Compound Overview and Properties

Ethyl 5-(tert-butyl)-1H-pyrazole-3-carboxylate (SKU E1369778) is a pyrazole heterocycle bearing a sterically demanding tert-butyl group at the 5-position and an ethyl ester functionality at the 3-position. The molecular formula is C₁₀H₁₆N₂O₂. The compound exists as a tautomeric mixture of 3- and 5-substituted 1H-pyrazole forms in solution, a behaviour characteristic of NH-pyrazoles.

The tert-butyl group confers steric bulk and enhanced lipophilicity, making this scaffold particularly attractive as a building block in drug discovery programs and in the synthesis of agrochemically active molecules. The ethyl ester moiety provides a versatile handle for further chemical transformations including hydrolysis to the carboxylic acid, amide coupling, and reduction.

Safety and Storage Guidelines

Before handling Ethyl 5-(tert-butyl)-1H-pyrazole-3-carboxylate, consult the current Safety Data Sheet (SDS) provided by Aladdin Scientific. Observe the following general precautions:

• Personal Protective Equipment (PPE): Wear appropriate laboratory coat, nitrile gloves, and safety goggles at all times during weighing and dissolution steps.
• Ventilation: Handle in a well-ventilated fume hood to avoid inhalation of dust or vapours.
• Storage: Store in a tightly sealed container in a cool, dry location away from direct light, heat sources, and incompatible materials (strong oxidisers, strong bases).
• Moisture sensitivity: Although not classified as highly moisture-sensitive, it is good practice to seal the container promptly after use and to use dried solvents when preparing stock solutions intended for sensitive reactions.
• Disposal: Dispose of waste in accordance with local institutional and governmental regulations for organic chemical waste.

Preparation of Stock Solutions and Dissolution Protocol

The following protocol describes the preparation of a stock solution suitable for use in organic synthesis or biological screening assays.

1. Select solvent: Ethyl 5-(tert-butyl)-1H-pyrazole-3-carboxylate is soluble in common organic solvents including dichloromethane (DCM), dimethyl sulfoxide (DMSO), ethanol, ethyl acetate, and tetrahydrofuran (THF). For biological assays requiring aqueous compatibility, prepare a concentrated DMSO stock and dilute into aqueous buffer immediately before use.
2. Weigh the compound: Using a calibrated analytical balance, transfer the required mass of compound into a clean, dry vial. Record the exact mass.
3. Add solvent: Add the calculated volume of dry solvent to achieve the desired concentration. For a 100 mM stock solution in DMSO, dissolve the appropriate number of milligrams per millilitre based on the molecular weight.
4. Mix: Vortex or sonicate gently at room temperature until complete dissolution is confirmed visually. Avoid prolonged sonication at elevated temperatures.
5. Aliquot and store: Divide the stock solution into single-use aliquots in capped microcentrifuge tubes. Store aliquots at −20 °C to minimise freeze-thaw cycles and potential degradation.
6. Quality check: Verify solution clarity before each use; discard any aliquot showing precipitation or discolouration.

Note: Exact molecular weight should be confirmed from the current product certificate of analysis (CoA) available from Aladdin Scientific for SKU E1369778.

Synthetic Applications and Reaction Protocol

Ethyl 5-(tert-butyl)-1H-pyrazole-3-carboxylate serves as a multifunctional intermediate. Representative transformations include:

1. Ester Hydrolysis to Carboxylic Acid

Dissolve the compound in a mixture of ethanol and aqueous sodium hydroxide solution (2 M, 3 equivalents). Stir at room temperature or gentle reflux until TLC or LC-MS confirms complete conversion. Acidify the reaction mixture to pH 2–3 with aqueous HCl, extract with ethyl acetate, dry over anhydrous MgSO₄, filter, and concentrate under reduced pressure to yield 5-(tert-butyl)-1H-pyrazole-3-carboxylic acid.

2. Amide Bond Formation

Hydrolyse the ester to the free acid as above. Activate the carboxylic acid using a standard coupling reagent (e.g., HATU, EDC·HCl) in the presence of a base (e.g., DIPEA, 2–3 equivalents) in DMF at room temperature. Add the amine coupling partner and stir for 2–16 hours. Work up by dilution with ethyl acetate, washing with saturated aqueous NaHCO₃ and brine, drying, filtering, and concentrating. Purify by column chromatography.

3. N-Alkylation of the Pyrazole NH

Dissolve the compound in DMF. Add a base such as K₂CO₃ (1.5–2 equivalents) followed by an alkyl halide (1.1–1.3 equivalents). Stir at room temperature to 60 °C, monitoring by TLC or LC-MS. Both N1- and N2-alkylated regioisomers may form; separation by column chromatography is typically required.

All reactions should be optimised by the end user. Reaction conditions listed here are indicative only and require experimental verification.

Quality Control and Analytical Characterisation

Researchers receiving SKU E1369778 from Aladdin Scientific should verify compound identity and purity before use by consulting the accompanying Certificate of Analysis (CoA) and, where required, performing in-house analytical checks:

• Purity assessment: Reverse-phase HPLC with UV detection (254 nm) is the standard method for purity determination. The CoA will specify the lot-specific purity value.
• Identity confirmation: ¹H NMR in DMSO-d₆ or CDCl₃ should show characteristic signals for the NH proton (broad, ~12–13 ppm), the vinyl/aromatic pyrazole CH (~6.7–7.0 ppm), the ethyl ester quartet and triplet (~4.3 ppm and ~1.3 ppm), and the tert-butyl singlet (~1.3 ppm, 9H).
• Mass spectrometry: ESI-MS should give [M+H]⁺ consistent with the molecular formula C₁₀H₁₆N₂O₂.
• Tautomer consideration: In NMR spectra, the NH-pyrazole tautomers may give broadened or doubled signals; this is a known property and does not indicate impurity.

Contact Aladdin Scientific technical support if analytical results deviate significantly from the CoA specifications.