Tele-substitution Reactions in the Synthesis of a Promising Class of 1,2,4-Triazolo[4,3-a]pyrazine-Based Antimalarials.
Korsik, Marat; Tse, Edwin; Smith, David G.; Lewis, William; Rutledge, Peter J.; Todd, Matthew H.; The Journal of organic chemistry  (2020) –; doi:10.1021/acs.joc.0c01045

data_4038892
_publ_section_title
;
 Tele-substitution Reactions in the Synthesis of a Promising Class of
 1,2,4-Triazolo[4,3-a]pyrazine-Based Antimalarials.
;
_journal_name_full               'The Journal of organic chemistry'
_journal_paper_doi               10.1021/acs.joc.0c01045
_journal_year                    2020
_chemical_formula_moiety         'C20 H19 N5 O'
_chemical_formula_sum            'C20 H19 N5 O'
_chemical_formula_weight         345.40
_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   mixed
_atom_sites_solution_primary     iterative
_audit_creation_date             2019-05-23
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_cell_angle_alpha                71.511(6)
_cell_angle_beta                 82.118(6)
_cell_angle_gamma                82.695(6)
_cell_formula_units_Z            2
_cell_length_a                   7.6546(6)
_cell_length_b                   10.4869(7)
_cell_length_c                   11.4484(8)
_cell_measurement_reflns_used    6961
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      71.9240
_cell_measurement_theta_min      4.4720
_cell_volume                     859.90(11)
_computing_cell_refinement       'CrysAlisPro 1.171.40.53a (Rigaku OD, 2019)'
_computing_data_collection       'CrysAlisPro 1.171.40.53a (Rigaku OD, 2019)'
_computing_data_reduction        'CrysAlisPro 1.171.40.53a (Rigaku OD, 2019)'
_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    'olex2.solve (Bourhis et al., 2015)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      100(2)
_diffrn_detector                 'CCD area detector'
_diffrn_detector_area_resol_mean 5.2930
_diffrn_detector_type            'Agilent Diffraction Atlas detector'
_diffrn_measured_fraction_theta_full 0.997
_diffrn_measured_fraction_theta_max 0.971
_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   -110.00 -50.00   1.00   10.00    --  -39.07 -57.00   0.00   60
  2  \w   -122.00 -37.00   1.00   10.00    --  -39.07 178.00 -60.00   85
  3  \w   -107.00 -46.00   1.00   10.00    --  -39.07 -57.00-150.00   61
  4  \w     -1.00  42.00   1.00   10.00    --  -39.07  19.00 -30.00   43
  5  \w    -40.00 -10.00   1.00   10.00    --  -39.07 -57.00   0.00   30
  6  \w    -42.00  -8.00   1.00   10.00    --  -39.07 -57.00-150.00   34
  7  \w      2.00  27.00   1.00   10.00    --   40.00  87.00-146.72   25
  8  \w     11.00  36.00   1.00   10.00    --   44.00  82.00 -36.82   25
  9  \w     13.00  38.00   1.00   10.00    --   48.00  78.00 116.00   25
 10  \w     13.00  38.00   1.00   10.00    --   48.00  77.00 163.54   25
 11  \w     13.00  38.00   1.00   10.00    --   48.00  76.00  44.82   25
 12  \w     13.00  38.00   1.00   10.00    --   48.00  77.00 -45.34   25
 13  \w     23.00  55.00   1.00   10.00    --   56.00  72.00-173.65   32
 14  \w     25.00  51.00   1.00   10.00    --   56.00  74.00-135.41   26
 15  \w     85.00 140.00   1.00   10.00    --   60.00  74.00  55.17   55
 16  \w     36.00  62.00   1.00   10.00    --   60.00  66.00 103.57   26
 17  \w     26.00  62.00   1.00   10.00    --   60.00  74.00  55.17   36
 18  \w    113.00 144.00   1.00   10.00    --   68.00  72.00 -79.32   31
 19  \w     38.00  71.00   1.00   10.00    --   68.00  56.00-146.15   33
 20  \w     35.00  63.00   1.00   10.00    --   68.00  72.00 -79.32   28
 21  \w     35.00  76.00   1.00   10.00    --   68.00  71.00 -16.64   41
 22  \w     87.00 143.00   1.00   10.00    --   68.00  72.00 125.21   56
 23  \w    111.00 147.00   1.00   10.00    --   68.00  71.00 -16.64   36
 24  \w     35.00  62.00   1.00   10.00    --   68.00  69.00-109.59   27
 25  \w     34.00  76.00   1.00   10.00    --   68.00  72.00 125.21   42
 26  \w     87.00 140.00   1.00   10.00    --   68.00  69.00-109.59   53
 27  \w     38.00  70.00   1.00   10.00    --   72.00  71.00 -36.07   32
 28  \w    114.00 170.00   1.00   40.00    --   92.00  68.00  71.27   56
 29  \w     59.00  85.00   1.00   40.00    --   92.00  68.00  71.27   26
 30  \w     76.00 146.00   1.00   40.00    --  106.69  57.00-116.18   70
 31  \w     57.00  93.00   1.00   40.00    --  106.69 -61.00 -90.00   36
 32  \w     82.00 121.00   1.00   40.00    --  106.69  45.00 -90.00   39
 33  \w     75.00 145.00   1.00   40.00    --  106.69  61.00-150.00   70
 34  \w     62.00  88.00   1.00   40.00    --  106.69 -95.00 -60.00   26
 35  \w     79.00 138.00   1.00   40.00    --  106.69  45.00  90.00   59
 36  \w     22.00  61.00   1.00   40.00    --  106.69 -95.00 -60.00   39
 37  \w     76.00 163.00   1.00   40.00    --  106.69  61.00 -90.00   87
 38  \w    141.00 173.00   1.00   40.00    --  106.69  61.00 120.00   32
 39  \w     75.00 160.00   1.00   40.00    --  106.69  61.00 -60.00   85
 40  \w     75.00 133.00   1.00   40.00    --  106.69  61.00 120.00   58
 41  \w    136.00 170.00   1.00   40.00    --  106.69  61.00 150.00   34
 42  \w     76.00 165.00   1.00   40.00    --  106.69  61.00  30.00   89
 43  \w     78.00 124.00   1.00   40.00    --  106.69  61.00 150.00   46
 44  \w    137.00 176.00   1.00   40.00    --  106.69  61.00-180.00   39
 45  \w     75.00 120.00   1.00   40.00    --  106.69  61.00-180.00   45
 46  \w     61.00  95.00   1.00   40.00    --  106.69 -95.00-180.00   34
 47  \w    128.00 176.00   1.00   40.00    --  106.69  61.00 -30.00   48
 48  \w     75.00 102.00   1.00   40.00    --  106.69  61.00 -30.00   27
 49  \w     24.00 106.00   1.00   40.00    --  106.69 -95.00  90.00   82
 50  \w     74.00 106.00   1.00   40.00    --  106.69-111.00  30.00   32
 51  \w     31.00  74.00   1.00   40.00    --  106.69 -61.00 120.00   43
 52  \w     30.00  68.00   1.00   40.00    --  106.69 -45.00  60.00   38
 53  \w    141.00 171.00   1.00   40.00    --  106.69  61.00  90.00   30
 54  \w     76.00 103.00   1.00   40.00    --  106.69  61.00  90.00   27
 55  \w     41.00  86.00   1.00   40.00    --  106.69 -61.00 -30.00   45
 56  \w    147.00 174.00   1.00   40.00    --  106.69  61.00   0.00   27
 57  \w     75.00 144.00   1.00   40.00    --  106.69  61.00   0.00   69
 58  \w     49.00 109.00   1.00   40.00    --  106.69-111.00 -90.00   60
;
_diffrn_measurement_device       '\k-geometry diffractometer'
_diffrn_measurement_device_type  'SuperNova-Duo, Atlas'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.1813591000
_diffrn_orient_matrix_UB_12      0.0109795000
_diffrn_orient_matrix_UB_13      0.0383668000
_diffrn_orient_matrix_UB_21      0.0122605000
_diffrn_orient_matrix_UB_22      0.1382657000
_diffrn_orient_matrix_UB_23      -0.0999419000
_diffrn_orient_matrix_UB_31      -0.0925769000
_diffrn_orient_matrix_UB_32      0.0703366000
_diffrn_orient_matrix_UB_33      0.0942741000
_diffrn_radiation_collimation    'focusing mirrors'
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_radiation_wavelength_determination fundamental
_diffrn_reflns_av_R_equivalents  0.0299
_diffrn_reflns_av_unetI/netI     0.0241
_diffrn_reflns_Laue_measured_fraction_full 0.997
_diffrn_reflns_Laue_measured_fraction_max 0.971
_diffrn_reflns_limit_h_max       9
_diffrn_reflns_limit_h_min       -9
_diffrn_reflns_limit_k_max       12
_diffrn_reflns_limit_k_min       -12
_diffrn_reflns_limit_l_max       14
_diffrn_reflns_limit_l_min       -13
_diffrn_reflns_number            12353
_diffrn_reflns_point_group_measured_fraction_full 0.997
_diffrn_reflns_point_group_measured_fraction_max 0.971
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         72.964
_diffrn_reflns_theta_min         4.093
_diffrn_source                   'microfocus sealed tube'
_diffrn_source_current           0.8
_diffrn_source_power             0.04
_diffrn_source_target            Cu
_diffrn_source_type              'Agilent Diffraction microfocus tube'
_diffrn_source_voltage           50
_exptl_absorpt_coefficient_mu    0.693
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.653
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.40.53a (Rigaku Oxford Diffraction, 2019)
Numerical absorption correction based on gaussian integration over
			a multifaceted crystal model
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    1.334
_exptl_crystal_description       plank
_exptl_crystal_F_000             364
_exptl_crystal_size_max          0.247
_exptl_crystal_size_mid          0.061
_exptl_crystal_size_min          0.037
_refine_diff_density_max         0.320
_refine_diff_density_min         -0.250
_refine_diff_density_rms         0.042
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.031
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     239
_refine_ls_number_reflns         3334
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.031
_refine_ls_R_factor_all          0.0417
_refine_ls_R_factor_gt           0.0358
_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^)+(0.0560P)^2^+0.2016P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0938
_refine_ls_wR_factor_ref         0.0987
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2917
_reflns_number_total             3334
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            mht19_s1787.cif
_cod_data_source_block           mht19_s1787
_cod_database_code               4038892
_sydney_internal_submission_code mht19_s1787
_sydney_internal_submission_date 2019-05-01
_sydney_internal_submission_number s1787
_sydney_internal_client_code     mkr
_sydney_internal_client_email    mkor7275@uni.sydney.edu.au
_sydney_internal_client_name     'Marat Korsik'
_sydney_internal_supervisor_code mht
_sydney_internal_supervisor_name 'Matt Todd'
_sydney_internal_collection_date 2019-05-03
_sydney_internal_collection_user wlew0588
_sydney_internal_process_date    2019-05-06
_sydney_internal_process_user    wlew0588
_sydney_internal_solution_date   2019-05-07
_sydney_internal_solution_user   wlew0588
_sydney_internal_refine_date     2019-05-07
_sydney_internal_refine_user     wlew0588
_sydney_internal_check_and_archive_date 2019-05-23
_sydney_internal_check_user      wlew0588
_shelx_shelxl_version_number     2018/3
_chemical_oxdiff_formula         'C20 H21 N5 O'
_chemical_oxdiff_usercomment     MK128-2d
_shelx_estimated_absorpt_t_max   0.975
_shelx_estimated_absorpt_t_min   0.847
_reflns_odcompleteness_completeness 99.77
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     67.13
_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 Secondary CH2 refined with riding coordinates:
 C18(H18A,H18B), C23(H23A,H23B)
2.b Aromatic/amide H refined with riding coordinates:
 C11(H11), C12(H12), C13(H13), C15(H15), C16(H16), C17(H17), C19(H19),
 C20(H20), C22(H22), C25(H25), C26(H26)
2.c Idealised Me refined as rotating group:
 C21(H21A,H21B,H21C)
;
_shelx_res_checksum              39700
_shelx_hkl_checksum              32120
_olex2_date_sample_data_collection 2019-05-03
_olex2_date_sample_submission    2019-05-01
_olex2_exptl_crystal_mounting_method 'in paratone on a micromount'
_olex2_submission_original_sample_id MK128-2d
_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 1.363
_oxdiff_exptl_absorpt_empirical_full_min 0.739