Development of an Asymmetric Synthesis of a Chiral Quaternary FLAP Inhibitor.
Fandrick, Keith R.; Mulder, Jason A.; Patel, Nitinchandra D.; Gao, Joe; Konrad, Michael; Archer, Elizabeth; Buono, Frederic G.; Duran, Adil; Schmid, Rolf; Daeubler, Juergen; Desrosiers, Jean-Nicolas; Zeng, Xingzhong; Rodriguez, Sonia; Ma, Shengli; Qu, Bo; Li, Zhibin; Fandrick, Daniel R.; Grinberg, Nelu; Lee, Heewon; Bosanac, Todd; Takahashi, Hidenori; Chen, Zhidong; Bartolozzi, Alessandra; Nemoto, Peter; Busacca, Carl A.; Song, Jinhua J.; Yee, Nathan K.; Mahaney, Paige E.; Senanayake, Chris H.; The Journal of organic chemistry 80 (2015) 1651–1660; doi:10.1021/jo502550h

data_4030756
_publ_section_title
;
 Development of an Asymmetric Synthesis of a Chiral Quaternary FLAP
 Inhibitor.
;
_journal_issue                   3
_journal_name_full               'The Journal of organic chemistry'
_journal_page_first              1651
_journal_page_last               1660
_journal_paper_doi               10.1021/jo502550h
_journal_volume                  80
_journal_year                    2015
_chemical_absolute_configuration unk
_chemical_formula_moiety         'C12 H15 Br N2 O'
_chemical_formula_sum            'C12 H15 Br N2 O'
_chemical_formula_weight         283.17
_space_group_crystal_system      triclinic
_space_group_IT_number           1
_space_group_name_Hall           'P 1'
_space_group_name_H-M_alt        'P 1'
_symmetry_Int_Tables_number      1
_symmetry_space_group_name_Hall  'P 1'
_symmetry_space_group_name_H-M   'P 1'
_audit_creation_date             2014-12-18
_audit_creation_method
;
Olex2 1.2
(compiled 2014.09.19 svn.r3010 for OlexSys, GUI svn.r4874)
;
_cell_angle_alpha                65.119(11)
_cell_angle_beta                 89.810(12)
_cell_angle_gamma                89.633(11)
_cell_formula_units_Z            4
_cell_length_a                   9.3644(19)
_cell_length_b                   11.804(3)
_cell_length_c                   11.909(3)
_cell_measurement_reflns_used    6916
_cell_measurement_theta_max      65.83
_cell_measurement_theta_min      4.09
_cell_volume                     1194.2(5)
_computing_cell_refinement       'SAINT v7.68A (Bruker, 2009)'
_computing_data_reduction        'SAINT v7.68A (Bruker, 2009)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'olex2.refine (Bourhis et al., 2013)'
_diffrn_ambient_temperature      100.02
_diffrn_measured_fraction_theta_full 0.6852
_diffrn_measured_fraction_theta_max 0.6851
_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  0.0407
_diffrn_reflns_av_unetI/netI     0.0584
_diffrn_reflns_limit_h_max       11
_diffrn_reflns_limit_h_min       -11
_diffrn_reflns_limit_k_max       13
_diffrn_reflns_limit_k_min       -14
_diffrn_reflns_limit_l_max       14
_diffrn_reflns_limit_l_min       -14
_diffrn_reflns_number            10139
_diffrn_reflns_theta_full        67.3392
_diffrn_reflns_theta_max         67.34
_diffrn_reflns_theta_min         4.09
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    4.535
_exptl_absorpt_correction_T_max  0.7528
_exptl_absorpt_correction_T_min  0.5665
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
;
SADABS-2008/1 (Bruker,2008) was used for absorption correction.
wR2(int) was 0.1543 before and 0.0706 after correction.
The Ratio of minimum to maximum transmission is 0.7525.
The \l/2 correction factor is 0.0015.
;
_exptl_crystal_colour            colourless
_exptl_crystal_colour_primary    colourless
_exptl_crystal_density_diffrn    1.5749
_exptl_crystal_description       tabular
_exptl_crystal_F_000             574.6134
_exptl_crystal_size_max          0.2
_exptl_crystal_size_mid          0.1
_exptl_crystal_size_min          0.1
_refine_diff_density_max         0.6647
_refine_diff_density_min         -1.1221
_refine_diff_density_rms         0.1614
_refine_ls_abs_structure_details
'Flack, H. D. (1983). Acta Cryst. A39, 876-881.'
_refine_ls_abs_structure_Flack   0.06(3)
_refine_ls_d_res_high            0.8354
_refine_ls_d_res_low             10.8032
_refine_ls_goodness_of_fit_ref   1.0878
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_constraints    99
_refine_ls_number_parameters     587
_refine_ls_number_reflns         5866
_refine_ls_number_restraints     0
_refine_ls_restrained_S_all      1.0878
_refine_ls_R_factor_all          0.0549
_refine_ls_R_factor_gt           0.0510
_refine_ls_shift/su_max          0.0074
_refine_ls_shift/su_mean         0.0006
_refine_ls_structure_factor_coef Fsqd
_refine_ls_weighting_details
'w=1/[\s^2^(Fo^2^)+(0.0322P)^2^+11.5776P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1356
_refine_ls_wR_factor_ref         0.1477
_reflns_Friedel_coverage         0.474
_reflns_limit_h_max              11
_reflns_limit_h_min              -11
_reflns_limit_k_max              13
_reflns_limit_k_min              -14
_reflns_limit_l_max              14
_reflns_limit_l_min              -14
_reflns_number_gt                5567
_reflns_number_total             5866
_reflns_threshold_expression     I>=2u(I)
_cod_data_source_file            jo502550h_si_002.cif
_cod_data_source_block           scan_0m
_cod_original_cell_volume        1194.2(4)
_cod_database_code               4030756
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H,H) groups
 At 1.5 times of:
  All C(H,H,H) groups, All O(H) groups
2.a Rotating group:
 N7(H7a,H7b)
2.b Ternary CH refined with riding coordinates:
 C2(H2), C22(H22), C30(H30), C46(H46)
2.c Secondary CH2 refined with riding coordinates:
 C1(H1a,H1b), C9(H9a,H9b), C23(H23a,H23b), C24(H24a,H24b), C31(H31a,H31b),
 C35(H35a,H35b), C47(H47a,H47b), C48(H48a,H48b)
2.d Aromatic/amide H refined with riding coordinates:
 C49(H49), C5(H5), C6(H6), C8(H8), C13(H13), C14(H14), C19(H19), C20(H20),
 C26(H26), C27(H27), C32(H32), C33(H33), C40(H40), C41(H41), C43(H43), C44(H44)
2.e X=CH2 refined with riding coordinates:
 N9(H9c,H9d), N4(H4a,H4b), N5(H5a,H5b)
2.f Idealised Me refined as rotating group:
 C10(H10a,H10b,H10c), C21(H21a,H21b,H21c), C34(H34a,H34b,H34c), C45(H45a,H45b,
 H45c)
2.g Idealised tetrahedral OH refined as rotating group:
 O2(H2a), O3(H3), O4(H4)
;
_olex2_submission_special_instructions 'No special instructions were received'