# Electronic Supplementary Material (ESI) for MedChemComm.
# This journal is © The Royal Society of Chemistry 2019

####################################################################### 
# 
# 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_HDA1
_database_code_depnum_ccdc_archive 'CCDC 1884066'
loop_
_audit_author_name
_audit_author_address
'Henrietta Dede Attram'
;University of Cape Town
South Africa
;
_audit_update_record             
;
2018-12-10 deposited with the CCDC.	2019-02-14 downloaded from the CCDC.
;

_audit_creation_method           SHELXL-2014/7
_shelx_SHELXL_version_number     2014/7
_chemical_name_systematic        ?
_chemical_name_common            ?
_chemical_melting_point          ?
_chemical_formula_moiety         ?
_chemical_formula_sum            'C18 H23 F N4 O2'
_chemical_formula_weight         346.40

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'
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'
F F 0.0171 0.0103 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'

_space_group_crystal_system      monoclinic
_space_group_IT_number           14
_space_group_name_H-M_alt        'P 21/c'
_space_group_name_Hall           '-P 2ybc'

_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.
;

loop_
_space_group_symop_operation_xyz
'x, y, z'
'-x, y+1/2, -z+1/2'
'-x, -y, -z'
'x, -y-1/2, z-1/2'

_cell_length_a                   13.6252(16)
_cell_length_b                   10.5144(12)
_cell_length_c                   12.6246(13)
_cell_angle_alpha                90
_cell_angle_beta                 96.075(2)
_cell_angle_gamma                90
_cell_volume                     1798.5(3)
_cell_formula_units_Z            4
_cell_measurement_temperature    173(2)
_cell_measurement_reflns_used    2947
_cell_measurement_theta_min      2.451
_cell_measurement_theta_max      24.94

_exptl_crystal_description       block
_exptl_crystal_colour            colorless
_exptl_crystal_density_meas      'not measured'
_exptl_crystal_density_diffrn    1.279
_exptl_crystal_F_000             736
_exptl_transmission_factor_min   0.875
_exptl_transmission_factor_max   1.000
_exptl_crystal_size_max          0.270
_exptl_crystal_size_mid          0.260
_exptl_crystal_size_min          0.070
_exptl_absorpt_coefficient_mu    0.093
_shelx_estimated_absorpt_T_min   0.975
_shelx_estimated_absorpt_T_max   0.994
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_correction_T_min  0.875
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_process_details   'SADABS (Sheldrick, 2001)'
_exptl_absorpt_special_details   ?
_diffrn_ambient_temperature      173(2)
_diffrn_radiation_wavelength     0.71073
_diffrn_radiation_type           MoK\a
_diffrn_source                   'fine-focus sealed tube'
_diffrn_measurement_device_type  'Bruker Kappa Duo Apex II Diffractometer'
_diffrn_measurement_method       '0.5° φ scans and ω scans'
_diffrn_detector_area_resol_mean ?
_diffrn_reflns_number            13245
_diffrn_reflns_av_unetI/netI     0.0436
_diffrn_reflns_av_R_equivalents  0.0445
_diffrn_reflns_limit_h_min       -17
_diffrn_reflns_limit_h_max       17
_diffrn_reflns_limit_k_min       -13
_diffrn_reflns_limit_k_max       13
_diffrn_reflns_limit_l_min       -8
_diffrn_reflns_limit_l_max       16
_diffrn_reflns_theta_min         1.503
_diffrn_reflns_theta_max         27.491
_diffrn_reflns_theta_full        25.242
_diffrn_measured_fraction_theta_max 0.999
_diffrn_measured_fraction_theta_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.999
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.999
_diffrn_reflns_point_group_measured_fraction_full 0.999
_reflns_number_total             4132
_reflns_number_gt                2914
_reflns_threshold_expression     'I > 2σ(I)'
_reflns_Friedel_coverage         0.000
_reflns_Friedel_fraction_max     .
_reflns_Friedel_fraction_full    .

_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.
;

_computing_data_collection       
'SAINT (7.60a, Bruker AXS Inc., Madison, WI, USA, 2006)'
_computing_cell_refinement       
'SAINT (7.60a, Bruker AXS Inc., Madison, WI, USA, 2006)'
_computing_data_reduction        
'SAINT (7.60a, Bruker AXS Inc., Madison, WI, USA, 2006)'
_computing_structure_solution    'SHELXS-97 (Sheldrick, 1997)'
_computing_structure_refinement  'SHELXL-2014/7 (Sheldrick, 2014)'
_computing_molecular_graphics    'X-Seed (Barbour, 2001'
_computing_publication_material  'SHELXL-2014/7 (Sheldrick, 2014)'
_refine_special_details          ?
_refine_ls_structure_factor_coef Fsqd
_refine_ls_matrix_type           full
_refine_ls_weighting_scheme      calc
_refine_ls_weighting_details     
'w=1/[σ²(Fo²)+(0.0446P)²+0.3906P] where P=(Fo²+2Fc²)/3'
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_atom_sites_solution_hydrogens   mixed
_refine_ls_hydrogen_treatment    mixed
_refine_ls_extinction_method     none
_refine_ls_extinction_coef       .
_refine_ls_number_reflns         4132
_refine_ls_number_parameters     247
_refine_ls_number_restraints     3
_refine_ls_R_factor_all          0.0673
_refine_ls_R_factor_gt           0.0432
_refine_ls_wR_factor_ref         0.1137
_refine_ls_wR_factor_gt          0.1001
_refine_ls_goodness_of_fit_ref   1.017
_refine_ls_restrained_S_all      1.017
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000

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
F1 F 0.37802(9) 0.45567(11) 0.02906(8) 0.0631(3) Uani 1 1 d . . . . .
O1 O 0.23658(8) 0.33988(10) 0.12822(8) 0.0373(3) Uani 1 1 d D . . . .
H1O H 0.2019(15) 0.2784(17) 0.1684(15) 0.089(8) Uiso 1 1 d D . . . .
O2 O 0.10018(8) 0.53274(10) 0.09724(8) 0.0323(2) Uani 1 1 d D . . . .
H2A H 0.1561(9) 0.4777(15) 0.1009(14) 0.059(6) Uiso 1 1 d D . . . .
H2B H 0.1112(16) 0.5841(18) 0.1598(11) 0.083(7) Uiso 1 1 d D . . . .
N1 N -0.12722(10) 0.30465(13) 0.07612(10) 0.0368(3) Uani 1 1 d . . . . .
H1 H -0.1084(13) 0.3632(18) 0.0333(14) 0.048(5) Uiso 1 1 d . . . . .
N2 N -0.12431(9) 0.17496(12) 0.21783(9) 0.0329(3) Uani 1 1 d . . . . .
N3 N 0.00524(10) 0.32484(13) 0.21310(11) 0.0377(3) Uani 1 1 d . . . . .
H3N H 0.0304(13) 0.3852(18) 0.1776(13) 0.048(5) Uiso 1 1 d . . . . .
N4 N 0.18851(9) 0.15945(12) 0.24661(9) 0.0327(3) Uani 1 1 d . . . . .
C1 C -0.28370(13) 0.21914(17) -0.02698(13) 0.0450(4) Uani 1 1 d . . . . .
H1C H -0.2859 0.2756 -0.0859 0.054 Uiso 1 1 calc R U . . .
C2 C -0.35406(13) 0.12478(19) -0.02135(14) 0.0490(4) Uani 1 1 d . . . . .
H2 H -0.4054 0.1161 -0.0779 0.059 Uiso 1 1 calc R U . . .
C3 C -0.35123(12) 0.04265(18) 0.06515(14) 0.0469(4) Uani 1 1 d . . . . .
H3A H -0.4002 -0.0215 0.0662 0.056 Uiso 1 1 calc R U . . .
C4 C -0.27799(12) 0.05275(16) 0.15023(13) 0.0410(4) Uani 1 1 d . . . . .
H4 H -0.2768 -0.0029 0.2097 0.049 Uiso 1 1 calc R U . . .
C5 C -0.20663(11) 0.14640(15) 0.14591(11) 0.0335(3) Uani 1 1 d . . . . .
C6 C -0.20996(12) 0.22737(15) 0.05725(12) 0.0358(4) Uani 1 1 d . . . . .
C7 C -0.07923(11) 0.26864(14) 0.17176(12) 0.0328(3) Uani 1 1 d . . . . .
C8 C 0.05498(12) 0.28636(15) 0.31563(12) 0.0369(4) Uani 1 1 d . . . . .
H8A H 0.0061 0.2834 0.3683 0.044 Uiso 1 1 calc R U . . .
H8B H 0.1050 0.3513 0.3398 0.044 Uiso 1 1 calc R U . . .
C9 C 0.10523(12) 0.15763(15) 0.31293(12) 0.0366(4) Uani 1 1 d . . . . .
H9A H 0.1300 0.1322 0.3865 0.044 Uiso 1 1 calc R U . . .
H9B H 0.0563 0.0934 0.2843 0.044 Uiso 1 1 calc R U . . .
C10 C 0.19374(12) 0.04214(15) 0.18244(13) 0.0418(4) Uani 1 1 d . . . . .
H10A H 0.1876 -0.0331 0.2285 0.050 Uiso 1 1 calc R U . . .
H10B H 0.2587 0.0378 0.1542 0.050 Uiso 1 1 calc R U . . .
C11 C 0.11241(14) 0.03918(19) 0.09044(14) 0.0533(5) Uani 1 1 d . . . . .
H11A H 0.0480 0.0390 0.1184 0.080 Uiso 1 1 calc R U . . .
H11B H 0.1190 -0.0378 0.0480 0.080 Uiso 1 1 calc R U . . .
H11C H 0.1177 0.1144 0.0456 0.080 Uiso 1 1 calc R U . . .
C12 C 0.28349(12) 0.18410(16) 0.31194(13) 0.0407(4) Uani 1 1 d . . . . .
H12A H 0.3074 0.1042 0.3472 0.049 Uiso 1 1 calc R U . . .
H12B H 0.2727 0.2465 0.3683 0.049 Uiso 1 1 calc R U . . .
C13 C 0.36096(11) 0.23436(15) 0.24634(12) 0.0358(4) Uani 1 1 d . . . . .
C14 C 0.46111(13) 0.20936(18) 0.27335(15) 0.0492(4) Uani 1 1 d . . . . .
H14 H 0.4807 0.1534 0.3308 0.059 Uiso 1 1 calc R U . . .
C15 C 0.53238(13) 0.2647(2) 0.21778(16) 0.0569(5) Uani 1 1 d . . . . .
H15 H 0.6002 0.2459 0.2367 0.068 Uiso 1 1 calc R U . . .
C16 C 0.50512(14) 0.3472(2) 0.13510(15) 0.0532(5) Uani 1 1 d . . . . .
H16 H 0.5535 0.3864 0.0971 0.064 Uiso 1 1 calc R U . . .
C17 C 0.40660(13) 0.37153(17) 0.10865(12) 0.0427(4) Uani 1 1 d . . . . .
C18 C 0.33319(11) 0.31532(14) 0.16044(11) 0.0328(3) Uani 1 1 d . . . . .


_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
F1 C17 1.364(2) . ?
O1 C18 1.3607(18) . ?
O1 H1O 0.974(5) . ?
O2 H2A 0.954(5) . ?
O2 H2B 0.956(5) . ?
N1 C7 1.3645(19) . ?
N1 C6 1.390(2) . ?
N1 H1 0.876(19) . ?
N2 C7 1.3271(19) . ?
N2 C5 1.3989(19) . ?
N3 C7 1.349(2) . ?
N3 C8 1.454(2) . ?
N3 H3N 0.868(18) . ?
N4 C9 1.4799(19) . ?
N4 C10 1.482(2) . ?
N4 C12 1.4820(19) . ?
C1 C6 1.386(2) . ?
C1 C2 1.387(3) . ?
C1 H1C 0.9500 . ?
C2 C3 1.389(2) . ?
C2 H2 0.9500 . ?
C3 C4 1.391(2) . ?
C3 H3A 0.9500 . ?
C4 C5 1.389(2) . ?
C4 H4 0.9500 . ?
C5 C6 1.403(2) . ?
C8 C9 1.519(2) . ?
C8 H8A 0.9900 . ?
C8 H8B 0.9900 . ?
C9 H9A 0.9900 . ?
C9 H9B 0.9900 . ?
C10 C11 1.518(2) . ?
C10 H10A 0.9900 . ?
C10 H10B 0.9900 . ?
C11 H11A 0.9800 . ?
C11 H11B 0.9800 . ?
C11 H11C 0.9800 . ?
C12 C13 1.505(2) . ?
C12 H12A 0.9900 . ?
C12 H12B 0.9900 . ?
C13 C14 1.396(2) . ?
C13 C18 1.399(2) . ?
C14 C15 1.385(3) . ?
C14 H14 0.9500 . ?
C15 C16 1.377(3) . ?
C15 H15 0.9500 . ?
C16 C17 1.373(3) . ?
C16 H16 0.9500 . ?
C17 C18 1.384(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
C18 O1 H1O 103.1(14) . . ?
H2A O2 H2B 104.4(17) . . ?
C7 N1 C6 107.07(13) . . ?
C7 N1 H1 126.7(12) . . ?
C6 N1 H1 126.2(12) . . ?
C7 N2 C5 104.56(12) . . ?
C7 N3 C8 121.40(13) . . ?
C7 N3 H3N 119.2(12) . . ?
C8 N3 H3N 119.4(12) . . ?
C9 N4 C10 112.50(12) . . ?
C9 N4 C12 111.35(12) . . ?
C10 N4 C12 111.11(12) . . ?
C6 C1 C2 117.02(16) . . ?
C6 C1 H1C 121.5 . . ?
C2 C1 H1C 121.5 . . ?
C1 C2 C3 121.54(16) . . ?
C1 C2 H2 119.2 . . ?
C3 C2 H2 119.2 . . ?
C2 C3 C4 121.17(17) . . ?
C2 C3 H3A 119.4 . . ?
C4 C3 H3A 119.4 . . ?
C5 C4 C3 118.15(15) . . ?
C5 C4 H4 120.9 . . ?
C3 C4 H4 120.9 . . ?
C4 C5 N2 130.03(14) . . ?
C4 C5 C6 119.85(14) . . ?
N2 C5 C6 110.09(13) . . ?
C1 C6 N1 132.61(15) . . ?
C1 C6 C5 122.26(15) . . ?
N1 C6 C5 105.12(13) . . ?
N2 C7 N3 124.83(14) . . ?
N2 C7 N1 113.15(14) . . ?
N3 C7 N1 122.02(14) . . ?
N3 C8 C9 113.39(12) . . ?
N3 C8 H8A 108.9 . . ?
C9 C8 H8A 108.9 . . ?
N3 C8 H8B 108.9 . . ?
C9 C8 H8B 108.9 . . ?
H8A C8 H8B 107.7 . . ?
N4 C9 C8 112.06(12) . . ?
N4 C9 H9A 109.2 . . ?
C8 C9 H9A 109.2 . . ?
N4 C9 H9B 109.2 . . ?
C8 C9 H9B 109.2 . . ?
H9A C9 H9B 107.9 . . ?
N4 C10 C11 111.22(14) . . ?
N4 C10 H10A 109.4 . . ?
C11 C10 H10A 109.4 . . ?
N4 C10 H10B 109.4 . . ?
C11 C10 H10B 109.4 . . ?
H10A C10 H10B 108.0 . . ?
C10 C11 H11A 109.5 . . ?
C10 C11 H11B 109.5 . . ?
H11A C11 H11B 109.5 . . ?
C10 C11 H11C 109.5 . . ?
H11A C11 H11C 109.5 . . ?
H11B C11 H11C 109.5 . . ?
N4 C12 C13 112.16(12) . . ?
N4 C12 H12A 109.2 . . ?
C13 C12 H12A 109.2 . . ?
N4 C12 H12B 109.2 . . ?
C13 C12 H12B 109.2 . . ?
H12A C12 H12B 107.9 . . ?
C14 C13 C18 118.76(16) . . ?
C14 C13 C12 121.59(15) . . ?
C18 C13 C12 119.50(14) . . ?
C15 C14 C13 121.11(18) . . ?
C15 C14 H14 119.4 . . ?
C13 C14 H14 119.4 . . ?
C16 C15 C14 120.08(17) . . ?
C16 C15 H15 120.0 . . ?
C14 C15 H15 120.0 . . ?
C17 C16 C15 118.69(17) . . ?
C17 C16 H16 120.7 . . ?
C15 C16 H16 120.7 . . ?
F1 C17 C16 119.71(16) . . ?
F1 C17 C18 117.43(15) . . ?
C16 C17 C18 122.85(17) . . ?
O1 C18 C17 120.15(14) . . ?
O1 C18 C13 121.40(14) . . ?
C17 C18 C13 118.45(15) . . ?

loop_
_geom_torsion_atom_site_label_1
_geom_torsion_atom_site_label_2
_geom_torsion_atom_site_label_3
_geom_torsion_atom_site_label_4
_geom_torsion
_geom_torsion_site_symmetry_1
_geom_torsion_site_symmetry_2
_geom_torsion_site_symmetry_3
_geom_torsion_site_symmetry_4
_geom_torsion_publ_flag
C6 C1 C2 C3 0.4(3) . . . . ?
C1 C2 C3 C4 0.6(3) . . . . ?
C2 C3 C4 C5 -0.8(3) . . . . ?
C3 C4 C5 N2 -177.99(15) . . . . ?
C3 C4 C5 C6 0.0(2) . . . . ?
C7 N2 C5 C4 176.96(16) . . . . ?
C7 N2 C5 C6 -1.16(16) . . . . ?
C2 C1 C6 N1 177.00(17) . . . . ?
C2 C1 C6 C5 -1.3(2) . . . . ?
C7 N1 C6 C1 -178.56(17) . . . . ?
C7 N1 C6 C5 -0.05(16) . . . . ?
C4 C5 C6 C1 1.1(2) . . . . ?
N2 C5 C6 C1 179.46(14) . . . . ?
C4 C5 C6 N1 -177.59(14) . . . . ?
N2 C5 C6 N1 0.76(16) . . . . ?
C5 N2 C7 N3 -178.99(14) . . . . ?
C5 N2 C7 N1 1.16(17) . . . . ?
C8 N3 C7 N2 -0.5(2) . . . . ?
C8 N3 C7 N1 179.34(13) . . . . ?
C6 N1 C7 N2 -0.72(17) . . . . ?
C6 N1 C7 N3 179.43(14) . . . . ?
C7 N3 C8 C9 72.35(18) . . . . ?
C10 N4 C9 C8 -140.25(13) . . . . ?
C12 N4 C9 C8 94.26(15) . . . . ?
N3 C8 C9 N4 66.19(17) . . . . ?
C9 N4 C10 C11 73.32(17) . . . . ?
C12 N4 C10 C11 -161.06(13) . . . . ?
C9 N4 C12 C13 -158.60(13) . . . . ?
C10 N4 C12 C13 75.14(16) . . . . ?
N4 C12 C13 C14 -149.37(15) . . . . ?
N4 C12 C13 C18 35.1(2) . . . . ?
C18 C13 C14 C15 1.0(3) . . . . ?
C12 C13 C14 C15 -174.52(16) . . . . ?
C13 C14 C15 C16 0.7(3) . . . . ?
C14 C15 C16 C17 -0.8(3) . . . . ?
C15 C16 C17 F1 178.11(16) . . . . ?
C15 C16 C17 C18 -1.0(3) . . . . ?
F1 C17 C18 O1 3.1(2) . . . . ?
C16 C17 C18 O1 -177.73(15) . . . . ?
F1 C17 C18 C13 -176.37(13) . . . . ?
C16 C17 C18 C13 2.8(2) . . . . ?
C14 C13 C18 O1 177.81(14) . . . . ?
C12 C13 C18 O1 -6.5(2) . . . . ?
C14 C13 C18 C17 -2.7(2) . . . . ?
C12 C13 C18 C17 172.94(14) . . . . ?

_refine_diff_density_max         0.179
_refine_diff_density_min         -0.268
_refine_diff_density_rms         0.039



