Asymmetric construction of densely functionalized three-dimensional aza-tetracyclic scaffolds for drug discovery
Umedera, Kohei; Morita, Taiki; Nakamura, Hiroyuki; Chemical Communications  (2022) –; doi:10.1039/D2CC05700J

data_7131005
_publ_section_title
;
 Asymmetric construction of densely functionalized three-dimensional
 aza-tetracyclic scaffolds for drug discovery
;
_journal_name_full               'Chemical Communications'
_journal_paper_doi               10.1039/D2CC05700J
_journal_year                    2022
_chemical_formula_moiety         'Cl, C27 H31 N3 O3'
_chemical_formula_sum            'C27 H31 Cl N3 O3'
_chemical_formula_weight         481.00
_space_group_crystal_system      orthorhombic
_space_group_IT_number           19
_space_group_name_Hall           'P 2ac 2ab'
_space_group_name_H-M_alt        'P 21 21 21'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2022-06-22
_audit_creation_method
;
Olex2 1.3
(compiled 2020.11.12 svn.r5f609507 for OlexSys, GUI svn.r6408)
;
_audit_update_record
;
2022-10-15 deposited with the CCDC.	2022-11-14 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   6.18430(10)
_cell_length_b                   11.55650(10)
_cell_length_c                   34.6069(3)
_cell_measurement_reflns_used    12456
_cell_measurement_temperature    90
_cell_measurement_theta_max      76.5200
_cell_measurement_theta_min      4.0080
_cell_volume                     2473.32(5)
_computing_cell_refinement       'CrysAlisPro 1.171.42.57a (Rigaku OD, 2022)'
_computing_data_collection       'CrysAlisPro 1.171.42.57a (Rigaku OD, 2022)'
_computing_data_reduction        'CrysAlisPro 1.171.42.57a (Rigaku OD, 2022)'
_computing_molecular_graphics    'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2018/3 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2018/2 (Sheldrick, 2018)'
_diffrn_ambient_temperature      90
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            HyPix
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.982
_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     35.00 118.00   0.50    0.20    --   47.66  57.00  60.00  166
  2  \w     89.00 148.00   0.50    0.80    --  102.75 111.00 145.00  118
  3  \w     98.00 171.00   0.50    0.80    --  102.75  45.00 -30.00  146
  4  \w     79.00 105.00   0.50    0.80    --  102.75 -77.00  30.00   52
  5  \w     34.00  59.00   0.50    0.80    --  102.75 -77.00  30.00   50
  6  \w     37.00  62.00   0.50    0.80    --  102.75 -61.00  90.00   50
  7  \w     36.00  64.00   0.50    0.80    --  102.75 -61.00 120.00   56
  8  \w     42.00 102.00   0.50    0.80    --  102.75 -77.00 120.00  120
  9  \w     44.00 104.00   0.50    0.80    --  102.75-125.00  90.00  120
 10  \w    -39.00  25.00   0.50    0.20    --  -47.66  37.00-180.00  128
 11  \w    -61.00 -31.00   0.50    0.80    -- -102.75  61.00 -90.00   60
 12  \w    -66.00 -34.00   0.50    0.80    -- -102.75  61.00   0.00   64
 13  \w    -67.00 -34.00   0.50    0.80    -- -102.75  61.00  30.00   66
 14  \w    -26.00  23.00   0.50    0.20    --  -47.66  19.00  60.00   98
 15  \w    -66.00 -35.00   0.50    0.80    -- -102.75  61.00 120.00   62
 16  \w    -73.00 -22.00   0.50    0.20    --  -47.66 111.00 145.00  102
 17  \w   -163.00 -99.00   0.50    0.80    -- -102.75 -35.00 134.00  128
 18  \w   -173.00 -85.00   0.50    0.80    -- -102.75 -91.00 -53.00  176
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB Synergy R, DW system, HyPix'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0935696000
_diffrn_orient_matrix_UB_12      -0.0199199000
_diffrn_orient_matrix_UB_13      -0.0407127000
_diffrn_orient_matrix_UB_21      0.0602126000
_diffrn_orient_matrix_UB_22      0.1291225000
_diffrn_orient_matrix_UB_23      -0.0026239000
_diffrn_orient_matrix_UB_31      0.2228971000
_diffrn_orient_matrix_UB_32      -0.0265764000
_diffrn_orient_matrix_UB_33      0.0177880000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0446
_diffrn_reflns_av_unetI/netI     0.0344
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.982
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -6
_diffrn_reflns_limit_k_max       14
_diffrn_reflns_limit_k_min       -14
_diffrn_reflns_limit_l_max       42
_diffrn_reflns_limit_l_min       -43
_diffrn_reflns_number            15784
_diffrn_reflns_point_group_measured_fraction_full 0.996
_diffrn_reflns_point_group_measured_fraction_max 0.962
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         76.681
_diffrn_reflns_theta_min         2.554
_diffrn_source                   'Rotating-anode X-ray tube'
_diffrn_source_type              'Rigaku (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    1.636
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.52945
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.42.57a (Rigaku Oxford Diffraction, 2022)
Empirical absorption correction using spherical harmonics,
implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'clear light colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_modifier   light
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.292
_exptl_crystal_description       block
_exptl_crystal_F_000             1020
_exptl_crystal_size_max          0.193
_exptl_crystal_size_mid          0.082
_exptl_crystal_size_min          0.047
_refine_diff_density_max         1.925
_refine_diff_density_min         -0.421
_refine_diff_density_rms         0.109
_refine_ls_abs_structure_details
;
 Flack x determined using 1828 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.020(19)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.054
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     384
_refine_ls_number_reflns         5034
_refine_ls_number_restraints     738
_refine_ls_restrained_S_all      1.030
_refine_ls_R_factor_all          0.0946
_refine_ls_R_factor_gt           0.0934
_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^)+(0.1506P)^2^+6.4678P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.2541
_refine_ls_wR_factor_ref         0.2563
_reflns_Friedel_coverage         0.692
_reflns_Friedel_fraction_full    0.991
_reflns_Friedel_fraction_max     0.933
_reflns_number_gt                4922
_reflns_number_total             5034
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d2cc05700j2.cif
_cod_data_source_block           crl41-1740_autored
_cod_database_code               7131005
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         C27H31N3O3
_shelx_estimated_absorpt_t_max   0.927
_shelx_estimated_absorpt_t_min   0.743
_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 C(H,H,H,H) groups, All N(H) groups
 At 1.5 times of:
  All O(H) groups
2. Uiso/Uaniso restraints and constraints
All non-hydrogen atoms have similar U: within 2A with sigma of 0.01 and sigma
for terminal atoms of 0.02 within 2A
N7: within 2A with sigma of 0.001 and sigma for terminal atoms of 0.002 within
2A
All non-hydrogen atoms restrained to be isotropic: with sigma of 0.01 and sigma
for terminal atoms of 0.02
Uanis(N7) \\sim Ueq: with sigma of 0.001 and sigma for terminal atoms of 0.002
3. Others
 Sof(H00P)=Sof(H00Q)=Sof(C32)=Sof(H32)=Sof(O6)=Sof(C22)=Sof(C24)=Sof(H24A)=
 Sof(H24B)=Sof(N7)=Sof(H7)=Sof(C25)=Sof(H25)=Sof(C26)=Sof(H26)=Sof(C27)=
 Sof(H27)=Sof(C28)=Sof(H28)=Sof(C29)=Sof(H29)=Sof(C30)=1-FVAR(1)
 Sof(H00N)=Sof(H00O)=Sof(C31)=Sof(H31)=Sof(O5)=Sof(C13)=Sof(N6)=Sof(H6)=
 Sof(C15)=Sof(H15A)=Sof(H15B)=Sof(C16)=Sof(C17)=Sof(H17)=Sof(C18)=Sof(H18)=
 Sof(C19)=Sof(H19)=Sof(C20)=Sof(H20)=Sof(C21)=Sof(H21)=FVAR(1)
4.a Ternary CH refined with riding coordinates:
 C008(H008), C009(H009), C00B(H00B), C00D(H00D), C00F(H00G), C31(H31), C32(H32)
4.b Secondary CH2 refined with riding coordinates:
 C00C(H00A,H00C), C00E(H00E,H00F), C00I(H00J,H00K), C00J(H00L,H00M), C00K(H00N,
 H00O), C00K(H00P,H00Q), C15(H15A,H15B), C24(H24A,H24B)
4.c Aromatic/amide H refined with riding coordinates:
 N8(H8), C00G(H00H), C00H(H00I), C00L(H00R), C00O(H00S), C00P(H00T), N6(H6),
 C17(H17), C18(H18), C19(H19), C20(H20), C21(H21), N7(H7), C25(H25), C26(H26),
 C27(H27), C28(H28), C29(H29)
4.d Fitted hexagon refined as free rotating group:
 C16(C17,C18,C19,C20,C21), C25(C26,C27,C28,C29,C30)
4.e Idealised tetrahedral OH refined as rotating group:
 O002(H002)
;
_shelx_res_checksum              43024
_shelx_hkl_checksum              47526
_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 1.596
_oxdiff_exptl_absorpt_empirical_full_min 0.706