An Expeditious Synthesis of the MDM2-p53 Inhibitor AM-8553
Brian S. Lucas; Benjamin Fisher; Lawrence R. McGee; Steven H. Olson; Julio C. Medina; Eugene Cheung; Journal of the American Chemical Society 134 (2012) 12855–12860; doi:10.1021/ja305123v

data_4118429
_publ_contact_author_address
;
Amgen Inc.
One Amgen Center Drive
Thousand Oaks, CA 91320
USA
;
_publ_contact_author_email       blucas@amgen.com
_publ_contact_author_name        'Brian Lucas'
_publ_section_title
;
 An Expeditious Synthesis of the MDM2-p53 Inhibitor AM-8553
;
_journal_name_full               'Journal of the American Chemical Society'
_journal_page_first              12855
_journal_page_last               12860
_journal_paper_doi               10.1021/ja305123v
_journal_volume                  134
_journal_year                    2012
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C26 H31 Cl2 N O2'
_chemical_formula_sum            'C26 H31 Cl2 N O2'
_chemical_formula_weight         460.42
_space_group_IT_number           19
_symmetry_cell_setting           orthorhombic
_symmetry_space_group_name_Hall  'P 2ac 2ab'
_symmetry_space_group_name_H-M   'P 21 21 21'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_audit_creation_method           SHELXL-97
_audit_update_record
;
2012-05-22 # Formatted by publCIF
;
_cell_angle_alpha                90.00
_cell_angle_beta                 90.00
_cell_angle_gamma                90.00
_cell_formula_units_Z            4
_cell_length_a                   10.4852(9)
_cell_length_b                   13.3205(11)
_cell_length_c                   17.2875(17)
_cell_measurement_reflns_used    3534
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      59.94
_cell_measurement_theta_min      4.933
_cell_volume                     2414.5(4)
_computing_cell_refinement       'Apex2 (Bruker AXS, 2006)'
_computing_data_collection       'Apex2 (Bruker AXS, 2006)'
_computing_data_reduction        'Apex2 (Bruker AXS, 2006)'
_computing_molecular_graphics    'publCIF (Westrip, 2010)'
_computing_publication_material  'publCIF (Westrip, 2010)'
_computing_structure_refinement  'SHELXL-97 (Sheldrick, 1997)'
_computing_structure_solution    'SHELXS-97 (Sheldrick, 1990)'
_diffrn_ambient_temperature      100(2)
_diffrn_measured_fraction_theta_full 0.961
_diffrn_measured_fraction_theta_max 0.961
_diffrn_measurement_device       'Bruker Kappa Apex2'
_diffrn_measurement_device_type  Area
_diffrn_measurement_method       '\f & \w scans'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_source         'fine-focus sealed tube'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.1351
_diffrn_reflns_av_sigmaI/netI    0.1368
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -12
_diffrn_reflns_limit_k_max       12
_diffrn_reflns_limit_k_min       -15
_diffrn_reflns_limit_l_max       11
_diffrn_reflns_limit_l_min       -19
_diffrn_reflns_number            15740
_diffrn_reflns_theta_full        63.17
_diffrn_reflns_theta_max         63.17
_diffrn_reflns_theta_min         4.19
_exptl_absorpt_coefficient_mu    2.587
_exptl_absorpt_correction_T_max  0.7523
_exptl_absorpt_correction_T_min  0.5780
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   'Apex2 (Bruker AXS, 2006)'
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.267
_exptl_crystal_description       prism
_exptl_crystal_F_000             976
_exptl_crystal_size_max          0.2
_exptl_crystal_size_mid          0.1
_exptl_crystal_size_min          0.1
_refine_diff_density_max         0.610
_refine_diff_density_min         -0.343
_refine_diff_density_rms         0.073
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   0.02(3)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.044
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     284
_refine_ls_number_reflns         3657
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.044
_refine_ls_R_factor_all          0.0835
_refine_ls_R_factor_gt           0.0664
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.0000P)^2^+3.9556P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1672
_refine_ls_wR_factor_ref         0.1817
_reflns_number_gt                3028
_reflns_number_total             3657
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            ja305123v_si_003.cif
_cod_data_source_block           p212121a
_cod_original_sg_symbol_H-M      'P 21 21 21 '
_cod_database_code               4118429