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_1567875
_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 H27 Cl N2 O, 2(C2 F3 O2)'
_chemical_formula_sum            'C22 H27 Cl F6 N2 O5'
_chemical_formula_weight         548.90
_space_group_crystal_system      triclinic
_space_group_IT_number           2
_space_group_name_Hall           '-P 1'
_space_group_name_H-M_alt        'P -1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_creation_date             2020-10-07
_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                77.831(2)
_cell_angle_beta                 85.1830(10)
_cell_angle_gamma                67.565(2)
_cell_formula_units_Z            2
_cell_length_a                   9.12500(10)
_cell_length_b                   10.2780(2)
_cell_length_c                   13.8974(3)
_cell_measurement_reflns_used    18071
_cell_measurement_temperature    100.0(1)
_cell_measurement_theta_max      79.6140
_cell_measurement_theta_min      3.2370
_cell_volume                     1177.66(4)
_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 0.998
_diffrn_measured_fraction_theta_max 0.969
_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     25.00  51.00   0.50    0.10    --   48.62  77.00   0.00   52
  2  \w     26.00  52.00   0.50    0.10    --   48.62  77.00  90.00   52
  3  \w     33.00  67.00   0.50    0.10    --   48.62  57.00  90.00   68
  4  \w     33.00  98.00   0.50    0.10    --   48.62  57.00   0.00  130
  5  \w     35.00  92.00   0.50    0.10    --   48.62  57.00-120.00  114
  6  \w     76.00 119.00   0.50    0.10    --   58.00  79.00 110.04   86
  7  \w     36.00  69.00   0.50    0.10    --   58.00  79.00 110.04   66
  8  \w     46.00  77.00   0.50    0.10    --   70.00  79.00  88.37   62
  9  \w     46.00  74.00   0.50    0.10    --   70.00  79.00 153.71   56
 10  \w     46.00  71.00   0.50    0.10    --   70.00  79.00  29.94   50
 11  \w     80.00 107.00   0.50    0.10    --   70.00  79.00 153.71   54
 12  \w    107.00 139.00   0.50    0.10    --   74.00  79.00 -17.49   64
 13  \w     51.00  83.00   0.50    0.10    --   74.00  79.00 -17.49   64
 14  \w     50.00  84.00   0.50    0.10    --   74.00  79.00 -39.54   68
 15  \w     93.00 134.00   0.50    0.10    --   74.00  78.00 179.92   82
 16  \w     51.00  84.00   0.50    0.10    --   74.00  78.00 179.92   66
 17  \w     42.00  67.00   0.50    0.10    --   66.00  78.00  22.22   50
 18  \w     43.00  80.00   0.50    0.10    --   66.00  78.00-133.48   74
 19  \w     34.00  80.00   0.50    0.10    --   58.00  78.00-152.00   92
 20  \w     46.00  83.00   0.50    0.10    --   70.00  77.00 128.14   74
 21  \w     46.00  71.00   0.50    0.10    --   70.00  77.00 -41.14   50
 22  \w     86.00 115.00   0.50    0.13    --  110.00  77.00 -30.00   58
 23  \w    128.00 154.00   0.50    0.13    --  110.00  77.00  60.00   52
 24  \w     86.00 123.00   0.50    0.13    --  110.00  77.00  60.00   74
 25  \w     87.00 175.00   0.50    0.13    --  110.00  77.00-120.00  176
 26  \w     86.00 175.00   0.50    0.13    --  110.00  77.00 120.00  178
 27  \w     86.00 170.00   0.50    0.13    --  110.00  77.00-150.00  168
 28  \w     86.00 176.00   0.50    0.13    --  110.00  77.00 -60.00  180
 29  \w     86.00 173.00   0.50    0.13    --  110.00  77.00  90.00  174
 30  \w     89.00 176.00   0.50    0.13    --  110.00  77.00 -90.00  174
 31  \w    128.00 176.00   0.50    0.13    --  110.00  77.00 150.00   96
 32  \w     89.00 125.00   0.50    0.13    --  110.00  77.00 150.00   72
 33  \w    119.00 171.00   0.50    0.13    --  110.00  77.00 -30.00  104
 34  \w     36.00  61.00   0.50    0.10    --   58.00  76.00 162.49   50
 35  \w     53.00  85.00   0.50    0.10    --   74.00  74.00  58.66   64
 36  \w     53.00  94.00   0.50    0.10    --   74.00  73.00-135.00   82
 37  \w     53.00  79.00   0.50    0.10    --   74.00  71.00 -80.38   52
 38  \w     85.00 113.00   0.50    0.10    --   74.00  71.00 -80.38   56
 39  \w    153.00 178.00   0.50    0.13    --  110.00  57.00 -90.00   50
 40  \w     96.00 127.00   0.50    0.13    --  110.00  57.00 -90.00   62
 41  \w     95.00 121.00   0.50    0.13    --  110.00  57.00 150.00   52
 42  \w     95.00 139.00   0.50    0.13    --  110.00  57.00  60.00   88
 43  \w    150.00 178.00   0.50    0.13    --  110.00  57.00   0.00   56
 44  \w     94.00 163.00   0.50    0.13    --  110.00  57.00  90.00  138
 45  \w    142.00 177.00   0.50    0.13    --  110.00  57.00  30.00   70
 46  \w     95.00 125.00   0.50    0.13    --  110.00  57.00   0.00   60
 47  \w     94.00 177.00   0.50    0.13    --  110.00  57.00-180.00  166
 48  \w     97.00 139.00   0.50    0.13    --  110.00  57.00  30.00   84
 49  \w    108.00 140.00   0.50    0.13    --  110.00  38.00  30.00   64
 50  \w     82.00 108.00   0.50    0.13    --  110.00-125.00  60.00   52
 51  \w     71.00 113.00   0.50    0.13    --  110.00-125.00 120.00   84
 52  \w     42.00  68.00   0.50    0.13    --  110.00 -99.00-120.00   52
 53  \w     48.00 100.00   0.50    0.13    --  110.00 -99.00-180.00  104
 54  \w     73.00 103.00   0.50    0.13    --  110.00 -99.00-120.00   60
 55  \w     77.00 103.00   0.50    0.13    --  110.00 -99.00 -90.00   52
 56  \w     70.00  96.00   0.50    0.13    --  110.00 -99.00 -60.00   52
 57  \w     40.00  66.00   0.50    0.13    --  110.00 -99.00 -60.00   52
 58  \w     41.00  67.00   0.50    0.13    --  110.00 -99.00 -90.00   52
 59  \w     47.00  90.00   0.50    0.13    --  110.00 -99.00 120.00   86
 60  \w     62.00 118.00   0.50    0.10    --   48.62 178.00-180.00  112
 61  \w     68.00 120.00   0.50    0.10    --   48.62 178.00  60.00  104
 62  \w     46.00 121.00   0.50    0.13    --  110.00 -77.00 -60.00  150
 63  \w     40.00  68.00   0.50    0.13    --  110.00 -57.00  30.00   56
 64  \w    -19.00   6.00   0.50    0.10    --   48.62 -19.00-150.00   50
 65  \w    -84.00 -27.00   0.50    0.10    --  -26.00 150.00  58.39  114
 66  \w    -85.00 -18.00   0.50    0.13    --  -70.00 125.00-120.00  134
 67  \w     -1.00  26.00   0.50    0.10    --  -48.62  19.00 -30.00   54
 68  \w    -50.00 -25.00   0.50    0.10    --  -48.62 -77.00-120.00   50
 69  \w    -50.00 -25.00   0.50    0.10    --  -48.62 -77.00   0.00   50
 70  \w    -79.00 -38.00   0.50    0.10    --  -48.62 -38.00-120.00   82
 71  \w   -119.00 -92.00   0.50    0.10    --  -48.62 -38.00 -30.00   54
 72  \w    -88.00 -35.00   0.50    0.10    --  -48.62 -38.00-150.00  106
 73  \w    -90.00 -36.00   0.50    0.10    --  -48.62 -38.00 -30.00  108
 74  \w   -124.00 -55.00   0.50    0.10    --  -48.62 -19.00   0.00  138
 75  \w    -71.00 -46.00   0.50    0.13    --  -70.00 -77.00 -90.00   50
 76  \w    -72.00 -47.00   0.50    0.13    --  -70.00 -76.00  67.97   50
 77  \w    -78.00 -47.00   0.50    0.13    --  -70.00 -75.00 -54.37   62
;
_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      0.1734566000
_diffrn_orient_matrix_UB_12      -0.1064776000
_diffrn_orient_matrix_UB_13      0.0103435000
_diffrn_orient_matrix_UB_21      0.0075025000
_diffrn_orient_matrix_UB_22      0.0309402000
_diffrn_orient_matrix_UB_23      0.1028451000
_diffrn_orient_matrix_UB_31      -0.0567375000
_diffrn_orient_matrix_UB_32      -0.1226022000
_diffrn_orient_matrix_UB_33      0.0466457000
_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  0.0344
_diffrn_reflns_av_unetI/netI     0.0213
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.969
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -11
_diffrn_reflns_limit_k_max       12
_diffrn_reflns_limit_k_min       -13
_diffrn_reflns_limit_l_max       17
_diffrn_reflns_limit_l_min       -17
_diffrn_reflns_number            28389
_diffrn_reflns_point_group_measured_fraction_full 0.998
_diffrn_reflns_point_group_measured_fraction_max 0.969
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         79.776
_diffrn_reflns_theta_min         3.253
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    2.223
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.560
_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    1.548
_exptl_crystal_description       block
_exptl_crystal_F_000             568
_exptl_crystal_size_max          0.259
_exptl_crystal_size_mid          0.116
_exptl_crystal_size_min          0.087
_refine_diff_density_max         0.316
_refine_diff_density_min         -0.303
_refine_diff_density_rms         0.047
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.073
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     337
_refine_ls_number_reflns         4976
_refine_ls_number_restraints     6
_refine_ls_restrained_S_all      1.072
_refine_ls_R_factor_all          0.0340
_refine_ls_R_factor_gt           0.0316
_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^)+(0.0394P)^2^+0.5108P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0828
_refine_ls_wR_factor_ref         0.0842
_reflns_Friedel_coverage         0.000
_reflns_number_gt                4577
_reflns_number_total             4976
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d2sc05182f2.cif
_cod_data_source_block           jb051020_1_1
_cod_database_code               1567875
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         C20H26ClF3N2O3
_reflns_odcompleteness_completeness 99.90
_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,H) groups
2. Restrained distances
 N1-H1A = N1-H1B = N2-H2A = N2-H2B
 0.93 with sigma of 0.02
 H2A-H2B
 1.44 with sigma of 0.02
 H1A-H1B
 1.44 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(H2), C3(H3), C4(H4), C5(H5)
;
_shelx_res_checksum              99259
_olex2_date_sample_data_collection 2020-10-05
_olex2_date_sample_submission    2020-10-02
_olex2_submission_original_sample_id jb051020_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 1.214
_oxdiff_exptl_absorpt_empirical_full_min 0.800