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Crystal structure of rilpivirine hydrochloride, N6H19C22Cl

Published online by Cambridge University Press:  20 May 2024

Petr Buikin ,
Alexander Korlyukov ,
Elizaveta Kulikova ,
Roman Novikov  and
Anna Vologzhanina Open the ORCID record for Anna Vologzhanina [Opens in a new window]
Petr Buikin
Affiliation:
A. N. Nesmeyanov Institute of Organoelement Compounds RAS, Vavilova Str. 28, Moscow 119334, Russia Institute of General and Inorganic Chemistry RAS, Leninsky Prosp. 31, Moscow 119991, Russia
Alexander Korlyukov
Affiliation:
A. N. Nesmeyanov Institute of Organoelement Compounds RAS, Vavilova Str. 28, Moscow 119334, Russia
Elizaveta Kulikova
Affiliation:
Kurchatov Institute, National Research Center, Pl. Akad. Kurchatova 1, Moscow123182, Russia
Roman Novikov
Affiliation:
N. D. Zelinsky Institute of Organic Chemistry, RAS, Leninsky Prosp. 47, Moscow 119991, Russia
Anna Vologzhanina*
Affiliation:
A. N. Nesmeyanov Institute of Organoelement Compounds RAS, Vavilova Str. 28, Moscow 119334, Russia
*
a)Author to whom correspondence should be addressed. Electronic mail: vologzhanina@mail.ru
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Abstract

A monoclinic C form of rilpivirine hydrochloride, (N6H19C22)Cl, has been obtained and characterized using solid-state 15N, 13C, and 35Cl NMR spectroscopy and multitemperature synchrotron X-ray powder diffraction. The title compound crystallizes in the monoclinic system (space group C2/c, #15) at both room (295.0(2) K) and low (100.0(2) K) temperatures. At room temperature, the following parameters are a = 19.43051(3), b = 13.09431(14), c = 17.10254(18) Å, β = 109.3937(7), V = 4104.48(9) Å3, and Z = 8. The folded molecular conformation of the cation is similar with that of free base rilpivirine with the exception of cyanovinyl group disposition. The anion links cations to infinite chains parallel to the crystallographic c axis using N–H⋯Cl bonds where both amino groups and the protonated pyrimidine ring take part in the H-bonding. The powder patterns have been submitted to the ICDD for inclusion in the Powder Diffraction File™ (PDF®).

Keywords

multitemperature studypowder diffractionRietveld refinementrilpivirine

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Type
New Diffraction Data
Information
Powder Diffraction , Volume 39 , Issue 3 , September 2024 , pp. 151 - 158
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Copyright
Copyright © The Author(s), 2024. Published by Cambridge University Press on behalf of International Centre for Diffraction Data

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References

REFERENCES

Barbas, R., Portell, A., Prohens, R., and Frontera, A.. 2022. “DFT–Assisted Structure Determination from Powder X-ray Diffraction Data of a New Zonisamide/ε-Caprolactam Cocrystal.” Crystals 12 (8): 1020. doi:10.3390/cryst12081020.CrossRefGoogle Scholar
Blöchl, P. E. 1994. “Projector Augmented-Wave Method.” Physical Review B 50 (24): 17953–79. doi:10.1103/PhysRevB.50.17953.CrossRefGoogle ScholarPubMed
Braga, D., Grepioni, F., Lampronti, G. I., Maini, L., and Turrina, A.. 2011. “Ionic Co-Crystals of Organic Molecules with Metal Halides: A New Prospect in the Solid Formulation of Active Pharmaceutical Ingredients.” Crystal Growth and Design 11 (12): 5621–27. doi:10.1021/cg201177p.CrossRefGoogle Scholar
Bruker. 2014. Bruker TOPAS 5 User Manual. Karlsruhe, Germany, Bruker AXS GmbH.Google Scholar
Buikin, P., Vologzhanina, A., Novikov, R., Dorovatovskii, P., and Korlyukov, A.. 2023. “Abiraterone Acetate Complexes with Biometals: Synthesis, Characterization in Solid and Solution, and the Nature of Chemical Bonding.” Pharmaceutics 15 (9): 2180. doi:10.3390/pharmaceutics15092180.CrossRefGoogle ScholarPubMed
Coelho, A. A. 2003. “Indexing of Powder Diffraction Patterns by Iterative Use of Singular Value Decomposition.” Journal of Applied Crystallography 36 (1): 86–95. doi:10.1107/S0021889802019878.CrossRefGoogle Scholar
Dhondale, M. R., Thakor, P., Nambiar, A. G., Singh, M., Agrawal, A. K., Shastri, N. R., and Kumar, D.. 2023. “Co-Crystallization Approach to Enhance the Stability of Moisture-Sensitive Drugs.” Pharmaceutics 15 (1): 189. doi:10.3390/pharmaceutics15010189.CrossRefGoogle ScholarPubMed
Goloveshkin, A. S., Korlyukov, A. A., and Vologzhanina, A. V.. 2021. “Novel Polymorph of Favipiravir — An Antiviral Medication.” Pharmaceutics 13 (2): 139. doi:10.3390/pharmaceutics13020139.CrossRefGoogle ScholarPubMed
Guerain, M., Derollez, P., Roca-Paixão, L., Dejoie, C., Correia, N. T., and Affouard, F.. 2020. “Structure Determination of a New Cocrystal of Carbamazepine and Dl-tartaric Acid by Synchrotron Powder X-ray Diffraction.” Acta Crystallographica Section C: Structural Chemistry 76 (3): 225–30. doi:10.1107/S2053229620000868.Google ScholarPubMed
Hilfiker, R., Blatter, F., & Raumer, M. V.. 2006. Relevance of Solid-state Properties for Pharmaceutical Products in Hilfiker, R. (Ed.), Polymorphism (pp. 1–19). Wiley. doi:10.1002/3527607889.ch1CrossRefGoogle Scholar
Hotter, A., Pichler, A., Adamer, V., & Griesser, U.. 2013. “Novel Polymorph of Rilpivirine Hydrochloride.” World Intellectual Property Organization Patent WO2013153161A2. https://patents.google.com/patent/WO2013153161A2/en?oq=WO2013153161A2.Google Scholar
Kaduk, J. A., Zhong, K., and Blanton, T. N.. 2015. “Crystal Structure of Rilpivirine, C22H18N6.” Powder Diffraction 30 (2): 170–74. doi:10.1017/S0885715615000196.CrossRefGoogle Scholar
Kaduk, J. A., Gates-Rector, S., and Blanton, T. N.. 2023a. “Crystal Structure of Besifloxacin Hydrochloride, C19H22ClFN3O3Cl.” Powder Diffraction 38 (1): 43–52. doi:10.1017/S0885715622000586.CrossRefGoogle Scholar
Kaduk, J. A., Gates-Rector, S., and Blanton, T. N.. 2023b. “Crystal Structure of Butenafine Hydrochloride, C23H28NCl.” Powder Diffraction 38 (1): 30–6. doi:10.1017/S0885715622000562.CrossRefGoogle Scholar
Kommavarapu, P., Maruthapillai, A., Palanisamy, K., and Sunkara, M.. 2015. “Preparation and Characterization of Rilpivirine Solid Dispersions with the Application of Enhanced Solubility and Dissolution Rate.” Beni-Suef University Journal of Basic and Applied Sciences 4 (1): 71–9. doi:10.1016/j.bjbas.2015.02.010.CrossRefGoogle Scholar
Korlyukov, A. A., Dorovatovskii, P. V., and Vologzhanina, A. V.. 2022. “N-(4-Methyl-3-((4-(pyridin-3-yl)pyrimidin-2-yl)amino)phenyl)-4-((4-methylpiperazin-1-yl)methyl)benzamide.” Molbank 2022 (4): M1461. doi:10.3390/M1461.CrossRefGoogle Scholar
Korlyukov, A. A., Buikin, P. A., Dorovatovskii, P. V., and Vologzhanina, A. V.. 2023. “Synthesis, NoSpherA2 Refinement, and Noncovalent Bonding of Abiraterone Bromide Monohydrate.” Structural Chemistry 34 (5): 1927–34. doi:10.1007/s11224-023-02210-3.CrossRefGoogle Scholar
Kresse, G., and Furthmüller, J.. 1996a. “Efficiency of Ab-initio Total Energy Calculations for Metals and Semiconductors using a Plane-Wave Basis Set.” Computational Materials Science 6 (1): 15–50. doi:10.1016/0927-0256(96)00008-0.CrossRefGoogle Scholar
Kresse, G., and Furthmüller, J.. 1996b. “Efficient Iterative Schemes for Ab initio Total-Energy Calculations Using a Plane-Wave Basis Set.” Physical Review B - Condensed Matter and Materials Physics 54 (16): 11169–86. doi:10.1103/PhysRevB.54.11169.CrossRefGoogle ScholarPubMed
Kresse, G., and Hafner, J.. 1993. “Ab Initio Molecular Dynamics for Liquid Metals.” Physical Review B 47 (1): 558–61. doi:10.1103/PhysRevB.47.558.CrossRefGoogle ScholarPubMed
Kresse, G., and Hafner, J.. 1994. “Ab Initio Molecular-Dynamics Simulation of the Liquid-Metal–Amorphous-Semiconductor Transition in Germanium.” Physical Review B 49 (20): 14251–69. doi:10.1103/PhysRevB.49.14251.CrossRefGoogle ScholarPubMed
Kresse, G., and Hafner, J.. 2000. “First-Principles Study of the Adsorption of Atomic H on Ni (111), (100) and (110).” Surface Science 459 (3): 287–302. doi:10.1016/S0039-6028(00)00457-X.CrossRefGoogle Scholar
Kresse, G., and Joubert, D.. 1999. “From Ultrasoft Pseudopotentials to the Projector Augmented-Wave Method.” Physical Review B 59 (3): 1758–75. doi:10.1103/PhysRevB.59.1758.CrossRefGoogle Scholar
Momma, K., and Izumi, F.. 2011. “VESTA 3 for Three-Dimensional Visualization of Crystal, Volumetric and Morphology Data.” Journal of Applied Crystallography 44 (6): 1272–76. doi:10.1107/S0021889811038970.CrossRefGoogle Scholar
O'Boyle, N. M., Banck, M., James, C. A., Morley, C., Vandermeersch, T., and Hutchison, G. R.. 2011. “Open Babel: An Open Chemical Toolbox.” Journal of Cheminformatics 3 (1): 33. doi:10.1186/1758-2946-3-33.CrossRefGoogle ScholarPubMed
Paulekuhn, G. S., Dressman, J. B., and Saal, C.. 2007. “Trends in Active Pharmaceutical Ingredient Salt Selection based on Analysis of the Orange Book Database.” Journal of Medicinal Chemistry 50 (26): 6665–72. doi:10.1021/jm701032y.CrossRefGoogle ScholarPubMed
Perdew, J. P., Kurth, S., Zupan, A., and Blaha, P.. 1999. “Accurate Density Functional with Correct Formal Properties: A Step Beyond the Generalized Gradient Approximation.” Physical Review Letters 82 (12): 2544–47. doi:10.1103/PhysRevLett.82.2544.CrossRefGoogle Scholar
Putcharoen, O., Kerr, S. J., and Ruxrungtham, K.. 2013. “An Update on Clinical Utility of Rilpivirine in the Management of HIV Infection in Treatment-Naive Patients.” HIV/AIDS – Research and Palliative Care 5 (September): 231–41. doi:10.2147/HIV.S25712.Google ScholarPubMed
Rendell, J., Mittelman, A., Erlich, M., and Ratkaj, M.. 2012. “Solid State Forms of Rilpivirine Base, and Rilipivirine salts.” World Intellectual Property Organization Patent WO2012125993A1. https://patents.google.com/patent/WO2012125993A1/en?oq=WO2012125993A1+Google Scholar
Rietveld, H. M. 1967. “Line Profiles of Neutron Powder-Diffraction Peaks for Structure Refinement.” Acta Crystallographica 22 (1): 151–52. doi:10.1107/S0365110X67000234.CrossRefGoogle Scholar
Sandoz, A. Z. 2013. “Novel Crystalline Form of Rilpivirine Hydrochloride.” European Patent EP2628732A1. https://patents.google.com/patent/EP2628732A1/de?oq=EP2628732A1Google Scholar
Stokbroekx, S. C. M. 2010. “Crystalline Form of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]-amino]-2-pyrimidinyl]amino]benzonitrile.” US Patent US20100189796A1. https://patents.google.com/patent/US20100189796A1/en?oq=US2010189796Google Scholar
Surov, A. O., Drozd, K. V., Ramazanova, A. G., Churakov, A. V., Vologzhanina, A. V., Kulikova, E. S., and Perlovich, G. L.. 2023. “Polymorphism of Carbamazepine Pharmaceutical Cocrystal: Structural Analysis and Solubility Performance.” Pharmaceutics 15 (6): 1747. doi:10.3390/pharmaceutics15061747.CrossRefGoogle ScholarPubMed
Svetogorov, R. D. 2018. Dionis – Diffraction Open Integration Software. Moscow, National Research Center Kurchatov Institute.Google Scholar
Svetogorov, R. D., Dorovatovskii, P. V., and Lazarenko, V. A.. 2020. “Belok/XSA Diffraction Beamline for Studying Crystalline Samples at Kurchatov Synchrotron Radiation Source.” Crystal Research and Technology 55 (5): 1900184. doi:10.1002/crat.201900184.CrossRefGoogle Scholar
Wermuth, C. G., and Stahl, P. H.. 2001. Pharmaceutical Salts, Properties, Selection, and Use. A Handbook. Zürich, Helvetica Chimica Acta/Wiley-VCH.Google Scholar
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