Development of a Large-Scale Route to Glecaprevir: Synthesis of the Macrocycle via Intramolecular Etherification
Kallemeyn, Jeffrey M.; Engstrom, Kenneth M.; Pelc, Matthew J.; Lukin, Kirill A.; Morrill, Westin H.; Wei, Haojuan; Towne, Timothy B.; Henle, Jeremy; Nere, Nandkishor K.; Welch, Dennie S.; Shekhar, Shashank; Ravn, Matthew M.; Zhao, Gang; Fickes, Michael G.; Ding, Chen; Vinci, John C.; Marren, James; Cink, Russell D.; Organic Process Research & Development  (2020) –; doi:10.1021/acs.oprd.0c00244

data_1558669
_publ_section_title
;
 Development of a Large-Scale Route to Glecaprevir: Synthesis of the
 Macrocycle via Intramolecular Etherification
;
_journal_name_full               'Organic Process Research &amp; Development'
_journal_paper_doi               10.1021/acs.oprd.0c00244
_journal_year                    2020
_chemical_absolute_configuration syn
_chemical_formula_sum            'C24.75 H29.25 F1.5 N3 O5.62'
_chemical_formula_weight         487.26
_space_group_crystal_system      trigonal
_space_group_IT_number           152
_space_group_name_Hall           'P 31 2"'
_space_group_name_H-M_alt        'P 31 2 1'
_atom_sites_solution_hydrogens   mixed
_audit_creation_method           SHELXL-2016/6
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                120
_cell_formula_units_Z            8
_cell_length_a                   20.700(3)
_cell_length_b                   20.700(3)
_cell_length_c                   13.6652(17)
_cell_measurement_reflns_used    7067
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      19.945
_cell_measurement_theta_min      2.272
_cell_volume                     5070.9(12)
_computing_structure_refinement  'SHELXL-2016/6 (Sheldrick, 2016)'
_diffrn_ambient_temperature      100(2)
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.999
_diffrn_measurement_device_type  CCD
_diffrn_measurement_method       'Omega Scan'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.1720
_diffrn_reflns_av_unetI/netI     0.1234
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.999
_diffrn_reflns_limit_h_max       26
_diffrn_reflns_limit_h_min       -26
_diffrn_reflns_limit_k_max       26
_diffrn_reflns_limit_k_min       -26
_diffrn_reflns_limit_l_max       17
_diffrn_reflns_limit_l_min       -17
_diffrn_reflns_number            58675
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 0.997
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         27.466
_diffrn_reflns_theta_min         1.136
_diffrn_source                   'Sealed Tube'
_exptl_absorpt_coefficient_mu    0.098
_exptl_absorpt_correction_type   multi-scan
_exptl_crystal_colour            colourless
_exptl_crystal_density_diffrn    1.277
_exptl_crystal_description       rod
_exptl_crystal_F_000             2058
_exptl_crystal_size_max          0.300
_exptl_crystal_size_mid          0.100
_exptl_crystal_size_min          0.100
_exptl_transmission_factor_max   1
_exptl_transmission_factor_min   0.864
_refine_diff_density_max         0.293
_refine_diff_density_min         -0.271
_refine_diff_density_rms         0.052
_refine_ls_abs_structure_details
;
 Flack x determined using 1529 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.7(5)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.072
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     474
_refine_ls_number_reflns         7740
_refine_ls_number_restraints     96
_refine_ls_restrained_S_all      1.087
_refine_ls_R_factor_all          0.1344
_refine_ls_R_factor_gt           0.0585
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+0.7632P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0593
_refine_ls_wR_factor_ref         0.0691
_reflns_Friedel_coverage         0.845
_reflns_Friedel_fraction_full    1.000
_reflns_Friedel_fraction_max     0.996
_reflns_number_gt                4560
_reflns_number_total             7740
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            op0c00244_si_002.cif
_cod_data_source_block           Macrocycle_3_p-xylene
_cod_original_cell_volume        5070.8(16)
_cod_original_formula_sum        'C24.75 H29.25 F1.50 N3 O5.62'
_cod_database_code               1558669
_shelx_shelxl_version_number     2016/6
_shelx_estimated_absorpt_t_min   0.971
_shelx_estimated_absorpt_t_max   0.990
_shelx_res_checksum              93360
_shelx_hkl_checksum              25249