Regioselective multicomponent synthesis of α-boryl ureas: discovery of a potent main protease inhibitor.
Gyasi, Yusif I.; Nyalata, Satyanarayana; Pa, Sophea; Gunasekera, Disni; Vulupala, Veerabhadra R.; Mallampudi, Nagarjun R.; Ramidi, Gopal R.; Xu, Shiqing; Organic & biomolecular chemistry 24 (2026) 1033–1041; doi:10.1039/d5ob01846c

data_7160949
_publ_section_title
;
 Regioselective multicomponent synthesis of &#x3b1;-boryl ureas: discovery
 of a potent main protease inhibitor.
;
_journal_issue                   5
_journal_name_full               'Organic &amp; biomolecular chemistry'
_journal_page_first              1033
_journal_page_last               1041
_journal_paper_doi               10.1039/d5ob01846c
_journal_volume                  24
_journal_year                    2026
_chemical_formula_moiety         'C23 H31 B N2 O3, H2 O'
_chemical_formula_sum            'C23 H33 B N2 O4'
_chemical_formula_weight         412.32
_space_group_crystal_system      monoclinic
_space_group_IT_number           14
_space_group_name_Hall           '-P 2ybc'
_space_group_name_H-M_alt        'P 1 21/c 1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_block_doi                 10.5517/ccdc.csd.cc2p3khw
_audit_creation_date             2025-04-03
_audit_creation_method
;
Olex2 1.5
(compiled 2023.08.24 svn.re1ec1418 for OlexSys, GUI svn.r6817)
;
_audit_update_record
;
2025-07-25 deposited with the CCDC.	2025-12-29 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 97.027(4)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   7.2002(3)
_cell_length_b                   14.5736(8)
_cell_length_c                   21.7237(10)
_cell_measurement_reflns_used    6512
_cell_measurement_temperature    99.9(4)
_cell_measurement_theta_max      77.6290
_cell_measurement_theta_min      3.5540
_cell_volume                     2262.41(19)
_computing_cell_refinement       'CrysAlisPro 1.171.43.143a (Rigaku OD, 2024)'
_computing_data_collection
'CrysAlisPro system (CCD 43.142a 64-bit (release 17-10-2024))'
_computing_data_reduction        'CrysAlisPro 1.171.43.143a (Rigaku OD, 2024)'
_computing_molecular_graphics    'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.5 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2019/1 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT  (Sheldrick, 2015)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      99.9(4)
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            HyPix
_diffrn_measured_fraction_theta_full 0.995
_diffrn_measured_fraction_theta_max 0.981
_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   -120.00 -62.00   0.50    8.96    --  -47.48-142.00  72.00  116
  2  \w   -118.00 -71.00   0.50    8.96    --  -47.48-129.00-116.00   94
  3  \w    -89.00 -15.00   0.50    8.96    --  -47.48 129.00 -42.00  148
  4  \w     44.00 105.00   0.50    8.96    --   47.48-142.00  72.00  122
  5  \w     37.00  96.00   0.50    8.96    --   47.48-129.00-116.00  118
  6  \w   -155.00 -62.00   0.50   35.85    --  -91.75-142.00  72.00  186
  7  \w    -88.00 -21.00   0.50   35.85    --  -91.75 129.00 -42.00  134
  8  \w     79.00 113.00   0.50   35.85    --  113.25-129.00-116.00   68
  9  \w    104.00 133.00   0.50   35.85    --  113.25 129.00 -42.00   58
 10  \w     92.00 124.00   0.50   35.85    --  113.25-142.00  72.00   64
 11  \w     47.00  86.00   0.50   35.85    --  113.25-142.00  72.00   78
 12  \w    -12.00  27.00   0.50    8.96    --  -47.48  19.00  60.00   78
 13  \w    -12.00  28.00   0.50    8.96    --  -47.48  19.00 150.00   80
 14  \w    -27.00  10.00   0.50    8.96    --   47.48 -19.00-180.00   74
 15  \w   -158.00-108.00   0.50   35.85    --  -91.75 -61.00   0.00  100
 16  \w    -46.00 -21.00   0.50   35.85    --  -91.75  45.00 120.00   50
 17  \w    -49.00 -20.00   0.50   35.85    --  -91.75  45.00-180.00   58
 18  \w     42.00 106.00   0.50   35.85    --  113.25 -95.00  90.00  128
 19  \w    101.00 173.00   0.50   35.85    --  113.25  15.00  90.00  144
 20  \w     42.00  74.00   0.50   35.85    --  113.25 -61.00 150.00   64
 21  \w     42.00  74.00   0.50   35.85    --  113.25 -61.00 -60.00   64
 22  \w    147.00 178.00   0.50   35.85    --  113.25  30.00  60.00   62
 23  \w    101.00 126.00   0.50   35.85    --  113.25  30.00  60.00   50
 24  \w     42.00 136.00   0.50   35.85    --  113.25 -77.00-120.00  188
 25  \w    104.00 129.00   0.50   35.85    --  113.25 142.00 128.00   50
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB Synergy, Dualflex, HyPix'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0004475000
_diffrn_orient_matrix_UB_12      0.0192461000
_diffrn_orient_matrix_UB_13      0.0697668000
_diffrn_orient_matrix_UB_21      -0.0104024000
_diffrn_orient_matrix_UB_22      -0.1037952000
_diffrn_orient_matrix_UB_23      0.0124990000
_diffrn_orient_matrix_UB_31      0.2152269000
_diffrn_orient_matrix_UB_32      -0.0049604000
_diffrn_orient_matrix_UB_33      0.0089353000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_unetI/netI     0.0181
_diffrn_reflns_Laue_measured_fraction_full 0.995
_diffrn_reflns_Laue_measured_fraction_max 0.981
_diffrn_reflns_limit_h_max       8
_diffrn_reflns_limit_h_min       -4
_diffrn_reflns_limit_k_max       18
_diffrn_reflns_limit_k_min       -18
_diffrn_reflns_limit_l_max       26
_diffrn_reflns_limit_l_min       -27
_diffrn_reflns_number            5286
_diffrn_reflns_point_group_measured_fraction_full 0.995
_diffrn_reflns_point_group_measured_fraction_max 0.981
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         74.479
_diffrn_reflns_theta_min         3.661
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_current           '1 mA'
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_diffrn_source_voltage           '50 kV'
_exptl_absorpt_coefficient_mu    0.653
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.43071
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.43.143a (Rigaku Oxford Diffraction, 2024)
Empirical absorption correction using spherical harmonics,
implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.211
_exptl_crystal_description       needle
_exptl_crystal_F_000             888
_exptl_crystal_size_max          0.48
_exptl_crystal_size_mid          0.024
_exptl_crystal_size_min          0.013
_refine_diff_density_max         0.246
_refine_diff_density_min         -0.254
_refine_diff_density_rms         0.049
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.065
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     279
_refine_ls_number_reflns         5286
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.065
_refine_ls_R_factor_all          0.0521
_refine_ls_R_factor_gt           0.0456
_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^)+(0.0631P)^2^+0.9677P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1144
_refine_ls_wR_factor_ref         0.1221
_reflns_Friedel_coverage         0.000
_reflns_number_gt                4694
_reflns_number_total             5286
_reflns_threshold_expression     'I > 2\s(I)'
_twin_special_details
;
Component 2 rotated by -179.9752\% 
around [0.94 0.00 -0.34] (reciprocal) or [1.00 0.00 -0.00] (direct)
;
_cod_data_source_file            d5ob01846c2.cif
_cod_data_source_block           sx_nsa195_twin1_hklf4
_cod_database_code               7160949
_shelx_shelxl_version_number     2019/1
_chemical_oxdiff_formula         C23H31N2BO3
_shelx_estimated_absorpt_t_max   0.992
_shelx_estimated_absorpt_t_min   0.745
_olex2_refinement_description
;
1. Twinned data refinement
 Scales: 0.7537(13)
 0.2463(13)
2. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H,H) groups
3.a Free rotating group:
 O4(H4D,H4E)
3.b Ternary CH refined with riding coordinates:
 C8(H8)
3.c Secondary CH2 refined with riding coordinates:
 C9(H9A,H9B), C10(H10A,H10B), C17(H17A,H17B)
3.d Aromatic/amide H refined with riding coordinates:
 C12(H12), C13(H13), C14(H14), C15(H15), C16(H16), C19(H19), C20(H20),
 C21(H21), C22(H22), C23(H23)
3.e X=CH2 refined with riding coordinates:
 N2(H2A,H2B)
3.f Idealised Me refined as rotating group:
 C3(H3A,H3B,H3C), C4(H4A,H4B,H4C), C5(H5A,H5B,H5C), C6(H6A,H6B,H6C)
;
_shelx_res_checksum              37697
_olex2_exptl_crystal_mounting_method
'The crystal was mounted on a MITIGEN holder'
_olex2_submission_original_sample_id SXB_SN_250402_Sc_A195
_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
- Detector area scaling
;
_oxdiff_exptl_absorpt_empirical_full_max 1.637
_oxdiff_exptl_absorpt_empirical_full_min 0.459
_oxdiff_twin_integration_method  simultaneous
_oxdiff_twin_items               2