4-Fluorogramine - ≥96% , CAS No.101909-46-0

CAS: 101909-46-0 Cat. No.: F1067779 Formula: C₁₁H₁₃FN₂ Molecular Weight: 192.23 PubChem CID: 2774470

GRADE & PURITY ≥96%

Storage

Room temperature

Specifications

Specifications & Purity

≥96%

Storage

Room temperature

Purity

≥96%

Names and Identifiers

• Canonical Smiles: CN(C)CC1=CNC2=C1C(=CC=C2)F
• IUPAC Name: 1-(4-fluoro-1H-indol-3-yl)-N,N-dimethylmethanamine
• InChIKey: GPYAFVBWLYCAMD-UHFFFAOYSA-N
• INCHI: 1S/C11H13FN2/c1-14(2)7-8-6-13-10-5-3-4-9(12)11(8)10/h3-6,13H,7H2,1-2H3
• Isomeric SMILES: CN(C)CC1=CNC2=C1C(=CC=C2)F
• PubChem CID: 2774470
• Molecular Weight: 192.23

Taxonomic Classification

Taxonomy Tree

• Kingdom Organic compounds
  • Superclass Organoheterocyclic compounds
    • Class Indoles and derivatives
      • Subclass Indoles

• Kingdom: Organic compounds
• Superclass: Organoheterocyclic compounds
• Class: Indoles and derivatives
• Subclass: Indoles
• Intermediate Tree Nodes: Not available
• Direct Parent: 3-alkylindoles
• Alternative Parents: Aralkylamines Substituted pyrroles Benzenoids Aryl fluorides Heteroaromatic compounds Trialkylamines Azacyclic compounds Organopnictogen compounds Organofluorides Hydrocarbon derivatives
• Molecular Framework: Aromatic heteropolycyclic compounds
• Substituents: 3-alkylindole - Aralkylamine - Aryl fluoride - Aryl halide - Substituted pyrrole - Benzenoid - Pyrrole - Heteroaromatic compound - Tertiary amine - Tertiary aliphatic amine - Azacycle - Hydrocarbon derivative - Organonitrogen compound - Organofluoride - Organohalogen compound - Organopnictogen compound - Organic nitrogen compound - Amine - Aromatic heteropolycyclic compound
• Description: This compound belongs to the class of organic compounds known as 3-alkylindoles. These are compounds containing an indole moiety that carries an alkyl chain at the 3-position.
• 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

Chemical and Physical Properties

• Molecular Weight: 192.230 g/mol
• XLogP3: 2.100
• Hydrogen Bond Donor Count: 1
• Hydrogen Bond Acceptor Count: 2
• Rotatable Bond Count: 2
• Exact Mass: 192.106 Da
• Monoisotopic Mass: 192.106 Da
• Topological Polar Surface Area: 19.000 Ų
• Heavy Atom Count: 14
• Formal Charge: 0
• Complexity: 196.000
• 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

Not applicable. No tested biological assay protocols (e.g., WB, IHC, IF, FC) or recommended dilutions are provided for this small-molecule building block.

General handling suggestions (non-item-specific):

• For biochemical assays, prepare a 10–100 mM stock solution in DMSO; dilute into assay buffer while keeping final DMSO at or below tolerated levels (commonly ≤0.1–1% v/v).
• For synthetic use, see Reaction Conditions and Synthetic Utility tabs for general procedures.

Biological Roles

Item-specific biological data: Not specified for this item; for research use only per Product Data.

General context (literature):

• Gramine is a known plant indole alkaloid involved in defense; 4-fluorogramine is a synthetic analog typically used as a chemical probe or building block in medicinal chemistry to explore electronic effects of a para-fluoro substituent on the indole ring.
• The tertiary amine allows formation of water-soluble ammonium salts, facilitating in vitro assay preparation; the indole core can interact with protein aromatic pockets via π–π and hydrogen bonding (through the indole NH), though actual binding is target- and substituent-dependent.
• Fluorine is frequently employed to modulate lipophilicity, metabolic stability (e.g., block benzylic oxidation paths), and to serve as a 19F NMR reporter in biophysical studies. 4-fluorinated indoles can be tracked by 19F NMR without isotopic enrichment.
• Protonation state impacts membrane permeability and target engagement: the free base is more permeable; the ammonium salt is more soluble. pH control is critical in biological assay design.

Caveat: No pharmacological, toxicological, or in vivo/clinical properties are claimed for this SKU. All uses are restricted to laboratory research conducted by qualified professionals.

Buffer Applications

This product is a small-molecule indole building block and is not a buffering agent. Consequently, it is not typically used to formulate buffers or control pH.

Practical notes (general):

• To dissolve the compound in aqueous buffers for assays, prepare a concentrated stock in DMSO or ethanol and dilute into buffer, or convert to a water-soluble salt (e.g., HCl salt) prior to dissolution.
• Maintain final DMSO below assay tolerance (commonly ≤0.1–1% v/v) and control pH to keep the desired protonation state (the tertiary amine is predominantly protonated below pH ~9–10; literature).

For actual buffer preparation, refer to standard systems (PBS, HEPES, Tris, acetate, citrate) appropriate to your biological workflow; these are unrelated to the function of 4-fluorogramine.

Green Alternatives

Context: 4-Fluorogramine is a building block rather than a solvent or reagent of high EHS concern; “greener” considerations focus on solvent choice and milder activation strategies in its transformations.

Greener choices (literature-guided, non-item-specific):

• Solvents: Favor 2-MeTHF or CPME over THF/Et2O; EtOAc or Me-THF over DCM where chromatography allows; MeCN over DMF/DMSO for easier workup; ethanol/water blends where compatible.
• Activation: Use catalytic Brønsted acids (e.g., TFA) or benign Lewis acids (Zn(OTf)2) to form iminium in situ rather than stoichiometric toxic halides. Avoid MeI when possible; MeOTf or benign sulfonates can be alternatives, acknowledging safety trade-offs.
• Cyanation: Replace HCN with TMSCN or K4[Fe(CN)6] protocols under phase-transfer catalysis, minimizing free cyanide.
• Energy: Many gramine substitutions proceed at rt–50 C; avoid unnecessary reflux; consider flow methods for heat/mass transfer efficiency.

Illustrative comparison (general):

• Traditional: DCM or DMF; MeI quaternization; cryogenic organolithium steps.
• Greener: 2-MeTHF/EtOAc; catalytic acid activation; organozinc/copper or enolate nucleophiles under milder conditions; aqueous workups with brine minimize solvent use.

Trade-offs:

• 2-MeTHF/CPME may alter selectivity and rates; peroxides can form—test and manage.
• Avoiding MeI reduces toxicity but may require higher loadings or longer times with alternative alkylators.

Waste minimization: Use salt forms to aid crystallization and reduce chromatographic silica waste when feasible.

Pharmaceutical Uses

No item-specific pharmacopeial status, excipient role, or GMP grade is provided for this SKU; refer to the CoA/Spec Sheet.

General R&D context only (non-clinical):

• Discovery chemistry: 4-Fluorogramine can serve as a starting point for libraries of 3-substituted indoles, enabling structure–activity relationship (SAR) exploration where a 4-F substituent tunes potency, selectivity, or metabolic stability relative to the parent gramine-derived series.
• Salt formation: Readily forms crystalline hydrochloride or hydrobromide salts that can aid in solid-state handling, milling, and formulation studies in preclinical assays (not for human use).
• Analytical reference: The presence of fluorine enables 19F NMR assay development for binding or reaction monitoring in biochemical systems.

Important restrictions:

• Not intended for therapeutic, diagnostic, or clinical use. No claims regarding safety, efficacy, or dose are made or implied. For research use only, as stated in the Product Data.

Physical Properties

Item-specific specifications (this SKU):

• Appearance: Not specified for this item; refer to CoA/Spec Sheet.
• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
• Molecular Weight (item-specific): Not specified for this item; refer to CoA/Spec Sheet.

Literature/computational (general, non-item-specific values for the neutral free base; provided for reference only):

• Molecular formula: C11H14FN2 (literature for 4-fluoro analog of gramine)
• Molecular weight: ~193.24 g/mol (calculated from formula)
• Acid–base properties: tertiary amine pKaH (conjugate acid) typically ~9–10; indole N is weakly acidic (pKa ~16–17 in DMSO). Values are literature-typical for gramine-like amines.
• LogP (estimated): moderate, likely in the 2–3 range for the free base (literature estimate for indole tertiary amines); increases with N-alkylation; decreases markedly upon protonation to the ammonium salt.
• Solubility profile: free base expected to be soluble in polar organic solvents (DMSO, DMF, MeCN, alcohols, chlorinated solvents) and moderately in ethers; forms water-soluble salts with mineral acids (e.g., HCl salt).
• Boiling point / melting point / density / refractive index: Not broadly reported for this specific analog in common handbooks; consult primary literature or the CoA.

Practical notes (general):

• The free base is hygroscopic to a limited extent due to the tertiary amine; forming the HCl salt improves handling and aqueous solubility.
• Indole chromophore shows UV absorbance (typical λmax ~220–290 nm; literature), useful for HPLC/UV detection.

Quality and Grades

Product-specific quality details (this SKU):

• Grade/Purity: Not specified for this item; refer to CoA/Spec Sheet.
• Stabilizers/Inhibitors: 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; impurity profiles (water, residual solvents, metal content) vary by lot. Verify by NMR/LC if critical.

• 95–98% purity (typical for building blocks): adequate for many reactions without further purification. For sensitive catalysis, consider re-purification.

• HPLC grade (for solvents) or LC/MS grade (for analytes) indicates low UV background and minimal non-volatile residue; not directly applicable here unless formulated as analytical standard.

Analytical control suggestions (general):

• Identity: 1H/13C NMR (characteristic indole signals; benzylic CH2 near 3.5–4.0 ppm; N(CH3)2 near 2.2–2.4 ppm), HRMS (M+H+ ~194 for free base), and IR (N–H stretch ~3400 cm−1; C–F stretch 1000–1400 cm−1 region).
• Purity: HPLC with UV detection at 220–280 nm; check for dimethylamine-related volatiles; verify absence of quaternary ammonium salts if free base is required.
• Residual solvents/water/metals: Not specified for this item; refer to CoA/Spec Sheet. If critical, apply KF for water and ICP-MS for metals.

Note: Always defer to the lot-specific CoA/SDS for authoritative grade, assay, and impurity specifications.

Reaction and Applications

General applications (literature) of gramine analogs extended to 4-fluorogramine:

• C3 Functionalization platform for indoles: The 3-(dimethylaminomethyl) group can be converted to a benzyl iminium/quaternary ammonium, enabling nucleophilic substitution to introduce diverse groups at C3. Nucleophiles include cyanide, thiols, malonates, indolates, and organometallics (e.g., Mg, Cu reagents). This is a classic “gramine displacement” route to 3-substituted indoles under mild conditions.
• Quaternization as activation: Alkylation (e.g., MeI, MeOTf) affords quaternary ammonium salts that act as leaving-group-activated electrophiles for subsequent substitution or elimination sequences.
• Protecting/activating group synergy: The dimethylaminomethyl can behave as a removable activating group for C3, obviating harsh Friedel–Crafts conditions.
• Fluorine handle and electronics: The 4-F substituent tunes ring electronics and can modulate regioselectivity in electrophilic substitution and metalation at other positions. It serves as a spectroscopic probe (19F NMR) for reaction monitoring, although oxidative addition into aryl–F is generally challenging.
• Late-stage diversification: Useful in SAR programs to compare 4-H vs 4-F effects on potency and metabolic stability after elaboration at C3.

Practical tips:

• Generate quaternary ammonium salts freshly (dry conditions) to minimize hydrolysis.
• For cyanation at C3, use HCN surrogates (e.g., TMSCN) with Lewis/Brønsted activation; ensure proper cyanide safety controls.
• If strong bases are used, protect the indole N (e.g., Boc) to prevent N-alkylation.
• Monitor by LC/UV (220–280 nm) or 19F NMR when feasible.

Note: No manufacturer-application text was provided for this SKU; the above reflects literature practices with gramine-type substrates.

Reaction Conditions

Typical conditions for gramine-based C3 substitution (literature, general guidance; not item-specific specs):

• Quaternization/activation: Treat 4-fluorogramine (1.0 eq) with MeOTf or MeI (1.1–1.5 eq) in dry DCM, MeCN, or Et2O at 0–25 C for 0.5–3 h to form the quaternary ammonium salt. Monitor by TLC/HPLC.
• Nucleophilic displacement at C3: Add nucleophile (1.2–2.0 eq) and a base/acidolysis protocol depending on nucleophile type (e.g., NaCN or TMSCN with catalytic ZnCl2/TfOH; malonate anions with K2CO3; thiols with base) at 0–25 C for 1–6 h. Typical isolated yields: 50–85% depending on nucleophile and workup (literature ranges).
• Protection: If N-protection is needed, install Boc (Boc2O, DMAP, THF/MeCN, rt) prior to activation to suppress N-alkylation; deprotect under acidic conditions post-substitution.
• Workup: Partition between aqueous bicarbonate and organic solvent; quaternary ammonium byproducts are water-soluble as amines or salts, simplifying separation.
• Purification: Flash chromatography on silica; add 0.1–1% NEt3 to prevent tailing. Alternatively, crystallize target as HCl salt.

Other transformations:

• Electrophilic halogenation: NBS or NCS in DMF/MeCN at 0–25 C can install halogens at activated positions (subject to regioselectivity influenced by 4-F).
• Metal-catalyzed C–H functionalization: Pd/Cu-catalyzed reactions at C2 are possible with appropriate directing groups and protection; conditions vary widely in temperature (25–120 C) and ligands.

Always optimize on small scale; moisture control and exclusion of air may be necessary for sensitive nucleophiles.

Safety and Handling

Item-specific hazard information (from Product Data):

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

Authoritative safety information should be obtained from the product SDS for this exact SKU.

General safety considerations for indole tertiary amines (literature/experience-based; not item-specific):

• Likely hazards: Irritation to skin, eyes, and respiratory tract; harmful if swallowed; tertiary amines can be corrosive to some plastics and may have an amine odor. Avoid inhalation of dust/aerosols.
• Peroxide formation: Not a concern for this substrate itself (not an ether). However, use peroxide-free solvents when required by your reaction.
• Incompatibilities: Strong oxidizers (risk of exotherm/oxidation); strong acids/bases (may generate heat or salts); acylating/alkylating agents (can quaternize the amine). Avoid nitrosating conditions (tertiary amines can form N-nitrosamines under harsh nitrosation regimes).
• Recommended PPE: lab coat, nitrile gloves, safety glasses; use a fume hood to control vapors and dust.
• First-aid overview: in case of skin/eye contact, rinse with water for at least 15 minutes; remove contaminated clothing; if inhaled, move to fresh air; if ingested, rinse mouth. Seek medical attention in all cases of exposure.
• Fire safety: Treat as a combustible organic solid/liquid (depending on form). Use CO2, dry chemical, or foam. Thermal decomposition may release nitrogen oxides, HF (if fluorinated aromatics burn), and other irritants.

Waste: Collect organic amine waste in halogenated/non-halogenated containers as appropriate; neutralize to ammonium salts only if permitted by local regulations. Follow institutional and local regulations.

Solvent Selection

Compound type and polarity (general):

• 4-Fluorogramine is a moderately lipophilic indole bearing a basic tertiary amine. The free base dissolves well in polar aprotic organics; the protonated salt dissolves in water and alcohols.

Recommended solvent choices (general guidance):

• Stock solutions for screening/biology: DMSO (50–100 mg/mL typical), DMF, or ethanol. For aqueous systems, prepare an HCl or HBr salt and dissolve in water or buffer.
• Synthetic transformations: THF, 2-MeTHF, toluene, MeCN, dichloromethane, methanol/ethanol, depending on reaction. For strong bases/nucleophiles, use anhydrous polar aprotics (DMF/DMSO/MeCN).
• Purification: Silica gel chromatography using hexanes/EtOAc or DCM/MeOH gradients; tertiary amine may streak—add 0.1–1% NEt3 to eluent or pre-treat silica with base.

Miscibility/behavior (literature-typical):

• Free base: poor water solubility; good solubility in DCM, EtOAc, MeOH, MeCN, DMF, DMSO; moderate in ethers.
• Protonated salts: high water and alcohol solubility; reduced solubility in non-polar solvents.

When to choose alternatives:

• If base-sensitive co-reagents are present, use neutral/alcoholic media to mitigate amine basicity.
• For biophysical assays sensitive to autofluorescence, consider lower concentrations or alternative detection wavelengths since indoles absorb ~280 nm.

Note: No item-specific solubility specs are provided for this SKU; verify experimentally for your matrix and scale.

Storage and Reconstitution

Item-specific storage/shipping (from Product Data):

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

General storage guidance (literature/practice; not item-specific specs):

• Keep tightly closed in a dry, well-ventilated place at ambient temperature away from heat and light. Protect from strong oxidants and acids/bases.
• If long-term storage is anticipated, consider maintaining under inert gas (N2/Ar) to minimize oxidative discoloration of indoles. Store desiccated to avoid moisture uptake.
• Indole derivatives can slowly oxidize; monitor color and purity periodically by HPLC/NMR.

Reconstitution/use:

• For stock solutions: dissolve the free base in dry DMSO, DMF, MeCN, EtOH, or DCM. Typical lab stocks: 10–100 mM in DMSO. Filter (0.2 µm) if particulate is present.
• For aqueous work: convert to the hydrochloride salt (treat with HCl in ether/EtOH and isolate) to enhance water solubility; or dissolve as a DMSO cosolvent system.
• Freeze–thaw: If storing solutions, aliquot to avoid repeated freeze–thaw cycles. DMSO stocks are generally stable at −20 C for weeks to months; verify by LC/MS before critical experiments.

Note: Always refer to the lot-specific CoA and SDS for definitive storage and handling requirements for this SKU.

Structure and Identity

Brief description: 4-Fluorogramine is a fluorinated gramine analog, i.e., an indole bearing a 3-(dimethylaminomethyl) substituent and a fluorine substituent at the 4-position of the benzene ring. It is a tertiary amine indole building block often used to introduce 3-substituted indole motifs via the “gramine displacement” strategy.

• Item-specific identifiers (from Product Data)

  • CAS: 101909-46-0
  • PubChem CID: 2774470
  • InChIKey: Not specified for this item; refer to CoA/Spec Sheet. (Product Data field shows a placeholder)
  • SMILES: Not specified for this item; refer to CoA/Spec Sheet.

• Literature structural features (general, non-item-specific)

  • Core scaffold: indole (fused benzene–pyrrole system)
  • Substituents: 3-(dimethylaminomethyl) group; 4-fluoro on the benzene part of indole
  • Functional groups: tertiary aliphatic amine; indole NH; aryl fluoride
  • Stereochemistry: none (achiral as typically supplied)

• 2D structure in words (literature): an indole ring with an –CH2–N(CH3)2 substituent at C3 (adjacent to the pyrrolic nitrogen) and an F substituent para to the C3 position on the benzene ring (the 4-position). The molecule contains a basic tertiary amine and a mildly acidic indole NH.

• Formula and molecular weight

  • Molecular formula (literature for the neutral free base): approximately C11H14FN2
  • Molecular weight (literature): approximately 193 g/mol

Note: Identity fields not explicitly provided in the Product Data should be confirmed against the Certificate of Analysis (CoA) or Specification Sheet for this specific SKU.

Synthetic Utility

Key functional elements and reactivity (literature):

• 3-(Dimethylaminomethyl) group: convertible to an iminium or quaternary ammonium, enabling substitution by carbon, nitrogen, oxygen, sulfur, or halide nucleophiles to furnish 3-substituted indoles. This “gramine method” is a practical alternative to direct C3 electrophilic substitution.
• Indole NH: can be protected (Boc, SEM, Ts) to control chemoselectivity (avoid N-alkylation) and direct substitutions on the ring.
• 4-Fluoro substituent: modulates electronics and can act as a spectroscopic handle (19F NMR); while aryl–F is generally inert to standard Pd cross-couplings, specialized borylation/C–F activation methods exist for late-stage diversification.

Representative transformations (general examples):

• Quaternization and displacement: MeOTf or MeI to quaternary ammonium salt → nucleophilic substitution at C3 with malonates, thiols, cyanide, or enolates to install functionality.
• Reductive transformations: Hydrogenolysis or hydride delivery to modify benzylic positions after activation; Eschenmoser–type salt chemistry for rearrangements.
• Metalation chemistry: Directed lithiation at C2 or side chain under strong base with N-protection; subsequent electrophile trapping.
• Electrophilic substitution: Halogenation, sulfonylation, or formylation on the indole ring controlled by the 4-F substituent’s deactivation pattern.

Utility in retrosynthesis:

• 4-Fluorogramine serves as a convergent handle to rapidly access 3-substituted 4-fluoroindoles from a single precursor, allowing parallel synthesis and rapid SAR without refunctionalizing the ring each time.

Target Specificity

Not applicable. This product is a small-molecule building block, not a biological macromolecule or antibody. No target, antigen, epitope, clone, isotype, or species reactivity information applies to this SKU.

Frequently Asked Questions

What is the purity of this product?

This product is supplied at ≥96% purity (chemical assay). Lot-specific values are stated on the Certificate of Analysis.

How should this product be stored?

Store at room temperature.

What are the CAS number, molecular formula and molecular weight?

The CAS Number is 101909-46-0, the molecular formula is C11H13FN2, and the molecular weight is 192.23 g/mol. InChIKey GPYAFVBWLYCAMD-UHFFFAOYSA-N.

What documentation is provided?

Available product documentation, including Certificates of Analysis (COA), Safety Data Sheets (SDS), and specification sheets, is shown in the product document area. Document availability and access follow the current site policy.