New forms of apremilast with halogen derivatives of benzoic acid
Naumkina, Yelizaveta; Kratochvíl, Bohumil; Korotkova, Elena; Čejka, Jan; CrystEngComm 27 (2025) 7713–7720; doi:10.1039/D5CE00770D

data_7251007
_publ_section_title
;
 New forms of apremilast with halogen derivatives of benzoic acid
;
_journal_issue                   47
_journal_name_full               CrystEngComm
_journal_page_first              7713
_journal_page_last               7720
_journal_paper_doi               10.1039/D5CE00770D
_journal_volume                  27
_journal_year                    2025
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C22 H24 N2 O7 S, 1/2(C7 H5 Br O2)'
_chemical_formula_sum            'C25.5 H26.5 Br0.5 N2 O8 S'
_chemical_formula_weight         561.02
_chemical_melting_point          ?
_chemical_name_common            'bis(apremilast) 4-bromobenzoic acid'
_chemical_name_systematic
'bis(N-{2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}acetamide) 4-bromobenzoic acid'
_space_group_IT_number           19
_space_group_name_Hall           'P 2ac 2ab'
_space_group_name_H-M_alt        'P 21 21 21'
_symmetry_cell_setting           orthorhombic
_symmetry_space_group_name_H-M   'P 21 21 21'
_atom_sites_solution_hydrogens   difmap
_atom_sites_solution_primary     direct
_audit_update_record
;
2025-07-30 deposited with the CCDC.	2025-10-13 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   13.2266(3)
_cell_length_b                   13.4694(3)
_cell_length_c                   28.8772(6)
_cell_measurement_reflns_used    9838
_cell_measurement_temperature    180
_cell_measurement_theta_max      42.39
_cell_measurement_theta_min      3.06
_cell_volume                     5144.6(2)
_computing_cell_refinement       'SAINT V8.40B (Bruker AXS LLC, 2019)'
_computing_data_collection       'Bruker Instrument Service vV6.2.15'
_computing_data_reduction        'SAINT V8.40B (Bruker AXS LLC, 2019)'
_computing_molecular_graphics    'CAMERON (Watkin et al., 1996)'
_computing_publication_material  'CRYSTALS (Betteridge et al., 2003)'
_computing_structure_refinement  'CRYSTALS (Betteridge et al., 2003)'
_computing_structure_solution    'SHELXT (Sheldrick, 2015)'
_diffrn_ambient_temperature      180
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.999
_diffrn_measurement_device       Area
_diffrn_measurement_device_type  'Bruker Venture D8'
_diffrn_measurement_method       '\f & \w scans'
_diffrn_radiation_monochromator  polycapillary
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.54180
_diffrn_reflns_av_R_equivalents  0.0389
_diffrn_reflns_av_unetI/netI     0.023
_diffrn_reflns_limit_h_max       16
_diffrn_reflns_limit_h_min       -16
_diffrn_reflns_limit_k_max       16
_diffrn_reflns_limit_k_min       0
_diffrn_reflns_limit_l_max       35
_diffrn_reflns_limit_l_min       0
_diffrn_reflns_number            10186
_diffrn_reflns_theta_full        72.382
_diffrn_reflns_theta_max         72.382
_diffrn_reflns_theta_min         3.061
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    2.481
_exptl_absorpt_correction_T_max  0.67
_exptl_absorpt_correction_T_min  0.58
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   'SADABS (Siemens, 1996)'
_exptl_crystal_colour            yellow
_exptl_crystal_density_diffrn    1.449
_exptl_crystal_density_meas      ?
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       bipyramidal
_exptl_crystal_F_000             2327.987
_exptl_crystal_recrystallization_method
'Re-crystallisation from solvent: Methyl Ethyl Ketone'
_exptl_crystal_size_max          0.200
_exptl_crystal_size_mid          0.162
_exptl_crystal_size_min          0.160
_refine_diff_density_max         0.67
_refine_diff_density_min         -0.86
_refine_ls_abs_structure_details
; 
 Parsons, Flack & Wagner (2013), 
 4003 Friedel Pairs 
;
_refine_ls_abs_structure_Flack   0.001(2)
_refine_ls_extinction_method     None
_refine_ls_goodness_of_fit_ref   1.0000
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     680
_refine_ls_number_reflns         10180
_refine_ls_number_restraints     10
_refine_ls_R_factor_all          0.0423
_refine_ls_R_factor_gt           0.0414
_refine_ls_shift/su_max          0.0004565
_refine_ls_shift/su_mean         0.0000579
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
;
 Method= Modified Sheldrick 
 w=1/[\s^2^(F^2^) + ( 0.08P)^2^ + 4.03P] 
 ,where P=(max(Fo^2^,0) + 2Fc^2^)/3 
;
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_all         0.1185
_refine_ls_wR_factor_gt          0.1181
_refine_ls_wR_factor_ref         0.1185
_reflns_limit_h_max              16
_reflns_limit_h_min              -16
_reflns_limit_k_max              16
_reflns_limit_k_min              0
_reflns_limit_l_max              35
_reflns_limit_l_min              0
_reflns_number_gt                9877
_reflns_number_total             10186
_reflns_threshold_expression     I>2.0\s(I)
_oxford_diffrn_Wilson_B_factor   2.88
_oxford_diffrn_Wilson_scale      13.30
_oxford_refine_ls_scale          0.2873(2)
_cod_data_source_file            d5ce00770d3.cif
_cod_data_source_block           APR_4BrBA
_cod_depositor_comments
;
The following automatic conversions were performed:

data item '_chemical_melting_point' value '-' was changed to '?' --
the value is undefined or not given.

data item '_exptl_crystal_density_meas' value 'not measured' was
changed to '?' -- the value is perceived as not measured.

Automatic conversion script
Id: cif_fix_values 8170 2020-07-09 18:12:32Z antanas 

 Adding full bibliography for 7251003--7251007.cif.
;
_cod_original_sg_symbol_H-M      'P 21 21 21 '
_cod_original_formula_sum        'C25.50 H26.50 Br0.50 N2 O8 S'
_cod_database_code               7251007
_oxford_refine_reflns_threshold_expression I>-3.0\s(I)
_refine_ls_r_factor_ref          0.0423
_reflns_number_all               10180
_oxford_hooft_y                  -0.002(5)
_oxford_bijvoet_difference       0.001(2)
_oxford_refined_flack_x          -0.003(13)