5-Chloro-N-methylpyridin-2-amine - ≥97% , CAS No.4214-80-6

CAS: 4214-80-6 Cat. No.: C193352 Formula: C₆H₇ClN₂ Peso molecolare: 142.59 Numero EC: 867-605-7

GRADE & PURITY ≥97%

Synonyms

FT-0664767 | DS-7043 | Z359297632 | A872943 | KSISYWKRGRATSK-UHFFFAOYSA-N | AB07756 | DTXSID90397113 | 5-chloro-N-methylpyridin-2-amine | C75129 | 5-Chloro-N-methyl-2-pyridineamine | 5-chloro-N-methyl-2-pyridinamine | AKOS000431604 | EN300-72983 | 5-Chlor

Storage

Room temperature

Shipped In

Normal

Specifications

Sinonimi

FT-0664767 | DS-7043 | Z359297632 | A872943 | KSISYWKRGRATSK-UHFFFAOYSA-N | AB07756 | DTXSID90397113 | 5-chloro-N-methylpyridin-2-amine | C75129 | 5-Chloro-N-methyl-2-pyridineamine | 5-chloro-N-methyl-2-pyridinamine | AKOS000431604 | EN300-72983 | 5-Chlor

Specifiche e purezza

≥97%

Condizioni di conservazione di stoccaggio

Room temperature

Spedito in

Normal

Purezza

≥97%

Nomi e identificatori

Sorrisi canonici

CNC1=NC=C(C=C1)Cl

IUPAC Name

5-chloro-N-methylpyridin-2-amine

InChIKey

KSISYWKRGRATSK-UHFFFAOYSA-N

INCHI

1S/C6H7ClN2/c1-8-6-3-2-5(7)4-9-6/h2-4H,1H3,(H,8,9)

Isomeri SMILES

CNC1=NC=C(C=C1)Cl

Peso molecolare

142.59

Reaxy-Rn

471842

Reaxys-RN_link_address

https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=471842&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Classe Pyridines and derivatives
      • Subclass Aminopyridines and derivatives

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Classe: Pyridines and derivatives
• Subclass: Aminopyridines and derivatives
• Intermediate Tree Nodes: Not available
• Direct Parent: Aminopyridines and derivatives
• Alternative Parents: Imidolactams Aryl chlorides Heteroaromatic compounds Azacyclic compounds Organochlorides Hydrocarbon derivatives Amines
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Aminopyridine - Imidolactam - Aryl halide - Aryl chloride - Heteroaromatic compound - Azacycle - Organic nitrogen compound - Hydrocarbon derivative - Organonitrogen compound - Organochloride - Organohalogen compound - Amine - Aromatic heteromonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as aminopyridines and derivatives. These are organic heterocyclic compounds containing an amino group attached to a pyridine 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: 142.580 g/mol
• XLogP3: 1.800
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 1
• Exact Mass: 142.03 Da
• Monoisotopic Mass: 142.03 Da
• Topological Polar Surface Area: 24.900 Ų
• Heavy Atom Count: 9
• Formal Charge: 0
• Complexity: 87.100
• 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 protocols (WB, IHC, IF, FC, etc.) are associated with this small-molecule building block in our catalog entry.

General laboratory use (guidance):

• For chemical synthesis: follow standard protocols for cross-coupling, acylation, or SNAr as outlined in the Reaction Conditions tab; adjust stoichiometry and catalyst loading based on substrate reactivity and scale.
• For screening solutions: prepare 10–50 mM DMSO stocks; vortex and sonicate if needed. Filter through 0.2 µm PTFE if particulates persist. Record final DMSO % in assays.

For any application requiring specification-controlled parameters (e.g., residual metals, water content), consult the CoA for the specific lot prior to use.

Biological Roles

Item is supplied for research use only; no clinical or diagnostic use is implied.

General context (literature/biochemistry):

• Pyridine motifs are prevalent in bioactive molecules, often modulating basicity and H-bonding while maintaining aromaticity. They can mimic the electronic properties of pyridyl moieties present in cofactors (e.g., NAD+/NADH contain a pyridinium core), though this compound itself is not a cofactor or metabolite.
• Secondary anilines like N-methylaminopyridines can act as H-bond donors/acceptors and coordinate metal centers in enzyme models or synthetic metallo-complex probes.
• The chloropyridyl handle allows late-stage diversification for generating small-molecule libraries to probe SAR against diverse biochemical targets in discovery settings.

Limitations and cautions:

• This compound is not known to have intrinsic biological roles in cellular metabolism, signaling, or structural biology. Any observed bioactivity in assays would be context-dependent and should be interpreted with appropriate controls.
• Due to basic amine functionality, nonspecific binding and pH-dependent partitioning may occur in biochemical assays; buffer composition and compound salt form can substantially affect apparent potency or binding readouts.

Buffer Applications

This product is not a buffering reagent and is not typically used to prepare defined pH buffer systems.

Practical notes (general):

• In biochemical assays, if this compound must be dissolved for screening, prepare stock solutions in DMSO and dilute into the assay buffer (maintaining low final DMSO, e.g., ≤1–2%).
• Because it is a basic amine, it may shift assay pH at high concentrations or interact with buffer components; use well-buffered systems (e.g., HEPES, phosphate) and verify pH after dosing.
• Salt forms (e.g., HCl) may be employed to improve aqueous compatibility, but this is formulation for solubility rather than buffering capacity.

If a true buffer is required, choose standard systems (e.g., phosphate pH 6–8, HEPES pH 6.8–8.2, citrate pH 3–6) appropriate to your experimental pH window.

Green Alternatives

Strategies to improve the sustainability profile when working with chloropyridyl amines (literature/general):

• Solvent swaps:

  • Replace DMF/DMAc/NMP with greener polar aprotics where feasible (e.g., Cyrene, propylene carbonate, dimethyl sulfone, or 2-MeTHF for couplings that tolerate ether solvents).
  • Use 2-MeTHF or CPME instead of THF/Et2O for extractions and couplings; they offer lower peroxide formation rates and better safety profiles.
  • Favor EtOAc or IPA for workups and crystallizations over chlorinated solvents when solubility allows.

• Catalysis optimization:

  • For aryl chloride couplings, use modern Pd catalysts/ligands active at lower loadings and milder temperatures to reduce energy and catalyst usage.
  • Explore Ni catalysis for C–C/C–N bond formation to reduce reliance on precious metals.

• Process intensification:

  • Conduct telescoped sequences (e.g., in situ acylation after coupling) to reduce solvent exchanges and waste.
  • Leverage micellar catalysis (e.g., TPGS-750-M) for some cross-couplings in water, provided the amine’s basicity and salt forms are compatible.

Illustrative solvent comparison (general):

• DMF: excellent solvency, but reproductive toxin and problematic EHS profile.
• Cyrene: bio-based dipolar aprotic; higher viscosity, may require heat but avoids DMF hazards.
• 2-MeTHF: renewable, hydrophobic ether; good for extractions and many couplings, forms fewer peroxides than THF; not as polar as DMF, so dissolution may require co-solvent.

Pharmaceutical Uses

No therapeutic claims are made. For research and process development contexts only.

Typical roles of 5-chloro-N-methylpyridin-2-amine-like scaffolds (literature/general):

• Synthetic intermediate: provides a handle for diversification at the 5-position (via aryl chloride) and functional derivatization of the secondary amine. Useful in constructing pyridinyl-containing fragments within candidate APIs.
• Salt screening: the basic secondary amine forms stable salts (e.g., hydrochloride, fumarate) that can be evaluated for improved crystallinity, hygroscopicity, and processability during pre-formulation research.
• Impurity/degradant reference: in route scouting, chloropyridyl amines can arise as impurities or intermediates; authentic material supports analytical method development and impurity qualification.

Regulatory/compendial status:

• Pharmacopeial listings: Not specified for this item; refer to CoA/Spec Sheet.
• Residual solvent/elemental impurity expectations follow ICH Q3 guidelines in GMP settings; for discovery-scale use, consult internal specs and the item’s CoA.

Formulation considerations (non-clinical research):

• Convert to a suitable salt for aqueous studies; screen counterions for solubility and stability.
• For in vitro DMPK assays, DMSO stock solutions (10–50 mM) are commonly employed; filter through 0.2 µm if particulate forms upon dilution.

Physical Properties

Item-specific specifications (this catalog entry):

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

Typical physicochemical data (literature/general, for 5-chloro-N-methylpyridin-2-amine):

• Molecular formula: C6H7ClN2 (literature)
• Molecular weight: ~142.59 g/mol (calculated from literature formula)
• Physical state: usually a solid or low-melting solid for related 2-aminopyridine derivatives (literature/general)
• Basicity: secondary aniline-type base; pyridine ring also contributes weak basicity (literature)
• Solubility: good in polar aprotic organics (DMF, DMSO, NMP, acetonitrile, ethyl acetate); moderate in alcohols; limited in nonpolar hydrocarbons; low in water except as protonated salts (literature/general)
• Partitioning: expected moderate polarity due to ring N and secondary amine; logP typically in low-to-moderate range for chloropyridyl amines (literature/general)
• UV absorbance: aromatic chromophore; strong absorbance in 200–300 nm region (literature/general)

Notes:

• Exact BP/MP, density, refractive index, pKa, and UV cutoff are Not specified for this item; refer to CoA/Spec Sheet.
• Values above are provided as general literature context to aid method development; verify with the lot-specific CoA when needed for specification-critical work.

Quality and Grades

Item-specific quality information:

• 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 interpreting common grades for heteroaromatic amines (general):

• Research grade: suitable for most synthetic applications; typical purity by HPLC/GC ≥95%. Trace residual solvents/related substances are common and should be within acceptable lab limits (verify CoA).
• ≥98% or ≥99% purity: preferred for medicinal chemistry SAR or analytical reference purposes; minimizes byproduct formation in coupling chemistry.
• Water/peroxide/metal specifications: Not specified for this item; refer to CoA/Spec Sheet. For moisture-sensitive couplings, determine KF on receipt.

Analytical controls typically applied (general best practice):

• Identity: 1H/13C NMR, HRMS or accurate mass, and IR. For pyridinyl amines, diagnostic signals include downfield ring protons and NH resonance (may exchange/broaden).
• Purity: HPLC-UV at 254 nm; LC–MS for mass/impurities. Residual halides or overalkylated amines can be monitored by LC–MS.

What to expect from Aladdin Scientific:

• Lot-traceable CoA with assay and key impurities where applicable.
• Packaging intended to minimize atmospheric moisture and contamination.
• For sensitive transformations, contact us for current batch analytical details before placing critical orders.

Reaction and Applications

This chloropyridyl secondary amine is a versatile building block for heteroaromatic synthesis and medicinal chemistry.

Representative application areas (literature/general):

• Scaffold diversification: nucleophilic substitution or cross-coupling at the 5-chloro position to install aryl/alkyl/heteroaryl groups, giving 5-substituted 2-(methylamino)pyridines.
• C–N bond formation: the secondary amine can undergo acylation (to amides, ureas, carbamates), sulfonylation (sulfonamides), or reductive amination after deprotection/derivatization.
• Metal-catalyzed cross-coupling: the aryl chloride on the pyridine often participates in Pd-catalyzed Suzuki, Sonogashira, or Buchwald–Hartwig couplings with appropriate ligands (e.g., BrettPhos, XPhos variants) tailored for aryl chlorides.
• SNAr: activated by the ring nitrogen; under strong base/nucleophile and elevated temperature, displacement of Cl by amines/alkoxides is feasible for certain substitution patterns.
• Salt and prodrug analog exploration: formation of hydrochloride or mesylate salts for solubility tuning in screening libraries.

Practical tips:

• Protect the secondary amine (e.g., Boc, Cbz) if it poisons catalysts or participates in side reactions; Boc often aids crystallinity and handling.
• The pyridine nitrogen can coordinate to metals; ligand/catalyst selection and base choice (e.g., bulky alkoxides or carbonates) mitigate inhibition in coupling.
• For SNAr, ensure rigorously dry polar aprotic solvent and sufficient base; consider cesium carbonate or sodium tert-butoxide.
• Monitor by LC–MS (ESI+) exploiting the basic amine for sensitive detection.

Reaction Conditions

General literature guidance for typical transformations of 5-chloro-N-methylpyridin-2-amine and close analogs (optimize per substrate/catalyst; values are indicative, not specifications):

• Suzuki–Miyaura coupling (C5–Cl → C5–Ar):

  • Catalyst/ligand: Pd(dba)2 (1–2 mol%) + XPhos/Buchwald-type ligand (2–4 mol%) or precatalysts (e.g., XPhos Pd G3, 1–2 mol%).
  • Base: K3PO4 or Cs2CO3 (2–3 equiv).
  • Solvent: 1,4-dioxane/H2O (10:1) or toluene; 80–110 °C, 4–16 h.
  • Notes: Protect the secondary amine if it coordinates strongly; Boc protection often improves yield.

• Buchwald–Hartwig amination (C5–Cl → C5–NR2):

  • Catalyst/ligand: Pd2(dba)3 (1 mol% Pd) + BrettPhos or RuPhos (2–4 mol%).
  • Base: NaOtBu or Cs2CO3 (2–3 equiv).
  • Solvent: toluene, dioxane, or tAmOH; 80–110 °C, 6–18 h.

• Sonogashira coupling (C5–Cl → C5–C≡CR):

  • Catalyst: Pd(PPh3)2Cl2 (1–2 mol%) + CuI (5–10 mol%).
  • Base: Et3N or DIPEA (3–4 equiv), solvent: THF or DMF; 50–80 °C, 4–12 h.

• Amide/sulfonamide formation (at secondary amine):

  • Reagents: acyl chloride or sulfonyl chloride (1.1–1.5 equiv), base: DIPEA or pyridine (2–3 equiv).
  • Solvent: DCM or THF; 0 °C to rt, 1–4 h. For carbamates, use chloroformates under similar conditions.

• SNAr (Cl displacement):

  • Nucleophile: amines/alkoxides; Base: NaH/NaOMe/Cs2CO3; Solvent: DMSO/DMF; 80–140 °C, 6–24 h; success depends on substitution pattern and nucleophile strength.

Yields vary widely with ligand/base/solvent; run small-scale screens to identify optimal conditions.

Safety and Handling

Authoritative safety information should be taken from the product SDS.

Item-specific hazard data in this listing:

• 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 safety considerations for chloropyridyl secondary amines (literature/general):

• Likely to be harmful if swallowed, in contact with skin, or inhaled; may cause skin/eye irritation and respiratory tract irritation.
• Amines can be sensitizers in some cases; avoid repeated skin contact.
• Aromatic amines may be harmful to aquatic life; prevent release to the environment.

Handling and PPE (good laboratory practice):

• Use in a fume hood. Avoid dust/aerosols.
• Wear lab coat, nitrile gloves, and splash goggles. For scale-up, consider a disposable sleeve/chemically resistant apron.
• Avoid contact with strong oxidizers and acylating agents; secondary amine may form salts with strong acids.

First aid (overview; consult SDS):

• Skin/eye: Rinse with water for several minutes; remove contaminated clothing; seek medical attention if irritation persists.
• Inhalation: Move to fresh air; seek medical advice if symptoms occur.
• Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.

Fire and reactivity (general):

• Combustible organic solid; use CO2, dry chemical, or foam. Thermal decomposition can release nitrogen oxides and HCl-containing fumes.

Solvent Selection

Compound type: moderately polar heteroaromatic secondary amine with an aryl chloride.

Solubility/miscibility profile (literature/general):

• Highly soluble: DMSO, DMF, DMAc, NMP, acetonitrile.
• Soluble: ethyl acetate, dichloromethane, methanol/ethanol (protonation possible), THF (moderate to good).
• Limited: toluene, hexanes (use heat or co-solvent).
• Aqueous media: low at neutral pH; increases in acidic media as ammonium salt.

Selection guidance by use-case:

• Cross-coupling (Buchwald–Hartwig, Suzuki after halogen activation on ring): choose dry toluene/dioxane/THF or polar amide solvents (DMF/DMAc/NMP) depending on catalyst system and base.
• SNAr on the aryl chloride (if activating substituents/conditions): polar aprotic (DMSO/DMF) with inorganic bases.
• Salt formation/purification: dissolve in EtOAc or MeOH, then treat with HCl in ether/IPA to precipitate hydrochloride salt.
• Workup/extraction: amines extract into organic at basic pH; protonate to move to aqueous if needed.

Quick comparison (general):

• DMSO/DMF: maximum solubility and reactivity for SNAr; harder to remove.
• THF/1,4-dioxane: coupling-friendly, easy to remove; may need co-solvent for full dissolution.
• EtOAc/MeOH: convenient for crystallization or salt formation; watch for transesterification or alkylation under forcing conditions.

Storage and Reconstitution

Item-specific conditions:

• Storage: Room temperature (per Product Data). Protect from excessive heat and direct sunlight.
• Shipped: Normal (ambient) conditions.

General handling and storage guidance for heteroaromatic amines:

• Keep tightly closed in a dry container. Minimize exposure to atmospheric moisture and acidic vapors to avoid salt formation on surfaces.
• If long-term storage is anticipated, placing the primary container in a desiccator or adding a desiccant pouch can help maintain low humidity.

Reconstitution/dissolution (for stock solutions; general):

• Organic stocks: readily dissolves in DMSO, DMF, or acetonitrile to prepare 10–100 mM solutions. Filter through 0.2 µm PTFE/nylon if required.
• Aqueous use: prepare a salt (e.g., HCl) or dilute from DMSO stock into buffered aqueous media; avoid high local concentrations to prevent precipitation.
• Stability of solutions: Not specified for this item; refer to CoA/Spec Sheet. As a general practice, store DMSO stocks at 2–8 °C or −20 °C in aliquots to limit freeze–thaw cycles and air exposure.

Disposal: Follow institutional and local regulations for amine-containing organic chemicals; typically treated as hazardous organic waste.

Structure and Identity

Heteroaromatic amine building block: a chlorinated pyridine bearing a secondary amine at C2.

• SKU: C193352
• Product name: 5-Chloro-N-methylpyridin-2-amine
• CAS: 4214-80-6 (item-specific)
• PubChem CID: 3837024 (literature)
• Molecular formula: Not specified for this item; refer to CoA/Spec Sheet. (Typical for 5-chloro-N-methylpyridin-2-amine: C6H7ClN2, literature)
• Molecular weight: Not specified for this item; refer to CoA/Spec Sheet. (Calculated from literature formula C6H7ClN2: ~142.59 g/mol)
• InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
• SMILES: Not specified for this item; refer to CoA/Spec Sheet. (Representative, literature: a 2-(methylamino)-5-chloropyridine SMILES)

Structural features (general description):

• Core ring: six-membered aromatic pyridine ring containing one ring nitrogen.
• Substituents: chloro at the 5-position (meta to the ring nitrogen) and N-methylamino at the 2-position (ortho to the ring nitrogen).
• Functional groups: secondary amine (N–H, N–CH3) conjugated to an electron-deficient pyridine; aryl chloride (C–Cl) suitable for SNAr and cross-coupling.
• Stereochemistry: none (achiral). 2D depiction would show a pyridine ring with N at position 1, NHCH3 at position 2, and Cl at position 5.

Synthetic Utility

Key reactive sites:

• Aryl chloride (C–Cl) at C5 of a pyridine: platform for Pd/Ni-catalyzed cross-coupling (Suzuki, Sonogashira, Negishi, Kumada) and, under appropriate activation, nucleophilic aromatic substitution.
• Secondary amine at C2: undergoes acylation, sulfonylation, carbamoylation, and alkylation. It can be protected (Boc, Cbz) to guide chemoselectivity.
• Ring nitrogen: coordinates to metals and can be quaternized to give pyridinium salts.

Representative transformations (literature/general):

• Suzuki coupling at C5 to append aryl/heteroaryl groups using Pd(dba)2/XPhos or Pd-PEPPSI-IPr (for chlorides), K3PO4 or Cs2CO3 base, in toluene/dioxane at 80–110 °C.
• Buchwald–Hartwig amination at C5 to introduce anilines or alkyl amines; ligand choice (BrettPhos, RuPhos) is crucial for aryl chlorides.
• Sonogashira coupling to install alkynes (Pd/Cu co-catalysis), followed by further derivatization (e.g., cyclizations).
• Formation of amides/sulfonamides from the secondary amine using acid chlorides/anhydrides or sulfonyl chlorides with non-nucleophilic bases (DIPEA, pyridine) at 0–25 °C.
• Directed lithiation/metalation adjacent to the pyridine N (under strong base, low temperature) for further functionalization, if compatible with the amine (often protected).

Retrosynthetic value:

• Serves as a convergent node: amine derivatization sets physicochemical properties while C5 functionalization installs diversity elements, ideal for parallel synthesis and SAR exploration.

Target Specificity

Not an antibody, enzyme, or biological targeting reagent. No target specificity data are provided for this chemical building block.

• Antigen/epitope: Not applicable.
• Species reactivity/clone/isotype: Not applicable.

Use this compound as a small-molecule intermediate; any biological target engagement would be context-specific to derivatives synthesized from it.