Preparation and characterization of two crystalline forms of 4-amino-5-chloro-2-methoxy-N-[(2S,4S)-1-ethyl-2-pyrrolidinyl]benzamide (TKS159)

For 4-amino-5-chloro-2-methoxy-N-[(2S,4S)-1-ethyl-2-hydroxymethyl-4-pyrroli dinyl]benzamide (TKS 159). two polymorphs, forms alpha and beta, were prepa red and characterized by means of X-ray powder diffractometry, thermal anal ysis, infrared spectroscopy and C-13-NMR spectroscopy, both in the solution and solid phases. The Xray powder diffraction analysis save different patt erns for forms alpha and beta. In the thermogravimetry and differential the rmal analysis profiles, form beta exhibited characteristic endo- and exothe rmic peaks at 112.7 degrees C and 116.2 degrees C, respectively due to the partial melting-induced phase transition to form alpha without accompanying weight loss, and these were followed by an additional endothermic peak at 138.2 degrees C due to fusion, For form alpha, only an endothermic peak at 137.8 degrees C due to fusion was observed. The IR spectroscopic analyses o f forms alpha and beta gave different absorption bands assigned to N-H and O-H stretching, N-H bending, and C=O stretching vibrations. From the data o btained by thermal analysis, form alpha was shown to be thermodynamically m ore stable than form beta.