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_7160950
_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         'C18 H27 B Br F N2 O3, C3 H7'
_chemical_formula_sum            'C21 H34 B Br F N2 O3'
_chemical_formula_weight         472.22
_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   geom
_atom_sites_solution_primary     dual
_audit_block_doi                 10.5517/ccdc.csd.cc2p3lr5
_audit_creation_date             2025-05-13
_audit_creation_method
;
Olex2 1.5
(compiled 2025.04.05 svn.rf049d14d for OlexSys, GUI svn.r7224)
;
_audit_update_record
;
2025-07-25 deposited with the CCDC.	2025-12-29 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 114.717(2)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   11.3295(2)
_cell_length_b                   22.0996(3)
_cell_length_c                   10.3207(2)
_cell_measurement_reflns_used    12258
_cell_measurement_temperature    99.9(7)
_cell_measurement_theta_max      73.4170
_cell_measurement_theta_min      3.9520
_cell_volume                     2347.33(8)
_computing_cell_refinement       'CrysAlisPro 1.171.43.142a (Rigaku OD, 2024)'
_computing_data_collection       'CrysAlisPro 1.171.43.142a (Rigaku OD, 2024)'
_computing_data_reduction        'CrysAlisPro 1.171.43.142a (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  'XL  (Sheldrick, 2008)'
_computing_structure_solution    'SHELXT  (Sheldrick, 2015)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      99.9(7)
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            HyPix
_diffrn_measured_fraction_theta_full 0.991
_diffrn_measured_fraction_theta_max 0.917
_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   -116.00 -77.00   0.50    2.00    --  -47.48-129.00 -89.00   78
  2  \w    -69.00 -43.00   0.50    2.00    --  -47.48 129.00 -17.00   52
  3  \w   -115.00 -88.00   0.50    2.00    --  -47.48-142.00  98.00   54
  4  \w     56.00 104.00   0.50    2.00    --   47.48-142.00  98.00   96
  5  \w     60.00  85.00   0.50    2.00    --   47.48-129.00 -89.00   50
  6  \w    -65.00 -40.00   0.50    8.00    --  -91.75 142.00 154.00   50
  7  \w   -133.00-108.00   0.50    8.00    --  -91.75-142.00  98.00   50
  8  \w    -97.00 -72.00   0.50    8.00    --  -91.75-129.00 -89.00   50
  9  \w   -162.00-102.00   0.50    8.00    --  -91.75-129.00 -89.00  120
 10  \w     82.00 107.00   0.50    8.00    --  103.50-129.00 -89.00   50
 11  \w     93.00 139.00   0.50    8.00    --  103.50 142.00 154.00   92
 12  \w    111.00 137.00   0.50    8.00    --  103.50 129.00 -17.00   52
 13  \w     97.00 122.00   0.50    8.00    --  103.50-142.00  98.00   50
 14  \w    -12.00  28.00   0.50    2.00    --  -47.48  19.00   0.00   80
 15  \w    -11.00  28.00   0.50    2.00    --  -47.48  19.00-120.00   78
 16  \w    -10.00  27.00   0.50    2.00    --  -47.48  19.00-180.00   74
 17  \w    -71.00 -39.00   0.50    2.00    --  -47.48 142.00 154.00   64
 18  \w    -39.00  19.00   0.50    2.00    --  -47.48  38.00 -90.00  116
 19  \w    -12.00  18.00   0.50    2.00    --  -47.48  19.00  60.00   60
 20  \w    -23.00   3.00   0.50    2.00    --   47.48 -19.00-180.00   52
 21  \w    -20.00  11.00   0.50    2.00    --   47.48 -19.00  30.00   62
 22  \w    -27.00   5.00   0.50    2.00    --   47.48 -19.00 -60.00   64
 23  \w   -148.00-111.00   0.50    8.00    --  -91.75 -77.00-180.00   74
 24  \w   -163.00-116.00   0.50    8.00    --  -91.75 -61.00  90.00   94
 25  \w    -49.00 -24.00   0.50    8.00    --  -91.75  45.00 -60.00   50
 26  \w    -49.00 -24.00   0.50    8.00    --  -91.75  45.00 -30.00   50
 27  \w   -163.00-107.00   0.50    8.00    --  -91.75 -61.00   0.00  112
 28  \w    -48.00 -23.00   0.50    8.00    --  -91.75  45.00   0.00   50
 29  \w   -163.00-108.00   0.50    8.00    --  -91.75 -61.00-150.00  110
 30  \w   -158.00-118.00   0.50    8.00    --  -91.75 -95.00 -30.00   80
 31  \w    -46.00 -20.00   0.50    8.00    --  -91.75  45.00-150.00   52
 32  \w    -49.00 -21.00   0.50    8.00    --  -91.75  45.00 150.00   56
 33  \w    -70.00 -19.00   0.50    8.00    --  -91.75  61.00 -30.00  102
 34  \w    -47.00 -20.00   0.50    8.00    --  -91.75  45.00-180.00   54
 35  \w    -49.00 -24.00   0.50    8.00    --  -91.75  45.00  30.00   50
 36  \w    -48.00 -21.00   0.50    8.00    --  -91.75  45.00  90.00   54
 37  \w   -162.00-106.00   0.50    8.00    --  -91.75 -61.00  30.00  112
 38  \w     72.00 103.00   0.50    8.00    --  103.50 -95.00 -60.00   62
 39  \w     38.00  64.00   0.50    8.00    --  103.50 -95.00 -60.00   52
 40  \w     62.00 103.00   0.50    8.00    --  103.50 -95.00 120.00   82
 41  \w     96.00 123.00   0.50    8.00    --  103.50 -77.00 -90.00   54
 42  \w     31.00  83.00   0.50    8.00    --  103.50 -77.00 -90.00  104
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'XtaLAB Synergy, Dualflex, HyPix'
_diffrn_measurement_method       '\w scans'
_diffrn_measurement_specimen_support 'Mitegen 50um'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      -0.1084772000
_diffrn_orient_matrix_UB_12      0.0415226000
_diffrn_orient_matrix_UB_13      0.0019776000
_diffrn_orient_matrix_UB_21      -0.0838129000
_diffrn_orient_matrix_UB_22      -0.0559135000
_diffrn_orient_matrix_UB_23      -0.0075705000
_diffrn_orient_matrix_UB_31      0.0601373000
_diffrn_orient_matrix_UB_32      -0.0030621000
_diffrn_orient_matrix_UB_33      0.1641472000
_diffrn_radiation_collimation    0.12
_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  0.0480
_diffrn_reflns_av_unetI/netI     0.0315
_diffrn_reflns_Laue_measured_fraction_full 0.991
_diffrn_reflns_Laue_measured_fraction_max 0.917
_diffrn_reflns_limit_h_max       14
_diffrn_reflns_limit_h_min       -14
_diffrn_reflns_limit_k_max       25
_diffrn_reflns_limit_k_min       -26
_diffrn_reflns_limit_l_max       12
_diffrn_reflns_limit_l_min       -9
_diffrn_reflns_number            22936
_diffrn_reflns_point_group_measured_fraction_full 0.991
_diffrn_reflns_point_group_measured_fraction_max 0.917
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         75.487
_diffrn_reflns_theta_min         4.001
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_current           1.0
_diffrn_source_power             0.05
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_diffrn_source_voltage           50.0
_exptl_absorpt_coefficient_mu    2.643
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.75668
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.43.142a (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    1.336
_exptl_crystal_description       plate
_exptl_crystal_F_000             988
_exptl_crystal_size_max          0.2
_exptl_crystal_size_mid          0.1
_exptl_crystal_size_min          0.005
_refine_diff_density_max         1.082
_refine_diff_density_min         -0.571
_refine_diff_density_rms         0.088
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.089
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     269
_refine_ls_number_reflns         4457
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.089
_refine_ls_R_factor_all          0.0513
_refine_ls_R_factor_gt           0.0467
_refine_ls_shift/su_max          0.001
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0712P)^2^+2.9569P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1276
_refine_ls_wR_factor_ref         0.1307
_reflns_Friedel_coverage         0.000
_reflns_number_gt                4050
_reflns_number_total             4457
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5ob01846c2.cif
_cod_data_source_block           xi_2025_5_13_ns
_cod_original_cell_volume        2347.32(8)
_cod_database_code               7160950
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         CHNBFBrO
_shelx_estimated_absorpt_t_max   0.987
_shelx_estimated_absorpt_t_min   0.620
_diffrn_oxdiff_digest_hkl
;
4344dd6303dc28050f7f599d4d61dc705c6da1
;
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2.a Ternary CH refined with riding coordinates:
 C7(H7)
2.b Secondary CH2 refined with riding coordinates:
 C9(H9A,H9B), C11(H11A,H11B), C19(H19A,H19B), C20(H20A,H20B)
2.c Aromatic/amide H refined with riding coordinates:
 N1(H1), C4(H4), C5(H5), C6(H6)
2.d Idealised Me refined as rotating group:
 C10(H10A,H10B,H10C), C12(H12A,H12B,H12C), C15(H15A,H15B,H15C), C16(H16A,H16B,
 H16C), C17(H17A,H17B,H17C), C18(H18A,H18B,H18C), C21(H21A,H21B,H21C)
;
_shelx_res_checksum              78214
_olex2_diffrn_ambient_temperature_device 'Oxford Cryosystems'
_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 2.080
_oxdiff_exptl_absorpt_empirical_full_min 0.562