NMR study of desmotropy in Irbesartan, a tetrazole-containing pharmaceutical compound

Abstract

Irbesartan, a novel anti-hypertensive agent (Angiotensin II antagonist), has been found to exist in two crystal forms. The solution-state structure and the solid-state structure of the two forms, designated Form A and Form B, have been probed using a series of NMR methods and correlated with single-crystal X-ray results for Form B. The prototropic tautomerism generally exhibited by tetrazole ring systems has been probed using solid-state NMR and it is seen that Irbesartan offers a rare example of desmotropic behaviour, whereby the isolated crystal forms are stable in the solid state yet related through a tautomeric equilibrium in the solution state. Nitrogen-15 solid-state CPMAS data have been used to understand the structures of the stable Irbesartan crystal forms. Form B is shown to undergo an exchange process involving the tetrazole ring. Two-dimensional EXSY ¹⁵N spectra are used to understand this process, which involves simultaneous proton-hopping and internal rotation.