Synthesis and separation of the enantiomers of the neuropeptide S receptor antagonist (9R/S)-3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic acid 4-fluoro-benzylamide (SHA 68).
Trapella, Claudio; Pela, Michela; Del Zoppo, Luisa; Calo, Girolamo; Camarda, Valeria; Ruzza, Chiara; Cavazzini, Alberto; Costa, Valentina; Bertolasi, Valerio; Reinscheid, Rainer K.; Salvadori, Severo; Guerrini, Remo; Journal of medicinal chemistry 54 (2011) 2738–2744; doi:10.1021/jm200138r

data_1501660
_publ_section_title
;
 Synthesis and separation of the enantiomers of the neuropeptide S
 receptor antagonist
 (9R/S)-3-oxo-1,1-diphenyl-tetrahydro-oxazolo[3,4-a]pyrazine-7-carboxylic
 acid 4-fluoro-benzylamide (SHA 68).
;
_journal_issue                   8
_journal_name_full               'Journal of medicinal chemistry'
_journal_page_first              2738
_journal_page_last               2744
_journal_paper_doi               10.1021/jm200138r
_journal_volume                  54
_journal_year                    2011
_chemical_absolute_configuration syn
_chemical_formula_moiety         'C26 H26 N2 O2'
_chemical_formula_sum            'C26 H26 N2 O2'
_chemical_formula_weight         398.49
_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
_cell_angle_alpha                90.00
_cell_angle_beta                 90.00
_cell_angle_gamma                90.00
_cell_formula_units_Z            4
_cell_length_a                   11.2339(2)
_cell_length_b                   11.6808(3)
_cell_length_c                   16.4783(5)
_cell_measurement_reflns_used    16307
_cell_measurement_temperature    295
_cell_measurement_theta_max      26.00
_cell_measurement_theta_min      3.53
_cell_volume                     2162.30(9)
_computing_cell_refinement       'Denzo-SMN (Otwinowski & Minor, 1997)'
_computing_data_collection       'COLLECT (Nonius, 1998)'
_computing_data_reduction        'Denzo-SMN (Otwinowski & Minor, 1997)'
_computing_molecular_graphics    'ORTEPIII (Burnett & Johnson, 1996)'
_computing_publication_material
'SHELXL-97 (Sheldrick, 1997), PARST (Nardelli, 1995)'
_computing_structure_refinement  'SHELXL-97 (Sheldrick, 1997)'
_computing_structure_solution    'SIR97 (Altomare et al., 1999)'
_diffrn_ambient_temperature      295
_diffrn_measured_fraction_theta_full 0.994
_diffrn_measured_fraction_theta_max 0.994
_diffrn_measurement_device_type  'Nonius Kappa CCD'
_diffrn_measurement_method       '\f scans and \w 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  0.0360
_diffrn_reflns_av_sigmaI/netI    0.0321
_diffrn_reflns_limit_h_max       13
_diffrn_reflns_limit_h_min       -13
_diffrn_reflns_limit_k_max       14
_diffrn_reflns_limit_k_min       -14
_diffrn_reflns_limit_l_max       20
_diffrn_reflns_limit_l_min       -20
_diffrn_reflns_number            16307
_diffrn_reflns_theta_full        26.00
_diffrn_reflns_theta_max         26.00
_diffrn_reflns_theta_min         3.53
_exptl_absorpt_coefficient_mu    0.078
_exptl_absorpt_correction_type   none
_exptl_crystal_colour            colorless
_exptl_crystal_density_diffrn    1.224
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       prismatic
_exptl_crystal_F_000             848
_exptl_crystal_size_max          0.35
_exptl_crystal_size_mid          0.24
_exptl_crystal_size_min          0.12
_refine_diff_density_max         0.086
_refine_diff_density_min         -0.091
_refine_diff_density_rms         0.023
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   1.0(12)
_refine_ls_extinction_coef       0.050(3)
_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   1.048
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     273
_refine_ls_number_reflns         4215
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.048
_refine_ls_R_factor_all          0.0527
_refine_ls_R_factor_gt           0.0365
_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^)+(0.0369P)^2^+0.2379P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0813
_refine_ls_wR_factor_ref         0.0904
_reflns_number_gt                3460
_reflns_number_total             4215
_reflns_threshold_expression     I>2sigma(I)
_cod_data_source_file            jm200138r_si_002.cif
_cod_data_source_block           7
_cod_original_sg_symbol_H-M      'P 212121'
_cod_database_code               1501660