Improving the Solubility and Bioavailability of Pemafibrate via a New Polymorph Form II.
Li, Long; Yin, Xian-Hong; Diao, Kai-Sheng; ACS omega 5 (2020) 26245–26252; doi:10.1021/acsomega.0c04005

data_4518116
_publ_section_title
;
 Improving the Solubility and Bioavailability of Pemafibrate via a New
 Polymorph Form II.
;
_journal_issue                   40
_journal_name_full               'ACS omega'
_journal_page_first              26245
_journal_page_last               26252
_journal_paper_doi               10.1021/acsomega.0c04005
_journal_volume                  5
_journal_year                    2020
_chemical_absolute_configuration unk
_chemical_formula_moiety         'C28 H30 N2 O6'
_chemical_formula_sum            'C28 H30 N2 O6'
_chemical_formula_weight         490.54
_space_group_crystal_system      monoclinic
_space_group_IT_number           4
_space_group_name_Hall           'P 2yb'
_space_group_name_H-M_alt        'P 1 21 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     iterative
_audit_creation_date             2020-09-11
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_cell_angle_alpha                90
_cell_angle_beta                 105.418(8)
_cell_angle_gamma                90
_cell_formula_units_Z            2
_cell_length_a                   11.6007(8)
_cell_length_b                   5.3802(3)
_cell_length_c                   20.9518(16)
_cell_measurement_reflns_used    1745
_cell_measurement_temperature    293(2)
_cell_measurement_theta_max      24.8290
_cell_measurement_theta_min      3.9470
_cell_volume                     1260.63(16)
_computing_cell_refinement       'CrysAlisPro 1.171.38.43 (Rigaku OD, 2015)'
_computing_data_collection       'CrysAlisPro 1.171.38.43 (Rigaku OD, 2015)'
_computing_data_reduction        'CrysAlisPro 1.171.38.43 (Rigaku OD, 2015)'
_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
;
Superflip (Palatinus & Chapuis, 2007;Palatinus & van der Lee, 2008;
Palatinus et al., 2012)
;
_diffrn_ambient_temperature      293.15
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 16.0874
_diffrn_detector_type            Eos
_diffrn_measured_fraction_theta_full 0.997
_diffrn_measured_fraction_theta_max 0.997
_diffrn_measurement_details
;
List of Runs (angles in degrees, time in seconds):

  # Type    Start    End  Width  t~exp~   \w     \q     \k     \f   Frames
--------------------------------------------------------------------------
  1  \w    -29.00  51.50   0.70   15.00    --  -14.81  38.00 120.00  115
  2  \w     -9.00  20.40   0.70   15.00    --  -14.81 -99.00 120.00   42
  3  \w    -32.00  31.00   0.70   15.00    --   16.92 -57.00 -60.00   90
  4  \w    -10.00  32.00   0.70   15.00    --   16.92  77.00  90.00   60
  5  \w    -76.00 -48.00   0.70   15.00    --  -14.65 -57.00 120.00   40
  6  \w    -40.00  28.60   0.70   15.00    --   16.76 -57.00-180.00   98
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'Xcalibur, Eos'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0420513000
_diffrn_orient_matrix_UB_12      -0.0053733000
_diffrn_orient_matrix_UB_13      0.0191343000
_diffrn_orient_matrix_UB_21      0.0473077000
_diffrn_orient_matrix_UB_22      0.0028148000
_diffrn_orient_matrix_UB_23      0.0294841000
_diffrn_orient_matrix_UB_31      -0.0026857000
_diffrn_orient_matrix_UB_32      0.1316867000
_diffrn_orient_matrix_UB_33      0.0001323000
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0195
_diffrn_reflns_av_unetI/netI     0.0421
_diffrn_reflns_Laue_measured_fraction_full 0.997
_diffrn_reflns_Laue_measured_fraction_max 0.997
_diffrn_reflns_limit_h_max       13
_diffrn_reflns_limit_h_min       -14
_diffrn_reflns_limit_k_max       6
_diffrn_reflns_limit_k_min       -6
_diffrn_reflns_limit_l_max       25
_diffrn_reflns_limit_l_min       -26
_diffrn_reflns_number            8453
_diffrn_reflns_point_group_measured_fraction_full 0.917
_diffrn_reflns_point_group_measured_fraction_max 0.907
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         26.373
_diffrn_reflns_theta_min         3.026
_diffrn_source                   'fine-focus sealed X-ray tube'
_diffrn_source_type              'Enhance (Mo) X-ray Source'
_exptl_absorpt_coefficient_mu    0.091
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.89320
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.38.43 (Rigaku Oxford Diffraction, 2015)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.292
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       block
_exptl_crystal_F_000             520
_exptl_crystal_size_max          0.35
_exptl_crystal_size_mid          0.3
_exptl_crystal_size_min          0.05
_refine_diff_density_max         0.644
_refine_diff_density_min         -0.284
_refine_diff_density_rms         0.040
_refine_ls_abs_structure_details
;
 Flack x determined using 956 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.8(6)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.059
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     328
_refine_ls_number_reflns         4664
_refine_ls_number_restraints     15
_refine_ls_restrained_S_all      1.074
_refine_ls_R_factor_all          0.0949
_refine_ls_R_factor_gt           0.0657
_refine_ls_shift/su_max          0.068
_refine_ls_shift/su_mean         0.004
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0736P)^2^+0.3945P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1509
_refine_ls_wR_factor_ref         0.1707
_reflns_Friedel_coverage         0.636
_reflns_Friedel_fraction_full    0.815
_reflns_Friedel_fraction_max     0.794
_reflns_number_gt                3368
_reflns_number_total             4664
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            ao0c04005_si_001.cif
_cod_data_source_block           190703_s6_kl_ll_a407
_cod_depositor_comments          'Adding full bibliography for 4518116.cif.'
_cod_database_code               4518116
_shelx_shelxl_version_number     2014/7
_chemical_oxdiff_formula         c12h12n2o3
_shelx_estimated_absorpt_t_max   0.995
_shelx_estimated_absorpt_t_min   0.969
_reflns_odcompleteness_completeness 99.65
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     26.32
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H) groups
2. Rigid bond restraints
 C20, C21
 with sigma for 1-2 distances of 0.02 and sigma for 1-3 distances of 0.02
 N2, C19
 with sigma for 1-2 distances of 0.002 and sigma for 1-3 distances of 0.002
3. Uiso/Uaniso restraints and constraints
C20 \\sim C21: within 2A with sigma of 0.005 and sigma for terminal atoms of
0.01
N2 \\sim C19: within 2A with sigma of 0.005 and sigma for terminal atoms of 0.01
4.a Ternary CH refined with riding coordinates:
 C15(H15)
4.b Secondary CH2 refined with riding coordinates:
 C8(H8A,H8B), C17(H17A,H17B), C19(H19A,H19B), C20(H20A,H20B), C21(H21A,H21B)
4.c Aromatic/amide H refined with riding coordinates:
 C3(H3), C4(H4A), C5(H5), C6(H6), C10(H10), C12(H12), C13(H13), C14(H14),
 C23(H23), C24(H24), C26(H26), C27(H27)
4.d Idealised Me refined as rotating group:
 C18(H18A,H18B,H18C), C28(H28A,H28B,H28C)
4.e Idealised tetrahedral OH refined as rotating group:
 O4(H4)
;
_shelx_res_checksum              22170
_shelx_hkl_checksum              31696
_olex2_date_sample_data_collection 2009-06-04
_olex2_submission_special_instructions 'No special instructions were received'
_oxdiff_exptl_absorpt_empirical_details
;
Empirical correction (ABSPACK) includes:
- Absorption correction using spherical harmonics
- Frame scaling
;
_oxdiff_exptl_absorpt_empirical_full_max 1.140
_oxdiff_exptl_absorpt_empirical_full_min 0.800