Enantioselective Synthesis of a γ-Secretase Modulator via Vinylogous Dynamic Kinetic Resolution.
Strotman, Neil A.; Ramirez, Antonio; Simmons, Eric M.; Soltani, Omid; Parsons, Andrew T.; Fan, Yu; Sawyer, James R.; Rosner, Thorsten; Janey, Jacob M.; Tran, Kristy; Li, Jun; La Cruz, Thomas E.; Pathirana, Charles; Ng, Alicia T.; Deerberg, Joerg; The Journal of organic chemistry 83 (2018) 11133–11144; doi:10.1021/acs.joc.8b01734

data_4035628
_publ_section_title
;
 Enantioselective Synthesis of a \g-Secretase Modulator via Vinylogous
 Dynamic Kinetic Resolution.
;
_journal_issue                   18
_journal_name_full               'The Journal of organic chemistry'
_journal_page_first              11133
_journal_page_last               11144
_journal_paper_doi               10.1021/acs.joc.8b01734
_journal_volume                  83
_journal_year                    2018
_chemical_absolute_configuration S
_chemical_formula_sum            'C24 H25 Cl F N7 O'
_chemical_formula_weight         481.96
_chemical_name_systematic
;
 (S)-7-(4-fluorophenyl)-N2-(3-methoxy-4-(3-methyl-1H-1,2,4-triazol-1-yl)phenyl)-N4-methyl-
 6,7-dihydro-5H-cyclopenta[d]pyrimidine-2,4-diamine
;
_space_group_crystal_system      orthorhombic
_space_group_IT_number           19
_space_group_name_Hall           'P 2ac 2ab'
_space_group_name_H-M_alt        'P 21 21 21'
_atom_sites_solution_hydrogens   geom
_audit_creation_method           SHELXL-2014/7
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   6.7121(2)
_cell_length_b                   13.5402(4)
_cell_length_c                   26.5180(8)
_cell_measurement_reflns_used    9892
_cell_measurement_temperature    296(2)
_cell_measurement_theta_max      70.08
_cell_measurement_theta_min      3.33
_cell_volume                     2410.04(12)
_computing_cell_refinement       'Bruker SAINT'
_computing_data_collection       'Bruker APEX2'
_computing_data_reduction        'Bruker SAINT'
_computing_molecular_graphics    'Mercury CFC 3.9 (CCDC 2001-2016)'
_computing_publication_material  'Bruker SHELXTL'
_computing_structure_refinement  'SHELXL-2014/7 (Sheldrick, 2014)'
_computing_structure_solution    'SHELXS-97 (Sheldrick, 2008)'
_diffrn_ambient_temperature      296(2)
_diffrn_measured_fraction_theta_full 0.993
_diffrn_measured_fraction_theta_max 0.971
_diffrn_measurement_device_type  'Bruker APEX-II CCD area detector'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0342
_diffrn_reflns_av_unetI/netI     0.0193
_diffrn_reflns_Laue_measured_fraction_full 0.993
_diffrn_reflns_Laue_measured_fraction_max 0.971
_diffrn_reflns_limit_h_max       8
_diffrn_reflns_limit_h_min       -8
_diffrn_reflns_limit_k_max       12
_diffrn_reflns_limit_k_min       -15
_diffrn_reflns_limit_l_max       32
_diffrn_reflns_limit_l_min       -32
_diffrn_reflns_number            49464
_diffrn_reflns_point_group_measured_fraction_full 0.991
_diffrn_reflns_point_group_measured_fraction_max 0.963
_diffrn_reflns_theta_full        67.679
_diffrn_reflns_theta_max         71.712
_diffrn_reflns_theta_min         3.333
_diffrn_source                   'Incoatec microfocus ImuS sealed tube'
_exptl_absorpt_coefficient_mu    1.731
_exptl_absorpt_correction_type   none
_exptl_crystal_density_diffrn    1.328
_exptl_crystal_description       block
_exptl_crystal_F_000             1008
_exptl_crystal_size_max          0.402
_exptl_crystal_size_mid          0.175
_exptl_crystal_size_min          0.106
_refine_diff_density_max         0.119
_refine_diff_density_min         -0.147
_refine_diff_density_rms         0.028
_refine_ls_abs_structure_details
;
 Flack x determined using 1810 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.023(3)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.053
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     310
_refine_ls_number_reflns         4557
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.053
_refine_ls_R_factor_all          0.0269
_refine_ls_R_factor_gt           0.0259
_refine_ls_shift/su_max          0.002
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0387P)^2^+0.2945P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0714
_refine_ls_wR_factor_ref         0.0721
_reflns_Friedel_coverage         0.720
_reflns_Friedel_fraction_full    0.987
_reflns_Friedel_fraction_max     0.952
_reflns_number_gt                4420
_reflns_number_total             4557
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            jo8b01734_si_002.cif
_cod_data_source_block           BMS932481
_cod_database_code               4035628
_publ_contact                    'Alicia Ng'
_publ_contact_email              alicia.ng@bms.com
_shelx_shelxl_version_number     2014/7