Numerous reports for the synthesis of 2-aminothiazole motifs can be found in the literature. Standard Hantszch conditions still rule the pasture. Because the structural pharmacophore can be modified in many ways, it is a good target for new methodologies as well as potential analog possibilities.

Substituted 2-aminothiazoles

Substituted 2-aminothiazoles

5H-

5H-thiazolo[3,2-a]pyrimidine-5-ones

A recent report illustrates a creative approach using a tandem alkylation-cylization reaction under microwave conditions to provide substituted 2-aminothiazoles and 5H-thiazolo[3,2-a]pyrimidine-5-ones. Following scheme I, substituted thioureas and various propargyl bromides in DMF with a stoichiometric amount of K2CO3 provided the desired amino thiazole in high yield with 2 cycles of 5 min MW reaction at 130C.

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DMF, K2CO3 MW 130C 2×5 min

Although interesting for the thiazole formation, the application for the formation of the thiazo-pyrimidones provided the utility of the reaction sequence. Same MW protocol: if the R group is bulky enough, the preference is preferentially driven to isomers the desired isomer (almost exclusively). When small, there is still a preference but at a 2:1 ratio. Take a look at the explanation of the mechanism sequence in the paper.

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5H-thiazo[3,2a]pyridimidine-5-ones

Although the two-sequence is reasonably straightforward, the microwave provides another good example of combining reaction sequences, provided some thought has gone into the steps and they can are accessible without adding new reagents or or switching solvents.

 

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