A Prolific Solvate Former, Galunisertib, under the Pressure of Crystal Structure Prediction, Produces Ten Diverse Polymorphs.
Bhardwaj, Rajni M.; McMahon, Jennifer A.; Nyman, Jonas; Price, Louise S.; Konar, Sumit; Oswald, Iain D. H.; Pulham, Colin R.; Price, Sarah L.; Reutzel-Edens, Susan M; Journal of the American Chemical Society 141 (2019) 13887–13897; doi:10.1021/jacs.9b06634

data_4128849
_publ_section_title
;
 A Prolific Solvate Former, Galunisertib, under the Pressure of Crystal
 Structure Prediction, Produces Ten Diverse Polymorphs.
;
_journal_issue                   35
_journal_name_full               'Journal of the American Chemical Society'
_journal_page_first              13887
_journal_page_last               13897
_journal_paper_doi               10.1021/jacs.9b06634
_journal_volume                  141
_journal_year                    2019
_chemical_formula_moiety         'C22 H19 N5 O'
_chemical_formula_sum            'C22 H19 N5 O'
_chemical_formula_weight         369.42
_chemical_name_systematic
4-[2-(6-methylpyridin-2-yl)-5,6-dihydro-4H-pyrrolo[1,2-b]pyrazol-3-yl]quinoline
_space_group_crystal_system      monoclinic
_space_group_IT_number           15
_space_group_name_Hall           '-C 2yc'
_space_group_name_H-M_alt        'C 1 2/c 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2019-06-04
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_cell_angle_alpha                90
_cell_angle_beta                 133.41(8)
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   27.654(13)
_cell_length_b                   8.108(8)
_cell_length_c                   21.934(11)
_cell_measurement_reflns_used    579
_cell_measurement_temperature    293
_cell_measurement_theta_max      13.8960
_cell_measurement_theta_min      1.9980
_cell_volume                     3573(6)
_computing_cell_refinement       'CrysAlisPro 1.171.38.46 (Rigaku OD, 2015)'
_computing_data_collection       'CrysAlisPro 1.171.38.46 (Rigaku OD, 2015)'
_computing_data_reduction        'CrysAlisPro 1.171.38.46 (Rigaku OD, 2015)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'XL (Sheldrick, 2008)'
_computing_structure_solution    'XT (Sheldrick, 2015)'
_diffrn_ambient_temperature      293
_diffrn_detector_area_resol_mean 0.0350
_diffrn_detector_type            'Pilatus '
_diffrn_measured_fraction_theta_full 0.572
_diffrn_measured_fraction_theta_max 0.572
_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   -150.00 -94.00   0.20    0.20    --  -20.00  70.00 -24.23  280
  2  \w   -150.00 -94.00   0.20    0.20    --  -20.00  70.00 155.77  280
  3  \w   -105.00 -74.00   0.20    0.20    --   20.00  70.00 155.77  155
  4  \w   -105.00 -74.00   0.20    0.20    --   20.00  70.00 -24.23  155
  5  \w    -96.00 -30.00   0.20    0.20    --   20.00 -70.00  24.23  330
  6  \w   -106.00 -66.00   0.20    0.20    --  -20.00 -70.00-155.77  200
  7  \w   -106.00 -66.00   0.20    0.20    --  -20.00 -70.00  24.23  200
  8  \w    -96.00 -30.00   0.20    0.20    --   20.00 -70.00-155.77  330
;
_diffrn_measurement_device_type  'four-circle diffractometer at I19 beamline'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.0016942000
_diffrn_orient_matrix_UB_12      0.0579972000
_diffrn_orient_matrix_UB_13      0.0044010000
_diffrn_orient_matrix_UB_21      0.0166600000
_diffrn_orient_matrix_UB_22      -0.0081181000
_diffrn_orient_matrix_UB_23      0.0301087000
_diffrn_orient_matrix_UB_31      0.0173362000
_diffrn_orient_matrix_UB_32      0.0139058000
_diffrn_orient_matrix_UB_33      0.0005506000
_diffrn_radiation_collimation    '0.3 x 1.5 Double Pinhole'
_diffrn_radiation_monochromator  synchrotron
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           Synchrotron
_diffrn_radiation_wavelength     0.4859
_diffrn_reflns_av_R_equivalents  0.2458
_diffrn_reflns_av_unetI/netI     0.1843
_diffrn_reflns_Laue_measured_fraction_full 0.572
_diffrn_reflns_Laue_measured_fraction_max 0.572
_diffrn_reflns_limit_h_max       27
_diffrn_reflns_limit_h_min       -27
_diffrn_reflns_limit_k_max       5
_diffrn_reflns_limit_k_min       -4
_diffrn_reflns_limit_l_max       21
_diffrn_reflns_limit_l_min       -21
_diffrn_reflns_number            4412
_diffrn_reflns_point_group_measured_fraction_full 0.572
_diffrn_reflns_point_group_measured_fraction_max 0.572
_diffrn_reflns_theta_full        14.060
_diffrn_reflns_theta_max         14.060
_diffrn_reflns_theta_min         2.020
_diffrn_source                   synchrotron
_diffrn_source_type              'Undulator, I19, DLS, RAL'
_exptl_absorpt_coefficient_mu    0.046
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.56477
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.38.46 (Rigaku Oxford Diffraction, 2015)
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    1.374
_exptl_crystal_description       block
_exptl_crystal_F_000             1552
_exptl_crystal_recrystallization_method
'Recrystallisation from melt at 0.3 GPa inside a DAC'
_exptl_crystal_size_max          0.15
_exptl_crystal_size_mid          0.15
_exptl_crystal_size_min          0.12
_refine_diff_density_max         0.229
_refine_diff_density_min         -0.300
_refine_diff_density_rms         0.067
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.105
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     242
_refine_ls_number_reflns         1072
_refine_ls_number_restraints     237
_refine_ls_restrained_S_all      0.991
_refine_ls_R_factor_all          0.2209
_refine_ls_R_factor_gt           0.1157
_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^)+(0.2000P)^2^] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.2699
_refine_ls_wR_factor_ref         0.3500
_reflns_Friedel_coverage         0.000
_reflns_number_gt                502
_reflns_number_total             1072
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            ja9b06634_si_001.cif
_cod_data_source_block           Galunisertib_FORMX_HIGHP
_cod_original_cell_volume        3573(5)
_cod_database_code               4128849
_shelx_shelxl_version_number     2014/7
_chemical_oxdiff_formula         'C22 H19 N5 O'
_reflns_odcompleteness_completeness 60.65
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     14.06
_olex2_refinement_description
;
1. Others
 Fixed Uiso: H19(0.087) H18(0.087) H14A(0.094) H14B(0.094) H12A(0.095)
 H12B(0.095) H20(0.09) H2(0.076) H13A(0.104) H13B(0.104) H8(0.075) H7(0.087)
 H5(0.066) H0AA(0.081) H1AA(0.098) H1(0.079) H15(0.138) H16(0.138) H17(0.138)
 Fixed X: H19(0.5105) H18(0.4762) H14A(0.256) H14B(0.2761) H12A(0.4368)
 H12B(0.3882) H20(0.5178) H2(0.2224) H13A(0.3541) H13B(0.3133) H8(0.1984)
 H7(0.2979) H5(0.3921) H0AA(0.5117) H1AA(0.5624) H1(0.1293) H15(0.3775)
 H16(0.433) H17(0.3688)
 Fixed Y: H19(0.7562) H18(0.6743) H14A(0.5764) H14B(0.7464) H12A(0.621)
 H12B(0.474) H20(0.2238) H2(0.4266) H13A(0.7952) H13B(0.6716) H8(0.6459)
 H7(0.741) H5(0.6211) H0AA(0.072) H1AA(0.0682) H1(0.4425) H15(0.1209)
 H16(0.2415) H17(0.3118)
 Fixed Z: H19(0.316) H18(0.3382) H14A(0.4163) H14B(0.4034) H12A(0.6246)
 H12B(0.5995) H20(0.5331) H2(0.2923) H13A(0.5398) H13B(0.545) H8(0.033)
 H7(0.0786) H5(0.3156) H0AA(0.355) H1AA(0.4955) H1(0.148) H15(0.1957)
 H16(0.2205) H17(0.1961)
;
_shelx_res_checksum              66136
_shelx_hkl_checksum              16940
_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 2.629
_oxdiff_exptl_absorpt_empirical_full_min 0.444