# Supplementary Information (SI) for RSC Medicinal Chemistry.
# This journal is © The Royal Society of Chemistry 2025

####################################################################### 
# 
# This file contains crystal structure data downloaded from the 
# Cambridge Structural Database (CSD) hosted by the Cambridge 
# Crystallographic Data Centre (CCDC).
# 
# Full information about CCDC data access policies and citation 
# guidelines are available at http://www.ccdc.cam.ac.uk/access/V1 
# 
# Audit and citation data items may have been added by the CCDC. 
# Please retain this information to preserve the provenance of 
# this file and to allow appropriate attribution of the data. 
# 
#######################################################################

data_1212s36_0m
_database_code_depnum_ccdc_archive 'CCDC 2243568'
loop_
_audit_author_name
_audit_author_address
'Jieru Hui'
;Guangdong Pharmaceutical University
China
;
_audit_update_record             
;
2023-02-19 deposited with the CCDC.	2025-10-16 downloaded from the CCDC.
;
_audit_creation_date             2022-12-12
_audit_creation_method           
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_shelx_SHELXL_version_number     2018/3
_chemical_name_common            ?
_chemical_name_systematic        ?
_chemical_formula_moiety         'I, 0.5(C2 H4 Cl2), C25 H27 F N3 O2'
_chemical_formula_sum            'C26 H29 Cl F I N3 O2'
_chemical_formula_weight         596.87
_chemical_melting_point          ?
loop_
_atom_type_symbol
_atom_type_description
_atom_type_scat_dispersion_real
_atom_type_scat_dispersion_imag
_atom_type_scat_source
C C 0.0033 0.0016 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'
H H 0.0000 0.0000 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'
Cl Cl 0.1484 0.1585 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'
F F 0.0171 0.0103 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'
I I -0.4742 1.8119 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'
N N 0.0061 0.0033 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'
O O 0.0106 0.0060 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'

_shelx_space_group_comment       
;
The symmetry employed for this shelxl refinement is uniquely defined
by the following loop, which should always be used as a source of
symmetry information in preference to the above space-group names.
They are only intended as comments.
;
_space_group_crystal_system      monoclinic
_space_group_IT_number           15
_space_group_name_H-M_alt        'C 1 2/c 1'
_space_group_name_Hall           '-C 2yc'
loop_
_space_group_symop_operation_xyz
'x, y, z'
'-x, y, -z+1/2'
'x+1/2, y+1/2, z'
'-x+1/2, y+1/2, -z+1/2'
'-x, -y, -z'
'x, -y, z-1/2'
'-x+1/2, -y+1/2, -z'
'x+1/2, -y+1/2, z-1/2'

_cell_length_a                   37.035(3)
_cell_length_b                   9.0602(6)
_cell_length_c                   15.6080(11)
_cell_angle_alpha                90
_cell_angle_beta                 94.353(3)
_cell_angle_gamma                90
_cell_volume                     5222.1(7)
_cell_formula_units_Z            8
_cell_measurement_reflns_used    4905
_cell_measurement_temperature    150
_cell_measurement_theta_max      26.119
_cell_measurement_theta_min      2.206
_shelx_estimated_absorpt_T_max   0.935
_shelx_estimated_absorpt_T_min   0.822
_exptl_absorpt_coefficient_mu    1.363
_exptl_absorpt_correction_T_max  0.9281
_exptl_absorpt_correction_T_min  0.7351
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   
'SADABS-2016/2 (Bruker,2016/2) was used for absorption correction. wR2(int) was 0.0707 before and 0.0543 after correction. The Ratio of minimum to maximum transmission is 0.7920. The λ/2 correction factor is Not present.'
_exptl_absorpt_special_details   ?
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.518
_exptl_crystal_density_meas      ?
_exptl_crystal_density_method    ?
_exptl_crystal_description       block
_exptl_crystal_F_000             2408
_exptl_crystal_size_max          0.15
_exptl_crystal_size_mid          0.08
_exptl_crystal_size_min          0.05
_exptl_transmission_factor_max   ?
_exptl_transmission_factor_min   ?
_diffrn_reflns_av_R_equivalents  0.0694
_diffrn_reflns_av_unetI/netI     0.0645
_diffrn_reflns_Laue_measured_fraction_full 0.991
_diffrn_reflns_Laue_measured_fraction_max 0.987
_diffrn_reflns_limit_h_max       43
_diffrn_reflns_limit_h_min       -46
_diffrn_reflns_limit_k_max       10
_diffrn_reflns_limit_k_min       -11
_diffrn_reflns_limit_l_max       19
_diffrn_reflns_limit_l_min       -19
_diffrn_reflns_number            19359
_diffrn_reflns_point_group_measured_fraction_full 0.991
_diffrn_reflns_point_group_measured_fraction_max 0.987
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         26.411
_diffrn_reflns_theta_min         2.206
_diffrn_ambient_temperature      150.0
_diffrn_detector_area_resol_mean ?
_diffrn_measured_fraction_theta_full 0.991
_diffrn_measured_fraction_theta_max 0.987
_diffrn_measurement_device_type  'Bruker D8 VENTURE'
_diffrn_measurement_method       'φ and ω scans'
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_source                   ?
_diffrn_standards_number         0
_reflns_Friedel_coverage         0.000
_reflns_Friedel_fraction_full    .
_reflns_Friedel_fraction_max     .
_reflns_number_gt                4089
_reflns_number_total             5302
_reflns_special_details          
;
 Reflections were merged by SHELXL according to the crystal
 class for the calculation of statistics and refinement.
 
 _reflns_Friedel_fraction is defined as the number of unique
 Friedel pairs measured divided by the number that would be
 possible theoretically, ignoring centric projections and
 systematic absences.
;
_reflns_threshold_expression     'I > 2σ(I)'
_computing_cell_refinement       'SAINT V8.40A (?, 2016)'
_computing_data_collection       ?
_computing_data_reduction        'SAINT V8.40A (?, 2016)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2015)'
_computing_structure_solution    'ShelXT (Sheldrick, 2015)'
_refine_diff_density_max         0.680
_refine_diff_density_min         -1.080
_refine_diff_density_rms         0.124
_refine_ls_extinction_coef       .
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.086
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     328
_refine_ls_number_reflns         5302
_refine_ls_number_restraints     334
_refine_ls_R_factor_all          0.0782
_refine_ls_R_factor_gt           0.0526
_refine_ls_restrained_S_all      1.057
_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/[σ²(Fo²)+(0.0411P)²+33.6774P] where P=(Fo²+2Fc²)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1133
_refine_ls_wR_factor_ref         0.1267
_refine_special_details          ?
_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. Rigid bond restraints
 All non-hydrogen atoms
 with sigma for 1-2 distances of 0.01 and sigma for 1-3 distances of 0.01
3. Uiso/Uaniso restraints and constraints
All non-hydrogen atoms have similar U: within 2A with sigma of 0.04 and sigma
for terminal atoms of 0.08
Uanis(C26) \\sim Ueq, Uanis(Cl1) \\sim Ueq, Uanis(C27) \\sim Ueq, Uanis(Cl2)
\\sim Ueq: with sigma of 0.005 and sigma for terminal atoms of 0.01
Uanis(Cl1) \\sim Ueq, Uanis(Cl2) \\sim Ueq: with sigma of 0.005 and sigma for
terminal atoms of 0.01
4. Others
 Fixed Sof: Cl1(0.5) Cl2(0.5) C26(0.5) H26A(0.5) H26B(0.5) C27(0.5) H27A(0.5)
 H27B(0.5)
5.a Riding coordinates:
 N2(H2)
5.b Secondary CH2 refined with riding coordinates:
 C16(H16A,H16B), C15(H15A,H15B), C7(H7A,H7B), C26(H26A,H26B), C27(H27A,H27B)
5.c Aromatic/amide H refined with riding coordinates:
 C13(H13), C21(H21), C12(H12), C24(H24), C9(H9), C23(H23), C2(H2A), C3(H3),
 C4(H4), C6(H6), C5(H5)
5.d Idealised Me refined as rotating group:
 C17(H17A,H17B,H17C), C19(H19A,H19B,H19C), C18(H18A,H18B,H18C)
;
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_atom_sites_solution_secondary   ?
loop_
_atom_site_label
_atom_site_type_symbol
_atom_site_fract_x
_atom_site_fract_y
_atom_site_fract_z
_atom_site_U_iso_or_equiv
_atom_site_adp_type
_atom_site_occupancy
_atom_site_site_symmetry_order
_atom_site_calc_flag
_atom_site_refinement_flags_posn
_atom_site_refinement_flags_adp
_atom_site_refinement_flags_occupancy
_atom_site_disorder_assembly
_atom_site_disorder_group
I1 I 0.29123(2) 0.98192(4) 0.39641(2) 0.02950(13) Uani 1 1 d . U . . .
Cl1 Cl 0.45793(18) 0.5978(8) 0.2263(4) 0.0728(18) Uani 0.5 1 d . U P A -1
Cl2 Cl 0.54650(16) 0.6668(6) 0.2616(4) 0.0488(12) Uani 0.5 1 d . U P A -1
F1 F 0.39068(9) 0.9856(4) 0.8730(2) 0.0468(9) Uani 1 1 d . U . . .
O2 O 0.43677(10) 0.3790(4) 0.4379(2) 0.0299(9) Uani 1 1 d . U . . .
O1 O 0.33974(11) 0.3431(4) 0.6563(3) 0.0337(10) Uani 1 1 d . U . . .
N3 N 0.26474(11) 0.5642(4) 0.8634(3) 0.0202(9) Uani 1 1 d . U . . .
N1 N 0.34154(12) 0.5738(4) 0.7133(3) 0.0216(9) Uani 1 1 d . U . . .
N2 N 0.33384(11) 0.7526(5) 0.5657(3) 0.0245(9) Uani 1 1 d . U . . .
H2 H 0.325769 0.819280 0.528029 0.029 Uiso 1 1 d R . . . .
C10 C 0.36807(13) 0.5236(5) 0.5759(3) 0.0187(10) Uani 1 1 d . U . . .
C25 C 0.34729(13) 0.8153(5) 0.6451(3) 0.0207(10) Uani 1 1 d . U . . .
C8 C 0.40992(14) 0.4615(6) 0.4709(3) 0.0252(11) Uani 1 1 d . U . . .
C16 C 0.28704(13) 0.6069(5) 0.7893(3) 0.0189(10) Uani 1 1 d . U . . .
H16A H 0.272186 0.591493 0.734632 0.023 Uiso 1 1 calc R . . . .
H16B H 0.292880 0.713367 0.793897 0.023 Uiso 1 1 calc R . . . .
C11 C 0.35859(14) 0.6523(5) 0.5320(3) 0.0215(11) Uani 1 1 d . U . . .
C20 C 0.35354(14) 0.7250(5) 0.7157(4) 0.0241(11) Uani 1 1 d . U . . .
C14 C 0.34871(13) 0.4733(5) 0.6515(3) 0.0209(10) Uani 1 1 d . U . . .
C17 C 0.28546(15) 0.5905(6) 0.9478(3) 0.0290(12) Uani 1 1 d . U . . .
H17A H 0.306180 0.523064 0.953996 0.043 Uiso 1 1 calc GR . . . .
H17B H 0.269674 0.573121 0.994416 0.043 Uiso 1 1 calc GR . . . .
H17C H 0.294145 0.692733 0.950452 0.043 Uiso 1 1 calc GR . . . .
C13 C 0.39939(15) 0.5870(6) 0.4251(4) 0.0282(12) Uani 1 1 d . U . . .
H13 H 0.409781 0.608251 0.372643 0.034 Uiso 1 1 calc R . . . .
C19 C 0.23132(14) 0.6590(6) 0.8583(4) 0.0249(12) Uani 1 1 d . U . . .
H19A H 0.238349 0.763220 0.861795 0.037 Uiso 1 1 calc GR . . . .
H19B H 0.216646 0.634803 0.906047 0.037 Uiso 1 1 calc GR . . . .
H19C H 0.217179 0.640739 0.803676 0.037 Uiso 1 1 calc GR . . . .
C21 C 0.36908(15) 0.7819(6) 0.7928(4) 0.0280(12) Uani 1 1 d . U . . .
H21 H 0.374610 0.719572 0.840998 0.034 Uiso 1 1 calc R . . . .
C12 C 0.37404(15) 0.6815(6) 0.4547(4) 0.0263(12) Uani 1 1 d . U . . .
H12 H 0.366987 0.767032 0.422445 0.032 Uiso 1 1 calc R . . . .
C24 C 0.35505(14) 0.9647(6) 0.6524(4) 0.0270(12) Uani 1 1 d . U . . .
H24 H 0.350775 1.027039 0.603763 0.032 Uiso 1 1 calc R . . . .
C15 C 0.32207(15) 0.5205(6) 0.7864(4) 0.0281(12) Uani 1 1 d . U . . .
H15A H 0.337290 0.534489 0.840773 0.034 Uiso 1 1 calc R . . . .
H15B H 0.316702 0.413959 0.779554 0.034 Uiso 1 1 calc R . . . .
C22 C 0.37612(15) 0.9294(6) 0.7973(4) 0.0328(13) Uani 1 1 d . U . . .
C9 C 0.39351(14) 0.4262(6) 0.5453(3) 0.0231(11) Uani 1 1 d . U . . .
H9 H 0.399460 0.337061 0.575148 0.028 Uiso 1 1 calc R . . . .
C18 C 0.25297(16) 0.4065(6) 0.8569(4) 0.0334(14) Uani 1 1 d . U . . .
H18A H 0.238237 0.391357 0.802761 0.050 Uiso 1 1 calc GR . . . .
H18B H 0.238630 0.382335 0.905227 0.050 Uiso 1 1 calc GR . . . .
H18C H 0.274341 0.342498 0.858373 0.050 Uiso 1 1 calc GR . . . .
C7 C 0.45107(15) 0.2564(6) 0.4883(4) 0.0302(12) Uani 1 1 d . U . . .
H7A H 0.432250 0.179550 0.492002 0.036 Uiso 1 1 calc R . . . .
H7B H 0.458910 0.289472 0.547214 0.036 Uiso 1 1 calc R . . . .
C1 C 0.48265(15) 0.1954(6) 0.4453(4) 0.0284(12) Uani 1 1 d . U . . .
C23 C 0.36888(14) 1.0237(6) 0.7293(4) 0.0335(13) Uani 1 1 d . U . . .
H23 H 0.373279 1.126671 0.735159 0.040 Uiso 1 1 calc R . . . .
C2 C 0.47978(16) 0.0647(7) 0.4005(4) 0.0336(13) Uani 1 1 d . U . . .
H2A H 0.457566 0.011850 0.397135 0.040 Uiso 1 1 calc R . . . .
C3 C 0.50905(18) 0.0093(7) 0.3601(4) 0.0431(15) Uani 1 1 d . U . . .
H3 H 0.506814 -0.080286 0.328423 0.052 Uiso 1 1 calc R . . . .
C4 C 0.54119(18) 0.0849(9) 0.3662(4) 0.0477(17) Uani 1 1 d . U . . .
H4 H 0.561389 0.046942 0.339284 0.057 Uiso 1 1 calc R . . . .
C6 C 0.51544(17) 0.2690(8) 0.4507(5) 0.0478(18) Uani 1 1 d . U . . .
H6 H 0.517947 0.358414 0.482343 0.057 Uiso 1 1 calc R . . . .
C5 C 0.54435(19) 0.2145(9) 0.4109(5) 0.058(2) Uani 1 1 d . U . . .
H5 H 0.566629 0.266967 0.414309 0.070 Uiso 1 1 calc R . . . .
C26 C 0.4888(5) 0.4791(18) 0.2800(11) 0.056(4) Uani 0.5 1 d . U P A -1
H26A H 0.490059 0.502019 0.342189 0.067 Uiso 0.5 1 calc R . P A -1
H26B H 0.479928 0.376508 0.272427 0.067 Uiso 0.5 1 calc R . P A -1
C27 C 0.5277(5) 0.490(2) 0.2479(13) 0.061(4) Uani 0.5 1 d . U P A -1
H27A H 0.526603 0.463252 0.186231 0.073 Uiso 0.5 1 calc R . P A -1
H27B H 0.543611 0.417554 0.279775 0.073 Uiso 0.5 1 calc R . P A -1


_geom_special_details            
;
 All esds (except the esd in the dihedral angle between two l.s. planes)
 are estimated using the full covariance matrix.  The cell esds are taken
 into account individually in the estimation of esds in distances, angles
 and torsion angles; correlations between esds in cell parameters are only
 used when they are defined by crystal symmetry.  An approximate (isotropic)
 treatment of cell esds is used for estimating esds involving l.s. planes.
;
loop_
_geom_bond_atom_site_label_1
_geom_bond_atom_site_label_2
_geom_bond_distance
_geom_bond_site_symmetry_2
_geom_bond_publ_flag
Cl1 C26 1.737(17) . ?
Cl2 C27 1.756(19) . ?
F1 C22 1.359(7) . ?
O2 C8 1.375(6) . ?
O2 C7 1.439(7) . ?
O1 C14 1.229(6) . ?
N3 C16 1.521(6) . ?
N3 C17 1.492(7) . ?
N3 C19 1.504(6) . ?
N3 C18 1.495(6) . ?
N1 C20 1.440(6) . ?
N1 C14 1.367(7) . ?
N1 C15 1.476(6) . ?
N2 C25 1.419(7) . ?
N2 C11 1.420(6) . ?
C10 C11 1.384(7) . ?
C10 C14 1.499(7) . ?
C10 C9 1.401(7) . ?
C25 C20 1.377(7) . ?
C25 C24 1.387(7) . ?
C8 C13 1.384(8) . ?
C8 C9 1.388(7) . ?
C16 C15 1.519(7) . ?
C11 C12 1.399(7) . ?
C20 C21 1.394(8) . ?
C13 C12 1.376(7) . ?
C21 C22 1.362(8) . ?
C24 C23 1.377(8) . ?
C22 C23 1.374(9) . ?
C7 C1 1.498(7) . ?
C1 C2 1.375(8) . ?
C1 C6 1.382(8) . ?
C2 C3 1.389(8) . ?
C3 C4 1.370(10) . ?
C4 C5 1.366(10) . ?
C6 C5 1.370(9) . ?
C26 C27 1.56(2) . ?

loop_
_geom_angle_atom_site_label_1
_geom_angle_atom_site_label_2
_geom_angle_atom_site_label_3
_geom_angle
_geom_angle_site_symmetry_1
_geom_angle_site_symmetry_3
_geom_angle_publ_flag
C8 O2 C7 117.5(4) . . ?
C17 N3 C16 111.0(4) . . ?
C17 N3 C19 108.8(4) . . ?
C17 N3 C18 109.9(4) . . ?
C19 N3 C16 107.8(4) . . ?
C18 N3 C16 111.3(4) . . ?
C18 N3 C19 107.9(4) . . ?
C20 N1 C15 117.3(4) . . ?
C14 N1 C20 125.1(4) . . ?
C14 N1 C15 117.4(4) . . ?
C25 N2 C11 112.7(4) . . ?
C11 C10 C14 121.9(4) . . ?
C11 C10 C9 120.9(4) . . ?
C9 C10 C14 116.8(4) . . ?
C20 C25 N2 119.2(4) . . ?
C20 C25 C24 119.5(5) . . ?
C24 C25 N2 121.3(5) . . ?
O2 C8 C13 115.9(5) . . ?
O2 C8 C9 124.3(5) . . ?
C13 C8 C9 119.8(5) . . ?
C15 C16 N3 113.9(4) . . ?
C10 C11 N2 120.1(4) . . ?
C10 C11 C12 118.7(5) . . ?
C12 C11 N2 121.1(5) . . ?
C25 C20 N1 120.8(5) . . ?
C25 C20 C21 120.3(5) . . ?
C21 C20 N1 118.7(5) . . ?
O1 C14 N1 121.9(5) . . ?
O1 C14 C10 119.1(5) . . ?
N1 C14 C10 118.9(4) . . ?
C12 C13 C8 120.7(5) . . ?
C22 C21 C20 118.2(5) . . ?
C13 C12 C11 120.4(5) . . ?
C23 C24 C25 120.8(5) . . ?
N1 C15 C16 108.8(4) . . ?
F1 C22 C21 118.3(6) . . ?
F1 C22 C23 118.7(5) . . ?
C21 C22 C23 123.1(6) . . ?
C8 C9 C10 119.2(5) . . ?
O2 C7 C1 107.9(4) . . ?
C2 C1 C7 120.9(5) . . ?
C2 C1 C6 118.7(5) . . ?
C6 C1 C7 120.5(5) . . ?
C22 C23 C24 118.0(5) . . ?
C1 C2 C3 120.6(6) . . ?
C4 C3 C2 119.4(6) . . ?
C5 C4 C3 120.4(6) . . ?
C5 C6 C1 120.8(6) . . ?
C4 C5 C6 120.1(7) . . ?
C27 C26 Cl1 113.3(12) . . ?
C26 C27 Cl2 112.6(14) . . ?


_olex2_submission_special_instructions 'No special instructions were received'
