Brexpiprazole-Catechol Cocrystal: Structure Elucidation, Excipient Compatibility and Stability
Arabiani, Mohsin Razakbhai; Bal Raju, K.; Bhunia, Surojit; Teja, Pyla Kranthi; Lodagekar, Anurag; Chavan, Rahul B.; Shastri, Nalini R.; Reddy, Chilla Malla; Shelat, Pragna; Dave, Divyang; CrystEngComm  (2019) –; doi:10.1039/C9CE01182J

data_7234442
_publ_section_title
;
 Brexpiprazole-Catechol Cocrystal: Structure Elucidation, Excipient
 Compatibility and Stability
;
_journal_name_full               CrystEngComm
_journal_paper_doi               10.1039/C9CE01182J
_journal_year                    2019
_chemical_formula_moiety         'C25 H27 N3 O2 S, C6 H6 O2'
_chemical_formula_sum            'C31 H33 N3 O4 S'
_chemical_formula_weight         543.66
_chemical_name_systematic        'Brexpiprazole Catechol Co-crystal'
_space_group_crystal_system      monoclinic
_space_group_IT_number           14
_space_group_name_Hall           '-P 2ybc'
_space_group_name_H-M_alt        'P 1 21/c 1'
_symmetry_space_group_name_Hall  '-P 2ybc'
_symmetry_space_group_name_H-M   'P 1 21/c 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     iterative
_audit_creation_date             2019-02-07
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_audit_update_record
;
2019-02-07 deposited with the CCDC.    2019-10-03 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 102.918(5)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   12.1386(6)
_cell_length_b                   18.4630(9)
_cell_length_c                   13.0343(6)
_cell_measurement_reflns_used    4322
_cell_measurement_temperature    293(2)
_cell_measurement_theta_max      24.8950
_cell_measurement_theta_min      2.0140
_cell_volume                     2847.2(2)
_computing_cell_refinement       'CrysAlisPro 1.171.38.43 (Rigaku OD, 2015)'
_computing_data_collection       'CrysAlisPro 1.171.38.43 (Rigaku OD, 2015)'
_computing_data_reduction        'CrysAlisPro 1.171.38.43 (Rigaku OD, 2015)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2015)'
_computing_structure_solution    'olex2.solve (Bourhis et al., 2015)'
_diffrn_ambient_temperature      293(2)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 7.9580
_diffrn_detector_type            Eos
_diffrn_measured_fraction_theta_full 0.994
_diffrn_measured_fraction_theta_max 0.902
_diffrn_measurement_details
;
List of Runs (angles in degrees, time in seconds):

  # Type    Start    End  Width  t~exp~   \w     \q     \k     \f   Frames
  1  \w   -122.00 -55.00   1.00   40.00    --  -25.76 178.00-120.00   67
  2  \w    -20.00  83.00   1.00   40.00    --   27.17 -99.00-180.00  103
  3  \w    -59.00 115.00   1.00   40.00    --   27.17  19.00 -30.00  174
  4  \w    -11.00  39.00   1.00   40.00    --   27.17  57.00 120.00   50
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at zero, Eos'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0282622000
_diffrn_orient_matrix_UB_12      0.0319185000
_diffrn_orient_matrix_UB_13      0.0219723000
_diffrn_orient_matrix_UB_21      -0.0431849000
_diffrn_orient_matrix_UB_22      0.0213673000
_diffrn_orient_matrix_UB_23      -0.0315410000
_diffrn_orient_matrix_UB_31      -0.0305164000
_diffrn_orient_matrix_UB_32      -0.0006569000
_diffrn_orient_matrix_UB_33      0.0404813000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0333
_diffrn_reflns_av_unetI/netI     0.0443
_diffrn_reflns_Laue_measured_fraction_full 0.994
_diffrn_reflns_Laue_measured_fraction_max 0.902
_diffrn_reflns_limit_h_max       14
_diffrn_reflns_limit_h_min       -15
_diffrn_reflns_limit_k_max       23
_diffrn_reflns_limit_k_min       -22
_diffrn_reflns_limit_l_max       16
_diffrn_reflns_limit_l_min       -15
_diffrn_reflns_number            15248
_diffrn_reflns_point_group_measured_fraction_full 0.994
_diffrn_reflns_point_group_measured_fraction_max 0.902
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         27.405
_diffrn_reflns_theta_min         1.946
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Mo) X-ray Source'
_exptl_absorpt_coefficient_mu    0.154
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.82703
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.38.43 (Rigaku Oxford Diffraction, 2015)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.268
_exptl_crystal_description       needle
_exptl_crystal_F_000             1152
_exptl_crystal_recrystallization_method 'Re-crystallisation from solvent: THF'
_exptl_crystal_size_max          0.3
_exptl_crystal_size_mid          0.2
_exptl_crystal_size_min          0.1
_refine_diff_density_max         0.245
_refine_diff_density_min         -0.253
_refine_diff_density_rms         0.034
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.042
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     357
_refine_ls_number_reflns         5850
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.042
_refine_ls_R_factor_all          0.0912
_refine_ls_R_factor_gt           0.0558
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0316P)^2^+1.1834P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1087
_refine_ls_wR_factor_ref         0.1251
_reflns_Friedel_coverage         0.000
_reflns_number_gt                3835
_reflns_number_total             5850
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c9ce01182j2.cif
_cod_data_source_block           sb_bxp_cat
_cod_original_cell_volume        2847.3(2)
_cod_database_code               7234442
_shelx_shelxl_version_number     2017/1
_chemical_oxdiff_formula         'C H N O'
_shelx_estimated_absorpt_t_max   0.985
_shelx_estimated_absorpt_t_min   0.955
_reflns_odcompleteness_completeness 99.84
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     25.63
_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 O(H) groups
2.a Secondary CH2 refined with riding coordinates:
 C8AA(H8AA,H8AB), C2BA(H2BA,H2BB), C3BA(H3BA,H3BB), C9CA(H9CA,H9CB), C6BA(H6BA,
 H6BB), C1DA(H1DA,H1DB), C8BA(H8BA,H8BB), C1CA(H1CA,H1CB)
2.b Aromatic/amide H refined with riding coordinates:
 N1AA(H1AA), C2AA(H2AA), C4AA(H4AA), C7AA(H7AA), C0BA(H0BA), C0DA(H0DA),
 C2DA(H2DA), C3DA(H3DA), C9BA(H9BA), C0CA(H0CA), C4DA(H4DA), C2CA(H2CA),
 C3CA(H3CA), C4CA(H4CA), C5CA(H5CA)
2.c Idealised tetrahedral OH refined as rotating group:
 O0AA(H0AA)
;
_olex2_submission_special_instructions 'No special instructions were received'
_oxdiff_exptl_absorpt_empirical_details
;
Empirical correction (ABSPACK) includes:
- Absorption correction using spherical harmonics
- Frame scaling
;
_oxdiff_exptl_absorpt_empirical_full_max 1.339
_oxdiff_exptl_absorpt_empirical_full_min 0.751