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Stereoselectivity and Regioselectivity in Nucleophilic Ring Opening in Derivatives of 3-Phenylisoxazolo[2,3-a]pyrimidine. Unpredicted Dimerization and Ring Transformation. Syntheses of Derivatives of Pyrimidinylmethylamine, Pyrimidinylmethylamino Acid Amides, and α-Amino-2-pyrimidinylacetamides1
dataset
posted on 2004-07-23, 00:00 authored by Gury Zvilichovsky, Isra Gbara-Haj-YahiaThe nucleophilic ring opening of the isoxazolone ring in 2-oxo-3-phenylisoxazolo[2,3-a]pyrimidine
derivatives by optically active amino acid amides and ephedrine led to pyrimidinylmethylamino
acid amides. Using amides of different l-amino acids and (−)-ephedrine resulted in different degrees
of stereoselectivity. The degree of streoselectivity depended mostly on the nucleophile used. When
applying hydroxy amines such as ephedrine, the attack via the secondary amino group was found
as the favored regioselectivity. Upon replacement of the oxo group in position 2 in the phenylisoxazolo[2,3-a]pyrimidine system by an imino group, it was expected that the spontaneous decarboxylation that follows the ring opening would not take place, thus achieving amino acid amide
derivatives of 2-pyrimidinylacetamide, which are closely related to pyrimidoblamic acid, an
important constituent of Bleomycins, used in cancer therapy. However, by heating 5,7-dimethyl-2-imino-3-phenylisoxazolo[2,3-a]pyrimidine in solution, it underwent an unprecedented dimerization
process that involved both the phenyl and the imino group. After protecting the imino group by
acetylation, the ring opening by nucleophiles was possible, resulting in the formation of derivatives
of 2-pyrimidinylacetamide. 2-Acetylimino-5,7-dimethyl-3-phenylisoxazolo[2,3-a]pyrimidine also
underwent a ring transformation, yielding an interesting indolone derivative. Selectivity in ring
opening and mechanisms of dimerization and ring transformation are discussed.