Two-stage one-pot synthetic strategy for the key triazone-triazole intermediate of ensitrelvir (S-217622), an oral clinical candidate for treating COVID-19
Hu, Wei; Zhang, Xiang; Liu, Yuanchang; Liu, Teng; Wen, Jiale; Peng, Xiaopeng; Xie, Xin; Chen, Weiming; RSC Advances 12 (2022) 34808–34814; doi:10.1039/D2RA06841A

data_1568060
_publ_section_title
;
 Two-stage one-pot synthetic strategy for the key triazone-triazole
 intermediate of ensitrelvir (S-217622), an oral clinical candidate for
 treating COVID-19
;
_journal_issue                   54
_journal_name_full               'RSC Advances'
_journal_page_first              34808
_journal_page_last               34814
_journal_paper_doi               10.1039/D2RA06841A
_journal_volume                  12
_journal_year                    2022
_chemical_formula_moiety         'C16 H15 F3 N6 O2 S'
_chemical_formula_sum            'C16 H15 F3 N6 O2 S'
_chemical_formula_weight         412.40
_space_group_crystal_system      monoclinic
_space_group_IT_number           14
_space_group_name_Hall           '-P 2yn'
_space_group_name_H-M_alt        'P 1 21/n 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_block_doi                 10.5517/ccdc.csd.cc2d8llw
_audit_creation_date             2022-05-09
_audit_creation_method
;
Olex2 1.5-beta
(compiled 2021.12.09 svn.r5202d8cf for OlexSys, GUI svn.r6439)
;
_audit_update_record
;
2022-10-13 deposited with the CCDC.	2022-12-06 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 95.723(10)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   11.715(6)
_cell_length_b                   7.738(4)
_cell_length_c                   19.834(9)
_cell_measurement_reflns_used    4037
_cell_measurement_temperature    296.15
_cell_measurement_theta_max      20.27
_cell_measurement_theta_min      2.83
_cell_volume                     1789.0(15)
_computing_molecular_graphics    'Olex2 1.5-beta (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5-beta (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2017/1 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2014/5 (Sheldrick, 2014)'
_diffrn_ambient_temperature      296.15
_diffrn_measured_fraction_theta_full 0.991
_diffrn_measured_fraction_theta_max 0.991
_diffrn_measurement_device_type  'CCD area detector'
_diffrn_measurement_method       'phi and omega scans'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.1091
_diffrn_reflns_av_unetI/netI     0.0843
_diffrn_reflns_Laue_measured_fraction_full 0.991
_diffrn_reflns_Laue_measured_fraction_max 0.991
_diffrn_reflns_limit_h_max       13
_diffrn_reflns_limit_h_min       -13
_diffrn_reflns_limit_k_max       9
_diffrn_reflns_limit_k_min       -9
_diffrn_reflns_limit_l_max       23
_diffrn_reflns_limit_l_min       -23
_diffrn_reflns_number            38273
_diffrn_reflns_point_group_measured_fraction_full 0.991
_diffrn_reflns_point_group_measured_fraction_max 0.991
_diffrn_reflns_theta_full        25.104
_diffrn_reflns_theta_max         25.104
_diffrn_reflns_theta_min         2.064
_diffrn_source_current           30.0
_diffrn_source_power             1.5
_diffrn_source_voltage           50.0
_exptl_absorpt_coefficient_mu    0.238
_exptl_absorpt_correction_T_max  0.977
_exptl_absorpt_correction_T_min  0.968
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   SADABS
_exptl_crystal_colour            colorless
_exptl_crystal_density_diffrn    1.531
_exptl_crystal_description       block
_exptl_crystal_F_000             848
_exptl_crystal_size_max          0.14
_exptl_crystal_size_mid          0.12
_exptl_crystal_size_min          0.1
_refine_diff_density_max         0.222
_refine_diff_density_min         -0.270
_refine_diff_density_rms         0.061
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.056
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     255
_refine_ls_number_reflns         3161
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.056
_refine_ls_R_factor_all          0.1600
_refine_ls_R_factor_gt           0.0593
_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^)+(0.0542P)^2^+0.9059P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1132
_refine_ls_wR_factor_ref         0.1501
_reflns_Friedel_coverage         0.000
_reflns_number_gt                1585
_reflns_number_total             3161
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d2ra06841a2.cif
_cod_data_source_block           dr
_cod_original_cell_volume        1788.9(15)
_cod_database_code               1568060
_shelx_shelxl_version_number     2017/1
_shelx_estimated_absorpt_t_max   0.977
_shelx_estimated_absorpt_t_min   0.968
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2.a Secondary CH2 refined with riding coordinates:
 C4(H4A,H4B), C8(H8A,H8B), C15(H15A,H15B)
2.b Aromatic/amide H refined with riding coordinates:
 C6(H6), C10(H10), C13(H13)
2.c Idealised Me refined as rotating group:
 C7(H7A,H7B,H7C), C16(H16A,H16B,H16C)
;
_shelx_res_checksum              69860
_shelx_hkl_checksum              60577
_olex2_submission_special_instructions 'No special instructions were received'