Ibrutinib-d5 - ≥98% , CAS No.1553977-17-5

CAS: 1553977-17-5 Cat. No.: I648129 Formula: C₂₅H₁₉D₅N₆O₂ Molecular Weight: 445.53

GRADE & PURITY ≥98%

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

Overview

Ibrutinib-d 5 is a deuterium labeled Ibrutinib. Ibrutinib is a selective, irreversible Btk inhibitor.

Form:Solid

Specifications

Specifications & Purity

≥98%

Biochemical and Physiological Mechanisms

Ibrutinib-d 5 is a deuterium labeled Ibrutinib. Ibrutinib is a selective, irreversible Btk inhibitor.

Storage

Store at -20°C

Shipped In

Ice chest + Ice pads

This product requires cold chain shipping. Ground and other economy services are not available.

Action Type

INHIBITOR

Purity

≥98%

Names and Identifiers

Canonical Smiles

C=CC(=O)N1CCCC(C1)N2C3=NC=NC(=C3C(=N2)C4=CC=C(C=C4)OC5=CC=CC=C5)N

IUPAC Name

1-[(3R)-3-[4-amino-3-[4-(2,3,4,5,6-pentadeuteriophenoxy)phenyl]pyrazolo[3,4-d]pyrimidin-1-yl]piperidin-1-yl]prop-2-en-1-one

InChIKey

XYFPWWZEPKGCCK-OZUAZJOXSA-N

INCHI

1S/C25H24N6O2/c1-2-21(32)30-14-6-7-18(15-30)31-25-22(24(26)27-16-28-25)23(29-31)17-10-12-20(13-11-17)33-19-8-4-3-5-9-19/h2-5,8-13,16,18H,1,6-7,14-15H2,(H2,26,27,28)/t18-/m1/s1/i3D,4D,5D,8D,9D

Isomeric SMILES

[2H]C1=C(C(=C(C(=C1[2H])[2H])OC2=CC=C(C=C2)C3=NN(C4=NC=NC(=C34)N)[C@@H]5CCCN(C5)C(=O)C=C)[2H])[2H]

Molecular Weight

445.53

Reaxy-Rn

13102237

Reaxys-RN_link_address

https://www.reaxys.com/reaxys/secured/hopinto.do?context=S&query=IDE.XRN=13102237&ln=

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Benzenoids
    • Class Benzene and substituted derivatives
      • Subclass Diphenylethers

• Kingdom: Organic compounds
• Superclass: Benzenoids
• Class: Benzene and substituted derivatives
• Subclass: Diphenylethers
• Intermediate Tree Nodes: Not available
• Direct Parent: Diphenylethers
• Alternative Parents: Diarylethers Phenylpyrazoles Pyrazolo[3,4-d]pyrimidines N-acylpiperidines Phenoxy compounds Phenol ethers Aminopyrimidines and derivatives Imidolactams Acrylic acids and derivatives Heteroaromatic compounds Tertiary carboxylic acid amides Amino acids and derivatives Azacyclic compounds Hydrocarbon derivatives Primary amines Carbonyl compounds Organic oxides
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: Diphenylether - Diaryl ether - Phenylpyrazole - N-acyl-piperidine - Pyrazolo[3,4-d]pyrimidine - Pyrazolopyrimidine - Phenoxy compound - Phenol ether - Aminopyrimidine - Piperidine - Pyrimidine - Imidolactam - Azole - Acrylic acid or derivatives - Heteroaromatic compound - Pyrazole - Tertiary carboxylic acid amide - Amino acid or derivatives - Carboxamide group - Ether - Carboxylic acid derivative - Azacycle - Organoheterocyclic compound - Organic nitrogen compound - Hydrocarbon derivative - Organic oxide - Organooxygen compound - Organonitrogen compound - Organic oxygen compound - Carbonyl group - Primary amine - Amine - Aromatic heteropolycyclic compound
• Description: This compound belongs to the class of organic compounds known as diphenylethers. These are aromatic compounds containing two benzene rings linked to each other through an ether 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

Application Protocols

Tested applications, recommended dilutions, and positive controls: Not specified for this item; refer to CoA/Spec Sheet.

Note: As an analytical standard, typical protocols involve LC–MS/MS internal standard spiking and sample preparation. However, since no item-specific, validated protocols are supplied with this listing, users should adapt established literature methods for ibrutinib quantitation and validate in their own laboratory context.

Biological Roles

Item-specific biological/target data: Not specified for this item; refer to CoA/Spec Sheet.

General context for ibrutinib isotopologues in biochemical research:

• Mechanistic class: Covalent kinase-binding small molecule bearing a Michael acceptor (acrylamide) that can target nucleophilic cysteine residues in specific kinase active sites (e.g., Bruton’s tyrosine kinase, BTK) in biochemical systems (literature/general). No clinical/therapeutic claims are made here.
• Role of deuteration: d5 substitution is isosteric with minimal effect on binding or reactivity but provides a mass signature facilitating tracking of parent compound and derived adducts/metabolites by mass spectrometry.
• Applications:
  • Quantitative proteomics: Spike-in standard to calibrate detection of protein-bound adducts in pull-down or activity-based profiling (research use only).
  • ADME studies (in vitro): Differentiation of parent-related signals from background using isotope dilution methods.
• Considerations:
  • Ensure that the deuterium label is not positioned at exchangeable sites under assay conditions; otherwise the isotopic signature may scramble.
  • Maintain consistent chromatographic conditions so the labeled and unlabeled forms co-elute, enabling accurate ratioing in LC–MS/MS workflows.

Buffer Applications

This product is a hydrophobic small-molecule analytical standard and is not a buffering reagent.

• Not typically used to prepare buffer systems. For biochemical assays involving Ibrutinib-d5, select buffers based on target protein stability and LC–MS compatibility (e.g., 10–50 mM ammonium formate/acetate, pH adjusted with formic/acetic acid; literature/general guidance).
• Practical notes (general):
  • Use volatile salts/acids for LC–MS workflows to minimize ion suppression and contamination.
  • Avoid high concentrations of nucleophiles (e.g., excess tris(hydroxymethyl)aminomethane) that could, in principle, react with electrophilic moieties over long exposures.
  • Include 0.1% formic acid for positive-ion ESI; consider 2–10 mM ammonium acetate for improved peak shape if needed.

Item-specific buffer roles or recipes: Not applicable/not specified for this item.

Green Alternatives

While Ibrutinib-d5 itself is a specialized analytical standard (no direct “green” substitute), greener choices can be made around its use, particularly in solvent systems for LC–MS and sample prep.

Comparison of common options (general guidance):

• DMSO vs. greener stock solvents:
  • DMSO: Excellent solvency and stability; relatively benign but high boiling point complicates removal.
  • Ethanol (anhydrous): Greener, renewable; may offer lower solubility and different LC selectivity.
• LC–MS mobile phases:
  • Acetonitrile: Efficient, lower viscosity; derived from petrochemical sources; toxicity concerns.
  • Methanol/ethanol blends: Renewable alternatives with higher viscosity; may require adjusted gradients and pressures.
• Extraction solvents:
  • MTBE/ethyl acetate over chlorinated solvents (e.g., DCM): Lower environmental impact; adequate for nonpolar analytes.

Tradeoffs and practices:

• Use miniaturized workflows (microextractions, 96-well plates) to reduce solvent consumption.
• Recycle high-purity ACN using solvent purification systems when feasible.
• Prefer aqueous buffers with volatile salts (ammonium formate/acetate) for LC–MS to lower hazard footprint.
• Waste minimization: Pool compatible waste streams and employ in-house distillation where regulations and safety permit.

All solvent substitutions should be validated to confirm co-elution and ionization behavior remain suitable for accurate quantitation.

Pharmaceutical Uses

No therapeutic or clinical claims are made for this product. It is intended strictly for research use only (per Product Data).

Relevant roles in pharmaceutical research/manufacturing (general):

• Bioanalytical internal standard: Ibrutinib-d5 is commonly used in method development and validation of LC–MS/MS assays quantifying ibrutinib in preclinical/analytical studies (e.g., plasma, stability studies, in vitro systems). The isotopic label supports accurate calibration, matrix-effect correction, and process-control tracking.
• Reference material: Useful for assessing extraction recovery, carryover, and instrument performance in regulated analytical labs (when accompanied by appropriate documentation). For GMP/GLP settings, verify suitability and traceability in the CoA and any supplemental certification.
• Formulation analytics: Supports forced-degradation studies and stability-indicating methods by providing a co-eluting internal standard signal for the parent analyte.

Item-specific pharmacopeial status or compendial listings: Not specified for this item; refer to CoA/Spec Sheet.

Physical Properties

Item-specific physico-chemical specifications (melting point, boiling point, density, refractive index, pKa, logP, water/peroxide/metal content, UV cutoff): Not specified for this item; refer to CoA/Spec Sheet.

General/literature guidance for ibrutinib isotopologues (for planning only; not product specifications):

• Physical state: typically a solid at ambient temperature; appearance can vary by batch and salt form.
• Solubility profile (literature):
  • Soluble in DMSO and DMF; moderate solubility in acetonitrile and methanol; very low solubility in water at neutral pH due to hydrophobic aromatic content.
  • Improved aqueous solubility in acidic media (protonation of basic amine).
• Partitioning (literature): High lipophilicity (parent ibrutinib cLogP reported in the 2–4 range in various sources; actual value depends on algorithm; deuteration minimally affects logP).
• Spectral shift: d5 exhibits a +5.0347 Da mass shift versus protiated analog; identical UV–vis profile within experimental error (literature).
• Stability (general): Stable to brief ambient handling in dry conditions; prolonged exposure to moisture/strong base can promote Michael addition or hydrolysis of the acrylamide (mechanistic expectation). Always confirm with the item’s CoA/SDS for definitive values and handling limits.

Quality & Grades

• Item-specific 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 for interpreting grades for deuterated analytical standards (general):

• Isotopic enrichment: For LC–MS internal standards, high deuterium incorporation (e.g., ≥98 atom % D at labeled positions) is typically desired to minimize interference from the unlabeled analyte. Actual enrichment for this item is not specified; check CoA.
• Chemical purity vs. isotopic purity: Both influence quantitation accuracy. Chemical impurities can co-elute or fragment similarly, while lower isotopic enrichment reduces mass separation. Review CoA for both metrics.
• Residual solvents/water content: Can impact solution stability and LC–MS ionization; if critical, request specific limits from CoA.
• Suitability for use:
  • Quantitative bioanalysis (LC–MS/MS): Prefer material with certificate of isotopic distribution and retention time equivalence to ibrutinib.
  • Mechanistic/kinetic work: Purity of the electrophilic acrylamide and absence of adducts are important; verify by LC–MS and NMR before use.
• Documentation: For regulated workflows, retain batch CoA, isotopic labeling map, and stability statements with your records.

Reaction & Applications

Item-specific manufacturer applications: Not specified for this item; refer to CoA/Spec Sheet.

General research applications for Ibrutinib-d5:

• LC–MS/MS internal standard: The +5 Da mass shift provides co-elution with the parent analyte while enabling selective MRM transitions. Ideal for quantitative determination of ibrutinib in complex matrices (plasma, tissue homogenates, formulation studies) in research settings.
• Mechanistic probe: Retains the electrophilic acrylamide Michael acceptor of ibrutinib, enabling studies of covalent engagement with nucleophilic cysteines in kinase active sites. Deuteration does not materially change reactivity but allows tracking by MS (literature/general).
• Metabolic profiling: Supports investigation of phase I/II biotransformations and adduct mapping by providing a deuterium signature across metabolites.
• Sample preparation tips (general):
  • Spike known amounts of Ibrutinib-d5 early in the workflow (e.g., prior to protein precipitation or extraction) to correct for recovery and matrix effects.
  • Use protein precipitation with ACN/MeOH (2–4× sample volume), or liquid–liquid extraction with MTBE/ethyl acetate; evaporate gently at ≤40 °C; reconstitute in initial LC mobile phase.
• Chromatography (general): Reversed-phase C18 or phenyl-hexyl columns; gradient 10–95% organic (ACN or MeOH) with 0.1% formic acid or volatile buffers; monitor protonated molecular ions with MRM transitions offset by +5 Da from ibrutinib.

Reaction Conditions

No item-specific reaction condition data are provided for this product; refer to CoA/Spec Sheet.

General conditions for analytical use and covalent engagement studies (literature/guidance):

• LC–MS sample prep:
  • Spike Ibrutinib-d5 at a fixed concentration (e.g., 5–100 ng/mL) into samples prior to extraction.
  • Protein precipitation: Add 2–4 volumes cold ACN or MeOH containing the internal standard; vortex, incubate on ice, centrifuge; evaporate supernatant and reconstitute in initial mobile phase.
• Chromatography/MS:
  • Column: Reversed-phase C18 or phenyl-hexyl, 2.1 mm ID.
  • Mobile phase A: Water with 0.1% formic acid or 5 mM ammonium formate; B: ACN or MeOH.
  • Gradient: 10–90% B over 3–8 min (optimize per system).
  • Detection: Positive ESI; monitor MRM transitions shifted by +5 Da relative to ibrutinib.
• Covalent labeling (protein target studies):
  • Buffer: 20–50 mM HEPES or ammonium bicarbonate, pH 7.4–8.0; include reducing agent (e.g., 1–2 mM TCEP) to expose cysteines.
  • Temperature/time: 25–37 °C, 0.5–2 h (optimize to balance specificity vs. off-target addition; general guidance).

All conditions above are general literature-style guidance and must be optimized for specific systems.

Safety & Handling

Item-specific hazard classification (GHS classes, pictograms, H-statements, signal word): Not specified for this item; refer to SDS.

General laboratory safety guidance for small-molecule research standards:

• Likely hazards (general for acrylamide-bearing electrophiles): May cause skin/eye irritation; avoid inhalation/ingestion; acrylamides can be sensitizers in some contexts. Treat as potentially harmful. Use inside a chemical fume hood.
• PPE: Lab coat, nitrile gloves (double-glove for extended handling), safety glasses or face shield; avoid skin contact. Change gloves frequently when handling DMSO solutions.
• Handling considerations:
  • Avoid contact with strong nucleophiles/bases that can add to the Michael acceptor.
  • Prevent aerosol formation; handle powders gently.
  • Use amber glassware or minimize light exposure if long manipulations are required (precautionary).
• Incompatibilities (general): Strong oxidizers; strong bases/nucleophiles; moisture for extended periods.
• First aid overview (consult SDS for definitive procedures):
  • Skin/eye contact: Rinse with water for ≥15 min; remove contaminated clothing; seek medical evaluation.
  • Inhalation: Move to fresh air; monitor breathing; seek medical evaluation.
  • Ingestion: Rinse mouth; do not induce vomiting; seek medical attention.
• Waste: Collect solutions/solids as organic hazardous waste per institutional and local regulations.
• Always defer to the specific product SDS for authoritative safety information.

Solvent Selection

For Ibrutinib-d5, solvent choice is driven by hydrophobicity and the need for LC–MS compatibility.

• Polarity/miscibility (general for ibrutinib analogs):
  • Highly soluble: DMSO, DMF.
  • Moderately soluble: Acetonitrile (ACN), methanol, isopropanol, ethyl acetate.
  • Poorly soluble: Water at neutral pH; solubility may improve under mildly acidic conditions due to amine protonation.
• Recommended stock preparation (general practice):
  • Prepare 1–10 mM stocks in anhydrous DMSO; store aliquots at −20 °C to minimize freeze–thaw.
  • For LC–MS injection, dilute DMSO stocks into 50–80% ACN or MeOH with 0.1% formic acid or 2–10 mM ammonium formate/acetate as needed.
• When to choose each solvent:
  • DMSO: Maximum solubilization; stable for concentrated stocks; avoid high final DMSO in biological matrices.
  • ACN: Preferred LC–MS organic phase; low viscosity and strong elution strength in reversed-phase.
  • MeOH: Useful for sample prep/extractions; slightly higher viscosity, different elution selectivity.
• Practical notes:
  • Filter or centrifuge before LC–MS to remove particulates.
  • Avoid strong bases/nucleophiles in solution to protect the acrylamide moiety.
  • Use glass vials with PTFE-lined caps; some plastics may sorb hydrophobic analytes.

Storage & Reconstitution

• Storage (item-specific): Store at −20 °C (from Product Data). Shipments are provided in an ice chest with ice pads to maintain cold chain during transit.
• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Reconstitution (general guidance for small-molecule standards):
  • Allow vial to equilibrate to room temperature in a desiccated environment before opening to prevent moisture condensation.
  • Prepare concentrated stocks (e.g., 1–10 mM) in anhydrous DMSO. Vortex to ensure complete dissolution. If needed, sonicate briefly.
  • For LC–MS use, dilute the DMSO stock into ACN/MeOH with aqueous buffer (e.g., 0.1% formic acid or 2–10 mM ammonium acetate) just prior to analysis.
• Aliquoting: Divide into single-use aliquots to avoid repeated freeze–thaw cycles. Store aliquots in amber vials at −20 °C or below, under inert gas if feasible.
• Stability: Item-specific stability data are not provided; refer to CoA/Spec Sheet. As a precaution, minimize exposure to moisture, light, and elevated temperatures.
• Thawing/refreezing: Avoid multiple freeze–thaw cycles; thaw on ice or at room temperature, use promptly, and refreeze any remaining aliquot only once if necessary.

Structure & Identity

Ibrutinib-d5 is the stable-isotope–labeled analog of ibrutinib, typically incorporating five deuterium atoms for use as a mass spectrometric internal standard and mechanistic probe.

• Item-specific identifiers (from Product Data):
  • CAS: 1553977-17-5
  • CID: 73053689
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet.
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.
• Formula and molecular weight: Not specified for this item; refer to CoA/Spec Sheet.
• Structural features (general/literature description for ibrutinib isotopologues):
  • Contains an electrophilic Michael acceptor (acrylamide) capable of covalent conjugation to nucleophilic cysteine residues in proteins (general mechanistic feature of ibrutinib analogs).
  • Polycyclic/aromatic motif with a lipophilic biaryl segment; tertiary amine functionality provides basicity and aids solubility in polar aprotic solvents.
  • d5 labeling: Five protium atoms in the parent scaffold are replaced by deuterium (location depends on the specific labeling scheme; commonly on an aromatic ring), enabling a precise mass shift (+5 Da) for LC–MS/MS discrimination (literature/general).
• 2D structure (words; general for ibrutinib analogs): A biaryl ether/aryl segment linked via a urea/amide-like connection to a heteroaryl/amine-bearing core that terminates in an α,β-unsaturated carbonyl (acrylamide). Deuteriums typically decorate one aromatic ring without altering connectivity (literature/general).

Synthetic Utility

As a fully assembled, deuterated small molecule, Ibrutinib-d5 is not typically used as a synthetic building block. Its main synthetic relevance is as a labeled analog to interrogate mechanisms or pathways.

General/literature utility of deuterated analogs of electrophilic kinase binders:

• Kinetic isotope tracing: d5 labeling enables MS-based tracking of reaction pathways (e.g., covalent addition to cysteine residues) without materially altering reactivity.
• Metabolic fate mapping: Distinguish parent-derived metabolites from background or artifacts via characteristic mass shifts.
• Stability studies: Compare degradation routes (hydrolysis/Michael addition/oxidation) under stress conditions by monitoring d5 parent and derivatives.
• Calibration of quantitative NMR (qNMR) or LC–MS: Use as internal calibrant where structural congruence with analyte minimizes bias.

If synthetic modification is required (e.g., biotinylation or photoaffinity tagging), it is more common to start from functionalized ibrutinib precursors rather than altering Ibrutinib-d5, to preserve the isotopic integrity and avoid label scrambling.

Target Specificity

Item-specific target, clone, isotype, epitope, or species reactivity data are not applicable to this small-molecule standard and are not provided for this item.

General note (literature): The parent ibrutinib scaffold is known to covalently engage kinases bearing a suitably positioned cysteine via its acrylamide warhead (e.g., BTK in biochemical assays), but this product listing does not specify target data. Users should verify target engagement experimentally for their system of interest.