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Crystal structure of brigatinib Form A (Alunbrig®), C29H39ClN7O2P

Published online by Cambridge University Press:  04 October 2021

Ryan L. Hodge
Affiliation:
North Central College, 131 S. Loomis St., Naperville, Illinois 60540, USA
James A. Kaduk*
Affiliation:
North Central College, 131 S. Loomis St., Naperville, Illinois 60540, USA
Amy M. Gindhart
Affiliation:
ICDD, 12 Campus Blvd., Newtown Square, Pennsylvania 19073-3273, USA
Thomas N. Blanton
Affiliation:
ICDD, 12 Campus Blvd., Newtown Square, Pennsylvania 19073-3273, USA
*
a)Author to whom correspondence should be addressed. Electronic mail: kaduk@polycrystallography.com

Abstract

The crystal structure of brigatinib Form A has been solved and refined using synchrotron X-ray powder diffraction data and optimized using density functional theory techniques. Brigatinib Form A crystallizes in space group P-1 (#2) with a = 9.59616(20), b = 10.9351(3), c = 14.9913(6) Å, α = 76.1210(13), β = 79.9082(11), γ = 74.0802(6)°, V = 1458.497(15) Å3, and Z = 2. Structure solution was complicated by the lowest cost factor solution having an unreasonable conformation of the dimethylphosphoryl group. The second-best structure yielded a better refinement. The crystal structure is characterized by alternating layers of aliphatic and aromatic portions of the molecules along the b-axis. Strong N–H⋯N hydrogen bonds link the molecules into pairs, with a graph set R2,2(8). There is a strong intramolecular N–H⋯O hydrogen bond to the phosphoryl group, which determines the orientation of this group. The powder pattern has been submitted to ICDD® for inclusion in the Powder Diffraction File™ (PDF®).

Type
New Diffraction Data
Copyright
Copyright © The Author(s), 2021. Published by Cambridge University Press on behalf of International Centre for Diffraction Data

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References

Bernstein, J., Davis, R. E., Shimoni, L., and Chang, N. L. (1995). “Patterns in hydrogen bonding: functionality and graph set analysis in crystals,” Angew. Chem. Int. Ed. 34(15), 15551573 (in English).CrossRefGoogle Scholar
Bravais, A. (1866). Etudes Cristallographiques (Gauthier Villars, Paris).Google Scholar
Bruno, I. J., Cole, J. C., Kessler, M., Luo, J., Motherwell, W. D. S., Purkis, L. H., Smith, B. R., Taylor, R., Cooper, R. I., Harris, S. E., and Orpen, A. G. (2004). “Retrieval of crystallographically-derived molecular geometry information,” J. Chem. Inf. Sci. 44, 21332144.CrossRefGoogle ScholarPubMed
Camidge, D. R., Kim, H. R., Ahn, M. J., Yang, J. C. H., Han, J. Y., Lee, J. S., Hochmair, M. J., Li, J. Y. C., Chang, G. C., Lee, K. H., and Gridelli, C. (2018). “Brigatinib versus crizotinib in ALK-positive non-small-cell lung cancer,” N. Engl. J. Med. 379(21), 20272039.CrossRefGoogle ScholarPubMed
Dassault Systèmes (2021). Materials Studio 2021 (BIOVIA, San Diego, CA).Google Scholar
Donnay, J. D. H. and Harker, D. (1937). “A new law of crystal morphology extending the law of Bravais,” Am. Mineral. 22, 446447.Google Scholar
Dovesi, R., Orlando, R., Erba, A., Zicovich-Wilson, C. M., Civalleri, B., Casassa, S., Maschio, L., Ferrabone, M., De La Pierre, M., D-Arco, P., Noël, Y., Causà, M., and Kirtman, B. (2014). “CRYSTAL14: a program for the ab initio investigation of crystalline solids,” Int. J. Quantum Chem. 114, 12871317.CrossRefGoogle Scholar
Etter, M. C. (1990). “Encoding and decoding hydrogen-bond patterns of organic compounds,” Acc. Chem. Res. 23(4), 120126.CrossRefGoogle Scholar
Favre-Nicolin, V. and Černý, R. (2002). “FOX, free objects for crystallography: a modular approach to ab initio structure determination from powder diffraction,” J. Appl. Crystallogr. 35, 734743.CrossRefGoogle Scholar
Friedel, G. (1907). “Etudes sur la loi de Bravais,” Bull. Soc. Fr. Mineral. 30, 326455.Google Scholar
Gates-Rector, S. and Blanton, T. N. (2019). “The Powder Diffraction File: a quality materials characterization database,” Powder Diffr. 34(4), 352–260.CrossRefGoogle Scholar
Gatti, C., Saunders, V. R., and Roetti, C. (1994). “Crystal-field effects on the topological properties of the electron-density in molecular crystals - the case of urea,” J. Chem. Phys. 101, 1068610696.CrossRefGoogle Scholar
Groom, C. R., Bruno, I. J., Lightfoot, M. P., and Ward, S. C. (2016). “The Cambridge Structural Database,” Acta Crystallogr. Sect. B: Struct. Sci., Cryst. Eng. Mater. 72, 171179.CrossRefGoogle ScholarPubMed
Hirshfeld, F. L. (1977). “Bonded-atom fragments for describing molecular charge densities,” Theor. Chem. Acta 44, 129138.CrossRefGoogle Scholar
Kaduk, J. A., Crowder, C. E., Zhong, K., Fawcett, T. G., and Suchomel, M. R. (2014). “Crystal structure of atomoxetine hydrochloride (strattera), C17H22NOCl,” Powder Diffr. 29(3), 269273.CrossRefGoogle Scholar
Kim, S., Chen, J., Cheng, T., Gindulyte, A., He, J., He, S., Li, Q., Shoemaker, B. A., Thiessen, P. A., Yu, B., Zaslavsky, L., Zhang, J., and Bolton, E. E. (2019). “Pubchem in 2021: new data content and improved web interfaces,” Nucleic Acids Res. 49(D1), D1388D1395. doi:10.1093/nar/gkaa971.CrossRefGoogle Scholar
Lee, P. L., Shu, D., Ramanathan, M., Preissner, C., Wang, J., Beno, M. A., Von Dreele, R. B., Ribaud, L., Kurtz, C., Antao, S. M., Jiao, X., and Toby, B. H. (2008). “A twelve-analyzer detector system for high-resolution powder diffraction,” J. Synchroton Radiat. 15(5), 427432.CrossRefGoogle ScholarPubMed
Macrae, C. F., Sovago, I., Cottrell, S. J., Galek, P. T. A., McCabe, P., Pidcock, E., Platings, M., Shields, G. P., Stevens, J. S., Towler, M., and Wood, P. A. (2020). “Mercury 4.0; from visualization to design and prediction,” J. Appl. Crystallogr. 53, 226235.CrossRefGoogle ScholarPubMed
Martin, N. (2019). “Pharmaceutical composition of brigatinib,” International Patent Application WO 2019/158421 A1.Google Scholar
MDI (2021). JADE Pro Version 8.1 (Computer Software) (Materials Data, Livermore, CA, USA).Google Scholar
O'Boyle, N., Banck, M., James, C. A., Morley, C., Vandermeersch, T., and Hutchison, G. R. (2011). “Open Babel: an open chemical toolbox,” J. Chem. Informatics 3, 33. doi:10.1186/1758-2946-3-33.Google ScholarPubMed
Peintinger, M. F., Vilela Oliveira, D., and Bredow, T. (2013). “Consistent Gaussian basis sets of triple-zeta valence with polarization quality for solid-state calculations,” J. Comput. Chem. 34, 451459.CrossRefGoogle ScholarPubMed
Rozamus, L. W. (2016). “Crystalline forms of 5-chloro-N4-[-2-(dimethylphosphoryl)phenyl]-N2-{2-methoxy-4-[4-(4-methylpiperazin-1-yl)piperidin-1-yl]pyrimidine-2,4-diamine,” International Patent Application WO 2016/065028 A1.Google Scholar
Shields, G. P., Raithby, P. R., Allen, F. H., and Motherwell, W. S. (2000). “The assignment and validation of metal oxidation states in the Cambridge Structural Database,” Acta Crystallogr. Sec. B: Struct. Sci. 56(3), 455465.CrossRefGoogle ScholarPubMed
Silk Scientific (2013). UN-SCAN-IT 7.0 (Silk Scientific Corporation, Orem, UT).Google Scholar
Sykes, R. A., McCabe, P., Allen, F. H., Battle, G. M., Bruno, I. J., and Wood, P. A. (2011). “New software for statistical analysis of Cambridge Structural Database data,” J. Appl. Crystallogr. 44, 882886.CrossRefGoogle ScholarPubMed
Toby, B. H. and Von Dreele, R. B. (2013). “GSAS II: the genesis of a modern open source all purpose crystallography software package,” J. Appl. Crystallogr. 46, 544549.CrossRefGoogle Scholar
Turner, M. J., McKinnon, J. J., Wolff, S. K., Grimwood, D. J., Spackman, P. R., Jayatilaka, D., and Spackman, M. A. (2017). CrystalExplorer17 (University of Western Australia). Available at: http://hirshfeldsurface.net.Google Scholar
van de Streek, J. and Neumann, M. A. (2014). “Validation of molecular crystal structures from powder diffraction data with dispersion-corrected density functional theory (DFT-D),” Acta Crystallogr. Sect. B: Struct. Sci., Cryst. Eng. Mater. 70(6), 10201032.CrossRefGoogle Scholar
Wang, J., Toby, B. H., Lee, P. L., Ribaud, L., Antao, S. M., Kurtz, C., Ramanathan, M., Von Dreele, R. B., and Beno, M. A. (2008). “A dedicated powder diffraction beamline at the advanced photon source: commissioning and early operational results,” Rev. Sci. Instrum. 79, 085105.CrossRefGoogle Scholar
Wavefunction, Inc. (2018). Spartan ‘18 Version 1.2.0, Wavefunction Inc., 18401 Von Karman Ave., Suite 370, Irvine, CA 92612.Google Scholar
Wheatley, A. M. and Kaduk, J. A. (2019). “Crystal structures of ammonium citrates,” Powder Diffr. 34, 3543.CrossRefGoogle Scholar

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Crystal structure of brigatinib Form A (Alunbrig®), C29H39ClN7O2P
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