A Spectroscopic and Diffractometric Study of Polymorphism
in Ethyl 3‑{3-[((2<i>R</i>)‑3-{[2-(2,3-dihydro‑1<i>H</i>‑inden-2-yl)-1,1-dimethylethyl]amino}-2-hydroxypropyl)oxy]-4,5-difluorophenyl}propanoate
Hydrochloride
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Abstract
Two polymorphic forms of ethyl 3-{3-[((2<i>R</i>)-3-{[2-(2,3-dihydro-1<i>H</i>-inden-2-yl)-1,1-dimethylethyl]amino}-2-hydroxypropyl)oxy]-4,5-difluorophenyl}
propanoate hydrochloride, an investigational pharmaceutical compound,
are characterized using spectroscopic and diffractometric techniques.
These polymorphic forms exhibit very similar spectra and diffraction
patterns and present challenges for analytical and physical characterization
techniques. Capillary powder X-ray diffraction (PXRD) patterns for
the two forms show minor but distinct differences. A single crystal
X-ray diffraction structure for one of the forms was obtained. The
unit cell of the other form was obtained by PXRD indexing. Detailed
solid-state nuclear magnetic resonance (SSNMR) studies observing the <sup>1</sup>H, <sup>13</sup>C, <sup>15</sup>N, <sup>19</sup>F, and <sup>35</sup>Cl nuclei are performed to characterize the subtle structural
differences between the two forms. Molecular spectroscopic methods
including infrared, Raman, UV–visible, and fluorescence spectroscopy
are also applied. The combined results, particularly the results obtained
from X-ray diffraction analysis, <sup>13</sup>C, <sup>15</sup>N, and <sup>35</sup>Cl SSNMR, and fluorescence spectroscopy, are consistent with
the more thermodynamically stable form having a structure that is
an extended, perturbed superstructure of the less stable form