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_1567874
_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_absolute_configuration ad
_chemical_formula_moiety         'C13 H12 F3 N O2, H2 O'
_chemical_formula_sum            'C13 H14 F3 N O3'
_chemical_formula_weight         289.25
_space_group_crystal_system      orthorhombic
_space_group_IT_number           19
_space_group_name_Hall           'P 2ac 2ab'
_space_group_name_H-M_alt        'P 21 21 21'
_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
;
2022-04-29 deposited with the CCDC.	2022-10-28 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   5.36257(3)
_cell_length_b                   8.48172(5)
_cell_length_c                   27.61854(18)
_cell_measurement_reflns_used    25134
_cell_measurement_temperature    100.0(1)
_cell_measurement_theta_max      79.7950
_cell_measurement_theta_min      5.4480
_cell_volume                     1256.197(13)
_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 0.993
_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    --   48.87  77.00 -30.00   52
  2  \w     29.00  66.00   0.50    0.10    --   50.00  77.00 -92.58   74
  3  \w     25.00  51.00   0.50    0.10    --   48.87  77.00-180.00   52
  4  \w     37.00  64.00   0.50    0.10    --   48.87  57.00-150.00   54
  5  \w     37.00  92.00   0.50    0.10    --   48.87  38.00-180.00  110
  6  \w     76.00 102.00   0.50    0.10    --   48.87  57.00-150.00   52
  7  \w     57.00  84.00   0.50    0.10    --   48.87  38.00  60.00   54
  8  \w     29.00  67.00   0.50    0.10    --   54.00  80.00  32.65   76
  9  \w     49.00  75.00   0.50    0.10    --   74.00  80.00 -17.48   52
 10  \w     49.00 113.00   0.50    0.10    --   74.00  80.00  -3.61  128
 11  \w     39.00  73.00   0.50    0.10    --   62.00  79.00  76.13   68
 12  \w     29.00  56.00   0.50    0.10    --   54.00  80.00 147.84   54
 13  \w     45.00  75.00   0.50    0.10    --   70.00  80.00 157.05   60
 14  \w     34.00  59.00   0.50    0.10    --   54.00  79.00  79.49   50
 15  \w     46.00  71.00   0.50    0.10    --   70.00  78.00 -52.15   50
 16  \w    114.00 144.00   0.50    0.10    --   78.00  79.00-136.49   60
 17  \w     86.00 133.00   0.50    0.10    --  110.00  77.00 -60.00   94
 18  \w     52.00  78.00   0.50    0.10    --   74.00  77.00 -32.93   52
 19  \w     34.00  62.00   0.50    0.10    --   58.00  78.00-165.86   56
 20  \w     50.00  75.00   0.50    0.10    --   74.00  79.00-127.61   50
 21  \w     54.00 102.00   0.50    0.10    --   78.00  79.00-136.49   96
 22  \w     87.00 124.00   0.50    0.10    --  110.00  77.00-150.00   74
 23  \w    132.00 171.00   0.50    0.10    --  110.00  77.00-150.00   78
 24  \w     87.00 175.00   0.50    0.10    --  110.00  77.00 -30.00  176
 25  \w     89.00 114.00   0.50    0.10    --  110.00  77.00-120.00   50
 26  \w    131.00 175.00   0.50    0.10    --  110.00  77.00-120.00   88
 27  \w    145.00 175.00   0.50    0.10    --  110.00  77.00 -60.00   60
 28  \w    123.00 161.00   0.50    0.10    --  110.00  77.00  30.00   76
 29  \w     87.00 112.00   0.50    0.10    --  110.00  77.00  30.00   50
 30  \w     87.00 155.00   0.50    0.10    --  110.00  77.00  60.00  136
 31  \w    137.00 173.00   0.50    0.10    --  110.00  77.00 120.00   72
 32  \w     86.00 176.00   0.50    0.10    --  110.00  77.00 150.00  180
 33  \w     87.00 123.00   0.50    0.10    --  110.00  77.00 120.00   72
 34  \w     97.00 131.00   0.50    0.10    --   74.00  75.00 122.18   68
 35  \w     51.00  91.00   0.50    0.10    --   74.00  75.00 122.18   80
 36  \w     86.00 166.00   0.50    0.10    --  110.00  77.00  90.00  160
 37  \w     89.00 176.00   0.50    0.10    --  110.00  77.00   0.00  174
 38  \w     59.00  86.00   0.50    0.10    --   82.00  75.00 -64.67   54
 39  \w     61.00  86.00   0.50    0.10    --   82.00  70.00 -94.01   50
 40  \w     79.00 112.00   0.50    0.10    --   90.00  71.00 -67.80   66
 41  \w     88.00 174.00   0.50    0.10    --  110.00  77.00-180.00  172
 42  \w    134.00 178.00   0.50    0.10    --  110.00  57.00 -90.00   88
 43  \w    101.00 126.00   0.50    0.10    --  110.00  57.00 -90.00   50
 44  \w    119.00 146.00   0.50    0.10    --   82.00  75.00 -64.67   54
 45  \w     98.00 126.00   0.50    0.10    --  110.00  38.00-180.00   56
 46  \w     97.00 134.00   0.50    0.10    --  110.00  57.00  60.00   74
 47  \w     98.00 123.00   0.50    0.10    --  110.00  38.00  60.00   50
 48  \w    111.00 137.00   0.50    0.10    --   78.00  57.00  37.96   52
 49  \w     65.00 110.00   0.50    0.10    --   78.00  57.00  37.96   90
 50  \w    -78.00 -49.00   0.50    0.10    --  -70.00 -70.00  48.79   58
 51  \w    -70.00 -45.00   0.50    0.10    --  -70.00 -79.00   9.64   50
 52  \w    -71.00 -46.00   0.50    0.10    --  -70.00 -77.00  30.00   50
 53  \w    -64.00 -37.00   0.50    0.10    --  -62.00 -79.00 -57.17   54
 54  \w    -63.00 -37.00   0.50    0.10    --  -62.00 -79.00-134.54   52
 55  \w    -83.00 -50.00   0.50    0.10    --  -70.00 -72.00-175.40   66
 56  \w    -72.00 -47.00   0.50    0.10    --  -70.00 -76.00-104.48   50
 57  \w   -127.00 -82.00   0.50    0.10    --  -62.00 -79.00 -57.17   90
 58  \w    -90.00 -47.00   0.50    0.10    --  -70.00 -76.00 165.71   86
 59  \w    -81.00 -49.00   0.50    0.10    --  -70.00 -72.00  88.94   64
 60  \w    -67.00 -35.00   0.50    0.10    --  -48.87 -38.00 -60.00   64
 61  \w    -64.00 -33.00   0.50    0.10    --  -48.87 -57.00  90.00   62
 62  \w    -77.00 -34.00   0.50    0.10    --  -48.87 -57.00 150.00   86
 63  \w    -58.00 -33.00   0.50    0.10    --  -48.87 -57.00-180.00   50
 64  \w   -109.00 -82.00   0.50    0.10    --  -48.87 -57.00-180.00   54
 65  \w    -65.00 -33.00   0.50    0.10    --  -48.87 -57.00   0.00   64
 66  \w    -93.00  -4.00   0.50    0.10    --  -70.00  77.00  30.00  178
 67  \w    -89.00 -26.00   0.50    0.10    --  -26.00 150.00 133.31  126
 68  \w     38.00  66.00   0.50    0.10    --  110.00 -57.00 120.00   56
 69  \w     82.00 134.00   0.50    0.10    --  110.00 -77.00 150.00  104
 70  \w     72.00 134.00   0.50    0.10    --  110.00 -77.00 -30.00  124
 71  \w     74.00 117.00   0.50    0.10    --   48.87 178.00-150.00   86
 72  \w     53.00 106.00   0.50    0.10    --  110.00 -99.00 150.00  106
 73  \w     69.00 110.00   0.50    0.10    --  110.00-125.00 120.00   82
 74  \w     61.00 113.00   0.50    0.10    --  110.00-125.00  30.00  104
 75  \w     54.00 127.00   0.50    0.10    --  110.00-144.00   1.12  146
 76  \w     68.00 113.00   0.50    0.10    --  110.00-125.00-120.00   90
;
_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      -0.2864858000
_diffrn_orient_matrix_UB_12      0.0023967000
_diffrn_orient_matrix_UB_13      -0.0041460000
_diffrn_orient_matrix_UB_21      -0.0090585000
_diffrn_orient_matrix_UB_22      -0.1756985000
_diffrn_orient_matrix_UB_23      0.0140263000
_diffrn_orient_matrix_UB_31      -0.0197286000
_diffrn_orient_matrix_UB_32      0.0459333000
_diffrn_orient_matrix_UB_33      0.0538273000
_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  0.0366
_diffrn_reflns_av_unetI/netI     0.0147
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.993
_diffrn_reflns_limit_h_max       6
_diffrn_reflns_limit_h_min       -6
_diffrn_reflns_limit_k_max       10
_diffrn_reflns_limit_k_min       -10
_diffrn_reflns_limit_l_max       34
_diffrn_reflns_limit_l_min       -31
_diffrn_reflns_number            29963
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 0.990
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         80.089
_diffrn_reflns_theta_min         3.200
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    1.196
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.587
_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    1.529
_exptl_crystal_description       plank
_exptl_crystal_F_000             600
_exptl_crystal_size_max          0.224
_exptl_crystal_size_mid          0.134
_exptl_crystal_size_min          0.084
_refine_diff_density_max         0.199
_refine_diff_density_min         -0.200
_refine_diff_density_rms         0.046
_refine_ls_abs_structure_details
;
 Flack x determined using 1074 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.02(4)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.069
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     190
_refine_ls_number_reflns         2708
_refine_ls_number_restraints     4
_refine_ls_restrained_S_all      1.069
_refine_ls_R_factor_all          0.0271
_refine_ls_R_factor_gt           0.0268
_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^)+(0.0357P)^2^+0.3964P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0694
_refine_ls_wR_factor_ref         0.0696
_reflns_Friedel_coverage         0.677
_reflns_Friedel_fraction_full    1.000
_reflns_Friedel_fraction_max     0.985
_reflns_number_gt                2680
_reflns_number_total             2708
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d2sc05182f2.cif
_cod_data_source_block           jb180920_1_1
_cod_database_code               1567874
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         C13H12F3NO2
_reflns_odcompleteness_completeness 99.93
_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
 At 1.5 times of:
  All O(H,H) groups
2. Restrained distances
 O3-H3B = O3-H3A
 0.93 with sigma of 0.02
 N007-H007
 0.93 with sigma of 0.02
 H3A-H3B
 1.44 with sigma of 0.02
3.a Ternary CH refined with riding coordinates:
 C7(H7), C9(H9), C10(H10)
3.b Secondary CH2 refined with riding coordinates:
 C8(H8A,H8B), C11(H11A,H11B), C13(H13A,H13B)
3.c Aromatic/amide H refined with riding coordinates:
 C2(H2), C6(H6)
;
_shelx_res_checksum              64992
_olex2_date_sample_submission    2020-09-16
_olex2_submission_original_sample_id jb180920_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 1.123
_oxdiff_exptl_absorpt_empirical_full_min 0.889