Microbatch under-oil salt screening of organic cations: single-crystal growth of active pharmaceutical ingredients
Babor, Martin; Nievergelt, Philipp P.; Čejka, Jan; Zvoníček, Vít; Spingler, Bernhard; IUCrJ 6 (2019) 145–151; doi:10.1107/S2052252518017876

data_1550452
_publ_section_title
;
 Microbatch under-oil salt screening of organic cations: single-crystal
 growth of active pharmaceutical ingredients
;
_journal_issue                   1
_journal_name_full               IUCrJ
_journal_page_first              145
_journal_page_last               151
_journal_paper_doi               10.1107/S2052252518017876
_journal_volume                  6
_journal_year                    2019
_chemical_formula_moiety         '1(C19 H23 Cl N5 O), C N S'
_chemical_formula_sum            'C20 H23 Cl N6 O S'
_chemical_formula_weight         430.95
_space_group_crystal_system      triclinic
_space_group_IT_number           2
_space_group_name_Hall           '-P 1'
_space_group_name_H-M_alt        'P -1'
_symmetry_space_group_name_Hall  '-P 1'
_symmetry_space_group_name_H-M   'P -1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2018-08-21
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_cell_angle_alpha                90.2630(12)
_cell_angle_beta                 90.2180(12)
_cell_angle_gamma                108.0045(15)
_cell_formula_units_Z            4
_cell_length_a                   12.1482(2)
_cell_length_b                   13.1848(2)
_cell_length_c                   13.82510(17)
_cell_measurement_reflns_used    34827
_cell_measurement_temperature    159.99(10)
_cell_measurement_theta_max      78.6650
_cell_measurement_theta_min      3.5170
_cell_volume                     2105.90(6)
_computing_cell_refinement       'CrysAlisPro 1.171.39.46 (Rigaku OD, 2018)'
_computing_data_collection       'CrysAlisPro 1.171.39.46 (Rigaku OD, 2018)'
_computing_data_reduction        'CrysAlisPro 1.171.39.46 (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_environment      N~2~
_diffrn_ambient_temperature      159.99(10)
_diffrn_detector                 'CCD plate'
_diffrn_detector_type            'Pilatus 200K'
_diffrn_measured_fraction_theta_full 0.950
_diffrn_measured_fraction_theta_max 0.925
_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    -89.00 -35.00   0.50    0.25    --  -50.46 -57.00-180.00  108
  2  \w    -80.00 -38.00   0.50    0.25    --  -50.46 -57.00-120.00   84
  3  \w    -65.00 -39.00   0.50    0.25    --  -50.46 -57.00 -30.00   52
  4  \w    -60.00 -35.00   0.50    0.25    --  -50.46 -57.00 120.00   50
  5  \w    -33.00   9.00   0.50    0.25    --  -50.46  57.00 150.00   84
  6  \w    -72.00 -46.00   0.50    1.00    --  -86.25  60.00 166.42   52
  7  \w    -69.00 -43.00   0.50    1.00    --  -86.25  60.00  79.04   52
  8  \w    -93.00 -67.00   0.50    1.00    --  -86.25  60.00 125.16   52
  9  \w    -92.00 -63.00   0.50    1.00    --  -86.25  60.00  31.45   58
 10  \w    -77.00 -51.00   0.50    1.00    --  -86.25  60.00 -64.27   52
 11  \w   -121.00 -65.00   0.50    0.25    --  -50.46 -57.00 120.00  112
 12  \w   -121.00 -89.00   0.50    0.25    --  -50.46 -57.00  60.00   64
 13  \w    -21.00   5.00   0.50    0.25    --   50.46 -60.00 -28.26   52
 14  \w     21.00  66.00   0.50    0.25    --   50.46 -60.00 -28.26   90
 15  \w     64.00  89.00   0.50    1.00    --  107.75 -58.00 -31.90   50
 16  \w     80.00 106.00   0.50    1.00    --  107.75 -60.00 -40.20   52
 17  \w     90.00 116.00   0.50    1.00    --  107.75 -60.00  17.59   52
 18  \w     75.00 104.00   0.50    1.00    --  107.75 -15.00  30.00   58
 19  \w     95.00 125.00   0.50    1.00    --  107.75  15.00  90.00   60
 20  \w    125.00 178.00   0.50    1.00    --  107.75  42.00  53.04  106
 21  \w    127.00 176.00   0.50    1.00    --  107.75  15.00 150.00   98
 22  \w    112.00 138.00   0.50    1.00    --  107.75  32.00  36.61   52
 23  \w     87.00 115.00   0.50    0.25    --   50.46  57.00   0.00   56
 24  \w    145.00 176.00   0.50    1.00    --  107.75  30.00 -90.00   62
 25  \w    138.00 175.00   0.50    1.00    --  107.75  15.00-180.00   74
 26  \w    127.00 178.00   0.50    1.00    --  107.75  45.00-148.92  102
 27  \w    109.00 135.00   0.50    1.00    --  107.75  30.00 -90.00   52
 28  \w     98.00 133.00   0.50    1.00    --  107.75  15.00-120.00   70
 29  \w     98.00 126.00   0.50    1.00    --  107.75  15.00-180.00   56
 30  \w     81.00 107.00   0.50    1.00    --  107.75 -60.00-174.15   52
 31  \w     64.00 110.00   0.50    1.00    --  107.75 -60.00-135.99   92
 32  \w     58.00  94.00   0.50    1.00    --  107.75 -60.00-101.89   72
 33  \w     50.00 101.00   0.50    1.00    --  107.75 -59.00 -83.65  102
 34  \w     46.00  71.00   0.50    1.00    --  107.75 -59.00-173.99   50
 35  \w     41.00  69.00   0.50    1.00    --  107.75 -45.00-120.00   56
 36  \w     50.00  75.00   0.50    1.00    --  107.75 -50.00-153.39   50
 37  \w     51.00  77.00   0.50    1.00    --  107.75 -45.00-150.00   52
 38  \w     35.00 102.00   0.50    1.00    --  107.75 -15.00-120.00  134
 39  \w    100.00 158.00   0.50    1.00    --  107.75  15.00 -90.00  116
 40  \w     70.00 108.00   0.50    1.00    --  107.75 -60.00  88.14   76
 41  \w     81.00 124.00   0.50    1.00    --  107.75 -60.00 136.87   86
 42  \w     71.00 107.00   0.50    1.00    --  107.75 -60.00 166.31   72
 43  \w     61.00  98.00   0.50    1.00    --  107.75 -60.00  78.55   74
 44  \w     49.00  78.00   0.50    1.00    --  107.75 -46.00 168.52   58
 45  \w     40.00  98.00   0.50    1.00    --  107.75 -60.00 120.05  116
 46  \w     43.00 112.00   0.50    1.00    --  107.75 -60.00  45.09  138
 47  \w     51.00 103.00   0.50    1.00    --  107.75 -60.00 -68.77  104
 48  \w     50.00  75.00   0.50    1.00    --  107.75 -52.00 -39.62   50
 49  \w     36.00  75.00   0.50    1.00    --  107.75 -59.00  10.56   78
 50  \w     36.00 106.00   0.50    1.00    --  107.75 -60.00 -13.71  140
 51  \w     37.00  90.00   0.50    1.00    --  107.75 -59.00  24.62  106
 52  \w     39.00  64.00   0.50    1.00    --  107.75 -60.00 136.87   50
 53  \w     33.00  59.00   0.50    1.00    --  107.75 -30.00  90.00   52
 54  \w     29.00  68.00   0.50    1.00    --  107.75 -30.00  60.00   78
 55  \w     38.00  67.00   0.50    1.00    --  107.75 -15.00  30.00   58
 56  \w     34.00  74.00   0.50    1.00    --  107.75 -45.00  60.00   80
 57  \w     32.00  63.00   0.50    1.00    --  107.75 -30.00 120.00   62
 58  \w     35.00  67.00   0.50    1.00    --  107.75 -53.00 153.80   64
 59  \w     29.00  57.00   0.50    1.00    --  107.75 -30.00 150.00   56
 60  \w     31.00  64.00   0.50    0.25    --   50.46 -57.00 150.00   66
 61  \w     35.00  72.00   0.50    0.25    --   50.46  57.00  90.00   74
 62  \w     35.00  79.00   0.50    0.25    --   50.46  59.00  41.94   88
 63  \w     35.00  82.00   0.50    0.25    --   50.46  57.00   0.00   94
 64  \w     35.00  75.00   0.50    0.25    --   50.46  57.00 -60.00   80
 65  \w     35.00  65.00   0.50    0.25    --   50.46  59.00 -23.68   60
 66  \w     35.00  95.00   0.50    1.00    --  107.75  -9.00 -75.56  120
 67  \w     36.00  65.00   0.50    0.25    --   50.46 -57.00-180.00   58
 68  \w     29.00  54.00   0.50    1.00    --  107.75 -30.00-120.00   50
 69  \w     35.00  63.00   0.50    1.00    --  107.75 -45.00-166.76   56
 70  \w     36.00  67.00   0.50    1.00    --  107.75 -55.00-163.59   62
 71  \w     29.00  54.00   0.50    1.00    --  107.75 -30.00 -90.00   50
 72  \w     37.00  76.00   0.50    1.00    --  107.75 -45.00 -75.62   78
 73  \w     33.00  61.00   0.50    1.00    --  107.75 -45.00 -60.00   56
 74  \w     32.00  76.00   0.50    1.00    --  107.75 -45.00   0.00   88
 75  \w     35.00  72.00   0.50    0.25    --   50.46  57.00 150.00   74
 76  \w     36.00  74.00   0.50    0.25    --   50.46  57.00-180.00   76
 77  \w     -9.00  36.00   0.50    0.25    --    6.00  59.00 102.59   90
 78  \w    -57.00 -31.00   0.50    0.25    --  -46.00 -60.00  37.28   52
 79  \w    -61.00 -35.00   0.50    0.25    --  -50.00 -60.00  73.90   52
 80  \w    -61.00 -35.00   0.50    0.25    --  -50.00 -59.00 -50.03   52
 81  \w   -120.00 -95.00   0.50    0.25    --  -50.00 -59.00 -50.03   50
 82  \w   -118.00 -91.00   0.50    0.25    --  -50.00 -60.00  73.90   54
 83  \w    -64.00 -38.00   0.50    0.25    --  -50.46 -38.00   0.00   52
 84  \w   -128.00 -93.00   0.50    0.25    --  -50.46 -38.00   0.00   70
 85  \w     18.00  54.00   0.50    0.25    --   50.46 -57.00 -90.00   72
 86  \w    -75.00 -40.00   0.50    0.25    --  -54.00 -58.00-144.74   70
 87  \w    -64.00 -38.00   0.50    0.25    --  -54.00 -60.00 116.61   52
 88  \w    -76.00 -42.00   0.50    0.25    --  -58.00 -60.00 167.61   68
 89  \w    -69.00 -43.00   0.50    0.25    --  -58.00 -60.00-112.28   52
 90  \w    -69.00 -43.00   0.50    0.25    --  -58.00 -58.00  32.35   52
 91  \w    -77.00 -42.00   0.50    0.25    --  -58.00 -60.00   5.62   70
 92  \w    -67.00 -42.00   0.50    0.25    --  -58.00 -59.00 -82.65   50
 93  \w   -129.00-103.00   0.50    0.25    --  -58.00 -59.00 -82.65   52
 94  \w   -117.00 -90.00   0.50    0.25    --  -58.00 -60.00 167.61   54
 95  \w    -81.00 -52.00   0.50    0.25    --  -66.00 -60.00 -50.14   58
 96  \w   -123.00 -97.00   0.50    1.00    --  -70.00 -60.00  43.15   52
 97  \w    -81.00 -55.00   0.50    1.00    --  -70.00 -60.00 -82.12   52
 98  \w     54.00  80.00   0.50    0.25    --   70.00  60.00 130.16   52
 99  \w    -79.00 -54.00   0.50    1.00    --  -70.00 -60.00 117.59   50
100  \w    -80.00 -54.00   0.50    1.00    --  -70.00 -60.00  43.15   52
101  \w    -81.00 -55.00   0.50    1.00    --  -70.00 -60.00 -28.22   52
102  \w    -86.00 -78.50   0.50    1.00    --  -74.00 -59.00  33.16   15
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB Synergy, Dualflex, Pilatus 200K'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0735116000
_diffrn_orient_matrix_UB_12      0.1153264000
_diffrn_orient_matrix_UB_13      -0.0224963000
_diffrn_orient_matrix_UB_21      0.0997303000
_diffrn_orient_matrix_UB_22      -0.0404534000
_diffrn_orient_matrix_UB_23      -0.0338894000
_diffrn_orient_matrix_UB_31      -0.0493045000
_diffrn_orient_matrix_UB_32      -0.0125931000
_diffrn_orient_matrix_UB_33      -0.1037459000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0319
_diffrn_reflns_av_unetI/netI     0.0179
_diffrn_reflns_Laue_measured_fraction_full 0.950
_diffrn_reflns_Laue_measured_fraction_max 0.925
_diffrn_reflns_limit_h_max       15
_diffrn_reflns_limit_h_min       -15
_diffrn_reflns_limit_k_max       16
_diffrn_reflns_limit_k_min       -16
_diffrn_reflns_limit_l_max       14
_diffrn_reflns_limit_l_min       -16
_diffrn_reflns_number            52525
_diffrn_reflns_point_group_measured_fraction_full 0.950
_diffrn_reflns_point_group_measured_fraction_max 0.925
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         78.923
_diffrn_reflns_theta_min         3.197
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    2.729
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.532
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.39.46 (Rigaku Oxford Diffraction, 2018)
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            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.359
_exptl_crystal_description       plate
_exptl_crystal_F_000             904
_exptl_crystal_size_max          0.234
_exptl_crystal_size_mid          0.189
_exptl_crystal_size_min          0.073
_refine_diff_density_max         0.514
_refine_diff_density_min         -0.548
_refine_diff_density_rms         0.049
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.050
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     723
_refine_ls_number_reflns         8412
_refine_ls_number_restraints     45
_refine_ls_restrained_S_all      1.055
_refine_ls_R_factor_all          0.0599
_refine_ls_R_factor_gt           0.0574
_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^)+(0.0411P)^2^+2.3014P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1344
_refine_ls_wR_factor_ref         0.1358
_reflns_Friedel_coverage         0.000
_reflns_number_gt                7824
_reflns_number_total             8412
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            lt5016.cif
_cod_data_source_block           pn180815_uo_traz_1_180814_scn
_cod_original_cell_volume        2105.89(6)
_cod_database_code               1550452
_shelx_shelxl_version_number     2014/7
_chemical_oxdiff_formula         'C20 H23 Cl N6 O S'
_reflns_odcompleteness_completeness 93.92
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     74.33
_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
 S59B-C58B = S59-C58
 1.64 with sigma of 0.001
 N32-C41 \\sim N32-C41B
 with sigma of 0.02
3. Rigid body (RIGU) restrains
 C50, C51, C52, C55
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
 N32, C41B, C42B
 with sigma for 1-2 distances of 0.001 and sigma for 1-3 distances of 0.001
 S59B, N57B, C58B
 with sigma for 1-2 distances of 0.001 and sigma for 1-3 distances of 0.001
 S59, N57, C58
 with sigma for 1-2 distances of 0.001 and sigma for 1-3 distances of 0.001
4. Others
 Sof(S29B)=Sof(N27B)=Sof(C28B)=1-FVAR(1)
 Sof(S29)=Sof(N27)=Sof(C28)=FVAR(1)
 Sof(Cl57)=Sof(S59B)=Sof(N44B)=Sof(H44B)=Sof(N47B)=Sof(N57B)=Sof(C41B)=
 Sof(H41C)=Sof(H41D)=Sof(C42B)=Sof(H42C)=Sof(H42D)=Sof(C43B)=Sof(H43C)=
 Sof(H43D)=Sof(C45B)=Sof(H45C)=Sof(H45D)=Sof(C46B)=Sof(H46C)=Sof(H46D)=
 Sof(C48B)=Sof(H48C)=Sof(H48D)=Sof(C49B)=Sof(H49C)=Sof(H49D)=Sof(C50B)=
 Sof(C51B)=Sof(H51B)=Sof(C52B)=Sof(C53B)=Sof(H53B)=Sof(C54B)=Sof(H54B)=
 Sof(C55B)=Sof(H55B)=Sof(C58B)=1-FVAR(2)
 Sof(Cl56)=Sof(S59)=Sof(N44)=Sof(H44)=Sof(N47)=Sof(N57)=Sof(C41)=Sof(H41A)=
 Sof(H41B)=Sof(C42)=Sof(H42A)=Sof(H42B)=Sof(C43)=Sof(H43A)=Sof(H43B)=Sof(C45)=
 Sof(H45A)=Sof(H45B)=Sof(C46)=Sof(H46A)=Sof(H46B)=Sof(C48)=Sof(H48A)=Sof(H48B)=
 Sof(C49)=Sof(H49A)=Sof(H49B)=Sof(C50)=Sof(C51)=Sof(H51)=Sof(C52)=Sof(C53)=
 Sof(H53)=Sof(C54)=Sof(H54)=Sof(C55)=Sof(H55)=Sof(C58)=FVAR(2)
5.a Ternary CH refined with riding coordinates:
 N14(H14), N44(H44), N44B(H44B)
5.b Secondary CH2 refined with riding coordinates:
 C11(H11A,H11B), C12(H12A,H12B), C13(H13A,H13B), C15(H15A,H15B), C16(H16A,
 H16B), C18(H18A,H18B), C19(H19A,H19B), C41(H41A,H41B), C41B(H41C,H41D),
 C42(H42A,H42B), C42B(H42C,H42D), C43(H43A,H43B), C43B(H43C,H43D), C45(H45A,
 H45B), C45B(H45C,H45D), C46(H46A,H46B), C46B(H46C,H46D), C48(H48A,H48B),
 C48B(H48C,H48D), C49(H49A,H49B), C49B(H49C,H49D)
5.c Aromatic/amide H refined with riding coordinates:
 C4(H4), C5(H5), C6(H6), C7(H7), C21(H21), C23(H23), C24(H24), C25(H25),
 C34(H34), C35(H35), C36(H36), C37(H37), C51(H51), C51B(H51B), C53(H53),
 C53B(H53B), C54(H54), C54B(H54B), C55(H55), C55B(H55B)
;
_shelx_res_checksum              91508
_shelx_hkl_checksum              92417
_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 1.360
_oxdiff_exptl_absorpt_empirical_full_min 0.813