A Design of Experiments Approach to a Robust Final Deprotection and Reactive Crystallization of IPI-926, A Novel Hedgehog Pathway Inhibitor
Martinot, Theodore A.; Austad, Brian C.; Côté, Alexandre; Depew, Kristopher M.; Genov, Daniel; Grenier, Louis; Helble, Joseph; Lescarbeau, Andre; Nair, Somarajan; Trudeau, Martin; White, Priscilla; Yu, Lin-Chen; Organic Process Research & Development 19 (2015) 1693–; doi:10.1021/acs.oprd.5b00214

data_1530690
_publ_section_title
;
 A Design of Experiments Approach to a Robust Final Deprotection and
 Reactive Crystallization of IPI-926, A Novel Hedgehog Pathway Inhibitor
;
_journal_issue                   11
_journal_name_full               'Organic Process Research &amp; Development'
_journal_page_first              1693
_journal_paper_doi               10.1021/acs.oprd.5b00214
_journal_volume                  19
_journal_year                    2015
_chemical_absolute_configuration ad
_chemical_formula_moiety         '4(C35 H53 Br N2 O5 S2), 2(C6 H14), H2 O '
_chemical_formula_sum            'C38 H60.5 Br N2 O5.25 S2'
_chemical_formula_weight         773.41
_space_group_IT_number           4
_symmetry_cell_setting           monoclinic
_symmetry_Int_Tables_number      4
_symmetry_space_group_name_Hall  'P 2yb'
_symmetry_space_group_name_H-M   'P 1 21 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_audit_creation_method           SHELXL-97
_cell_angle_alpha                90.00
_cell_angle_beta                 92.3600(10)
_cell_angle_gamma                90.00
_cell_formula_units_Z            4
_cell_length_a                   7.3780(5)
_cell_length_b                   14.3067(10)
_cell_length_c                   36.570(3)
_cell_measurement_reflns_used    5928
_cell_measurement_temperature    173(2)
_cell_measurement_theta_max      23.03
_cell_measurement_theta_min      2.65
_cell_volume                     3856.9(5)
_computing_cell_refinement       'APEX2 (BRUKER, V2008.5-0, 2006)'
_computing_data_collection       'COSMO (BRUKER, V1.58, 2006)'
_computing_data_reduction        'SAINT (BRUKER, V7.34A, 2006)'
_computing_molecular_graphics
'SHELXTL (Sheldrick, Acta Cryst. A64 2008, 112-122)'
_computing_publication_material
'SHELXTL (Sheldrick, Acta Cryst. A64 2008, 112-122)'
_computing_structure_refinement
'SHELXL (Sheldrick, Acta Cryst. A64 2008, 112-122)'
_computing_structure_solution
'SHELXS (Sheldrick, Acta Cryst. A64 2008, 112-122)'
_diffrn_ambient_temperature      173(2)
_diffrn_detector_area_resol_mean 836.6
_diffrn_measured_fraction_theta_full 0.997
_diffrn_measured_fraction_theta_max 0.997
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       '\w,and/f 0.5 deg'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0686
_diffrn_reflns_av_sigmaI/netI    0.1211
_diffrn_reflns_limit_h_max       8
_diffrn_reflns_limit_h_min       -8
_diffrn_reflns_limit_k_max       17
_diffrn_reflns_limit_k_min       -17
_diffrn_reflns_limit_l_max       43
_diffrn_reflns_limit_l_min       -44
_diffrn_reflns_number            28115
_diffrn_reflns_theta_full        25.36
_diffrn_reflns_theta_max         25.36
_diffrn_reflns_theta_min         1.53
_diffrn_source                   'fine-focus sealed tube'
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    1.218
_exptl_absorpt_correction_T_max  0.9003
_exptl_absorpt_correction_T_min  0.6914
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   SADABS
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.332
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       plate
_exptl_crystal_F_000             1646
_exptl_crystal_size_max          0.33
_exptl_crystal_size_mid          0.21
_exptl_crystal_size_min          0.09
_refine_diff_density_max         0.808
_refine_diff_density_min         -0.509
_refine_diff_density_rms         0.093
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   -0.019(11)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   0.981
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     849
_refine_ls_number_reflns         13835
_refine_ls_number_restraints     18
_refine_ls_restrained_S_all      1.018
_refine_ls_R_factor_all          0.1177
_refine_ls_R_factor_gt           0.0678
_refine_ls_shift/su_max          0.001
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.0966P)^2^+0.0000P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1592
_refine_ls_wR_factor_ref         0.1880
_reflns_number_gt                8649
_reflns_number_total             13835
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            op5b00214_si_002.cif
_cod_data_source_block           ip209_0m
_cod_depositor_comments
;
The following automatic conversions were performed:

'_exptl_absorpt_correction_type' value 'Multi-scan' changed to
'multi-scan' according to
/usr/data/users/saulius/crontab/automatic-downloads/rss-feeds/ACS/lib/dictionaries/cif_core.dic
dictionary named 'cif_core.dic' version 2.4.2 from 2011-04-26.

Automatic conversion script
Id: cif_fix_values 3271 2015-04-21 07:52:19Z andrius 

 Adding full bibliography for 1530688--1530690.cif.
;
_cod_original_cell_volume        3856.8(5)
_cod_original_sg_symbol_H-M      'P 21'
_cod_original_formula_sum        'C38 H60.50 Br N2 O5.25 S2'
_cod_database_code               1530690
_contact_crystallographer_name   'Richard Staples'
_contact_crystallographer_email  xraystaples@chemistry.msu.com