Suzuki-Miyaura Approach to JNJ-26076713, an Orally Active Tetrahydroquinoline-Containing α~v~β~3~/α~v~β~5~ Integrin Antagonist. Enantioselective Synthesis and Stereochemical Studies
William A. Kinney; Christopher A. Teleha; Andrew S. Thompson; Maria Newport; Ryan Hansen; Scott Ballentine; Shyamali Ghosh; Andrew Mahan; Gabriela Grasa; Antonio Zanotti-Gerosa; Jules Dingenen; Carsten Schubert; Yong Zhou; Gregory C. Leo; David F. McComsey; Rosemary J. Santulli; Bruce E. Maryanoff; Journal of Organic Chemistry 73 (2008) 2302–2310; doi:10.1021/jo702551t

data_4023342
_publ_section_title
;
 Suzuki-Miyaura Approach to JNJ-26076713, an Orally Active
 Tetrahydroquinoline-Containing \a~v~\b~3~/\a~v~\b~5~
 Integrin Antagonist. Enantioselective Synthesis
 and Stereochemical Studies
;
_journal_name_full               'Journal of Organic Chemistry'
_journal_page_first              2302
_journal_page_last               2310
_journal_paper_doi               10.1021/jo702551t
_journal_volume                  73
_journal_year                    2008
_chemical_formula_sum            'C40 H56 N2 O9'
_chemical_formula_weight         708.87
_chemical_name_systematic
; 
 4-[1-(4,7,7-Trimethyl-3-oxo-2-oxa-bicyclo[2.2.1]heptane-1-carbonyl)-
piperidin-4-yl]-3-[1-(4,7,7-trimethyl-3-oxo-2-oxa-bicyclo[2.2.1]heptane-
1-carbonyl)-1,2,3,4-tetrahydro-quinolin-3-yl]-butyric acid methyl ester 
;
_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
_cell_angle_alpha                90.00
_cell_angle_beta                 91.23(3)
_cell_angle_gamma                90.00
_cell_formula_units_Z            2
_cell_length_a                   6.8900(14)
_cell_length_b                   13.610(3)
_cell_length_c                   19.800(4)
_cell_measurement_temperature    100(2)
_cell_volume                     1856.3(6)
_computing_cell_refinement       'Proteum 1.4'
_computing_data_collection       'Proteum 1.4'
_computing_data_reduction        SADABS
_computing_structure_refinement  'SHELXL-97 (Sheldrick, 1997)'
_computing_structure_solution    'SHELXS-97 (Sheldrick, 1990)'
_diffrn_ambient_temperature      100(2)
_diffrn_measured_fraction_theta_full 0.968
_diffrn_measured_fraction_theta_max 0.968
_diffrn_measurement_device_type  'Bruker D8'
_diffrn_measurement_method       'omaga and phi scans'
_diffrn_radiation_monochromator  'multilayer optics'
_diffrn_radiation_source         'rotating anode'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0251
_diffrn_reflns_av_sigmaI/netI    0.0131
_diffrn_reflns_limit_h_max       8
_diffrn_reflns_limit_h_min       -7
_diffrn_reflns_limit_k_max       16
_diffrn_reflns_limit_k_min       -15
_diffrn_reflns_limit_l_max       22
_diffrn_reflns_limit_l_min       -23
_diffrn_reflns_number            33897
_diffrn_reflns_theta_full        68.84
_diffrn_reflns_theta_max         68.84
_diffrn_reflns_theta_min         2.23
_exptl_absorpt_coefficient_mu    0.723
_exptl_absorpt_correction_type   empirical
_exptl_absorpt_process_details
;  
'empirical absorption correction as implemented in SHELX-97'
;
_exptl_crystal_density_diffrn    1.268
_exptl_crystal_density_method    'not measured'
_exptl_crystal_F_000             764
_exptl_crystal_size_max          'not measured'
_exptl_crystal_size_mid          'not measured'
_exptl_crystal_size_min          'not measured'
_refine_diff_density_max         0.354
_refine_diff_density_min         -0.303
_refine_diff_density_rms         0.033
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   0.09(12)
_refine_ls_extinction_coef       0.00056(16)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     SHELXL
_refine_ls_goodness_of_fit_ref   1.075
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     671
_refine_ls_number_reflns         6386
_refine_ls_number_restraints     1
_refine_ls_restrained_S_all      1.075
_refine_ls_R_factor_all          0.0300
_refine_ls_R_factor_gt           0.0299
_refine_ls_shift/su_max          0.165
_refine_ls_shift/su_mean         0.026
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.0442P)^2^+0.4135P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0793
_refine_ls_wR_factor_ref         0.0793
_reflns_number_gt                6369
_reflns_number_total             6386
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            jo702551t-File002.cif
_cod_data_source_block           Isomer_2
_cod_original_sg_symbol_H-M      'P 21'
_cod_database_code               4023342