Practical Synthesis of (3aR, 9bR)-8-Fluoro-7-(perfluoropropan-2-yl)-9b-(phenylsulfonyl)-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]indole: An Advanced Intermediate to Access the RORγt Inverse Agonist BMT-362265
Karmakar, Ananta; Nimje, Roshan Y.; Silamkoti, Arundutt; Pitchai, Manivel; Basha, Mushkin; Singarayer, Christuraj; Ramasamy, Duraisamy; Babu, G. T. Venkatesh; Samikannu, Ramesh; Subramaniam, Srinath; Anjanappa, Prakash; Vetrichelvan, Muthalagu; Kumar, Hemantha; Dikundwar, Amol G.; Gupta, Anuradha; Gupta, Arun Kumar; Rampulla, Richard; Dhar, T. G. Murali; Mathur, Arvind; Organic Process Research & Development  (2021) –; doi:10.1021/acs.oprd.1c00019

data_1561044
_publ_section_title
;
 Practical Synthesis of (3aR,
 9bR)-8-Fluoro-7-(perfluoropropan-2-yl)-9b-(phenylsulfonyl)-2,3,3a,4,5,9b-hexahydro-1H-benzo[e]indole:
 An Advanced Intermediate to Access the ROR\gt Inverse Agonist BMT-362265
;
_journal_name_full               'Organic Process Research &amp; Development'
_journal_paper_doi               10.1021/acs.oprd.1c00019
_journal_year                    2021
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C44 H50 F2 N2 O6 S4'
_chemical_formula_sum            'C44 H50 F2 N2 O6 S4'
_chemical_formula_weight         869.10
_chemical_name_common            compound-31
_chemical_name_systematic
;
(3aR,3'aR,9bR,9'bR)-3-((R)-tert-butylsulfinyl)-
3'-(tert-butylsulfinyl)-8,8'-difluoro-9b,9'b-bis(phenylsulfonyl)
-2,2',3,3a,3',3'a,4,4',5,5',9b,9'b-dodecahydro-1H,1'H-7,7'-bibenzo[e]indole
;
_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_date             2020-11-03
_audit_creation_method
;
Olex2 1.3
(compiled 2020.07.31 svn.rc2a77460 for OlexSys, GUI svn.r6145)
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   9.7957(5)
_cell_length_b                   14.9403(8)
_cell_length_c                   30.1708(15)
_cell_measurement_reflns_used    9773
_cell_measurement_temperature    296(2)
_cell_measurement_theta_max      28.42
_cell_measurement_theta_min      2.44
_cell_volume                     4415.5(4)
_computing_cell_refinement       'SAINT V8.40A (Bruker, 2019)'
_computing_data_reduction        'SAINT V8.40A (Bruker, 2019)'
_computing_molecular_graphics    'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 1.3 (Dolomanov et al., 2009)'
_computing_structure_refinement  'SHELXL 2016/6 (Sheldrick, 2015)'
_computing_structure_solution    'SHELXT 2014/5 (Sheldrick, 2014)'
_diffrn_ambient_temperature      296(2)
_diffrn_detector                 'Bruker PHOTON II detector'
_diffrn_detector_area_resol_mean 7.4
_diffrn_detector_type            'CPAD area detector'
_diffrn_measured_fraction_theta_full 1.000
_diffrn_measured_fraction_theta_max 0.954
_diffrn_measurement_device       'three-circle diffractometer'
_diffrn_measurement_device_type  'Bruker SMART APEX'
_diffrn_measurement_method       '\w and \f scans'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           MoK\a
_diffrn_radiation_wavelength     0.71073
_diffrn_reflns_av_R_equivalents  0.0833
_diffrn_reflns_av_unetI/netI     0.0795
_diffrn_reflns_Laue_measured_fraction_full 1.000
_diffrn_reflns_Laue_measured_fraction_max 0.954
_diffrn_reflns_limit_h_max       13
_diffrn_reflns_limit_h_min       -13
_diffrn_reflns_limit_k_max       20
_diffrn_reflns_limit_k_min       -21
_diffrn_reflns_limit_l_max       40
_diffrn_reflns_limit_l_min       -41
_diffrn_reflns_number            58552
_diffrn_reflns_point_group_measured_fraction_full 1.000
_diffrn_reflns_point_group_measured_fraction_max 0.922
_diffrn_reflns_theta_full        25.242
_diffrn_reflns_theta_max         30.415
_diffrn_reflns_theta_min         1.521
_diffrn_source                   'fine focus sealed X-ray tube'
_diffrn_source_current           35.0
_diffrn_source_power             1.75
_diffrn_source_type              'sealed tube'
_diffrn_source_voltage           50.0
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.272
_exptl_absorpt_correction_T_max  0.7461
_exptl_absorpt_correction_T_min  0.6903
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS-2016/2 (Bruker,2016/2) was used for absorption correction.
wR2(int) was 0.1472 before and 0.0807 after correction.
The Ratio of minimum to maximum transmission is 0.9252.
The \l/2 correction factor is Not present.
;
_exptl_crystal_colour            'clear light colourless'
_exptl_crystal_colour_lustre     clear
_exptl_crystal_colour_modifier   light
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.307
_exptl_crystal_description       plate
_exptl_crystal_F_000             1832
_exptl_crystal_recrystallization_method
'The material was recrystallised from a mixture of methanol and THF  by slow evaporation'
_exptl_crystal_size_max          0.25
_exptl_crystal_size_mid          0.15
_exptl_crystal_size_min          0.1
_refine_diff_density_max         0.283
_refine_diff_density_min         -0.316
_refine_diff_density_rms         0.045
_refine_ls_abs_structure_details
;
 Flack x determined using 2869 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   -0.03(4)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   0.999
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     529
_refine_ls_number_reflns         12304
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      0.999
_refine_ls_R_factor_all          0.0852
_refine_ls_R_factor_gt           0.0460
_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^)+(0.0420P)^2^] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.0946
_refine_ls_wR_factor_ref         0.1062
_reflns_Friedel_coverage         0.752
_reflns_Friedel_fraction_full    1.000
_reflns_Friedel_fraction_max     0.882
_reflns_number_gt                8256
_reflns_number_total             12304
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            op1c00019_si_002.cif
_cod_data_source_block           compound-31
_cod_database_code               1561044
_shelx_shelxl_version_number     2016/6
_shelx_estimated_absorpt_t_max   0.973
_shelx_estimated_absorpt_t_min   0.935
_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.a Ternary CH refined with riding coordinates:
 C24(H24), C8(H8)
2.b Secondary CH2 refined with riding coordinates:
 C25(H25A,H25B), C27(H27A,H27B), C10(H10A,H10B), C26(H26A,H26B), C5(H5A,H5B),
 C9(H9A,H9B), C6(H6A,H6B), C28(H28A,H28B)
2.c Aromatic/amide H refined with riding coordinates:
 C18(H18), C21(H21), C16(H16), C38(H38), C34(H34), C13(H13), C40(H40),
 C44(H44), C36(H36), C35(H35), C37(H37), C43(H43), C41(H41), C42(H42)
2.d Idealised Me refined as rotating group:
 C32(H32A,H32B,H32C), C30(H30A,H30B,H30C), C2(H2A,H2B,H2C), C31(H31A,H31B,
 H31C), C4(H4A,H4B,H4C), C3(H3A,H3B,H3C)
;
_smtbx_masks_void_probe_radius   1.2
_smtbx_masks_void_truncation_radius 1.2
_shelx_res_checksum              26109
_shelx_hkl_checksum              83099
_shelx_fab_checksum              696
_olex2_diffrn_ambient_temperature_device 'Oxford Cryosystems'
_olex2_exptl_crystal_mounting_method
'The crystal was mounted on a Hampton Cryo loop using Paratone Oil'
_olex2_submission_special_instructions 'No special instructions were received'