Asymmetric Synthesis of Merck's Potent hNK1 Antagonist and Its Stereoisomers via Tandem Acylation/[3,3]-Rearrangement of 1,2-Oxazine-N-oxides.
Dorokhov, Valentin; Nelyubina, Yulia; Ioffe, Sema; Sukhorukov, Alexey Yu; The Journal of organic chemistry  (2020) –; doi:10.1021/acs.joc.0c01322

data_4038701
_publ_section_title
;
 Asymmetric Synthesis of Merck's Potent hNK1 Antagonist and Its
 Stereoisomers via Tandem Acylation/[3,3]-Rearrangement of
 1,2-Oxazine-N-oxides.
;
_journal_name_full               'The Journal of organic chemistry'
_journal_paper_doi               10.1021/acs.joc.0c01322
_journal_year                    2020
_chemical_formula_moiety         'C22 H18 F7 N O3'
_chemical_formula_sum            'C22 H18 F7 N O3'
_chemical_formula_weight         477.37
_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'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     dual
_audit_creation_date             2020-03-01
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_cell_angle_alpha                90
_cell_angle_beta                 105.0830(10)
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   8.5733(5)
_cell_length_b                   30.5985(18)
_cell_length_c                   8.2945(5)
_cell_measurement_reflns_used    2606
_cell_measurement_temperature    120
_cell_measurement_theta_max      21.65
_cell_measurement_theta_min      2.55
_cell_volume                     2100.9(2)
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'XL (Sheldrick, 2008)'
_computing_structure_solution    'ShelXT (Sheldrick, 2015)'
_diffrn_ambient_temperature      120.0
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 1.000
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0692
_diffrn_reflns_av_unetI/netI     0.0537
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 1.000
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -11
_diffrn_reflns_limit_k_max       40
_diffrn_reflns_limit_k_min       -40
_diffrn_reflns_limit_l_max       10
_diffrn_reflns_limit_l_min       -10
_diffrn_reflns_number            24147
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 1.000
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         27.998
_diffrn_reflns_theta_min         2.460
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.141
_exptl_absorpt_correction_T_max  0.7461
_exptl_absorpt_correction_T_min  0.6673
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS-2008/1 (Bruker,2008) was used for absorption correction.
wR2(int) was 0.0633 before and 0.0563 after correction.
The Ratio of minimum to maximum transmission is 0.8944.
The \l/2 correction factor is 0.0015.
;
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.509
_exptl_crystal_description       plate
_exptl_crystal_F_000             976
_exptl_crystal_size_max          0.35
_exptl_crystal_size_mid          0.15
_exptl_crystal_size_min          0.03
_refine_diff_density_max         0.375
_refine_diff_density_min         -0.387
_refine_diff_density_rms         0.053
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.014
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     319
_refine_ls_number_reflns         5079
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.014
_refine_ls_R_factor_all          0.0911
_refine_ls_R_factor_gt           0.0526
_refine_ls_shift/su_max          0.001
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0405P)^2^+1.3486P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1056
_refine_ls_wR_factor_ref         0.1264
_reflns_Friedel_coverage         0.000
_reflns_number_gt                3315
_reflns_number_total             5079
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            jo0c01322_si_002.cif
_cod_data_source_block           1
_cod_database_code               4038701
_shelxl_version_number           2014/6
_shelx_estimated_absorpt_t_max   0.996
_shelx_estimated_absorpt_t_min   0.952
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2. Uiso/Uaniso restraints and constraints
Uanis(F3') = Uanis(F2)
Uanis(F2') = Uanis(F4)
Uanis(F4') = Uanis(F3)
Uanis(F6') = Uanis(F6)
Uanis(F7') = Uanis(F7)
Uanis(F5') = Uanis(F5)
3. Others
 Sof(F2')=Sof(F3')=Sof(F4')=1-FVAR(1)
 Sof(F2)=Sof(F3)=Sof(F4)=FVAR(1)
 Sof(F5')=Sof(F6')=Sof(F7')=1-FVAR(2)
 Sof(F5)=Sof(F6)=Sof(F7)=FVAR(2)
4.a Ternary CH refined with riding coordinates:
 C3(H3), C4(H4), C5(H5), C13(H13)
4.b Secondary CH2 refined with riding coordinates:
 C2(H2A,H2B), C6(H6A,H6B)
4.c Aromatic/amide H refined with riding coordinates:
 C8(H8), C9(H9), C11(H11), C12(H12), C16(H16), C18(H18), C20(H20)
4.d Idealised Me refined as rotating group:
 C14(H14A,H14B,H14C)
;
_olex2_submission_special_instructions 'No special instructions were received'