# Electronic Supplementary Material (ESI) for Medicinal Chemistry Communications # This journal is © The Royal Society of Chemistry 2012 data_global _journal_name_full 'Chemical Science' _journal_coden_cambridge 1475 _journal_year ? _journal_volume ? _journal_page_first ? loop_ _publ_author_name _publ_author_address P.A.MacFaul ; Cardiovascular and Gastrointestinal Innovative Medicines Unit, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, United Kingdom ; K.Goldberg ; Cardiovascular and Gastrointestinal Innovative Medicines Unit, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, United Kingdom ; S.Groombridge ; Cardiovascular and Gastrointestinal Innovative Medicines Unit, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, United Kingdom ; J.Hudson ; Cardiovascular and Gastrointestinal Innovative Medicines Unit, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, United Kingdom ; A.G.Leach ; Cardiovascular and Gastrointestinal Innovative Medicines Unit, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, United Kingdom ; ; A.Pickup ; ; Cardiovascular and Gastrointestinal Innovative Medicines Unit, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, United Kingdom ; R.Poultney ; Cardiovascular and Gastrointestinal Innovative Medicines Unit, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, United Kingdom ; J.S.Scott ; Cardiovascular and Gastrointestinal Innovative Medicines Unit, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, United Kingdom ; A.Pickup ; Cardiovascular and Gastrointestinal Innovative Medicines Unit, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, United Kingdom ; J.Sweeney ; Department of Chemistry University of Huddersfield, Queensgate, Huddersfield West Yorkshire. HD1 3DH, United Kingdom. ; P.H.Svensson ; AstraZeneca R&D Sodertalje Medicines Evaluation CNSP, B341:3, SE 151 85 Sodertalje Sweden ; _publ_contact_author_address ; Cardiovascular and Gastrointestinal Innovative Medicines Unit, AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire, SK10 4TG, United Kingdom ; _publ_contact_author_email Philip.MacFaul@astrazeneca.com _publ_contact_author_name 'Dr. P. A. MacFaul' # Attachment '- 4-((2-(4-(5-isopropyl-1,2,4-oxadiazol-3-yl)-2-methylpiperazin-1-yl)pyrimidin-5-yloxy)methyl)nicotinonitrile_2.CIF' data_1 _database_code_depnum_ccdc_archive 'CCDC 854369' _audit_creation_method SHELXL-97 _chemical_name_systematic ; 4-((2-(4-(5-isopropyl-1,2,4-oxadiazol-3-yl)-2-methylpiperazin-1-yl)pyrimidin-5-yloxy)methyl)nicotinonitrile ; _chemical_name_common ; 4-((2-(4-(5-isopropyl-1,2,4-oxadiazol-3-yl)-2-methylpiperazin- 1-yl)pyrimidin-5-y ; _chemical_melting_point ? _chemical_formula_moiety 'C21 H20 N8 O2, 3(H)' _chemical_formula_sum 'C21 H23 N8 O2' _chemical_formula_weight 419.47 loop_ _atom_type_symbol _atom_type_description _atom_type_scat_dispersion_real _atom_type_scat_dispersion_imag _atom_type_scat_source C C 0.0033 0.0016 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' H H 0.0000 0.0000 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' N N 0.0061 0.0033 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' O O 0.0106 0.0060 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' _symmetry_cell_setting Triclinic _symmetry_space_group_name_H-M 'P -1' _symmetry_space_group_name_Hall '-P 1' loop_ _symmetry_equiv_pos_as_xyz 'x, y, z' '-x, -y, -z' _cell_length_a 9.1873(3) _cell_length_b 10.2806(2) _cell_length_c 11.8644(3) _cell_angle_alpha 94.876(1) _cell_angle_beta 103.767(2) _cell_angle_gamma 102.245(1) _cell_volume 1052.76(5) _cell_formula_units_Z 2 _cell_measurement_temperature 200(2) _cell_measurement_reflns_used 9576 _cell_measurement_theta_min 2.35 _cell_measurement_theta_max 24.81 _exptl_crystal_description Needle _exptl_crystal_colour colourless _exptl_crystal_size_max 0.1 _exptl_crystal_size_mid 0.04 _exptl_crystal_size_min 0.02 _exptl_crystal_density_diffrn 1.323 _exptl_crystal_density_method 'not measured' _exptl_crystal_F_000 442 _exptl_absorpt_coefficient_mu 0.091 _exptl_absorpt_correction_type empirical _exptl_absorpt_correction_T_min 0.99 _exptl_absorpt_correction_T_max 1.0 _exptl_absorpt_process_details 'Bruker ApexII' _exptl_special_details ; ? ; _diffrn_ambient_temperature 200(2) _diffrn_radiation_wavelength 0.71073 _diffrn_radiation_type MoK\a _diffrn_radiation_source 'fine-focus sealed tube' _diffrn_radiation_monochromator graphite _diffrn_measurement_device_type 'Bruker APEX-II CCD' _diffrn_measurement_method '\f and \w scans' _diffrn_detector_area_resol_mean ? _diffrn_reflns_number 23164 _diffrn_reflns_av_R_equivalents 0.0368 _diffrn_reflns_av_sigmaI/netI 0.0264 _diffrn_reflns_limit_h_min -10 _diffrn_reflns_limit_h_max 10 _diffrn_reflns_limit_k_min -12 _diffrn_reflns_limit_k_max 12 _diffrn_reflns_limit_l_min -13 _diffrn_reflns_limit_l_max 14 _diffrn_reflns_theta_min 2.35 _diffrn_reflns_theta_max 25.00 _reflns_number_total 3671 _reflns_number_gt 3138 _reflns_threshold_expression >2sigma(I) _computing_data_collection 'Bruker APEX2' _computing_cell_refinement 'Bruker SAINT' _computing_data_reduction 'Bruker SAINT' _computing_structure_solution 'SHELXS-97 (Sheldrick, 2008)' _computing_structure_refinement 'SHELXL-97 (Sheldrick, 2008)' _computing_molecular_graphics 'Bruker SHELXTL' _computing_publication_material 'Bruker SHELXTL' _refine_special_details ; Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ > 2sigma(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ; _refine_ls_structure_factor_coef Fsqd _refine_ls_matrix_type full _refine_ls_weighting_scheme calc _refine_ls_weighting_details 'calc w=1/[\s^2^(Fo^2^)+(0.0139P)^2^+3.0990P] where P=(Fo^2^+2Fc^2^)/3' _atom_sites_solution_primary direct _atom_sites_solution_secondary difmap _atom_sites_solution_hydrogens Geom _refine_ls_hydrogen_treatment constr _refine_ls_extinction_method SHELXL _refine_ls_extinction_coef 0.0116(9) _refine_ls_extinction_expression Fc^*^=kFc[1+0.001xFc^2^\l^3^/sin(2\q)]^-1/4^ _refine_ls_number_reflns 3671 _refine_ls_number_parameters 295 _refine_ls_number_restraints 1 _refine_ls_R_factor_all 0.0999 _refine_ls_R_factor_gt 0.0892 _refine_ls_wR_factor_ref 0.1846 _refine_ls_wR_factor_gt 0.1812 _refine_ls_goodness_of_fit_ref 1.215 _refine_ls_restrained_S_all 1.216 _refine_ls_shift/su_max 0.000 _refine_ls_shift/su_mean 0.000 loop_ _atom_site_label _atom_site_type_symbol _atom_site_fract_x _atom_site_fract_y _atom_site_fract_z _atom_site_U_iso_or_equiv _atom_site_adp_type _atom_site_occupancy _atom_site_symmetry_multiplicity _atom_site_calc_flag _atom_site_refinement_flags _atom_site_disorder_assembly _atom_site_disorder_group C1 C 0.4725(5) 0.0996(4) 0.2627(3) 0.0311(9) Uani 1 1 d . . . C2 C 0.4538(5) 0.0467(4) 0.1466(4) 0.0373(10) Uani 1 1 d . . . H2 H 0.5162 -0.0121 0.1314 0.045 Uiso 1 1 calc R . . C3 C 0.2723(6) 0.1585(5) 0.0804(4) 0.0487(12) Uani 1 1 d . . . H3 H 0.1993 0.1789 0.0172 0.058 Uiso 1 1 calc R . . C4 C 0.2869(5) 0.2200(5) 0.1934(4) 0.0433(11) Uani 1 1 d . . . H4 H 0.2261 0.2814 0.2052 0.052 Uiso 1 1 calc R . . C5 C 0.3888(5) 0.1917(4) 0.2870(3) 0.0306(9) Uani 1 1 d . . . C6 C 0.5775(5) 0.0563(4) 0.3541(4) 0.0374(10) Uani 1 1 d . . . C7 C 0.4114(5) 0.2536(4) 0.4114(3) 0.0312(9) Uani 1 1 d . . . H7A H 0.3892 0.1824 0.4604 0.037 Uiso 1 1 calc R . . H7B H 0.5194 0.3058 0.4445 0.037 Uiso 1 1 calc R . . C8 C 0.3096(5) 0.4046(4) 0.5169(3) 0.0317(9) Uani 1 1 d . . . C9 C 0.4075(4) 0.4022(4) 0.6235(3) 0.0289(9) Uani 1 1 d . . . H9 H 0.4861 0.3545 0.6270 0.035 Uiso 1 1 calc R . . C10 C 0.2844(4) 0.5328(4) 0.7142(3) 0.0290(9) Uani 1 1 d . . . C11 C 0.2026(5) 0.4811(5) 0.5167(4) 0.0388(11) Uani 1 1 d . . . H11 H 0.1362 0.4877 0.4437 0.047 Uiso 1 1 calc R . . C12 C 0.3391(5) 0.5509(5) 0.9258(4) 0.0410(11) Uani 1 1 d . . . H12 H 0.4425 0.5378 0.9214 0.049 Uiso 1 1 calc R A 2 C13 C 0.3659(5) 0.6567(5) 1.0307(4) 0.0446(12) Uani 1 1 d . C . H13A H 0.4031 0.6206 1.1041 0.054 Uiso 1 1 calc R . . H13B H 0.4455 0.7368 1.0268 0.054 Uiso 1 1 calc R . . C14 C 0.1593(5) 0.7482(4) 0.9224(3) 0.0352(10) Uani 1 1 d . C . H14A H 0.2351 0.8289 0.9147 0.042 Uiso 1 1 calc R . . H14B H 0.0628 0.7747 0.9261 0.042 Uiso 1 1 calc R . . C15 C 0.1269(5) 0.6398(4) 0.8161(3) 0.0326(10) Uani 1 1 d D . . H15 H 0.1012 0.6839 0.7444 0.039 Uiso 1 1 calc R B 1 C16 C 0.0026(7) 0.5351(6) 0.8089(7) 0.041(3) Uani 0.508(11) 1 d PD C 1 H99A H -0.0050 0.4649 0.7450 0.062 Uiso 0.50 1 calc PR . . H99B H -0.0921 0.5677 0.7934 0.062 Uiso 0.50 1 calc PR . . H99C H 0.0161 0.4980 0.8831 0.062 Uiso 0.50 1 calc PR . . C17 C 0.2543(11) 0.4290(9) 0.9426(8) 0.041(3) Uani 0.492(11) 1 d P C 2 H10A H 0.1464 0.4330 0.9326 0.061 Uiso 0.50 1 calc PR . . H10B H 0.2966 0.4106 1.0219 0.061 Uiso 0.50 1 calc PR . . H10C H 0.2597 0.3572 0.8850 0.061 Uiso 0.50 1 calc PR . . C18 C 0.2090(4) 0.7524(4) 1.1341(3) 0.0297(9) Uani 1 1 d . C . C19 C 0.1221(5) 0.8489(4) 1.2548(3) 0.0339(10) Uani 1 1 d . C . C20 C 0.0381(5) 0.9215(4) 1.3229(4) 0.0355(10) Uani 1 1 d . . . H20 H 0.1163 0.9975 1.3775 0.043 Uiso 1 1 calc R . . C21 C -0.0358(6) 0.8290(5) 1.3967(4) 0.0515(13) Uani 1 1 d . . . H21A H -0.1118 0.7524 1.3455 0.077 Uiso 1 1 calc R . . H21B H -0.0872 0.8782 1.4431 0.077 Uiso 1 1 calc R . . H21C H 0.0438 0.7964 1.4494 0.077 Uiso 1 1 calc R . . C22 C -0.0760(7) 0.9815(6) 1.2420(5) 0.0648(17) Uani 1 1 d . . . H22A H -0.0242 1.0321 1.1903 0.097 Uiso 1 1 calc R . . H22B H -0.1157 1.0419 1.2887 0.097 Uiso 1 1 calc R . . H22C H -0.1618 0.9091 1.1945 0.097 Uiso 1 1 calc R . . N1 N 0.3541(5) 0.0735(4) 0.0562(3) 0.0421(9) Uani 1 1 d . . . N2 N 0.6596(5) 0.0192(5) 0.4257(4) 0.0547(11) Uani 1 1 d . . . N3 N 0.3948(4) 0.4657(3) 0.7230(3) 0.0300(8) Uani 1 1 d . . . N4 N 0.1879(4) 0.5459(4) 0.6139(3) 0.0367(9) Uani 1 1 d . . . N5 N 0.2710(4) 0.5974(4) 0.8169(3) 0.0322(8) Uani 1 1 d . C . N6 N 0.2205(4) 0.6944(4) 1.0298(3) 0.0343(8) Uani 1 1 d . . . N7 N 0.3046(5) 0.7461(4) 1.2341(3) 0.0496(11) Uani 1 1 d . . . N8 N 0.0949(4) 0.8171(3) 1.1430(3) 0.0323(8) Uani 1 1 d . . . O1 O 0.3087(4) 0.3396(3) 0.4103(2) 0.0415(8) Uani 1 1 d . . . O2 O 0.2426(4) 0.8107(3) 1.3174(2) 0.0456(8) Uani 1 1 d . C . loop_ _atom_site_aniso_label _atom_site_aniso_U_11 _atom_site_aniso_U_22 _atom_site_aniso_U_33 _atom_site_aniso_U_23 _atom_site_aniso_U_13 _atom_site_aniso_U_12 C1 0.034(2) 0.029(2) 0.033(2) 0.0000(17) 0.0154(18) 0.0095(18) C2 0.050(3) 0.029(2) 0.037(2) -0.0019(18) 0.021(2) 0.010(2) C3 0.055(3) 0.062(3) 0.029(2) -0.001(2) 0.008(2) 0.021(3) C4 0.049(3) 0.057(3) 0.029(2) -0.001(2) 0.010(2) 0.026(2) C5 0.034(2) 0.033(2) 0.024(2) -0.0017(17) 0.0093(17) 0.0065(18) C6 0.041(3) 0.039(2) 0.036(2) -0.005(2) 0.017(2) 0.012(2) C7 0.034(2) 0.038(2) 0.024(2) -0.0049(17) 0.0065(17) 0.0175(18) C8 0.035(2) 0.039(2) 0.024(2) -0.0007(17) 0.0096(17) 0.0166(19) C9 0.028(2) 0.034(2) 0.027(2) 0.0038(17) 0.0075(16) 0.0145(17) C10 0.029(2) 0.033(2) 0.026(2) 0.0005(17) 0.0098(16) 0.0099(17) C11 0.046(3) 0.053(3) 0.023(2) 0.0035(19) 0.0062(18) 0.027(2) C12 0.043(3) 0.060(3) 0.026(2) 0.000(2) 0.0044(19) 0.032(2) C13 0.040(3) 0.070(3) 0.028(2) -0.006(2) 0.0056(19) 0.029(2) C14 0.040(2) 0.040(2) 0.029(2) 0.0003(18) 0.0104(18) 0.018(2) C15 0.037(2) 0.040(2) 0.027(2) 0.0016(18) 0.0090(17) 0.024(2) C16 0.047(6) 0.048(6) 0.034(5) -0.003(4) 0.011(4) 0.027(5) C17 0.052(6) 0.042(6) 0.030(5) -0.002(4) 0.010(4) 0.018(5) C18 0.028(2) 0.036(2) 0.026(2) -0.0009(17) 0.0074(16) 0.0103(17) C19 0.037(2) 0.037(2) 0.030(2) -0.0021(18) 0.0112(18) 0.0126(19) C20 0.046(3) 0.036(2) 0.031(2) 0.0001(18) 0.0173(19) 0.014(2) C21 0.060(3) 0.054(3) 0.050(3) 0.009(2) 0.035(3) 0.011(3) C22 0.082(4) 0.087(4) 0.054(3) 0.022(3) 0.033(3) 0.060(4) N1 0.059(2) 0.037(2) 0.0305(19) -0.0028(16) 0.0174(18) 0.0086(19) N2 0.056(3) 0.066(3) 0.047(2) 0.002(2) 0.012(2) 0.031(2) N3 0.0294(18) 0.0377(19) 0.0243(17) -0.0005(14) 0.0051(14) 0.0151(15) N4 0.045(2) 0.048(2) 0.0255(18) 0.0040(16) 0.0102(16) 0.0284(18) N5 0.0327(18) 0.046(2) 0.0219(16) 0.0003(15) 0.0064(14) 0.0211(16) N6 0.0355(19) 0.047(2) 0.0234(17) -0.0028(15) 0.0067(14) 0.0211(17) N7 0.052(2) 0.074(3) 0.029(2) -0.0085(19) 0.0079(18) 0.039(2) N8 0.0352(19) 0.038(2) 0.0286(18) 0.0006(15) 0.0121(15) 0.0162(16) O1 0.0504(19) 0.059(2) 0.0220(14) -0.0035(13) 0.0080(13) 0.0346(16) O2 0.0496(19) 0.069(2) 0.0236(15) -0.0049(14) 0.0064(13) 0.0334(17) _geom_special_details ; All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. ; loop_ _geom_bond_atom_site_label_1 _geom_bond_atom_site_label_2 _geom_bond_distance _geom_bond_site_symmetry_2 _geom_bond_publ_flag C1 C5 1.393(5) . ? C1 C2 1.394(6) . ? C1 C6 1.439(6) . ? C2 N1 1.325(6) . ? C2 H2 0.9500 . ? C3 N1 1.323(6) . ? C3 C4 1.396(6) . ? C3 H3 0.9500 . ? C4 C5 1.368(6) . ? C4 H4 0.9500 . ? C5 C7 1.504(5) . ? C6 N2 1.144(6) . ? C7 O1 1.422(5) . ? C7 H7A 0.9900 . ? C7 H7B 0.9900 . ? C8 C9 1.373(5) . ? C8 O1 1.377(4) . ? C8 C11 1.383(6) . ? C9 N3 1.342(5) . ? C9 H9 0.9500 . ? C10 N3 1.331(5) . ? C10 N4 1.340(5) . ? C10 N5 1.381(5) . ? C11 N4 1.331(5) . ? C11 H11 0.9500 . ? C12 C17 1.386(10) . ? C12 N5 1.462(5) . ? C12 C13 1.517(6) . ? C12 H12 1.0000 . ? C13 N6 1.466(5) . ? C13 H13A 0.9900 . ? C13 H13B 0.9900 . ? C14 N6 1.469(5) . ? C14 C15 1.537(5) . ? C14 H14A 0.9900 . ? C14 H14B 0.9900 . ? C15 C16 1.374(2) . ? C15 N5 1.478(5) . ? C15 H15 1.0000 . ? C16 H99A 0.9800 . ? C16 H99B 0.9800 . ? C16 H99C 0.9800 . ? C17 H10A 0.9800 . ? C17 H10B 0.9800 . ? C17 H10C 0.9800 . ? C18 N7 1.313(5) . ? C18 N6 1.364(5) . ? C18 N8 1.375(5) . ? C19 N8 1.290(5) . ? C19 O2 1.332(5) . ? C19 C20 1.497(5) . ? C20 C21 1.511(6) . ? C20 C22 1.515(6) . ? C20 H20 1.0000 . ? C21 H21A 0.9800 . ? C21 H21B 0.9800 . ? C21 H21C 0.9800 . ? C22 H22A 0.9800 . ? C22 H22B 0.9800 . ? C22 H22C 0.9800 . ? N7 O2 1.435(4) . ? loop_ _geom_angle_atom_site_label_1 _geom_angle_atom_site_label_2 _geom_angle_atom_site_label_3 _geom_angle _geom_angle_site_symmetry_1 _geom_angle_site_symmetry_3 _geom_angle_publ_flag C5 C1 C2 119.4(4) . . ? C5 C1 C6 121.9(4) . . ? C2 C1 C6 118.7(4) . . ? N1 C2 C1 123.8(4) . . ? N1 C2 H2 118.1 . . ? C1 C2 H2 118.1 . . ? N1 C3 C4 123.8(4) . . ? N1 C3 H3 118.1 . . ? C4 C3 H3 118.1 . . ? C5 C4 C3 120.0(4) . . ? C5 C4 H4 120.0 . . ? C3 C4 H4 120.0 . . ? C4 C5 C1 116.6(4) . . ? C4 C5 C7 123.3(4) . . ? C1 C5 C7 120.2(4) . . ? N2 C6 C1 178.6(5) . . ? O1 C7 C5 107.9(3) . . ? O1 C7 H7A 110.1 . . ? C5 C7 H7A 110.1 . . ? O1 C7 H7B 110.1 . . ? C5 C7 H7B 110.1 . . ? H7A C7 H7B 108.4 . . ? C9 C8 O1 126.3(4) . . ? C9 C8 C11 116.6(4) . . ? O1 C8 C11 117.0(4) . . ? N3 C9 C8 121.4(4) . . ? N3 C9 H9 119.3 . . ? C8 C9 H9 119.3 . . ? N3 C10 N4 125.5(3) . . ? N3 C10 N5 117.2(3) . . ? N4 C10 N5 117.2(3) . . ? N4 C11 C8 123.2(4) . . ? N4 C11 H11 118.4 . . ? C8 C11 H11 118.4 . . ? C17 C12 N5 113.6(5) . . ? C17 C12 C13 110.3(5) . . ? N5 C12 C13 111.0(4) . . ? C17 C12 H12 107.2 . . ? N5 C12 H12 107.2 . . ? C13 C12 H12 107.2 . . ? N6 C13 C12 109.0(4) . . ? N6 C13 H13A 109.9 . . ? C12 C13 H13A 109.9 . . ? N6 C13 H13B 109.9 . . ? C12 C13 H13B 109.9 . . ? H13A C13 H13B 108.3 . . ? N6 C14 C15 109.1(3) . . ? N6 C14 H14A 109.9 . . ? C15 C14 H14A 109.9 . . ? N6 C14 H14B 109.9 . . ? C15 C14 H14B 109.9 . . ? H14A C14 H14B 108.3 . . ? C16 C15 N5 113.8(5) . . ? C16 C15 C14 113.4(5) . . ? N5 C15 C14 108.5(3) . . ? C16 C15 H15 106.9 . . ? N5 C15 H15 106.9 . . ? C14 C15 H15 106.9 . . ? C15 C16 H99A 109.5 . . ? C15 C16 H99B 109.5 . . ? H99A C16 H99B 109.5 . . ? C15 C16 H99C 109.5 . . ? H99A C16 H99C 109.5 . . ? H99B C16 H99C 109.5 . . ? C12 C17 H10A 109.5 . . ? C12 C17 H10B 109.5 . . ? H10A C17 H10B 109.5 . . ? C12 C17 H10C 109.5 . . ? H10A C17 H10C 109.5 . . ? H10B C17 H10C 109.5 . . ? N7 C18 N6 121.8(4) . . ? N7 C18 N8 115.2(3) . . ? N6 C18 N8 123.0(3) . . ? N8 C19 O2 114.3(3) . . ? N8 C19 C20 129.4(4) . . ? O2 C19 C20 116.3(3) . . ? C19 C20 C21 110.0(4) . . ? C19 C20 C22 110.8(4) . . ? C21 C20 C22 113.1(4) . . ? C19 C20 H20 107.6 . . ? C21 C20 H20 107.6 . . ? C22 C20 H20 107.6 . . ? C20 C21 H21A 109.5 . . ? C20 C21 H21B 109.5 . . ? H21A C21 H21B 109.5 . . ? C20 C21 H21C 109.5 . . ? H21A C21 H21C 109.5 . . ? H21B C21 H21C 109.5 . . ? C20 C22 H22A 109.5 . . ? C20 C22 H22B 109.5 . . ? H22A C22 H22B 109.5 . . ? C20 C22 H22C 109.5 . . ? H22A C22 H22C 109.5 . . ? H22B C22 H22C 109.5 . . ? C3 N1 C2 116.4(4) . . ? C10 N3 C9 117.4(3) . . ? C11 N4 C10 115.7(3) . . ? C10 N5 C12 116.9(3) . . ? C10 N5 C15 118.7(3) . . ? C12 N5 C15 114.0(3) . . ? C18 N6 C13 116.4(3) . . ? C18 N6 C14 118.7(3) . . ? C13 N6 C14 112.3(3) . . ? C18 N7 O2 102.0(3) . . ? C19 N8 C18 102.4(3) . . ? C8 O1 C7 117.0(3) . . ? C19 O2 N7 106.1(3) . . ? _diffrn_measured_fraction_theta_max 0.990 _diffrn_reflns_theta_full 25.00 _diffrn_measured_fraction_theta_full 0.990 _refine_diff_density_max 0.506 _refine_diff_density_min -0.394 _refine_diff_density_rms 0.064 data_2 _database_code_depnum_ccdc_archive 'CCDC 854370' _audit_creation_method SHELXL-97 _chemical_name_systematic ; 4-((2-(4-(5-(difluoromethyl)-1,2,4- oxadiazol-3-yl)-2-methylpiperazin-1-yl) pyrimidin-5-yloxy)methyl)nicotinonitrile ; _chemical_name_common ; 4-((2-(4-(5-(difluoromethyl)-1,2,4-oxadiazol-3-yl)-2- methylpiperazin-1-yl) pyrimidin-5-yloxy)methyl)nicotinonitrile ; _chemical_melting_point ? _chemical_formula_moiety 'C19 H18 F2 N8 O2' _chemical_formula_sum 'C19 H18 F2 N8 O2' _chemical_formula_weight 428.41 loop_ _atom_type_symbol _atom_type_description _atom_type_scat_dispersion_real _atom_type_scat_dispersion_imag _atom_type_scat_source C C 0.0033 0.0016 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' H H 0.0000 0.0000 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' N N 0.0061 0.0033 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' O O 0.0106 0.0060 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' F F 0.0171 0.0103 'International Tables Vol C Tables 4.2.6.8 and 6.1.1.4' _symmetry_cell_setting Orthorhombic _symmetry_space_group_name_H-M 'P 21 21 21' _symmetry_space_group_name_Hall 'P 2ac 2ab' loop_ _symmetry_equiv_pos_as_xyz 'x, y, z' '-x+1/2, -y, z+1/2' '-x, y+1/2, -z+1/2' 'x+1/2, -y+1/2, -z' _cell_length_a 6.8535(17) _cell_length_b 11.759(3) _cell_length_c 24.167(8) _cell_angle_alpha 90.00 _cell_angle_beta 90.00 _cell_angle_gamma 90.00 _cell_volume 1947.6(9) _cell_formula_units_Z 4 _cell_measurement_temperature 200(2) _cell_measurement_reflns_used ? _cell_measurement_theta_min ? _cell_measurement_theta_max ? _exptl_crystal_description block _exptl_crystal_colour colourless _exptl_crystal_size_max 0.13 _exptl_crystal_size_mid 0.05 _exptl_crystal_size_min 0.04 _exptl_crystal_density_diffrn 1.461 _exptl_crystal_density_method 'not measured' _exptl_crystal_F_000 888 _exptl_absorpt_coefficient_mu 0.114 _exptl_absorpt_correction_type empirical _exptl_absorpt_correction_T_min 0.98 _exptl_absorpt_correction_T_max 0.99 _exptl_absorpt_process_details 'Bruker ApexII' _chemical_absolute_configuration unk _exptl_special_details ; ? ; _diffrn_ambient_temperature 200(2) _diffrn_radiation_wavelength 0.71073 _diffrn_radiation_type MoK\a _diffrn_radiation_source 'fine-focus sealed tube' _diffrn_radiation_monochromator graphite _diffrn_measurement_device_type 'Bruker APEX-II CCD' _diffrn_measurement_method '\f and \w scans' _diffrn_detector_area_resol_mean ? _diffrn_reflns_number 2329 _diffrn_reflns_av_R_equivalents 0.0000 _diffrn_reflns_av_sigmaI/netI 0.0178 _diffrn_reflns_limit_h_min 0 _diffrn_reflns_limit_h_max 8 _diffrn_reflns_limit_k_min 0 _diffrn_reflns_limit_k_max 14 _diffrn_reflns_limit_l_min 0 _diffrn_reflns_limit_l_max 30 _diffrn_reflns_theta_min 1.69 _diffrn_reflns_theta_max 26.49 _reflns_number_total 2329 _reflns_number_gt 2037 _reflns_threshold_expression >2sigma(I) _computing_data_collection 'Bruker APEX2' _computing_cell_refinement 'Bruker SAINT' _computing_data_reduction 'Bruker SAINT' _computing_structure_solution 'SHELXS-97 (Sheldrick, 2008)' _computing_structure_refinement 'SHELXL-97 (Sheldrick, 2008)' _computing_molecular_graphics 'Bruker SHELXTL' _computing_publication_material 'Bruker SHELXTL' _refine_special_details ; Refinement of F^2^ against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F^2^, conventional R-factors R are based on F, with F set to zero for negative F^2^. The threshold expression of F^2^ > 2sigma(F^2^) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F^2^ are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. ; _refine_ls_structure_factor_coef Fsqd _refine_ls_matrix_type full _refine_ls_weighting_scheme calc _refine_ls_weighting_details 'calc w=1/[\s^2^(Fo^2^)+(0.0679P)^2^+0.0000P] where P=(Fo^2^+2Fc^2^)/3' _atom_sites_solution_primary direct _atom_sites_solution_secondary difmap _atom_sites_solution_hydrogens geom _refine_ls_hydrogen_treatment constr _refine_ls_extinction_method none _refine_ls_extinction_coef ? _refine_ls_abs_structure_details 'Flack H D (1983), Acta Cryst. A39, 876-881' _refine_ls_abs_structure_Flack 1.1(10) _refine_ls_number_reflns 2329 _refine_ls_number_parameters 281 _refine_ls_number_restraints 0 _refine_ls_R_factor_all 0.0411 _refine_ls_R_factor_gt 0.0317 _refine_ls_wR_factor_ref 0.0999 _refine_ls_wR_factor_gt 0.0848 _refine_ls_goodness_of_fit_ref 1.113 _refine_ls_restrained_S_all 1.113 _refine_ls_shift/su_max 0.000 _refine_ls_shift/su_mean 0.000 loop_ _atom_site_label _atom_site_type_symbol _atom_site_fract_x _atom_site_fract_y _atom_site_fract_z _atom_site_U_iso_or_equiv _atom_site_adp_type _atom_site_occupancy _atom_site_symmetry_multiplicity _atom_site_calc_flag _atom_site_refinement_flags _atom_site_disorder_assembly _atom_site_disorder_group C1 C 0.3879(3) 0.84409(18) -0.07650(9) 0.0319(5) Uani 1 1 d . . . C2 C 0.4075(3) 0.92687(16) -0.11748(8) 0.0313(5) Uani 1 1 d . . . C3 C 0.4204(4) 0.89417(19) -0.17252(9) 0.0391(5) Uani 1 1 d . . . H3 H 0.4340 0.9521 -0.1997 0.047 Uiso 1 1 calc R . . C4 C 0.3940(4) 0.7086(2) -0.14986(10) 0.0426(6) Uani 1 1 d . . . H4 H 0.3882 0.6311 -0.1609 0.051 Uiso 1 1 calc R . . C5 C 0.3802(3) 0.73224(18) -0.09437(9) 0.0374(5) Uani 1 1 d . . . H5 H 0.3656 0.6722 -0.0684 0.045 Uiso 1 1 calc R . . C6 C 0.4163(3) 1.04677(19) -0.10475(9) 0.0363(5) Uani 1 1 d . . . C7 C 0.3781(4) 0.87664(17) -0.01681(9) 0.0364(5) Uani 1 1 d . . . H7A H 0.5015 0.9137 -0.0054 0.044 Uiso 1 1 calc R . . H7B H 0.2698 0.9309 -0.0107 0.044 Uiso 1 1 calc R . . C8 C 0.3712(3) 0.78522(18) 0.07092(8) 0.0325(5) Uani 1 1 d . . . C9 C 0.3672(3) 0.88317(17) 0.10214(9) 0.0342(5) Uani 1 1 d . . . H9 H 0.3497 0.9540 0.0839 0.041 Uiso 1 1 calc R . . C10 C 0.4102(3) 0.77922(16) 0.18077(8) 0.0312(5) Uani 1 1 d . . . C11 C 0.3954(3) 0.68395(18) 0.09914(8) 0.0328(5) Uani 1 1 d . . . H11 H 0.3983 0.6151 0.0786 0.039 Uiso 1 1 calc R . . C12 C 0.3939(4) 0.87378(16) 0.27120(9) 0.0406(6) Uani 1 1 d . . . H12A H 0.2660 0.8621 0.2894 0.049 Uiso 1 1 calc R . . H12B H 0.3852 0.9431 0.2481 0.049 Uiso 1 1 calc R . . C13 C 0.5494(4) 0.88940(18) 0.31453(9) 0.0460(6) Uani 1 1 d . . . H13A H 0.6736 0.9122 0.2968 0.055 Uiso 1 1 calc R . . H13B H 0.5103 0.9500 0.3407 0.055 Uiso 1 1 calc R . . C14 C 0.6266(4) 0.68662(18) 0.30893(9) 0.0406(5) Uani 1 1 d . . . H14A H 0.6408 0.6170 0.3316 0.049 Uiso 1 1 calc R . . H14B H 0.7528 0.7016 0.2903 0.049 Uiso 1 1 calc R . . C15 C 0.4692(4) 0.66919(16) 0.26618(9) 0.0395(6) Uani 1 1 d . . . H15 H 0.5174 0.6117 0.2389 0.047 Uiso 1 1 calc R . . C16 C 0.2831(5) 0.6237(2) 0.29157(11) 0.0569(7) Uani 1 1 d . . . H16A H 0.2428 0.6731 0.3222 0.085 Uiso 1 1 calc R . . H16B H 0.3058 0.5465 0.3055 0.085 Uiso 1 1 calc R . . H16C H 0.1801 0.6219 0.2634 0.085 Uiso 1 1 calc R . . C17 C 0.6227(3) 0.78059(16) 0.39824(9) 0.0328(5) Uani 1 1 d . . . C18 C 0.6383(3) 0.83243(16) 0.47955(9) 0.0314(5) Uani 1 1 d . . . C19 C 0.6302(3) 0.88971(18) 0.53489(9) 0.0367(5) Uani 1 1 d . . . H19 H 0.5638 0.8399 0.5626 0.044 Uiso 1 1 calc R . . F1 F 0.5339(3) 0.98932(11) 0.52931(6) 0.0630(5) Uani 1 1 d . . . F2 F 0.8112(2) 0.91528(16) 0.55154(7) 0.0707(5) Uani 1 1 d . . . N1 N 0.4150(3) 0.78715(17) -0.18956(8) 0.0451(5) Uani 1 1 d . . . N2 N 0.4240(4) 1.14168(18) -0.09619(9) 0.0521(6) Uani 1 1 d . . . N3 N 0.3868(3) 0.88202(14) 0.15688(7) 0.0341(4) Uani 1 1 d . . . N4 N 0.4149(3) 0.67892(14) 0.15371(7) 0.0330(4) Uani 1 1 d . . . N5 N 0.4391(3) 0.77639(13) 0.23649(7) 0.0391(5) Uani 1 1 d . . . N6 N 0.5758(3) 0.78239(14) 0.34422(7) 0.0412(5) Uani 1 1 d . . . N7 N 0.5852(3) 0.87231(15) 0.43280(7) 0.0342(4) Uani 1 1 d . . . N8 N 0.6981(3) 0.69053(16) 0.42271(7) 0.0375(4) Uani 1 1 d . . . O1 O 0.3476(3) 0.77718(12) 0.01455(6) 0.0464(5) Uani 1 1 d . . . O2 O 0.7056(3) 0.72664(12) 0.47921(6) 0.0399(4) Uani 1 1 d . . . loop_ _atom_site_aniso_label _atom_site_aniso_U_11 _atom_site_aniso_U_22 _atom_site_aniso_U_33 _atom_site_aniso_U_23 _atom_site_aniso_U_13 _atom_site_aniso_U_12 C1 0.0301(11) 0.0355(11) 0.0302(11) 0.0009(8) -0.0022(10) 0.0031(9) C2 0.0311(11) 0.0317(11) 0.0312(11) 0.0001(8) -0.0008(9) 0.0020(9) C3 0.0464(13) 0.0396(12) 0.0313(11) 0.0022(9) 0.0008(11) 0.0028(11) C4 0.0479(13) 0.0373(12) 0.0427(13) -0.0067(10) -0.0052(11) 0.0016(12) C5 0.0397(12) 0.0337(11) 0.0389(12) 0.0015(10) -0.0023(11) 0.0029(10) C6 0.0393(13) 0.0372(12) 0.0324(11) 0.0010(9) -0.0004(10) -0.0006(10) C7 0.0471(13) 0.0319(11) 0.0301(11) 0.0030(9) -0.0003(11) 0.0021(11) C8 0.0388(11) 0.0312(11) 0.0276(10) 0.0021(8) -0.0006(9) -0.0043(10) C9 0.0405(12) 0.0310(11) 0.0313(11) 0.0054(9) -0.0005(10) -0.0017(10) C10 0.0388(11) 0.0239(10) 0.0308(11) 0.0018(8) 0.0025(10) -0.0006(10) C11 0.0383(11) 0.0298(10) 0.0305(11) -0.0023(8) 0.0010(10) -0.0035(10) C12 0.0705(16) 0.0221(10) 0.0292(11) -0.0008(8) -0.0018(12) 0.0092(12) C13 0.0760(18) 0.0248(11) 0.0372(12) 0.0047(9) -0.0041(13) -0.0007(11) C14 0.0590(14) 0.0271(11) 0.0358(12) 0.0016(9) -0.0005(12) 0.0080(11) C15 0.0693(16) 0.0191(10) 0.0300(11) 0.0025(8) -0.0021(11) 0.0049(10) C16 0.0747(18) 0.0421(14) 0.0539(15) 0.0118(12) -0.0143(15) -0.0124(14) C17 0.0368(11) 0.0260(10) 0.0357(11) 0.0035(9) -0.0026(10) -0.0015(10) C18 0.0328(10) 0.0264(10) 0.0352(11) 0.0035(8) -0.0021(10) -0.0028(9) C19 0.0398(12) 0.0291(11) 0.0413(13) -0.0008(9) -0.0055(11) -0.0021(10) F1 0.0944(12) 0.0374(8) 0.0570(9) -0.0081(7) -0.0158(9) 0.0187(8) F2 0.0469(9) 0.1027(13) 0.0625(10) -0.0256(10) -0.0144(8) -0.0109(9) N1 0.0516(12) 0.0488(12) 0.0348(10) -0.0055(9) -0.0026(10) 0.0055(10) N2 0.0633(15) 0.0383(12) 0.0548(13) -0.0022(10) 0.0017(12) -0.0040(10) N3 0.0474(11) 0.0246(9) 0.0302(9) 0.0032(7) 0.0000(9) -0.0002(9) N4 0.0438(10) 0.0248(8) 0.0304(9) 0.0004(7) 0.0027(9) -0.0002(8) N5 0.0687(13) 0.0218(8) 0.0268(9) 0.0008(7) -0.0017(9) 0.0074(9) N6 0.0672(14) 0.0223(9) 0.0341(9) 0.0017(7) -0.0090(10) 0.0034(9) N7 0.0399(10) 0.0272(9) 0.0355(10) 0.0021(7) -0.0032(9) -0.0027(8) N8 0.0464(11) 0.0338(9) 0.0322(9) -0.0014(8) -0.0047(9) 0.0044(9) O1 0.0756(13) 0.0369(9) 0.0266(8) 0.0025(6) -0.0043(8) -0.0124(8) O2 0.0507(9) 0.0339(8) 0.0351(8) 0.0014(7) -0.0074(8) 0.0076(7) _geom_special_details ; All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. ; loop_ _geom_bond_atom_site_label_1 _geom_bond_atom_site_label_2 _geom_bond_distance _geom_bond_site_symmetry_2 _geom_bond_publ_flag C1 C5 1.385(3) . ? C1 C2 1.395(3) . ? C1 C7 1.494(3) . ? C2 C3 1.388(3) . ? C2 C6 1.444(3) . ? C3 N1 1.325(3) . ? C3 H3 0.9500 . ? C4 N1 1.340(3) . ? C4 C5 1.373(3) . ? C4 H4 0.9500 . ? C5 H5 0.9500 . ? C6 N2 1.136(3) . ? C7 O1 1.409(2) . ? C7 H7A 0.9900 . ? C7 H7B 0.9900 . ? C8 O1 1.375(3) . ? C8 C9 1.377(3) . ? C8 C11 1.382(3) . ? C9 N3 1.330(3) . ? C9 H9 0.9500 . ? C10 N4 1.349(3) . ? C10 N3 1.349(3) . ? C10 N5 1.362(3) . ? C11 N4 1.327(3) . ? C11 H11 0.9500 . ? C12 N5 1.453(3) . ? C12 C13 1.506(4) . ? C12 H12A 0.9900 . ? C12 H12B 0.9900 . ? C13 N6 1.460(3) . ? C13 H13A 0.9900 . ? C13 H13B 0.9900 . ? C14 N6 1.455(3) . ? C14 C15 1.508(3) . ? C14 H14A 0.9900 . ? C14 H14B 0.9900 . ? C15 N5 1.465(2) . ? C15 C16 1.513(4) . ? C15 H15 1.0000 . ? C16 H16A 0.9800 . ? C16 H16B 0.9800 . ? C16 H16C 0.9800 . ? C17 N8 1.318(3) . ? C17 N6 1.345(3) . ? C17 N7 1.388(3) . ? C18 N7 1.276(3) . ? C18 O2 1.327(2) . ? C18 C19 1.499(3) . ? C19 F2 1.338(3) . ? C19 F1 1.351(3) . ? C19 H19 1.0000 . ? N8 O2 1.431(2) . ? loop_ _geom_angle_atom_site_label_1 _geom_angle_atom_site_label_2 _geom_angle_atom_site_label_3 _geom_angle _geom_angle_site_symmetry_1 _geom_angle_site_symmetry_3 _geom_angle_publ_flag C5 C1 C2 116.42(19) . . ? C5 C1 C7 122.85(18) . . ? C2 C1 C7 120.73(18) . . ? C3 C2 C1 119.56(19) . . ? C3 C2 C6 118.17(18) . . ? C1 C2 C6 122.27(19) . . ? N1 C3 C2 124.0(2) . . ? N1 C3 H3 118.0 . . ? C2 C3 H3 118.0 . . ? N1 C4 C5 124.6(2) . . ? N1 C4 H4 117.7 . . ? C5 C4 H4 117.7 . . ? C4 C5 C1 119.6(2) . . ? C4 C5 H5 120.2 . . ? C1 C5 H5 120.2 . . ? N2 C6 C2 178.2(2) . . ? O1 C7 C1 108.26(17) . . ? O1 C7 H7A 110.0 . . ? C1 C7 H7A 110.0 . . ? O1 C7 H7B 110.0 . . ? C1 C7 H7B 110.0 . . ? H7A C7 H7B 108.4 . . ? O1 C8 C9 126.72(18) . . ? O1 C8 C11 116.33(18) . . ? C9 C8 C11 116.91(19) . . ? N3 C9 C8 122.31(19) . . ? N3 C9 H9 118.8 . . ? C8 C9 H9 118.8 . . ? N4 C10 N3 125.37(18) . . ? N4 C10 N5 117.03(17) . . ? N3 C10 N5 117.54(17) . . ? N4 C11 C8 122.74(19) . . ? N4 C11 H11 118.6 . . ? C8 C11 H11 118.6 . . ? N5 C12 C13 110.3(2) . . ? N5 C12 H12A 109.6 . . ? C13 C12 H12A 109.6 . . ? N5 C12 H12B 109.6 . . ? C13 C12 H12B 109.6 . . ? H12A C12 H12B 108.1 . . ? N6 C13 C12 108.93(19) . . ? N6 C13 H13A 109.9 . . ? C12 C13 H13A 109.9 . . ? N6 C13 H13B 109.9 . . ? C12 C13 H13B 109.9 . . ? H13A C13 H13B 108.3 . . ? N6 C14 C15 109.59(19) . . ? N6 C14 H14A 109.8 . . ? C15 C14 H14A 109.8 . . ? N6 C14 H14B 109.8 . . ? C15 C14 H14B 109.8 . . ? H14A C14 H14B 108.2 . . ? N5 C15 C14 108.62(18) . . ? N5 C15 C16 112.6(2) . . ? C14 C15 C16 111.93(19) . . ? N5 C15 H15 107.8 . . ? C14 C15 H15 107.8 . . ? C16 C15 H15 107.8 . . ? C15 C16 H16A 109.5 . . ? C15 C16 H16B 109.5 . . ? H16A C16 H16B 109.5 . . ? C15 C16 H16C 109.5 . . ? H16A C16 H16C 109.5 . . ? H16B C16 H16C 109.5 . . ? N8 C17 N6 122.80(19) . . ? N8 C17 N7 115.27(18) . . ? N6 C17 N7 121.85(18) . . ? N7 C18 O2 115.99(19) . . ? N7 C18 C19 127.92(18) . . ? O2 C18 C19 116.08(18) . . ? F2 C19 F1 106.74(18) . . ? F2 C19 C18 109.60(19) . . ? F1 C19 C18 108.57(17) . . ? F2 C19 H19 110.6 . . ? F1 C19 H19 110.6 . . ? C18 C19 H19 110.6 . . ? C3 N1 C4 115.8(2) . . ? C9 N3 C10 116.54(17) . . ? C11 N4 C10 116.13(17) . . ? C10 N5 C12 121.38(17) . . ? C10 N5 C15 121.73(16) . . ? C12 N5 C15 115.19(15) . . ? C17 N6 C14 119.98(17) . . ? C17 N6 C13 121.36(17) . . ? C14 N6 C13 114.12(17) . . ? C18 N7 C17 101.21(17) . . ? C17 N8 O2 101.76(16) . . ? C8 O1 C7 117.27(16) . . ? C18 O2 N8 105.76(15) . . ? _diffrn_measured_fraction_theta_max 0.997 _diffrn_reflns_theta_full 26.49 _diffrn_measured_fraction_theta_full 0.997 _refine_diff_density_max 0.228 _refine_diff_density_min -0.303 _refine_diff_density_rms 0.107