Chemoselective Defluorinative Amination of (Trifluoromethyl)alkenes with Amidines: Synthesis of 6-Fluoro-1,4-dihydropyrimidines
Li, Han; Long, Xujing; Zhu, Chuanle; Organic & Biomolecular Chemistry  (2025) –; doi:10.1039/D5OB01554E

data_7160861
_publ_section_title
;
 Chemoselective Defluorinative Amination of (Trifluoromethyl)alkenes with
 Amidines: Synthesis of 6-Fluoro-1,4-dihydropyrimidines
;
_journal_name_full               'Organic &amp; Biomolecular Chemistry'
_journal_paper_doi               10.1039/D5OB01554E
_journal_year                    2025
_chemical_formula_moiety         '2(C20 H20 Br F N2)'
_chemical_formula_sum            'C40 H40 Br2 F2 N4'
_chemical_formula_weight         774.58
_chemical_name_systematic
5-(4-bromophenyl)-2-(tert-butyl)-6-fluoro-1-phenyl-1,4-dihydropyrimidine
_chemical_properties_physical    Air-sensitive
_space_group_crystal_system      triclinic
_space_group_IT_number           2
_space_group_name_Hall           '-P 1'
_space_group_name_H-M_alt        'P -1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2025-07-21
_audit_creation_method
;
Olex2 1.3
(compiled 2020.11.12 svn.r5f609507 for OlexSys, GUI svn.r6408)
;
_audit_update_record
;
2025-07-23 deposited with the CCDC.	2025-11-14 downloaded from the CCDC.
;
_cell_angle_alpha                92.300(6)
_cell_angle_beta                 90.755(6)
_cell_angle_gamma                93.448(6)
_cell_formula_units_Z            1
_cell_length_a                   5.8689(4)
_cell_length_b                   11.6621(10)
_cell_length_c                   12.8743(10)
_cell_measurement_reflns_used    2220
_cell_measurement_temperature    293(2)
_cell_measurement_theta_max      70.2940
_cell_measurement_theta_min      3.7950
_cell_volume                     878.75(12)
_computing_cell_refinement       'CrysAlisPro 1.171.42.99a (Rigaku OD, 2023)'
_computing_data_collection       'CrysAlisPro 1.171.42.99a (Rigaku OD, 2023)'
_computing_data_reduction        'CrysAlisPro 1.171.42.99a (Rigaku OD, 2023)'
_computing_molecular_graphics    'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2018/3 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2018/2 (Sheldrick, 2018)'
_diffrn_ambient_temperature      293(2)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 8.0606
_diffrn_detector_type            Eos
_diffrn_measured_fraction_theta_full 0.998
_diffrn_measured_fraction_theta_max 0.972
_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     -2.00  39.00   1.00    1.50    --   35.25 -77.00  30.00   41
  2  \w     42.00 102.00   1.00    1.50    --   35.25  57.00   0.00   60
  3  \w    -13.00  28.00   1.00    1.50    --   35.25 -77.00  90.00   41
  4  \w     46.00  82.00   1.00    1.50    --   35.25-125.00 -30.00   36
  5  \w    -21.00  52.00   1.00    1.50    --   35.25 -57.00 120.00   73
  6  \w     33.00  94.00   1.00    1.50    --   35.25  57.00 -60.00   61
  7  \w     55.00  84.00   1.00    1.50    --   35.25-125.00-180.00   29
  8  \w     16.00  95.00   1.00    1.50    --   35.25  37.00 -90.00   79
  9  \w     41.00  67.00   1.00    1.00    --  105.75 -94.00-120.00   26
 10  \w    142.00 168.00   1.00    1.00    --  105.75 111.00  30.00   26
 11  \w     37.00 123.00   1.00    1.00    --  105.75 -30.00  60.00   86
 12  \w    111.00 149.00   1.00    1.00    --  105.75 111.00 120.00   38
 13  \w     39.00 132.00   1.00    1.00    --  105.75 -77.00  90.00   93
 14  \w     39.00 100.00   1.00    1.00    --  105.75-111.00  90.00   61
 15  \w     48.00 108.00   1.00    1.00    --  105.75-111.00   0.00   60
 16  \w     88.00 164.00   1.00    1.00    --  105.75  61.00-120.00   76
 17  \w    131.00 157.00   1.00    1.00    --  105.75  15.00-180.00   26
 18  \w     84.00 112.00   1.00    1.00    --  105.75  15.00-180.00   28
 19  \w     81.00 106.00   1.00    1.00    --  105.75-111.00-180.00   25
 20  \w     70.00 105.00   1.00    1.00    --  105.75 -94.00-120.00   35
 21  \w     61.00 124.00   1.00    1.00    --  105.75 178.00 120.00   63
 22  \w    110.00 135.00   1.00    1.00    --  105.75 111.00  30.00   25
 23  \w     44.00 127.00   1.00    1.00    --  105.75 -30.00-150.00   83
 24  \w     88.00 170.00   1.00    1.00    --  105.75  61.00-150.00   82
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'Xcalibur, Eos, Gemini'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.1247005000
_diffrn_orient_matrix_UB_12      -0.0030326000
_diffrn_orient_matrix_UB_13      0.1058130000
_diffrn_orient_matrix_UB_21      -0.1061043000
_diffrn_orient_matrix_UB_22      -0.1222415000
_diffrn_orient_matrix_UB_23      0.0146159000
_diffrn_orient_matrix_UB_31      0.2058199000
_diffrn_orient_matrix_UB_32      -0.0509036000
_diffrn_orient_matrix_UB_33      -0.0541817000
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0499
_diffrn_reflns_av_unetI/netI     0.0691
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.972
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -4
_diffrn_reflns_limit_k_max       13
_diffrn_reflns_limit_k_min       -14
_diffrn_reflns_limit_l_max       15
_diffrn_reflns_limit_l_min       -15
_diffrn_reflns_number            5372
_diffrn_reflns_point_group_measured_fraction_full 0.998
_diffrn_reflns_point_group_measured_fraction_max 0.972
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         71.051
_diffrn_reflns_theta_min         3.436
_diffrn_source                   'fine-focus sealed X-ray tube'
_diffrn_source_type              'Enhance (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    3.290
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.62455
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.42.99a (Rigaku Oxford Diffraction, 2023)
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    1.464
_exptl_crystal_description       block
_exptl_crystal_F_000             396
_exptl_crystal_size_max          0.2
_exptl_crystal_size_mid          0.1
_exptl_crystal_size_min          0.1
_refine_diff_density_max         0.468
_refine_diff_density_min         -0.634
_refine_diff_density_rms         0.083
_refine_ls_extinction_coef       0.0121(11)
_refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^
_refine_ls_extinction_method     'SHELXL-2018/3 (Sheldrick 2018)'
_refine_ls_goodness_of_fit_ref   1.041
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     221
_refine_ls_number_reflns         3312
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.041
_refine_ls_R_factor_all          0.0588
_refine_ls_R_factor_gt           0.0511
_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^)+(0.0786P)^2^+0.0995P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1377
_refine_ls_wR_factor_ref         0.1501
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2784
_reflns_number_total             3312
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5ob01554e2.cif
_cod_data_source_block           exp_15114_auto
_cod_database_code               7160861
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.734
_shelx_estimated_absorpt_t_min   0.559
_reflns_odcompleteness_completeness 99.90
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     66.97
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2.a Secondary CH2 refined with riding coordinates:
 C8(H8A,H8B)
2.b Aromatic/amide H refined with riding coordinates:
 C19(H19), C15(H15), C3(H3), C18(H18), C2(H2), C17(H17), C16(H16), C6(H6),
 C5(H5)
2.c Idealised Me refined as rotating group:
 C13(H13A,H13B,H13C), C12(H12A,H12B,H12C), C11(H11A,H11B,H11C)
;
_shelx_res_checksum              97798
_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 1.754
_oxdiff_exptl_absorpt_empirical_full_min 0.619