Chemical Identity and Physical Properties

Ethyl 5-iodo-1-methyl-1H-pyrazole-4-carboxylate (CAS number should be verified; Aladdin SKU: E768363) is a substituted pyrazole derivative bearing three distinct functional handles: a reactive aryl carbon–iodine bond at the 5-position, a carboxylate ester at the 4-position, and an N-methyl group on the pyrazole nitrogen. Its molecular formula is C₇H₉IN₂O₂, giving a molecular weight of approximately 280.06 g/mol.

The compound typically appears as a white to off-white crystalline solid. The aryl iodide functionality is among the most reactive carbon–halogen bonds toward oxidative addition to low-valent transition metals, making this compound particularly valuable as a coupling electrophile. The ester group provides an additional handle for further derivatization through hydrolysis, amide coupling, or reduction. The N-methyl group on the pyrazole ring locks the regiochemistry of the heterocycle and prevents tautomerism, ensuring consistent reactivity in downstream transformations.

Synthetic Applications and Reaction Protocols

The aryl iodide moiety of Ethyl 5-iodo-1-methyl-1H-pyrazole-4-carboxylate is ideally suited for palladium-catalyzed cross-coupling reactions. The high polarizability of the C–I bond facilitates rapid oxidative addition, often allowing milder conditions compared with the analogous bromide or chloride counterparts.

Suzuki–Miyaura Coupling: This compound can be coupled with aryl- or heteroarylboronic acids in the presence of a Pd(0) or Pd(II) precatalyst (e.g., Pd(PPh₃)₄ or Pd(dppf)Cl₂), a base such as K₂CO₃ or Cs₂CO₃, and a suitable solvent system (e.g., DMF/H₂O or dioxane/H₂O) at 60–90 °C to furnish biaryl pyrazole products useful in drug discovery.

Sonogashira Coupling: Reaction with terminal alkynes under Pd/Cu catalysis (e.g., PdCl₂(PPh₃)₂, CuI, Et₃N as base) provides alkynyl-pyrazole intermediates, which are valuable scaffolds in kinase inhibitor programs.

Negishi and Kumada Couplings: Organozinc and organomagnesium reagents can also be employed to introduce alkyl or aryl substituents at the 5-position, expanding molecular diversity.

Ester Derivatization: Following cross-coupling, the ethyl ester may be saponified to the carboxylic acid under standard basic hydrolysis conditions, then converted to amides or other acyl derivatives for SAR studies in medicinal chemistry programs.

Handling, Safety, and Storage Guidelines

Personal Protective Equipment (PPE): As with all iodinated organic intermediates, researchers should wear appropriate PPE including nitrile gloves, a laboratory coat, and safety glasses when handling Ethyl 5-iodo-1-methyl-1H-pyrazole-4-carboxylate. Work in a well-ventilated fume hood to minimize inhalation exposure to dust or vapors.

Storage: Store the compound in a tightly sealed container in a cool, dry location away from direct light and moisture. Prolonged exposure to light or moisture may promote decomposition of the aryl iodide functionality. A desiccant is recommended when storing opened containers. Refer to the product's Safety Data Sheet (SDS) for specific hazard classifications and first-aid measures.

Stability: The C–I bond, while highly reactive in catalytic cycles, is generally stable under ambient storage conditions when protected from UV light and moisture. The ethyl ester is susceptible to hydrolysis under strongly acidic or basic aqueous conditions; avoid prolonged contact with water.

Waste Disposal: Dispose of iodine-containing organic waste according to your institution's chemical waste management procedures and applicable local regulations. Do not pour down the drain.

Role in Medicinal Chemistry and Drug Discovery

Pyrazole-containing scaffolds are among the most prevalent heterocyclic motifs in approved pharmaceuticals and drug candidates. The 1-methylpyrazole-4-carboxylate core present in this compound appears in numerous bioactive molecules, including kinase inhibitors, anti-inflammatory agents, and antifungal compounds.

Ethyl 5-iodo-1-methyl-1H-pyrazole-4-carboxylate functions as a privileged starting material in fragment-based drug design and combinatorial library synthesis. The aryl iodide at the 5-position allows rapid diversification through cross-coupling, while the ester group enables transformation into pharmacophoric amide bonds, hydroxymethyl groups, or carboxylic acid bioisosteres. This two-point diversification strategy makes the compound exceptionally efficient for generating structure–activity relationship (SAR) data.

Medicinal chemists frequently exploit the electronic properties of the pyrazole ring—its moderate electron-withdrawing character when substituted with an ester—to tune the reactivity and binding affinity of derived compounds toward biological targets such as protein kinases, GPCRs, and ion channels.

Quality Specifications and Ordering Information

Aladdin Scientific supplies Ethyl 5-iodo-1-methyl-1H-pyrazole-4-carboxylate under SKU E768363. Researchers and procurement teams should request the current Certificate of Analysis (CoA) for each lot to confirm purity, identity (typically verified by ¹H NMR, ¹³C NMR, and/or HPLC), and other quality parameters prior to use in critical synthetic steps.

When ordering, specify the required quantity and purity grade. For sensitive applications such as late-stage pharmaceutical synthesis or reference standard use, request high-purity (≥98%) grade material and confirm that residual solvent levels comply with ICH Q3C guidelines. For early-stage medicinal chemistry or methodology development, standard reagent grade is typically sufficient.

Contact Aladdin Scientific's technical support team for custom quantities, bulk pricing, or additional analytical documentation. The Safety Data Sheet (SDS) is available upon request and should be reviewed before first use.