Susceptibility of Methyl 3-Amino-1H-pyrazole-5-carboxylate to Acylation

Abstract

In the search for a new method of synthesis of hybrid peptides with aminopyrazole carboxylic acid, we tried to force selective acylation at the aromatic amino group instead of at the ring nitrogen atom with fairly gentle acylating agents. The acylating agents used were acid anhydrides: acetic anhydride, tert-butyl pyrocarbonate, and 2-(2-methoxyethoxy)ethoxyacetic acid/dicyclohexylcarbodiimide. We succceded in acylation at this amino group with almost none at the ring nitrogen atom. Sometimes, however, acylation in small quantities at the ring nitrogen atom was observed as a by-product. To remove this by-product, imidazole was used. Thus, we were able to obtain the hybrid peptides in question with no protection and subsequent removal required. We synthesized a few these free peptides with no protection of the pyrazole ring. This is a simpler method than that being used currently.

Keywords:

• Acetylation
• acylation
• aromatic amine
• 2-(2-methoxyethoxy)ethoxyacetylation
• methyl 3-amino-1H-pyrazole-5-carboxylate
• tert-butyloxycarbonylation

ACKNOWLEDGMENT

The authors gratefully acknowledge the University of Opole for grant number 1/ICh/S-2007.