Defluoro Aprepitant - ≥95% , CAS No.170729-76-7

CAS: 170729-76-7 Cat. No.: D1010095 Formula: C₂₃H₂₂F₆N₄O₃ Peso molecolare: 516.44 PubChem CID: 135547943

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: CC(C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)OC2C(N(CCO2)CC3=NNC(=O)N3)C4=CC=CC=C4
• IUPAC Name: 3-[[(2R,3S)-2-[(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethoxy]-3-phenylmorpholin-4-yl]methyl]-1,4-dihydro-1,2,4-triazol-5-one
• InChIKey: YOBMIXIISZAQGF-CAYVGHNUSA-N
• INCHI: 1S/C23H22F6N4O3/c1-13(15-9-16(22(24,25)26)11-17(10-15)23(27,28)29)36-20-19(14-5-3-2-4-6-14)33(7-8-35-20)12-18-30-21(34)32-31-18/h2-6,9-11,13,19-20H,7-8,12H2,1H3,(H2,30,31,32,34)/t13-,19+,20-/m1/s1
• Isomeri SMILES: C[C@H](C1=CC(=CC(=C1)C(F)(F)F)C(F)(F)F)O[C@@H]2[C@@H](N(CCO2)CC3=NNC(=O)N3)C4=CC=CC=C4
• PubChem CID: 135547943
• Peso molecolare: 516.44

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Classe Oxazinanes
      • Subclass Morpholines

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Classe: Oxazinanes
• Subclass: Morpholines
• Intermediate Tree Nodes: Not available
• Direct Parent: Phenylmorpholines
• Alternative Parents: Trifluoromethylbenzenes Aralkylamines Triazoles Heteroaromatic compounds Trialkylamines Oxacyclic compounds Azacyclic compounds Acetals Organopnictogen compounds Organofluorides Organic oxides Hydrocarbon derivatives Alkyl fluorides
• Molecular Framework: Aromatic heteromonocyclic compounds
• Substituents: Phenylmorpholine - Trifluoromethylbenzene - Aralkylamine - Monocyclic benzene moiety - Benzenoid - Azole - 1,2,4-triazole - Heteroaromatic compound - Tertiary amine - Tertiary aliphatic amine - Azacycle - Oxacycle - Acetal - Hydrocarbon derivative - Alkyl fluoride - Organic oxygen compound - Organooxygen compound - Organonitrogen compound - Organofluoride - Organohalogen compound - Organic nitrogen compound - Organopnictogen compound - Amine - Organic oxide - Alkyl halide - Aromatic heteromonocyclic compound
• Descrizione: This compound belongs to the class of organic compounds known as phenylmorpholines. These are aromatic compounds containing a morpholine ring and a benzene ring linked to each other through a CC or a CN bond.
• 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: 516.400 g/mol
• XLogP3: 4.100
• Hydrogen Bond Donor Count: 2
• Hydrogen Bond Acceptor Count: 11
• Rotatable Bond Count: 6
• Exact Mass: 516.16 Da
• Monoisotopic Mass: 516.16 Da
• Topological Polar Surface Area: 75.200 Ų
• Heavy Atom Count: 36
• Formal Charge: 0
• Complexity: 780.000
• Isotope Atom Count: 0
• Defined Atom Stereocenter Count: 3
• 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

• Item-specific (Product Data)

  • No tested applications or recommended dilutions are provided for this item. Research use only.

• General protocols for small-molecule screening (guidance; not item-specific)

  • Preparation of DMSO stocks: weigh compound quickly, cap immediately, and dissolve to 10 mM in anhydrous DMSO. Vortex, then sonicate up to 5 min if needed. Aliquot into low-bind tubes; store desiccated.
  • Plate handling: equilibrate to room temperature before opening. Dispense using positive-displacement tips. Backfill with assay buffer to achieve final DMSO ≤0.5–1.0% v/v.
  • Solubility check: after dilution, visually inspect for turbidity/precipitation; if present, increase surfactant slightly or reduce top concentration.
  • QC prior to screening: verify identity by LC-MS and purity by UPLC. Quantify concentration by UV or qNMR if accurate dosing is critical.

• Analytical method snippet (example starting point)

  • UPLC: C18, 50 × 2.1 mm, 1.7 µm; 0.1% formic acid in water (A) / acetonitrile (B); 5–95% B in 5 min; 0.3 mL/min; UV 210–300 nm; MS ESI+.

Adapt these steps to your assay and instrumentation. Validate all conditions experimentally.

Biological Roles

• Item-specific (Product Data)

  • No biological activity annotations are provided for this SKU. Use is limited to research only.

• Literature/general context (not item-specific; for orientation only)

  • Aprepitant is a well-known neurokinin-1 (NK1) receptor antagonist. “Defluoro” analogs are frequently prepared in medicinal chemistry to study the contribution of aryl fluorination or CF3 groups to receptor affinity, lipophilicity, and metabolic stability.
  • Defluorination can affect halogen bonding, π–π stacking, permeability, and susceptibility to oxidative metabolism. Comparative assays (binding, functional antagonism, microsomal stability) are commonly used to quantify these effects.
  • In chemical biology, such analogs can help deconvolute SAR by isolating the role of fluorine in target engagement and off-target profiles.

• Practical research guidance

  • If used as a tool compound in receptor-binding or signaling assays, verify target engagement and potency empirically under your assay conditions; do not assume parity with aprepitant.
  • Confirm compound identity, purity, and concentration prior to biological testing. Employ appropriate vehicle controls to account for DMSO or co-solvent effects.

No therapeutic or diagnostic claims are made for this item. All studies should be conducted under approved research protocols.

Buffer Applications

This product is a hydrophobic research small molecule and is not used to prepare laboratory buffers. If incorporation into aqueous buffers is required for assays:

• Use a concentrated DMSO stock and spike into the buffer to a final DMSO content typically ≤0.5–1.0% v/v, verifying assay tolerance.
• Adjust pH only if the compound bears titratable groups; without a confirmed structure, do not assume pKa. Empirically check solubility vs. pH.
• Consider solubilizing excipients (e.g., 2-hydroxypropyl-β-cyclodextrin) or nonionic surfactants at low percentages.

Otherwise, refer to Solvent Selection and Application Protocols for practical dissolution advice.

Green Alternatives

For this type of hydrophobic, drug-like molecule, environmental impact is largely driven by solvent selection in dissolution, purification, and analytics. Consider greener solvent strategies without compromising performance.

• Greener dissolution and handling alternatives (general guidance)

  • Prefer ethanol or isopropanol as co-solvents over DMF/NMP when assay-compatible; combine with ≤0.5% DMSO to reach target concentrations.
  • Where feasible, employ aqueous buffers with cyclodextrins or mild surfactants to reduce neat organic solvent usage.
  • For chromatography, use ethanol or isopropanol modifiers instead of acetonitrile/THF where resolution allows; consider water-rich gradients.

• Comparison snapshot (general; not item-specific)

  • DMSO: high solvency, low volatility; acceptable but persistent in waste streams.
  • DMF/NMP: powerful but regulatory scrutiny and higher toxicity concerns; seek to minimize or replace.
  • Ethanol/i-PrOH: renewable feedstocks available; higher viscosity and different eluotropic strength may require method adjustment.

• Process-scale considerations

  • Implement microscale solubility screens to minimize solvent consumption.
  • Use closed systems and solvent recovery (rotary evaporation with cold traps) to reduce VOC emissions.

Note: Solubility limits and assay performance must be validated experimentally; green substitutions should be justified by data to maintain scientific rigor.

Pharmaceutical Uses

• Item-specific (Product Data)

  • No pharmacopoeial status or excipient role is specified for this product. Research use only.

• General formulation research context (not item-specific)

  • Aprepitant-like chemotypes are often used as model hydrophobic drug substances in pre-formulation studies, including solubility screening, supersaturation/precipitation kinetics, and enabling formulations (cyclodextrins, lipid-based systems, amorphous dispersions). A defluoro analog may offer altered lipophilicity and crystallinity relative to the parent, informing SAR–formulation interplay.
  • For analytical development, such compounds can aid in establishing LC-UV/MS methods, forced degradation protocols, and extraction recoveries from biological matrices (non-clinical).

• Practical notes

  • Establish a robust reference standard file: purity, identity spectra, and stability-indicating chromatographic methods.
  • Document vehicle effects on assay outcomes; maintain consistent DMSO percentages and pre-wet plasticware to minimize adsorption.

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

Physical Properties

• Item-specific (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/computational values (not item specifications)

  • Defluoro analogs of aprepitant are typically high–molecular-mass, lipophilic solids with low aqueous solubility and good solubility in polar aprotic organics (DMSO/DMF). Exact mp/bp/density/logP cannot be asserted without the definitive structure.

• What to expect (general guidance for compound handling; not specifications)

  • Physical state: likely an off-white to white solid if analogous to aprepitant derivatives; verify visually upon receipt.
  • Solubility strategy: prepare concentrated stock solutions in anhydrous DMSO (e.g., 10–50 mM) then dilute into assay media with surfactant or co-solvent to mitigate precipitation. Confirm compatibility with assay components.
  • Hygroscopicity/solvate formation: drug-like amides can exhibit solvation; dry under high vacuum at ambient temperature if needed and confirm by weight constancy.

• Not provided for this item (consult CoA/SDS)

  • Melting point, boiling point, density, refractive index, pKa, logP/logD, water content, and residual solvents: Not specified for this item; refer to CoA/Spec Sheet.

Note: Do not treat literature expectations as specifications. Always base method development on the batch-specific CoA.

Quality and Grades

• Item-specific (Product Data)

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

• Guidance on interpreting quality for screening compounds (general)

  • Screening/medchem-grade small molecules are generally supplied at high chemical purity (often ≥95% by HPLC/UPLC) with orthogonal identity confirmation (HRMS/1H NMR). Exact acceptance criteria must be verified on the CoA for this SKU.
  • Chromatographic purity vs. assay readiness: low levels of residual solvents, salts, or formers can influence bioassay results. Review residual solvent and counter-ion information on the CoA.
  • Stereochemistry: many aprepitant analogs are chiral. If this item is stereodefined, the CoA should list optical rotation or chiral purity; if racemic, consider potential activity differences.
  • Stabilizers: Not indicated for this item. If present in a specific batch, stabilizers will be declared on the CoA/SDS and may affect UV or mass-spec baselines.

• Documentation to request/use

  • CoA including purity, analytical methods, and batch number.
  • NMR and LC/UPLC chromatograms.
  • Mass spectrum and, where relevant, chiral analysis.

Note: Do not infer analytical specifications from literature; rely on the provided CoA/Spec Sheet for this item.

Reaction and Applications

This product is primarily intended as a research compound for screening, SAR, and chemical biology rather than as a synthetic reagent.

• Most relevant applications (general, non-item-specific)

  • Screening library member in NK1 receptor–related panels when studying aprepitant analog space (literature context). Useful for probing halogen effects on binding and ADME by comparing defluoro vs. fluorinated congeners.
  • Reference material in analytical method development (LC/UPLC-MS) to assess retention and ionization behavior of aprepitant-like chemotypes.
  • Tool compound for permeability, solubility, and formulation feasibility studies (e.g., solvent effect, excipient screening) in preclinical research.

• Not typically applicable as a reagent

  • Not commonly used in named organic reactions or as a building block; complex, late-stage analogs are usually endpoints, not synthons.

• Practical tips for assay deployment

  • Prepare DMSO stocks under low moisture; aliquot to avoid freeze–thaw and adsorption losses.
  • Confirm concentration by UV or quantitative 1H NMR when critical; drug-like chromophores often have UV absorbance suitable for qNMR internal standardization.
  • Perform solubility and stability pre-screens at assay pH and temperature; monitor for precipitation or adsorption to plastics.

All uses are for research only. No clinical or diagnostic use is intended or implied.

Reaction Conditions

Not typically applicable. Defluoro Aprepitant is supplied as a finished small-molecule research compound rather than a reagent for conducting chemical reactions.

• For analytical and assay preparation (general guidance)

  • Stock solutions: dissolve in dry DMSO at 5–50 mM; vortex and sonicate briefly if needed. Avoid prolonged heating; keep below 40 °C.
  • Dilutions: add DMSO stock to assay buffer or media with vigorous mixing to prevent local supersaturation. Target final DMSO ≤0.5–1.0% v/v unless your system tolerates more.
  • Stability checks: run short-term stability at assay temperature (e.g., 2–24 h) and light exposure tests; use amber vials if photosensitivity is suspected.

• If engaging in method development (chromatography; general, not item-specific)

  • LC: C18 columns with water/ACN or water/MeOH ± 0.1% formic acid are typical. Start with 30–90% organic gradient over 10–15 min; tune based on retention.
  • MS: ESI+ often suitable for amide-containing drug-like compounds; optimize source temperature and desolvation gas to minimize adducts.

These guidelines are generic and should be validated empirically for this item.

Safety and Handling

• Item-specific (Product Data)

  • GHS Classification: Not specified for this item; refer to SDS.
  • Signal Word / H-Statements / Pictograms: Not specified for this item; refer to SDS.
  • Storage Conditions: Room temperature.

• General laboratory precautions for drug-like small molecules (not item-specific)

  • PPE: lab coat, safety glasses, and appropriate chemically resistant gloves (e.g., nitrile). Use in a fume hood to avoid inhalation of dust or aerosols.
  • Avoid contact with skin and eyes. Prevent ingestion and inhalation. Wash hands thoroughly after handling.
  • Incompatibilities: strong oxidizers and strong acids/bases may cause degradation. Keep away from ignition sources when using organic solvents.
  • First aid overview: if inhaled, move to fresh air; if on skin, wash with soap and water; if in eyes, rinse cautiously with water for several minutes and remove contact lenses if present; if swallowed, rinse mouth. Seek medical attention in all cases. Defer to SDS for detailed instructions.
  • Spill response: avoid dust generation; collect solids by gentle sweeping or HEPA vacuum; absorb solvent solutions with inert material (vermiculite), then dispose as hazardous waste.

• Transport/Shipping

  • Shipped in: Not specified for this item; refer to SDS/shipping documents. Given room-temperature storage, ambient shipment is typically acceptable unless otherwise indicated.

Always consult the batch-specific SDS for authoritative hazard classification and response measures.

Solvent Selection

Defluoro Aprepitant is best approached as a lipophilic, drug-like research compound. Without item-specific solubility data, select solvents empirically, beginning with polar aprotic media.

• Practical dissolution strategy (general guidance)

  • Primary stock: anhydrous DMSO (5–50 mM typical) to ensure complete dissolution for screening assays.
  • Secondary options: DMF, NMP. For less polar vehicles, use ethanol or isopropanol as co-solvents (≤10% v/v) with aqueous buffers.
  • Aqueous work: employ surfactants (e.g., 0.01–0.1% Tween 80 or Pluronic F-68) or cyclodextrin complexation to enhance apparent solubility; confirm assay compatibility.
  • Filtration: use 0.22 µm PTFE/RC filters; avoid nylon if amide-binding is a concern. Warm gently (≤40 °C) if needed to complete dissolution; avoid prolonged heating.

• Polarity/miscibility profile (literature-general for drug-like amides)

  • Likely poor water solubility; good solubility in DMSO/DMF; moderate in alcohols and chlorinated solvents. Confirm experimentally.

• When to choose alternatives

  • For cell-based assays requiring low DMSO, build a solvent matrix (e.g., 1–2% ethanol + ≤0.5% DMSO) and validate signal/background.
  • For LC-MS sample prep, prefer acetonitrile with 0.1% formic acid after making a DMSO concentrate, ensuring final DMSO ≤2% to protect MS signal.

Note: None of the above are specifications for this item; tailor to your assay and verify with small-scale tests.

Storage and Reconstitution

• Item-specific (Product Data)

  • Storage Conditions: Room temperature.
  • Shipped In: Not specified for this item; refer to shipping documents.

• General best practices for this compound class (not item-specific)

  • Solid storage: keep tightly sealed in the original container, protected from moisture and prolonged light. Store in a desiccator or with desiccant packs at room temperature unless otherwise indicated on the CoA/SDS.
  • Reconstitution: prepare concentrated stock solutions in anhydrous DMSO (e.g., 10–50 mM). Filter if particulate persists (0.22 µm PTFE). Record the exact solvent lot and concentration.
  • Aliquoting: divide stocks into single-use aliquots to avoid repeated freeze–thaw and atmospheric moisture uptake. For long-term stability, consider storing DMSO stocks at −20 °C to −80 °C in amber vials; verify stability upon thaw.
  • Stability monitoring: periodically assess by LC/UPLC to detect degradation or precipitation during storage. Avoid aqueous storage unless stability is demonstrated.

• Not specified for this item (consult CoA/SDS)

  • Exact shelf life, impurity limits, water content, and stabilizers: Not specified for this item; refer to CoA/Spec Sheet.

Always follow the batch-specific CoA and SDS for authoritative storage and handling instructions.

Structure and Identity

Brief overview: Defluoro Aprepitant is supplied as a research-use small-molecule library member. Detailed structural identifiers for this specific catalog item are limited in the Product Data.

• Item-specific (Product Data)

  • SKU: D1010095
  • Product Name: Defluoro Aprepitant
  • CAS: 170729-76-7
  • PubChem CID: 135547943
  • InChIKey: 442405 (format appears truncated/non-standard; confirm on CoA/SDS)
  • Molecular Formula: Not specified for this item; refer to CoA/Spec Sheet.
  • Molecular Weight: Not specified for this item; refer to CoA/Spec Sheet.
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Literature/general context (clearly labeled as non-item-specific)

  • Naming suggests a structural relationship to the NK1 antagonist aprepitant, with one or more fluorine atoms removed (“defluoro” analog). Exact substitution pattern, stereochemistry, and ring connectivities should be confirmed from the certificate of analysis (CoA) for this SKU.
  • Typical aprepitant scaffolds feature a morpholine-containing amide framework and substituted (often halogenated) aromatics; defluorinated analogs are used to probe halogen effects on potency and ADME in SAR campaigns (literature).

• Structural description (provisional, method-neutral)

  • Without a confirmed structure file (SMILES/InChI), a precise 2D narrative cannot be provided. Obtain the vendor structure file or CoA to capture functional groups, ring systems, and stereocenters for ELN registration and screening panel setup.

Synthetic Utility

This compound is best regarded as a target molecule for screening rather than a synthetic building block.

• Not typically used as a reagent

  • Due to its complexity and likely presence of multiple functional groups and stereocenters (by analogy to aprepitant chemotypes), it is not commonly employed as a substrate or coupling partner in standard synthetic transformations.

• Where it may be informative (general, non-item-specific)

  • As a reference in late-stage diversification studies to quantify how defluorination impacts physicochemical properties (e.g., logD, pKa, polarity) and reaction selectivity during analog generation.
  • Benchmark for comparing chiral resolution strategies if enantiopurity is relevant to the scaffold.

• Retrosynthetic considerations (conceptual)

  • Aprepitant analogs often arise from convergent coupling of an amino/morpholine fragment with an aryl/heteroaryl acid chloride or activated ester, followed by side-chain installations. Defluorination alters aryl fragment electronics, which can affect cross-coupling or electrophilic substitution steps (literature insight).

If you require a precursor/building-block form of this scaffold, contact us for availability of intermediate fragments tailored for synthesis.

Target Specificity

• Item-specific (Product Data)

  • No validated biological target, binding constants, or selectivity data are provided for this SKU.

• Literature/general context (not item-specific)

  • Aprepitant derivatives are commonly investigated as ligands of the neurokinin-1 (NK1) receptor. A defluoro analog would typically be evaluated in that context to assess the contribution of fluorine to affinity and selectivity; however, no target assignment is made for this catalog item.

Please consult your internal data or generate de novo profiling (e.g., radioligand binding, SPR, or functional assays) to establish target engagement under your conditions.