Route exploration and synthesis of the reported pyridone-based PDI inhibitor STK076545.
Greve, Eric; Lindeman, Sergey V.; Scartelli, Christina; Lin, Lin; Flaumenhaft, Robert; Dockendorff, Chris; Organic & biomolecular chemistry 18 (2020) 6665–6681; doi:10.1039/d0ob01205j

data_7157663
_publ_section_title
;
 Route exploration and synthesis of the reported pyridone-based PDI
 inhibitor STK076545.
;
_journal_issue                   34
_journal_name_full               'Organic &amp; biomolecular chemistry'
_journal_page_first              6665
_journal_page_last               6681
_journal_paper_doi               10.1039/d0ob01205j
_journal_volume                  18
_journal_year                    2020
_chemical_formula_moiety         'C20 H25 N3 O3'
_chemical_formula_sum            'C20 H25 N3 O3'
_chemical_formula_weight         355.43
_space_group_crystal_system      monoclinic
_space_group_IT_number           14
_space_group_name_Hall           '-P 2ybc'
_space_group_name_H-M_alt        'P 1 21/c 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     iterative
_audit_creation_date             2019-12-12
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_audit_update_record
;
2020-05-14 deposited with the CCDC.	2020-08-13 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 112.379(2)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   13.9620(3)
_cell_length_b                   8.28868(13)
_cell_length_c                   17.5984(3)
_cell_measurement_reflns_used    8540
_cell_measurement_temperature    101(2)
_cell_measurement_theta_max      70.4890
_cell_measurement_theta_min      5.1810
_cell_volume                     1883.22(7)
_computing_cell_refinement       'CrysAlisPro 1.171.39.46 (Rigaku OD, 2018)'
_computing_data_collection       'CrysAlisPro 1.171.39.46 (Rigaku OD, 2018)'
_computing_data_reduction        'CrysAlisPro 1.171.39.46 (Rigaku OD, 2018)'
_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    'olex2.solve (Bourhis et al., 2015)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      101(2)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 10.3756
_diffrn_detector_type            Atlas
_diffrn_measured_fraction_theta_full 0.985
_diffrn_measured_fraction_theta_max 0.985
_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   -117.00 -18.00   0.50    1.00    --  -42.46 -37.00   0.00  198
  2  \w    -92.00  -2.00   0.50    1.00    --  -42.46 125.00-180.00  180
  3  \w   -117.00 -18.00   0.50    1.00    --  -42.46 -37.00  90.00  198
  4  \w     22.00  97.00   0.50    1.00    --   42.46-123.00 -74.00  150
  5  \w     74.00 173.00   0.50    4.00    --  100.00  45.00-150.00  198
  6  \w     24.00 128.00   0.50    4.00    --  100.00 -30.00  90.00  208
  7  \w     27.00 126.00   0.50    4.00    --  100.00 -45.00 -60.00  198
  8  \w     94.00 173.00   0.50    4.00    --  100.00 125.00 -60.00  158
  9  \w     17.00 110.00   0.50    4.00    --  100.00 -94.00   0.00  186
 10  \w     17.00 110.00   0.50    4.00    --  100.00 -94.00 -90.00  186
 11  \w     71.00 172.00   0.50    4.00    --  100.00  61.00  90.00  202
 12  \w    -92.00  -2.00   0.50    1.00    --  -42.46 125.00  60.00  180
 13  \w   -115.00 -14.00   0.50    1.00    --  -42.46 -57.00 -90.00  202
 14  \w   -119.00 -10.00   0.50    1.00    --  -42.46 -77.00-150.00  218
 15  \w     71.00  98.00   0.50    4.00    --  100.00  61.00 150.00   54
 16  \w     74.00 173.00   0.50    4.00    --  100.00  45.00  30.00  198
 17  \w     74.00 173.00   0.50    4.00    --  100.00  45.00 -90.00  198
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at home/near, Atlas'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0195464000
_diffrn_orient_matrix_UB_12      0.1522267000
_diffrn_orient_matrix_UB_13      -0.0422453000
_diffrn_orient_matrix_UB_21      0.0449728000
_diffrn_orient_matrix_UB_22      -0.1054571000
_diffrn_orient_matrix_UB_23      -0.0505223000
_diffrn_orient_matrix_UB_31      -0.1087757000
_diffrn_orient_matrix_UB_32      -0.0161763000
_diffrn_orient_matrix_UB_33      -0.0679837000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0241
_diffrn_reflns_av_unetI/netI     0.0149
_diffrn_reflns_Laue_measured_fraction_full 0.985
_diffrn_reflns_Laue_measured_fraction_max 0.985
_diffrn_reflns_limit_h_max       16
_diffrn_reflns_limit_h_min       -16
_diffrn_reflns_limit_k_max       10
_diffrn_reflns_limit_k_min       -9
_diffrn_reflns_limit_l_max       21
_diffrn_reflns_limit_l_min       -21
_diffrn_reflns_number            17568
_diffrn_reflns_point_group_measured_fraction_full 0.985
_diffrn_reflns_point_group_measured_fraction_max 0.985
_diffrn_reflns_theta_full        70.471
_diffrn_reflns_theta_max         70.471
_diffrn_reflns_theta_min         3.423
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.689
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.414
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.39.46 (Rigaku Oxford Diffraction, 2018)
Numerical absorption correction based on gaussian integration over
			a multifaceted crystal model
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.254
_exptl_crystal_description       block
_exptl_crystal_F_000             760
_exptl_crystal_size_max          0.485
_exptl_crystal_size_mid          0.258
_exptl_crystal_size_min          0.175
_refine_diff_density_max         0.291
_refine_diff_density_min         -0.475
_refine_diff_density_rms         0.045
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.056
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     326
_refine_ls_number_reflns         3541
_refine_ls_number_restraints     14
_refine_ls_restrained_S_all      1.054
_refine_ls_R_factor_all          0.0524
_refine_ls_R_factor_gt           0.0479
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0684P)^2^+0.7578P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1260
_refine_ls_wR_factor_ref         0.1307
_reflns_Friedel_coverage         0.000
_reflns_number_gt                3156
_reflns_number_total             3541
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d0ob01205j2.cif
_cod_data_source_block           dock1o
_cod_depositor_comments
'Adding full bibliography for 7157660--7157663.cif.'
_cod_database_code               7157663
_shelx_shelxl_version_number     2018/1
_chemical_oxdiff_formula         'C20 H25 N3 O3'
_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 C(H,H,H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2. Rigid bond restraints
 C5, C6, C7, C8, C9
 with sigma for 1-2 distances of 0.01 and sigma for 1-3 distances of 0.01
 C5A, C6A, C7A, C8A, C9A
 with sigma for 1-2 distances of 0.01 and sigma for 1-3 distances of 0.01
3. Uiso/Uaniso restraints and constraints
Uanis(C5) = Uanis(C5A)
4. Others
 Fixed Sof: N3(0.5) N3A(0.5) C5(0.5) H5(0.5) C5A(0.5) H5A(0.5) C6(0.5) H6(0.5)
 C6A(0.5) H6A(0.5) C7(0.5) H7(0.5) C7A(0.5) H7A(0.5) C8(0.5) H8(0.5) C8A(0.5)
 H8A(0.5) C9(0.5) H9(0.5) C9A(0.5) H9A(0.5) H15A(0.5) H15B(0.5) H15C(0.5)
 H15D(0.5) C16(0.5) H16A(0.5) H16B(0.5) C16A(0.5) H16C(0.5) H16D(0.5) C17(0.5)
 H17A(0.5) H17B(0.5) C17A(0.5) H17C(0.5) H17D(0.5) C18(0.5) H18A(0.5) H18B(0.5)
 H18C(0.5) C18A(0.5) H18D(0.5) H18E(0.5) H18F(0.5) C19(0.5) H19A(0.5) H19B(0.5)
 C19A(0.5) H19C(0.5) H19D(0.5) C20(0.5) H20A(0.5) H20B(0.5) H20C(0.5) C20A(0.5)
 H20D(0.5) H20E(0.5) H20F(0.5)
5.a Ternary CH refined with riding coordinates:
 C1(H1)
5.b Secondary CH2 refined with riding coordinates:
 C15(H15A,H15B), C15(H15C,H15D), C16(H16A,H16B), C16A(H16C,H16D), C17(H17A,
 H17B), C17A(H17C,H17D), C19(H19A,H19B), C19A(H19C,H19D)
5.c Aromatic/amide H refined with riding coordinates:
 C5(H5), C5A(H5A), C6(H6), C6A(H6A), C7(H7), C7A(H7A), C8(H8), C8A(H8A),
 C9(H9), C9A(H9A), C11(H11), C12(H12), C13(H13), C14(H14)
5.d Idealised Me refined as rotating group:
 C18(H18A,H18B,H18C), C18A(H18D,H18E,H18F), C20(H20A,H20B,H20C), C20A(H20D,
 H20E,H20F)
;
_olex2_date_sample_data_collection 2019-12-11
_olex2_date_sample_submission    2019-12-11
_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 3.608
_oxdiff_exptl_absorpt_empirical_full_min 0.763