Overcoming the Challenges of Making a Single Enantiomer N-1 Substituted Tetrazole Prodrug Using a Tin-Mediated Alkylation and Enzymatic Resolution
Akin, Anne; Barilla, Mark T.; Brandt, Thomas A.; Brennan, John; Henegar, Kevin E.; Hoagland, Steve; Kumar, Rajesh; Magano, Javier; McInturff, Emma L.; Nematalla, Asaad; Piotrowski, David W.; Van Haitsma, Jared; Wei, Liuqing; Xiao, Jun; Yu, Shu; Organic Process Research & Development 23 (2019) 1167–; doi:10.1021/acs.oprd.9b00104

data_1554186
_publ_section_title
;
 Overcoming the Challenges of Making a Single Enantiomer N-1 Substituted
 Tetrazole Prodrug Using a Tin-Mediated Alkylation and Enzymatic
 Resolution
;
_journal_issue                   6
_journal_name_full               'Organic Process Research &amp; Development'
_journal_page_first              1167
_journal_paper_doi               10.1021/acs.oprd.9b00104
_journal_volume                  23
_journal_year                    2019
_chemical_formula_moiety         '0.5(C34 H62 I2 N12 Sn2)'
_chemical_formula_sum            'C17 H31 I N6 Sn'
_chemical_formula_weight         565.09
_space_group_crystal_system      monoclinic
_space_group_IT_number           14
_space_group_name_Hall           '-P 2yn'
_space_group_name_H-M_alt        'P 1 21/n 1'
_symmetry_Int_Tables_number      14
_audit_creation_date             2019-01-16
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_cell_angle_alpha                90
_cell_angle_beta                 93.7250(10)
_cell_angle_gamma                90
_cell_formula_units_Z            8
_cell_length_a                   18.3878(3)
_cell_length_b                   12.7469(2)
_cell_length_c                   19.6536(3)
_cell_measurement_reflns_used    9838
_cell_measurement_temperature    296(2)
_cell_measurement_theta_max      68.03
_cell_measurement_theta_min      3.40
_cell_volume                     4596.83(13)
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'olex2.refine (Bourhis et al., 2015)'
_diffrn_ambient_temperature      296.15
_diffrn_measured_fraction_theta_full 0.9941
_diffrn_measured_fraction_theta_max 0.9941
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_type           'Cu K\a'
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0606
_diffrn_reflns_av_unetI/netI     0.0327
_diffrn_reflns_limit_h_max       21
_diffrn_reflns_limit_h_min       -22
_diffrn_reflns_limit_k_max       15
_diffrn_reflns_limit_k_min       -15
_diffrn_reflns_limit_l_max       23
_diffrn_reflns_limit_l_min       -23
_diffrn_reflns_number            56783
_diffrn_reflns_theta_full        68.6005
_diffrn_reflns_theta_max         68.60
_diffrn_reflns_theta_min         3.19
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    19.476
_exptl_absorpt_correction_type   empirical
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.6329
_exptl_crystal_description       PLATE
_exptl_crystal_F_000             2229.2607
_exptl_crystal_size_max          0.36
_exptl_crystal_size_mid          0.34
_exptl_crystal_size_min          0.08
_refine_diff_density_max         3.3107
_refine_diff_density_min         -4.0405
_refine_diff_density_rms         0.1956
_refine_ls_d_res_high            0.8280
_refine_ls_d_res_low             13.8556
_refine_ls_goodness_of_fit_ref   1.0350
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_constraints    118
_refine_ls_number_parameters     535
_refine_ls_number_reflns         8415
_refine_ls_number_restraints     20
_refine_ls_restrained_S_all      1.0337
_refine_ls_R_factor_all          0.0616
_refine_ls_R_factor_gt           0.0582
_refine_ls_shift/su_max          0.0028
_refine_ls_shift/su_mean         0.0001
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0789P)^2^+49.4946P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1542
_refine_ls_wR_factor_ref         0.1577
_reflns_Friedel_coverage         0.0
_reflns_limit_h_max              15
_reflns_limit_h_min              -22
_reflns_limit_k_max              15
_reflns_limit_k_min              0
_reflns_limit_l_max              23
_reflns_limit_l_min              -15
_reflns_number_gt                7774
_reflns_number_total             8415
_reflns_threshold_expression     I>=2u(I)
_cod_data_source_file            op9b00104_si_001.cif
_cod_data_source_block           Z556
_cod_original_sg_symbol_Hall     '-P 2ybc (x-z,y,z)'
_cod_database_code               1554186
_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. Restrained distances
 C33-C34
 1.5 with sigma of 0.02
 Sn2-C28C
 2.1 with sigma of 0.02
 Sn2-C28D
 2.1 with sigma of 0.02
 C29D-C30D
 1.54 with sigma of 0.02
 C34-C35 \\sim C26B-C27B
 with sigma of 0.02
 C33-C34 \\sim C25B-C26B
 with sigma of 0.02
 C32-C33 \\sim C24B-C25B
 with sigma of 0.02
 C34-C35 \\sim C26A-C27A
 with sigma of 0.02
 C33-C34 \\sim C25A-C26A
 with sigma of 0.02
 C32-C33 \\sim C24A-C25A
 with sigma of 0.02
 Sn2-C32 \\sim Sn2-C24B
 with sigma of 0.02
 Sn2-C32 \\sim Sn2-C24A
 with sigma of 0.02
3. Rigid body (RIGU) restrains
 Sn2, C28C, C28D, C29C, C29D
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
4. Others
 Sof(C24B)=Sof(H24c)=Sof(H24d)=Sof(C25B)=Sof(H25c)=Sof(H25d)=Sof(C26B)=
 Sof(H26c)=Sof(H26d)=Sof(C27B)=Sof(H27d)=Sof(H27e)=Sof(H27f)=1-FVAR(1)
 Sof(C24A)=Sof(H24a)=Sof(H24b)=Sof(C25A)=Sof(H25a)=Sof(H25b)=Sof(C26A)=
 Sof(H26a)=Sof(H26b)=Sof(C27A)=Sof(H27a)=Sof(H27b)=Sof(H27c)=FVAR(1)
 Sof(C28C)=Sof(H28a)=Sof(H28b)=Sof(C29D)=Sof(H29c)=Sof(H29d)=Sof(C30D)=
 Sof(H30c)=Sof(H30d)=Sof(C31D)=Sof(H31d)=Sof(H31e)=Sof(H31f)=1-FVAR(2)
 Sof(C28D)=Sof(H28c)=Sof(H28d)=Sof(C29C)=Sof(H29a)=Sof(H29b)=Sof(C30C)=
 Sof(H30a)=Sof(H30b)=Sof(C31C)=Sof(H31a)=Sof(H31b)=Sof(H31c)=FVAR(2)
5.a Secondary CH2 refined with riding coordinates:
 C6(H6a,H6b), C7(H7a,H7b), C8(H8a,H8b), C10(H10a,H10b), C11(H11a,H11b),
 C12(H12a,H12b), C14(H14a,H14b), C15(H15a,H15b), C16(H16a,H16b), C24A(H24a,
 H24b), C24B(H24c,H24d), C25A(H25a,H25b), C25B(H25c,H25d), C26A(H26a,H26b),
 C26B(H26c,H26d), C28C(H28a,H28b), C28D(H28c,H28d), C29C(H29a,H29b), C29D(H29c,
 H29d), C30C(H30a,H30b), C30D(H30c,H30d), C32(H32a,H32b), C33(H33a,H33b),
 C34(H34a,H34b)
5.b Aromatic/amide H refined with riding coordinates:
 C2(H2), C19(H19)
5.c Idealised Me refined as rotating group:
 C3(H3a,H3b,H3c), C9(H9a,H9b,H9c), C13(H13a,H13b,H13c), C37(H37a,H37b,H37c),
 C21(H21a,H21b,H21c), C27A(H27a,H27b,H27c), C27B(H27d,H27e,H27f), C31C(H31a,
 H31b,H31c), C31D(H31d,H31e,H31f), C35(H35a,H35b,H35c)
;
_olex2_submission_special_instructions 'No special instructions were received'