Continuous flow synthesis of the antiviral drug tecovirimat and related sp<sup>3</sup>-rich scaffolds.
Bonner, Arlene; Baumann, Marcus; Organic & biomolecular chemistry 22 (2024) 8323–8327; doi:10.1039/d4ob01379d

data_7160157
_publ_section_title
;
 Continuous flow synthesis of the antiviral drug tecovirimat and related
 sp<sup>3</sup>-rich scaffolds.
;
_journal_issue                   41
_journal_name_full               'Organic &amp; biomolecular chemistry'
_journal_page_first              8323
_journal_page_last               8327
_journal_paper_doi               10.1039/d4ob01379d
_journal_volume                  22
_journal_year                    2024
_chemical_formula_moiety         'C11 H12 O3'
_chemical_formula_sum            'C11 H12 O3'
_chemical_formula_weight         192.21
_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   mixed
_atom_sites_solution_primary     dual
_audit_creation_date             2023-11-15
_audit_creation_method
;
Olex2 1.5
(compiled 2023.08.24 svn.re1ec1418 for OlexSys, GUI svn.r6817)
;
_audit_update_record
;
2024-08-20 deposited with the CCDC.	2024-09-18 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 94.5670(10)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   6.28270(10)
_cell_length_b                   6.33670(10)
_cell_length_c                   23.1722(3)
_cell_measurement_reflns_used    8807
_cell_measurement_temperature    104.70(14)
_cell_measurement_theta_max      76.0860
_cell_measurement_theta_min      3.8100
_cell_volume                     919.59(2)
_computing_cell_refinement       'CrysAlisPro 1.171.42.92a (Rigaku OD, 2023)'
_computing_data_collection       'CrysAlisPro 1.171.42.92a (Rigaku OD, 2023)'
_computing_data_reduction        'CrysAlisPro 1.171.42.92a (Rigaku OD, 2023)'
_computing_molecular_graphics    'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2018/3 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2018/2 (Sheldrick, 2018)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      104.70(14)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 10.3196
_diffrn_detector_type            Atlas
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.996
_diffrn_measurement_details
;
List of Runs (angles in degrees, time in seconds):

  # Type    Start    End  Width  t~exp~   \w     \q     \k     \f   Frames
  1  \w    -99.00 -14.00   1.00    1.00    --  -41.95 142.00 -62.00   85
  2  \w   -114.00 -66.00   1.00    1.00    --  -41.95-142.00-119.00   48
  3  \w    -88.00  -7.00   1.00    1.00    --  -41.95 127.00 126.00   81
  4  \w     29.00  98.00   1.00    1.00    --   41.95-127.00  51.00   69
  5  \w     87.00 172.00   1.00    1.00    --  112.00 142.00 -62.00   85
  6  \w     40.00 114.00   1.00    1.00    --  112.00-127.00  51.00   74
  7  \w     96.00 178.00   1.00    1.00    --  112.00 127.00 126.00   82
  8  \w     40.00 126.00   1.00    1.00    --  112.00-142.00-119.00   86
  9  \w    -66.00  33.00   1.00    1.00    --  -41.95  37.00  30.00   99
 10  \w   -116.00 -18.00   1.00    1.00    --  -41.95 -37.00-150.00   98
 11  \w    103.00 178.00   1.00    1.00    --  112.00  77.00   0.00   75
 12  \w    104.00 178.00   1.00    1.00    --  112.00 111.00  90.00   74
 13  \w     39.00 109.00   1.00    1.00    --  112.00-111.00-120.00   70
 14  \w     29.00 107.00   1.00    1.00    --  112.00 -94.00 -90.00   78
 15  \w     84.00 178.00   1.00    1.00    --  112.00  30.00 -60.00   94
 16  \w     39.00 109.00   1.00    1.00    --  112.00-111.00  90.00   70
 17  \w     39.00 109.00   1.00    1.00    --  112.00-111.00  60.00   70
 18  \w    104.00 178.00   1.00    1.00    --  112.00 111.00 120.00   74
 19  \w     39.00 109.00   1.00    1.00    --  112.00-111.00 -90.00   70
 20  \w     39.00 109.00   1.00    1.00    --  112.00-111.00  30.00   70
 21  \w    103.00 178.00   1.00    1.00    --  112.00  77.00-150.00   75
 22  \w    -66.00  33.00   1.00    1.00    --  -41.95  37.00 -90.00   99
 23  \w   -115.00 -14.00   1.00    1.00    --  -41.95 -57.00 -30.00  101
 24  \w   -115.00 -14.00   1.00    1.00    --  -41.95 -57.00  90.00  101
 25  \w     10.00  36.00   1.00    1.00    --   41.95  75.00 119.79   26
 26  \w      8.00  42.00   1.00    1.00    --   41.95  81.00  61.31   34
 27  \w      8.00  34.00   1.00    1.00    --   41.95  83.00-145.32   26
 28  \w     84.00 178.00   1.00    1.00    --  112.00  30.00  90.00   94
 29  \w     83.00 178.00   1.00    1.00    --  112.00  59.00 -47.55   95
 30  \w     83.00 178.00   1.00    1.00    --  112.00  61.00 120.00   95
 31  \w     83.00 178.00   1.00    1.00    --  112.00  61.00-150.00   95
 32  \w    104.00 178.00   1.00    1.00    --  112.00 111.00-120.00   74
 33  \w     86.00 178.00   1.00    1.00    --  112.00  45.00   0.00   92
 34  \w     83.00 178.00   1.00    1.00    --  112.00  61.00  30.00   95
 35  \w     83.00 178.00   1.00    1.00    --  112.00  61.00-120.00   95
 36  \w     83.00 118.00   1.00    1.00    --  112.00  61.00-180.00   35
 37  \w     84.00 178.00   1.00    1.00    --  112.00  56.00  79.50   94
 38  \w     84.00 178.00   1.00    1.00    --  112.00  30.00-180.00   94
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at home/near, Atlas'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0475517000
_diffrn_orient_matrix_UB_12      -0.0041438000
_diffrn_orient_matrix_UB_13      -0.0642107000
_diffrn_orient_matrix_UB_21      -0.0130916000
_diffrn_orient_matrix_UB_22      -0.2427589000
_diffrn_orient_matrix_UB_23      0.0001677000
_diffrn_orient_matrix_UB_31      -0.2409287000
_diffrn_orient_matrix_UB_32      0.0123843000
_diffrn_orient_matrix_UB_33      -0.0181013000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0336
_diffrn_reflns_av_unetI/netI     0.0143
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.996
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -7
_diffrn_reflns_limit_k_max       7
_diffrn_reflns_limit_k_min       -7
_diffrn_reflns_limit_l_max       29
_diffrn_reflns_limit_l_min       -29
_diffrn_reflns_number            15698
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.996
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         76.259
_diffrn_reflns_theta_min         3.827
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.830
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.428
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.42.92a (Rigaku Oxford Diffraction, 2023)
Numerical absorption correction based on gaussian integration over
a multifaceted crystal model
Empirical absorption correction using spherical harmonics,
implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'translucent light colourless'
_exptl_crystal_density_diffrn    1.388
_exptl_crystal_description       block
_exptl_crystal_F_000             408
_exptl_crystal_size_max          0.341
_exptl_crystal_size_mid          0.281
_exptl_crystal_size_min          0.138
_refine_diff_density_max         0.255
_refine_diff_density_min         -0.219
_refine_diff_density_rms         0.039
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.036
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     131
_refine_ls_number_reflns         1910
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.036
_refine_ls_R_factor_all          0.0385
_refine_ls_R_factor_gt           0.0345
_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^)+(0.0338P)^2^+0.5281P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0817
_refine_ls_wR_factor_ref         0.0850
_reflns_Friedel_coverage         0.000
_reflns_number_gt                1730
_reflns_number_total             1910
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d4ob01379d2.cif
_cod_data_source_block           exp_1817_AB-89-2-5F29
_cod_depositor_comments
'Adding full bibliography for 7160156--7160157.cif.'
_cod_database_code               7160157
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C11H12O3 '
_chemical_oxdiff_usercomment     AB-89-2-5F29_ArleneBonner_Baumann
_shelx_estimated_absorpt_t_max   0.894
_shelx_estimated_absorpt_t_min   0.765
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups
2.a Ternary CH refined with riding coordinates:
 C1(H1), C3(H3), C4(H4), C5(H5), C6(H6), C7(H7), C9(H9)
2.b Secondary CH2 refined with riding coordinates:
 C2(H2A,H2B)
2.c Aromatic/amide H refined with riding coordinates:
 C10(H10), C11(H11)
;
_shelx_res_checksum              35035
_olex2_submission_special_instructions 'No special instructions were received'
_oxdiff_exptl_absorpt_empirical_details
;
Empirical correction (ABSPACK) includes:
- Absorption correction using spherical harmonics
- Frame scaling
;
_oxdiff_exptl_absorpt_empirical_full_max 1.871
_oxdiff_exptl_absorpt_empirical_full_min 0.645