A Vending Machine for Drug-like Molecules - Automated Synthesis of Virtual Screening Hits
McMillan, Angus E.; Wu, Wilson W. X.; Nichols, Paula L.; Wanner, Benedikt M.; Bode, Jeffrey W.; Chemical Science  (2022) –; doi:10.1039/D2SC05182F

data_1567873
_publ_section_title
;
 A Vending Machine for Drug-like Molecules - Automated Synthesis of
 Virtual Screening Hits
;
_journal_name_full               'Chemical Science'
_journal_paper_doi               10.1039/D2SC05182F
_journal_year                    2022
_chemical_formula_moiety         'C18 H25 Cl N2 O'
_chemical_formula_sum            'C18 H25 Cl N2 O'
_chemical_formula_weight         320.85
_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     dual
_audit_creation_date             2020-09-18
_audit_creation_method
;
Olex2 1.3
(compiled 2020.07.31 svn.rc2a77460 for OlexSys, GUI svn.r6145)
;
_audit_update_record
;
2022-04-28 deposited with the CCDC.	2022-10-28 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 94.6950(10)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   6.01210(10)
_cell_length_b                   24.36780(10)
_cell_length_c                   11.42100(10)
_cell_measurement_reflns_used    32882
_cell_measurement_temperature    100.0(1)
_cell_measurement_theta_max      79.5890
_cell_measurement_theta_min      3.6180
_cell_volume                     1667.58(3)
_computing_cell_refinement       'CrysAlisPro 1.171.40.68a (Rigaku OD, 2019)'
_computing_data_collection       'CrysAlisPro 1.171.40.68a (Rigaku OD, 2019)'
_computing_data_reduction        'CrysAlisPro 1.171.40.68a (Rigaku OD, 2019)'
_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 2014/4 (Sheldrick, 2014)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      100.0(1)
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 5.8140
_diffrn_detector_type            'Pilatus 300K'
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.991
_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    -86.00 -39.00   0.50    0.10    --  -48.87 -38.00   0.00   94
  2  \w    -64.00 -33.00   0.50    0.10    --  -48.87 -57.00   0.00   62
  3  \w    -91.00 -57.00   0.50    0.10    --  -48.87 -77.00 -60.00   68
  4  \w    -50.00 -25.00   0.50    0.10    --  -48.87 -77.00 -60.00   50
  5  \w    -62.00  22.00   0.50    0.10    --  -48.87  57.00  90.00  168
  6  \w    -99.00 -37.00   0.50    0.10    --  -48.87 -38.00  60.00  124
  7  \w    -87.00 -33.00   0.50    0.10    --  -48.87 -57.00 150.00  108
  8  \w     25.00  60.00   0.50    0.10    --   48.87  77.00-150.00   70
  9  \w     83.00 108.00   0.50    0.10    --   48.87  77.00-150.00   50
 10  \w     33.00  63.00   0.50    0.10    --   48.87  57.00-150.00   60
 11  \w     39.00  85.00   0.50    0.10    --   48.87  38.00-180.00   92
 12  \w     25.00  56.00   0.50    0.10    --   48.87  77.00-180.00   62
 13  \w     25.00  51.00   0.50    0.10    --   48.87  77.00  90.00   52
 14  \w     90.00 116.00   0.50    0.10    --   48.87  19.00 150.00   52
 15  \w     25.00  55.00   0.50    0.10    --   48.87  77.00 -30.00   60
 16  \w     63.00 119.00   0.50    0.10    --   48.87 178.00 -90.00  112
 17  \w     70.00 118.00   0.50    0.10    --   48.87-178.00 120.00   96
 18  \w     38.00  88.00   0.50    0.10    --   48.87  19.00 150.00  100
 19  \w     34.00  59.00   0.50    0.10    --   58.00  79.00 -50.07   50
 20  \w     33.00  64.00   0.50    0.10    --   58.00  80.00   4.48   62
 21  \w     33.00  59.00   0.50    0.10    --   58.00  80.00 -85.64   52
 22  \w     98.00 123.00   0.50    0.10    --   62.00  79.00-144.07   50
 23  \w     38.00  63.00   0.50    0.10    --   62.00  78.00 108.53   50
 24  \w     38.00  64.00   0.50    0.10    --   62.00  79.00-144.07   52
 25  \w    -75.00 -46.00   0.50    0.14    --  -70.00 -77.00  48.48   58
 26  \w    -85.00 -19.00   0.50    0.14    --  -70.00 125.00-120.00  132
 27  \w     45.00  75.00   0.50    0.10    --   70.00  80.00-152.93   60
 28  \w    110.00 136.00   0.50    0.10    --   70.00  80.00-152.93   52
 29  \w    -83.00 -48.00   0.50    0.14    --  -70.00 -77.00 -60.00   70
 30  \w     91.00 117.00   0.50    0.10    --   70.00  80.00 162.99   52
 31  \w    -72.00 -47.00   0.50    0.14    --  -70.00 -76.00-137.39   50
 32  \w     45.00  70.00   0.50    0.10    --   70.00  80.00 162.99   50
 33  \w    -99.00 -46.00   0.50    0.14    --  -70.00 -78.00  98.50  106
 34  \w    -73.00 -46.00   0.50    0.14    --  -70.00 -78.00-170.79   54
 35  \w    -72.00 -46.00   0.50    0.14    --  -70.00 -79.00 142.71   52
 36  \w     48.00  79.00   0.50    0.10    --   70.00  76.00  35.06   62
 37  \w     48.00  77.00   0.50    0.10    --   70.00  73.00  18.83   58
 38  \w    -73.00 -47.00   0.50    0.14    --  -70.00 -75.00-117.79   52
 39  \w    -74.00 -46.00   0.50    0.14    --  -70.00 -77.00 -30.00   56
 40  \w   -135.00-108.00   0.50    0.14    --  -70.00 -78.00  98.50   54
 41  \w    -73.00 -46.00   0.50    0.14    --  -70.00 -77.00  31.90   54
 42  \w    -71.00 -46.00   0.50    0.14    --  -70.00 -78.00  65.71   50
 43  \w   -135.00 -98.00   0.50    0.14    --  -70.00 -77.00  31.90   74
 44  \w    -81.00 -46.00   0.50    0.14    --  -70.00 -78.00 118.56   70
 45  \w     54.00  91.00   0.50    0.10    --   74.00  72.00 142.31   74
 46  \w     89.00 131.00   0.50    0.10    --   74.00  75.00 -85.10   84
 47  \w     53.00  85.00   0.50    0.10    --   74.00  75.00 -85.10   64
 48  \w    115.00 140.00   0.50    0.10    --   74.00  72.00 142.31   50
 49  \w    118.00 159.00   0.50    0.14    --   90.00  51.00 118.61   82
 50  \w     76.00 105.00   0.50    0.14    --   90.00  51.00 118.61   58
 51  \w    128.00 167.00   0.50    0.14    --   94.00  53.00  28.51   78
 52  \w     81.00 112.00   0.50    0.14    --   94.00  53.00  28.51   62
 53  \w     39.00 113.00   0.50    0.14    --  110.00-125.00-150.00  148
 54  \w     90.00 116.00   0.50    0.14    --  110.00 -77.00 -30.00   52
 55  \w     47.00  80.00   0.50    0.14    --  110.00 -77.00 -30.00   66
 56  \w     86.00 113.00   0.50    0.14    --  110.00  77.00 -60.00   54
 57  \w     96.00 178.00   0.50    0.14    --  110.00  57.00   0.00  164
 58  \w    116.00 155.00   0.50    0.14    --  110.00  38.00-120.00   78
 59  \w     41.00  92.00   0.50    0.14    --  110.00 -99.00 -90.00  102
 60  \w    101.00 150.00   0.50    0.14    --  110.00  38.00  90.00   98
 61  \w     96.00 132.00   0.50    0.14    --  110.00  57.00-150.00   72
 62  \w     58.00 110.00   0.50    0.14    --  110.00-113.00  63.67  104
 63  \w    139.00 168.00   0.50    0.14    --  110.00  77.00 120.00   58
 64  \w     86.00 126.00   0.50    0.14    --  110.00  77.00 120.00   80
 65  \w    147.00 173.00   0.50    0.14    --  110.00  77.00  30.00   52
 66  \w     87.00 112.00   0.50    0.14    --  110.00  77.00  30.00   50
 67  \w     99.00 127.00   0.50    0.14    --  110.00  38.00-180.00   56
 68  \w     50.00  76.00   0.50    0.14    --  110.00-125.00-120.00   52
 69  \w     81.00 106.00   0.50    0.14    --  110.00 -99.00 -30.00   50
 70  \w     40.00  75.00   0.50    0.14    --  110.00 -99.00 -30.00   70
 71  \w     88.00 113.00   0.50    0.14    --  110.00-125.00 -90.00   50
 72  \w     57.00  82.00   0.50    0.14    --  110.00-125.00 -90.00   50
 73  \w     88.00 114.00   0.50    0.14    --  110.00  77.00  90.00   52
 74  \w     96.00 153.00   0.50    0.14    --  110.00  57.00 -30.00  114
 75  \w     86.00 176.00   0.50    0.14    --  110.00  77.00-150.00  180
 76  \w    123.00 176.00   0.50    0.14    --  110.00  77.00 150.00  106
 77  \w     86.00 112.00   0.50    0.14    --  110.00  77.00 150.00   52
 78  \w     61.00 112.00   0.50    0.14    --  110.00-125.00 150.00  102
 79  \w    142.00 170.00   0.50    0.14    --  110.00  77.00 -30.00   56
 80  \w     86.00 112.00   0.50    0.14    --  110.00  77.00 -30.00   52
 81  \w     90.00 176.00   0.50    0.14    --  110.00  77.00-120.00  172
 82  \w     96.00 122.00   0.50    0.14    --  110.00  57.00 120.00   52
 83  \w     88.00 113.00   0.50    0.14    --  110.00-125.00   0.00   50
 84  \w    130.00 168.00   0.50    0.14    --  110.00  77.00  90.00   76
 85  \w     99.00 125.00   0.50    0.14    --  110.00  38.00-150.00   52
 86  \w     98.00 158.00   0.50    0.14    --  110.00  57.00 -60.00  120
 87  \w    131.00 175.00   0.50    0.14    --  110.00  77.00 -90.00   88
 88  \w     98.00 128.00   0.50    0.14    --  110.00  38.00 -60.00   60
 89  \w     86.00 112.00   0.50    0.14    --  110.00  77.00 -90.00   52
 90  \w     88.00 113.00   0.50    0.14    --  110.00-125.00-120.00   50
 91  \w     96.00 125.00   0.50    0.14    --  110.00  57.00  30.00   58
 92  \w     86.00 167.00   0.50    0.14    --  110.00  77.00-180.00  162
 93  \w    149.00 178.00   0.50    0.14    --  110.00  57.00  60.00   58
 94  \w    101.00 141.00   0.50    0.14    --  110.00  57.00  60.00   80
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB Synergy, Dualflex, Pilatus 300K'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0197729000
_diffrn_orient_matrix_UB_12      0.0630168000
_diffrn_orient_matrix_UB_13      0.0041581000
_diffrn_orient_matrix_UB_21      0.0115053000
_diffrn_orient_matrix_UB_22      -0.0017783000
_diffrn_orient_matrix_UB_23      0.1352072000
_diffrn_orient_matrix_UB_31      0.2560603000
_diffrn_orient_matrix_UB_32      -0.0047746000
_diffrn_orient_matrix_UB_33      0.0047302000
_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  0.0378
_diffrn_reflns_av_unetI/netI     0.0149
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.991
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -6
_diffrn_reflns_limit_k_max       31
_diffrn_reflns_limit_k_min       -31
_diffrn_reflns_limit_l_max       14
_diffrn_reflns_limit_l_min       -14
_diffrn_reflns_number            45091
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 0.991
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         80.091
_diffrn_reflns_theta_min         3.628
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    2.045
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.549
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.40.68a (Rigaku Oxford Diffraction, 2019)
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            'clear colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.278
_exptl_crystal_description       block
_exptl_crystal_F_000             688
_exptl_crystal_recrystallization_method 'Vapour deposition'
_exptl_crystal_size_max          0.247
_exptl_crystal_size_mid          0.212
_exptl_crystal_size_min          0.088
_refine_diff_density_max         0.289
_refine_diff_density_min         -0.257
_refine_diff_density_rms         0.044
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.074
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     205
_refine_ls_number_reflns         3611
_refine_ls_number_restraints     2
_refine_ls_restrained_S_all      1.074
_refine_ls_R_factor_all          0.0319
_refine_ls_R_factor_gt           0.0309
_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^)+(0.0399P)^2^+0.5885P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0810
_refine_ls_wR_factor_ref         0.0817
_reflns_Friedel_coverage         0.000
_reflns_number_gt                3450
_reflns_number_total             3611
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d2sc05182f2.cif
_cod_data_source_block           jb190920_1_1
_cod_database_code               1567873
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         C18H25ClN2O
_reflns_odcompleteness_completeness 99.97
_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 N(H) groups
2. Restrained distances
 N1-H1 = N2-H2
 0.93 with sigma of 0.02
3.a Ternary CH refined with riding coordinates:
 C7(H7), C12(H12), C16(H16)
3.b Secondary CH2 refined with riding coordinates:
 C8(H8A,H8B), C10(H10A,H10B), C11(H11A,H11B), C13(H13A,H13B), C14(H14A,H14B),
 C15(H15A,H15B), C17(H17A,H17B), C18(H18A,H18B)
3.c Aromatic/amide H refined with riding coordinates:
 C2(H2A), C3(H3), C4(H4), C5(H5)
;
_shelx_res_checksum              1
_olex2_submission_original_sample_id jb190920_1_1
_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 1.340
_oxdiff_exptl_absorpt_empirical_full_min 0.745