3-Morpholinopyridin-4-amine - ≥97% , CAS No.144864-28-8

CAS: 144864-28-8 Cat. No.: M980651 Formula: C₉H₁₃N₃O Peso molecolare: 179.220

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

C1COCCN1C2=C(C=CN=C2)N

IUPAC Name

3-morpholin-4-ylpyridin-4-amine

InChIKey

HWABPMNYOPPSHZ-UHFFFAOYSA-N

INCHI

1S/C9H13N3O/c10-8-1-2-11-7-9(8)12-3-5-13-6-4-12/h1-2,7H,3-6H2,(H2,10,11)

Peso molecolare

179.220

Taxonomic Classification

Taxonomy Tree

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

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Classe: Pyridines and derivatives
• Subclass: Halopyridines
• Intermediate Tree Nodes: Not available
• Direct Parent: Polyhalopyridines
• Alternative Parents: Dialkylarylamines Aminopyridines and derivatives Morpholines Heteroaromatic compounds Trialkylamines Propargyl-type 1,3-dipolar organic compounds Oxacyclic compounds Enamines Dialkyl ethers Azacyclic compounds Aldimines Organopnictogen compounds Monoalkylamines Hydrocarbon derivatives
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Polyhalopyridine - Dialkylarylamine - Tertiary aliphatic/aromatic amine - Aminopyridine - Oxazinane - Morpholine - Heteroaromatic compound - Tertiary aliphatic amine - Tertiary amine - Oxacycle - Azacycle - Organic 1,3-dipolar compound - Propargyl-type 1,3-dipolar organic compound - Ether - Enamine - Dialkyl ether - Aldimine - Organic nitrogen compound - Organic oxygen compound - Organopnictogen compound - Hydrocarbon derivative - Primary amine - Organooxygen compound - Organonitrogen compound - Primary aliphatic amine - Imine - Amine - Aromatic heteromonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as polyhalopyridines. These are organic compounds containing a pyridine ring substituted at two or more positions by a halogen 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

Proprietà chimiche e fisiche

• Peso molecolare: 179.220 g/mol
• XLogP3: -0.100
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 4
• Rotatable Bond Count: 1
• Exact Mass: 179.106 Da
• Monoisotopic Mass: 179.106 Da
• Topological Polar Surface Area: 51.400 Ų
• Heavy Atom Count: 13
• Formal Charge: 0
• Complexity: 159.000
• 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 vendor-validated bioassay protocols (WB, IHC, IF, FC) are associated with this small-molecule reagent.

• Item-specific tested applications and recommended dilutions: Not specified for this item; refer to CoA/Spec Sheet.

General lab usage suggestions:

• For biochemical screening or assay development, prepare stock solutions in DMSO (e.g., 10–100 mM), then dilute into assay buffer ensuring final DMSO ≤1–2% v/v as tolerated by the system.
• Filter sterilize through 0.22 µm PTFE or PVDF if sterility is required for cell-free assays (note: product is for research use only; no clinical/cell therapy use).

Biological Roles

• Item-specific biological/biochemical role data: Not specified for this item; research use only.

• General context (literature; no clinical claims):

  • The 3-morpholinyl–4-aminopyridine scaffold is widely explored in medicinal chemistry as a polarity-balanced, H-bonding-capable fragment. The morpholine ring modulates basicity and aqueous solubility, while the 4-aminopyridine can serve as a hydrogen-bond donor/acceptor pair in ligand design.
  • Such heteroaryl amines are common in libraries targeting kinases, enzymes with hinge-binding motifs, and protein–protein interaction interfaces, due to the pyridine nitrogen’s ability to accept H-bonds and the aniline nitrogen’s donor capacity.
  • No endogenous biological role is known; it is an entirely synthetic small molecule used for research and synthesis. Any biological activity is context-dependent on derivatization and target systems.

Buffer Applications

This item is a heteroaryl amine building block and is not typically used as a buffering agent or pH standard.

• Not applicable: There are no established buffer systems based on 3-morpholinopyridin-4-amine.
• Practical note: If dissolution in aqueous media is required for assays, temporary acidification (e.g., dilute HCl) can form soluble amine salts, but this is a solubilization tactic rather than buffering. Adjust pH with appropriate buffer systems (e.g., phosphate, acetate) separate from the analyte.

Green Alternatives

While the product itself is a solid reagent, greener choices often relate to solvent/base/reagent selection in its transformations.

• Greener solvent swaps (general guidance):

  • Replace DMF/NMP/DMAc with MeCN, EtOAc, 2-MeTHF, or propylene carbonate where feasible.
  • Employ EtOAc or 2-MeTHF for acylations/sulfonylations instead of DCM/THF when compatibility is demonstrated.
  • For extractions, consider cyclopentyl methyl ether (CPME) or MTBE over diethyl ether (lower peroxide risk; always monitor peroxides as standard best practice).

• Reagent and base considerations:

  • Use carbodiimide couplings with catalytic additives (Oxyma) or enzyme-mimetic alternatives when suitable, minimizing hazardous coupling byproducts.
  • Favor inorganic bases (K2CO3, NaHCO3) over strongly basic, high-toxicity amines when reaction scope allows.

• Small comparison (literature-based):

  • THF vs 2-MeTHF: similar polarity; 2-MeTHF often offers improved safety and renewability.
  • DCM vs EtOAc: EtOAc is less hazardous and biodegradable; may require optimization for solubility/kinetics.

All substitutions should be verified by small-scale trials to ensure yield and selectivity are maintained.

Pharmaceutical Uses

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

• General, non-clinical context:

  • This compound is best viewed as a synthetic intermediate/building block in process and medicinal chemistry programs. The morpholine–pyridine–aniline triad is frequently incorporated to tune polarity, solubility, and binding interactions in small-molecule candidates.
  • In formulation development studies (preclinical research), the free base or acid-addition salts (e.g., HCl, sulfate, mesylate) of related amines are sometimes screened for physical properties (crystallinity, hygroscopicity, dissolution) — applicable to derivatives of this scaffold.
  • No medical or therapeutic claims are made. For research use only.

Physical Properties

• Item-specific (from Product Data):

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

• Literature/computed (general reference values; not item specifications):

  • Molecular formula (structural inference): C9H13N3O (literature/computed based on 3-(morpholin-4-yl)pyridin-4-amine).
  • Molecular weight (calculated): ≈179.22 g/mol.
  • Acid/base characteristics: contains a basic pyridine N (pKaH typically ~5–6 for pyridines, literature) and a tertiary amine in morpholine (pKaH typically ~8.3–8.6, literature), plus an aniline-type –NH2 that is weakly basic.
  • Solubility (qualitative, literature expectations): soluble in polar aprotic solvents (DMSO, DMF, NMP) and often alcohols; limited aqueous solubility may increase substantially under acidic conditions (salt formation).
  • LogP/logD (qualitative): expected to be moderate polarity (morpholine and aniline functionalities reduce hydrophobicity relative to simple aryl amines).
  • Physical state: typically a solid for similar heteroaryl amines (literature expectation).

• Not specified for this item; refer to CoA/Spec Sheet: exact MP/BP, density, refractive index, UV cutoff, water/peroxide/metal limits.

Quality and Grades

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

• How to interpret common grades (general guidance):

  • Research grade: suitable for most synthetic and discovery workflows; typical assays include HPLC purity and identity (NMR/HRMS).
  • Analytical/AR grade: tighter control on inorganic/organic impurities; useful when trace contaminants affect analytical outcomes.
  • Pharm. or GMP-related grades: include expanded quality attributes and documentation; not typically required for exploratory synthesis.

• Impurities to monitor for heteroaryl amines (general):

  • Residual starting reagents (e.g., halo-pyridines), over-acylated byproducts, oxidative dimers, inorganic salts.
  • For amines, check residual water, volatile amines/solvents, and potential salification state (free base vs. salt) by titration or NMR.

• Documentation:

  • For this SKU, please consult the latest CoA/Spec Sheet for confirmed purity assay, residual solvent profile (ICH Q3C), and identity data (NMR/HRMS/LC).

Reaction and Applications

3-Morpholinopyridin-4-amine is a versatile heteroaryl amine useful as a fragment or late-stage diversification handle in medicinal and materials chemistry.

• Typical applications (general/literature):

  • Amide formation at the aniline –NH2 with acid chlorides, anhydrides, or via coupling (EDC/HOBt, HATU, PyBOP). Electron-deficient pyridyl anilines often acylate cleanly under mild base (DIPEA, pyridine).
  • Sulfonamide formation using sulfonyl chlorides in DCM/THF with base.
  • Carbamate/urea synthesis with chloroformates or isocyanates; CDI-mediated routes also effective.
  • N-oxide formation on the pyridine ring using m-CPBA or H2O2/AcOH, enabling further Chichibabin-like rearrangements or regioselective substitutions (literature strategies).
  • Quaternization of the morpholine nitrogen with alkyl halides to give morpholinium salts (used to tune solubility/PK of derivatives).
  • Electrophilic aromatic substitutions are limited on pyridine; instead, use directed metalation or C–H activation tactics for ring diversification (e.g., Pd-catalyzed C–H amination/arylation on related substrates, literature).

• Role in discovery chemistry:

  • The 3-morpholinyl motif is a common polarity and solubility enhancer, while the 4-aminopyridine site enables rapid parallel library generation via acylation/sulfonylation.

• Practical tips:

  • Protect the aniline (e.g., Boc, Cbz) if selectivity over the morpholine N is needed.
  • For clean acylations, pre-form amine salts or employ mixed anhydrides to minimize overacylation.
  • Confirm site-selectivity by 1H/13C NMR; morpholine N-acylation vs aniline acylation give distinct shifts.

Reaction Conditions

General literature guidance for common transformations of 3-morpholinopyridin-4-amine and close analogs (not item specifications):

• Amide formation (aniline –NH2):

  • Solvent: DCM, DMF, 2-MeTHF, or EtOAc.
  • Reagents: acid chloride (1.1–1.5 eq) with DIPEA or pyridine; or HATU/EDC with base (DIPEA).
  • Temperature: 0–25 °C (acid chlorides) or 20–40 °C (carbodiimide couplings).
  • Time: 1–16 h; monitor by LC.

• Sulfonamide formation:

  • Solvent: DCM/THF; Base: Et3N or DIPEA.
  • 0–25 °C, 1–6 h.

• Urea/carbamate formation:

  • Reagents: CDI (1.2–1.5 eq) in DMF/MeCN; or chloroformates (phosgene alternatives) with base.
  • 20–50 °C, 2–16 h.

• Pyridine N-oxide formation:

  • Oxidant: m-CPBA (1.1–1.5 eq) in DCM/MeCN, 0–25 °C; reduction post-functionalization via PCl3 or Zn/AcOH.

• Morpholine N-alkylation (quaternization):

  • Solvent: MeCN or acetone; Alkyl halide (1.2–2.0 eq); Heat: 40–80 °C; 2–24 h.

• Workup/purification:

  • Acid–base extraction to separate neutral vs. cationic forms; silica gel chromatography with EtOAc/MeOH or DCM/MeOH gradients; salt switches for crystallization.

Actual conditions require optimization based on substrate and scale. Use inert atmosphere and anhydrous solvents where moisture-sensitive reagents are employed.

Safety and Handling

• Item-specific (from Product Data):

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

• General safety guidance (literature/standard practice; defer to SDS):

  • Likely hazards for aromatic amines/tertiary amines: may cause skin/eye irritation and respiratory tract irritation; avoid dust/aerosols. Some aniline-type compounds can be harmful if absorbed; handle with care.
  • PPE: lab coat, nitrile gloves, safety glasses; use in a chemical fume hood.
  • Incompatibilities: strong oxidizers, strong acids/bases (may lead to salt formation or degradation), and acylating/sulfonylating agents (will react with the –NH2). Avoid prolonged exposure to air moisture if purity is critical (amine salts can form under acidic atmospheres).
  • First aid overview: if inhaled, move to fresh air; if on skin/eyes, rinse with water for 15 minutes; if ingested, rinse mouth; seek medical attention as needed. Remove contaminated clothing.
  • Spill/cleanup: avoid dust, ventilate, collect with inert absorbent, dispose per local regulations.
  • Fire: use CO2, dry chemical, or foam extinguishers; combustion may release nitrogen oxides and other irritants.

Always consult the product’s SDS for authoritative hazard classification and response procedures.

Solvent Selection

This compound is a polar, heteroatom-rich aromatic amine; solvent choice is typically guided by reaction task (acylation, coupling) and desired ionization state.

• Polarity and miscibility (literature expectations):

  • Soluble in polar aprotic media (DMSO, DMF, DMAc, NMP) and often in alcohols (MeOH, EtOH). Limited solubility in nonpolar solvents unless protonated or co-solvated.
  • Aqueous solubility increases upon acidification (amine salt formation); select volatile acids (e.g., HCl, TFA) when facile removal is required.

• Selection guidance by application:

  • Acylation/sulfonylation: use anhydrous DCM, THF, MeCN, or DMF with base (e.g., DIPEA, pyridine). For greener options, consider 2-MeTHF or ethyl acetate when compatible.
  • N-alkylation (morpholine quaternization): polar aprotic solvents (MeCN, acetone, DMF) can accelerate SN2; avoid protic media that suppress nucleophilicity.
  • Salt formation/crystallization: alcoholic solvents with antisolvent addition (Et2O/MTBE/hexanes) are often effective for isolating amine salts.

• Quick comparison (general):

  • DMSO/DMF: excellent solubilization; difficult removal.
  • MeCN/EtOAc: moderate polarity; easier workup.
  • Alcohols: good for salt manipulations and protection/deprotection steps.

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 (literature/standard best practice):

  • Keep in a tightly closed container, in a dry place, protected from excessive heat and direct light.
  • If hygroscopicity is observed, store under desiccation or inert gas. Avoid prolonged exposure to acidic vapors to prevent unintentional salt formation.
  • For solution stocks: dissolve in anhydrous DMSO, DMF, or alcohols to prepare concentrates (e.g., 10–100 mM). Aliquot and store at −20 °C to minimize freeze–thaw cycles; allow to reach room temperature before opening to prevent moisture condensation.
  • Stability in solution depends on solvent and acidity; avoid strong acids/oxidants unless intended for derivatization.

• Reconstitution tips:

  • Sonication and gentle warming (≤40 °C) can aid dissolution in high-boiling polar aprotic solvents.
  • For aqueous use, prepare an acidic aqueous stock (e.g., dilute HCl) to form a soluble salt, then adjust to the desired medium as needed.

Always refer to the latest CoA/SDS for item-specific stability and handling recommendations.

Structure and Identity

A heteroaromatic, bifunctional building block combining a pyridine ring and a morpholine moiety, bearing a primary aniline-type amine at the 4-position of the pyridine.

• Item-specific (from Product Data):

  • Product name: 3-Morpholinopyridin-4-amine
  • CAS: 144864-28-8
  • PubChem CID: 75422287
  • InChIKey (as provided): 132532
  • Storage: Room temperature

• Literature/computed (typical identity information; not item specifications):

  • Preferred IUPAC-style name (literature): 3-(morpholin-4-yl)pyridin-4-amine
  • Structural features: pyridine (aza-arene) ring with a para-amine (4-aminopyridine) and a morpholin-4-yl substituent at the 3-position; one ring nitrogen in pyridine, one tertiary amine nitrogen in morpholine, plus one primary aryl amine on the pyridine ring.
  • Functional groups: aromatic heterocycle (pyridine), primary aniline-type amine (–NH2), tertiary amine within morpholine, cyclic ether (morpholine oxygen).
  • Stereochemistry: None (achiral, no stereocenters).
  • 2D description in words: a six-membered pyridine ring with N at position 1; the 4-position bears –NH2; the 3-position is bonded to the morpholin-4-yl nitrogen of a six-membered saturated ring containing one N and one O (morpholine).

• Not specified for this item; refer to CoA/Spec Sheet: SMILES, standard InChI, definitive InChIKey for this batch.

Synthetic Utility

Key reactivity stems from three distinct sites: the aniline –NH2 (nucleophilic, acylatable), the morpholine tertiary amine (alkylation/quaternization, selective acylation under certain conditions), and the pyridine ring (N-oxidation, directed functionalization).

• Transformations (literature/general):

  • Amide/sulfonamide formation at the 4-amino group using acid chlorides, anhydrides, or sulfonyl chlorides with base; peptide-coupling reagents (HATU/EDC) enable mild conditions.
  • Urea/carbamate assembly via CDI, triphosgene alternatives, or isocyanates; selective protection (e.g., Boc on morpholine) may be applied.
  • Pyridine N-oxide formation (m-CPBA) to enable regioselective substitutions, then reduction (PCl3, Zn/AcOH) to regenerate pyridine.
  • Quaternization of morpholine N with MeI/MeOTf or alkyl halides (tailored solubility and ionic properties).
  • Electrophilic tagging on the aniline (e.g., diazotization→Sandmeyer variants) is less typical for pyridyl anilines but can be explored under controlled conditions.

• Retrosynthetic value:

  • Often accessed from 3-halo-4-aminopyridines via nucleophilic substitution with morpholine or by Buchwald–Hartwig amination (Pd-catalyzed C–N coupling). Conversely, it serves as a diversification node to rapidly generate analogs by acylation/sulfonylation.

• Selectivity tips:

  • Exploit differential basicity: aniline –NH2 acylates faster than morpholine N under many conditions; however, in highly activated systems, competitive morpholine acylation can occur — use protecting groups or stoichiometry control.

Target Specificity

Not applicable. This product is a small-molecule chemical building block, not a biological macromolecule or affinity reagent.

• Item-specific antigen/epitope/clone/isotype data: Not specified for this item.