Selective nucleophilic chemistry in the synthesis of 5-carbamoyl-3-sulfanylmethylisoxazole-4-carboxylic acids.
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.
Robins
Lori I
LI
Department of Chemistry, University of California, One Shields Avenue, Davis, California 95616-5295, USA.
Fettinger
James C
JC
Tinti
Dino S
DS
Kurth
Mark J
MJ
D002264:Carboxylic Acids / Q000138:chemical synthesis*; D020650:Combinatorial Chemistry Techniques / Q000379:methods; D018360:Crystallography, X-Ray; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008958:Models, Molecular
D002264:Carboxylic Acids; D007555:Isoxazoles