Otamixaban is a potent (Ki=0.5 nM) fXa inhibitor currently in late-stage clinical development at Sanofi for the management of acute coronary syndrome. Being unproductive in obtaining a suitable crystal of Otamixaban, the required enantiomeric characterization has been accomplished using vibrational circular dichroism (VCD) spectroscopy. Selected by a spectrum similarity index, the calculated spectra of several higher energy conformers were found to match well with the observed spectra. The characteristic IR bands of these conformers were also identified and attributed to the solvation effect. Combined with both the single crystal x-ray diffraction results for an intermediate and the proton NMR study, the absolute configuration of Otamixaban is unambiguously determined to be (R,R).

, 358 (1993). The crystal structures of N, N'-di(2-acetylcyclohexenyl)ethylenediamine (L,) and its copper(I1) complex, which crystallizes with one solvent molecule of chloroform (Cu(L,-2H). CHC13), were determined. Crystallographic details are as follows: L, is monoclinic, space group P2,/c, with a = 8.280(2), b = 1 1.692(2), and c = 9.355(2) A, P = 1 14.10(2)", V = 826.7(3) A~, Z = 2; p, = 1.22 g cm-j, k(Cu Ka) = 5.93 cm-I, with the final residual indices of R = 0.046 and R,,. = 0.070 for 991sunique reflections. Cu(L,-2H). CHCI3 is triclinic, space group P I , with a = 1 1.121(3), b = 11.713(3), and c = 8.974(2) A, cu = 99.35(2)", P = 110.83(2)", y = 82.33(2)", V = 1074(1) A~, Z = 2; p, = 1.50 g c K 3 , ~( C U Ka) = 50.74 cm-I, with the final residual indices of R = 0.048 and R,,. = 0.077 for 2369 unique reflections. The X-ray diffraction study shows that in the crystal state the ligand L, is in the methylketone-cyclohexanonenamine isomeric form. For the copper complex Cu(LI-2H). CHCI,, the geometry around the metal atom is distorted square planar, and the angle between the chelate ring planes in the complex is 15. lo. An NMR study shows that L, in solution has the same structure as that observed in the solid state by X-ray diffraction. [Traduit par la redaction]