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_7120847
_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         'C14 H25 N O4'
_chemical_formula_sum            'C14 H25 N O4'
_chemical_formula_weight         271.35
_chemical_name_systematic
;
 tert-Butyl N-{[(4aR*,8aR*)-octahydropyrano[4,3-b]pyran-4a-yl]methyl}carbamate 
;
_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'
_symmetry_space_group_name_Hall  '-P 2ybc'
_symmetry_space_group_name_H-M   'P 1 21/c 1'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_audit_creation_date             2016-07-18
_audit_creation_method
;
Olex2 1.2
(compiled 2016.02.19 svn.r3266 for OlexSys, GUI svn.r5155)
;
_audit_update_record
;
2017-08-03 deposited with the CCDC.
2017-11-02 downloaded from the CCDC.
;
_cell_angle_alpha                90.00
_cell_angle_beta                 91.7913(16)
_cell_angle_gamma                90.00
_cell_formula_units_Z            4
_cell_length_a                   11.04739(18)
_cell_length_b                   12.2038(2)
_cell_length_c                   10.96322(18)
_cell_measurement_reflns_used    3537
_cell_measurement_temperature    120.01(19)
_cell_measurement_theta_max      73.6110
_cell_measurement_theta_min      5.3490
_cell_volume                     1477.34(4)
_computing_cell_refinement       'CrysAlisPro 1.171.38.43b (Rigaku OD, 2015)'
_computing_data_collection       'CrysAlisPro 1.171.38.43b (Rigaku OD, 2015)'
_computing_data_reduction        'CrysAlisPro 1.171.38.43b (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      120.01(19)
_diffrn_detector                 'CCD plate'
_diffrn_detector_area_resol_mean 5.3095
_diffrn_detector_type            Atlas
_diffrn_measured_fraction_theta_full 0.964
_diffrn_measured_fraction_theta_max 0.964
_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    -64.00  29.00   1.00    2.00    --  -38.50  57.00   0.00   93
  2  \w     79.00 106.00   1.00    2.00    --   42.71  37.00-150.00   27
  3  \w     38.00  63.00   1.00    2.00    --   42.71  37.00-180.00   25
  4  \w     31.00 144.00   1.00    8.00    --  104.98 -15.00-120.00  113
  5  \w     86.00 126.00   1.00    8.00    --  104.98 -30.00   0.00   40
  6  \w     87.00 119.00   1.00    8.00    --  104.98  45.00  60.00   32
  7  \w    124.00 175.00   1.00    8.00    --  104.98  45.00  60.00   51
  8  \w     86.00 119.00   1.00    8.00    --  104.98 -45.00 120.00   33
  9  \w     66.00  93.00   1.00    8.00    --  104.98 -61.00 -60.00   27
 10  \w     65.00  92.00   1.00    8.00    --  104.98 -62.00-151.96   27
 11  \w     37.00 127.00   1.00    8.00    --  104.98 -64.00 -94.96   90
 12  \w     37.00  92.00   1.00    8.00    --  104.98 -64.00-126.58   55
 13  \w   -106.00 -18.00   1.00    2.00    --  -38.50 -37.00-180.00   88
;
_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      0.0034961000
_diffrn_orient_matrix_UB_12      -0.0864043000
_diffrn_orient_matrix_UB_13      -0.1022753000
_diffrn_orient_matrix_UB_21      -0.0539672000
_diffrn_orient_matrix_UB_22      0.0840406000
_diffrn_orient_matrix_UB_23      -0.0914416000
_diffrn_orient_matrix_UB_31      0.1285894000
_diffrn_orient_matrix_UB_32      0.0374848000
_diffrn_orient_matrix_UB_33      -0.0308441000
_diffrn_radiation_monochromator  mirror
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54184
_diffrn_reflns_av_R_equivalents  0.0214
_diffrn_reflns_av_unetI/netI     0.0256
_diffrn_reflns_limit_h_max       13
_diffrn_reflns_limit_h_min       -9
_diffrn_reflns_limit_k_max       14
_diffrn_reflns_limit_k_min       -14
_diffrn_reflns_limit_l_max       13
_diffrn_reflns_limit_l_min       -13
_diffrn_reflns_number            6401
_diffrn_reflns_theta_full        73.75
_diffrn_reflns_theta_max         73.75
_diffrn_reflns_theta_min         4.00
_diffrn_source                   'micro-focus sealed X-ray tube'
_diffrn_source_type              'SuperNova (Cu) X-ray Source'
_exptl_absorpt_coefficient_mu    0.721
_exptl_absorpt_correction_T_max  1.000
_exptl_absorpt_correction_T_min  0.740
_exptl_absorpt_correction_type   gaussian
_exptl_absorpt_process_details
;
CrysAlisPro 1.171.38.43b (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    1.220
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       irregular
_exptl_crystal_F_000             592
_exptl_crystal_size_max          0.21
_exptl_crystal_size_mid          0.12
_exptl_crystal_size_min          0.09
_refine_diff_density_max         0.293
_refine_diff_density_min         -0.190
_refine_diff_density_rms         0.035
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.052
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     175
_refine_ls_number_reflns         2882
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.052
_refine_ls_R_factor_all          0.0435
_refine_ls_R_factor_gt           0.0374
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.0393P)^2^+0.4832P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0880
_refine_ls_wR_factor_ref         0.0918
_reflns_number_gt                2549
_reflns_number_total             2882
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            c7cc06078e2.cif
_cod_data_source_block           jml160_cu
_cod_original_cell_volume        1477.35(4)
_cod_database_code               7120847
_chemical_oxdiff_formula         'C14 H25 N1 O4'
_reflns_odcompleteness_completeness 99.39
_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:
 C5(H5)
2.b Secondary CH2 refined with riding coordinates:
 C2(H2A,H2B), C3(H3A,H3B), C4(H4A,H4B), C6(H6A,H6B), C7(H7A,H7B), C8(H8A,H8B),
 C9(H9A,H9B)
2.c Aromatic/amide H refined with riding coordinates:
 N1(H1)
2.d Idealised Me refined as rotating group:
 C12(H12A,H12B,H12C), C13(H13A,H13B,H13C), C14(H14A,H14B,H14C)
;
_olex2_date_sample_data_collection 2016-07-18
_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 1.264
_oxdiff_exptl_absorpt_empirical_full_min 0.880