An approach to synthesis of 2‐, 4‐, and 5‐bromooxazoles is described. The method was optimized, and its scope was extended to all three isomeric parents, as well as various alkyl‐ and aryl‐substituted bromooxazoles. It was found that direct regiocontrolled lithiation followed by reaction with electrophilic bromine source was common for all substrates and led exclusively to the target substituted 2‐, 4‐ and 5‐bromooxazoles on multigram scale. The utility of the multipurpose building blocks obtained in this work was demonstrated in the Suzuki–Miyaura cross‐coupling reaction under parallel synthesis conditions.
Ethyl azol-2-ylglyoxylates react smoothly with acetone in the presence of catalytic amounts of proline and trifluoroacetic acid to give the corresponding azolyl aldols in 93-98% yield. The products are easily transformed into azolyl pyridazinones in 85-98% yield by cyclization with hydrazine hydrate.
A practical approach to imidazo[1,2]hetarylglyoxylates via Friedel-Crafts acylation of the parent fused imidazoles with ethyl oxalyl chloride is reported. The reaction is strongly influenced by the electron-donating properties of the starting heterocycle. The generated imidazo[1,2]hetarylglyoxylates undergo standard transformations typical of a-keto esters upon reaction with various nucleophiles. All the products contain an imidazoheterocyclic scaffold which is considered a privileged structure for drug discovery.
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