Ethyl 3-(4-nitropyrazol-1-yl)propanoate - ≥97% , CAS No.512809-69-7

CAS: 512809-69-7 Cat. No.: E1027150 Formula: C₈H₁₁N₃O₄ Peso molecolare: 213.190

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

CCOC(=O)CCN1C=C(C=N1)[N+](=O)[O-]

IUPAC Name

ethyl 3-(4-nitropyrazol-1-yl)propanoate

InChIKey

RTUQSGIUSVTNEX-UHFFFAOYSA-N

INCHI

1S/C8H11N3O4/c1-2-15-8(12)3-4-10-6-7(5-9-10)11(13)14/h5-6H,2-4H2,1H3

Peso molecolare

213.190

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organic 1,3-dipolar compounds
    • Classe Allyl-type 1,3-dipolar organic compounds
      • Subclass Organic nitro compounds
        • Level5 C-nitro compounds
          • Level6 Nitroaromatic compounds

• Kingdom: Organic compounds
• Superclass: Organic 1,3-dipolar compounds
• Classe: Allyl-type 1,3-dipolar organic compounds
• Subclass: Organic nitro compounds
• Intermediate Tree Nodes: C-nitro compounds
• Direct Parent: Nitroaromatic compounds
• Alternative Parents: Pyrazoles Heteroaromatic compounds Carboxylic acid esters Propargyl-type 1,3-dipolar organic compounds Organic oxoazanium compounds Monocarboxylic acids and derivatives Azacyclic compounds Organonitrogen compounds Organic salts Organic oxides Hydrocarbon derivatives Carbonyl compounds Organic cations
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Nitroaromatic compound - Azole - Pyrazole - Heteroaromatic compound - Carboxylic acid ester - Carboxylic acid derivative - Monocarboxylic acid or derivatives - Organic oxoazanium - Propargyl-type 1,3-dipolar organic compound - Organoheterocyclic compound - Azacycle - Organic oxide - Organooxygen compound - Organonitrogen compound - Carbonyl group - Organic salt - Organic oxygen compound - Organic nitrogen compound - Hydrocarbon derivative - Organic cation - Aromatic heteromonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as nitroaromatic compounds. These are c-nitro compounds where the nitro group is C-substituted with an aromatic 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

Proprietà chimiche e fisiche

• Peso molecolare: 213.190 g/mol
• XLogP3: 0.200
• Hydrogen Bond Donor Count: 0
• Hydrogen Bond Acceptor Count: 5
• Rotatable Bond Count: 5
• Exact Mass: 213.075 Da
• Monoisotopic Mass: 213.075 Da
• Topological Polar Surface Area: 89.900 Ų
• Heavy Atom Count: 15
• Formal Charge: 0
• Complexity: 241.000
• 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 manufacturer-validated bioassay or analytical protocols are provided for this item.

General laboratory usage notes (non-validated, for guidance only):

• Stock solutions: Prepare at 10–100 mM in dry DMSO or DMF; filter (0.2 µm PTFE) if needed. Record exact concentration gravimetrically.
• Reaction setup: For moisture-sensitive steps (couplings), use anhydrous solvents and inert atmosphere. Additives such as Oxyma/HOBt can improve coupling efficiency after saponification to the acid.
• Analytical QC: Verify identity and purity by 1H NMR, LC–MS, and, if needed, 13C NMR/HRMS.

For any application-specific protocol, develop and validate conditions in your laboratory.

Biological Roles

This product is a synthetic heteroaromatic building block supplied for laboratory research. No endogenous biological role or biochemical activity is assigned.

• Biological function: Not applicable. Pyrazole motifs can appear in bioactive molecules, but this specific compound is a research intermediate and not a characterized biochemical metabolite.
• Biotransformations (general/literature): In biological systems, nitro groups can be reduced to amines under certain reductive conditions; esters may be hydrolyzed by esterases. Such information is provided for chemical context only and not as a claim of biological activity.
• Use context: Suitable as a structural motif in SAR exploration or as a linker-bearing fragment in chemical biology tool synthesis. Any use in cells or organisms must be designed and validated by the researcher.

Research Use Note: For research use only. Not for human or veterinary use, clinical diagnosis, or therapeutic applications.

Buffer Applications

This compound is not a buffering reagent and does not form conventional laboratory buffer systems. It lacks a conjugate acid/base pair in the physiological pH range when in ester form.

• Practical note: If used in biochemical assays, dissolve in a compatible co-solvent (e.g., DMSO) and dilute into the assay buffer per experimental design. Assess solubility and precipitation limits empirically.

For pH control in reactions or assays, select an appropriate buffer (e.g., phosphate, HEPES, Tris) independent of this reagent.

Green Alternatives

While the substance itself is a target building block rather than a solvent, greener choices can be made around its use, especially in reductions and couplings (general/literature guidance):

• Solvent choices for common steps:

  • Replacement of DMF/NMP: Use MeCN, 2-MeTHF, CPME, or ethyl acetate when feasible for couplings or extractions.
  • Hydrogenation media: Prefer EtOH, water/EtOH mixtures, or 2-MeTHF over dichloromethane or THF (when catalyst compatibility allows).

• Reagent alternatives:

  • Nitro reduction: Consider catalytic hydrogenation (H2, Pd/C) in ethanol at ambient temperature/pressure over tin(II) chloride or iron/acid, which generate inorganic waste. Transfer hydrogenation with formic acid or ammonium formate can also reduce waste.
  • Amide couplings: Use greener coupling systems (e.g., EDC/Oxyma in EtOAc or MeCN) instead of HATU/HBTU in DMF to minimize HF-generating waste and improve solvent profile.

• Workup considerations:

  • Favor aqueous ethanol or EtOAc over chlorinated solvents for phase separations when compatible.
  • Employ solvent recycling for MeCN/EtOAc, and minimize siliceous waste with optimized gradients.

Comparison (general):

• DMF vs MeCN/EtOAc: MeCN/EtOAc offer lower toxicity and easier recovery but may reduce solubility for highly polar intermediates.
• SnCl2 vs H2/Pd: Catalytic H2 methods cut waste but require pressure apparatus and careful catalyst handling.

Adopt green metrics (E-factor, PMI) during route design to quantify improvements.

Pharmaceutical Uses

No pharmacopeial status or excipient role is indicated for this item.

• Formulation role: Not applicable. This product is a research-grade synthetic intermediate/building block and is not supplied for formulation use.
• Regulatory status: Not established; not intended for API or excipient use.

Research Use Note: For research use only. Not for clinical, diagnostic, or therapeutic applications.

Physical Properties

Item-specific physico-chemical specifications are not provided in the Product Data. Values below are general expectations for this scaffold, offered as literature-style guidance only; they are not product specifications.

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Melting point / boiling point: Not specified for this item; refer to CoA/Spec Sheet.
• Density, refractive index: Not specified for this item; refer to CoA/Spec Sheet.
• Solubility (general/literature expectations):
  • Organic solvents: typically soluble in polar aprotic media (DMSO, DMF, NMP) and moderately soluble in ethyl acetate, CH2Cl2, MeCN.
  • Aqueous solubility: expected to be low due to ester and heteroaryl nitro functionality; can increase upon saponification to the carboxylate salt (literature observation for related analogs).
• Acid/base behavior (general): the molecule is largely neutral; the pyrazole N2 can engage in H-bonding but is not strongly basic; the ester is non-ionizable. Upon hydrolysis, the carboxylic acid (pKa typically ~4–5 for analogous heteroaryl propionates; literature) can ionize.
• Partitioning (general/literature): moderately polar heteroaromatic ester; cLogP expected in the low-to-moderate range for comparable nitropyrazolyl propanoates.

For exact specification values (mp, purity, water, residual solvents, UV cutoff), please refer to the CoA/Spec Sheet for this specific lot.

Quality and Grades

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

Guidance on quality considerations for heteroaromatic building blocks (general):

• Assay/purity reporting: Typically provided by HPLC/GC with area% or weight% assay, and corroborated by 1H NMR integration. For nitro-heteroaromatics, monitoring reduction-sensitive impurities is advisable.
• Residual solvents and water: Karl Fischer and GC headspace data, if provided, are critical to reaction planning (e.g., for moisture/base-sensitive couplings). If not listed here, consult the CoA.
• Stabilizers/inhibitors: None are indicated in the Product Data. If a stabilizer is present for this item, it will be listed on the label/CoA.
• Chromatographic grade notes: Not applicable to this solid/liquid building block unless explicitly designated. If HPLC-grade suitability is required (e.g., for assay prep), low-UV-absorbance solvents and clean sample prep are recommended.

What to check on receipt (best practice):

• Visual appearance compared to CoA; verify NMR against literature structure (diagnostic pyrazole protons, ethyl ester quartet/triplet, and propyl chain methylenes).
• Confirm mass by LC–MS; nitro to amine reduction products or hydrolyzed acids can appear as minor peaks—quantify if your application is sensitive.

For definitive grade, impurity profile, and acceptance criteria, rely on the lot-specific CoA/Specification Sheet.

Reaction and Applications

Ethyl 3-(4-nitropyrazol-1-yl)propanoate is a versatile bifunctional building block for heterocycle-rich libraries and linkers.

Key application families (general/literature):

• Chemoselective reduction of the nitro group to 4-aminopyrazol-1-yl derivatives:
  • Catalytic hydrogenation (H2, Pd/C or Raney Ni) or transfer hydrogenation (e.g., hydrazine/Raney Ni) affords the aniline-like pyrazole-4-amine, enabling subsequent acylation, urea formation, or diazotization-based diversification.
• Ester transformations for linker and conjugation chemistry:
  • Saponification (NaOH, MeOH/H2O) furnishes the 3-(4-nitropyrazol-1-yl)propanoic acid, ready for peptide-like amide couplings (EDC/HOBt, HATU, PyBOP). Transesterification to other alkyl esters or activation to acid chlorides (SOCl2) expands reactivity.
• Nucleophilic substitution on activated derivatives:
  • After nitro reduction to the amine, carbamate/urea formation (with chloroformates or isocyanates) and sulfonamide installation (sulfonyl chlorides) proceed readily.
• Heteroaromatic functionalization:
  • The pyrazole ring can participate in N→metal coordination for directed transformations; however, electrophilic substitution on a nitro-substituted pyrazole is typically deactivated (literature caution).

Applications in discovery chemistry:

• Acts as a heteroaryl–aliphatic spacer with orthogonal handles (nitro/amine convertible, ester/acid convertible) useful in fragment growth, linker optimization, and PROTAC-like exploratory constructs (research context).

Practical tips:

• Protect the ester during strong basic conditions; sequence planning (reduce vs hydrolyze first) affects selectivity. Use mild hydrogenation to avoid ester cleavage; monitor by LC–MS.

Reaction Conditions

The following conditions are general literature guidance for analogous nitropyrazolyl esters and are not product specifications.

• Nitro reduction to amine:

  • Catalytic hydrogenation: 5–10 wt% Pd/C (5–10 mol% cat. relative to substrate), H2 1–3 bar, EtOH or EtOAc, 20–30 °C, 2–6 h. Monitor for ester stability; avoid acidic supports if transesterification is a concern.
  • Alternative: Fe (3–5 equiv) in AcOH/H2O or SnCl2·2H2O in EtOH/conc. HCl at 50–70 °C, 1–4 h; increased inorganic waste.

• Ester hydrolysis (saponification):

  • NaOH (1–2 equiv) in MeOH/H2O (4:1 to 9:1), 0–25 °C, 1–3 h. Acidify to pH ~2 for isolation. For acid-sensitive steps, consider LiOH in THF/H2O.

• Amide coupling (from acid):

  • HATU (1.1 equiv), DIPEA (2–3 equiv), DMF or MeCN, 0–25 °C, 1–12 h; or EDC·HCl (1.2 equiv) with Oxyma (1.2 equiv) in EtOAc/MeCN for a greener profile.

• Transesterification:

  • Catalytic acid (p-TsOH) or base (NaOMe) in ROH solvent, reflux 1–6 h; monitor to avoid pyrazole ring degradation under strong basic conditions.

• Purification:

  • Silica gel chromatography using EtOAc/hexanes or DCM/MeOH gradients. The amine product typically elutes later and may require base-deactivated silica.

Typical isolated yields for these transformations in the literature range from 60–90% depending on substrate and conditions.

Always optimize on small scale and monitor by LC–MS/NMR.

Safety and Handling

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

General safety considerations for nitro-heteroaromatic esters (literature guidance; not product-specific):

• Hazards: May cause irritation to skin, eyes, and respiratory tract. Nitroaromatics can present methemoglobin-forming risks upon significant exposure; handle to minimize inhalation/ingestion. Esters and polar aprotic solvents used with it can enhance dermal absorption—wear appropriate PPE.
• PPE: Lab coat, nitrile gloves, splash goggles. Use inside a chemical fume hood to avoid vapor/aerosol exposure, especially during solvent handling or scale-up.
• Incompatibilities: Avoid strong reducing agents unless intentional reduction (nitro → amine) is conducted in a controlled apparatus. Avoid strong bases when ester stability must be preserved. Oxidizers may react with organic material.
• Special risks: Nitro groups are reducible; catalytic hydrogenations can release heat and form amine intermediates—use pressure-rated equipment with proper gas management. Ethers/esters may form peroxides in certain solvents—monitor solvent quality.
• First aid (overview, defer to SDS):
  • Inhalation: Move to fresh air; seek medical attention if symptoms persist.
  • Skin/eye contact: Rinse with water for at least 15 minutes; remove contaminated clothing; obtain medical advice.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.

Always consult the Aladdin SDS for definitive hazard classification and response measures.

Solvent Selection

This compound is a moderately polar heteroaromatic ester. While item-specific solubility data are not provided, the following guidance reflects common behavior of nitropyrazolyl esters (literature/general):

• Preferred dissolution media:

  • Polar aprotic: DMSO, DMF, NMP—excellent solubility for stock solutions and coupling reactions.
  • Medium polarity: CH2Cl2, EtOAc, MeCN—often provide workable solubility for extractions and chromatography.
  • Alcohols: MeOH, EtOH—moderate solubility; may promote transesterification under basic/acidic conditions.
  • Water: typically poor solubility in neutral water; solubility increases after saponification to the acid salt.

• Selection by task:

  • Amide coupling after hydrolysis: dissolve the acid in DMF/MeCN with a coupling base (DIPEA) and additive (e.g., HOBt/HOAt or Oxyma).
  • Catalytic hydrogenation (nitro → amine): mixed solvents (EtOH/THF, EtOAc, or MeOH) are common; DCM is avoided under high H2 pressures.
  • SN-type alkylations at the side chain (e.g., post-saponification): use polar aprotic solvents (DMF/DMSO) to maximize base solvation.

• Workup/chromatography tips:

  • Silica gel with EtOAc/hexanes or EtOAc/CH2Cl2 gradients typically resolves nitro vs amine congeners.
  • Avoid prolonged exposure to basic alumina to minimize ester cleavage.

Solvent selection should consider the sensitivity of the nitro group (to reduction) and the ester (to hydrolysis/transesterification).

Storage and Reconstitution

• Storage (Product Data): Room temperature.
• Shipped in: Not specified for this item; refer to CoA/Spec Sheet.
• Formulation/appearance: Not specified for this item; refer to CoA/Spec Sheet.

Best practices (general):

• Store tightly capped in a dry, inert atmosphere (desiccator with desiccant). Protect from prolonged light exposure to minimize potential nitro-photoactivity.
• If preparing solutions: Use anhydrous, oxygen-free solvents when relevant; aliquot and store solutions at 2–8 °C or −20 °C depending on solvent stability to minimize hydrolysis and oxidation. Avoid repeated freeze–thaw of DMSO stocks by using single-use aliquots.
• Stability notes (general): Esters can undergo slow hydrolysis in moist air/solvents; prepare reaction solutions fresh and limit exposure to bases/acids if ester integrity is required.

Always consult the lot-specific CoA and SDS for definitive storage guidance and stability information.

Structure and Identity

Ethyl 3-(4-nitropyrazol-1-yl)propanoate is a heteroaromatic N-alkylated pyrazole bearing a nitro substituent and an ethyl ester terminus. It serves as a bifunctional building block combining an N-linked heteroaryl unit with a transformable nitro group and an ester handle.

• Item-specific identifiers (Product Data):

  • CAS: 512809-69-7
  • SKU: E1027150
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Molecular descriptors (general/literature):

  • Core scaffold: pyrazole ring (1,2-diazole) with N1-alkyl linkage to a 3-carbon chain terminated by an ethyl ester; nitro group at the 4-position of the ring.
  • Functional groups: heteroaromatic pyrazole, nitro (–NO2) at C4, ethyl ester (–CO2Et), and an N–alkyl linkage (N1–(CH2)3–CO2Et).

• 2D structural description (general):

  • Five-membered pyrazole ring with two adjacent nitrogens (N1 and N2). N1 is substituted by a propyl-ester chain; C4 of the ring bears a nitro group. The distal terminus is an ethyl ester, providing a protected carboxyl function.

• Molecular formula and molecular weight: Not specified for this item; refer to CoA/Spec Sheet.

Note: For authoritative identifiers (InChI, SMILES) and elemental analysis, consult the product CoA/Specification Sheet.

Synthetic Utility

Ethyl 3-(4-nitropyrazol-1-yl)propanoate combines two orthogonal, high-value handles that enable convergent route planning.

Transformational handles (general/literature):

• Nitro at C4 (electrophilic surrogate):
  • Reduction to amine unlocks a versatile nucleophile for diversification: acylation to amides, sulfonylation, urea/carbamate formation, or further diazotization–substitution sequences (caution: heteroaryl diazonium stability is substrate-dependent).
• Ethyl ester side chain:
  • Hydrolysis to the acid facilitates coupling to amines (amide synthesis), alcohols (ester interchange), or activation as acid chloride/anhydride for advanced coupling chemistry.

Strategic use in synthesis:

• Linker installation: The propanoate spacer provides a defined three-carbon tether from the heteroaryl nucleus to downstream functionality (useful in conformational scans and SAR).
• Protecting-group logic: The ester protects the acid during nitro reduction; sequence planning avoids base-promoted saponification during reductions.
• Late-stage diversification: Reduce first to amine, derivatize (e.g., sulfonamide library), then hydrolyze/activate the ester for bioconjugation-like couplings.

Analytical signatures (practical):

• 1H NMR typically shows: ethyl quartet/triplet (–OCH2CH3), three methylene signals for –N–(CH2)3–, and characteristic pyrazole protons (pattern influenced by the nitro substituent).
• LC–MS: expect a strong [M+H]+; upon reduction, +2 hydrogen equivalents and +16 mass change (–NO2 → –NH2) relative to the nitro form.

The scaffold is well-suited for parallel synthesis and combinatorial diversification.

Target Specificity

Not applicable. This product is a small-molecule building block and is not an antibody, ligand-standard, or assay-specific probe with defined biological target binding.

• No antigen/epitope, species reactivity, clone, or isotype information applies.