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_7155777
_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_absolute_configuration ad
_chemical_formula_sum            'C24 H27 N3 O2'
_chemical_formula_weight         389.48
_space_group_crystal_system      tetragonal
_space_group_IT_number           78
_space_group_name_Hall           'P 4cw'
_space_group_name_H-M_alt        'P 43'
_symmetry_space_group_name_Hall  'P 4cw'
_symmetry_space_group_name_H-M   'P 43'
_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                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   13.7270(3)
_cell_length_b                   13.7270(3)
_cell_length_c                   10.9453(3)
_cell_measurement_reflns_used    9895
_cell_measurement_temperature    100.(2)
_cell_measurement_theta_max      68.2882
_cell_measurement_theta_min      5.1684
_cell_volume                     2062.43(9)
_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 0.994
_diffrn_measured_fraction_theta_max 0.994
_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  0.0259
_diffrn_reflns_av_unetI/netI     0.0175
_diffrn_reflns_limit_h_max       16
_diffrn_reflns_limit_h_min       -15
_diffrn_reflns_limit_k_max       16
_diffrn_reflns_limit_k_min       -16
_diffrn_reflns_limit_l_max       13
_diffrn_reflns_limit_l_min       -11
_diffrn_reflns_number            25621
_diffrn_reflns_theta_full        68.39
_diffrn_reflns_theta_max         68.39
_diffrn_reflns_theta_min         3.22
_diffrn_source                   'Cu ImS'
_diffrn_source_type              'micro focus tube'
_exptl_absorpt_coefficient_mu    0.640
_exptl_absorpt_correction_T_max  0.92
_exptl_absorpt_correction_T_min  0.84
_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    1.254
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       prism
_exptl_crystal_F_000             832
_exptl_crystal_size_max          0.288
_exptl_crystal_size_mid          0.266
_exptl_crystal_size_min          0.142
_refine_diff_density_max         0.107
_refine_diff_density_min         -0.156
_refine_ls_abs_structure_details
;
Flack x determined using 1598 quotients [(I+)-(I-)]/[(I+)+(I-)]
(Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.01(5)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.103
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     262
_refine_ls_number_reflns         3636
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.103
_refine_ls_R_factor_all          0.0267
_refine_ls_R_factor_gt           0.0260
_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^)+(0.0340P)^2^+0.3333P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0636
_refine_ls_wR_factor_ref         0.0643
_reflns_number_gt                3579
_reflns_number_total             3636
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c7ob01530e2.cif
_cod_data_source_block           dan8114
_cod_original_cell_volume        2062.43(11)
_cod_database_code               7155777
_shelx_res_checksum              83634