Rapid synthesis of pomalidomide-conjugates for the development of protein degrader libraries
Brownsey, Duncan K.; Rowley, Ben C.; Gorobets, Evgueni; Gelfand, Benjamin S.; Derksen, Darren J.; Chemical Science 12 (2021) 4519–4525; doi:10.1039/D0SC05442A

data_1560279
_publ_section_title
;
 Rapid synthesis of pomalidomide-conjugates for the development of protein
 degrader libraries
;
_journal_issue                   12
_journal_name_full               'Chemical Science'
_journal_page_first              4519
_journal_page_last               4525
_journal_paper_doi               10.1039/D0SC05442A
_journal_volume                  12
_journal_year                    2021
_chemical_formula_moiety
'C15 H15 N3 O4, 0.377(C4 H8 O2), 0.123(C6 H14)'
_chemical_formula_sum            'C17.24 H19.73 N3 O4.75'
_chemical_formula_weight         345.09
_space_group_crystal_system      triclinic
_space_group_IT_number           2
_space_group_name_Hall           '-P 1'
_space_group_name_H-M_alt        'P -1'
_atom_sites_solution_hydrogens   mixed
_atom_sites_solution_primary     dual
_audit_creation_date             2019-11-06
_audit_creation_method
;
Olex2 1.2
(compiled 2018.05.29 svn.r3508 for OlexSys, GUI svn.r5506)
;
_audit_update_record
;
2020-09-24 deposited with the CCDC.	2021-02-02 downloaded from the CCDC.
;
_cell_angle_alpha                92.523(2)
_cell_angle_beta                 106.963(2)
_cell_angle_gamma                100.062(2)
_cell_formula_units_Z            2
_cell_length_a                   7.2814(2)
_cell_length_b                   10.1224(2)
_cell_length_c                   12.1780(3)
_cell_measurement_reflns_used    9480
_cell_measurement_temperature    173(2)
_cell_measurement_theta_max      68.208
_cell_measurement_theta_min      3.814
_cell_volume                     841.02(4)
_computing_cell_refinement       'SAINT v8.37A (Bruker, 2015)'
_computing_data_reduction        'SAINT v8.37A (Bruker, 2015)'
_computing_molecular_graphics    'Olex2 (Dolomanov et al., 2009)'
_computing_publication_material  'Olex2 (Dolomanov et al., 2009)'
_computing_structure_refinement  'ShelXL (Sheldrick, 2015)'
_computing_structure_solution    'ShelXT (Sheldrick, 2015)'
_diffrn_ambient_temperature      173.0
_diffrn_measured_fraction_theta_full 0.998
_diffrn_measured_fraction_theta_max 0.997
_diffrn_measurement_device_type  'Bruker APEX-II CCD'
_diffrn_measurement_method       '\f and \w scans'
_diffrn_radiation_type           CuK\a
_diffrn_radiation_wavelength     1.54178
_diffrn_reflns_av_R_equivalents  0.0315
_diffrn_reflns_av_unetI/netI     0.0109
_diffrn_reflns_Laue_measured_fraction_full 0.998
_diffrn_reflns_Laue_measured_fraction_max 0.997
_diffrn_reflns_limit_h_max       8
_diffrn_reflns_limit_h_min       -8
_diffrn_reflns_limit_k_max       12
_diffrn_reflns_limit_k_min       -12
_diffrn_reflns_limit_l_max       14
_diffrn_reflns_limit_l_min       -14
_diffrn_reflns_number            3077
_diffrn_reflns_point_group_measured_fraction_full 0.998
_diffrn_reflns_point_group_measured_fraction_max 0.997
_diffrn_reflns_theta_full        67.679
_diffrn_reflns_theta_max         68.282
_diffrn_reflns_theta_min         3.814
_diffrn_standards_number         0
_exptl_absorpt_coefficient_mu    0.839
_exptl_absorpt_correction_T_max  0.7531
_exptl_absorpt_correction_T_min  0.6985
_exptl_absorpt_correction_type   multi-scan
_exptl_absorpt_process_details
'SADABS-2016/2 (Bruker,2016/2) was used for absorption correction. wR2(int) was 0.0679 before and 0.0366 after correction. The Ratio of minimum to maximum transmission is 0.9275. The \l/2 correction factor is Not present.'
_exptl_crystal_colour            yellow
_exptl_crystal_colour_primary    yellow
_exptl_crystal_density_diffrn    1.363
_exptl_crystal_description       block
_exptl_crystal_F_000             364.5
_exptl_crystal_size_max          0.341
_exptl_crystal_size_mid          0.263
_exptl_crystal_size_min          0.206
_refine_diff_density_max         0.309
_refine_diff_density_min         -0.332
_refine_diff_density_rms         0.075
_refine_ls_extinction_method     none
_refine_ls_goodness_of_fit_ref   1.068
_refine_ls_hydrogen_treatment    mixed
_refine_ls_matrix_type           full
_refine_ls_number_parameters     323
_refine_ls_number_reflns         3077
_refine_ls_number_restraints     286
_refine_ls_restrained_S_all      1.031
_refine_ls_R_factor_all          0.0490
_refine_ls_R_factor_gt           0.0482
_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^)+(0.0836P)^2^+0.4639P] where P=(Fo^2^+2Fc^2^)/3'
_refine_ls_weighting_scheme      calc
_refine_ls_wR_factor_gt          0.1237
_refine_ls_wR_factor_ref         0.1247
_reflns_Friedel_coverage         0.000
_reflns_number_gt                2989
_reflns_number_total             3077
_reflns_threshold_expression     'I > 2\s(I)'
_cod_data_source_file            d0sc05442a2.cif
_cod_data_source_block           db-3-281
_cod_depositor_comments          'Adding full bibliography for 1560279.cif.'
_cod_database_code               1560279
_shelx_shelxl_version_number     2018/3
_shelx_estimated_absorpt_t_max   0.846
_shelx_estimated_absorpt_t_min   0.763
_olex2_refinement_description
;
1. Fixed Uiso
 At 1.2 times of:
  All C(H) groups, All C(H,H) groups, All N(H) groups
 At 1.5 times of:
  All C(H,H,H) groups
2. Restrained distances
 C6T-C2S
 1.51 with sigma of 0.02
 O1S-C2S
 1.2 with sigma of 0.02
 O2S-C2S
 1.35 with sigma of 0.02
 O2S-C3S
 1.45 with sigma of 0.02
 C4S-C3S
 1.52 with sigma of 0.02
 C1T-C2T = C2T-C3T = C3T-C4T = C4T-C5T = C5T-C6T
 1.53 with sigma of 0.02
 C1T-C5T = C3T-C6T
 -2.75 with sigma of 0.02
 C1T-C3T = C2T-C4T = C3T-C5T = C4T-C6T
 2.54 with sigma of 0.04
 O1S-C6T
 2.25 with sigma of 0.04
 C6T-O2S
 2.52 with sigma of 0.04
 O2S-O1S
 2.25 with sigma of 0.04
 C2S-C3S
 2.37 with sigma of 0.04
 O2S-C4S
 2.46 with sigma of 0.04
3. Restrained planarity
 O1S, O2S, C6T, C2S
 with sigma of 0.1
4. Uiso/Uaniso restraints and constraints
C2T \\sim C3T \\sim C4T \\sim C1T \\sim C5T \\sim C6T \\sim C4S \\sim O1S \\sim
C2S \\sim O2S \\sim C1SA \\sim C3S: within 2.6A with sigma of 0.03 and sigma
for terminal atoms of 0.06
5. Rigid body (RIGU) restrains
 C5T, C3T, C2T, C4T, C1T, C6T
 with sigma for 1-2 distances of 0.004 and sigma for 1-3 distances of 0.004
6. Others
 Sof(C3T)=Sof(H3TA)=Sof(H3TB)=Sof(C6T)=Sof(H6TA)=Sof(H6TB)=Sof(H6TC)=Sof(C1T)=
 Sof(H1TA)=Sof(H1TB)=Sof(H1TC)=Sof(C2T)=Sof(H2TA)=Sof(H2TB)=Sof(C4T)=Sof(H4TA)=
 Sof(H4TB)=Sof(C5T)=Sof(H5TA)=Sof(H5TB)=0.5*(1-FVAR(2))
 Sof(O1S)=Sof(O2S)=Sof(C2S)=Sof(C3S)=Sof(H3SA)=Sof(H3SB)=Sof(C4S)=Sof(H4SA)=
 Sof(H4SB)=Sof(H4SC)=Sof(C1SA)=Sof(H1SA)=Sof(H1SB)=Sof(H1SC)=0.5*FVAR(2)
 Sof(C15)=Sof(H15A)=Sof(H15B)=FVAR(2)
7.a Ternary CH refined with riding coordinates:
 C11(H11)
7.b Secondary CH2 refined with riding coordinates:
 C14(H14A,H14B), C15(H15A,H15B), C3T(H3TA,H3TB), C2T(H2TA,H2TB), C3S(H3SA,
 H3SB), C4T(H4TA,H4TB), C5T(H5TA,H5TB)
7.c Aromatic/amide H refined with riding coordinates:
 N3(H3), C4(H4), C5(H5), C6(H6)
7.d Idealised Me refined as rotating group:
 C1(H1A,H1B,H1C), C6T(H6TA,H6TB,H6TC), C1T(H1TA,H1TB,H1TC), C4S(H4SA,H4SB,
 H4SC), C1SA(H1SA,H1SB,H1SC)
;
_shelx_res_checksum              54748
_shelx_hkl_checksum              63504
_olex2_submission_special_instructions 'No special instructions were received'