Modular synthesis of thirty lead-like scaffolds suitable for CNS drug discovery
Mayol-Llinàs, Joan; Farnaby, William; Nelson, Adam; Chemical Communications  (2017) –; doi:10.1039/C7CC06078E

data_7120848
_publ_section_title
;
 Modular synthesis of thirty lead-like scaffolds suitable for CNS drug
 discovery
;
_journal_name_full               'Chemical Communications'
_journal_paper_doi               10.1039/C7CC06078E
_journal_year                    2017
_chemical_formula_moiety         'C15 H17 N O3'
_chemical_formula_sum            'C15 H17 N O3'
_chemical_formula_weight         259.29
_chemical_name_systematic
;
 (4aR*,9bS*)-8-Methoxy-4a-(prop-2-en-1-yl)-2H,3H,4H,4aH,5H,9bH-indeno[2,1-e][1,3] oxazin-2-one
;
_space_group_crystal_system      triclinic
_space_group_IT_number           2
_space_group_name_Hall           '-P 1'
_space_group_name_H-M_alt        'P -1'
_symmetry_space_group_name_Hall  '-P 1'
_symmetry_space_group_name_H-M   'P -1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2017-06-02
_audit_creation_method
;
Olex2 1.2
(compiled 2017.03.28 svn.r3405 for OlexSys, GUI svn.r5337)
;
_audit_update_record
;
2017-08-03 deposited with the CCDC.
2017-11-02 downloaded from the CCDC.
;
_cell_angle_alpha                63.764(7)
_cell_angle_beta                 79.148(6)
_cell_angle_gamma                74.800(6)
_cell_formula_units_Z            2
_cell_length_a                   6.7483(5)
_cell_length_b                   9.9314(7)
_cell_length_c                   11.0967(8)
_cell_measurement_reflns_used    2337
_cell_measurement_temperature    119.97(16)
_cell_measurement_theta_max      73.6950
_cell_measurement_theta_min      5.0600
_cell_volume                     641.50(9)
_computing_cell_refinement       'CrysAlisPro 1.171.38.46 (Rigaku OD, 2015)'
_computing_data_collection       'CrysAlisPro 1.171.38.46 (Rigaku OD, 2015)'
_computing_data_reduction        'CrysAlisPro 1.171.38.46 (Rigaku OD, 2015)'
_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 (Sheldrick, 2015)'
_diffrn_ambient_environment      N~2~
_diffrn_ambient_temperature      119.97(16)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 5.3095
_diffrn_detector_type            Atlas
_diffrn_measured_fraction_theta_full 0.961
_diffrn_measured_fraction_theta_max 0.921
_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    -42.00 -13.00   1.00    1.00    --  -38.50 -57.00  90.00   29
  2  \w    -59.00 -17.00   1.00    1.00    --  -38.50 -65.00  56.67   42
  3  \w    -96.00 -62.00   1.00    1.00    --  -38.50 -65.00  56.67   34
  4  \w    -64.00 -20.00   1.00    1.00    --  -38.50  63.00 -90.00   44
  5  \w    -65.00  29.00   1.00    1.00    --  -38.50  65.00 -45.44   94
  6  \w     78.00 109.00   1.00    1.00    --   42.96  37.00 120.00   31
  7  \w    148.00 174.00   1.00    4.00    --  104.98  45.00  90.00   26
  8  \w     97.00 174.00   1.00    4.00    --  104.98  45.00 -90.00   77
  9  \w     84.00 126.00   1.00    4.00    --  104.98  45.00  90.00   42
 10  \w     73.00 100.00   1.00    4.00    --  104.98 -65.00  25.58   27
 11  \w     61.00  93.00   1.00    4.00    --  104.98 -65.00   5.56   32
 12  \w     56.00 119.00   1.00    4.00    --  104.98 -64.00 -44.72   63
 13  \w     50.00  96.00   1.00    4.00    --  104.98 -65.00-112.49   46
 14  \w     39.00 124.00   1.00    4.00    --  104.98 -30.00 -90.00   85
 15  \w     52.00 113.00   1.00    4.00    --  104.98 -65.00  81.10   61
 16  \w     52.00 112.00   1.00    4.00    --  104.98 -64.00 164.23   60
 17  \w     31.00 141.00   1.00    4.00    --  104.98 -15.00  90.00  110
 18  \w     31.00  66.00   1.00    1.00    --   42.96 -65.00 -25.82   35
 19  \w     17.00  53.00   1.00    1.00    --   42.96  63.00  48.85   36
 20  \w     22.00  87.00   1.00    1.00    --   42.96  65.00-175.43   65
;
_diffrn_measurement_device       'four-circle diffractometer'
_diffrn_measurement_device_type  'SuperNova, Dual, Cu at zero, Atlas'
_diffrn_measurement_method       '\w scans'
_diffrn_orient_matrix_type
'CrysAlisPro convention (1999,Acta A55,543-557)'
_diffrn_orient_matrix_UB_11      0.0884466000
_diffrn_orient_matrix_UB_12      0.1315749000
_diffrn_orient_matrix_UB_13      -0.1174983000
_diffrn_orient_matrix_UB_21      0.1720831000
_diffrn_orient_matrix_UB_22      -0.0251018000
_diffrn_orient_matrix_UB_23      0.0858641000
_diffrn_orient_matrix_UB_31      0.1375550000
_diffrn_orient_matrix_UB_32      -0.1151190000
_diffrn_orient_matrix_UB_33      -0.0542760000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0277
_diffrn_reflns_av_unetI/netI     0.0391
_diffrn_reflns_Laue_measured_fraction_full 0.961
_diffrn_reflns_Laue_measured_fraction_max 0.921
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -8
_diffrn_reflns_limit_k_max       10
_diffrn_reflns_limit_k_min       -12
_diffrn_reflns_limit_l_max       12
_diffrn_reflns_limit_l_min       -13
_diffrn_reflns_number            4223
_diffrn_reflns_point_group_measured_fraction_full 0.961
_diffrn_reflns_point_group_measured_fraction_max 0.921
_diffrn_reflns_theta_full        67.684
_diffrn_reflns_theta_max         73.970
_diffrn_reflns_theta_min         4.458
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.762
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.903
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.38.46 (Rigaku Oxford Diffraction, 2015)
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            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.342
_exptl_crystal_description       block
_exptl_crystal_F_000             276
_exptl_crystal_size_max          0.15
_exptl_crystal_size_mid          0.08
_exptl_crystal_size_min          0.06
_refine_diff_density_max         0.348
_refine_diff_density_min         -0.218
_refine_diff_density_rms         0.043
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.028
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     173
_refine_ls_number_reflns         2397
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.028
_refine_ls_R_factor_all          0.0450
_refine_ls_R_factor_gt           0.0379
_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^)+(0.0496P)^2^+0.1214P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0941
_refine_ls_wR_factor_ref         0.0996
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2070
_reflns_number_total             2397
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            c7cc06078e2.cif
_cod_data_source_block           jml397_cu
_cod_original_cell_volume        641.49(9)
_cod_database_code               7120848
_shelx_shelxl_version_number     2014/7
_chemical_oxdiff_formula         'C30 H34 N2 O6'
_reflns_odcompleteness_completeness 96.33
_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) groups
 At 1.5 times of:
  All C(H,H,H) groups
2.a Ternary CH refined with riding coordinates:
 C4(H4)
2.b Secondary CH2 refined with riding coordinates:
 C6(H6A,H6B), C11(H11A,H11B), C13(H13A,H13B)
2.c Aromatic/amide H refined with riding coordinates:
 N1(H1), C2(H2), C8(H8), C9(H9), C14(H14)
2.d X=CH2 refined with riding coordinates:
 C15(H15A,H15B)
2.e Idealised Me refined as rotating group:
 C10(H10A,H10B,H10C)
;
_olex2_date_sample_data_collection 2017-06-02
_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 1.230
_oxdiff_exptl_absorpt_empirical_full_min 0.864