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_4038893
_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         'C10 H13 N5'
_chemical_formula_sum            'C10 H13 N5'
_chemical_formula_weight         203.25
_space_group_crystal_system      monoclinic
_space_group_IT_number           14
_space_group_name_Hall           '-P 2ybc'
_space_group_name_H-M_alt        'P 1 21/c 1'
_atom_sites_solution_hydrogens   geom
_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                90
_cell_angle_beta                 92.8415(17)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   9.27494(16)
_cell_length_b                   8.81723(13)
_cell_length_c                   12.0155(2)
_cell_measurement_reflns_used    9526
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      75.9920
_cell_measurement_theta_min      3.6890
_cell_volume                     981.41(3)
_computing_cell_refinement       'CrysAlisPro 1.171.40.35a (Rigaku OD, 2018)'
_computing_data_collection       'CrysAlisPro 1.171.40.35a (Rigaku OD, 2018)'
_computing_data_reduction        'CrysAlisPro 1.171.40.35a (Rigaku OD, 2018)'
_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_temperature      100(2)
_diffrn_detector                 'CCD area detector'
_diffrn_detector_area_resol_mean 10.5861
_diffrn_detector_type            'Agilent Diffraction Atlas detector'
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.994
_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    -49.00 -22.00   1.00    1.00    --  -40.33  57.00  60.00   27
  2  \w     10.00  76.00   1.00    1.00    --   40.33  64.00 -45.87   66
  3  \w     11.00 114.00   1.00    1.00    --   40.33  64.00-127.01  103
  4  \w     58.00  84.00   1.00    1.00    --   40.33  57.00 120.00   26
  5  \w     10.00  71.00   1.00    1.00    --   40.33  64.00 159.38   61
  6  \w     77.00 114.00   1.00    1.00    --   40.33  64.00 -45.87   37
  7  \w     85.00 114.00   1.00    1.00    --   40.33  64.00 159.38   29
  8  \w     12.00  51.00   1.00    1.00    --   40.33  57.00 120.00   39
  9  \w     16.00  97.00   1.00    1.00    --   40.33  64.00  15.22   81
 10  \w     37.00  70.00   1.00    3.00    --  113.00 -33.00-118.76   33
 11  \w     90.00 115.00   1.00    3.00    --  113.00  45.00 -60.00   25
 12  \w    134.00 177.00   1.00    3.00    --  113.00  45.00-120.00   43
 13  \w    121.00 178.00   1.00    3.00    --  113.00  45.00 -60.00   57
 14  \w     54.00  84.00   1.00    3.00    --  113.00 -65.00 -84.60   30
 15  \w    119.00 144.00   1.00    3.00    --  113.00 -65.00 -17.42   25
 16  \w     84.00 112.00   1.00    3.00    --  113.00 -64.00 142.18   28
 17  \w     89.00 124.00   1.00    3.00    --  113.00  45.00-120.00   35
 18  \w    107.00 161.00   1.00    3.00    --  113.00  45.00 -30.00   54
 19  \w     73.00 100.00   1.00    3.00    --  113.00 -65.00  86.24   27
 20  \w     96.00 126.00   1.00    3.00    --  113.00  45.00 -90.00   30
 21  \w     39.00 114.00   1.00    3.00    --  113.00 -65.00 -17.42   75
 22  \w    106.00 135.00   1.00    3.00    --  113.00  52.00  38.00   29
 23  \w    145.00 175.00   1.00    3.00    --  113.00  45.00-150.00   30
 24  \w     94.00 137.00   1.00    3.00    --  113.00  45.00-150.00   43
 25  \w    137.00 164.00   1.00    3.00    --  113.00  45.00  90.00   27
 26  \w     62.00 121.00   1.00    3.00    --  113.00 -65.00 -99.81   59
 27  \w     40.00 142.00   1.00    3.00    --  113.00 -61.00 120.00  102
 28  \w     81.00 106.00   1.00    3.00    --  113.00 -64.00 -66.98   25
 29  \w     62.00  92.00   1.00    3.00    --  113.00 -65.00  23.09   30
 30  \w    106.00 132.00   1.00    3.00    --  113.00  61.00   0.00   26
 31  \w     63.00 106.00   1.00    3.00    --  113.00 -65.00 105.31   43
 32  \w     96.00 139.00   1.00    3.00    --  113.00  45.00 120.00   43
 33  \w     94.00 119.00   1.00    3.00    --  113.00  45.00   0.00   25
 34  \w     83.00 112.00   1.00    3.00    --  113.00  61.00 150.00   29
 35  \w     39.00  79.00   1.00    3.00    --  113.00 -45.00 -30.00   40
 36  \w     50.00  76.00   1.00    3.00    --  113.00 -45.00  30.00   26
 37  \w    106.00 166.00   1.00    3.00    --  113.00  45.00-180.00   60
 38  \w     70.00  96.00   1.00    3.00    --  113.00 -38.00  56.06   26
 39  \w     72.00 143.00   1.00    3.00    --  113.00 -63.00-164.14   71
 40  \w     40.00 113.00   1.00    3.00    --  113.00 -65.00  37.73   73
 41  \w     54.00  92.00   1.00    3.00    --  113.00 -65.00 178.43   38
 42  \w    -69.00  33.00   1.00    1.00    --  -40.58  57.00-150.00  102
 43  \w    -68.00  17.00   1.00    1.00    --  -40.58  57.00 120.00   85
 44  \w    -60.00 -14.00   1.00    1.00    --  -40.58 -57.00 -30.00   46
 45  \w   -113.00 -87.00   1.00    1.00    --  -40.58 -57.00-150.00   26
 46  \w    -88.00 -50.00   1.00    1.00    --  -40.58 -38.00  30.00   38
 47  \w    -46.00 -17.00   1.00    1.00    --  -40.58 -57.00 150.00   29
 48  \w    -99.00 -64.00   1.00    1.00    --  -40.58 -57.00 150.00   35
 49  \w    -60.00 -13.00   1.00    1.00    --  -40.58 -57.00-150.00   47
 50  \w    -47.00 -16.00   1.00    1.00    --  -40.58 -38.00  30.00   31
 51  \w    -16.00  70.00   1.00    1.00    --   40.58 -57.00 -90.00   86
 52  \w     40.00  67.00   1.00    1.00    --   40.58 -57.00-180.00   27
 53  \w     83.00 108.00   1.00    3.00    --  113.00  61.00  60.00   25
 54  \w    153.00 178.00   1.00    3.00    --  113.00  62.00  78.74   25
 55  \w    124.00 150.00   1.00    3.00    --  113.00  61.00  60.00   26
 56  \w     87.00 113.00   1.00    3.00    --  113.00  45.00 -90.00   26
 57  \w     86.00 112.00   1.00    3.00    --  113.00  45.00 -30.00   26
 58  \w     82.00 108.00   1.00    3.00    --  113.00  62.00  78.74   26
 59  \w     85.00 111.00   1.00    3.00    --  113.00  55.00 176.75   26
 60  \w     38.00  70.00   1.00    3.00    --  113.00 -34.00 -85.57   32
 61  \w     83.00 124.00   1.00    3.00    --  113.00  61.00  90.00   41
 62  \w    150.00 176.00   1.00    3.00    --  113.00  61.00 -60.00   26
 63  \w     83.00 108.00   1.00    3.00    --  113.00  61.00-120.00   25
 64  \w    150.00 175.00   1.00    3.00    --  113.00  61.00-120.00   25
 65  \w     86.00 112.00   1.00    3.00    --  113.00  45.00  30.00   26
 66  \w    123.00 165.00   1.00    3.00    --  113.00  45.00  30.00   42
 67  \w     83.00 109.00   1.00    3.00    --  113.00  61.00-180.00   26
 68  \w     83.00 108.00   1.00    3.00    --  113.00  61.00 120.00   25
 69  \w    130.00 176.00   1.00    3.00    --  113.00  61.00 120.00   46
 70  \w     85.00 130.00   1.00    3.00    --  113.00  45.00  60.00   45
 71  \w     83.00 109.00   1.00    3.00    --  113.00  61.00 -90.00   26
 72  \w     83.00 113.00   1.00    3.00    --  113.00  61.00 -60.00   30
 73  \w    108.00 137.00   1.00    3.00    --  113.00 -37.00 139.19   29
 74  \w    139.00 176.00   1.00    3.00    --  113.00  60.00 -17.04   37
 75  \w     87.00 113.00   1.00    3.00    --  113.00  45.00 120.00   26
 76  \w     83.00 108.00   1.00    3.00    --  113.00  61.00-150.00   25
 77  \w     88.00 138.00   1.00    3.00    --  113.00  45.00-150.00   50
 78  \w     85.00 110.00   1.00    3.00    --  113.00  45.00-180.00   25
 79  \w     83.00 108.00   1.00    3.00    --  113.00  61.00   0.00   25
 80  \w     86.00 114.00   1.00    3.00    --  113.00  45.00  90.00   28
 81  \w     84.00 109.00   1.00    3.00    --  113.00  52.00  38.00   25
 82  \w    139.00 174.00   1.00    3.00    --  113.00  52.00  38.00   35
 83  \w    116.00 175.00   1.00    3.00    --  113.00  45.00 150.00   59
 84  \w     73.00  99.00   1.00    3.00    --  113.00 -37.00 139.19   26
 85  \w    104.00 140.00   1.00    3.00    --  113.00 -34.00 -85.57   36
 86  \w     85.00 113.00   1.00    3.00    --  113.00  45.00 150.00   28
 87  \w     83.00 109.00   1.00    3.00    --  113.00  61.00 -30.00   26
 88  \w    127.00 167.00   1.00    3.00    --  113.00  61.00 -90.00   40
 89  \w     41.00  67.00   1.00    3.00    --  113.00 -37.00 139.19   26
 90  \w     83.00 109.00   1.00    3.00    --  113.00  60.00 -17.04   26
 91  \w    144.00 171.00   1.00    3.00    --  113.00  54.00   1.02   27
 92  \w     87.00 116.00   1.00    3.00    --  113.00  54.00   1.02   29
;
_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      -0.1359236000
_diffrn_orient_matrix_UB_12      0.0140471000
_diffrn_orient_matrix_UB_13      0.0679707000
_diffrn_orient_matrix_UB_21      -0.0248938000
_diffrn_orient_matrix_UB_22      0.1619637000
_diffrn_orient_matrix_UB_23      -0.0450970000
_diffrn_orient_matrix_UB_31      -0.0925544000
_diffrn_orient_matrix_UB_32      -0.0642017000
_diffrn_orient_matrix_UB_33      -0.0990445000
_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  0.0264
_diffrn_reflns_av_unetI/netI     0.0118
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.994
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -11
_diffrn_reflns_limit_k_max       11
_diffrn_reflns_limit_k_min       -11
_diffrn_reflns_limit_l_max       14
_diffrn_reflns_limit_l_min       -15
_diffrn_reflns_number            19400
_diffrn_reflns_point_group_measured_fraction_full 0.999
_diffrn_reflns_point_group_measured_fraction_max 0.994
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         76.312
_diffrn_reflns_theta_min         4.774
_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    0.722
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.720
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.40.35a (Rigaku Oxford Diffraction, 2018)
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 pinkish orange'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_modifier   pinkish
_exptl_crystal_colour_primary    orange
_exptl_crystal_density_diffrn    1.376
_exptl_crystal_description       block
_exptl_crystal_F_000             432
_exptl_crystal_size_max          0.246
_exptl_crystal_size_mid          0.166
_exptl_crystal_size_min          0.1
_refine_diff_density_max         0.297
_refine_diff_density_min         -0.240
_refine_diff_density_rms         0.040
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.068
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     136
_refine_ls_number_reflns         2040
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.068
_refine_ls_R_factor_all          0.0347
_refine_ls_R_factor_gt           0.0323
_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^)+(0.0463P)^2^+0.2577P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0863
_refine_ls_wR_factor_ref         0.0889
_reflns_Friedel_coverage         0.000
_reflns_number_gt                1886
_reflns_number_total             2040
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            mht18pt1_s1612.cif
_cod_data_source_block           mht18pt1_s1612
_cod_database_code               4038893
_sydney_internal_submission_code mht18_s1612
_sydney_internal_submission_date 2017-11-28
_sydney_internal_submission_number s1612
_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 2018-05-07
_sydney_internal_collection_user wlew0588
_sydney_internal_process_date    2019-05-22
_sydney_internal_process_user    wlew0588
_sydney_internal_solution_date   2019-05-22
_sydney_internal_solution_user   wlew0588
_sydney_internal_refine_date     2019-05-22
_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         C10H13N5
_shelx_estimated_absorpt_t_max   0.931
_shelx_estimated_absorpt_t_min   0.842
_reflns_odcompleteness_completeness 97.98
_reflns_odcompleteness_iscentric 1
_reflns_odcompleteness_theta     77.17
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups
2.a Secondary CH2 refined with riding coordinates:
 C11(H11A,H11B), C12(H12A,H12B), C13(H13A,H13B), C14(H14A,H14B), C15(H15A,H15B)
2.b Aromatic/amide H refined with riding coordinates:
 C2(H2), C8(H8), C9(H9)
;
_shelx_res_checksum              6796
_shelx_hkl_checksum              3958
_olex2_date_sample_data_collection 2018-05-07
_olex2_date_sample_submission    2017-11-28
_olex2_exptl_crystal_mounting_method 'in paratone on a loop'
_olex2_submission_original_sample_id MK026-1
_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 1.337
_oxdiff_exptl_absorpt_empirical_full_min 0.885