Methyl 3-tert-butyl-1,2,4-oxadiazole-5-carboxylate
[CAS# 1899834-30-0]

Identification

• Classification: Organic raw materials >> Carboxylic compounds and derivatives >> Salt of carboxylic acid ester and its derivatives
• Name: Methyl 3-tert-butyl-1,2,4-oxadiazole-5-carboxylate
• Molecular Formula: C₈H₁₂N₂O₃
• Molecular Weight: 184.19
• CAS Registry Number: 1899834-30-0
• SMILES: CC(C)(C)C1=NOC(=N1)C(=O)OC

Properties

• Density: 1.1±0.1 g/cm³ Calc.^*
• Boiling point: 256.1±23.0 ºC 760 mmHg (Calc.)^*
• Flash point: 108.7±22.6 ºC (Calc.)^*
• Index of refraction: 1.462 (Calc.)^*

^* Calculated using Advanced Chemistry Development (ACD/Labs) Software.

Safety Data

• Hazard Symbols: GHS07 Warning
• Hazard Statements: H302-H315-H319
• Precautionary Statements: P501-P270-P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330

Discovory and Applicatios

Methyl 3-tert-butyl-1,2,4-oxadiazole-5-carboxylate belongs to the broader class of 1,2,4-oxadiazole derivatives, a group of heterocyclic compounds that has been the subject of sustained investigation due to its structural stability and useful physicochemical properties. The compound contains the characteristic 1,2,4-oxadiazole ring formed by two nitrogen atoms and one oxygen atom arranged within a five-membered framework. This ring system has been evaluated in many research programs as a compact scaffold that can modulate polarity, hydrogen bonding patterns, and metabolic resistance. The tert-butyl substituent at the 3-position and the methyl ester at the 5-position place the compound among the common synthetic intermediates used in studies of substituted oxadiazole esters.

The discovery and early development of 1,2,4-oxadiazole derivatives arose from research into heterocycles that could serve as stable surrogates for functional groups in medicinal chemistry. Within this context, carboxylate-substituted oxadiazoles were examined as potential bioisosteres of amides and esters. Researchers recognized that the heterocycle could mimic the electronic distribution of these groups while maintaining greater hydrolytic stability. This observation motivated substantial work on their preparation, structure, and reactivity, as well as on the influence of substituents such as tert-butyl groups on steric shielding and lipophilicity.

The preparation of methyl 3-tert-butyl-1,2,4-oxadiazole-5-carboxylate relies on well-established cyclodehydration methodologies that convert amidoximes and carboxylic acid derivatives into the 1,2,4-oxadiazole ring. Cyclization reactions of this type have been widely explored and optimized, including the use of esters as electrophilic partners. Studies have documented that controlled dehydration enables formation of the heterocycle under conditions that preserve diverse substituents, making the method suitable for a range of alkyl- and aryl-substituted oxadiazole esters. The tert-butyl side group, introduced through standard alkylation or via corresponding amidoxime precursors, remains compatible with these procedures. The resulting ester products are typically stable, crystalline materials that can be purified by routine chromatographic or distillation techniques.

Interest in carboxylate-substituted 1,2,4-oxadiazoles expanded as their potential applications were investigated. In medicinal chemistry, this class has been used to explore structure–activity relationships in programs targeting enzymes, receptors, and transporters. The methyl ester functionality provides a handle for further transformation, including hydrolysis to the corresponding acid, conversion to amides, or participation in coupling reactions. The tert-butyl group can influence membrane permeability and metabolic behavior, prompting its incorporation into experimental series evaluating steric effects on bioactive molecules. While methyl 3-tert-butyl-1,2,4-oxadiazole-5-carboxylate itself has mainly been described as an intermediate rather than a final active compound, its structural features align with general strategies in the design of heterocyclic building blocks.

Beyond medicinal chemistry, substituted 1,2,4-oxadiazoles have been applied in materials research. Their rigid heterocyclic cores and tunable substituents allow modulation of thermal stability and electronic properties. Carboxylate-functionalized oxadiazoles may be incorporated into polymer frameworks or used as precursors for ligands in coordination chemistry. Studies investigating electron distribution within the ring have also contributed to understanding how substituents affect resonance and conjugation within these systems. Compounds bearing bulky alkyl groups such as tert-butyl have been used to probe steric effects on packing, crystallinity, and intermolecular interactions.

Overall, the development of this compound draws on a substantial body of verified experimental work on the synthesis and behavior of 1,2,4-oxadiazoles. The compound’s structural features represent typical modifications used to adjust stability, reactivity, and compatibility with downstream applications, particularly in the preparation of derivatives for biological or materials-oriented investigations. Its place in the literature arises from its role as a representative member of a well-studied family of heterocyclic carboxylate esters.

References

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URL: EP-4249073-A1

2023. Pyrimidines for degrading bruton's tyrosine kinase. World Intellectual Property Organization.
URL: WO-2023183811-A1

2022. Fused imidazopyridines as reversible inhibitors of bruton's tyrosine kinase (btk). World Intellectual Property Organization.
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