Synthesis of Biologically Active Piperidine Metabolites of Clopidogrel: Determination of Structure and Analyte Development.
Shaw, Scott A.; Balasubramanian, Balu; Bonacorsi, Samuel; Cortes, Janet Caceres; Cao, Kevin; Chen, Bang-Chi; Dai, Jun; Decicco, Carl; Goswami, Animesh; Guo, Zhiwei; Hanson, Ronald; Humphreys, W. Griffith; Lam, Patrick Y. S.; Li, Wenying; Mathur, Arvind; Maxwell, Brad D.; Michaudel, Quentin; Peng, Li; Pudzianowski, Andrew; Qiu, Feng; Su, Shun; Sun, Dawn; Tymiak, Adrienne A.; Vokits, Benjamin P.; Wang, Bei; Wexler, Ruth; Wu, Dauh-Rurng; Zhang, Yingru; Zhao, Rulin; Baran, Phil S.; The Journal of organic chemistry 80 (2015) 7019–7032; doi:10.1021/acs.joc.5b00632

data_4031167
_publ_section_title
;
 Synthesis of Biologically Active Piperidine Metabolites of Clopidogrel:
 Determination of Structure and Analyte Development.
;
_journal_issue                   14
_journal_name_full               'The Journal of organic chemistry'
_journal_page_first              7019
_journal_page_last               7032
_journal_paper_doi               10.1021/acs.joc.5b00632
_journal_volume                  80
_journal_year                    2015
_chemical_absolute_configuration ad
_chemical_formula_moiety         'C14 H22 O5'
_chemical_formula_sum            'C14 H22 O5'
_chemical_formula_weight         270.31
_space_group_crystal_system      trigonal
_space_group_IT_number           144
_space_group_name_Hall           'P 31'
_space_group_name_H-M_alt        'P 31'
_symmetry_space_group_name_Hall  'P 31'
_symmetry_space_group_name_H-M   'P 31'
_atom_sites_solution_hydrogens   geom
_atom_sites_solution_primary     direct
_atom_sites_solution_secondary   difmap
_audit_creation_date             2015-04-03
_audit_creation_method
;
Olex2 1.2-beta
(compiled 2015.01.26 svn.r3150 for OlexSys, GUI svn.r4998)
;
_cell_angle_alpha                90
_cell_angle_beta                 90
_cell_angle_gamma                120
_cell_formula_units_Z            3
_cell_length_a                   15.150(4)
_cell_length_b                   15.150
_cell_length_c                   5.685(2)
_cell_measurement_reflns_used    1885
_cell_measurement_temperature    100
_cell_measurement_theta_max      58.98
_cell_measurement_theta_min      3.37
_cell_volume                     1130.0(5)
_computing_cell_refinement       'Bruker SAINT'
_computing_data_collection       'Bruker APEX2'
_computing_data_reduction        'Bruker SAINT'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2008)'
_computing_structure_solution    'XS (Sheldrick, 2008)'
_diffrn_ambient_temperature      100.0
_diffrn_detector                 'Bruker APEX-II CCD'
_diffrn_detector_area_resol_mean 7.9
_diffrn_detector_type            'CCD Area Detector'
_diffrn_measured_fraction_theta_full 0.971
_diffrn_measured_fraction_theta_max 0.971
_diffrn_measurement_device       'Kappa Four-Circle Diffractometer'
_diffrn_measurement_device_type  'Bruker X8 APEX II'
_diffrn_measurement_method       '\w and \f scans'
_diffrn_radiation_monochromator  graphite
_diffrn_radiation_probe          x-ray
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_unetI/netI     0.0471
_diffrn_reflns_Laue_measured_fraction_full 0.971
_diffrn_reflns_Laue_measured_fraction_max 0.971
_diffrn_reflns_limit_h_max       17
_diffrn_reflns_limit_h_min       -17
_diffrn_reflns_limit_k_max       17
_diffrn_reflns_limit_k_min       -17
_diffrn_reflns_limit_l_max       6
_diffrn_reflns_limit_l_min       -6
_diffrn_reflns_number            5716
_diffrn_reflns_point_group_measured_fraction_full 0.929
_diffrn_reflns_point_group_measured_fraction_max 0.929
_diffrn_reflns_theta_full        64.757
_diffrn_reflns_theta_max         64.757
_diffrn_reflns_theta_min         3.368
_diffrn_source                   'sealed tube'
_diffrn_source_type              fine-focus
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.741
_exptl_absorpt_correction_T_max  0.7454
_exptl_absorpt_correction_T_min  0.6223
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS-2012/1 (Bruker,2012) was used for absorption correction.
wR2(int) was 0.1377 before and 0.0387 after correction.
The Ratio of minimum to maximum transmission is 0.8349.
The \l/2 correction factor is 0.0015.
;
_exptl_crystal_colour            Colorless
_exptl_crystal_colour_primary    Colorless
_exptl_crystal_density_diffrn    1.192
_exptl_crystal_description       Block
_exptl_crystal_F_000             438
_exptl_crystal_size_max          0.25
_exptl_crystal_size_mid          0.25
_exptl_crystal_size_min          0.08
_refine_diff_density_max         0.672
_refine_diff_density_min         -0.423
_refine_diff_density_rms         0.126
_refine_ls_abs_structure_details
;
 Flack x determined using 710 quotients [(I+)-(I-)]/[(I+)+(I-)]
 (Parsons, Flack and Wagner, Acta Cryst. B69 (2013) 249-259).
;
_refine_ls_abs_structure_Flack   0.12(14)
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.294
_refine_ls_hydrogen_treatment    constr
_refine_ls_matrix_type           full
_refine_ls_number_parameters     179
_refine_ls_number_reflns         5716
_refine_ls_number_restraints     157
_refine_ls_restrained_S_all      1.306
_refine_ls_R_factor_all          0.1210
_refine_ls_R_factor_gt           0.1168
_refine_ls_shift/su_max          0.000
_refine_ls_shift/su_mean         0.000
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.2000P)^2^] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.2844
_refine_ls_wR_factor_ref         0.2944
_reflns_Friedel_coverage         0.914
_reflns_Friedel_fraction_full    0.887
_reflns_Friedel_fraction_max     0.887
_reflns_number_gt                5428
_reflns_number_total             5716
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            jo5b00632_si_003.cif
_cod_data_source_block           Baran93
_cod_depositor_comments
;
The following automatic conversions were performed:

'_diffrn_radiation_probe' value 'X-ray' changed to 'x-ray' according
to
/usr/data/users/saulius/crontab/automatic-downloads/rss-feeds/ACS/lib/dictionaries/cif_core.dic
dictionary named 'cif_core.dic' version 2.4.2 from 2011-04-26.

Automatic conversion script
Id: cif_fix_values 3271 2015-04-21 07:52:19Z andrius 

 Adding full bibliography for 4031167--4031168.cif.
;
_cod_original_cell_volume        1130.1(7)
_cod_database_code               4031167
_shelx_estimated_absorpt_t_max   0.943
_shelx_estimated_absorpt_t_min   0.836
_olex2_refinement_description
;
1. Twinned data refinement
 Scales: 0.591(9) 0.409(9)
2. 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, All O(H) groups
3. Rigid body (RIGU) restrains
 All non-hydrogen atoms
 with sigma for 1-2 distances of 0.002 and sigma for 1-3 distances of 0.002
4.a Ternary CH refined with riding coordinates:
 C4(H4), C5(H5), C7(H7)
4.b Secondary CH2 refined with riding coordinates:
 C6(H6A,H6B)
4.c Aromatic/amide H refined with riding coordinates:
 C9(H9)
4.d Idealised Me refined as rotating group:
 C2(H2A,H2B,H2C), C3(H3A,H3B,H3C), C12(H12A,H12B,H12C), C13(H13A,H13B,H13C),
 C14(H14A,H14B,H14C)
4.e Idealised tetrahedral OH refined as rotating group:
 O3(H3)
;
_shelx_res_checksum              81251
_shelx_hkl_checksum              30034
_shelx_shelxl_version_number     2014/7
_olex2_submission_special_instructions 'No special instructions were received'