Utilizing biocatalysis and a sulfolane-mediated reductive acetal opening to access nemtabrutinib from cyrene
Kuhl, Nadine; Turnbull, Ben W. H.; Ji, Yining; Larson, Reed T.; Shevlin, Michael; Prier, Christopher K.; Chung, Cheol K.; Desmond, Richard; Guetschow, Erik; He, Cyndi Qixin; Itoh, Tetsuji; Kuethe, Jeffrey T.; Newman, Justin A.; Reibarkh, Mikhail; Rivera, Nelo R.; Shang, Gao; Wang, Zhixun; Zewge, Daniel; Thaisrivongs, David A.; Green Chemistry 25 (2023) 606–613; doi:10.1039/D2GC04117K

data_7246050
_publ_section_title
;
 Utilizing biocatalysis and a sulfolane-mediated reductive acetal opening
 to access nemtabrutinib from cyrene
;
_journal_issue                   2
_journal_name_full               'Green Chemistry'
_journal_page_first              606
_journal_page_last               613
_journal_paper_doi               10.1039/D2GC04117K
_journal_volume                  25
_journal_year                    2023
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C7 H7 O3 S, C6 H12 N O2'
_chemical_formula_sum            'C13 H19 N O5 S'
_chemical_formula_weight         301.35
_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
_atom_sites_solution_primary     dual
_audit_creation_date             2022-09-07
_audit_creation_method
;
Olex2 1.2
(compiled 2017.08.10 svn.r3458 for OlexSys, GUI svn.r5381)
;
_audit_update_record
;
2022-10-28 deposited with the CCDC.	2022-12-07 downloaded from the CCDC.
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                90
_cell_formula_units_Z            4
_cell_length_a                   6.1009(3)
_cell_length_b                   12.5179(6)
_cell_length_c                   19.3009(11)
_cell_measurement_reflns_used    3732
_cell_measurement_temperature    293(2)
_cell_measurement_theta_max      66.588
_cell_measurement_theta_min      4.210
_cell_volume                     1474.02(13)
_computing_cell_refinement       'SAINT v8.34A (Bruker, 2013)'
_computing_data_collection       'Bruker APEX2'
_computing_data_reduction        'SAINT v8.34A (Bruker, 2013)'
_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    'XT (Sheldrick, 2015)'
_diffrn_ambient_temperature      293(2)
_diffrn_measured_fraction_theta_full 0.999
_diffrn_measured_fraction_theta_max 0.999
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0306
_diffrn_reflns_av_unetI/netI     0.0291
_diffrn_reflns_Laue_measured_fraction_full 0.999
_diffrn_reflns_Laue_measured_fraction_max 0.999
_diffrn_reflns_limit_h_max       7
_diffrn_reflns_limit_h_min       -5
_diffrn_reflns_limit_k_max       14
_diffrn_reflns_limit_k_min       -14
_diffrn_reflns_limit_l_max       22
_diffrn_reflns_limit_l_min       -22
_diffrn_reflns_number            9588
_diffrn_reflns_point_group_measured_fraction_full 0.997
_diffrn_reflns_point_group_measured_fraction_max 0.996
_diffrn_reflns_theta_full        66.616
_diffrn_reflns_theta_max         66.616
_diffrn_reflns_theta_min         4.209
_diffrn_source                   'sealed-tube microsource X-ray generator'
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    2.129
_exptl_absorpt_correction_T_max  0.7528
_exptl_absorpt_correction_T_min  0.6754
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
'SADABS-2014/5 (Bruker,2014/5) was used for absorption correction. wR2(int) was 0.0921 before and 0.0578 after correction. The Ratio of minimum to maximum transmission is 0.8972. The \l/2 correction factor is 0.00150.'
_exptl_crystal_density_diffrn    1.358
_exptl_crystal_description       rod
_exptl_crystal_F_000             640
_exptl_crystal_size_max          0.15
_exptl_crystal_size_mid          0.09
_exptl_crystal_size_min          0.09
_refine_diff_density_max         0.245
_refine_diff_density_min         -0.281
_refine_diff_density_rms         0.034
_refine_ls_abs_structure_details
;
 Flack x determined using 878 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.064(11)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.074
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     211
_refine_ls_number_reflns         2602
_refine_ls_number_restraints     30
_refine_ls_restrained_S_all      1.072
_refine_ls_R_factor_all          0.0479
_refine_ls_R_factor_gt           0.0431
_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^)+(0.0472P)^2^+0.4108P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1073
_refine_ls_wR_factor_ref         0.1110
_reflns_Friedel_coverage         0.695
_reflns_Friedel_fraction_full    0.993
_reflns_Friedel_fraction_max     0.993
_reflns_number_gt                2361
_reflns_number_total             2602
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d2gc04117k2.cif
_cod_data_source_block           mdp019_0m
_cod_depositor_comments
'Adding full bibliography for 7246049--7246050.cif.'
_cod_database_code               7246050
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.832
_shelx_estimated_absorpt_t_min   0.741
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H,H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2. Uiso/Uaniso restraints and constraints
Uanis(O4A) \\sim Ueq, Uanis(O3A) \\sim Ueq, Uanis(O3) \\sim Ueq, Uanis(O4)
\\sim Ueq, Uanis(O5A) \\sim Ueq: with sigma of 0.05 and sigma for terminal
atoms of 0.1
3. Others
 Sof(O3A)=Sof(O4A)=Sof(O5A)=1-FVAR(1)
 Sof(O3)=Sof(O5)=Sof(O4)=FVAR(1)
4.a Ternary CH refined with riding coordinates:
 C1(H1), C2(H2), C4(H4)
4.b Secondary CH2 refined with riding coordinates:
 C6(H6A,H6B), C5(H5A,H5B), C3(H3A,H3B)
4.c Aromatic/amide H refined with riding coordinates:
 C11(H11), C8(H8), C12(H12), C9(H9)
4.d Idealised Me refined as rotating group:
 N1(H1A,H1B,H1C), C13(H13A,H13B,H13C)
;
_shelx_res_checksum              95947
_olex2_submission_special_instructions 'No special instructions were received'