Febuxostat ethanol monosolvate.

Thomas Gelbrich,Ulrich J Griesser,Sven Nerdinger,Volker Kahlenberg,Verena Adamer

doi:10.1107/s2056989020006076

Abstract

The title compound, 2-(3-cyano-4-iso-but-oxyphen-yl)-4-methyl-1,3-thia-zole-5-car-b-oxy-lic acid ethanol monosolvate, C16H16N2O3S·C2H6O, (I), displays inter-molecular O-H⋯O and O-H⋯N bonds in which the carboxyl group of the febuxostat mol-ecule and the hydroxyl group of the ethanol mol-ecule serve as hydrogen-bond donor sites. These inter-actions result in a helical hydrogen-bonded chain structure. The title structure is isostructural with a previously reported methanol analogue.

Highlights

Chemical context Febuxostat is a novel, small-molecule, non-purine-selective inhibitor of xanthine oxidase developed for the treatment of chronic gout and hyperuricemia, via oral administration (Pascual et al, 2009; Gray & Walters-Smith, 2011; Kataoka et al, 2015). This drug is currently marketed by Takeda Pharmaceuticals Inc. under the trade name Uloric
One of the key aspects of the novel route of synthesis was the introduction of a modified version of the Duff reaction (Duff & Bills, 1932, 1934) in the first step, which resulted in improved overall yields compared to the original synthesis by Hasegawa (1998)
The febuxostat molecule (Fig. 1) is essentially planar. This is illustrated by the fact that the mean plane defined by all its non-H atoms, except for C22 of the isobutyl group, results in a root-mean-square deviation for the 21 fitted atoms of only 0.0890 A

Summary

Structural commentary

The febuxostat molecule (Fig. 1) is essentially planar. This is illustrated by the fact that the mean plane defined by all its non-H atoms, except for C22 of the isobutyl group, results in a root-mean-square deviation for the 21 fitted atoms of only 0.0890 A. The relative mutual orientation of the CN substituent at the phenyl ring and the Me group at the thiazole ring is characterized by the torsion angle S1—C2—C6—C7 of À6.5 (3). This torsion is defined as in the Scheme.

Supramolecular features

Database survey

Synthesis

Refinement