Understanding the formation of apremilast cocrystals
Dudek, Marta K.; Wielgus, Ewelina; Paluch, Piotr; Śniechowska, Justyna; Kostrzewa, Maciej; Day, Graeme M.; Bujacz, Grzegorz D.; Potrzebowski, Marek J.; Acta Crystallographica Section B 75 (2019) –; doi:10.1107/S205252061900917X

data_2108475
_publ_section_title
;
 Understanding the formation of apremilast cocrystals
;
_journal_issue                   5
_journal_name_full               'Acta Crystallographica Section B'
_journal_page_first
;
;
_journal_paper_doi               10.1107/S205252061900917X
_journal_volume                  75
_journal_year                    2019
_chemical_absolute_configuration rmad
_chemical_formula_moiety         'C22 H24 N2 O7 S, 0.5(C6 H8 O3)'
_chemical_formula_sum            'C25 H28 N2 O8.5 S'
_chemical_formula_weight         524.55
_space_group_crystal_system      tetragonal
_space_group_IT_number           92
_space_group_name_Hall           'P 4abw 2nw'
_space_group_name_H-M_alt        'P 41 21 2'
_symmetry_space_group_name_Hall  'P 4abw 2nw'
_symmetry_space_group_name_H-M   'P 41 21 2'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     direct
_audit_creation_date             2019-05-16
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   12.88747(7)
_cell_length_b                   12.88747(7)
_cell_length_c                   29.5246(3)
_cell_measurement_reflns_used    31560
_cell_measurement_temperature    100.01(10)
_cell_measurement_theta_max      75.2150
_cell_measurement_theta_min      3.7130
_cell_volume                     4903.65(6)
_computing_cell_refinement
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35h (release 09-02-2015 CrysAlis171 .NET)
(compiled Feb  9 2015,16:26:32)
;
_computing_data_collection
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35h (release 09-02-2015 CrysAlis171 .NET)
(compiled Feb  9 2015,16:26:32)
;
_computing_data_reduction
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35h (release 09-02-2015 CrysAlis171 .NET)
(compiled Feb  9 2015,16:26:32)
;
_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    'ShelXS (Sheldrick, 2008)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      100.01(10)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 4.1685
_diffrn_detector_type            TitanS2
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.996
_diffrn_measurement_details
;
  1 omega -126.00  -44.00   1.0000    3.0000
omega____ theta____ kappa____ phi______ frames
    -      -43.8524 -166.0000  -45.0000 82

  2 omega -116.00  -19.00   1.0000    3.0000
omega____ theta____ kappa____ phi______ frames
    -      -43.8524  -37.0000   60.0000 97

  3 omega   34.00   91.00   1.0000   12.0000
omega____ theta____ kappa____ phi______ frames
    -      106.7090  -30.0000 -150.0000 57

  4 omega   24.00  109.00   1.0000   12.0000
omega____ theta____ kappa____ phi______ frames
    -      106.7090  -94.0000   30.0000 85

  5 omega   34.00   91.00   1.0000   12.0000
omega____ theta____ kappa____ phi______ frames
    -      106.7090  -30.0000  150.0000 57

  6 omega   34.00   91.00   1.0000   12.0000
omega____ theta____ kappa____ phi______ frames
    -      106.7090  -30.0000 -180.0000 57

  7 omega   99.00  178.00   1.0000   12.0000
omega____ theta____ kappa____ phi______ frames
    -      106.7090  116.0000 -169.0000 79

  8 omega -114.00  -18.00   1.0000    3.0000
omega____ theta____ kappa____ phi______ frames
    -      -43.8524  -57.0000  -30.0000 96

  9 omega -114.00  -18.00   1.0000    3.0000
omega____ theta____ kappa____ phi______ frames
    -      -43.8524  -57.0000 -180.0000 96

 10 omega   34.00   91.00   1.0000   12.0000
omega____ theta____ kappa____ phi______ frames
    -      106.7090  -30.0000   90.0000 57

 11 omega   80.00  178.00   1.0000   12.0000
omega____ theta____ kappa____ phi______ frames
    -      106.7090   30.0000  150.0000 98

 12 omega   24.00  109.00   1.0000   12.0000
omega____ theta____ kappa____ phi______ frames
    -      106.7090  -94.0000 -150.0000 85

 13 omega   81.00  177.00   1.0000   12.0000
omega____ theta____ kappa____ phi______ frames
    -      106.7090   45.0000  -90.0000 96

 14 omega -114.00  -22.00   1.0000    3.0000
omega____ theta____ kappa____ phi______ frames
    -      -43.8524  -57.0000 -120.0000 92

 15 omega   67.00  125.00   1.0000    3.0000
omega____ theta____ kappa____ phi______ frames
    -       43.8524  166.0000  -23.0000 58
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at zero, TitanS2'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_UB_11      -0.0692063000
_diffrn_orient_matrix_UB_12      0.0971522000
_diffrn_orient_matrix_UB_13      -0.0033469000
_diffrn_orient_matrix_UB_21      -0.0966126000
_diffrn_orient_matrix_UB_22      -0.0671912000
_diffrn_orient_matrix_UB_23      0.0091465000
_diffrn_orient_matrix_UB_31      0.0127482000
_diffrn_orient_matrix_UB_32      0.0184048000
_diffrn_orient_matrix_UB_33      0.0512646000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0265
_diffrn_reflns_av_unetI/netI     0.0130
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.996
_diffrn_reflns_limit_h_max       15
_diffrn_reflns_limit_h_min       -16
_diffrn_reflns_limit_k_max       15
_diffrn_reflns_limit_k_min       -15
_diffrn_reflns_limit_l_max       36
_diffrn_reflns_limit_l_min       -26
_diffrn_reflns_number            38399
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 0.991
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         75.434
_diffrn_reflns_theta_min         3.742
_diffrn_source                   'sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    1.658
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.60342
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro, Agilent Technologies,
Version 1.171.37.35h (release 09-02-2015 CrysAlis171 .NET)
(compiled Feb  9 2015,16:26:32)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_density_diffrn    1.421
_exptl_crystal_description
;
;
_exptl_crystal_F_000             2208
_exptl_crystal_size_max          0.261
_exptl_crystal_size_mid          0.160
_exptl_crystal_size_min          0.118
_refine_diff_density_max         1.228
_refine_diff_density_min         -0.968
_refine_diff_density_rms         0.088
_refine_ls_abs_structure_details
;
 Flack x determined using 2039 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.003(4)
_refine_ls_extinction_coef       0.0014(3)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     'SHELXL-2014/7 (Sheldrick 2014'
_refine_ls_goodness_of_fit_ref   1.055
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     359
_refine_ls_number_reflns         5046
_refine_ls_number_restraints     114
_refine_ls_restrained_S_all      1.121
_refine_ls_R_factor_all          0.0599
_refine_ls_R_factor_gt           0.0596
_refine_ls_shift/su_max          0.011
_refine_ls_shift/su_mean         0.001
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.1156P)^2^+5.1206P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1718
_refine_ls_wR_factor_ref         0.1722
_reflns_Friedel_coverage         0.700
_reflns_Friedel_fraction_full    1.000
_reflns_Friedel_fraction_max     0.985
_reflns_number_gt                5005
_reflns_number_total             5046
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            xk5057sup1.cif
_cod_data_source_block           cocr4lf
_cod_original_cell_volume        4903.65(7)
_cod_original_formula_sum        'C25 H28 N2 O8.50 S'
_cod_database_code               2108475
_shelx_shelxl_version_number     2014/7
_reflns_odcompleteness_completeness 99.92
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     66.97
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H) groups, All O(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H) groups
2. Restrained distances
 C51-O51 = C54-O54
 1.36 with sigma of 0.01
 O51-C52 = O51-C56 = O54-C53 = O54-C55
 2.38 with sigma of 0.005
3. Uiso/Uaniso restraints and constraints
C51 \\sim C52 \\sim C53 \\sim C54 \\sim C55 \\sim C56 \\sim O51 \\sim O54 \\sim
O1W: within 2A with sigma of 0.009 and sigma for terminal atoms of 0.018
Uanis(C51) \\sim Ueq, Uanis(C52) \\sim Ueq, Uanis(C53) \\sim Ueq, Uanis(C54)
\\sim Ueq, Uanis(C55) \\sim Ueq, Uanis(C56) \\sim Ueq, Uanis(O51) \\sim Ueq,
Uanis(O54) \\sim Ueq, Uanis(O1W) \\sim Ueq: with sigma of 0.009 and sigma for
terminal atoms of 0.018
4. Others
 Fixed Sof: C51(0.5) C52(0.5) H52(0.5) C53(0.5) H53(0.5) C54(0.5) C55(0.5)
 H55(0.5) C56(0.5) H56(0.5) O51(0.5) H51(0.5) O54(0.5) H54(0.5) H1WA(0.5)
 H1WB(0.5)
5.a Riding coordinates:
 O54(H54), O1W(H1WA,H1WB)
5.b Ternary CH refined with riding coordinates:
 C11(H11)
5.c Secondary CH2 refined with riding coordinates:
 C12(H12A,H12B), C20(H20A,H20B)
5.d Aromatic/amide H refined with riding coordinates:
 C2(H2), C3(H3), C4(H4), N2(H2A), C15(H15), C18(H18), C19(H19), C52(H52),
 C53(H53), C55(H55), C56(H56)
5.e Fitted hexagon refined as free rotating group:
 C51(C52,C53,C54,C55,C56)
5.f Tetrahedral OH refined with riding coordinates:
 O51(H51)
5.g Idealised Me refined as rotating group:
 C10(H10A,H10B,H10C), C13(H13A,H13B,H13C), C21(H21A,H21B,H21C), C22(H22A,H22B,
 H22C)
;
_shelx_res_checksum              93091
_shelx_hkl_checksum              36118
_olex2_date_sample_data_collection 2018-05-17
_olex2_submission_special_instructions 'No special instructions were received'
_cod_database_fobs_code 2108475