Conformational analysis and crystal structure of {[1-(3-chloro-4-fluorobenzoyl)-4-fluoropiperidin-4yl]methyl}[(5-methylpyridin-2-yl)methyl]amine, fumaric acid salt.

{[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)).

Absolute configuration of (+)-(S)-2-(5-fluoro-2-methoxy-1,4-benzodioxan-2-yl)imidazolinium bromide.

The title compound, C(12)H(14)FN(2)O(3)(+).Br(-), crystallizes in the non-centrosymmetric P2(1)2(1)2(1) space group. The absolute configuration of the pharmacologically active molecule could be resolved in the hydrobromide salt, the structure of which is reported. The molecule of the title compound has the S configuration. The molecular packing in the crystal is stabilized by weak N-H.Br [N.Br = 3.240 (4) and 3.302 (4) A] hydrogen bonding.

Characterization of polymorphs and solvates of 3-amino-1-(m-trifluoromethylphenyl)-6-methyl-1H-pyridazin-4-one.

The characterization of two polymorphs of the title compound (F2692; 1) by differential scanning calorimetry (DSC), microanalysis, proton nuclear magnetic resonance spectroscopy, thermogravimetry, thermomicroscopy, infrared spectroscopy, and X-ray diffractometry is described. Both polymorphs are crystalline, with form II being more stable at temperatures less than 160 degrees C. The thermal behavior was studied at different rates of heating, and the enthalpies of transition were calculated from DSC data. The transformation of aqueous suspensions of form I to the water-stable form II is described, and the heats of solution and intrinsic aqueous dissolution rates of both polymorphs were determined. 1 also formed solvates with dimethyl sulfoxide and 1-methyl-2-pyrrolidinone. The solvates were studied by thermogravimetry, DSC, and infrared spectroscopy.