2,8-Dimethylimidazo[1,2-a]pyridin-6-amine 98% Purity CAS 1216295-25-8 Research Grade Dimethyl-Substituted Imidazopyridine Building Block for Kinase In

Product Overview

2,8-Dimethylimidazo[1,2-a]pyridin-6-amine (CAS 1216295-25-8) is a high‑purity dimethyl‑substituted heterocyclic building block featuring an imidazo[1,2‑a]pyridine core with methyl groups at the 2‑ and 8‑positions and an amino group at the 6‑position. The molecular formula is C₉H₁₁N₃ with a molecular weight of 161.20 g/mol. The imidazo[1,2‑a]pyridine scaffold is a privileged structure in medicinal chemistry, found in several clinically approved drugs including the insomnia medication zolpidem, and has been extensively studied for its diverse pharmacological properties including kinase inhibition, anti‑inflammatory activity, and antimicrobial activity.

The presence of methyl groups at both the 2‑ and 8‑positions provides distinct steric and electronic effects. The 2‑methyl group contributes to the compound‘s steric profile and can influence target selectivity, while the 8‑methyl group enhances metabolic stability and lipophilicity. The methyl substituents also reduce the compound‘s susceptibility to oxidative metabolism at these positions, potentially improving pharmacokinetic properties. The amino group at the 6‑position serves as a versatile handle for further derivatization through acylation, alkylation, sulfonylation, and amidation reactions, enabling the construction of diverse compound libraries.

The compound is an off‑white to pale yellow crystalline powder with a calculated LogP of approximately 1.8, indicating moderate lipophilicity suitable for cell permeability. The topological polar surface area (TPSA) is 43.3 Ų, with one hydrogen bond donor and three hydrogen bond acceptors. It is soluble in polar organic solvents such as dimethyl sulfoxide and dimethylformamide, with limited aqueous solubility. The product is supplied at ≥98.0% purity as determined by HPLC and is intended exclusively for research and development purposes.

Synthetic Process

The synthesis of 2,8‑dimethylimidazo[1,2‑a]pyridin‑6‑amine typically involves the condensation of appropriately substituted 2‑aminopyridine precursors with α‑haloketones, followed by cyclization to form the fused imidazo[1,2‑a]pyridine ring system. A representative synthetic route is described below:

• Step 1 – Preparation of Aminopyridine Precursor: 2‑amino‑3‑methyl‑5‑nitropyridine serves as the starting material, with the nitro group serving as a masked amine precursor for subsequent reduction. The 3‑methyl substituent on the pyridine ring provides the eventual 8‑methyl group in the final product.

• Step 2 – Condensation and Cyclization: The aminopyridine derivative is condensed with 1‑bromo‑2‑propanone (bromoacetone) in a solvent such as ethanol or acetonitrile under reflux conditions. The reaction proceeds via nucleophilic substitution followed by intramolecular cyclodehydration to afford the nitro‑substituted imidazo[1,2‑a]pyridine intermediate. The 2‑methyl group is introduced during this step through the use of bromoacetone.

• Step 3 – Reduction: The nitro group at the 6‑position is reduced to the corresponding primary amine using catalytic hydrogenation (H₂, Pd/C) in methanol or ethanol at room temperature for 4‑6 hours under 1 atmosphere of hydrogen. Alternative reduction methods include the use of iron powder in acetic acid or tin(II) chloride in hydrochloric acid.

• Step 4 – Purification: The crude product is purified by recrystallization from ethanol or methanol, or by flash column chromatography on silica gel (eluting with ethyl acetate‑hexane or dichloromethane‑methanol mixtures) to achieve ≥98% purity.

• Quality Control: The final product is rigorously characterized by HPLC analysis (purity ≥98.0%), ¹H‑NMR, ¹³C‑NMR, and mass spectrometry to confirm structural identity and purity. The presence of both methyl groups is confirmed by ¹H‑NMR integration and ¹³C‑NMR signals at the expected chemical shifts.

Mechanism of Action

As a synthetic building block, 2,8‑dimethylimidazo[1,2‑a]pyridin‑6‑amine serves as a versatile precursor for:

• Kinase Inhibitor Synthesis: The imidazo[1,2‑a]pyridine core is a proven scaffold for the development of protein kinase inhibitors. Related dimethylated imidazopyridine derivatives have demonstrated potent activity against various kinase targets including c‑Met, PI3K, and CDK families. The 2,8‑dimethyl substitution pattern provides a distinct steric and electronic profile that can enhance binding affinity and selectivity for specific kinase targets.

• Drug Discovery Programs: The scaffold‘s ability to serve as both a hydrogen bond acceptor (via the ring nitrogen atoms) and a hydrogen bond donor (via the 6‑amino group) enables strong and favorable interactions with biological targets. The methyl groups contribute to hydrophobic interactions with protein pockets, enhancing binding affinity.

• Agrochemical Research: Imidazopyridine derivatives have shown potential as nematicides, fungicides, and herbicides, demonstrating the scaffold‘s versatility in crop protection research. The methyl substitution pattern can modulate physicochemical properties and biological activity in agrochemical applications.

• Covalent Inhibitor Design: The 6‑amino group can be functionalized to introduce electrophilic warheads for the development of targeted covalent inhibitors, an increasingly important strategy in drug discovery for difficult‑to‑drug targets.

Quality Specifications

Safety Information

Signal Word: Warning

Hazard Statements: H302 (Harmful if swallowed), H315 (Causes skin irritation), H319 (Causes serious eye irritation), H335 (May cause respiratory irritation)

Precautionary Statements: P261‑P264‑P270‑P271‑P280‑P302+P352‑P304+P340‑P305+P351+P338‑P312‑P330‑P332+P313‑P337+P313‑P362‑P403+P233‑P405‑P501

Packaging & Shipping

• Research quantities: Available in 1g, 5g, 10g, and 25g amber glass vials with PTFE‑lined caps.

• Bulk quantities: Available in 100g, 500g, and 1kg amber glass bottles.

• Shipping conditions: This product is not classified as dangerous goods under international transport regulations (IATA/IMO).

• Storage conditions: Store at 2‑8°C, protected from light and moisture for long‑term stability.

• Documentation: Each shipment includes a comprehensive Certificate of Analysis (COA), MSDS, and commercial invoice with full customs declarations.

Jinan Topfull Chemical Co., Ltd. is an international company rooted in China, specializing in the export of chemical products.

Our company is committed to making every effort to provide ideal chemical products to potential customers worldwide, including but not limited to: organic/inorganic reagents, biological reagents, plant extracts, pharmaceutical intermediates, active pharmaceutical ingredients (APIs), reference standards, reference substances, peptides, and more. Meanwhile, we have established long-term and stable cooperative relationships with university laboratories and off-campus research institutions, enabling us to offer tailored product services based on customers' actual needs.

We currently support customized services for most product categories, with supply quantities ranging from milligram (mg), gram (g) to kilogram (kg) levels, as well as wholesale. Product purity covers the full spectrum from 90% to 99.9%, providing customers with one-stop convenient services.

To date, our products have been exported to developed countries such as the United States, Australia, Canada, Mexico, as well as EU member states including France, Germany, and many other countries and regions such as Nigeria, Ghana, Southeast Asia, and other parts of Asia. Our product quality and services have consistently received high praise.

Looking ahead, our company will continue to serve as a bridge connecting China and the world, delivering high-quality products and services to global customers .