Synthesis of optically active SARS-CoV-2 Mpro inhibitor drug nirmatrelvir (Paxlovid): an approved treatment of COVID-19.
Ghosh, Arun K.; Yadav, Monika; Organic & biomolecular chemistry 21 (2023) 5768–5774; doi:10.1039/d3ob00653k

data_7159485
_publ_section_title
;
 Synthesis of optically active SARS-CoV-2 Mpro inhibitor drug nirmatrelvir
 (Paxlovid): an approved treatment of COVID-19.
;
_journal_issue                   28
_journal_name_full               'Organic &amp; biomolecular chemistry'
_journal_page_first              5768
_journal_page_last               5774
_journal_paper_doi               10.1039/d3ob00653k
_journal_volume                  21
_journal_year                    2023
_chemical_absolute_configuration ad
_chemical_formula_sum            'C16 H23 F3 N2 O4'
_chemical_formula_weight         364.36
_space_group_crystal_system      trigonal
_space_group_IT_number           146
_space_group_name_Hall           'R 3'
_space_group_name_H-M_alt        'R 3 :H'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_audit_creation_method           SHELXL-2018/3
_audit_update_record
;
2022-06-25 deposited with the CCDC.	2023-06-02 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                120
_cell_formula_units_Z            9
_cell_length_a                   23.5990(6)
_cell_length_b                   23.5990(6)
_cell_length_c                   10.4104(4)
_cell_measurement_reflns_used    9772
_cell_measurement_temperature    150(2)
_cell_measurement_theta_max      72.4903
_cell_measurement_theta_min      3.7461
_cell_volume                     5020.9(3)
_computing_cell_refinement       'SAINT V8.40B (Bruker, 2020)'
_computing_data_collection       'Apex4 v2021.4-0 (Bruker, 2021)'
_computing_data_reduction        'SAINT V8.40B (Bruker, 2020)'
_computing_structure_refinement
;  
SHELXL-2018/3 (Sheldrick, 2015, 2018), 
SHELXLE Rev1275(H\"ubschle et al., 2011)
SQUEEZE/PLATON -- Spek, A. L. (2003). J. Appl. Cryst. 36, 7-13.
;
_computing_structure_solution    'SHELXT (Sheldrick, 2015)'
_diffrn_ambient_temperature      150(2)
_diffrn_measured_fraction_theta_full 0.998
_diffrn_measured_fraction_theta_max 0.998
_diffrn_measurement_device_type
;
Bruker AXS D8 Quest diffractometer with PhotonIII_C14 charge-integrating and 
photon counting pixel array detector
;
_diffrn_measurement_method       'omega and phi scans'
_diffrn_radiation_monochromator  'laterally graded multilayer (Goebel) mirror'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0464
_diffrn_reflns_av_unetI/netI     0.0282
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.998
_diffrn_reflns_limit_h_max       29
_diffrn_reflns_limit_h_min       -29
_diffrn_reflns_limit_k_max       29
_diffrn_reflns_limit_k_min       -29
_diffrn_reflns_limit_l_max       12
_diffrn_reflns_limit_l_min       -9
_diffrn_reflns_number            48825
_diffrn_reflns_point_group_measured_fraction_full 0.915
_diffrn_reflns_point_group_measured_fraction_max 0.902
_diffrn_reflns_theta_full        67.679
_diffrn_reflns_theta_max         72.483
_diffrn_reflns_theta_min         4.767
_diffrn_source                   'I-mu-S microsource X-ray tube'
_diffrn_source_current           '1.0 mA'
_diffrn_source_voltage           '50 kV'
_exptl_absorpt_coefficient_mu    0.808
_exptl_absorpt_correction_T_max  0.7536
_exptl_absorpt_correction_T_min  0.6354
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS 2016/2: Krause, L., Herbst-Irmer, R., Sheldrick G.M. & Stalke D.
(2015). J. Appl. Cryst. 48, 3-10.
;
_exptl_crystal_colour            colorless
_exptl_crystal_density_diffrn    1.085
_exptl_crystal_description       needle
_exptl_crystal_F_000             1728
_exptl_crystal_size_max          0.432
_exptl_crystal_size_mid          0.186
_exptl_crystal_size_min          0.163
_refine_diff_density_max         0.102
_refine_diff_density_min         -0.104
_refine_diff_density_rms         0.023
_refine_ls_abs_structure_details
;
 Flack x determined using 1676 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.09(6)
_refine_ls_extinction_coef       0.00030(6)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     'SHELXL-2018/3 (Sheldrick 2018)'
_refine_ls_goodness_of_fit_ref   1.063
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     272
_refine_ls_number_reflns         3995
_refine_ls_number_restraints     160
_refine_ls_restrained_S_all      1.105
_refine_ls_R_factor_all          0.0262
_refine_ls_R_factor_gt           0.0258
_refine_ls_shift/su_max          0.009
_refine_ls_shift/su_mean         0.001
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0429P)^2^+0.6317P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0692
_refine_ls_wR_factor_ref         0.0695
_reflns_Friedel_coverage         0.807
_reflns_Friedel_fraction_full    0.832
_reflns_Friedel_fraction_max     0.805
_reflns_number_gt                3913
_reflns_number_total             3995
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d3ob00653k2.cif
_cod_data_source_block           my-05-133_re_sq
_cod_database_code               7159485
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_min   0.722
_shelx_estimated_absorpt_t_max   0.880
_shelx_res_checksum              97877
_shelx_fab_checksum              92070