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_2108473
_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 H6 N2 O)'
_chemical_formula_sum            'C25 H27 N3 O7.5 S'
_chemical_formula_weight         521.55
_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   geom
_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                   12.81222(8)
_cell_length_b                   12.81222(8)
_cell_length_c                   29.7274(3)
_cell_measurement_reflns_used    32527
_cell_measurement_temperature    100.00(10)
_cell_measurement_theta_max      75.1580
_cell_measurement_theta_min      3.3960
_cell_volume                     4879.84(7)
_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      100.00(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 0.992
_diffrn_measurement_details
;
  1 omega -103.00  -11.00   1.0000    2.0000
omega____ theta____ kappa____ phi______ frames
    -      -43.7274  140.0000  -33.0000 92

  2 omega -115.00  -19.00   1.0000    2.0000
omega____ theta____ kappa____ phi______ frames
    -      -43.7274  -37.0000   60.0000 96

  3 omega   34.00   91.00   1.0000    8.0000
omega____ theta____ kappa____ phi______ frames
    -      106.7090  -30.0000 -180.0000 57

  4 omega   24.00  109.00   1.0000    8.0000
omega____ theta____ kappa____ phi______ frames
    -      106.7090  -94.0000   30.0000 85

  5 omega   81.00  177.00   1.0000    8.0000
omega____ theta____ kappa____ phi______ frames
    -      106.7090   45.0000 -180.0000 96

  6 omega   36.00   98.00   1.0000    8.0000
omega____ theta____ kappa____ phi______ frames
    -      106.7090  -45.0000    0.0000 62

  7 omega -115.00  -19.00   1.0000    2.0000
omega____ theta____ kappa____ phi______ frames
    -      -43.7274  -37.0000  -60.0000 96

  8 omega -113.00  -18.00   1.0000    2.0000
omega____ theta____ kappa____ phi______ frames
    -      -43.7274  -57.0000 -150.0000 95

  9 omega   36.00   98.00   1.0000    8.0000
omega____ theta____ kappa____ phi______ frames
    -      106.7090  -45.0000   90.0000 62

 10 omega   80.00  178.00   1.0000    8.0000
omega____ theta____ kappa____ phi______ frames
    -      106.7090   30.0000    0.0000 98

 11 omega   80.00  178.00   1.0000    8.0000
omega____ theta____ kappa____ phi______ frames
    -      106.7090   30.0000  -90.0000 98

 12 omega   34.00   91.00   1.0000    8.0000
omega____ theta____ kappa____ phi______ frames
    -      106.7090  -30.0000 -120.0000 57

 13 omega -118.00  -12.00   1.0000    2.0000
omega____ theta____ kappa____ phi______ frames
    -      -43.7274  -77.0000  150.0000 106

 14 omega   23.00   97.00   1.0000    2.0000
omega____ theta____ kappa____ phi______ frames
    -       43.7274 -125.0000  -60.0000 74

 15 omega   24.00   53.00   1.0000    8.0000
omega____ theta____ kappa____ phi______ frames
    -      106.7090  -94.0000 -120.0000 29
;
_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      0.1076303000
_diffrn_orient_matrix_UB_12      -0.0534891000
_diffrn_orient_matrix_UB_13      0.0011682000
_diffrn_orient_matrix_UB_21      0.0533627000
_diffrn_orient_matrix_UB_22      0.1075952000
_diffrn_orient_matrix_UB_23      0.0027004000
_diffrn_orient_matrix_UB_31      -0.0051987000
_diffrn_orient_matrix_UB_32      -0.0044577000
_diffrn_orient_matrix_UB_33      0.0517388000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0210
_diffrn_reflns_av_unetI/netI     0.0111
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.992
_diffrn_reflns_limit_h_max       16
_diffrn_reflns_limit_h_min       -16
_diffrn_reflns_limit_k_max       16
_diffrn_reflns_limit_k_min       -15
_diffrn_reflns_limit_l_max       36
_diffrn_reflns_limit_l_min       -26
_diffrn_reflns_number            38165
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 0.989
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         75.235
_diffrn_reflns_theta_min         3.757
_diffrn_source                   'sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    1.645
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.74631
_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    1.420
_exptl_crystal_description
;
;
_exptl_crystal_F_000             2192
_exptl_crystal_size_max          0.4131
_exptl_crystal_size_mid          0.2753
_exptl_crystal_size_min          0.2468
_refine_diff_density_max         1.062
_refine_diff_density_min         -0.633
_refine_diff_density_rms         0.079
_refine_ls_abs_structure_details
;
 Flack x determined using 2008 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.002(4)
_refine_ls_extinction_coef       0.0009(2)
_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   1.068
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     363
_refine_ls_number_reflns         4980
_refine_ls_number_restraints     115
_refine_ls_restrained_S_all      1.319
_refine_ls_R_factor_all          0.0581
_refine_ls_R_factor_gt           0.0579
_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^)+(0.0952P)^2^+6.1533P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1596
_refine_ls_wR_factor_ref         0.1599
_reflns_Friedel_coverage         0.701
_reflns_Friedel_fraction_full    1.000
_reflns_Friedel_fraction_max     0.985
_reflns_number_gt                4953
_reflns_number_total             4980
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            xk5057sup1.cif
_cod_data_source_block           cocr2l
_cod_original_formula_sum        'C25 H27 N3 O7.50 S'
_cod_database_code               2108473
_shelx_shelxl_version_number     2014/7
_reflns_odcompleteness_completeness 99.96
_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 N(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2. Restrained distances
 C51-C57
 1.47 with sigma of 0.01
 C57-N52
 2 with sigma of 0.01
 C57-C56
 2 with sigma of 0.01
 C57-N0AA
 1.39 with sigma of 0.01
 C57-O1AA
 1.24 with sigma of 0.01
 N0AA-O1AA
 2.27 with sigma of 0.02
3. Restrained planarity
 C51, C57, N0AA, O1AA
 with sigma of 0.05
4. Uiso/Uaniso restraints and constraints
C51 \\sim N52 \\sim C53 \\sim C54 \\sim C55 \\sim C56 \\sim C57 \\sim N0AA
\\sim O1AA: within 2A with sigma of 0.007 and sigma for terminal atoms of 0.015
Uanis(C51) \\sim Ueq, Uanis(N52) \\sim Ueq, Uanis(C53) \\sim Ueq, Uanis(C54)
\\sim Ueq, Uanis(C55) \\sim Ueq, Uanis(C56) \\sim Ueq, Uanis(C57) \\sim Ueq,
Uanis(N0AA) \\sim Ueq, Uanis(O1AA) \\sim Ueq: with sigma of 0.007 and sigma for
terminal atoms of 0.015
5. Others
 Fixed Sof: C51(0.5) N52(0.5) C53(0.5) H53(0.5) C54(0.5) H54(0.5) C55(0.5)
 H55(0.5) C56(0.5) H56(0.5) C57(0.5) N0AA(0.5) H0AA(0.5) H0AB(0.5) O1AA(0.5)
6.a Ternary CH refined with riding coordinates:
 C11(H11)
6.b Secondary CH2 refined with riding coordinates:
 C12(H12A,H12B), C20(H20A,H20B)
6.c Aromatic/amide H refined with riding coordinates:
 C2(H2), C3(H3), C4(H4), N2(H2A), C15(H15), C18(H18), C19(H19), C53(H53),
 C54(H54), C55(H55), C56(H56)
6.d Fitted hexagon refined as free rotating group:
 C51(N52,C53,C54,C55,C56)
6.e X=CH2 refined with riding coordinates:
 N0AA(H0AA,H0AB)
6.f 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              80277
_shelx_hkl_checksum              93942
_olex2_date_sample_data_collection 2018-05-15
_olex2_submission_special_instructions 'No special instructions were received'
_cod_database_fobs_code 2108473