title: Preparation and characterization of two crystalline forms of 4-amino-5-chloro-2-methoxy-N-[(2S,4S)-1-ethyl-2-hydroxymethyl-4-pyrroli dinyl]benzamide (TKS159).
abstract: For 4-amino-5-chloro-2-methoxy-N-[(2S,4S)-1-ethyl-2-hydroxymethyl-4-pyrrolid inyl]benzamide (TKS159), two polymorphs, forms alpha and beta, were prepared and characterized by means of X-ray powder diffractometry, thermal analysis, infrared spectroscopy and 13C-NMR spectroscopy, both in the solution and solid phases. The X-ray powder diffraction analysis gave different patterns for forms alpha and beta. In the thermogravimetry and differential thermal analysis profiles, form beta exhibited characteristic endo- and exothermic 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 of 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 obtained by thermal analysis, form alpha was shown to be thermodynamically more stable than form beta.
authors.affiliation: Research and Development Department, Teikoku Chemical Industries Co., Ltd., Itami, Hyogo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Yanagi
authors.forename: J
authors.initials: J
authors.lastname: Mizoguchi
authors.forename: T
authors.initials: T
authors.lastname: Adachi
authors.forename: S
authors.initials: S
authors.lastname: Sato
authors.forename: K
authors.initials: K
authors.lastname: Kodama
authors.forename: K
authors.initials: K
authors.lastname: Anzai
authors.forename: Y
authors.initials: Y
authors.lastname: Takagishi
authors.forename: C
authors.initials: C
authors.lastname: Kamei
authors.forename: M
authors.initials: M
authors.lastname: Fujiwara
authors.forename: T
authors.initials: T
authors.lastname: Matsushita
authors.forename: Y
authors.initials: Y
authors.lastname: Yamashoji
authors.forename: Y
authors.initials: Y
authors.lastname: Inoue
mesh_terms: D001549:Benzamides / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004055:Differential Thermal Analysis; D005765:Gastrointestinal Agents / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D011759:Pyrrolidines / Q000737:chemistry*; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism; D013818:Thermogravimetry
chemical_list: D001549:Benzamides; D005765:Gastrointestinal Agents; D011759:Pyrrolidines; C409522:TSK 159