Methyl N-(tert-butoxycarbonyl)pyridine-2-carbimidothioate: A new reagent for the synthesis of N-phenylpyridinecarboxamidine (?arylimidamide?) DNA-minor groove binders from poorly nucleophilic amines

We report the synthesis and use of methyl N-(tert-butoxycarbonyl)pyridine-2-carbimidothioate as new reagent for the preparation of N-phenylpyridinecarboxamidines (arylimidamides), a class of DNA minor groove binding molecules with antiprotozoal activity. This versatile reagent allowed the access to electron-deficient halogen-containing bis(arylimidamides) that could not be obtained with the classical methods reported in the literature. With this two-step protocol, the N-Boc-protected arylimidamide intermediate, which is soluble in organic solvents, can be purified by centrifugal preparative thin layer chromatography on silica and/or by reverse-phase (C-18) chromatography. The target N-phenylpyridinecarboxamidines are obtained as salts by smooth hydrolysis of the Boc-protecting group with TFA. This methodology allows the synthesis of a pharmaceutically important class of antiparasitic compounds otherwise inaccessible.

Automated summary

The synthesis and use of a new reagent for the preparation of DNA minor groove binding molecules with antiprotozoal activity is reported. The reagent allows access to previously inaccessible compounds and can be purified using a two-step protocol. This methodology enables the synthesis of important antiparasitic compounds.