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_2108474
_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(C3 H6 N2 O)'
_chemical_formula_sum            'C23.5 H25 N3 O7.5 S'
_chemical_formula_weight         501.52
_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                   12.85808(14)
_cell_length_b                   12.85808(14)
_cell_length_c                   29.5715(4)
_cell_measurement_reflns_used    26834
_cell_measurement_temperature    100.01(10)
_cell_measurement_theta_max      74.8730
_cell_measurement_theta_min      3.6960
_cell_volume                     4889.06(10)
_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 0.997
_diffrn_measurement_details
;
  1 omega  -75.00   31.00   1.0000    6.0000
omega____ theta____ kappa____ phi______ frames
    -      -43.7274   77.0000 -150.0000 106

  2 omega   12.00  118.00   1.0000    6.0000
omega____ theta____ kappa____ phi______ frames
    -       43.7274   77.0000  -60.0000 106

  3 omega   75.00  178.00   1.0000   30.0000
omega____ theta____ kappa____ phi______ frames
    -      106.0840   77.0000 -120.0000 103

  4 omega   75.00  178.00   1.0000   30.0000
omega____ theta____ kappa____ phi______ frames
    -      106.0840   77.0000  -90.0000 103

  5 omega   75.00  178.00   1.0000   30.0000
omega____ theta____ kappa____ phi______ frames
    -      106.0840   77.0000   90.0000 103

  6 omega   75.00  178.00   1.0000   30.0000
omega____ theta____ kappa____ phi______ frames
    -      106.0840   77.0000   30.0000 103

  7 omega -113.00  -18.00   1.0000    6.0000
omega____ theta____ kappa____ phi______ frames
    -      -43.7274  -57.0000 -180.0000 95

  8 omega -113.00  -18.00   1.0000    6.0000
omega____ theta____ kappa____ phi______ frames
    -      -43.7274  -57.0000   90.0000 95

  9 omega   94.00  178.00   1.0000   30.0000
omega____ theta____ kappa____ phi______ frames
    -      106.0840  125.0000  150.0000 84

 10 omega   82.00  177.00   1.0000   30.0000
omega____ theta____ kappa____ phi______ frames
    -      106.0840   45.0000 -180.0000 95

 11 omega   32.00   97.00   1.0000   30.0000
omega____ theta____ kappa____ phi______ frames
    -      106.0840 -125.0000 -150.0000 65

 12 omega   75.00  178.00   1.0000   30.0000
omega____ theta____ kappa____ phi______ frames
    -      106.0840   77.0000  -30.0000 103
;
_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      -0.0615836000
_diffrn_orient_matrix_UB_12      -0.0793479000
_diffrn_orient_matrix_UB_13      -0.0283686000
_diffrn_orient_matrix_UB_21      0.0113837000
_diffrn_orient_matrix_UB_22      -0.0808284000
_diffrn_orient_matrix_UB_23      0.0381180000
_diffrn_orient_matrix_UB_31      -0.1022204000
_diffrn_orient_matrix_UB_32      0.0389147000
_diffrn_orient_matrix_UB_33      0.0213423000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0397
_diffrn_reflns_av_unetI/netI     0.0169
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.997
_diffrn_reflns_limit_h_max       15
_diffrn_reflns_limit_h_min       -15
_diffrn_reflns_limit_k_max       15
_diffrn_reflns_limit_k_min       -15
_diffrn_reflns_limit_l_max       36
_diffrn_reflns_limit_l_min       -36
_diffrn_reflns_number            38007
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 0.995
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         75.037
_diffrn_reflns_theta_min         3.749
_diffrn_source                   'sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    1.620
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.57587
_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    1.363
_exptl_crystal_description
;
;
_exptl_crystal_F_000             2104
_exptl_crystal_size_max          0.468
_exptl_crystal_size_mid          0.240
_exptl_crystal_size_min          0.122
_refine_diff_density_max         1.977
_refine_diff_density_min         -0.961
_refine_diff_density_rms         0.087
_refine_ls_abs_structure_details
;
 Flack x determined using 1984 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.006(6)
_refine_ls_extinction_coef       0.0008(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   1.048
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     335
_refine_ls_number_reflns         5005
_refine_ls_number_restraints     66
_refine_ls_restrained_S_all      1.085
_refine_ls_R_factor_all          0.0638
_refine_ls_R_factor_gt           0.0629
_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^)+(0.1179P)^2^+6.0959P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1775
_refine_ls_wR_factor_ref         0.1790
_reflns_Friedel_coverage         0.703
_reflns_Friedel_fraction_full    1.000
_reflns_Friedel_fraction_max     0.992
_reflns_number_gt                4888
_reflns_number_total             5005
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            xk5057sup1.cif
_cod_data_source_block           cocr3lf
_cod_original_cell_volume        4889.07(13)
_cod_original_formula_sum        'C23.50 H25 N3 O7.50 S'
_cod_database_code               2108474
_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 O(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2. Uiso/Uaniso restraints and constraints
N51 \\sim C52 \\sim C53 \\sim N54 \\sim C55 \\sim O1W: within 2A with sigma of
0.03 and sigma for terminal atoms of 0.06
Uanis(N51) \\sim Ueq, Uanis(C52) \\sim Ueq, Uanis(C53) \\sim Ueq, Uanis(N54)
\\sim Ueq, Uanis(C55) \\sim Ueq, Uanis(O1W) \\sim Ueq: with sigma of 0.005 and
sigma for terminal atoms of 0.01
3. Others
 Fixed Sof: N51(0.5) H51(0.5) C52(0.5) H52(0.5) C53(0.5) H53(0.5) N54(0.5)
 C55(0.5) H55(0.5) H1WB(0.5) H1WA(0.5)
4.a Riding coordinates:
 O1W(H1WB,H1WA)
4.b Ternary CH refined with riding coordinates:
 C11(H11)
4.c Secondary CH2 refined with riding coordinates:
 C12(H12A,H12B), C20(H20A,H20B)
4.d Aromatic/amide H refined with riding coordinates:
 C2(H2), C3(H3), C4(H4), N2(H2A), C15(H15), C18(H18), C19(H19), N51(H51),
 C52(H52), C53(H53), C55(H55)
4.e Fitted pentagon refined as free rotating group:
 N51(C52,C53,N54,C55)
4.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              36280
_shelx_hkl_checksum              90807
_olex2_date_sample_data_collection 2018-05-17
_olex2_submission_special_instructions 'No special instructions were received'
_cod_database_fobs_code 2108474