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#$Date: 2025-08-19 22:06:29 +0200 (Tue 19 de Aug de 2025) $
#$Revision: 301812 $
#$URL: svn://www.crystallography.net/cod/cif/4/02/80/4028066.cif $
#------------------------------------------------------------------------------
#
# This file is available in the Crystallography Open Database (COD),
# http://www.crystallography.net/
#
# All data on this site have been placed in the public domain by the
# contributors.
#
data_4028066
loop_
_publ_author_name
'Che-Wah Lee'
'Ricardo Lira'
'Jason Dutra'
'Kevin Ogilvie'
'Brian T. O'Neill'
'Michael Brodney'
'Christopher Helal'
'Joseph Young'
'Erik Lachapelle'
'Subas Sakya'
'John C. Murray'
_publ_section_title
;
 Stereoselective Synthesis of Spiropiperidines as BACE-1 Aspartyl Protease
 Inhibitors via Late Stage N-Arylation of a
 1,8-Diazaspiro[4.5]dec-3-en-2-one Pharmacophore
;
_journal_name_full               'Journal of Organic Chemistry'
_journal_page_first              2661
_journal_page_last               2669
_journal_paper_doi               10.1021/jo400016m
_journal_volume                  78
_journal_year                    2013
_chemical_absolute_configuration ad
_chemical_formula_sum            'C15 H18 Cl3 N O3'
_chemical_formula_weight         366.65
_space_group_IT_number           19
_symmetry_cell_setting           orthorhombic
_symmetry_space_group_name_Hall  'P 2ac 2ab'
_symmetry_space_group_name_H-M   'P 21 21 21'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_audit_creation_method           SHELXL-97
_cell_angle_alpha                90.00
_cell_angle_beta                 90.00
_cell_angle_gamma                90.00
_cell_formula_units_Z            4
_cell_length_a                   8.14750(10)
_cell_length_b                   11.0267(2)
_cell_length_c                   19.1568(4)
_cell_measurement_reflns_used    4578
_cell_measurement_temperature    298(2)
_cell_measurement_theta_max      67.30
_cell_measurement_theta_min      4.62
_cell_volume                     1721.05(5)
_computing_cell_refinement       'Bruker SMART'
_computing_data_collection       'Bruker SMART'
_computing_data_reduction        'Bruker SAINT'
_computing_molecular_graphics    'Bruker SHELXTL'
_computing_publication_material  'Bruker SHELXTL'
_computing_structure_refinement  'SHELXL-97 (Sheldrick, 1997)'
_computing_structure_solution    'SHELXS-97 (Sheldrick, 1990)'
_diffrn_ambient_temperature      298(2)
_diffrn_measured_fraction_theta_full 0.979
_diffrn_measured_fraction_theta_max 0.979
_diffrn_measurement_device_type  'CCD area detector'
_diffrn_measurement_method       'phi and omega scans'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_source         'fine-focus sealed tube'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0360
_diffrn_reflns_av_sigmaI/netI    0.0420
_diffrn_reflns_limit_h_max       9
_diffrn_reflns_limit_h_min       -9
_diffrn_reflns_limit_k_max       10
_diffrn_reflns_limit_k_min       -12
_diffrn_reflns_limit_l_max       22
_diffrn_reflns_limit_l_min       -20
_diffrn_reflns_number            7706
_diffrn_reflns_theta_full        67.34
_diffrn_reflns_theta_max         67.34
_diffrn_reflns_theta_min         4.62
_exptl_absorpt_coefficient_mu    4.919
_exptl_absorpt_correction_T_max  0.6390
_exptl_absorpt_correction_T_min  0.2156
_exptl_absorpt_correction_type   empirical
_exptl_crystal_density_diffrn    1.415
_exptl_crystal_density_meas      0
_exptl_crystal_F_000             760
_exptl_crystal_size_max          0.45
_exptl_crystal_size_mid          0.15
_exptl_crystal_size_min          0.10
_refine_diff_density_max         0.196
_refine_diff_density_min         -0.298
_refine_diff_density_rms         0.065
_refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881'
_refine_ls_abs_structure_Flack   0.023(19)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.025
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     201
_refine_ls_number_reflns         2952
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.025
_refine_ls_R_factor_all          0.0488
_refine_ls_R_factor_gt           0.0419
_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/[σ²(Fo²)+(0.0646P)²+0.0499P] where P=(Fo²+2Fc²)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1061
_refine_ls_wR_factor_ref         0.1119
_reflns_number_gt                2591
_reflns_number_total             2952
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            jo400016m_si_002.cif
_cod_data_source_block           i884
_cod_database_code               4028066
loop_
_symmetry_equiv_pos_as_xyz
'x, y, z'
'-x+1/2, -y, z+1/2'
'-x, y+1/2, -z+1/2'
'x+1/2, -y+1/2, -z'
loop_
_atom_site_label
_atom_site_type_symbol
_atom_site_fract_x
_atom_site_fract_y
_atom_site_fract_z
_atom_site_U_iso_or_equiv
_atom_site_adp_type
_atom_site_occupancy
_atom_site_symmetry_multiplicity
_atom_site_calc_flag
_atom_site_refinement_flags
C1 C 0.0084(4) 0.5621(3) -0.03048(19) 0.0568(8) Uani 1 1 d .
H1 H 0.0786 0.5412 -0.0668 0.068 Uiso 1 1 calc R
C2 C -0.1585(5) 0.5436(4) -0.0379(3) 0.0708(11) Uani 1 1 d .
H2 H -0.2006 0.5096 -0.0786 0.085 Uiso 1 1 calc R
C3 C -0.2614(5) 0.5765(4) 0.0159(3) 0.0744(12) Uani 1 1 d .
H3A H -0.3737 0.5638 0.0112 0.089 Uiso 1 1 calc R
C4 C -0.2038(5) 0.6265(4) 0.0751(2) 0.0779(12) Uani 1 1 d .
H4 H -0.2756 0.6487 0.1106 0.093 Uiso 1 1 calc R
C5 C -0.0336(5) 0.6449(4) 0.08276(18) 0.0648(9) Uani 1 1 d .
H5 H 0.0070 0.6799 0.1234 0.078 Uiso 1 1 calc R
C6 C 0.0732(4) 0.6113(3) 0.03042(17) 0.0464(7) Uani 1 1 d .
C7 C 0.2544(4) 0.6254(3) 0.0386(2) 0.0552(8) Uani 1 1 d .
H7A H 0.3027 0.6472 -0.0060 0.066 Uiso 1 1 calc R
H7B H 0.2773 0.6901 0.0714 0.066 Uiso 1 1 calc R
C8 C 0.3814(3) 0.5110(3) 0.13040(15) 0.0402(6) Uani 1 1 d .
C9 C 0.5285(4) 0.3911(3) 0.21593(15) 0.0441(7) Uani 1 1 d .
H9 H 0.5389 0.4721 0.2365 0.053 Uiso 1 1 calc R
C10 C 0.4115(4) 0.3211(4) 0.26222(18) 0.0586(9) Uani 1 1 d .
H10A H 0.3096 0.3644 0.2658 0.088 Uiso 1 1 calc R
H10B H 0.4588 0.3120 0.3078 0.088 Uiso 1 1 calc R
H10C H 0.3918 0.2425 0.2424 0.088 Uiso 1 1 calc R
C11 C 0.7038(3) 0.3394(3) 0.21047(16) 0.0430(7) Uani 1 1 d .
H11A H 0.7766 0.4033 0.1947 0.052 Uiso 1 1 calc R
H11B H 0.7396 0.3150 0.2567 0.052 Uiso 1 1 calc R
C12 C 0.7213(3) 0.2312(3) 0.16135(15) 0.0403(6) Uani 1 1 d .
C13 C 0.6464(4) 0.2615(3) 0.09038(15) 0.0433(7) Uani 1 1 d .
H13A H 0.7100 0.3251 0.0682 0.052 Uiso 1 1 calc R
H13B H 0.6500 0.1904 0.0606 0.052 Uiso 1 1 calc R
C14 C 0.4701(4) 0.3029(3) 0.09876(16) 0.0458(7) Uani 1 1 d .
H14A H 0.4253 0.3243 0.0535 0.055 Uiso 1 1 calc R
H14B H 0.4047 0.2372 0.1178 0.055 Uiso 1 1 calc R
C15 C 0.9058(4) 0.1969(3) 0.15248(17) 0.0513(8) Uani 1 1 d .
Cl1 Cl 0.99489(11) 0.15526(10) 0.23371(5) 0.0705(3) Uani 1 1 d .
Cl2 Cl 1.02414(11) 0.31667(11) 0.11634(6) 0.0823(3) Uani 1 1 d .
Cl3 Cl 0.92792(12) 0.06880(11) 0.09622(6) 0.0793(3) Uani 1 1 d .
N1 N 0.4613(3) 0.4082(2) 0.14550(12) 0.0422(5) Uani 1 1 d .
O1 O 0.3271(3) 0.5128(2) 0.06353(11) 0.0498(5) Uani 1 1 d .
O2 O 0.3633(3) 0.5963(2) 0.17012(11) 0.0558(6) Uani 1 1 d .
O3 O 0.6390(3) 0.12682(18) 0.18561(11) 0.0455(5) Uani 1 1 d .
H3 H 0.6524 0.1203 0.2279 0.068 Uiso 1 1 calc R
loop_
_atom_type_symbol
_atom_type_description
_atom_type_scat_dispersion_real
_atom_type_scat_dispersion_imag
_atom_type_scat_source
C C 0.0181 0.0091 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'
H H 0.0000 0.0000 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'
N N 0.0311 0.0180 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'
O O 0.0492 0.0322 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'
Cl Cl 0.3639 0.7018 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4'
loop_
_geom_angle_atom_site_label_1
_geom_angle_atom_site_label_2
_geom_angle_atom_site_label_3
_geom_angle
C2 C1 C6 121.1(4)
C3 C2 C1 118.9(4)
C4 C3 C2 121.8(4)
C3 C4 C5 119.3(4)
C6 C5 C4 120.5(4)
C5 C6 C1 118.4(3)
C5 C6 C7 121.3(3)
C1 C6 C7 120.2(3)
O1 C7 C6 110.3(3)
O2 C8 N1 125.3(3)
O2 C8 O1 122.6(3)
N1 C8 O1 112.0(2)
N1 C9 C10 111.7(3)
N1 C9 C11 109.3(2)
C10 C9 C11 115.8(3)
C12 C11 C9 114.7(2)
O3 C12 C11 112.9(2)
O3 C12 C13 106.4(2)
C11 C12 C13 109.9(2)
O3 C12 C15 107.2(2)
C11 C12 C15 110.3(2)
C13 C12 C15 110.0(2)
C14 C13 C12 110.5(2)
N1 C14 C13 110.4(2)
C12 C15 Cl2 112.7(2)
C12 C15 Cl1 111.2(2)
Cl2 C15 Cl1 108.17(18)
C12 C15 Cl3 110.8(2)
Cl2 C15 Cl3 107.35(17)
Cl1 C15 Cl3 106.44(19)
C8 N1 C9 119.3(2)
C8 N1 C14 124.2(2)
C9 N1 C14 116.1(2)
C8 O1 C7 117.1(2)
loop_
_geom_bond_atom_site_label_1
_geom_bond_atom_site_label_2
_geom_bond_distance
C1 C2 1.382(5)
C1 C6 1.391(5)
C2 C3 1.377(6)
C3 C4 1.346(6)
C4 C5 1.409(6)
C5 C6 1.378(5)
C6 C7 1.493(4)
C7 O1 1.457(4)
C8 O2 1.219(4)
C8 N1 1.338(4)
C8 O1 1.355(3)
C9 N1 1.468(4)
C9 C10 1.513(4)
C9 C11 1.541(4)
C11 C12 1.526(4)
C12 O3 1.411(3)
C12 C13 1.527(4)
C12 C15 1.559(4)
C13 C14 1.516(4)
C14 N1 1.468(4)
C15 Cl2 1.776(4)
C15 Cl1 1.777(3)
C15 Cl3 1.786(4)
loop_
_cod_related_entry_id
_cod_related_entry_database
_cod_related_entry_code
1 PubChem 57475605
