Synthesis of 2-Thio-Substituted 1,6-Diazabicyclo[3.2.1]octane Derivatives, Potent β-Lactamase Inhibitors.
Fujiu, Motohiro; Yokoo, Katsuki; Aoki, Toshiaki; Shibuya, Satoru; Sato, Jun; Komano, Kazuo; Kusano, Hiroki; Sato, Soichiro; Ogawa, Masayoshi; Yamawaki, Kenji; The Journal of organic chemistry  (2020) –; doi:10.1021/acs.joc.0c00980

data_4038594
_publ_section_title
;
 Synthesis of 2-Thio-Substituted 1,6-Diazabicyclo[3.2.1]octane
 Derivatives, Potent \b-Lactamase Inhibitors.
;
_journal_name_full               'The Journal of organic chemistry'
_journal_paper_doi               10.1021/acs.joc.0c00980
_journal_year                    2020
_chemical_absolute_configuration rmad
_chemical_formula_moiety         'C14 H18 N2 O3 S'
_chemical_formula_sum            'C14 H18 N2 O3 S'
_chemical_formula_weight         294.36
_space_group_crystal_system      monoclinic
_space_group_IT_number           5
_space_group_name_Hall           'C 2y'
_space_group_name_H-M_alt        'C 1 2 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2020-02-14
_audit_creation_method
;
Olex2 1.2-ac3
(compiled 2017.08.10 svn.r3458 for OlexSys, GUI svn.r5381)
;
_cell_angle_alpha                90
_cell_angle_beta                 101.089(4)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   20.2904(10)
_cell_length_b                   6.2175(3)
_cell_length_c                   11.6198(5)
_cell_measurement_reflns_used    6277
_cell_measurement_temperature    100
_cell_measurement_theta_max      73.4320
_cell_measurement_theta_min      3.8700
_cell_volume                     1438.53(12)
_computing_cell_refinement       'CrysAlisPro 1.171.39.46e (Rigaku OD, 2018)'
_computing_data_collection       'CrysAlisPro 1.171.39.46e (Rigaku OD, 2018)'
_computing_data_reduction        'CrysAlisPro 1.171.39.46e (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    'ShelXT (Sheldrick, 2015)'
_diffrn_ambient_temperature      100.0
_diffrn_detector                 'PLATUS 200K area detector'
_diffrn_detector_area_resol_mean 5.811
_diffrn_detector_type            'HPC area detector'
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.988
_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     16.00  44.00   0.50    0.50    --    5.00  18.00-150.00   56
  2  \w     50.00  92.00   0.50    0.50    --    5.00  18.00-150.00   84
  3  \w     67.00  92.00   0.50    0.50    --    5.00   0.00-120.00   50
  4  \w   -136.00 -47.00   0.50    0.50    --  -47.20  28.00-180.00  178
  5  \w    -43.00  35.00   0.50    0.50    --  -47.20  28.00-180.00  156
  6  \w   -120.00 -48.00   0.50    0.50    --  -47.20  55.00-120.00  144
  7  \w    -23.00  41.00   0.50    0.50    --  -47.20  55.00-120.00  128
  8  \w   -189.00-117.00   0.50    0.50    -- -100.90  28.00 120.00  144
  9  \w   -173.00-130.00   0.50    0.50    -- -100.90  54.00 174.40   86
 10  \w   -124.00 -87.00   0.50    0.50    -- -100.90  28.00  30.00   74
 11  \w   -185.00 -97.00   0.50    0.50    -- -100.90  28.00-120.00  176
 12  \w   -100.00 -12.00   0.50    0.50    -- -100.90  28.00 120.00  176
 13  \w    -38.00 -13.00   0.50    0.50    -- -100.90  46.00 120.00   50
 14  \w   -189.00 -15.00   0.50    0.50    -- -100.90  55.00-132.50  348
 15  \w   -183.00-148.00   0.50    0.50    -- -100.90  46.00 120.00   70
 16  \w    -48.00 -12.00   0.50    0.50    -- -100.90  46.00 -90.00   72
 17  \w    -39.00 -12.00   0.50    0.50    -- -100.90  37.00-120.00   54
 18  \w   -119.00 -83.00   0.50    0.50    -- -100.90  46.00 120.00   72
 19  \w   -178.00-137.00   0.50    0.50    -- -100.90  37.00-120.00   82
 20  \w   -186.00-153.00   0.50    0.50    -- -100.90  28.00  30.00   66
 21  \w   -138.00 -82.00   0.50    0.50    -- -100.90  46.00 -90.00  112
 22  \w    -52.00 -13.00   0.50    0.50    -- -100.90  28.00  30.00   78
 23  \w    -80.00 -18.00   0.50    0.50    -- -100.90  54.00 174.40  124
 24  \w   -103.00 -11.00   0.50    0.50    -- -100.90  54.00-121.33  184
 25  \w    -55.00 -12.00   0.50    0.50    -- -100.90  28.00-120.00   86
 26  \w   -172.00 -39.00   0.50    0.50    -- -100.90  55.00  95.68  266
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'Rigaku XtaLAB P200'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0251200000
_diffrn_orient_matrix_UB_12      0.0027337000
_diffrn_orient_matrix_UB_13      -0.1168548000
_diffrn_orient_matrix_UB_21      0.0208010000
_diffrn_orient_matrix_UB_22      0.2372307000
_diffrn_orient_matrix_UB_23      0.0214226000
_diffrn_orient_matrix_UB_31      0.0701729000
_diffrn_orient_matrix_UB_32      -0.0720140000
_diffrn_orient_matrix_UB_33      0.0641202000
_diffrn_radiation_monochromator  'multi-layer mirror optics'
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0236
_diffrn_reflns_av_unetI/netI     0.0207
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.988
_diffrn_reflns_limit_h_max       25
_diffrn_reflns_limit_h_min       -24
_diffrn_reflns_limit_k_max       7
_diffrn_reflns_limit_k_min       -7
_diffrn_reflns_limit_l_max       14
_diffrn_reflns_limit_l_min       -13
_diffrn_reflns_number            7080
_diffrn_reflns_point_group_measured_fraction_full 0.988
_diffrn_reflns_point_group_measured_fraction_max 0.958
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         73.965
_diffrn_reflns_theta_min         3.877
_diffrn_source                   'rotating anode X-ray generator'
_diffrn_source_type              micromax007
_exptl_absorpt_coefficient_mu    2.085
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.86064
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.39.46e (Rigaku Oxford Diffraction, 2018)
Empirical absorption correction using spherical harmonics,
 implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_density_diffrn    1.359
_exptl_crystal_description       plate
_exptl_crystal_F_000             624
_exptl_crystal_size_max          0.18
_exptl_crystal_size_mid          0.15
_exptl_crystal_size_min          0.1
_refine_diff_density_max         0.685
_refine_diff_density_min         -0.394
_refine_diff_density_rms         0.057
_refine_ls_abs_structure_details
;
 Flack x determined using 1166 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.01(3)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.048
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     182
_refine_ls_number_reflns         2798
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.048
_refine_ls_R_factor_all          0.0443
_refine_ls_R_factor_gt           0.0441
_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^)+(0.0408P)^2^+4.2349P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1070
_refine_ls_wR_factor_ref         0.1071
_reflns_Friedel_coverage         0.769
_reflns_Friedel_fraction_full    0.974
_reflns_Friedel_fraction_max     0.922
_reflns_number_gt                2772
_reflns_number_total             2798
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            jo0c00980_si_001.cif
_cod_data_source_block           x4143r3
_cod_database_code               4038594
_shelx_shelxl_version_number     2018/1
_chemical_oxdiff_formula         'C7 H12 N2 O3 S1'
_chemical_oxdiff_usercomment     -173C
_shelx_estimated_absorpt_t_max   0.819
_shelx_estimated_absorpt_t_min   0.705
_reflns_odcompleteness_completeness 99.86
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     68.13
_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
2.a Ternary CH refined with riding coordinates:
 C2(H2), C5(H5)
2.b Secondary CH2 refined with riding coordinates:
 C3(H3A,H3B), C8(H8A,H8B), C7(H7A,H7B), C4(H4A,H4B)
2.c Aromatic/amide H refined with riding coordinates:
 C14(H14), C10(H10), C13(H13), C12(H12), C11(H11)
2.d Idealised Me refined as rotating group:
 C1(H1A,H1B,H1C)
;
_shelx_res_checksum              84775
_shelx_hkl_checksum              88034
_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 1.199
_oxdiff_exptl_absorpt_empirical_full_min 0.825