5-Chloro-6-methoxypicolinic acid - ≥95% , CAS No.1214373-91-7

CAS: 1214373-91-7 Cat. No.: C190143 Formula: C₇H₆ClNO₃ Molecular Weight: 187.58 EC Number: 978-405-5

GRADE & PURITY ≥95%

Synonyms

5-Chloro-6-methoxypicolinic acid | 5-Chloro-6-methoxypyridine-2-carboxylic acid | 5-chloro-6-methoxypyridine-2-carboxylic acid; | 3-Chloro-2-methoxy-6-pyridinecarboxylic acid | A891713 | FT-0759605 | MFCD13185830 | 2-Pyridinecarboxylic acid, 5-chloro-6-me

Storage

Room temperature

Shipped In

Normal

Specifications

Synonyms

5-Chloro-6-methoxypicolinic acid | 5-Chloro-6-methoxypyridine-2-carboxylic acid | 5-chloro-6-methoxypyridine-2-carboxylic acid; | 3-Chloro-2-methoxy-6-pyridinecarboxylic acid | A891713 | FT-0759605 | MFCD13185830 | 2-Pyridinecarboxylic acid, 5-chloro-6-me

Specifications & Purity

≥95%

Storage

Room temperature

Shipped In

Normal

Purity

≥95%

Names and Identifiers

• Canonical Smiles: COC1=C(C=CC(=N1)C(=O)O)Cl
• IUPAC Name: 5-chloro-6-methoxypyridine-2-carboxylic acid
• InChIKey: UPTNUQSNINVJKT-UHFFFAOYSA-N
• INCHI: 1S/C7H6ClNO3/c1-12-6-4(8)2-3-5(9-6)7(10)11/h2-3H,1H3,(H,10,11)
• Isomeric SMILES: COC1=C(C=CC(=N1)C(=O)O)Cl
• Molecular Weight: 187.58
• Reaxy-Rn: 38102930
• Reaxys-RN_link_address: https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=38102930&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Class Pyridines and derivatives
      • Subclass Pyridinecarboxylic acids and derivatives

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Class: Pyridines and derivatives
• Subclass: Pyridinecarboxylic acids and derivatives
• Intermediate Tree Nodes: Not available
• Direct Parent: Pyridinecarboxylic acids
• Alternative Parents: Alkyl aryl ethers Aryl chlorides Heteroaromatic compounds Carboxylic acids Azacyclic compounds Organopnictogen compounds Organonitrogen compounds Organochlorides Organic oxides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Pyridine carboxylic acid - Alkyl aryl ether - Aryl chloride - Aryl halide - Heteroaromatic compound - Carboxylic acid derivative - Carboxylic acid - Ether - Azacycle - Organonitrogen compound - Organochloride - Organohalogen compound - Organic oxygen compound - Organic nitrogen compound - Organooxygen compound - Organic oxide - Organopnictogen compound - Hydrocarbon derivative - Aromatic heteromonocyclic compound
• Description: This compound belongs to the class of organic compounds known as pyridinecarboxylic acids. These are compounds containing a pyridine ring bearing a carboxylic acid group.
• 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

Chemical and Physical Properties

• Molecular Weight: 187.580 g/mol
• XLogP3: 1.600
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 2
• Exact Mass: 187.004 Da
• Monoisotopic Mass: 187.004 Da
• Topological Polar Surface Area: 59.400 Ų
• Heavy Atom Count: 12
• Formal Charge: 0
• Complexity: 176.000
• 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 antibody/assay protocols are associated with this small-molecule building block.

General handling suggestions (chemistry)

• For stock solutions, prepare at 10–100 mM in DMSO; filter if needed through a PTFE membrane. Record exact concentration by weight and solvent density.
• For parallel synthesis, pre-dissolve in DMF or DMSO and dispense gravimetrically or volumetrically using positive-displacement systems.

Biological Roles

Item-specific biological roles are not assigned; this product is provided strictly for research use only.

General context (literature)

• Picolinic acid (pyridine-2-carboxylic acid) is a known chelating ligand in coordination chemistry and occurs as a metabolite in tryptophan catabolism. Substituted picolinates, such as 5-chloro-6-methoxy derivatives, do not have established endogenous biological roles but are widely used as probes and intermediates in chemical biology and medicinal chemistry research.
• Metal binding: Picolinate motifs are bidentate (N,O) ligands. Substitution at C5/C6 can modulate electron density and sterics, tuning complex stability and spectroscopic properties for material or enzymology models.
• pH-dependent speciation: The carboxylate and ring nitrogen confer amphiprotic behavior. Ionization affects membrane permeability and protein binding in assay contexts—consider pH control to maintain a defined protonation state.

Note: No claims are made regarding pharmacology or clinical utility. Any biological testing should be performed under appropriate approvals and controls, and characterization of purity/identity (lot-specific CoA) is essential for reproducible results.

Buffer Applications

This compound is not typically used as a buffering agent. While it bears an ionizable carboxylic acid and a basic pyridine nitrogen, standard laboratory buffers (phosphate, HEPES, acetate, TRIS) are preferred for pH control.

Practical note

• For preparing assay stock solutions, dissolve in DMSO or DMF and dilute into the desired buffer at controlled pH to avoid precipitation. Adjust pH to deprotonate the carboxylate (pH ≥8) if aqueous solubility is limiting.

Green Alternatives

Opportunities to improve sustainability when working with this heteroaromatic acid primarily involve solvent and reagent choices.

Greener solvent options (literature guidance)

• Replace DMF/NMP in amide couplings with:
  • 2-MeTHF or CPME (with appropriate coupling reagents and bases); improved safety and lower EHS footprint versus DMF/NMP.
  • Ethyl acetate or Me-THF as media for Steglich esterifications.
  • Water or water/EtOH biphasic systems for EDC-mediated couplings (use phase-transfer catalysts if needed).
• Cross-coupling media upgrades:
  • EtOH/H2O or 2-MeTHF/H2O co-solvent systems with Pd/dppf or Pd/XPhos catalysts (often effective for Suzuki couplings of heteroaryl chlorides with appropriate bases, e.g., K3PO4).

Reagent considerations

• Favor Pd catalysts that operate at lower loadings and temperatures (e.g., precatalysts with bulky biaryl phosphines) to reduce energy use and metal consumption.
• For demethylation, consider milder alternatives to BBr3 where feasible (e.g., selective oxidative or enzymatic methods), recognizing that scope may be limited.

Comparison snapshot (qualitative)

• DMF vs 2-MeTHF: 2-MeTHF is biorenewable and less persistent; however, solubility of polar acids may be lower—co-solvent DMSO or slight base can assist.
• Toluene vs CPME: CPME offers broader liquid range, lower peroxide formation, and better safety profile.

Waste and work-up

• Exploit pH-switchable extraction (acid/base toggling) to minimize solvent volume and avoid chromatographic purification when possible.
• Capture and recycle Pd where permitted; consider metal scavengers to lower residuals in final materials.

Pharmaceutical Uses

No excipient or pharmacopeial role is specified for this item; it is offered for research use only.

General formulation/manufacturing context (literature/industry practice)

• Heteroaromatic carboxylic acids like substituted picolinic acids are common intermediates in medicinal chemistry programs. The 2-carboxyl functionality allows rapid elaboration to amides/esters, facilitating SAR studies.
• Salt forms: Carboxylate salts (e.g., sodium/potassium) can improve aqueous handling during process development. The basic pyridine nitrogen can also form acid addition salts for purification or crystallization studies.
• Analytical controls: For use as an intermediate, routine controls include HPLC purity, residual palladium (if prior steps used Pd), and polymorph/solvate assessment where crystallization is involved.

Compliance note

• No therapeutic, diagnostic, or clinical claims are made. Any use in a regulated environment requires independent qualification of materials and processes to applicable standards.

Physical Properties

Item-specific properties (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.

Literature/computed expectations for this structural class (for planning only; verify experimentally)

• Aggregation state: typically a crystalline solid for substituted picolinic acids.
• Ionization: carboxylic acid pKa typically ~2–5 (literature, heteroaromatic benzoic acid analogs). The pyridine ring can be protonated (pKaH of pyridine N typically ~1–6 depending on substitution), implying pH-dependent solubility.
• Solubility profile (qualitative, literature):
  • Good solubility in polar aprotic solvents (DMSO, DMF, NMP).
  • Limited solubility in nonpolar solvents; solubility increases in basic aqueous media (formation of carboxylate salt), and decreases in strongly acidic water (neutral acid).
• Melting point: Typically present for aromatic carboxylic acids but not specified for this item; refer to CoA/Spec Sheet.
• Boiling point, density, logP, refractive index: Not specified for this item; refer to CoA/Spec Sheet.

Practical notes

• Weighing/handling: hygroscopicity is generally low for halogenated picolinic acids, but moisture can influence apparent solubility and salt formation; dry before critical stoichiometric use.
• For quantitative property needs (mp, water content, residual solvents), consult the item’s CoA/Spec Sheet prior to scale-up.

Quality & Grades

• Item-specific grade/purity: Not specified for this item; refer to CoA/Spec Sheet.
• Storage conditions (from Product Data): Room temperature; shipped under normal conditions.

Interpreting grade (general guidance)

• Research-grade heteroaromatic building blocks are typically suitable for synthetic applications including coupling, amidation, and library synthesis. When low impurity levels (e.g., metal content, residual solvents, water content) or chromatographic performance are critical, request the lot-specific CoA.
• Stabilizers: None indicated for this item. If present in a particular lot, stabilizers will be listed on the CoA and may affect downstream reactions (e.g., acid/base scavengers or trace inhibitors).

What to check on the CoA/Spec Sheet

• Identity: 1H/13C NMR consistency with the 5-chloro/6-methoxy substitution pattern; HRMS for exact mass; HPLC purity.
• Residual metals/halides: Important if the material is produced via halogenation or Pd-catalyzed steps; request metals data if relevant to your use-case.
• Water content and residual solvents: Karl Fischer and GC headspace values impact solid dispensing, salt formation, and coupling efficiency.

Use case alignment

• For medicinal chemistry and SAR work, typical specifications include >95–98% HPLC purity and well-characterized identity. For process development, impurity profiling and polymorph/solvate assessment may be needed.

Reaction & Applications

This scaffold serves as a versatile heteroaromatic building block combining a cross-coupling handle (5-Cl) and a carboxylic acid at C2.

Representative application families (literature/general)

• Cross-coupling at C5 (aryl chloride): Suzuki–Miyaura (with aryl/heteroaryl boronic acids), Buchwald–Hartwig amination (with amines, often requiring tailored ligands for aryl chlorides), and Stille/Negishi couplings. Ligand selection (e.g., BrettPhos/XPhos/dppf) is important to enable activation of aryl chloride on a pyridine ring.
• Amide/ester formation from the 2-carboxylic acid: HATU/HBTU/EDC-mediated couplings, acid chloride formation (e.g., oxalyl chloride), Steglich esterification (DCC/DMAP) for late-stage diversification.
• Demethylation of the 6-methoxy group: Lewis acid-mediated O-demethylation (e.g., BBr3 or AlCl3) to access the corresponding 6-hydroxypicolinic acid for further derivatization (etherification, sulfonylation, Mitsunobu reactions).
• Directed metalation/functionalization: The ring nitrogen and/or carboxylate can direct lithiation or metalation adjacent to substituents under carefully controlled conditions, enabling further C–H functionalization (literature precedent for picolinic derivatives).
• Coordination chemistry: Picolinate motifs are bidentate ligands; derivatization at C5/C6 allows tuning metal-binding properties for materials/catalysis studies.

Practical tips

• For couplings on pyridyl chlorides, ensure rigorous exclusion of water/air and use bases such as K3PO4, Cs2CO3, or NaOtBu; temperatures 80–120 °C are common depending on ligand system.
• Carboxylic acids may coordinate to Pd; pre-forming acid chlorides or using coupling reagents with bases (DIPEA/DBU) can mitigate inhibition.
• If demethylation is planned, protect other acid-sensitive groups or perform sequence planning to tolerate BBr3 conditions.

Reaction Conditions

General, literature-based guidance for this structural class (verify and optimize for your system):

• Suzuki–Miyaura cross-coupling at C5

  • Catalyst: Pd(dppf)Cl2·DCM (1–3 mol%) or Pd2(dba)3 (1–2 mol%) with XPhos/BrettPhos (2–5 mol%).
  • Base: K3PO4 (2–3 eq) or Cs2CO3 (2–3 eq).
  • Solvent: 2-MeTHF/H2O (4:1), dioxane/H2O, or DMF/H2O.
  • Temperature/time: 80–100 °C, 4–16 h.
  • Notes: Heteroaryl chlorides often require stronger ligands; ensure degassing and inert atmosphere.

• Buchwald–Hartwig amination at C5

  • Catalyst/ligand: Pd2(dba)3 (1–2 mol%) with BrettPhos or RuPhos (3–6 mol%).
  • Base: NaOtBu or Cs2CO3 (2–3 eq).
  • Solvent: Toluene, 2-MeTHF, or dioxane; sometimes DMF.
  • Temperature: 90–120 °C.

• Amide coupling at C2 (from acid)

  • Reagents: HATU or EDC·HCl (1.1–1.5 eq) with DIPEA (2–3 eq).
  • Solvent: DMF, NMP, or MeCN; greener choices include 2-MeTHF with catalytic DMAP.
  • Temperature/time: 0–25 °C to start; 2–16 h.
  • Notes: Minimize water; preform acid chloride (oxalyl chloride, cat. DMF) if coupling is sluggish due to pyridine coordination.

• Demethylation (to 6-hydroxy derivative)

  • Reagent: BBr3 (1–3 eq) in anhydrous DCM.
  • Conditions: −78 to 0 °C addition; warm to RT, 2–12 h; quench cautiously with MeOH/H2O.
  • Caution: Acid-sensitive groups may not survive; protect the carboxyl (e.g., as tBu ester) if needed.

Yields: Highly substrate- and condition-dependent; consult literature precedents for closely related 5-chloro-6-methoxypyridyl systems.

Safety & Handling

Authoritative safety data are provided in the product SDS. The following is general guidance for heteroaromatic carboxylic acids and aryl chlorides.

Item-specific hazard data (from Product Data)

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

General laboratory precautions (guidance)

• Likely hazards: May cause skin/eye irritation and respiratory tract irritation if dust is generated. Avoid inhalation of particulates.
• PPE: Use lab coat, safety glasses or goggles, and appropriate chemical-resistant gloves (e.g., nitrile). Handle powders in a fume hood to minimize dust exposure.
• First aid (overview; consult SDS):
  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Skin contact: Wash with soap and water; remove contaminated clothing.
  • Eye contact: Rinse cautiously with water for several minutes; remove contact lenses if present and easy to do; seek medical advice if irritation continues.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Incompatibilities and stability:
  • Avoid strong bases and strong acids when not intended, as acid-base reactions alter solubility/ionization; avoid strong oxidizers.
  • Aryl chlorides are generally stable; methoxy groups can be cleaved by strong Lewis acids (e.g., BBr3) under forcing conditions.
• Spill response: Avoid dust formation. Collect mechanically or dampen and wipe; dispose according to local regulations.
• Fire safety: Use CO2, dry chemical, or foam. Combustion may produce HCl, NOx, and CO/CO2.

Always defer to the SDS for definitive hazard classification and response procedures.

Solvent Selection

Chemical class considerations

• Polarity/ionization: A heteroaromatic carboxylic acid with an ionizable –CO2H and a basic ring nitrogen; overall amphiprotic behavior leads to pH-dependent solubility.
• Practical implication: Use polar aprotic solvents for stock solutions; switch to basic aqueous media (carboxylate form) for aqueous processing.

Typical solvent performance (general guidance)

• Highly recommended (dissolution/stock solutions): DMSO, DMF, NMP.
• Good/conditional: Acetonitrile, acetone, ethyl acetate (limited by hydrogen bonding and ionization state).
• Aqueous systems: Soluble as sodium/potassium carboxylate at basic pH (≥8–9); limited solubility as the neutral acid at low pH.
• Poor: Alkanes, toluene, and other nonpolar solvents.

When to choose this compound vs alternatives

• Choose this building block when a 5-chloro handle is desired for Pd-catalyzed cross-couplings on a 6-methoxy-substituted picolinic core; the 2-carboxyl group enables straightforward amide/ester library elaboration.

Small comparison (literature-based, qualitative)

• DMSO vs DMF: DMSO offers excellent solubilization and is often preferred for bioassay stock solutions; DMF can be advantageous in amide couplings (HATU/EDC).
• 2-MeTHF/CPME: Greener alternatives for cross-couplings and esterifications with appropriate bases/co-solvents; verify solubility first.

Practical tips

• For analytical HPLC sample prep, dissolve first in DMSO then dilute with water/acetonitrile to avoid precipitation.
• Adjust pH to deprotonate the carboxylate for aqueous work-up or isolation of salts.

Storage & Reconstitution

Item-specific storage/shipping (from Product Data)

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

General guidance for this class of compounds

• Container: Store in a tightly closed, chemically compatible container (glass with PTFE-lined cap) to prevent moisture ingress and contamination.
• Light/moisture: Protect from prolonged exposure to direct light and avoid high humidity. Desiccation is recommended for long-term storage.
• Stability: Aromatic carboxylic acids with aryl chloride and methoxy substituents are typically stable at ambient conditions. Avoid strong acids/bases unless intended.

Reconstitution/solution preparation

• Solvents: DMSO or DMF for concentrated stock solutions; for aqueous use, adjust pH with base (e.g., NaHCO3/NaOH) to form the carboxylate salt and improve solubility.
• Concentrations: Common lab stocks 10–100 mM (verify solubility at your working temperature). Filter sterilize if sterility is required for bioassays (0.22 µm PTFE).
• Freeze-thaw: If solutions must be stored, aliquot and freeze (−20 to −80 °C) to avoid repeated freeze–thaw cycles; inspect for precipitation or degradation before use.

Note: For any parameters not specified above (e.g., exact solubility, stability in solution), consult the lot-specific CoA/Spec Sheet and the SDS.

Structure & Identity

Brief description: 5-Chloro-6-methoxypicolinic acid is a halogenated, methoxy-substituted pyridine-2-carboxylic acid (picolinic acid) derivative useful as a heteroaromatic building block.

• Item-specific identifiers (from Product Data)

  • CAS: 1214373-91-7
  • CID: 53485625
  • InChIKey: 366097 (as provided)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular formula: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular weight: Not specified for this item; refer to CoA/Spec Sheet.

• Structural features (general/literature description)

  • Core ring: pyridine (aromatic six-membered N-heteroaromatic) bearing a 2-carboxylic acid (picolinic acid) function.
  • Substituents: chloro at the 5-position and methoxy at the 6-position on the pyridine ring (relative to the ring nitrogen at position 1 and the carboxyl at position 2).
  • Functional groups: heteroaromatic ring (pyridine), carboxylic acid (–CO2H), aryl chloride (–Cl), aryl methoxy (–OCH3).
  • Stereochemistry: none (achiral).

• 2D structure in words (general)

  • A pyridine ring with N at position 1; the adjacent carbon (position 2) bears the carboxylic acid substituent. Proceeding around the ring, position 5 carries chlorine and position 6 carries a methoxy group. The arrangement provides an ortho relationship between the ring nitrogen and the carboxylate, and vicinal 5-Cl/6-OMe pattern on the heteroaromatic ring.

• Notes

  • For definitive structure strings (SMILES/InChI) and exact elemental composition, consult the item’s CoA/Spec Sheet.

Synthetic Utility

Functional group portfolio

• 2-Carboxylic acid: platform for amide coupling, esterification, and activation to acyl chlorides/anhydrides.
• 5-Chloro (aryl chloride): cross-coupling handle for C–C and C–N bond formation on a pyridine ring.
• 6-Methoxy: a masked phenol equivalent on a pyridine ring; available for demethylation or further ether manipulations.

Retrosynthetic value (literature/general)

• Divergent synthesis: From this node, access arrays of 5-substituted-6-methoxypicolinamides/esters via Suzuki, Sonogashira, or Buchwald–Hartwig reactions at C5, followed by acyl conversions at C2.
• Orthogonality: The acid can be temporarily protected (e.g., as a methyl/tert-butyl ester) to allow harsher coupling or metallation conditions; subsequent deprotection restores the acid.
• Directing effects: The picolinic motif can coordinate metals, aiding regioselective C–H functionalization strategies in neighboring positions (reported for related scaffolds).

Typical transformations

• Amide libraries: HATU/EDC/DIC couplings with DIPEA/DMAP in DMF/MeCN/2-MeTHF.
• Suzuki couplings: Aryl/heteroaryl boronic acids with Pd(dppf)Cl2 or Pd/XPhos systems; bases K3PO4 or Cs2CO3; 60–110 °C depending on substrate.
• Amination: Buchwald–Hartwig amination with primary/secondary amines; bulky electron-rich ligands to activate aryl chloride on heteroaromatics.
• Demethylation: BBr3 (1–3 eq) in DCM at −78 to 0 °C then warm to RT to obtain the 6-hydroxypicolinic acid derivative (protect acid functionality as needed).

Target Specificity

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