroxide, metals, residual solvents: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/general properties for the quinazoline family (context; not item specifications)

  • Acid–base: Weakly basic heteroaromatic; conjugate acid pKaH for quinazoline cores typically ~2–3 (literature), reflecting low basicity of ring nitrogens.
  • Solubility profile: Expected to be sparingly soluble in water and soluble in common organic solvents (e.g., DCM, chloroform, EtOAc, toluene, THF, MeCN, alcohols), with solubility enhanced in polar aprotic media; actual solubility depends on purity and form.
  • Volatility/phase: Many lower-alkyl quinazolines are low-volatility liquids or low-melting solids; confirm physical state on CoA prior to process design.
  • Spectroscopy: Aromatic UV absorption typically in the 250–330 nm range (literature, heteroaromatic π–π*). 1H NMR shows benzenoid and diazine-region aromatic signals with a benzylic-type methyl singlet near ~2.4–2.7 ppm (solvent-dependent; literature trend).
  • Partitioning: Moderately hydrophobic character is typical for methylated quinazolines (logP often ~1–2; literature trend), aiding extraction into organic phases.

Always confirm exact physical constants and handling limits using the item-specific CoA/Spec Sheet and SDS before scale-up.

Quality and Grades

• Item-specific details

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

• Guidance on typical grade considerations for heteroaromatic building blocks

  • Research/technical grade: Suitable for discovery chemistry, method scouting, and library synthesis; may contain trace organic or inorganic impurities that are generally acceptable for early-stage work.
  • High-purity or chromatographic grade: Preferred for SAR studies and sensitive reactions (e.g., metal-catalyzed couplings) to minimize catalyst poisoning by basic nitrogen or adventitious impurities.
  • LC/GC suitability: Low UV-absorbing excipients and tightly controlled residual solvents are beneficial when the compound serves as an analytical standard; verify UV baseline behavior if using as an HPLC reference.
  • Impurity profile: For diaza-arenes, common impurities include isomeric methylquinazoline regioisomers, over-oxidized species (N-oxides), and trace halogenated or metal residues from synthesis. Confirm limits on the CoA.

• Practical notes

  • If performing Pd- or Ni-catalyzed steps downstream, pre-wash or recrystallize if necessary, and confirm halide/metal content if catalyst sensitivity is a concern.
  • For QA/QC, confirm identity by 1H/13C NMR and HRMS; HPLC/GC to verify purity and isomer ratio. Reference spectra should be matched to an authenticated lot-specific CoA.

Reaction and Applications

• Building-block roles

  • Aromatic core for constructing quinazoline-derived libraries relevant to materials, ligand design, and probe discovery. The 7-methyl group modulates electronics and sterics on the benzenoid ring, affecting subsequent substitution patterns and directing tendencies.

• Representative transformations (literature context)

  • Electrophilic aromatic substitution on benzenoid positions (nitration, halogenation, sulfonylation) with regioselectivity influenced by the ring nitrogens and the 7-methyl substituent.
  • Directed metalation/lithiation adjacent to the methyl group or toward the diazine ring under strong bases (e.g., s-BuLi/TMEDA), enabling formylation, borylation, or halogenation.
  • Benzylic functionalization: Radical bromination (NBS/AIBN) or oxidation of the 7-methyl to aldehyde/acid, diversifying substitution at C7.
  • N-oxidation of the quinazoline ring to N-oxide, enabling subsequent rearrangements or activation for C–H functionalization.
  • Cross-coupling: While 7-methylquinazoline itself lacks a leaving group, prefunctionalization (e.g., halogenation) allows Suzuki–Miyaura, Buchwald–Hartwig (on aminated derivatives), or Chan–Lam couplings.
  • SNAr on activated quinazoline positions (e.g., 4-chloroquinazoline intermediates) when used as a scaffold in multistep sequences.

• Practical tips

  • Basic nitrogens can coordinate and inhibit catalysts; ligand and base choices (or temporary N-oxide protection) can improve cross-coupling performance.
  • Employ inert atmosphere and rigorously dry solvents for organometallic steps. Titrate base strengths carefully to avoid ring degradation.
  • Monitor by HPLC/UPLC with UV at ~260–320 nm and by LC–MS; benzylic oxidations benefit from GC or LC–MS tracking due to potential over-oxidation.

Reaction Conditions

The following conditions are literature-informed general guidance for quinazoline derivatives; optimize for your specific substrate and scale.

• Benzylic bromination (NBS)

  • Solvent: CCl4, CH2Cl2, or greener alternatives (EtOAc) where feasible
  • Initiator: AIBN or light; 0.1–0.2 equiv
  • Temperature: Reflux in chosen solvent or RT under photochemical initiation
  • Notes: Monitor to avoid over-bromination; proceed to substitution or oxidation without isolation if desired.

• Benzylic oxidation to aldehyde/acid

  • TEMPO/O2 (or NaOCl): MeCN/H2O or EtOAc; RT–40 °C
  • SeO2 (allylic/benzylic): Toluene or 1,4-dioxane; 60–100 °C
  • Metal-catalyzed aerobic oxidations: Cu/Mn/Co catalysts; AcOH or MeCN; air/O2; RT–80 °C

• Electrophilic aromatic substitution

  • Nitration: HNO3/Ac2O or HNO3/H2SO4 at 0–25 °C; short contact times
  • Sulfonylation: ClSO3H or SO3·pyridine; DCM/Ac2O; 0–25 °C
  • Halogenation: NBS/NCS in MeCN/AcOH; RT–reflux

• Directed metalation

  • Base: s-BuLi (± TMEDA)
  • Solvent: THF or 2-MeTHF; −78 to −40 °C
  • Quenches: DMF (formyl), B(OMe)3 (boryl), CO2 (carboxyl)

• Cross-coupling on pre-halogenated analogs

  • Suzuki–Miyaura: Pd catalyst (e.g., Pd(dppf)Cl2), base (K2CO3, K3PO4), solvent (dioxane/H2O, toluene/H2O, or MeCN), 60–100 °C
  • Buchwald–Hartwig amination: Pd/XPhos system; NaOtBu or Cs2CO3; toluene or dioxane; 80–110 °C

Monitor all reactions by HPLC/UPLC or LC–MS. Adjust equivalents and temperatures based on observed reactivity.

Safety and Handling

• Item-specific hazard classification

  • GHS classification, pictograms, signal word, H-statements: Not specified for this item; refer to SDS.

• General safety considerations for heteroaromatic bases (context; consult SDS)

  • Likely hazards: Combustible organic; may cause irritation to skin, eyes, or respiratory tract upon contact or inhalation. Avoid dust/vapor formation and ignition sources.
  • Personal protective equipment (PPE): Laboratory coat, safety glasses or splash goggles, and appropriate chemically-resistant gloves (e.g., nitrile). Use in a fume hood to minimize inhalation exposure.
  • Incompatibilities: Strong oxidizers (risk of exotherm/oxidation), strong acids (protonation, possible heat evolution), strong bases (possible side reactions). Keep away from reactive metals if using strong bases for lithiation/metalation steps.
  • Handling tips: Minimize exposure to air and moisture when conducting air-/moisture-sensitive transformations (e.g., directed lithiation). Use inert atmosphere for sensitive steps.
  • First aid (summary; see SDS):
    • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
    • Skin/eye contact: Rinse with water for several minutes; remove contaminated clothing; seek medical attention if irritation persists.
    • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
  • Fire safety: Use CO2, dry chemical, or foam. Combustion may produce NOx and CO/CO2; firefighters should wear SCBA.

Always defer to the product’s SDS for authoritative hazard classification, exposure limits, and emergency procedures.

Solvent Selection

7-Methylquinazoline is a neutral, weakly basic heteroaromatic; solvent choice is typically dictated by the downstream transformation.

• Polarity/miscibility (general)

  • Expected to be soluble in mid- to non-polar organic solvents (e.g., DCM, chloroform, toluene, EtOAc, MeCN, THF, alcohols). Water solubility is usually low for methylated quinazolines.
  • For extractions, partitioning into DCM/EtOAc from mildly acidic or neutral aqueous layers is generally effective; protonation under strong acid will increase aqueous solubility.

• Selection by application

  • Electrophilic aromatic substitution (EAS): Use polarizable, non-basic solvents (dichloroethane, nitromethane, acetic acid) as needed by the reagent system.
  • Metalation/lithiation: Anhydrous ethers (THF, MTBE, 2-MeTHF) at low temperature under inert atmosphere; avoid protic solvents.
  • Cross-coupling on pre-halogenated analogs: Polar aprotics (DMAc, DMF, DMSO) or mixed toluene/EtOH/H2O systems with appropriate ligands; base compatibility with ring nitrogens is critical.
  • N-oxidation: CH2Cl2, MeCN, or AcOH commonly used with peracids; monitor for over-oxidation.

• Practical comparison (literature-informed)

  • THF vs 2-MeTHF: 2-MeTHF offers better sustainability and higher boiling point; both support lithiation, but 2-MeTHF improves phase separation on workup.
  • DCM vs EtOAc: DCM provides higher capacity for aromatic bases; EtOAc is greener and often adequate for extractions and chromatography.

Always verify solubility and stability with a small-scale trial under your exact reaction conditions.

Storage and Reconstitution

• Item-specific storage conditions (from Product Data)

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

• General guidance

  • Keep container tightly closed in a dry, well-ventilated place. Protect from moisture and prolonged exposure to light.
  • If performing air-/moisture-sensitive chemistry (e.g., lithiation), consider storing under inert gas after opening to minimize aerial oxidation or water uptake.
  • If the material is a low-melting solid or viscous liquid, warm gently to homogenize before aliquoting; avoid overheating. Record any observed changes vs. CoA.
  • For solution preparation: Use anhydrous, oxygen-free solvents when required by downstream transformations. Filter through a PTFE syringe filter if particulates are present.
  • Stability: Heteroaromatic cores are generally robust at ambient conditions; however, avoid strong acids/bases and oxidizers in storage areas.

Always consult the lot-specific CoA and SDS for definitive storage, stability, and handling instructions. This product is supplied for research use only.

Structure and Identity

Brief overview: 7-Methylquinazoline is a bicyclic, diaza-heteroaromatic consisting of a quinazoline core bearing a methyl substituent at the 7-position on the benzenoid ring.

• Item-specific (from Product Data)

  • Product name: 7-Methylquinazoline
  • CAS: 7556-98-1
  • InChIKey: 408529 (as supplied in product data)
  • Storage conditions: Room temperature
  • Other identifiers (SMILES, CID, formula, MW): Not specified for this item; refer to CoA/Spec Sheet.

• Literature/structural description (general chemistry; not item-specific specs)

  • Core scaffold: Quinazoline (benzopyrimidine) contains two ring nitrogens (typically at the 1- and 3-positions of the diazine ring) fused to a benzene ring.
  • Substitution pattern: “7-methyl” denotes a methyl group on the benzenoid portion of the quinazoline at position 7 (meta to one ring N, para to the ring junction), leaving the diazine ring unsubstituted.
  • Functional groups: Aromatic C–H bonds, two ring nitrogens (sp2), one alkyl substituent (–CH3). No stereocenters.
  • 2D description: A six-membered benzene ring fused to a six-membered diazine (pyrimidine-like) ring; a methyl group projects from the benzenoid ring at C7.

• Typical identifiers (literature, for context only)

  • Molecular formula (literature): C9H8N2
  • Molecular weight (literature): ~144.17 g/mol
  • Example SMILES (literature): CC1=CC2=NC=NC=C2C=C1 (representative; confirm against CoA)

Note: When exact identifiers are required for regulatory, analytical, or database linkage, verify against the item’s CoA/Spec Sheet and SDS.

Synthetic Utility

7-Methylquinazoline offers multiple orthogonal vectors for diversification, making it a versatile scaffold in synthetic and discovery chemistry.

• Key reactive elements

  • Diazine ring nitrogens: H-bond acceptors; can be oxidized (N-oxide) to modulate electronics and enable C–H activation strategies.
  • Benzylic methyl (at C7): Amenable to radical bromination, oxidative functionalization (to CHO/CO2H), or conversion to alcohols/amines via classical sequences.
  • Aromatic C–H sites: Subject to EAS under appropriate conditions; regioselectivity shaped by the electron-withdrawing nature of the diazine ring and the donating/activating influence of the methyl group.

• Representative transformations (literature)

  • Benzylic oxidation: SeO2, MnO2, TEMPO/O2, or metal-catalyzed aerobic oxidation to access 7-formyl/7-carboxyl derivatives.
  • Halogenation: Selective bromination/chlorination on the benzenoid ring; subsequent metal-catalyzed couplings expand substitution patterns.
  • Directed ortho-metalation: s-BuLi/TMEDA at low temperature, then quench with electrophiles (CO2, DMF, B(OMe)3), enabling late-stage diversification.
  • N-oxide strategies: Formation of quinazoline N-oxides to enable rearrangements or increase reactivity in C–H functionalization.

• Retrosynthetic value

  • The scaffold can converge from anthranilamide/anthranilic acid and formamide/imidate chemistry; 7-methyl substitution can originate from a methylated anthranilate or via late-stage benzylic elaboration, providing flexible routes for library design.

Target Specificity

Not applicable. This product is a small-molecule chemical building block and is not an antibody, enzyme, nucleic acid, or biologic reagent with defined target specificity. No antigen/epitope, clone, isotype, or species reactivity information applies.