# Electronic Supplementary Material (ESI) for Medicinal Chemistry Communications # This journal is © The Royal Society of Chemistry 2012 ####################################################################### # # Cambridge Crystallographic Data Centre # CCDC # ####################################################################### # # This CIF contains data from an original supplementary publication # deposited with the CCDC, and may include chemical, crystal, # experimental, refinement, atomic coordinates, # anisotropic displacement parameters and molecular geometry data, # as required by the journal to which it was submitted. # # This CIF is provided on the understanding that it is used for bona # fide research purposes only. It may contain copyright material # of the CCDC or of third parties, and may not be copied or further # disseminated in any form, whether machine-readable or not, # except for the purpose of generating routine backup copies # on your local computer system. # # For further information on the CCDC, data deposition and # data retrieval see: # www.ccdc.cam.ac.uk # # Bona fide researchers may freely download Mercury and enCIFer # from this site to visualise CIF-encoded structures and # to carry out CIF format checking respectively. # ####################################################################### data_13 _database_code_depnum_ccdc_archive 'CCDC 885065' #TrackingRef '1. Tetrahydrofuran-3-yl 4-(5-((3-cyanopyridin-4-yl)methoxy)pyrimidin-2-yl)piperazine-1-carboxylate.cif' _audit_creation_method SHELXL-97 _chemical_name_systematic ; tetrahydrofuran-3-yl 4-(5-((3-cyanopyridin-4-yl) methoxy)pyrimidin-2-yl)piperazine-1-carboxylate ; _chemical_name_common ? _chemical_melting_point ? _chemical_formula_moiety 'C20 H22 N6 O4' _chemical_formula_sum 'C20 H22 N6 O4' _chemical_formula_weight 410.44 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 _space_group_name_Hall -P1 loop_ _symmetry_equiv_pos_as_xyz 'x, y, z' '-x, -y, -z' _cell_length_a 5.2885(7) _cell_length_b 11.2227(15) _cell_length_c 16.881(2) _cell_angle_alpha 85.165(6) _cell_angle_beta 83.895(6) _cell_angle_gamma 76.853(5) _cell_volume 968.3(2) _cell_formula_units_Z 2 _cell_measurement_temperature 200(2) _cell_measurement_reflns_used 5121 _cell_measurement_theta_min 2.43 _cell_measurement_theta_max 25.1 _exptl_crystal_description rod _exptl_crystal_colour colourless _exptl_crystal_size_max 0.23 _exptl_crystal_size_mid 0.06 _exptl_crystal_size_min 0.05 _exptl_crystal_density_meas N/A _exptl_crystal_density_diffrn 1.408 _exptl_crystal_density_method 'not measured' _exptl_crystal_F_000 432 _exptl_absorpt_coefficient_mu 0.101 _exptl_absorpt_correction_type empirical _exptl_absorpt_correction_T_min 0.975 _exptl_absorpt_correction_T_max 0.999 _exptl_absorpt_process_details 'Bruker Kappa 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 15781 _diffrn_reflns_av_R_equivalents 0.0337 _diffrn_reflns_av_sigmaI/netI 0.0313 _diffrn_reflns_limit_h_min -6 _diffrn_reflns_limit_h_max 6 _diffrn_reflns_limit_k_min -13 _diffrn_reflns_limit_k_max 13 _diffrn_reflns_limit_l_min -20 _diffrn_reflns_limit_l_max 20 _diffrn_reflns_theta_min 1.87 _diffrn_reflns_theta_max 25.1 _reflns_number_total 3457 _reflns_number_gt 1917 _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^)+(0.0668P)^2^+0.9645P] 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_number_reflns 2493 _refine_ls_number_parameters 271 _refine_ls_number_restraints 0 _refine_ls_R_factor_all 0.0742 _refine_ls_R_factor_gt 0.0549 _refine_ls_wR_factor_ref 0.1478 _refine_ls_wR_factor_gt 0.1402 _refine_ls_goodness_of_fit_ref 1.066 _refine_ls_restrained_S_all 1.066 _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 O10 O 1.2132(4) 0.30299(18) 1.18404(13) 0.0390(6) Uani 1 1 d . . . O25 O 0.1977(5) 0.26066(19) 0.70948(13) 0.0411(6) Uani 1 1 d . . . N17 N 0.6285(5) 0.2418(2) 0.95230(15) 0.0323(7) Uani 1 1 d . . . C14 C 0.7722(6) 0.2570(3) 1.01265(18) 0.0275(8) Uani 1 1 d . . . N20 N 0.3549(5) 0.1980(2) 0.82721(14) 0.0302(7) Uani 1 1 d . . . N13 N 0.8144(5) 0.1660(2) 1.06937(15) 0.0328(7) Uani 1 1 d . . . O24 O 0.2141(5) 0.0649(2) 0.75735(13) 0.0412(6) Uani 1 1 d . . . N15 N 0.8569(5) 0.3614(2) 1.01026(15) 0.0312(7) Uani 1 1 d . . . C11 C 1.0621(6) 0.2806(3) 1.12823(18) 0.0295(8) Uani 1 1 d . . . C9 C 1.2946(7) 0.2059(3) 1.24203(19) 0.0335(8) Uani 1 1 d . . . H9A H 1.3953 0.1322 1.2154 0.040 Uiso 1 1 calc R . . H9B H 1.1409 0.1845 1.2738 0.040 Uiso 1 1 calc R . . C1 C 1.4619(6) 0.2488(3) 1.29545(18) 0.0304(8) Uani 1 1 d . . . C12 C 0.9597(6) 0.1790(3) 1.12703(19) 0.0325(8) Uani 1 1 d . . . H12 H 0.9927 0.1161 1.1683 0.039 Uiso 1 1 calc R . . C16 C 1.0021(6) 0.3707(3) 1.06803(18) 0.0335(8) Uani 1 1 d . . . H16 H 1.0677 0.4428 1.0679 0.040 Uiso 1 1 calc R . . C23 C 0.2513(6) 0.1663(3) 0.76439(19) 0.0312(8) Uani 1 1 d . . . C22 C 0.6000(7) 0.3288(3) 0.88282(19) 0.0361(8) Uani 1 1 d . . . H22A H 0.7572 0.3091 0.8447 0.043 Uiso 1 1 calc R . . H22B H 0.5844 0.4127 0.8998 0.043 Uiso 1 1 calc R . . C19 C 0.3900(7) 0.1126(3) 0.89670(19) 0.0365(9) Uani 1 1 d . . . H19A H 0.4008 0.0284 0.8809 0.044 Uiso 1 1 calc R . . H19B H 0.2382 0.1336 0.9366 0.044 Uiso 1 1 calc R . . C21 C 0.3619(7) 0.3241(3) 0.8420(2) 0.0361(8) Uani 1 1 d . . . H21A H 0.2031 0.3605 0.8759 0.043 Uiso 1 1 calc R . . H21B H 0.3622 0.3736 0.7907 0.043 Uiso 1 1 calc R . . N4 N 1.7902(6) 0.3176(3) 1.39548(17) 0.0460(8) Uani 1 1 d . . . C18 C 0.6323(7) 0.1171(3) 0.9326(2) 0.0383(9) Uani 1 1 d . . . H18A H 0.6486 0.0620 0.9817 0.046 Uiso 1 1 calc R . . H18B H 0.7856 0.0880 0.8946 0.046 Uiso 1 1 calc R . . C3 C 1.6844(7) 0.2214(3) 1.4152(2) 0.0447(9) Uani 1 1 d . . . H3 H 1.7241 0.1752 1.4639 0.054 Uiso 1 1 calc R . . C5 C 1.7286(7) 0.3800(3) 1.3268(2) 0.0418(9) Uani 1 1 d . . . H5 H 1.7990 0.4502 1.3121 0.050 Uiso 1 1 calc R . . C30 C -0.1904(8) 0.2492(3) 0.6548(2) 0.0533(10) Uani 1 1 d . . . H30A H -0.2637 0.2123 0.6137 0.064 Uiso 1 1 calc R . . H30B H -0.2310 0.2094 0.7077 0.064 Uiso 1 1 calc R . . C2 C 1.5180(6) 0.1848(3) 1.36814(19) 0.0341(8) Uani 1 1 d . . . C6 C 1.5700(6) 0.3494(3) 1.2758(2) 0.0368(9) Uani 1 1 d . . . H6 H 1.5354 0.3973 1.2274 0.044 Uiso 1 1 calc R . . N8 N 1.3045(7) 0.0046(3) 1.4197(2) 0.0645(10) Uani 1 1 d . . . C26 C 0.0910(7) 0.2361(3) 0.6372(2) 0.0426(9) Uani 1 1 d . . . H26 H 0.1784 0.1541 0.6171 0.051 Uiso 1 1 calc R . . C27 C 0.1172(7) 0.3438(4) 0.5737(2) 0.0495(10) Uani 1 1 d . . . H27A H 0.2629 0.3814 0.5828 0.059 Uiso 1 1 calc R . . H27B H 0.1422 0.3161 0.5187 0.059 Uiso 1 1 calc R . . C28 C -0.1430(8) 0.4308(3) 0.5893(2) 0.0530(10) Uani 1 1 d . . . H28A H -0.1172 0.5107 0.6037 0.064 Uiso 1 1 calc R . . H28B H -0.2380 0.4448 0.5407 0.064 Uiso 1 1 calc R . . C7 C 1.4019(7) 0.0830(3) 1.3962(2) 0.0417(9) Uani 1 1 d . . . O29 O -0.2915(5) 0.3778(2) 0.65393(17) 0.0629(8) 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 O10 0.0572(16) 0.0289(13) 0.0370(13) 0.0048(10) -0.0223(12) -0.0159(11) O25 0.0544(16) 0.0354(13) 0.0391(14) 0.0058(11) -0.0242(12) -0.0153(11) N17 0.0459(18) 0.0229(14) 0.0326(15) 0.0043(12) -0.0151(13) -0.0140(13) C14 0.0315(19) 0.0224(17) 0.0283(18) -0.0001(15) -0.0015(15) -0.0061(15) N20 0.0390(17) 0.0261(15) 0.0284(15) 0.0029(12) -0.0090(13) -0.0118(12) N13 0.0444(17) 0.0249(15) 0.0322(16) 0.0041(13) -0.0122(14) -0.0123(13) O24 0.0582(16) 0.0304(14) 0.0395(14) -0.0002(11) -0.0144(12) -0.0150(12) N15 0.0425(17) 0.0229(15) 0.0307(15) 0.0027(12) -0.0086(13) -0.0115(13) C11 0.038(2) 0.0269(18) 0.0258(18) -0.0034(15) -0.0064(15) -0.0104(15) C9 0.043(2) 0.0247(18) 0.0335(19) 0.0001(15) -0.0123(16) -0.0061(15) C1 0.0334(19) 0.0274(18) 0.0269(18) -0.0071(15) -0.0018(15) 0.0024(15) C12 0.045(2) 0.0248(18) 0.0280(18) 0.0018(14) -0.0071(16) -0.0073(16) C16 0.047(2) 0.0245(18) 0.0311(19) -0.0014(15) -0.0085(17) -0.0114(16) C23 0.0289(19) 0.033(2) 0.0316(19) 0.0010(16) -0.0042(15) -0.0064(16) C22 0.043(2) 0.0298(19) 0.038(2) 0.0075(16) -0.0136(17) -0.0136(16) C19 0.050(2) 0.0299(19) 0.0335(19) 0.0068(15) -0.0122(17) -0.0167(17) C21 0.050(2) 0.0233(18) 0.037(2) 0.0023(14) -0.0138(17) -0.0087(16) N4 0.0471(19) 0.0513(19) 0.0429(19) -0.0065(16) -0.0155(15) -0.0110(16) C18 0.051(2) 0.0242(18) 0.044(2) 0.0030(15) -0.0171(18) -0.0120(16) C3 0.049(2) 0.050(2) 0.035(2) -0.0007(17) -0.0114(18) -0.0067(19) C5 0.044(2) 0.038(2) 0.046(2) -0.0093(18) -0.0084(18) -0.0084(17) C30 0.061(3) 0.045(2) 0.055(2) -0.0015(19) -0.003(2) -0.015(2) C2 0.037(2) 0.0332(19) 0.0304(19) -0.0035(15) -0.0030(16) -0.0041(16) C6 0.044(2) 0.0291(19) 0.036(2) -0.0035(15) -0.0069(17) -0.0040(17) N8 0.079(3) 0.061(2) 0.058(2) 0.0131(19) -0.0140(19) -0.027(2) C26 0.046(2) 0.036(2) 0.049(2) 0.0017(17) -0.0233(18) -0.0088(17) C27 0.048(2) 0.073(3) 0.031(2) 0.0001(19) -0.0103(18) -0.018(2) C28 0.064(3) 0.046(2) 0.050(2) 0.0047(19) -0.016(2) -0.013(2) C7 0.050(2) 0.044(2) 0.030(2) 0.0045(17) -0.0111(18) -0.005(2) O29 0.0600(18) 0.0510(17) 0.0735(19) 0.0066(14) -0.0008(15) -0.0098(14) _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 O10 C11 1.372(3) . ? O10 C9 1.424(4) . ? O25 C23 1.347(4) . ? O25 C26 1.469(4) . ? N17 C14 1.377(4) . ? N17 C22 1.459(4) . ? N17 C18 1.461(4) . ? C14 N13 1.336(4) . ? C14 N15 1.343(4) . ? N20 C23 1.351(4) . ? N20 C19 1.451(4) . ? N20 C21 1.467(4) . ? N13 C12 1.339(4) . ? O24 C23 1.216(4) . ? N15 C16 1.328(4) . ? C11 C12 1.371(4) . ? C11 C16 1.381(4) . ? C9 C1 1.505(4) . ? C9 H9A 0.9900 . ? C9 H9B 0.9900 . ? C1 C6 1.379(4) . ? C1 C2 1.394(4) . ? C12 H12 0.9500 . ? C16 H16 0.9500 . ? C22 C21 1.511(4) . ? C22 H22A 0.9900 . ? C22 H22B 0.9900 . ? C19 C18 1.488(4) . ? C19 H19A 0.9900 . ? C19 H19B 0.9900 . ? C21 H21A 0.9900 . ? C21 H21B 0.9900 . ? N4 C3 1.328(5) . ? N4 C5 1.334(4) . ? C18 H18A 0.9900 . ? C18 H18B 0.9900 . ? C3 C2 1.394(5) . ? C3 H3 0.9500 . ? C5 C6 1.377(4) . ? C5 H5 0.9500 . ? C30 O29 1.420(4) . ? C30 C26 1.462(5) . ? C30 H30A 0.9900 . ? C30 H30B 0.9900 . ? C2 C7 1.440(5) . ? C6 H6 0.9500 . ? N8 C7 1.141(4) . ? C26 C27 1.566(5) . ? C26 H26 1.0000 . ? C27 C28 1.508(5) . ? C27 H27A 0.9900 . ? C27 H27B 0.9900 . ? C28 O29 1.443(5) . ? C28 H28A 0.9900 . ? C28 H28B 0.9900 . ? 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 C11 O10 C9 116.8(2) . . ? C23 O25 C26 116.6(2) . . ? C14 N17 C22 120.7(2) . . ? C14 N17 C18 118.2(2) . . ? C22 N17 C18 112.4(2) . . ? N13 C14 N15 125.3(3) . . ? N13 C14 N17 116.9(2) . . ? N15 C14 N17 117.8(3) . . ? C23 N20 C19 118.6(2) . . ? C23 N20 C21 124.4(3) . . ? C19 N20 C21 114.3(2) . . ? C14 N13 C12 117.0(3) . . ? C16 N15 C14 116.0(3) . . ? C12 C11 O10 126.7(3) . . ? C12 C11 C16 116.6(3) . . ? O10 C11 C16 116.7(3) . . ? O10 C9 C1 107.8(2) . . ? O10 C9 H9A 110.1 . . ? C1 C9 H9A 110.1 . . ? O10 C9 H9B 110.1 . . ? C1 C9 H9B 110.1 . . ? H9A C9 H9B 108.5 . . ? C6 C1 C2 116.8(3) . . ? C6 C1 C9 123.2(3) . . ? C2 C1 C9 120.0(3) . . ? N13 C12 C11 121.9(3) . . ? N13 C12 H12 119.0 . . ? C11 C12 H12 119.0 . . ? N15 C16 C11 123.1(3) . . ? N15 C16 H16 118.5 . . ? C11 C16 H16 118.5 . . ? O24 C23 O25 123.8(3) . . ? O24 C23 N20 124.5(3) . . ? O25 C23 N20 111.7(3) . . ? N17 C22 C21 110.9(3) . . ? N17 C22 H22A 109.5 . . ? C21 C22 H22A 109.5 . . ? N17 C22 H22B 109.5 . . ? C21 C22 H22B 109.5 . . ? H22A C22 H22B 108.1 . . ? N20 C19 C18 110.4(3) . . ? N20 C19 H19A 109.6 . . ? C18 C19 H19A 109.6 . . ? N20 C19 H19B 109.6 . . ? C18 C19 H19B 109.6 . . ? H19A C19 H19B 108.1 . . ? N20 C21 C22 111.7(3) . . ? N20 C21 H21A 109.3 . . ? C22 C21 H21A 109.3 . . ? N20 C21 H21B 109.3 . . ? C22 C21 H21B 109.3 . . ? H21A C21 H21B 108.0 . . ? C3 N4 C5 116.3(3) . . ? N17 C18 C19 110.8(3) . . ? N17 C18 H18A 109.5 . . ? C19 C18 H18A 109.5 . . ? N17 C18 H18B 109.5 . . ? C19 C18 H18B 109.5 . . ? H18A C18 H18B 108.1 . . ? N4 C3 C2 123.3(3) . . ? N4 C3 H3 118.4 . . ? C2 C3 H3 118.4 . . ? N4 C5 C6 124.4(3) . . ? N4 C5 H5 117.8 . . ? C6 C5 H5 117.8 . . ? O29 C30 C26 104.5(3) . . ? O29 C30 H30A 110.9 . . ? C26 C30 H30A 110.9 . . ? O29 C30 H30B 110.9 . . ? C26 C30 H30B 110.9 . . ? H30A C30 H30B 108.9 . . ? C1 C2 C3 119.6(3) . . ? C1 C2 C7 120.9(3) . . ? C3 C2 C7 119.5(3) . . ? C5 C6 C1 119.5(3) . . ? C5 C6 H6 120.2 . . ? C1 C6 H6 120.2 . . ? C30 C26 O25 108.0(3) . . ? C30 C26 C27 104.2(3) . . ? O25 C26 C27 107.2(3) . . ? C30 C26 H26 112.3 . . ? O25 C26 H26 112.3 . . ? C27 C26 H26 112.3 . . ? C28 C27 C26 101.2(3) . . ? C28 C27 H27A 111.5 . . ? C26 C27 H27A 111.5 . . ? C28 C27 H27B 111.5 . . ? C26 C27 H27B 111.5 . . ? H27A C27 H27B 109.3 . . ? O29 C28 C27 108.6(3) . . ? O29 C28 H28A 110.0 . . ? C27 C28 H28A 110.0 . . ? O29 C28 H28B 110.0 . . ? C27 C28 H28B 110.0 . . ? H28A C28 H28B 108.4 . . ? N8 C7 C2 178.0(4) . . ? C30 O29 C28 106.1(3) . . ? _diffrn_measured_fraction_theta_max 0.981 _diffrn_reflns_theta_full 25.1 _diffrn_measured_fraction_theta_full 0.981 _refine_diff_density_max 0.345 _refine_diff_density_min -0.234 _refine_diff_density_rms 0.049