Solid-state characterization of an NR2B selective N-methyl d-aspartate (NMDA) antagonist polymorphs

(−)-6-{2-[4-(3-Fluorophenyl)-4-hydroxy-piperidin-1-yl]-1-hydroxyethyl}-3,4-dihydro-quinolin-2(1H)-one (compound A) is an NR2B selective N-methyl d-aspartate (NMDA) antagonist that has shown at least two polymorphs, forms I and II. In this report, we prepared two polymorphs, forms I and II and their crystal forms were identified and characterized by single crystal X-ray diffractometry, differential scanning calorimetry (DSC) and variable temperature powder X-ray diffractometry (VT-PXRD). The results of DSC and VT-PXRD suggested that compound A has at least three polymorphic forms: I, II and a new form III, and that forms II and III showed an enantiotropic relationship. We also performed single crystal X-ray analyses of specific conditions based on the results of VT-PXRD. The unit cell dimensions in crystallographic parameter and molecular arrangements of form I were quite different from forms II and III. Whereas, the crystal structures of forms II and III were similar with the exception of the C58–C59–C61–C62 torsion angle.