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Updated: Apr 30, 2026

A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products
Published on: September 9, 2016
General and rapid pyrimidine condensation by addressing the rate limiting aromatization
Daniel R Fandrick1, Delia Reinhardt, Jean-Nicolas Desrosiers
1Chemical Development, Boehringer-Ingelheim Pharmaceuticals, Inc. , 900 Ridgebury Road/P.O. Box 368, Ridgefield Connecticut 06877-0368, United States.
Abstract:
The rate limiting aromatization within the condensation approach toward pyrimidines utilizing amidines and activated olefins was addressed to provide for a general and rapid process. A strong solvent effect was elucidated to affect the rate for the initial alkoxide elimination from the intermediate Michael adduct wherein polar aprotic solvents demonstrate an addition controlled aromatization. Spectroscopic studies support a solvent dependent equilibrium between the amidine and alkoxide base wherein the rate for aromatization is optimal when the equilibrium toward the amidine anion was strongly favored.
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