6-Chloro-2-methyl-2H-indazole: Handling & Lab Protocol Guide

6-Chloro-2-methyl-2H-indazole is a chlorinated, N-methylated indazole heterocycle that serves as a versatile building block in medicinal chemistry and drug discovery programs targeting indazole-containing scaffolds.

Chemical Name

6-Chloro-2-methyl-2H-indazole

Aladdin SKU

C725187

Molecular Formula

C8H7ClN2

Regiochemistry

N2-methylated indazole; chlorine substituent at the 6-position of the benzene ring

Primary Application

Heterocyclic building block for medicinal chemistry and drug synthesis

Recommended Storage

Cool, dry place; sealed container; away from light and moisture

Compound Overview and Chemical Properties

6-Chloro-2-methyl-2H-indazole (Aladdin SKU C725187) is a bicyclic aromatic heterocycle belonging to the indazole family. The indazole core consists of a benzene ring fused with a pyrazole ring. In this compound, the nitrogen at the N2 position bears a methyl group, defining it as a 2H-indazole regioisomer, and a chlorine atom is located at the 6-position of the benzo ring.

The molecular formula is C₈H₇ClN₂. The presence of the chlorine substituent makes this compound a highly useful handle for downstream cross-coupling reactions (e.g., Suzuki, Buchwald-Hartwig), nucleophilic aromatic substitution, and other transition-metal-catalyzed transformations. The N-methyl group eliminates N–H acidity, simplifying reaction selectivity in many synthetic contexts.

Indazole-containing motifs are found in numerous approved pharmaceuticals and bioactive compounds, making chlorinated indazole building blocks such as this compound strategically valuable in lead optimization and fragment-based drug discovery.

Safety, Storage, and Handling

Personal Protective Equipment (PPE): Always wear appropriate PPE when handling 6-Chloro-2-methyl-2H-indazole. This includes chemical-resistant gloves (e.g., nitrile), a laboratory coat, and safety goggles. Work in a well-ventilated fume hood to minimize inhalation exposure to dust or vapors.

Storage Conditions: Store the compound in a tightly sealed container in a cool, dry location, away from direct light and sources of moisture. Segregate from strong oxidizing agents and strong acids. Ensure the storage area complies with local regulations for organic chemical storage.

Spill and Disposal: In the event of a spill, avoid generating dust, sweep up carefully with inert material, and place into a sealed waste container. Dispose of in accordance with applicable local, regional, and national regulations for organic chemical waste. Consult the Safety Data Sheet (SDS) for full hazard information before use.

Note: Specific GHS hazard classifications and pictograms should be verified against the current SDS provided by Aladdin Scientific at the time of purchase.

Solution Preparation Protocol

Solubility Considerations: 6-Chloro-2-methyl-2H-indazole is an organic solid. It is expected to dissolve readily in common polar aprotic solvents such as dimethyl sulfoxide (DMSO), N,N-dimethylformamide (DMF), and dichloromethane (DCM), and in protic solvents such as ethanol or methanol. Aqueous solubility is expected to be limited due to the lipophilic chloro-indazole scaffold.

Stock Solution Preparation (General Procedure):

1. Equilibrate the sealed vial to room temperature before opening to prevent moisture condensation on the solid.
2. Accurately weigh the required quantity of compound using a calibrated analytical balance.
3. Transfer to a clean, dry glass vial and add the appropriate volume of solvent (e.g., DMSO for biological assays, DCM for synthetic use) to achieve the desired concentration.
4. Vortex or sonicate briefly until complete dissolution is confirmed visually.
5. Filter through a 0.2 µm PTFE syringe filter if a particle-free solution is required.
6. Label the vial with compound name, lot number, concentration, solvent, preparation date, and preparer initials.

Recommended Storage of Solutions: Store prepared solutions at −20 °C under inert atmosphere (argon or nitrogen) when long-term stability is required. Avoid repeated freeze-thaw cycles. Verify solution stability by reviewing relevant literature or conducting in-house stability assessments.

Note: Exact solubility data should be verified experimentally, as specific values are not provided in the current source material.

Synthetic Applications and Downstream Reactions

6-Chloro-2-methyl-2H-indazole is primarily employed as an electrophilic aromatic building block in multi-step synthetic sequences. The C6–Cl bond is well-suited for the following transformations:

• Palladium-Catalyzed Cross-Coupling: The aryl chloride can participate in Suzuki-Miyaura (with arylboronic acids), Negishi (with organozinc reagents), and Heck reactions under standard Pd(0) or Pd(II) catalyst systems, enabling installation of diverse aryl, vinyl, or alkyl groups at the 6-position.
• Buchwald-Hartwig Amination: The C–Cl bond can be converted to C–N bonds via palladium-catalyzed amination, providing access to 6-amino-2-methyl-2H-indazole derivatives valuable in medicinal chemistry.
• Nucleophilic Aromatic Substitution (SNAr): When activated by the electron-withdrawing character of the indazole nitrogen system, the chloride may undergo SNAr with suitable nucleophiles (amines, alkoxides) under appropriate conditions.
• Further N-Functionalization: Although N2 is already methylated, the compound can be used as a template for elaboration at C3 via directed metalation or electrophilic substitution strategies.

Always optimize reaction conditions (catalyst loading, base, solvent, temperature) for each specific transformation. Consult primary literature for precedent reactions involving closely related indazole substrates.

Quality Control and Verification

Upon receipt of 6-Chloro-2-methyl-2H-indazole (Aladdin SKU C725187), the following checks are recommended before initiating sensitive synthetic steps:

• Visual Inspection: Confirm the solid is free-flowing and consistent in appearance with no signs of decomposition, discoloration, or excessive moisture uptake.
• NMR Verification: Acquire a ¹H NMR spectrum in an appropriate deuterated solvent (e.g., CDCl₃ or DMSO-d₆). Key diagnostic signals include the aromatic protons of the indazole ring, the singlet corresponding to the N-methyl group (expected ~3.9–4.1 ppm region, to be verified against literature), and the characteristic vinyl C3–H proton of the 2H-indazole tautomer.
• HPLC Purity Check: If purity is critical, perform reversed-phase HPLC analysis. Compare retention time and peak area against a reference standard.
• Mass Spectrometry: Confirm molecular ion [M+H]⁺ consistent with the molecular formula C₈H₇ClN₂ (MW ~166.6 g/mol, accounting for ³⁵Cl/³⁷Cl isotope pattern).

Document all QC results with the batch/lot number and store records for traceability. Contact Aladdin Scientific customer service if the product does not meet the stated specifications.

Frequently asked questions

What solvents are recommended for dissolving 6-Chloro-2-methyl-2H-indazole?

Based on the lipophilic chloroindazole scaffold, DMSO, DMF, and DCM are expected to be good solvents. For biological assays, DMSO stock solutions are typically preferred. Aqueous solubility is anticipated to be low; exact solubility values should be determined experimentally.

What is the difference between 1H-indazole and 2H-indazole regioisomers, and which form is 6-Chloro-2-methyl-2H-indazole?

In 1H-indazoles, the hydrogen (or substituent) is on the N1 nitrogen adjacent to the benzene ring, whereas in 2H-indazoles it resides on the N2 nitrogen. 6-Chloro-2-methyl-2H-indazole has a methyl group specifically on N2, making it a 2H-indazole. This regiochemical distinction affects electronic properties, reactivity, and biological activity profiles of downstream derivatives.

Can the C6 chloride in this compound be used in palladium-catalyzed cross-coupling reactions?

Yes. Aryl chlorides are established electrophilic partners in palladium-catalyzed cross-coupling reactions, including Suzuki-Miyaura, Buchwald-Hartwig amination, and Heck reactions, typically requiring more active Pd catalysts (e.g., Pd with bulky phosphine ligands) compared to aryl bromides or iodides. Optimization of catalyst, base, and solvent conditions is recommended for each specific coupling.

How should I store 6-Chloro-2-methyl-2H-indazole to maximize shelf life?

Store the compound in a tightly sealed container in a cool, dry place away from light and moisture. For long-term storage of solutions, −20 °C under an inert atmosphere (argon or nitrogen) is recommended. Always consult the SDS and certificate of analysis supplied with the product for manufacturer-specific storage recommendations.

Where can I obtain the Safety Data Sheet (SDS) for Aladdin SKU C725187?

The SDS for 6-Chloro-2-methyl-2H-indazole (SKU C725187) is available through the Aladdin Scientific website on the product page, or by contacting Aladdin Scientific customer service directly. Always review the SDS before first use to understand hazard classifications, first-aid measures, and disposal requirements.

References

1. Aladdin Scientific Product Page: 6-Chloro-2-methyl-2H-indazole, SKU C725187.
2. Comprehensive Heterocyclic Chemistry (textbook series): Indazoles chapter — general properties and reactivity of indazole regioisomers.
3. Miyaura, N.; Suzuki, A. Palladium-Catalyzed Cross-Coupling Reactions of Organoboron Compounds. Chem. Rev. 1995, 95, 2457–2483. doi:10.1021/cr00039a007
4. Hartwig, J. F. Palladium-catalyzed amination of aryl halides: mechanism and rational catalyst design. Acc. Chem. Res. 1998, 31, 852–860. doi:10.1021/ar970282g

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