Exploring the scope of DBU-promoted amidations of 7-methoxycarbonylpterin

Abstract

The synthetic utility of pterins is often hampered by the notorious insolubility of this heterocycle, slowing the development of medicinally relevant pteridine derivatives. Reactions which expedite the development of new pterins are thus of great importance. Through a dual role of diazabicycloundecene (DBU), 7-carboxymethylpterin is converted to the soluble DBU salt, with additional DBU promoting an ester-to-amide transformation. We have explored this reaction to assess its scope and identify structural features in the amines which significantly affect success, monitored the reaction kinetics using a pseudo-first order kinetics model, and further adapted the reaction conditions to allow for product formation in as little as 5 min, with yields often >80%.

Keywords: DBU; amidation; folate; pterin.

Figure 1

The dual role of DBU in the amidation of 7-CMP.

Scheme 1

DBU-promoted amidation of 7-CMP (1).

Figure 2

Role of a β-hydroxy group in aiding the amidation reaction.

Figure 3

Pseudo-first order kinetics for representative amines.