Practical Synthesis of a Cathepsin S Inhibitor: Route Identification, Purification Strategies, and Serendipitous Discovery of a Crystalline Salt Form
Xiaohu Deng; Jimmy T. Liang; Matthew Peterson; Raymond Rynberg; Eugene Cheung; Neelakandha S. Mani; Journal of Organic Chemistry 75 (2010) 1940–1947; doi:10.1021/jo902650b

data_4025311
_publ_contact_author_address
;
TransForm Pharmaceuticals
29 Hartwell Avenue
Lexington, MA 02421
USA
;
_publ_contact_author_email       xdeng@its.jnj.com
_publ_contact_author_fax         '1 858 320-3354'
_publ_contact_author_name        'Deng, Xiaohu'
_publ_contact_author_phone       '1 858 320-3338'
_publ_section_title
;
 Practical Synthesis of a Cathepsin S Inhibitor: Route Identification,
 Purification Strategies, and Serendipitous Discovery of a Crystalline
 Salt Form
;
_journal_name_full               'Journal of Organic Chemistry'
_journal_page_first              1940
_journal_page_last               1947
_journal_paper_doi               10.1021/jo902650b
_journal_volume                  75
_journal_year                    2010
_chemical_absolute_configuration syn
_chemical_formula_moiety         'C42 H46 N6 O7 Cl2'
_chemical_formula_sum            'C42 H46 Cl2 N6 O7'
_chemical_formula_weight         817.75
_chemical_name_systematic
; 
 ? 
;
_space_group_IT_number           4
_symmetry_cell_setting           monoclinic
_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
_audit_update_record
;
2009-11-11 # Formatted by publCIF
;
_cell_angle_alpha                90.00
_cell_angle_beta                 97.523(2)
_cell_angle_gamma                90.00
_cell_formula_units_Z            4
_cell_length_a                   9.1456(3)
_cell_length_b                   23.7838(8)
_cell_length_c                   18.5154(6)
_cell_measurement_reflns_used    8759
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      23.653
_cell_measurement_theta_min      2.405
_cell_volume                     3992.8(2)
_computing_structure_refinement  'SHELXL-97 (Sheldrick, 1997)'
_computing_structure_solution    'SHELXS-97 (Sheldrick, 1990)'
_diffrn_ambient_temperature      100(2)
_diffrn_measured_fraction_theta_full 0.993
_diffrn_measured_fraction_theta_max 0.993
_diffrn_measurement_device_type  'kappa APEX II CCD'
_diffrn_measurement_method       'phi and omega scans'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_source         'fine-focus sealed tube'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0399
_diffrn_reflns_av_sigmaI/netI    0.0658
_diffrn_reflns_limit_h_max       10
_diffrn_reflns_limit_h_min       -10
_diffrn_reflns_limit_k_max       23
_diffrn_reflns_limit_k_min       -26
_diffrn_reflns_limit_l_max       20
_diffrn_reflns_limit_l_min       -20
_diffrn_reflns_number            21785
_diffrn_reflns_theta_full        23.71
_diffrn_reflns_theta_max         23.71
_diffrn_reflns_theta_min         2.04
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.222
_exptl_absorpt_correction_T_max  0.9934
_exptl_absorpt_correction_T_min  0.9304
_exptl_absorpt_correction_type   none
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.360
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       needle
_exptl_crystal_F_000             1720
_exptl_crystal_size_max          0.33
_exptl_crystal_size_mid          0.05
_exptl_crystal_size_min          0.03
_refine_diff_density_max         0.406
_refine_diff_density_min         -0.309
_refine_diff_density_rms         0.050
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   -0.08(12)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.009
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     1037
_refine_ls_number_reflns         11655
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.009
_refine_ls_R_factor_all          0.0883
_refine_ls_R_factor_gt           0.0495
_refine_ls_shift/su_max          0.008
_refine_ls_shift/su_mean         0.001
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.0567P)^2^+0.3966P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1027
_refine_ls_wR_factor_ref         0.1189
_reflns_number_gt                7934
_reflns_number_total             11655
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            jo902650b_si_002.cif
_cod_data_source_block           p21_g
_cod_original_cell_volume        3992.7(2)
_cod_original_sg_symbol_Hall     P2yb
_cod_database_code               4025311