Conformational analysis and crystal structure of {[1-(3-chloro-4-fluorobenzoyl)-4-fluoro piperidin-4-yl]methyl}[(5-methylpyridin-2-yl)methyl]amine, fumaric acid salt
| Autor: | Jean-Paul Ribet, B. Bonnaud, Claude Belin, B. Vacher, F. Colpaert, Monique Tillard, Jean-Louis Maurel, R. Pena |
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| Přispěvatelé: | Centre de Recherche Pierre Fabre (Centre de R&D Pierre Fabre), PIERRE FABRE, Laboratoire des Agrégats Moléculaires et Matériaux Inorganiques (LAMMI), Centre National de la Recherche Scientifique (CNRS)-Université Montpellier 2 - Sciences et Techniques (UM2), Institut Charles Gerhardt Montpellier - Institut de Chimie Moléculaire et des Matériaux de Montpellier (ICGM ICMMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 1 (UM1)-Université Montpellier 2 - Sciences et Techniques (UM2)-Institut de Chimie du CNRS (INC) |
| Jazyk: | angličtina |
| Rok vydání: | 2005 |
| Předmět: |
Models
Molecular Magnetic Resonance Spectroscopy Pyridines 030303 biophysics Molecular Conformation Crystal structure Fluorine-19 NMR [CHIM.THER]Chemical Sciences/Medicinal Chemistry Triclinic crystal system Analytical Chemistry 03 medical and health sciences Differential scanning calorimetry Fumarates Piperidines X-Ray Diffraction [CHIM.CRIS]Chemical Sciences/Cristallography Deuterium Oxide Thermal analysis Instrumentation Spectroscopy ComputingMilieux_MISCELLANEOUS 030304 developmental biology 0303 health sciences Calorimetry Differential Scanning Chemistry Atomic and Molecular Physics and Optics Crystallography Polymorphism (materials science) Proton NMR Thermodynamics Powder diffraction |
| Zdroj: | Spectrochimica Acta Part A : Molecular Spectroscopy [1967-1993] Spectrochimica Acta Part A : Molecular Spectroscopy [1967-1993], Elsevier, 2005, 62 (1-3), pp.353-363. ⟨10.1016/j.saa.2005.01.002⟩ |
| ISSN: | 0584-8539 |
| DOI: | 10.1016/j.saa.2005.01.002⟩ |
| Popis: | {[1-(3-Chloro-4-fluorobenzoyl)-4-fluoropiperidin-4yl]methyl}[(5-methylpyridin-2-yl)methyl]amine, fumaric acid salt (C(20)H(22)ClF(2)N(3)O, C(4)H(4)O(4)) (1) was synthesized and characterized by the complete (1)H, (13)C and (19)F NMR analyses. The conformation of the piperidin ring, in the solution state, was particularly studied from the coupling constants determined by recording a double-quantum filtered COSY experiment in phase-sensitive mode. (1)H NMR line-shape analysis was used, at temperatures varying between -5 and +60 degrees C, to determine the enthalpy of activation of the rotational barrier around the CN bond. Compound 1 crystallizes in the triclinic space group P1 with a=8.517(3) Angstrom, b=12.384(2) Angstrom, c=12.472(3) Angstrom, alpha=70.88(2) degrees, beta=82.04(2) degrees, gamma=83.58(2) degrees. The results strongly indicate that the solid and solution conformations are similar. Thermal stability and phases transitions were investigated by thermal gravimetric analysis (TGA) and differential scanning calorimetry (DSC). Furthermore polymorphism screening was studied from recrystallization of 1 performed in seven solvents and by slurry conversion in water. The X-ray powder diffraction (XRPD) and differential scanning calorimetry results suggested that 1 crystallizes into one crystalline form which melts at 157 degrees C (DeltaH=132 J g(-1)). |
| Databáze: | OpenAIRE |
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