Crystal structure of tofacitinib dihydrogen citrate (Xeljanz®), (C16H21N6O) (H2C6H5O7)

The crystal structure of tofacitinib dihydrogen citrate (tofacitinib citrate) has been solved and refined using synchrotron X-ray powder diffraction data, and optimized using density functional techniques. Tofacitinib dihydrogen citrate crystallizes in space group P2(1)2(1)2(1) (#19) with a = 5.91113(1), b = 12.93131(3), c = 30.43499(7) angstrom, V = 2326.411(6) angstrom(3), and Z = 4. The crystal structure consists of corrugated layers perpendicular to the c-axis. Within the layers, cation center dot center dot center dot anion and anion center dot center dot center dot anion hydrogen bonds link the fragments into a two-dimensional network parallel to the ab-plane. Between the layers, there are only van der Waals contacts. A terminal carboxylic acid group in the citrate anion forms a strong charge-assisted hydrogen bond to the ionized central carboxylate group. The other carboxylic acid acts as a donor to the carbonyl group of the cation. The citrate hydroxy group forms an intramolecular charge-assisted hydrogen bond to the ionized central carboxylate. Two protonated nitrogen atoms in the cation act as donors to the ionized central carboxylate of the anion. These hydrogen bonds form a ring with the graph set symbol R2,2(8). The powder pattern has been submitted to ICDD (R) for inclusion in the Powder Diffraction File (TM) (PDF (R)). (C) The Author(s), 2021. Published by Cambridge University Press on behalf of International Centre for Diffraction Data.