Selection of a Suitable Physical Form and Development of a Crystallization Process for a PDE10A Inhibitor Exhibiting Enantiotropic Polymorphism
Kiang, Y.-H.; Bercot, Eric A.; Wu, Qiong; Liu, Jodi; Milburn, Robert R.; Cohen, Dawn E.; Borths, Christopher J.; Saw, Robert E.; Staples, Richard J.; Davis, Carl; Thiel, Oliver R.; Organic Process Research & Development 19 (2015) 1849–; doi:10.1021/acs.oprd.5b00031

data_1519692
_publ_section_title
;
 Selection of a Suitable Physical Form and Development of a
 Crystallization Process for a PDE10A Inhibitor Exhibiting Enantiotropic
 Polymorphism
;
_journal_issue                   12
_journal_name_full               'Organic Process Research &amp; Development'
_journal_page_first              1849
_journal_paper_doi               10.1021/acs.oprd.5b00031
_journal_volume                  19
_journal_year                    2015
_chemical_formula_moiety         'C25 H23 N5 O3'
_chemical_formula_sum            'C25 H23 N5 O3'
_chemical_formula_weight         441.48
_space_group_crystal_system      orthorhombic
_space_group_IT_number           33
_space_group_name_Hall           'P 2c -2n'
_space_group_name_H-M_alt        'P n a 21'
_symmetry_space_group_name_Hall  'P 2c -2n'
_symmetry_space_group_name_H-M   'P n a 21'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_audit_creation_date             2015-01-18
_audit_creation_method
;
Olex2 1.2-alpha
(compiled 2015.01.16 svn.r3137 for OlexSys, GUI svn.r4992)
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   14.8632(5)
_cell_length_b                   7.9124(2)
_cell_length_c                   18.9392(4)
_cell_measurement_temperature    173(2)
_cell_volume                     2227.32(10)
_computing_cell_refinement       'APEX2 (BRUKER, V2012.10-0, 2012)'
_computing_data_collection       'COSMO (BRUKER, V1.61, 2009)'
_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    'ShelXS (Sheldrick, 2008)'
_diffrn_ambient_temperature      173(2)
_diffrn_detector_area_resol_mean 836.6
_diffrn_measured_fraction_theta_full 0.994
_diffrn_measured_fraction_theta_max 0.993
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       '\w and \f scans'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0622
_diffrn_reflns_av_unetI/netI     0.0662
_diffrn_reflns_Laue_measured_fraction_full 0.994
_diffrn_reflns_Laue_measured_fraction_max 0.993
_diffrn_reflns_limit_h_max       17
_diffrn_reflns_limit_h_min       -17
_diffrn_reflns_limit_k_max       9
_diffrn_reflns_limit_k_min       -9
_diffrn_reflns_limit_l_max       22
_diffrn_reflns_limit_l_min       -22
_diffrn_reflns_number            15416
_diffrn_reflns_point_group_measured_fraction_full 0.980
_diffrn_reflns_point_group_measured_fraction_max 0.977
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         25.394
_diffrn_reflns_theta_min         2.151
_diffrn_source                   'sealed tube'
_exptl_absorpt_coefficient_mu    0.089
_exptl_absorpt_correction_T_max  0.7452
_exptl_absorpt_correction_T_min  0.3380
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   SADABS
_exptl_crystal_colour            yellow
_exptl_crystal_colour_primary    yellow
_exptl_crystal_density_diffrn    1.317
_exptl_crystal_description       block
_exptl_crystal_F_000             928
_exptl_crystal_recrystallization_method 'used as received'
_exptl_crystal_size_max          0.32
_exptl_crystal_size_mid          0.29
_exptl_crystal_size_min          0.18
_refine_diff_density_max         0.114
_refine_diff_density_min         -0.181
_refine_diff_density_rms         0.032
_refine_ls_abs_structure_details
;
 Flack x determined using 1493 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons and Flack (2004), Acta Cryst. A60, s61).
;
_refine_ls_abs_structure_Flack   -0.3(10)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.071
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     299
_refine_ls_number_reflns         4010
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.071
_refine_ls_R_factor_all          0.0466
_refine_ls_R_factor_gt           0.0413
_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^)+(0.0403P)^2^+0.0785P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1006
_refine_ls_wR_factor_ref         0.1060
_reflns_Friedel_coverage         0.906
_reflns_Friedel_fraction_full    0.966
_reflns_Friedel_fraction_max     0.960
_reflns_number_gt                3545
_reflns_number_total             4010
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            op5b00031_si_001.cif
_cod_data_source_block           amg4509
_cod_depositor_comments
'Adding full bibliography for 1519692--1519693.cif.'
_cod_database_code               1519692
_shelxl_version_number           2013-4
_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 C(H,H,H) groups
2.a Ternary CH refined with riding coordinates:
 C19(H19)
2.b Secondary CH2 refined with riding coordinates:
 C20(H20A,H20B), C21(H21A,H21B), C22(H22A,H22B), C23(H23A,H23B)
2.c Aromatic/amide H refined with riding coordinates:
 N1(H1), C2(H2), C3(H3), C5(H5), C6(H6), C10(H10), C11(H11), C12(H12),
 C13(H13), C17(H17), C18(H18)
2.d Idealised Me refined as rotating group:
 C25(H25A,H25B,H25C)
;
_olex2_diffrn_ambient_temperature_device 'Oxford Cryosystems'
_olex2_exptl_crystal_mounting_method
'The crystal was mounted on a nylon loop with paratone oil'
_olex2_submission_original_sample_id 'AR 146819 Vial 1,'
_olex2_submission_special_instructions 'No special instructions were received'