Compound Overview and Scientific Relevance

5-Chloro-1H-pyrrolo[3,2-b]pyridine (CAS catalog SKU C124823) belongs to the pyrrolopyridine family of fused bicyclic heterocycles. Its core structure consists of a pyrrole ring fused at the [3,2-b] positions of a pyridine ring, making it an isomer of the well-known 7-azaindole scaffold. The presence of the C-5 chlorine atom provides a highly reactive site for palladium-catalyzed cross-coupling reactions (e.g., Suzuki, Buchwald–Hartwig, and Negishi couplings) as well as nucleophilic aromatic substitution (SNAr) under appropriate conditions.

This compound is of significant interest in pharmaceutical research as the pyrrolopyridine core is frequently encountered in kinase inhibitor scaffolds and other bioactive small molecules targeting enzyme active sites. The NH group of the pyrrole ring also offers an additional handle for N-alkylation or N-arylation reactions, further expanding the synthetic utility of this building block.

Safety, Storage, and Handling

Personal Protective Equipment (PPE): Always wear appropriate PPE when handling 5-Chloro-1H-pyrrolo[3,2-b]pyridine. This includes nitrile gloves, a laboratory coat, and safety glasses or goggles. Work in a well-ventilated fume hood to minimize inhalation exposure to fine powder or aerosols.

Storage: Store the compound in a tightly sealed container in a cool, dry location away from direct light and moisture. Exposure to humidity may promote degradation over time. Refrigeration (2–8 °C) is acceptable for long-term storage; ensure the vial is allowed to equilibrate to room temperature before opening to prevent condensation.

Waste Disposal: Dispose of all waste materials containing this compound in accordance with local institutional and governmental regulations for chemical waste. Do not dispose of via drain or municipal waste streams.

First Aid: In case of skin or eye contact, flush immediately with copious amounts of water for at least 15 minutes and seek medical attention if irritation persists. If inhaled, move to fresh air immediately.

Stock Solution Preparation Protocol

The following protocol describes preparation of a stock solution of 5-Chloro-1H-pyrrolo[3,2-b]pyridine for use in synthetic or biological assay applications.

1. Determine target concentration and volume: Calculate the mass of compound required using the formula: mass (mg) = target concentration (mM) × volume (mL) × molecular weight (g/mol) × 10⁻³. For example, to prepare 10 mL of a 10 mM stock solution: mass = 10 × 10 × 152.58 × 10⁻³ = 15.26 mg.
2. Select an appropriate solvent: 5-Chloro-1H-pyrrolo[3,2-b]pyridine is expected to dissolve in polar aprotic solvents such as DMSO, DMF, or acetonitrile. For aqueous-compatible applications, co-solvent systems (e.g., DMSO/water) may be employed; verify compatibility with the downstream assay or reaction.
3. Weigh and dissolve: Accurately weigh the required mass on an analytical balance. Transfer to a clean, dry vial and add the calculated volume of solvent. Vortex or sonicate gently until complete dissolution is achieved. Warming to 30–40 °C may assist dissolution if required.
4. Verify dissolution: Inspect the solution visually for clarity. A turbid solution indicates incomplete dissolution; continue mixing or adjust solvent volume accordingly.
5. Aliquot and store: Divide the stock solution into single-use aliquots in microcentrifuge tubes to minimize freeze-thaw cycles. Store aliquots at −20 °C under inert atmosphere (nitrogen or argon blanket) when possible. Record preparation date and concentration on each vial.

Note: Solubility data should be experimentally confirmed for each specific application. The values cited above are estimates based on structural analogs; see review flags.

Typical Synthetic Applications and Reaction Guidance

5-Chloro-1H-pyrrolo[3,2-b]pyridine serves as a versatile electrophilic building block in heterocyclic synthesis. Key reaction types and practical guidance are outlined below.

1. Palladium-Catalyzed Cross-Coupling at C-5: The C-5 chloro group undergoes standard Pd(0)- or Pd(II)-catalyzed Suzuki–Miyaura coupling with aryl- or heteroarylboronic acids in the presence of a base (e.g., K₂CO₃ or Cs₂CO₃) and a palladium catalyst (e.g., Pd(PPh₃)₄ or Pd(dppf)Cl₂) in mixed aqueous/organic solvent systems (e.g., DMF/H₂O or dioxane/H₂O) at 80–100 °C. Buchwald–Hartwig amination with primary or secondary amines can also be performed using appropriate phosphine ligands.

2. N-Functionalization of the Pyrrole NH: The NH group can be protected or functionalized prior to C-5 transformations. Common N-protecting groups include SEM (2-(trimethylsilyl)ethoxymethyl), Boc, or tosyl groups. N-Alkylation is typically performed under basic conditions (NaH in DMF or K₂CO₃ in acetone) with alkyl halides.

3. Nucleophilic Aromatic Substitution (SNAr): Under forcing conditions with strong nucleophiles (amines, alkoxides), the electron-deficient pyridine ring can facilitate SNAr at C-5 as an alternative to metal-catalyzed pathways, particularly useful in late-stage diversification.

General Recommendations: Conduct reactions under inert atmosphere (N₂ or Ar) when using air- or moisture-sensitive catalysts or reagents. Monitor reaction progress by TLC or UPLC/MS. Purify products by flash column chromatography or preparative HPLC as appropriate.

Quality Control and Analytical Characterization

Prior to use in critical synthetic steps or biological evaluations, researchers are advised to confirm the identity and purity of 5-Chloro-1H-pyrrolo[3,2-b]pyridine (C124823) using the following standard analytical techniques:

• ¹H NMR Spectroscopy: Expected signals include the NH proton (broad singlet, typically δ 11–12 ppm in DMSO-d₆), aromatic and vinyl CH protons of the pyrrolopyridine core. The absence of unexpected signals confirms purity and structural integrity.
• LC-MS / HRMS: Confirm molecular ion [M+H]⁺ consistent with the molecular formula C₇H₅ClN₂ (MW 152.58 g/mol). High-resolution mass spectrometry provides definitive confirmation of elemental composition.
• HPLC Purity: Evaluate purity by reverse-phase HPLC (C18 column; acetonitrile/water with 0.1% TFA gradient; UV detection at 254 nm or 280 nm). Aladdin Scientific provides lot-specific purity data with each shipment; consult the Certificate of Analysis (CoA) accompanying the product.
• Melting Point: A consistent melting point (compare against literature values for the compound) provides an additional confirmation of identity and purity. See review flags for specific literature melting point data.

Always refer to the Certificate of Analysis (CoA) supplied with each lot of C124823 for lot-specific analytical data before use.