Crystal structure of paliperidone, C₂₃H₂₇FN₄O₃

Abstract

The crystal structure of paliperidone has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional techniques. Paliperidone crystallizes in space group P21/n (# 14) with a = 14.151 58(6), b = 21.537 80(9), c = 6.913 26(2) Å, β = 92.3176(2)°, V = 2105.396(13) Å3, and Z = 4. The unit-cell volume at 295 K is 1.5% larger than at 200 K, but the expansion is anisotropic; the b-axis is nearly constant at the two temperatures, while the a- and c-axes expand by 0.71 and 0.87%, respectively. There is only one significant hydrogen (H)-bond in the crystal structure. This H-bond is between the hydroxyl group O31–H58 and the ketone oxygen O25. The result is a chain along the c-axis with graph set C1,1(7). In addition to this H-bond, the molecular packing is dominated by van der Waals attractions. The powder pattern is included in the Powder Diffraction File™ as entry 00-064-1497.

Crystal structure of paliperidone palmitate (INVEGA SUSTENNA®), C39H57FN4O4

“…These angles represent the orientation of two portions of the paliperidone fragment. The paliperidone fragment in paliperidone palmitate has a different conformation than that in paliperidone (Kaduk et al, 2016) (Figure 8); the root-mean-square difference in the non-H atom positions is 1.877 Å. This difference can be decreased to 0.28 Å by allowing flexibility in Mercury (Figure 9).…”

“…The structure of the paliperidone molecule was taken from our previous determination (Kaduk et al , 2016). The structure of palmitic acid was taken from CSD Refcode YEFWEM01 (Moreno-Calvo et al , 2009).…”