An unusual ionic cocrystal of ponatinib hydrochloride: characterization by single-crystal X-ray diffraction and ultra-high field NMR spectroscopy.
Stirk, Alexander J.; Holmes, Sean T.; Souza, Fabio E. S.; Hung, Ivan; Gan, Zhehong; Britten, James F.; Rey, Allan W.; Schurko, Robert W.; CrystEngComm 26 (2024) 1219–1233; doi:10.1039/d3ce01062g

data_7248049
_publ_section_title
;
 An unusual ionic cocrystal of ponatinib hydrochloride: characterization
 by single-crystal X-ray diffraction and ultra-high field NMR
 spectroscopy.
;
_journal_issue                   9
_journal_name_full               CrystEngComm
_journal_page_first              1219
_journal_page_last               1233
_journal_paper_doi               10.1039/d3ce01062g
_journal_volume                  26
_journal_year                    2024
_chemical_formula_moiety
'C29 H29 F3 N6 O, C29 H28 F3 N6 O, 3(Cl), 3(H2 O)'
_chemical_formula_sum            'C58 H63 Cl3 F6 N12 O5'
_chemical_formula_weight         1228.55
_chemical_name_common            'Ponatinib HCl'
_chemical_name_systematic
'3-(imidazo[1,2-b]pyridazin-3-yylethynyl)-4-methyl-N-(4-((4-methylpiperazin-1-yl)methyl)-3-(trifluoromethyl)phenyl)benzamide hydrochloride'
_space_group_crystal_system      triclinic
_space_group_IT_number           2
_space_group_name_Hall           '-P 1'
_space_group_name_H-M_alt        'P -1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_creation_date             2019-04-21
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_audit_update_record
;
2023-10-19 deposited with the CCDC.	2024-01-30 downloaded from the CCDC.
;
_cell_angle_alpha                92.864(3)
_cell_angle_beta                 102.624(3)
_cell_angle_gamma                106.246(3)
_cell_formula_units_Z            2
_cell_length_a                   12.4408(7)
_cell_length_b                   15.1905(8)
_cell_length_c                   16.5411(9)
_cell_measurement_reflns_used    9942
_cell_measurement_temperature    100.0(1)
_cell_measurement_theta_max      23.95
_cell_measurement_theta_min      2.58
_cell_volume                     2907.9(3)
_computing_cell_refinement       'SAINT v8.34A (Bruker, 2013)'
_computing_data_reduction        'SAINT v8.34A (Bruker, 2013)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'XL (Sheldrick, 2008)'
_computing_structure_solution    'XT (Sheldrick, 2015)'
_diffrn_ambient_temperature      100.0(1)
_diffrn_measured_fraction_theta_full 0.998
_diffrn_measured_fraction_theta_max 0.993
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0692
_diffrn_reflns_av_unetI/netI     0.0588
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.993
_diffrn_reflns_limit_h_max       16
_diffrn_reflns_limit_h_min       -16
_diffrn_reflns_limit_k_max       20
_diffrn_reflns_limit_k_min       -20
_diffrn_reflns_limit_l_max       21
_diffrn_reflns_limit_l_min       -21
_diffrn_reflns_number            97752
_diffrn_reflns_point_group_measured_fraction_full 0.998
_diffrn_reflns_point_group_measured_fraction_max 0.993
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         28.086
_diffrn_reflns_theta_min         1.270
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.237
_exptl_absorpt_correction_T_max  0.8621
_exptl_absorpt_correction_T_min  0.7725
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
'SADABS-2014/4 (Bruker,2014/4) was used for absorption correction. wR2(int) was 0.0650 before and 0.0601 after correction. The Ratio of minimum to maximum transmission is 0.8961. The \l/2 correction factor is 0.00150.'
_exptl_crystal_colour            'clear light yellow'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_modifier   light
_exptl_crystal_colour_primary    yellow
_exptl_crystal_density_diffrn    1.403
_exptl_crystal_description       block
_exptl_crystal_F_000             1280
_exptl_crystal_recrystallization_method Layering
_exptl_crystal_size_max          0.3
_exptl_crystal_size_mid          0.28
_exptl_crystal_size_min          0.2
_refine_diff_density_max         0.668
_refine_diff_density_min         -0.413
_refine_diff_density_rms         0.083
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.096
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     782
_refine_ls_number_reflns         14060
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.096
_refine_ls_R_factor_all          0.0895
_refine_ls_R_factor_gt           0.0599
_refine_ls_shift/su_max          0.001
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0684P)^2^+4.1855P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1595
_refine_ls_wR_factor_ref         0.1733
_reflns_Friedel_coverage         0.000
_reflns_number_gt                9882
_reflns_number_total             14060
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d3ce01062g2.cif
_cod_data_source_block           grtv1661_0m
_cod_depositor_comments          'Adding full bibliography for 7248049.cif.'
_cod_database_code               7248049
_shelx_shelxl_version_number     2017/1
_shelx_estimated_absorpt_t_max   0.954
_shelx_estimated_absorpt_t_min   0.932
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H,H) groups
2.a Free rotating group:
 O3(H3C,H3D), O2(H2C,H2D), O1(H1C,H1D)
2.b Secondary CH2 refined with riding coordinates:
 C24A(H24A,H24B), C25A(H25A,H25B), C26A(H26A,H26B), C27A(H27A,H27B), C28A(H28A,
 H28B), C24B(H24C,H24D), C25B(H25C,H25D), C26B(H26C,H26D), C27B(H27C,H27D),
 C28B(H28C,H28D)
2.c Aromatic/amide H refined with riding coordinates:
 N4A(H4A), C1A(H1AA), C2A(H2A), C3A(H3A), C5A(H5A), C10A(H10A), C12A(H12A),
 C13A(H13A), C18A(H18A), C19A(H19A), C22A(H22A), N4B(H4B), C1B(H1B), C2B(H2B),
 C3B(H3B), C5B(H5B), C10B(H10B), C12B(H12B), C13B(H13B), C18B(H18B), C19B(H19B),
  C22B(H22B)
2.d Idealised Me refined as rotating group:
 C15A(H15A,H15B,H15C), C29A(H29A,H29B,H29C), C15B(H15D,H15E,H15F), C29B(H29D,
 H29E,H29F)
;
_shelx_res_checksum              68619
_shelx_hkl_checksum              56667
_olex2_submission_special_instructions 'No special instructions were received'