4-Ethyl-1,3-thiazol-5-amine - ≥95% , CAS No.1249955-33-6

CAS: 1249955-33-6 Cat. No.: E993475 Formula: C₅H₈N₂S Peso molecolare: 128.199 Numero EC: 892-462-2

GRADE & PURITY ≥95%

Storage

Room temperature

Specifications

Specifiche e purezza

≥95%

Condizioni di conservazione di stoccaggio

Room temperature

Purezza

≥95%

Nomi e identificatori

Sorrisi canonici

CCC1=C(SC=N1)N

IUPAC Name

4-ethyl-1,3-thiazol-5-amine

InChIKey

YTISIBIFDGLAOL-UHFFFAOYSA-N

INCHI

1S/C5H8N2S/c1-2-4-5(6)8-3-7-4/h3H,2,6H2,1H3

Peso molecolare

128.199

Proprietà chimiche e fisiche

• Peso molecolare: 128.199 g/mol
• XLogP3: 1.400
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 3
• Rotatable Bond Count: 1
• Exact Mass: 128.041 Da
• Monoisotopic Mass: 128.041 Da
• Topological Polar Surface Area: 67.200 Ų
• Heavy Atom Count: 8
• Formal Charge: 0
• Complexity: 76.800
• 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 immunoassay or bioassay protocols (e.g., WB, IHC, IF, FC) are associated with this small-molecule building block.

General handling suggestion for screening

• Prepare a DMSO stock (e.g., 10–100 mM) under dry conditions; vortex and, if needed, sonicate gently.
• Filter sterilize (0.22 µm PTFE) only if sterility is required for cell-based exploratory assays, recognizing potential adsorption losses for small hydrophobic molecules.
• Record final DMSO content in assay to maintain consistency across wells.

Biological Roles

Item-specific biological activity is not assigned; this product is supplied strictly for research use.

General biochemistry context (literature-based)

• Thiazole motif: The thiazole ring is a prevalent heteroaromatic motif in natural products and cofactors; notably, thiazolium chemistry underpins thiamine (vitamin B1) catalysis. While 4-ethyl-1,3-thiazol-5-amine is not a cofactor, the ring electronics (N and S) contribute to heteroatom-directed interactions in protein binding sites.
• Primary aryl amine handle: Provides a hydrogen-bond donor/acceptor site and a convenient point for derivatization in probe or ligand design.
• ADME-relevant features: The 4-ethyl substituent increases hydrophobicity relative to unsubstituted 5-aminothiazole, which can influence permeability and solubility in medicinal chemistry campaigns.

Caveat

• No specific biological function, pathway role, or target affinity is claimed or implied for this item. Any biological testing should be conducted under appropriate institutional approvals and recorded as exploratory research.

Buffer Applications

This compound is a heteroaromatic amine used primarily as a synthetic building block and is not a conventional buffering agent. It is not typically employed to control pH in biochemical assays.

Practical note

• If used in biological assays, prepare DMSO stock solutions (e.g., 10–50 mM) and dilute into the assay buffer, maintaining final DMSO at ≤1–2% v/v to minimize solvent effects. Protonated salts (e.g., HCl salt) may show improved aqueous compatibility.

Green Alternatives

Greener choices center on solvent and reagent selection during derivatization of 4-ethyl-1,3-thiazol-5-amine.

Greener solvent substitutions (general guidance)

• Replace DCM with EtOAc or 2-MeTHF for acylations and workups, where feasible.
• Use water/EtOH or MeCN/H2O mixtures for coupling reactions when compatible with reagents and catalysts.
• Consider propylene carbonate or Cyrene for high-polarity needs as alternatives to DMF/NMP in some transformations (evaluate solubility and reactivity case-by-case).

Catalyst and reagent choices

• Amide couplings: Favor carbodiimide-free systems (e.g., CDI, DMTMM, T3P) that reduce urea waste; or use enzyme-inspired coupling in aqueous media for simple systems.
• N-Arylation: Employ ligand-efficient Pd systems that operate at low loadings, or copper-catalyzed Ullmann-type couplings with benign bases (e.g., K2CO3) in greener solvents.
• Reductive amination: Use BH3·THF alternatives such as sodium triacetoxyborohydride in acetic acid/EtOH; where possible, hydrogenation over Pd/C in EtOH under H2 is atom-economical.

Compact comparison (general)

• Conventional vs greener options
  • DCM → EtOAc/2-MeTHF: Similar performance in acylations; greener disposal profile.
  • DMF/NMP → MeCN/2-MeTHF/propylene carbonate: Reduced toxicity; check solubility/yields.
  • Stoichiometric activators → catalytic or coupling in water: Less waste; may require optimization.

Note: Validate any substitution with small-scale trials to confirm yield, selectivity, and impurity profile.

Pharmaceutical Uses

No pharmacopeial or excipient status is provided for this item; it is intended for research and process development only.

Relevant roles in pharmaceutical R&D (general; not product-specific)

• Medicinal chemistry intermediate: The primary amine enables rapid parallel synthesis of amides, sulfonamides, ureas, and N-aryl analogs around a thiazole core frequently encountered in screening collections.
• Salt screening: Formation of crystalline salts (e.g., HCl, fumarate) can aid in solid-state studies and preformulation of candidate molecules derived from this scaffold.
• Impurity/reference standard: Can serve as a reference or impurity standard in analytical methods where thiazol-5-amine motifs arise.

No therapeutic, diagnostic, or clinical claims are made for this material.

Physical Properties

Item-specific specifications

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

Theoretical/literature expectations for this structure (for planning only; not product specs)

• Phase at ambient conditions: typically a crystalline solid or low-melting solid for small heteroaryl amines of this size.
• Acid–base behavior: primary aryl amine; conjugate acid expected to be weakly basic relative to aliphatic amines due to the electron-poor thiazole ring (literature trend for 5-aminothiazoles).
• Solubility profile (qualitative):
  • Good solubility expected in polar aprotic solvents (DMSO, DMF, NMP) and in alcohols upon warming.
  • Limited solubility anticipated in nonpolar hydrocarbons; moderate in ethyl acetate/acetone.
• UV characteristics: thiazole ring shows π→π* absorption in the near-UV; primary amine may cause bathochromic shift relative to unsubstituted thiazoles (literature trend). No item-specific UV cutoff provided.

Not provided for this specific item (consult CoA/SDS or measure as needed)

• Melting point, boiling point, density, refractive index, logP/logD, pKa (numerical), vapor pressure, water solubility (quantitative), UV cutoff, elemental/metals/peroxide/water limits.

Note: For quantitative properties critical to your method (e.g., solubility limits, extinction coefficients), verify experimentally on your batch or request a CoA.

Quality and Grades

Item-specific quality information

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

Guidance on interpreting grades (general; for planning only)

• Research/Chemical grade: Suitable for most synthesis and screening work. Trace metal/UV backgrounds are not controlled unless stated.
• High-purity/Analytical grades (when offered): Tighter controls on assay, residual solvents, and often on UV absorbance (for analytical work). For heteroaromatics used in discovery chemistry, low-UV grades can reduce baseline noise in LC/UV methods.
• Water/peroxide/metals limits: Not specified for this item; refer to CoA/Spec Sheet.

Batch documentation

• Request a Certificate of Analysis (CoA) for your lot to confirm: assay method (e.g., qNMR/GC), residual solvents, chromatographic purity, identity (NMR, HRMS), and any controlled impurities (isomeric content, inorganic residues).

Process notes

• Primary aryl amines can slowly discolor by air oxidation. If high chrom purity is critical (e.g., for SAR), consider using fresh material, storing under inert gas, and performing a short plug or recrystallization prior to use as needed.

Reaction and Applications

Use this heteroaromatic amine as a versatile synthon in heterocycle-rich libraries and SAR campaigns. The 5-amino group provides a gateway to diverse derivatives while the 4-ethyl substituent modulates lipophilicity.

Representative transformations (literature/general; adapt to your system)

• N-Acylation / N-Sulfonylation: Rapid formation of amides and sulfonamides using acyl/sulfonyl chlorides or activated esters (DMAP or base catalysis). Useful for tuning H-bonding and pKa.
• Urea / Thiourea / Carbamate formation: React with isocyanates/isothiocyanates or chloroformates (often at 0–25 °C) to access potent HBD/HBA motifs for medchem.
• Reductive amination (on carbonyl-bearing partners): First convert to a secondary/tertiary amine using aldehydes/ketones with NaBH3CN or BH(OAc)3 (often in MeOH/AcOH).
• Buchwald–Hartwig N-arylation: Couple the aniline-like nitrogen to aryl/vinyl halides or pseudohalides under Pd catalysis using appropriate ligands (e.g., BrettPhos, XPhos) to build N-aryl thiazol-5-amine derivatives.
• Diazotization/Sandmeyer-type approaches (heteroaryl context): Under controlled conditions, 5-aminothiazoles can be transformed via diazonium chemistry to access 5-halo or 5-cyano variants, enabling further cross-couplings (consult specialized literature for scope).
• Salt formation: Generate hydrochloride or mesylate salts to improve crystallinity and handling; can be leveraged for isolation/purification.

Applications in discovery chemistry (general)

• Privileged scaffold elaboration: Thiazoles occur in many bioactive libraries; 4-ethyl substitution subtly increases lipophilicity and steric bulk, aiding permeability optimization.
• Fragment-to-lead: Primary amine enables parallel derivatization; the small core keeps MW low, useful for fragment or Rule-of-3 contexts.

Reaction Conditions

Generalized conditions reported in the literature for closely related 5-aminothiazoles (guide only; optimize per substrate):

• N-Acylation / N-Sulfonylation

  • Solvents: DCM, EtOAc, MeCN, THF
  • Bases: Triethylamine, DIPEA, Na2CO3
  • Temperature: 0–25 °C (cooling for acid chlorides)
  • Time: 0.5–4 h typically; monitor by TLC/LCMS

• Urea/Carbamate Formation

  • Reagents: Isocyanates/isothiocyanates or chloroformates
  • Solvents: DCM, MeCN, toluene, or 2-MeTHF
  • Conditions: 0–25 °C; catalytic DMAP can accelerate

• Reductive Amination (to secondary/tertiary amines)

  • Solvent: MeOH, EtOH, or DCE with 1–3 equiv AcOH
  • Reductant: NaBH3CN or NaBH(OAc)3
  • Temperature: 0–25 °C; 2–16 h

• Buchwald–Hartwig N-Arylation

  • Catalyst: Pd2(dba)3 or Pd(OAc)2 (1–3 mol%)
  • Ligand: BrettPhos/XPhos/RuPhos (2–6 mol%)
  • Base: NaOtBu, Cs2CO3, or K3PO4
  • Solvent: Toluene, dioxane, or MeCN
  • Temperature: 60–110 °C; 6–18 h

• Diazotization/Sandmeyer-type (heteroaryl context)

  • Reagents: tBuONO or NaNO2/HX at 0–5 °C, followed by CuX for halogenation/cyanation
  • Caution: Temperature control and exclusion of moisture can be critical to stability/selectivity.

Typical outcomes

• Yields vary widely with substitution and electronics; 50–90% is common for acylations and urea formations; cross-couplings require ligand/base tuning. Always confirm by small-scale trials.

Safety and Handling

Compliance and intended use

• Research Use: For research use only (per Product Data). Not for human or veterinary applications.

GHS and hazard communication

• Signal word: Not specified for this item; refer to SDS.
• Hazard statements (H-phrases): Not specified for this item; refer to SDS.
• GHS classification and pictograms: Not specified for this item; refer to SDS.

General safety guidance for heteroaryl amines (literature-based; not product-specific)

• Potential hazards: May cause skin/eye irritation or respiratory irritation; aromatic amines can be sensitizers in some cases.
• PPE: Use lab coat, safety glasses, and nitrile gloves as a baseline. Handle powders in a fume hood to avoid inhalation of dust.
• Handling: Avoid dust generation. Use inert spatulas and closed containers. Minimize exposure to air humidity if hygroscopic behavior is observed experimentally.
• Incompatibilities: Strong oxidizers; nitrosating agents; acylating agents may react exothermically with the amine; avoid strong acids/bases when not intended for reaction.
• First aid overview: If on skin/eyes, rinse with water for ≥15 minutes. If inhaled, move to fresh air. If ingested, rinse mouth. Seek medical attention as per SDS.
• Fire safety: Treat as an organic solid; use CO2, dry chemical, or foam. Combustion may release NOx and SOx.

Waste disposal

• Collect organic solid waste according to institutional and local regulations. Do not discharge to drains. Consult SDS for regulatory classifications.

Solvent Selection

Compound type: Heteroaromatic primary amine (polar, H-bond donor/acceptor) with a compact thiazole core.

Practical solvent guidance (general expectations)

• Strong solvents for dissolution and reactions: DMSO, DMF, NMP.
• Moderately polar organic media: ethanol, methanol, isopropanol, acetonitrile, acetone, ethyl acetate (often with gentle heat or sonication).
• Limited solubility likely: toluene, hexanes, MTBE, cyclohexane (use co-solvent strategies).
• Aqueous systems: Free base shows limited water solubility; solubility increases upon protonation (e.g., dilute HCl to form the ammonium salt) if salt formation is compatible with your process.

When to choose which solvent

• Parallel synthesis/medchem: DMSO stock solutions (10–100 mM) are typical; dilute into assay buffers with ≤1–2% DMSO.
• N-acylation/sulfonylation/urea formation: Use dichloromethane (room temp) or acetonitrile/THF (0–25 °C) with base; for greener options, EtOAc or 2-MeTHF can be suitable.
• Cross-couplings (via prefunctionalization): DMF, dioxane, or toluene/EtOH/water mixtures under Pd catalysis after converting the amine to a suitable leaving group derivative.

Small comparison (general)

• DMSO vs DMF: DMSO offers broader solubility; DMF is lower viscosity and easier to remove. For moisture-sensitive steps, thoroughly dry either solvent.
• EtOAc vs DCM: EtOAc is greener and often adequate for acylations; DCM provides faster phase separation and higher volatility but with higher environmental burden.

Storage and Reconstitution

Item-specific conditions (from Product Data)

• Storage Conditions: Room temperature.
• Shipped In: Not specified for this item; refer to CoA/Spec Sheet.

General storage guidance for heteroaryl amines (supplemental)

• Container: Store in a tightly closed, chemically compatible container (e.g., amber glass vial) to limit moisture and light exposure.
• Atmosphere: If long-term storage is anticipated, consider purging headspace with inert gas (N2 or Ar) to minimize slow oxidative discoloration typical of aryl amines.
• Segregation: Keep away from strong oxidizers and acids.

Reconstitution and solution stability

• Stock solutions: Prepare in dry DMSO, DMF, or alcohols. For DMSO stocks (10–100 mM), store aliquots at 2–8 °C or −20 °C to reduce freeze–thaw cycles.
• Aqueous compatibility: Solubility improves upon protonation; if needed, dissolve in minimal DMSO then dilute into buffered aqueous media or prepare an HCl salt prior to dissolution.
• Stability: Solution stability is system-dependent; prepare fresh solutions for sensitive reactions and monitor by LC/MS if stored >24–48 h.

Note: For definitive, lot-specific guidance (including any stabilizers or assay), consult the CoA and SDS.

Structure and Identity

Brief description: 4-Ethyl-1,3-thiazol-5-amine is a substituted 1,3-thiazole bearing an ethyl group at C4 and a primary amino group at C5; it is a heteroaromatic N,S-containing building block.

• Item-specific identifiers (from Product Data)

  • SKU: E993475
  • Product Name: 4-Ethyl-1,3-thiazol-5-amine
  • CAS: 1249955-33-6
  • CID: 60044679
  • InChIKey: 446412 (as provided)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Theoretical/literature identifiers (computed from the name; not item-specific specs)

  • Core scaffold: 1,3-thiazole (five-membered aromatic ring containing one N and one S)
  • Substitution pattern: C4 = ethyl (–CH2–CH3); C5 = primary amine (–NH2)
  • Functional groups: heteroaromatic ring, primary aryl amine, thiazole nitrogen and sulfur heteroatoms
  • Molecular formula (theoretical): C5H8N2S
  • Molecular weight (theoretical): ~128.20 g/mol
  • Stereochemistry: None (achiral)

• 2D structural description (words)

  • The ring consists of S at position 1 and N at position 3 in an aromatic thiazole. Adjacent ring carbons (C4 and C5) are substituted: C4 bears an ethyl chain extending from the ring; C5 bears an –NH2 group oriented coplanar to the ring system. The remaining ring carbon (C2) is unsubstituted.

Synthetic Utility

Functional group synopsis

• Primary aryl amine at C5: Nucleophilic, enables coupling to acyl/sulfonyl/aryl electrophiles; can be transformed into diazonium intermediates under specific conditions.
• 1,3-Thiazole ring: Electron-deficient heteroaromatic; directs regioselectivity in electrophilic/nucleophilic substitutions on suitably activated derivatives; coordinates to metals, influencing catalysis outcomes.
• 4-Ethyl substituent: Lipophilic handle; can be oxidized or functionalized at the benzylic-like methylene under strong conditions (e.g., radical or bromination routes on heteroaryl-activated positions; scope depends on conditions).

Key transformations (literature/general)

• Amide/sulfonamide libraries via acyl or sulfonyl chlorides, anhydrides, or coupling agents (EDC·HCl/HOBt alternatives such as DMTMM, T3P, CDI).
• N-Arylation (Buchwald–Hartwig, Ullmann-type) to access N-aryl thiazol-5-amines.
• Ureas/thioureas/carbamates via isocyanates/isothiocyanates/chloroformates.
• Electrophilic diazotization at the amine followed by substitution (e.g., halogenation, cyanation) to furnish 5-substituted thiazoles amenable to cross-coupling (Suzuki, Negishi) if a suitable handle is introduced.

Retrosynthetic value

• Serves as a convergent point: diverse N-substituents can be introduced late-stage on a fixed heterocycle; the ethyl group preserves hydrophobicity while keeping molecular weight low, aiding property modulation in SAR.

Target Specificity

Not applicable. This product is a small-molecule building block and is not an antibody, enzyme, or affinity reagent. No antigen/epitope, clone, isotype, or species reactivity information applies.