Stereoselective synthesis of conformationally restricted KOR agonists based on the 2,5-diazabicyclo[2.2.2]octane scaffold
Wuensch, Bernhard; Wittig, Christian; Schepmann, Dirk; Soeberdt, Michael; Daniliuc, Constantin Gabriel; Org. Biomol. Chem.  (2017) –; doi:10.1039/C7OB01530E

data_7155778
_publ_section_title
;
 Stereoselective synthesis of conformationally restricted KOR agonists
 based on the 2,5-diazabicyclo[2.2.2]octane scaffold
;
_journal_name_full               'Org. Biomol. Chem.'
_journal_paper_doi               10.1039/C7OB01530E
_journal_year                    2017
_chemical_formula_sum            'C26 H27 Cl4 N3 O2'
_chemical_formula_weight         555.30
_space_group_crystal_system      monoclinic
_space_group_IT_number           13
_space_group_name_Hall           '-P 2yc'
_space_group_name_H-M_alt        'P 1 2/c 1'
_symmetry_space_group_name_Hall  '-P 2yc'
_symmetry_space_group_name_H-M   'P 1 2/c 1'
_atom_sites_solution_hydrogens   geom
_audit_update_record
;
2017-04-27 deposited with the CCDC.
2017-07-18 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 93.5410(10)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   24.6806(6)
_cell_length_b                   6.2455(2)
_cell_length_c                   16.1174(4)
_cell_measurement_reflns_used    9893
_cell_measurement_temperature    100.(2)
_cell_measurement_theta_max      68.2582
_cell_measurement_theta_min      3.5884
_cell_volume                     2479.64(12)
_computing_cell_refinement       'SAINT V8.34A (Bruker AXS Inc., 2013)'
_computing_data_collection
;
APEX2 v.2014.1-1 (Bruker AXS Inc., 2014)

;
_computing_data_reduction        'SAINT V8.34A (Bruker AXS Inc., 2013)'
_computing_molecular_graphics    'XP (Sheldrick, 2014)'
_computing_publication_material  'SHELXL-2014 (Sheldrick, 2014)'
_computing_structure_refinement  'SHELXL-2014/7 (Sheldrick, 2014)'
_computing_structure_solution    'SHELXL-2014 (Sheldrick, 2014)'
_diffrn_ambient_temperature      100.(2)
_diffrn_detector_area_resol_mean 10.4167
_diffrn_measured_fraction_theta_full 0.998
_diffrn_measured_fraction_theta_max 0.998
_diffrn_measurement_device_type  'Bruker D8 Venture PHOTON 100 CMOS'
_diffrn_measurement_method       'omega and phi scans'
_diffrn_radiation_monochromator  'MX mirror'
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0860
_diffrn_reflns_av_unetI/netI     0.0468
_diffrn_reflns_limit_h_max       29
_diffrn_reflns_limit_h_min       -29
_diffrn_reflns_limit_k_max       7
_diffrn_reflns_limit_k_min       -7
_diffrn_reflns_limit_l_max       19
_diffrn_reflns_limit_l_min       -19
_diffrn_reflns_number            31737
_diffrn_reflns_theta_full        68.36
_diffrn_reflns_theta_max         68.36
_diffrn_reflns_theta_min         3.59
_diffrn_source                   'Cu ImS'
_diffrn_source_type              'micro focus tube'
_exptl_absorpt_coefficient_mu    4.588
_exptl_absorpt_correction_T_max  0.93
_exptl_absorpt_correction_T_min  0.68
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
Bruker AXS (2014). SADABS, Version 2014/2, Bruker AXS Inc., Madison, Wisconsin,
USA.
;
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.487
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       needle
_exptl_crystal_F_000             1152
_exptl_crystal_size_max          0.228
_exptl_crystal_size_mid          0.051
_exptl_crystal_size_min          0.015
_refine_diff_density_max         0.618
_refine_diff_density_min         -0.443
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.055
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     316
_refine_ls_number_reflns         4563
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.055
_refine_ls_R_factor_all          0.0793
_refine_ls_R_factor_gt           0.0551
_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^)+(0.0644P)^2^+3.0587P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1299
_refine_ls_wR_factor_ref         0.1425
_reflns_number_gt                3427
_reflns_number_total             4563
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c7ob01530e2.cif
_cod_data_source_block           dan8093
_cod_database_code               7155778
_shelx_res_checksum              87339