The solution-phase syntheses of 5-carbamoyl-3-sulfanylmethylisoxazole-4- carboxylic acids were accomplished from dimethyl 3-chloromethylisoxazole-4,5- dicarboxylate by selective nucleophilic chemistry. For example, treatment of this trifunctionalized core with 3-bromobenzylamine and subsequent X-ray analysis identified the sole product as methyl 5-(3-bromobenzylcarbamoyl)-3- chloromethylisoxazole-4-carboxylate. Subjecting this amide/ester to thiophenol in the presence of 1 N NaOH completed the two-step transformation of this versatile starting material to the targeted 5-carbamoyl-3- sulfanylmethylisoxazole-4-carboxylic acid. Employing various amines and thiophenols, this chemistry was applied in the generation of a 90-compound library of druglike isoxazoles.
ASJC Scopus subject areas
- Drug Discovery
- Organic Chemistry
- Discrete Mathematics and Combinatorics