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. 2006 Sep 29;71(20):7706-14.
doi: 10.1021/jo061199m.

Concise synthesis of guanidine-containing heterocycles using the Biginelli reaction

Bradley L Nilsson  1 , Larry E Overman
Affiliations

Concise synthesis of guanidine-containing heterocycles using the Biginelli reaction

Bradley L Nilsson et al. J Org Chem. .

Abstract

Two general methods for the synthesis of 2-imino-5-carboxy-3,4-dihydropyrimidines were developed using the three-component Biginelli reaction. The first method utilizes pyrazole carboxamidine, a beta-ketoester, and an aldehyde in an initial Biginelli reaction. After Boc protection, these products undergo aminolysis and acidic deprotection to generate 2-imino-5-carboxy-3,4-dihydropyrimidines in a four-step sequence. The second method utilizes a triazone-protected guanidine, a beta-ketoester, and an aldehyde in a Biginelli reaction. Acidic cleavage of the triazone yields 2-imino-5-carboxy-3,4-dihydropyrimidines in a two-step sequence. We also describe the further elaboration of several of these products using a tethered Biginelli reaction to give triazaacenaphthalene structures similar to those found in crambescidin and batzelladine alkaloids.

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