Diversifying the Triquinazine Scaffold of a Janus Kinase Inhibitor
Mulliri, Kleni; Meier, Kris; Feuchter, Johanna-Dorothea; Javor, Sacha; Andrade Meirelles, Matheus; Reymond, Jean-Louis; RSC Medicinal Chemistry  (2025) –; doi:10.1039/D5MD00921A

data_7251301
_publ_section_title
;
 Diversifying the Triquinazine Scaffold of a Janus Kinase Inhibitor
;
_journal_name_full               'RSC Medicinal Chemistry'
_journal_paper_doi               10.1039/D5MD00921A
_journal_year                    2025
_chemical_formula_moiety         '2(Cl), C10 H20 N2'
_chemical_formula_sum            'C10 H20 Cl2 N2'
_chemical_formula_weight         239.18
_space_group_crystal_system      orthorhombic
_space_group_IT_number           61
_space_group_name_Hall           '-P 2ac 2ab'
_space_group_name_H-M_alt        'P b c a'
_atom_sites_solution_hydrogens   mixed
_audit_creation_date             2020-06-26
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_audit_update_record
;
2025-08-22 deposited with the CCDC.	2025-11-13 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   13.2264(2)
_cell_length_b                   10.8785(2)
_cell_length_c                   16.7754(3)
_cell_measurement_reflns_used    7681
_cell_measurement_temperature    173.00(10)
_cell_measurement_theta_max      76.5430
_cell_measurement_theta_min      5.2950
_cell_volume                     2413.70(7)
_computing_cell_refinement       'CrysAlisPro 1.171.41.72a (Rigaku OD, 2020)'
_computing_data_collection       'CrysAlisPro 1.171.41.72a (Rigaku OD, 2020)'
_computing_data_reduction        'CrysAlisPro 1.171.41.72a (Rigaku OD, 2020)'
_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 2014/5 (Sheldrick, 2014)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      173.00(10)
_diffrn_detector                 'Hybrid Pixel Array Detector'
_diffrn_detector_area_resol_mean 10.0000
_diffrn_detector_type            HyPix
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.979
_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    -62.00  -4.00   1.00    0.25    --  -21.00 114.00 -24.00   58
  2  \w    -93.00 -43.00   1.00    0.25    --  -21.00-173.00 105.00   50
  3  \w     27.00  91.00   1.00    0.25    --   47.89-114.00-114.00   64
  4  \w    102.00 171.00   1.00    1.00    --  106.80 114.00 -24.00   69
  5  \w     35.00 109.00   1.00    1.00    --  106.80-114.00-114.00   74
  6  \w    -93.00   2.00   1.00    0.25    --  -21.00 -77.00-120.00   95
  7  \w    -23.00  63.00   1.00    0.25    --   47.89 -57.00-150.00   86
  8  \w    -26.00  23.00   1.00    0.25    --   47.89 -19.00  60.00   49
  9  \w     35.00 102.00   1.00    1.00    --  106.80 -77.00 -90.00   67
 10  \w     95.00 171.00   1.00    1.00    --  106.80  45.00-120.00   76
 11  \w     35.00  68.00   1.00    1.00    --  106.80 -61.00  60.00   33
 12  \w     35.00 102.00   1.00    1.00    --  106.80 -77.00   0.00   67
 13  \w     95.00 171.00   1.00    1.00    --  106.80  30.00 150.00   76
 14  \w     35.00  68.00   1.00    1.00    --  106.80 -61.00 120.00   33
 15  \w     35.00  68.00   1.00    1.00    --  106.80 -61.00  90.00   33
 16  \w     26.00 119.00   1.00    0.25    --   47.89  77.00 -30.00   93
;
_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      -0.0270499000
_diffrn_orient_matrix_UB_12      -0.1284929000
_diffrn_orient_matrix_UB_13      -0.0321875000
_diffrn_orient_matrix_UB_21      0.0108763000
_diffrn_orient_matrix_UB_22      -0.0536234000
_diffrn_orient_matrix_UB_23      0.0845267000
_diffrn_orient_matrix_UB_31      -0.1127973000
_diffrn_orient_matrix_UB_32      0.0257318000
_diffrn_orient_matrix_UB_33      0.0158636000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0600
_diffrn_reflns_av_unetI/netI     0.0378
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.979
_diffrn_reflns_limit_h_max       12
_diffrn_reflns_limit_h_min       -16
_diffrn_reflns_limit_k_max       13
_diffrn_reflns_limit_k_min       -13
_diffrn_reflns_limit_l_max       20
_diffrn_reflns_limit_l_min       -21
_diffrn_reflns_number            14194
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.979
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         76.837
_diffrn_reflns_theta_min         5.274
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'PhotonJet (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    4.553
_exptl_absorpt_correction_T_max  1.00000
_exptl_absorpt_correction_T_min  0.25890
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.41.72a (Rigaku Oxford Diffraction, 2020)
Empirical absorption correction using spherical harmonics,
implemented in SCALE3 ABSPACK scaling algorithm.
;
_exptl_crystal_colour            'clear colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.316
_exptl_crystal_description       plate
_exptl_crystal_F_000             1024
_exptl_crystal_size_max          0.21
_exptl_crystal_size_mid          0.12
_exptl_crystal_size_min          0.07
_refine_diff_density_max         0.918
_refine_diff_density_min         -0.389
_refine_diff_density_rms         0.081
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.085
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     135
_refine_ls_number_reflns         2492
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.085
_refine_ls_R_factor_all          0.0587
_refine_ls_R_factor_gt           0.0518
_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^)+(0.0749P)^2^+1.9536P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1350
_refine_ls_wR_factor_ref         0.1453
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2198
_reflns_number_total             2492
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d5md00921a2.cif
_cod_data_source_block           20JLR006_KM-028-02
_cod_database_code               7251301
_shelx_shelxl_version_number     2014/7
_chemical_oxdiff_formula         'C80 H160 Cl16 N16 '
_shelx_estimated_absorpt_t_max   0.741
_shelx_estimated_absorpt_t_min   0.448
_diffrn_oxdiff_digest_frames
;
01ea111f80f385a60176d85528528a1426010235118
;
_diffrn_oxdiff_digest_hkl
;
01aaa987d16f0849f93a55d27b33bebd8c58e5
;
_reflns_odcompleteness_completeness 99.96
_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, All N(H,H) groups
2.a Ternary CH refined with riding coordinates:
 C5(H5), C9(H9)
2.b Secondary CH2 refined with riding coordinates:
 N10(H10A,H10B), C6(H6A,H6B), C12(H12A,H12B), C3(H3A,H3B), C7(H7A,H7B),
 C11(H11A,H11B), C8(H8A,H8B), C2(H2A,H2B)
;
_shelx_res_checksum              30836
_shelx_hkl_checksum              4504
_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 2.442
_oxdiff_exptl_absorpt_empirical_full_min 0.417