2,3-Dimethyl-2H-indazol-6-amine: Handling & Use Protocol

2,3-Dimethyl-2H-indazol-6-amine is a functionalized indazole building block bearing a primary aromatic amine at the 6-position and methyl substituents at the 2- and 3-positions, making it a versatile intermediate for medicinal chemistry and heterocyclic synthesis.

Chemical Name

2,3-Dimethyl-2H-indazol-6-amine

Molecular Formula

C9H11N3

Molecular Weight

161.20 g/mol

Core Scaffold

2H-Indazole (bicyclic pyrazole-benzene ring system)

Key Functional Groups

Primary aromatic amine (–NH2) at C6; N-methyl at N2; methyl at C3

Recommended Storage

Cool, dry, well-ventilated location; protect from moisture and light

SKU

D176504

Compound Overview and Properties

2,3-Dimethyl-2H-indazol-6-amine (SKU: D176504) belongs to the indazole family of bicyclic nitrogen heterocycles, which have broad relevance in pharmaceutical research and agrochemical development. The compound features an indazole ring system in which the nitrogen at position 2 carries a methyl group, the carbon at position 3 carries a methyl group, and the carbon at position 6 bears a free primary aromatic amine.

The primary amine moiety at C6 confers nucleophilic reactivity, enabling participation in amide coupling, reductive amination, diazotization, and condensation reactions. The N2-methyl group locks the compound in the 2H-tautomeric form, providing a defined and stable regiochemical identity compared with unsubstituted indazoles that exist as tautomeric mixtures.

Its moderate molecular weight (161.20 g/mol) and the presence of both hydrogen-bond donor (–NH2) and acceptor (ring nitrogens) sites suggest drug-like physicochemical character, making it of interest as a scaffold in lead optimization campaigns.

Safety and Personal Protective Equipment

As with all primary aromatic amines, 2,3-Dimethyl-2H-indazol-6-amine should be handled with appropriate caution. Primary aromatic amines as a chemical class are associated with potential mutagenicity and should be treated as hazardous until full toxicological data are established for this specific compound.

Recommended PPE:

• Nitrile gloves (double-gloving recommended for extended handling)
• Laboratory coat and closed-toe shoes
• Safety goggles or face shield
• Work in a fume hood or well-ventilated area to avoid inhalation of dust or aerosols

Waste disposal: Collect all waste containing this compound in labelled, sealed containers and dispose of according to local regulations governing aromatic amine waste streams. Do not pour down the drain.

Note: Consult the Safety Data Sheet (SDS) supplied with product D176504 for compound-specific hazard classifications, GHS pictograms, and first-aid measures before use.

Stock Solution Preparation Protocol

The following protocol describes preparation of a 10 mM stock solution as a typical starting concentration for biological or chemical assays. Adjust volumes proportionally for other concentrations.

Materials required:

• 2,3-Dimethyl-2H-indazol-6-amine (D176504), weighed on an analytical balance
• Anhydrous DMSO or DMF (preferred solvents for initial dissolution of aromatic amines)
• Amber glass vials or low-binding microcentrifuge tubes
• Calibrated pipettes and volumetric equipment

Procedure:

1. Allow the reagent vial to equilibrate to room temperature before opening to avoid condensation on the compound.
2. Weigh the required mass accurately. For a 10 mM solution: dissolve 1.612 mg of compound in 1.0 mL of anhydrous DMSO.
3. Vortex for 30–60 seconds, then sonicate in a water bath (ambient temperature) for up to 5 minutes if needed to ensure complete dissolution.
4. Visually inspect the solution; it should be clear. If particulates remain, centrifuge briefly at 2,000 × g and transfer the supernatant.
5. For aqueous assay buffers, prepare a 100× concentrated stock in DMSO and dilute 1:100 into the buffer immediately before use. Ensure final DMSO concentration does not exceed 0.1–1% v/v depending on assay tolerance.
6. Aliquot into single-use volumes to avoid repeated freeze–thaw cycles. Store at –20 °C under inert atmosphere (argon or nitrogen) in sealed amber vials.

Solubility data specific to this compound are not available in the current source material; confirm experimentally and add a review flag.

Typical Applications in Research

2,3-Dimethyl-2H-indazol-6-amine serves as a synthetic building block and pharmacophore component in several research contexts:

1. Medicinal chemistry synthesis: The free amine at C6 is a versatile handle for forming amide bonds via coupling reagents (e.g., HATU, EDC/NHS), sulfonamides via sulfonyl chlorides, ureas via isocyanates, or imines/Schiff bases via aldehydes. These transformations are standard methods for generating focused libraries around the indazole scaffold.

2. Kinase inhibitor research: The indazole scaffold is widely represented in kinase inhibitor pharmacology. N-methylindazole derivatives have appeared in programs targeting receptor tyrosine kinases and other enzyme classes. This compound may serve as an intermediate toward such targets.

3. Fluorescent probe development: Aromatic amines appended to heterocyclic scaffolds are used in the construction of environmentally sensitive fluorescent dyes and sensors. The amine group can be further functionalized with chromophore-conjugating moieties.

4. Structure–activity relationship (SAR) studies: As a regiochemically defined indazole amine, D176504 is useful for SAR investigations comparing activity profiles of differently substituted indazolamine isomers.

Specific published applications citing this exact compound were not identified in the provided source material. See review flags.

Quality, Purity, and Troubleshooting

Purity verification: Aladdin Scientific recommends confirming compound identity and purity before use in critical assays. Standard analytical methods include:

• HPLC: Reverse-phase C18 column with UV detection at 254 nm or 280 nm. Purity ≥95% is typically expected for reagent-grade material; consult the Certificate of Analysis (CoA) for the specific lot.
• NMR: 1H and 13C NMR in deuterated DMSO (DMSO-d6) or CDCl3 for structural confirmation. Key signals expected include methyl singlets (N-CH3 and C3-CH3) in the 2–4 ppm region and aromatic protons in the 6.5–7.8 ppm region. NH2 protons may appear as a broad signal.
• LC-MS: Confirm [M+H]+ at m/z 162.1 (C9H11N3 + H+, MW 161.20).

Common issues and troubleshooting:

• Incomplete dissolution: Switch to a more polar aprotic solvent (DMF > DMSO > acetonitrile). Gentle warming (40 °C) may assist; avoid temperatures >60 °C to prevent degradation.
• Color change upon storage: Primary aromatic amines can undergo aerial oxidation, leading to discoloration. Purge with inert gas before resealing; discard visibly degraded material.
• Low assay signal: Verify stock concentration by UV absorbance if an extinction coefficient is available, or by HPLC against an external standard.

Frequently asked questions

What solvents are recommended for dissolving 2,3-Dimethyl-2H-indazol-6-amine?

Anhydrous DMSO and DMF are the preferred solvents for preparing concentrated stock solutions of this aromatic amine. For aqueous assay systems, prepare a high-concentration DMSO stock first and then dilute into the aqueous buffer immediately before use, keeping the final DMSO content below 1% v/v where possible.

How should 2,3-Dimethyl-2H-indazol-6-amine be stored to maintain stability?

Store the solid compound in a tightly sealed container at –20 °C, protected from light and moisture, under an inert atmosphere of nitrogen or argon. Solutions should be aliquoted to avoid repeated freeze–thaw cycles. Allow the vial to reach room temperature before opening to prevent moisture condensation on the compound.

What reactions can be performed using the amine group of this compound?

The primary aromatic amine at the 6-position is nucleophilic and suitable for a wide range of transformations, including amide bond formation (using coupling reagents such as HATU or EDC), sulfonamide synthesis (via sulfonyl chlorides), urea formation (via isocyanates), Schiff base/imine condensation (with aldehydes or ketones), and diazotization followed by further functionalization. These reactions make it a versatile building block for medicinal chemistry libraries.

How do I confirm the identity and purity of the received compound?

Identity and purity can be confirmed by reverse-phase HPLC (C18, UV 254 nm), 1H/13C NMR in DMSO-d6, and LC-MS by verifying the [M+H]+ ion at m/z 162.1. Always cross-reference results with the Certificate of Analysis (CoA) provided with the specific lot of D176504.

Is 2,3-Dimethyl-2H-indazol-6-amine the same as the 1H-tautomer?

No. The 2H designation in the name specifies that the methyl group is on N2, fixing the compound in the 2H-tautomeric form. The 1H-tautomer would have the methyl on N1 instead. These are distinct regioisomeric structures with different chemical and potentially different biological properties, so it is important to use the correct regioisomer for your application.

References

1. Comprehensive Organic Transformations: A Guide to Functional Group Preparations, 3rd ed. Larock, R.C. Wiley-VCH. (General reference for amine functional group chemistry.)
2. Elguero, J. et al. Indazoles. In Comprehensive Heterocyclic Chemistry III. Elsevier, 2008. (Reference for indazole tautomerism and substitution chemistry.)
3. Aladdin Scientific Certificate of Analysis, Product D176504, 2,3-Dimethyl-2H-indazol-6-amine. (Lot-specific purity and analytical data.)

Products are supplied for research and development use only. Not for use in humans, animals, diagnosis, or therapy.