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_7251003
_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 Cl O2)'
_chemical_formula_sum            'C25.5 H26.5 Cl0.5 N2 O8 S'
_chemical_formula_weight         538.79
_chemical_melting_point          177
_chemical_name_common            'apremilast hemikis(2-chlorobenzoic acid)'
_chemical_name_systematic
'N-{2-[1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethyl]-1,3-dioxo-2,3-dihydro-1H-isoindol-4-yl}acetamide hemikis(2-chlorobenzoic acid)'
_space_group_IT_number           92
_space_group_name_Hall           'P 4abw 2nw'
_space_group_name_H-M_alt        'P 41 21 2'
_symmetry_cell_setting           tetragonal
_symmetry_space_group_name_H-M   'P 41 21 2'
_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                   13.0114(3)
_cell_length_b                   13.0114(3)
_cell_length_c                   29.2398(9)
_cell_measurement_reflns_used    9514
_cell_measurement_temperature    180
_cell_measurement_theta_max      72.17
_cell_measurement_theta_min      3.40
_cell_volume                     4950.2(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 1.000
_diffrn_measured_fraction_theta_max 1.000
_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  0.0492
_diffrn_reflns_av_unetI/netI     0.017
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       16
_diffrn_reflns_limit_k_min       0
_diffrn_reflns_limit_l_max       36
_diffrn_reflns_limit_l_min       0
_diffrn_reflns_number            4882
_diffrn_reflns_theta_full        72.167
_diffrn_reflns_theta_max         72.167
_diffrn_reflns_theta_min         3.718
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    2.130
_exptl_absorpt_correction_T_max  0.66
_exptl_absorpt_correction_T_min  0.59
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   'SADABS (Siemens, 1996)'
_exptl_crystal_colour            yellow
_exptl_crystal_density_diffrn    1.446
_exptl_crystal_density_meas      ?
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       bipyramidal
_exptl_crystal_F_000             2256
_exptl_crystal_recrystallization_method
'Re-crystallisation from solvent: Methyl Ethyl Ketone'
_exptl_crystal_size_max          0.218
_exptl_crystal_size_mid          0.217
_exptl_crystal_size_min          0.192
_refine_diff_density_max         0.84
_refine_diff_density_min         -0.43
_refine_ls_abs_structure_details
; 
 Parsons, Flack & Wagner (2013), 
 1782 Friedel Pairs 
;
_refine_ls_abs_structure_Flack   -0.002(4)
_refine_ls_extinction_method     None
_refine_ls_goodness_of_fit_ref   0.9999
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     388
_refine_ls_number_reflns         4882
_refine_ls_number_restraints     150
_refine_ls_R_factor_all          0.0460
_refine_ls_R_factor_gt           0.0456
_refine_ls_shift/su_max          0.0010984
_refine_ls_shift/su_mean         0.0000721
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
;
 Method= Modified Sheldrick 
 w=1/[\s^2^(F^2^) + ( 0.09P)^2^ + 4.15P] 
 ,where P=(max(Fo^2^,0) + 2Fc^2^)/3 
;
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_all         0.1304
_refine_ls_wR_factor_gt          0.1300
_refine_ls_wR_factor_ref         0.1304
_reflns_limit_h_max              11
_reflns_limit_h_min              -10
_reflns_limit_k_max              16
_reflns_limit_k_min              0
_reflns_limit_l_max              36
_reflns_limit_l_min              0
_reflns_number_gt                4812
_reflns_number_total             4882
_reflns_threshold_expression     I>2.0\s(I)
_oxford_diffrn_Wilson_B_factor   3.04
_oxford_diffrn_Wilson_scale      150.65
_oxford_refine_ls_scale          0.2903(4)
_cod_data_source_file            d5ce00770d3.cif
_cod_data_source_block           APR_2ClBA
_cod_depositor_comments
;
The following automatic conversions were performed:

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_cell_volume        4950.2(3)
_cod_original_sg_symbol_H-M      'P 41 21 2 '
_cod_original_formula_sum        'C25.50 H26.50 Cl0.50 N2 O8 S'
_cod_database_code               7251003
_oxford_refine_reflns_threshold_expression I>-3.0\s(I)
_refine_ls_r_factor_ref          0.0460
_reflns_number_all               4882
_oxford_hooft_y                  -0.0002(17)
_oxford_bijvoet_difference       -0.002(4)
_oxford_refined_flack_x          -0.00(2)