Application of Transition-Metal Catalysis, Biocatalysis, and Flow Chemistry as State-of-the-Art Technologies in the Synthesis of LCZ696.
Gu, Xingxian; Zhao, Jibin; Chen, Like; Li, Yunzhong; Yu, Bo; Tian, Xiangguang; Min, Zhongcheng; Xu, Su; Gu, Huijuan; Sun, Junjie; Lu, Xiaoquan; Chang, Meng; Wang, Xufan; Zhao, Liqun; Ye, Shengqing; Yang, Hongwei; Tian, Yingtao; Gao, Feng; Gai, Yu; Jia, Guanghua; Wu, Jingjing; Wang, Yan; Zhang, Jianghua; Zhang, Xuesong; Liu, Weichun; Gu, Xin; Luo, Xi; Dong, Hai; Wang, Huaimin; Schenkel, Berthold; Venturoni, Francesco; Filipponi, Paolo; Guelat, Bertrand; Allmendinger, Thomas; Wietfeld, Bernhard; Hoehn, Pascale; Kovacic, Nikola; Hermann, Luca; Schlama, Thierry; Ruch, Thomas; Derrien, Nadine; Piechon, Philippe; Kleinbeck, Florian; The Journal of organic chemistry  (2020) –; doi:10.1021/acs.joc.0c00473

data_4038363
_publ_section_title
;
 Application of Transition-Metal Catalysis, Biocatalysis, and Flow
 Chemistry as State-of-the-Art Technologies in the Synthesis of LCZ696.
;
_journal_name_full               'The Journal of organic chemistry'
_journal_paper_doi               10.1021/acs.joc.0c00473
_journal_year                    2020
_chemical_formula_moiety         C60H84Cl4Mg4O12
_chemical_formula_sum            'C64 H92 Cl4 Mg4 O13'
_chemical_formula_weight         1308.42
_chemical_name_common            LCZ696-FILIPPA9-087-PHCH3
_space_group_IT_number           14
_space_group_name_Hall           '-P 2yn'
_space_group_name_H-M_alt        'P 1 21/n 1'
_symmetry_cell_setting           monoclinic
_symmetry_space_group_name_H-M   'P 1 21/n 1'
_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                 100.954(15)
_cell_angle_gamma                90.00
_cell_formula_units_Z            4
_cell_length_a                   19.113(5)
_cell_length_b                   17.823(5)
_cell_length_c                   19.861(6)
_cell_measurement_reflns_used    8131
_cell_measurement_temperature    100(2)
_cell_measurement_theta_max      68.10
_cell_measurement_theta_min      2.94
_cell_volume                     6642(3)
_computing_cell_refinement       'Bruker SMART'
_computing_data_collection       'Bruker SMART'
_computing_data_reduction        'Bruker SAINT'
_computing_molecular_graphics    'Bruker SHELXTL'
_computing_structure_refinement  'SHELXL-97 (Sheldrick, 1997)'
_computing_structure_solution    'SHELXS-97 (Sheldrick, 1990)'
_diffrn_ambient_temperature      100(2)
_diffrn_measured_fraction_theta_full 0.996
_diffrn_measured_fraction_theta_max 0.996
_diffrn_measurement_device_type  'Bruker SMART6000 CCD'
_diffrn_measurement_method       '\w scans'
_diffrn_radiation_monochromator  'multilayer mirror'
_diffrn_radiation_source         'MicroStar rotating anode'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.1075
_diffrn_reflns_av_sigmaI/netI    0.0613
_diffrn_reflns_limit_h_max       22
_diffrn_reflns_limit_h_min       -23
_diffrn_reflns_limit_k_max       21
_diffrn_reflns_limit_k_min       -21
_diffrn_reflns_limit_l_max       23
_diffrn_reflns_limit_l_min       -23
_diffrn_reflns_number            72046
_diffrn_reflns_theta_full        68.29
_diffrn_reflns_theta_max         68.29
_diffrn_reflns_theta_min         2.94
_exptl_absorpt_coefficient_mu    2.479
_exptl_absorpt_correction_T_max  0.9521
_exptl_absorpt_correction_T_min  0.8655
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details   'SADABS (Sheldrick, 2008)'
_exptl_crystal_colour            colorless
_exptl_crystal_density_diffrn    1.308
_exptl_crystal_density_method    'not measured'
_exptl_crystal_description       plate
_exptl_crystal_F_000             2784
_exptl_crystal_recrystallization_method THF/TOL
_exptl_crystal_size_max          0.06
_exptl_crystal_size_mid          0.05
_exptl_crystal_size_min          0.02
_refine_diff_density_max         0.647
_refine_diff_density_min         -0.439
_refine_diff_density_rms         0.063
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.009
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     929
_refine_ls_number_reflns         12123
_refine_ls_number_restraints     1455
_refine_ls_restrained_S_all      1.026
_refine_ls_R_factor_all          0.0824
_refine_ls_R_factor_gt           0.0491
_refine_ls_shift/su_max          0.023
_refine_ls_shift/su_mean         0.001
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'calc w=1/[\s^2^(Fo^2^)+(0.0527P)^2^+5.1269P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1078
_refine_ls_wR_factor_ref         0.1237
_reflns_number_gt                8419
_reflns_number_total             12123
_reflns_threshold_expression     >2sigma(I)
_cod_data_source_file            jo0c00473_si_001.cif
_cod_data_source_block           FVE03a
_cod_original_sg_symbol_H-M      P21/n
_cod_database_code               4038363
_chemical_source_common          THF/TOL
_ccdc_publ_extra_info
; 
 mono THF solvate: THF molecule heavily disordered and refined on three positions (A/B/C): ratio 51:27:22, 
 tetrakis(mu-chloro)-bis(2-biphenyl-4-yl-ethene-1,1-diol)-octakis(tetrahydrofuran)-tetra-magnesium,
 three THF molecules disordered and refined on two positions (A/B): ratio 60:40 (O46 to C50), 58:42 (O66 to C70), 54:46 (O71 to C75)  
;