Process for the preparation of hexahydropyridazine-3-carboxylic acid derivatives

摘要

Production of hexahydropyridazine-1,3-dicarboxylic acid derivatives (I) comprises reacting a 2,5-disubstituted carboxylic acid ester (II) with a hydrazine-1,2-dicarboxylate ester (III) in the presence of a base with a pK above 8.5 in a ketone solvent and treating the resulting hexahydropyridazine-1,2,3-tricarboxylic acid ester (IV), which is not isolated, with a basic aqueous medium. Production of hexahydropyridazine-1,3-dicarboxylic acid derivatives of formula (I) comprises reacting a 2,5-disubstituted carboxylic acid ester of formula (II) with a hydrazine-1,2-dicarboxylate ester of formula (III) in the presence of a base with a pK above 8.5 in a ketone solvent and treating the resulting hexahydropyridazine-1,2,3-tricarboxylic acid ester (IV), which is not isolated, with a basic aqueous medium: [Image] R3>-CH2-CH2-CH2-CH(R3>)-C(O)OR2> (II) RO(O)C-NH-NH-C(O)OR (III) R : (un)saturated alkyl, aralkyl or aryl, all optionally substituted; R2>optionally substituted alkyl; and R3>halo or a nucleofuge organic group.