research communications
of a 1:1 of the anticancer drug gefitinib with azelaic acid
aPhysical and Materials Chemistry Division, CSIR-National Chemical Laboratory, Pune-411008, India, and bAcademy of Scientific and Innovative Research (AcSIR), Ghaziabad, Uttar Pradesh-201002, India
*Correspondence e-mail: rg.gonnade@ncl.res.in
In the title 22H24ClFN4O3·C9H16O4, gefitinib (GTB; quinazolin-4-amine) co-crystallizes with azelaic acid (AA; nonanedioic acid). The has the monoclinic P21/n centrosymmetric containing one molecule each of GTB and AA in the A structure overlay of the GTB molecule in the with that of its most stable polymorph revealed a significant difference in the conformation of the morpholine moiety. The significant deviation in the conformation of one of the acidic groups of azelaic acid from its usual linear chain structure could be due to the encapsulation of one acidic group in the pocket formed between the two pincers of GTB namely, the morpholine and phenyl moieties. Both GTB and AA molecules form N—H⋯O, O—H⋯N, C—H⋯O hydrogen bonds with C—H⋯F close contacts along with off-stacked aromatic π–π interactions between the GTB molecules.
CKeywords: anticancer; azelaic acid; co-crystal; crystal structure; gefitinib; hydrogen bond; π–π interactions.
CCDC reference: 2002536
1. Chemical context
Gefitinib (GTB, Iressa) is an orally administered chemotherapy treatment drug that inhibits tyrosine kinase (an enzyme that transports phosphates from ATP to the tyrosine residue of a protein) (Kobayashi & Hagiwara, 2013) for non-small-cell lung cancer (NSCLC), pancreatic cancer, breast cancer and several other types of cancer. Two polymorphs of GTB have been reported from our group previously, both of which crystallized in the triclinic P (Thorat et al., 2014). The drug–drug of GTB with furosemide has also been published (Thorat et al., 2015). Some of the major side effects of GTB include rash, acne and dry skin. To overcome these after effects, there is a need for combination drug therapy. In this regard, we chose azelaic acid (AA), which is used for treating mild to moderate acne, both comedonal acne and inflammatory acne (Fitton & Goa, 1991). Furthermore, GTB is also known to form co-crystals with aliphatic dicarboxylic acids through N—H⋯O and O—H⋯N hydrogen bonds (Gonnade, 2015). AA is an aliphatic dicarboxylic acid (heptane-dicarboxylic acid), having seven CH2 groups in the alkyl chain. Two polymorphs of AA have been reported earlier, the α form is monoclinic, P21/c (Caspari, 1928; Housty & Hospital, 1967) and the β form crystallizes in the monoclinic C2/c (Housty & Hospital, 1967). Both GTB and AA are non-volatile solids at room temperature and their respective melting points are in the ranges 192–195 K and 378–381 K.
2. Structural commentary
The title compound GTB–AA (1:1) crystallizes in the monoclinic P21/n centrosymmetric containing one molecule of each in the (Fig. 1, Table 1) (CCDC reference No. 2002536). The halophenyl ring of GTB and the alkyl (–CH2–) chain of AA exhibit positional disorder over two conformations, due to the around the N—C and C—C single bonds, respectively (Fig. 2a and 2b). A structure overlay of the GTB molecule based on a fit of the quinazoline groups in the structure with that of its stable polymorph [the of the stable polymorph of GTB was retrieved from the Cambridge Structural Database (Groom et al., 2016), refcode: FARRUM02; Thorat et al., 2014] revealed a considerable difference in the orientation of the morpholine moiety [torsion angles, C19—C20—C21—N22 = 54.0 (2)° for GTB in the while the corresponding torsion angle in the stable polymorph of GTB is 74.3 (2)°] because of the conformationally flexible –CH2– spacer (Fig. 3). Whereas the conformation of the phenyl group showed a slight difference with a dihedral angle of 14.1 (2)° (the angular difference between the planes of halophenyl ring of both structures). The quinazoline, morpholine and phenyl moieties of GTB have acquired a roughly planar geometry in the [torsion angle C12—C5—C19—N22 = 14.4 (2)°, only the N atom of morpholine is considered and not the full fragment], whereas in the stable polymorph of GTB, the morpholine moiety deviates significantly from the plane [the corresponding torsion angle is −75.7 (2)°]. The approximate planarity of the phenyl, quinazoline and morpholine (only N atom considered) moieties of GTB in the seems to be due to the engagement of these groups with one of the acid groups of AA via N—H⋯O and O—H⋯N hydrogen bonds. The conformation of this acid group of AA shows a considerable departure from its usual linear chain structure due to an acquired bend at the 7th carbon atom (C39) [torsional difference 105.15 (19)° from the other end of the acid group, torsion angles, C32—C33—C34—C35 = −174.15 (19)° and C37—C38—C39—C40 = −69.0 (3)°]. The conformational bend could be due to the inclusion of the acid moiety in the pocket formed between the morpholine and phenyl moieties (which have a molecular clip-like geometry) of GTB and the subsequent involvement of the carbonyl and hydroxyl groups of the included acid moiety in the formation of the N—H⋯O and O—H⋯N hydrogen bonds with the distantly located amine N—H and the N atom of the morpholine moiety, respectively (Fig. 4). The other acid group of AA forms an O—H⋯N hydrogen bond with the N atom of the quinazoline moiety.
3. Supramolecular features
The closely associated molecules of GTB and AA (through an O30—H30⋯N1 hydrogen bond) constitute a `zero-dimensional' supramolecular motif wherein a carboxyl OH of AA donates its H atom to the quinazoline N atom (Fig. 1). Adjacent n-glide symmetry-related `zero-dimensional' motifs are linked firmly along the ac diagonal by strong N—H⋯O, O—H⋯N and C—H⋯O hydrogen bonds to generate a one-dimensional linear chain structure (Fig. 5, Table 1). The cavity created by GTB as a result of its `molecular clip'-like geometry encapsulates the other carboxylic acid group of AA. In the cavity, the carboxyl oxygen (O42) accepts the H atoms from amine N11—H11 and C5—H5 to form N11—H11⋯O42i and C5—H5⋯O42i hydrogen bonds (symmetry operations are given in the footnote to Table 1). In turn, the carboxyl OH (O41—H41) of AA donates its H atom to the morpholine N22 to make a O41—H41⋯N22ii hydrogen bond. The neighbouring antiparallel chains are stitched centrosymmetrically through C2—H2⋯F1iii contacts and C29—H29B⋯O18iv hydrogen bonds to form a two-dimensional layered assembly in the ac plane (Fig. 6). A view of the molecular packing down the b axis reveals the stacking of the 2D layers by aromatic π–π interactions between centrosymmetrically related quinazoline rings [interplanar spacing, 3.396 (13) Å] (Cg2⋯Cg2vii, Cg2⋯Cg3vii, Cg2⋯Cg3viii and Cg3⋯Cg3vii; Cg2 is the centroid of the N1/C2/N3/C4/C10/C9 ring and Cg3 is the centroid of the C5–C10 ring, Table 1). Molecules between the two layers are also connected by C27—H27B⋯F1vi contacts and C23—H23B⋯O25v, C21—H21B⋯O31vii, C13—H13⋯O30viii and C39—H39A⋯O30ix hydrogen bonds to generate the three-dimensional packing (Fig. 7, Table 1).
4. Database survey
A search for the title et al., 2016) found no hits. However, searches for GTB and AA gave 8 and 35 hits, respectively. A search for the GTB molecule showed that the amine N—H moiety is involved in N—H⋯O hydrogen-bond formation either with the morpholine oxygen in both of its polymorphs (Thorat et al., 2014) or with the water oxygen (Gilday et al., 2005; Thorat et al., 2015). For the AA search, 17 hits were found only for its two polymorphs (refcodes: AZELAC01–AZELAC17) wherein the AA molecules are found to be associated by the conventional dimeric O—H⋯O hydrogen bonds (Caspari, 1928; Housty & Hospital, 1967). The remaining hits were for either co-crystals with (Tothadi & Phadkule, 2019; Thompson et al., 2011; Karki et al., 2009), pyridines (Braga et al., 2010; Martins et al., 2016; Krueger et al., 2017) or complexes with Ni (Zhao et al., 2012), Fe (Braga et al., 2006) or Ba (Grzesiak et al., 2012).
in the Cambridge Structural Database (CSD, Version 5.41, the update of March 2020; Groom5. Synthesis and crystallization
Co-crystallization was carried out using equimolar amounts of commercial samples of GTB and AA by grinding combined with a slow evaporation method. The grinding experiment was performed manually using a mortar and pestle. The 1:1 stoichiometric molar ratio of GTB (45 mg, 0.1 mmol) and AA (19 mg, 0.1 mmol) was ground for about 15 minutes using dry (neat) grinding. The ground sample was dissolved in n-butanol and heated for ∼10 minutes to ensure the complete dissolution of the sample. The solution was filtered into the crystallization flask to remove the impurity and undissolved compound, and the solution was allowed to evaporate at room temperature (298–300 K). Elongated needle-shaped colourless crystals were obtained after 1–2 h. The melting point of the obtained was 398–399 K.
6. Refinement
Crystal data, data collection and structure . All H atoms (except for hydroxy and amine H atoms) were placed in geometrically idealized positions, with C—H = 0.95 Å for phenyl H atoms, C—H = 0.99 Å for methylene H atoms and C—H = 0.98 Å for methyl H atoms. They were constrained to ride on their parent atoms, with Uiso(H) = 1.2Ueq(C) for phenyl and methylene, and 1.5Ueq(C) for methyl groups. The O- (O30) and N-bound H atoms were located in difference-Fourier maps and refined isotropically. However, the O-bound H atom was placed in a geometrically idealized positions using HFIX 148 as the O—H distance was longer when refined with its located position in the difference-Fourier map. It was constrained to ride on its parent atom (O41), with Uiso(H) = 1.5Ueq(O). The long O—H distance could be due to its involvement in the strong O—H⋯N hydrogen-bond formation with N22. The difference Fo–Fc map shows that the H atom could be residing part of the time on O41 and part of the time on N22.
details are summarized in Table 2
|
Supporting information
CCDC reference: 2002536
https://doi.org/10.1107/S2056989020006623/pk2627sup1.cif
contains datablock I. DOI:Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989020006623/pk2627Isup2.hkl
Supporting information file. DOI: https://doi.org/10.1107/S2056989020006623/pk2627Isup3.cml
Data collection: APEX3 (Bruker, 2016); cell
SAINT-Plus (Bruker, 2016); data reduction: SAINT-Plus (Bruker, 2016); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014/7 (Sheldrick, 2015); molecular graphics: ORTEP-3 (Farrugia, 2012), Mercury 2020.1 (Macrae et al., 2020); software used to prepare material for publication: SHELXTL (Sheldrick, 2008), PLATON (Spek, 2020), publCIF (Westrip, 2010).C22H24ClFN4O3·C9H16O4 | F(000) = 1344 |
Mr = 635.12 | Dx = 1.385 Mg m−3 |
Monoclinic, P21/n | Mo Kα radiation, λ = 0.71073 Å |
a = 10.7716 (10) Å | Cell parameters from 9964 reflections |
b = 7.4153 (13) Å | θ = 2.5–36.4° |
c = 38.175 (7) Å | µ = 0.19 mm−1 |
β = 92.311 (5)° | T = 100 K |
V = 3046.7 (8) Å3 | Thin Needle, colourless |
Z = 4 | 0.28 × 0.19 × 0.04 mm |
Bruker D8 VENTURE Kappa Duo PHOTON II CPAD diffractometer | 7338 independent reflections |
Radiation source: micro-focus sealed tube, Incoatech IµS HB | 5413 reflections with I > 2σ(I) |
Multilayer mirrors monochromator | Rint = 0.162 |
Detector resolution: 7.39 pixels mm-1 | θmax = 28.0°, θmin = 2.4° |
φ and ω scans | h = −14→14 |
Absorption correction: multi-scan (SADABS; Bruker, 2016) | k = −9→9 |
Tmin = 0.950, Tmax = 0.993 | l = −50→50 |
92337 measured reflections |
Refinement on F2 | 126 restraints |
Least-squares matrix: full | Hydrogen site location: mixed |
R[F2 > 2σ(F2)] = 0.045 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.110 | w = 1/[σ2(Fo2) + (0.0458P)2 + 1.2854P] where P = (Fo2 + 2Fc2)/3 |
S = 1.02 | (Δ/σ)max = 0.001 |
7338 reflections | Δρmax = 0.37 e Å−3 |
473 parameters | Δρmin = −0.32 e Å−3 |
Geometry. 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. |
x | y | z | Uiso*/Ueq | Occ. (<1) | |
N1 | 0.47579 (12) | 0.8204 (2) | 0.55135 (4) | 0.0133 (3) | |
C2 | 0.36066 (14) | 0.8699 (2) | 0.54311 (5) | 0.0148 (4) | |
H2 | 0.3136 | 0.9129 | 0.5619 | 0.018* | |
N3 | 0.30169 (12) | 0.8670 (2) | 0.51143 (4) | 0.0144 (3) | |
C4 | 0.36644 (14) | 0.8072 (2) | 0.48478 (4) | 0.0113 (3) | |
C5 | 0.56600 (14) | 0.6768 (2) | 0.46286 (4) | 0.0111 (3) | |
H5 | 0.5318 | 0.6671 | 0.4396 | 0.013* | |
C6 | 0.68614 (14) | 0.6245 (2) | 0.47037 (4) | 0.0109 (3) | |
C7 | 0.73862 (13) | 0.6397 (2) | 0.50508 (4) | 0.0116 (3) | |
C8 | 0.66847 (14) | 0.7041 (2) | 0.53159 (4) | 0.0117 (3) | |
H8 | 0.7033 | 0.7129 | 0.5548 | 0.014* | |
C9 | 0.54411 (14) | 0.7573 (2) | 0.52418 (4) | 0.0115 (3) | |
C10 | 0.49287 (14) | 0.7456 (2) | 0.48986 (4) | 0.0108 (3) | |
N11 | 0.31164 (12) | 0.8064 (2) | 0.45205 (4) | 0.0129 (3) | |
H11 | 0.3547 (17) | 0.784 (3) | 0.4348 (5) | 0.018 (5)* | |
C12 | 0.1907 (2) | 0.8603 (3) | 0.44138 (7) | 0.0084 (5) | 0.915 (7) |
C13 | 0.1724 (2) | 0.9202 (3) | 0.40659 (7) | 0.0103 (5) | 0.915 (7) |
H13 | 0.2409 | 0.9296 | 0.3918 | 0.012* | 0.915 (7) |
C14 | 0.0538 (2) | 0.9655 (3) | 0.39399 (6) | 0.0126 (5) | 0.915 (7) |
C15 | −0.0455 (2) | 0.9516 (5) | 0.41588 (7) | 0.0121 (6) | 0.915 (7) |
C16 | −0.0294 (2) | 0.8968 (3) | 0.45021 (8) | 0.0114 (5) | 0.915 (7) |
H16 | −0.0984 | 0.8906 | 0.4649 | 0.014* | 0.915 (7) |
C17 | 0.0893 (2) | 0.8503 (3) | 0.46331 (6) | 0.0103 (5) | 0.915 (7) |
H17 | 0.1014 | 0.8120 | 0.4870 | 0.012* | 0.915 (7) |
Cl1 | 0.03309 (6) | 1.0446 (3) | 0.35140 (2) | 0.0239 (3) | 0.915 (7) |
F1 | −0.1656 (19) | 0.981 (6) | 0.4079 (9) | 0.0207 (5) | 0.085 (7) |
C12' | 0.165 (3) | 0.869 (4) | 0.4489 (8) | 0.0084 (5) | 0.085 (7) |
C13' | 0.180 (3) | 0.904 (3) | 0.4171 (9) | 0.0103 (5) | 0.085 (7) |
H13' | 0.2607 | 0.8997 | 0.4082 | 0.012* | 0.085 (7) |
C14' | 0.088 (3) | 0.944 (3) | 0.3964 (9) | 0.0126 (5) | 0.085 (7) |
C15' | −0.034 (2) | 0.956 (6) | 0.4083 (11) | 0.0121 (6) | 0.085 (7) |
C16' | −0.038 (3) | 0.918 (4) | 0.4387 (10) | 0.0114 (5) | 0.085 (7) |
H16' | −0.1167 | 0.9307 | 0.4489 | 0.014* | 0.085 (7) |
C17' | 0.051 (3) | 0.863 (4) | 0.4588 (8) | 0.0103 (5) | 0.085 (7) |
H17' | 0.0340 | 0.8158 | 0.4813 | 0.012* | 0.085 (7) |
Cl1' | 0.0350 (8) | 0.977 (3) | 0.3483 (3) | 0.0239 (3) | 0.085 (7) |
F1' | −0.15929 (17) | 0.9946 (5) | 0.40135 (6) | 0.0207 (5) | 0.915 (7) |
O18 | 0.76536 (10) | 0.55753 (17) | 0.44664 (3) | 0.0146 (3) | |
C19 | 0.71844 (14) | 0.5374 (3) | 0.41114 (4) | 0.0140 (3) | |
H19A | 0.6840 | 0.6529 | 0.4021 | 0.017* | |
H19B | 0.6523 | 0.4447 | 0.4096 | 0.017* | |
C20 | 0.82895 (15) | 0.4798 (3) | 0.39031 (5) | 0.0167 (4) | |
H20A | 0.8851 | 0.5844 | 0.3879 | 0.020* | |
H20B | 0.8755 | 0.3852 | 0.4036 | 0.020* | |
C21 | 0.79365 (15) | 0.4080 (2) | 0.35412 (5) | 0.0162 (4) | |
H21A | 0.8708 | 0.3825 | 0.3418 | 0.019* | |
H21B | 0.7492 | 0.2923 | 0.3567 | 0.019* | |
N22 | 0.71453 (13) | 0.5303 (2) | 0.33193 (4) | 0.0170 (3) | |
C23 | 0.69993 (18) | 0.4460 (3) | 0.29657 (5) | 0.0252 (4) | |
H23A | 0.6568 | 0.3287 | 0.2985 | 0.030* | |
H23B | 0.7829 | 0.4231 | 0.2873 | 0.030* | |
C24 | 0.6265 (2) | 0.5668 (4) | 0.27160 (6) | 0.0392 (6) | |
H24A | 0.6195 | 0.5091 | 0.2482 | 0.047* | |
H24B | 0.5415 | 0.5827 | 0.2801 | 0.047* | |
O25 | 0.68388 (16) | 0.7383 (3) | 0.26857 (4) | 0.0467 (5) | |
C26 | 0.6932 (2) | 0.8207 (3) | 0.30238 (6) | 0.0426 (6) | |
H26A | 0.6088 | 0.8361 | 0.3113 | 0.051* | |
H26B | 0.7306 | 0.9419 | 0.3002 | 0.051* | |
C27 | 0.77011 (19) | 0.7117 (3) | 0.32823 (5) | 0.0261 (4) | |
H27A | 0.8558 | 0.7002 | 0.3201 | 0.031* | |
H27B | 0.7740 | 0.7734 | 0.3512 | 0.031* | |
O28 | 0.85921 (10) | 0.58683 (17) | 0.50862 (3) | 0.0148 (3) | |
C29 | 0.92077 (14) | 0.6098 (3) | 0.54230 (5) | 0.0162 (4) | |
H29A | 0.9179 | 0.7371 | 0.5491 | 0.024* | |
H29B | 1.0075 | 0.5712 | 0.5412 | 0.024* | |
H29C | 0.8790 | 0.5367 | 0.5597 | 0.024* | |
O30 | 0.58731 (10) | 0.86845 (18) | 0.61271 (3) | 0.0181 (3) | |
H30 | 0.533 (2) | 0.852 (4) | 0.5915 (7) | 0.056 (8)* | |
O31 | 0.41210 (11) | 0.90780 (19) | 0.64135 (4) | 0.0238 (3) | |
C32 | 0.52448 (15) | 0.9063 (2) | 0.64073 (5) | 0.0169 (4) | |
C33 | 0.60896 (16) | 0.9548 (3) | 0.67194 (5) | 0.0209 (4) | |
H33A | 0.6142 | 1.0879 | 0.6735 | 0.025* | |
H33B | 0.6934 | 0.9093 | 0.6676 | 0.025* | |
C34 | 0.57017 (16) | 0.8827 (3) | 0.70716 (5) | 0.0200 (4) | |
H34A | 0.5747 | 0.7494 | 0.7073 | 0.024* | |
H34B | 0.4834 | 0.9184 | 0.7112 | 0.024* | |
C35 | 0.6584 (3) | 0.9608 (5) | 0.73679 (8) | 0.0196 (6) | 0.770 (4) |
H35A | 0.7449 | 0.9243 | 0.7324 | 0.023* | 0.770 (4) |
H35B | 0.6546 | 1.0941 | 0.7360 | 0.023* | 0.770 (4) |
C36 | 0.6250 (3) | 0.8968 (3) | 0.77317 (6) | 0.0178 (6) | 0.770 (4) |
H36A | 0.6289 | 0.7634 | 0.7740 | 0.021* | 0.770 (4) |
H36B | 0.5388 | 0.9335 | 0.7777 | 0.021* | 0.770 (4) |
C37 | 0.7126 (2) | 0.9744 (4) | 0.80178 (8) | 0.0186 (6) | 0.770 (4) |
H37A | 0.7989 | 0.9407 | 0.7967 | 0.022* | 0.770 (4) |
H37B | 0.7070 | 1.1077 | 0.8011 | 0.022* | 0.770 (4) |
C38 | 0.6847 (2) | 0.9101 (3) | 0.83854 (7) | 0.0174 (6) | 0.770 (4) |
H38A | 0.6933 | 0.7772 | 0.8394 | 0.021* | 0.770 (4) |
H38B | 0.5973 | 0.9397 | 0.8432 | 0.021* | 0.770 (4) |
C39 | 0.7695 (3) | 0.9931 (5) | 0.86770 (8) | 0.0150 (7) | 0.770 (4) |
H39A | 0.7688 | 1.1260 | 0.8653 | 0.018* | 0.770 (4) |
H39B | 0.7366 | 0.9625 | 0.8908 | 0.018* | 0.770 (4) |
C35' | 0.6128 (9) | 0.9559 (19) | 0.7400 (3) | 0.0196 (6) | 0.230 (4) |
H35C | 0.6048 | 1.0888 | 0.7387 | 0.023* | 0.230 (4) |
H35D | 0.7025 | 0.9281 | 0.7433 | 0.023* | 0.230 (4) |
C36' | 0.5482 (8) | 0.8921 (13) | 0.7725 (2) | 0.023 (2) | 0.230 (4) |
H36C | 0.5562 | 0.7594 | 0.7743 | 0.027* | 0.230 (4) |
H36D | 0.4586 | 0.9209 | 0.7698 | 0.027* | 0.230 (4) |
C37' | 0.6007 (7) | 0.9780 (13) | 0.8072 (2) | 0.023 (2) | 0.230 (4) |
H37C | 0.5988 | 1.1109 | 0.8048 | 0.028* | 0.230 (4) |
H37D | 0.5456 | 0.9453 | 0.8264 | 0.028* | 0.230 (4) |
C38' | 0.7281 (8) | 0.9218 (12) | 0.8171 (3) | 0.0139 (19) | 0.230 (4) |
H38C | 0.7850 | 0.9748 | 0.8002 | 0.017* | 0.230 (4) |
H38D | 0.7333 | 0.7890 | 0.8149 | 0.017* | 0.230 (4) |
C39' | 0.7737 (12) | 0.9740 (19) | 0.8538 (3) | 0.019 (2) | 0.230 (4) |
H39C | 0.7657 | 1.1065 | 0.8559 | 0.023* | 0.230 (4) |
H39D | 0.7161 | 0.9199 | 0.8705 | 0.023* | 0.230 (4) |
C40 | 0.90344 (15) | 0.9248 (2) | 0.86617 (5) | 0.0153 (4) | |
O41 | 0.97487 (11) | 1.00506 (19) | 0.84437 (3) | 0.0235 (3) | |
H41 | 1.060 (2) | 0.950 (2) | 0.8463 (4) | 0.035* | |
O42 | 0.93796 (11) | 0.80413 (19) | 0.88602 (3) | 0.0224 (3) |
U11 | U22 | U33 | U12 | U13 | U23 | |
N1 | 0.0133 (6) | 0.0141 (7) | 0.0125 (7) | 0.0010 (6) | 0.0024 (5) | −0.0003 (6) |
C2 | 0.0139 (7) | 0.0173 (9) | 0.0133 (8) | 0.0029 (7) | 0.0036 (6) | −0.0007 (7) |
N3 | 0.0127 (6) | 0.0165 (8) | 0.0140 (7) | 0.0020 (6) | 0.0015 (5) | 0.0003 (6) |
C4 | 0.0119 (7) | 0.0092 (8) | 0.0128 (8) | −0.0007 (6) | 0.0005 (6) | 0.0004 (7) |
C5 | 0.0106 (7) | 0.0123 (8) | 0.0101 (8) | −0.0005 (6) | −0.0005 (6) | 0.0001 (7) |
C6 | 0.0109 (7) | 0.0106 (8) | 0.0114 (8) | −0.0002 (6) | 0.0027 (6) | 0.0000 (7) |
C7 | 0.0088 (7) | 0.0100 (8) | 0.0160 (9) | −0.0006 (6) | −0.0011 (6) | 0.0015 (7) |
C8 | 0.0126 (7) | 0.0116 (8) | 0.0107 (8) | −0.0007 (6) | −0.0023 (6) | 0.0007 (7) |
C9 | 0.0127 (7) | 0.0090 (8) | 0.0129 (8) | −0.0001 (6) | 0.0020 (6) | −0.0001 (7) |
C10 | 0.0112 (7) | 0.0078 (8) | 0.0135 (8) | 0.0005 (6) | 0.0012 (6) | 0.0011 (6) |
N11 | 0.0076 (6) | 0.0195 (8) | 0.0118 (7) | 0.0034 (6) | 0.0017 (5) | −0.0015 (6) |
C12 | 0.0041 (10) | 0.0098 (8) | 0.0114 (13) | 0.0021 (7) | 0.0028 (7) | −0.0018 (8) |
C13 | 0.0085 (8) | 0.0165 (10) | 0.0059 (12) | 0.0021 (7) | 0.0002 (9) | 0.0017 (8) |
C14 | 0.0071 (11) | 0.0177 (10) | 0.0127 (9) | 0.0050 (8) | −0.0034 (9) | 0.0015 (8) |
C15 | 0.0086 (8) | 0.0157 (9) | 0.0120 (17) | 0.0024 (7) | −0.0011 (7) | −0.0018 (11) |
C16 | 0.0083 (8) | 0.0165 (10) | 0.0093 (12) | 0.0008 (7) | 0.0016 (9) | −0.0005 (9) |
C17 | 0.0035 (10) | 0.0140 (9) | 0.0132 (9) | 0.0011 (8) | −0.0014 (8) | 0.0002 (7) |
Cl1 | 0.01550 (19) | 0.0375 (8) | 0.0185 (3) | 0.0082 (3) | −0.00091 (18) | 0.0091 (4) |
F1 | 0.0077 (5) | 0.0352 (9) | 0.0190 (13) | 0.0063 (5) | −0.0013 (6) | −0.0007 (9) |
C12' | 0.0041 (10) | 0.0098 (8) | 0.0114 (13) | 0.0021 (7) | 0.0028 (7) | −0.0018 (8) |
C13' | 0.0085 (8) | 0.0165 (10) | 0.0059 (12) | 0.0021 (7) | 0.0002 (9) | 0.0017 (8) |
C14' | 0.0071 (11) | 0.0177 (10) | 0.0127 (9) | 0.0050 (8) | −0.0034 (9) | 0.0015 (8) |
C15' | 0.0086 (8) | 0.0157 (9) | 0.0120 (17) | 0.0024 (7) | −0.0011 (7) | −0.0018 (11) |
C16' | 0.0083 (8) | 0.0165 (10) | 0.0093 (12) | 0.0008 (7) | 0.0016 (9) | −0.0005 (9) |
C17' | 0.0035 (10) | 0.0140 (9) | 0.0132 (9) | 0.0011 (8) | −0.0014 (8) | 0.0002 (7) |
Cl1' | 0.01550 (19) | 0.0375 (8) | 0.0185 (3) | 0.0082 (3) | −0.00091 (18) | 0.0091 (4) |
F1' | 0.0077 (5) | 0.0352 (9) | 0.0190 (13) | 0.0063 (5) | −0.0013 (6) | −0.0007 (9) |
O18 | 0.0105 (5) | 0.0228 (7) | 0.0106 (6) | 0.0042 (5) | −0.0001 (4) | −0.0030 (5) |
C19 | 0.0114 (7) | 0.0206 (9) | 0.0098 (8) | 0.0009 (7) | −0.0015 (6) | −0.0007 (7) |
C20 | 0.0121 (7) | 0.0224 (10) | 0.0156 (9) | 0.0028 (7) | 0.0009 (6) | −0.0040 (8) |
C21 | 0.0169 (8) | 0.0157 (9) | 0.0160 (9) | 0.0040 (7) | 0.0016 (7) | −0.0010 (7) |
N22 | 0.0211 (7) | 0.0188 (8) | 0.0113 (7) | 0.0053 (6) | 0.0028 (6) | −0.0004 (6) |
C23 | 0.0275 (9) | 0.0347 (12) | 0.0133 (9) | 0.0098 (9) | 0.0015 (7) | −0.0053 (9) |
C24 | 0.0400 (12) | 0.0615 (17) | 0.0161 (10) | 0.0193 (12) | 0.0034 (9) | 0.0049 (11) |
O25 | 0.0590 (10) | 0.0591 (12) | 0.0235 (9) | 0.0253 (9) | 0.0179 (7) | 0.0200 (8) |
C26 | 0.0637 (15) | 0.0314 (13) | 0.0347 (14) | 0.0212 (12) | 0.0252 (12) | 0.0158 (11) |
C27 | 0.0396 (11) | 0.0170 (10) | 0.0228 (11) | 0.0020 (8) | 0.0143 (9) | 0.0010 (8) |
O28 | 0.0096 (5) | 0.0212 (7) | 0.0135 (6) | 0.0038 (5) | −0.0025 (4) | −0.0022 (5) |
C29 | 0.0123 (7) | 0.0214 (10) | 0.0145 (9) | 0.0028 (7) | −0.0052 (6) | −0.0036 (7) |
O30 | 0.0150 (5) | 0.0276 (7) | 0.0116 (6) | 0.0001 (5) | −0.0004 (5) | −0.0023 (6) |
O31 | 0.0141 (6) | 0.0344 (8) | 0.0232 (7) | −0.0014 (5) | 0.0020 (5) | −0.0030 (6) |
C32 | 0.0174 (8) | 0.0181 (9) | 0.0153 (9) | −0.0011 (7) | 0.0011 (7) | 0.0000 (7) |
C33 | 0.0192 (8) | 0.0276 (11) | 0.0159 (9) | −0.0043 (8) | −0.0005 (7) | −0.0023 (8) |
C34 | 0.0254 (9) | 0.0197 (10) | 0.0148 (9) | 0.0011 (8) | −0.0001 (7) | −0.0006 (8) |
C35 | 0.0201 (15) | 0.0227 (11) | 0.0159 (12) | −0.0061 (15) | 0.0000 (13) | −0.0001 (9) |
C36 | 0.0162 (13) | 0.0209 (13) | 0.0161 (12) | −0.0027 (10) | −0.0023 (10) | −0.0003 (10) |
C37 | 0.0196 (12) | 0.0229 (15) | 0.0133 (14) | −0.0058 (11) | −0.0012 (11) | 0.0028 (12) |
C38 | 0.0125 (10) | 0.0247 (14) | 0.0149 (14) | −0.0037 (9) | −0.0005 (10) | 0.0013 (10) |
C39 | 0.0134 (11) | 0.0207 (15) | 0.0111 (16) | −0.0003 (10) | 0.0009 (14) | −0.0017 (15) |
C35' | 0.0201 (15) | 0.0227 (11) | 0.0159 (12) | −0.0061 (15) | 0.0000 (13) | −0.0001 (9) |
C36' | 0.014 (5) | 0.035 (5) | 0.019 (4) | 0.002 (4) | 0.001 (3) | −0.003 (4) |
C37' | 0.015 (4) | 0.033 (5) | 0.021 (5) | 0.000 (3) | −0.002 (3) | −0.006 (4) |
C38' | 0.017 (4) | 0.013 (4) | 0.011 (5) | −0.002 (3) | −0.004 (4) | 0.001 (4) |
C39' | 0.023 (4) | 0.021 (5) | 0.014 (6) | 0.003 (3) | 0.010 (5) | −0.005 (5) |
C40 | 0.0153 (7) | 0.0154 (9) | 0.0148 (9) | −0.0042 (7) | −0.0028 (7) | −0.0027 (7) |
O41 | 0.0185 (6) | 0.0302 (8) | 0.0215 (7) | −0.0046 (6) | −0.0012 (5) | 0.0094 (6) |
O42 | 0.0171 (6) | 0.0288 (8) | 0.0209 (7) | −0.0047 (5) | −0.0044 (5) | 0.0085 (6) |
N1—C2 | 1.319 (2) | C24—O25 | 1.421 (3) |
N1—C9 | 1.378 (2) | C24—H24A | 0.9900 |
C2—N3 | 1.343 (2) | C24—H24B | 0.9900 |
C2—H2 | 0.9500 | O25—C26 | 1.428 (3) |
N3—C4 | 1.333 (2) | C26—C27 | 1.499 (3) |
C4—N11 | 1.360 (2) | C26—H26A | 0.9900 |
C4—C10 | 1.442 (2) | C26—H26B | 0.9900 |
C5—C6 | 1.370 (2) | C27—H27A | 0.9900 |
C5—C10 | 1.417 (2) | C27—H27B | 0.9900 |
C5—H5 | 0.9500 | O28—C29 | 1.433 (2) |
C6—O18 | 1.3631 (19) | C29—H29A | 0.9800 |
C6—C7 | 1.424 (2) | C29—H29B | 0.9800 |
C7—O28 | 1.3585 (18) | C29—H29C | 0.9800 |
C7—C8 | 1.373 (2) | O30—C32 | 1.319 (2) |
C8—C9 | 1.414 (2) | O30—H30 | 0.99 (3) |
C8—H8 | 0.9500 | O31—C32 | 1.212 (2) |
C9—C10 | 1.404 (2) | C32—C33 | 1.513 (2) |
N11—C12 | 1.408 (2) | C33—C34 | 1.521 (3) |
N11—C12' | 1.64 (3) | C33—H33A | 0.9900 |
N11—H11 | 0.84 (2) | C33—H33B | 0.9900 |
C12—C17 | 1.404 (3) | C34—C35' | 1.426 (12) |
C12—C13 | 1.407 (3) | C34—C35 | 1.559 (4) |
C13—C14 | 1.389 (3) | C34—H34A | 0.9900 |
C13—H13 | 0.9500 | C34—H34B | 0.9900 |
C14—C15 | 1.387 (3) | C35—C36 | 1.525 (4) |
C14—Cl1 | 1.734 (3) | C35—H35A | 0.9900 |
C15—F1 | 1.335 (19) | C35—H35B | 0.9900 |
C15—C16 | 1.377 (3) | C36—C37 | 1.527 (4) |
C16—C17 | 1.397 (3) | C36—H36A | 0.9900 |
C16—H16 | 0.9500 | C36—H36B | 0.9900 |
C17—H17 | 0.9500 | C37—C38 | 1.524 (4) |
C12'—C13' | 1.26 (4) | C37—H37A | 0.9900 |
C12'—C17' | 1.31 (3) | C37—H37B | 0.9900 |
C13'—C14' | 1.27 (4) | C38—C39 | 1.540 (4) |
C13'—H13' | 0.9500 | C38—H38A | 0.9900 |
C14'—C15' | 1.41 (4) | C38—H38B | 0.9900 |
C14'—Cl1' | 1.92 (3) | C39—C40 | 1.533 (4) |
C15'—C16' | 1.20 (4) | C39—H39A | 0.9900 |
C15'—F1' | 1.395 (19) | C39—H39B | 0.9900 |
C16'—C17' | 1.27 (4) | C35'—C36' | 1.522 (14) |
C16'—H16' | 0.9500 | C35'—H35C | 0.9900 |
C17'—H17' | 0.9500 | C35'—H35D | 0.9900 |
O18—C19 | 1.435 (2) | C36'—C37' | 1.556 (12) |
C19—C20 | 1.519 (2) | C36'—H36C | 0.9900 |
C19—H19A | 0.9900 | C36'—H36D | 0.9900 |
C19—H19B | 0.9900 | C37'—C38' | 1.469 (11) |
C20—C21 | 1.515 (2) | C37'—H37C | 0.9900 |
C20—H20A | 0.9900 | C37'—H37D | 0.9900 |
C20—H20B | 0.9900 | C38'—C39' | 1.516 (15) |
C21—N22 | 1.486 (2) | C38'—H38C | 0.9900 |
C21—H21A | 0.9900 | C38'—H38D | 0.9900 |
C21—H21B | 0.9900 | C39'—C40 | 1.501 (13) |
N22—C27 | 1.482 (2) | C39'—H39C | 0.9900 |
N22—C23 | 1.490 (2) | C39'—H39D | 0.9900 |
C23—C24 | 1.509 (3) | C40—O42 | 1.221 (2) |
C23—H23A | 0.9900 | C40—O41 | 1.300 (2) |
C23—H23B | 0.9900 | O41—H41 | 1.01 (2) |
C2—N1—C9 | 116.13 (14) | O25—C26—C27 | 112.41 (18) |
N1—C2—N3 | 128.05 (15) | O25—C26—H26A | 109.1 |
N1—C2—H2 | 116.0 | C27—C26—H26A | 109.1 |
N3—C2—H2 | 116.0 | O25—C26—H26B | 109.1 |
C4—N3—C2 | 116.72 (14) | C27—C26—H26B | 109.1 |
N3—C4—N11 | 118.80 (14) | H26A—C26—H26B | 107.9 |
N3—C4—C10 | 121.53 (15) | N22—C27—C26 | 109.72 (18) |
N11—C4—C10 | 119.66 (14) | N22—C27—H27A | 109.7 |
C6—C5—C10 | 119.83 (15) | C26—C27—H27A | 109.7 |
C6—C5—H5 | 120.1 | N22—C27—H27B | 109.7 |
C10—C5—H5 | 120.1 | C26—C27—H27B | 109.7 |
O18—C6—C5 | 125.13 (15) | H27A—C27—H27B | 108.2 |
O18—C6—C7 | 114.31 (13) | C7—O28—C29 | 117.44 (13) |
C5—C6—C7 | 120.56 (14) | O28—C29—H29A | 109.5 |
O28—C7—C8 | 125.43 (15) | O28—C29—H29B | 109.5 |
O28—C7—C6 | 114.31 (14) | H29A—C29—H29B | 109.5 |
C8—C7—C6 | 120.26 (14) | O28—C29—H29C | 109.5 |
C7—C8—C9 | 119.64 (15) | H29A—C29—H29C | 109.5 |
C7—C8—H8 | 120.2 | H29B—C29—H29C | 109.5 |
C9—C8—H8 | 120.2 | C32—O30—H30 | 112.8 (15) |
N1—C9—C10 | 121.46 (14) | O31—C32—O30 | 124.29 (17) |
N1—C9—C8 | 118.33 (15) | O31—C32—C33 | 123.51 (16) |
C10—C9—C8 | 120.21 (14) | O30—C32—C33 | 112.16 (14) |
C9—C10—C5 | 119.48 (14) | C32—C33—C34 | 115.76 (15) |
C9—C10—C4 | 116.09 (14) | C32—C33—H33A | 108.3 |
C5—C10—C4 | 124.43 (15) | C34—C33—H33A | 108.3 |
C4—N11—C12 | 128.84 (17) | C32—C33—H33B | 108.3 |
C4—N11—C12' | 116.5 (11) | C34—C33—H33B | 108.3 |
C4—N11—H11 | 119.4 (13) | H33A—C33—H33B | 107.4 |
C12—N11—H11 | 111.4 (13) | C35'—C34—C33 | 123.6 (5) |
C12'—N11—H11 | 123.9 (17) | C33—C34—C35 | 109.25 (18) |
C17—C12—C13 | 119.82 (19) | C33—C34—H34A | 109.8 |
C17—C12—N11 | 123.1 (3) | C35—C34—H34A | 109.8 |
C13—C12—N11 | 117.1 (2) | C33—C34—H34B | 109.8 |
C14—C13—C12 | 119.7 (2) | C35—C34—H34B | 109.8 |
C14—C13—H13 | 120.2 | H34A—C34—H34B | 108.3 |
C12—C13—H13 | 120.2 | C36—C35—C34 | 112.7 (2) |
C15—C14—C13 | 119.6 (2) | C36—C35—H35A | 109.1 |
C15—C14—Cl1 | 121.1 (2) | C34—C35—H35A | 109.1 |
C13—C14—Cl1 | 119.2 (2) | C36—C35—H35B | 109.1 |
F1—C15—C16 | 110.4 (15) | C34—C35—H35B | 109.1 |
F1—C15—C14 | 127.9 (16) | H35A—C35—H35B | 107.8 |
C16—C15—C14 | 121.6 (2) | C35—C36—C37 | 111.9 (2) |
C15—C16—C17 | 119.50 (19) | C35—C36—H36A | 109.2 |
C15—C16—H16 | 120.3 | C37—C36—H36A | 109.2 |
C17—C16—H16 | 120.3 | C35—C36—H36B | 109.2 |
C16—C17—C12 | 119.7 (2) | C37—C36—H36B | 109.2 |
C16—C17—H17 | 120.1 | H36A—C36—H36B | 107.9 |
C12—C17—H17 | 120.1 | C38—C37—C36 | 113.7 (2) |
C13'—C12'—C17' | 116 (3) | C38—C37—H37A | 108.8 |
C13'—C12'—N11 | 89 (2) | C36—C37—H37A | 108.8 |
C17'—C12'—N11 | 152 (3) | C38—C37—H37B | 108.8 |
C12'—C13'—C14' | 122 (3) | C36—C37—H37B | 108.8 |
C12'—C13'—H13' | 119.2 | H37A—C37—H37B | 107.7 |
C14'—C13'—H13' | 119.2 | C37—C38—C39 | 114.0 (2) |
C13'—C14'—C15' | 122 (3) | C37—C38—H38A | 108.7 |
C13'—C14'—Cl1' | 145 (3) | C39—C38—H38A | 108.7 |
C15'—C14'—Cl1' | 93 (2) | C37—C38—H38B | 108.7 |
C16'—C15'—F1' | 99 (3) | C39—C38—H38B | 108.7 |
C16'—C15'—C14' | 112 (3) | H38A—C38—H38B | 107.6 |
F1'—C15'—C14' | 149 (4) | C40—C39—C38 | 111.9 (2) |
C15'—C16'—C17' | 127 (3) | C40—C39—H39A | 109.2 |
C15'—C16'—H16' | 116.4 | C38—C39—H39A | 109.2 |
C17'—C16'—H16' | 116.4 | C40—C39—H39B | 109.2 |
C16'—C17'—C12' | 121 (3) | C38—C39—H39B | 109.2 |
C16'—C17'—H17' | 119.7 | H39A—C39—H39B | 107.9 |
C12'—C17'—H17' | 119.7 | C34—C35'—C36' | 117.2 (8) |
C6—O18—C19 | 117.35 (12) | C34—C35'—H35C | 108.0 |
O18—C19—C20 | 105.66 (12) | C36'—C35'—H35C | 108.0 |
O18—C19—H19A | 110.6 | C34—C35'—H35D | 108.0 |
C20—C19—H19A | 110.6 | C36'—C35'—H35D | 108.0 |
O18—C19—H19B | 110.6 | H35C—C35'—H35D | 107.2 |
C20—C19—H19B | 110.6 | C35'—C36'—C37' | 113.9 (8) |
H19A—C19—H19B | 108.7 | C35'—C36'—H36C | 108.8 |
C21—C20—C19 | 113.76 (13) | C37'—C36'—H36C | 108.8 |
C21—C20—H20A | 108.8 | C35'—C36'—H36D | 108.8 |
C19—C20—H20A | 108.8 | C37'—C36'—H36D | 108.8 |
C21—C20—H20B | 108.8 | H36C—C36'—H36D | 107.7 |
C19—C20—H20B | 108.8 | C38'—C37'—C36' | 114.0 (7) |
H20A—C20—H20B | 107.7 | C38'—C37'—H37C | 108.8 |
N22—C21—C20 | 115.03 (15) | C36'—C37'—H37C | 108.8 |
N22—C21—H21A | 108.5 | C38'—C37'—H37D | 108.8 |
C20—C21—H21A | 108.5 | C36'—C37'—H37D | 108.8 |
N22—C21—H21B | 108.5 | H37C—C37'—H37D | 107.6 |
C20—C21—H21B | 108.5 | C37'—C38'—C39' | 115.5 (8) |
H21A—C21—H21B | 107.5 | C37'—C38'—H38C | 108.4 |
C27—N22—C21 | 112.56 (14) | C39'—C38'—H38C | 108.4 |
C27—N22—C23 | 108.83 (15) | C37'—C38'—H38D | 108.4 |
C21—N22—C23 | 107.32 (14) | C39'—C38'—H38D | 108.4 |
N22—C23—C24 | 110.88 (17) | H38C—C38'—H38D | 107.5 |
N22—C23—H23A | 109.5 | C40—C39'—C38' | 119.4 (8) |
C24—C23—H23A | 109.5 | C40—C39'—H39C | 107.5 |
N22—C23—H23B | 109.5 | C38'—C39'—H39C | 107.5 |
C24—C23—H23B | 109.5 | C40—C39'—H39D | 107.5 |
H23A—C23—H23B | 108.1 | C38'—C39'—H39D | 107.5 |
O25—C24—C23 | 111.37 (19) | H39C—C39'—H39D | 107.0 |
O25—C24—H24A | 109.4 | O42—C40—O41 | 124.03 (16) |
C23—C24—H24A | 109.4 | O42—C40—C39' | 129.0 (6) |
O25—C24—H24B | 109.4 | O41—C40—C39' | 104.8 (5) |
C23—C24—H24B | 109.4 | O42—C40—C39 | 118.8 (2) |
H24A—C24—H24B | 108.0 | O41—C40—C39 | 117.10 (19) |
C24—O25—C26 | 108.91 (17) | C40—O41—H41 | 109.5 |
C9—N1—C2—N3 | −0.2 (3) | N11—C12'—C13'—C14' | 171.7 (16) |
N1—C2—N3—C4 | −0.1 (3) | C12'—C13'—C14'—C15' | 1 (2) |
C2—N3—C4—N11 | −178.27 (15) | C12'—C13'—C14'—Cl1' | −168 (3) |
C2—N3—C4—C10 | 1.1 (2) | C13'—C14'—C15'—C16' | −2 (5) |
C10—C5—C6—O18 | −179.65 (15) | Cl1'—C14'—C15'—C16' | 171 (4) |
C10—C5—C6—C7 | −0.4 (2) | C13'—C14'—C15'—F1' | 177 (6) |
O18—C6—C7—O28 | 0.7 (2) | Cl1'—C14'—C15'—F1' | −10 (7) |
C5—C6—C7—O28 | −178.59 (15) | F1'—C15'—C16'—C17' | 177 (3) |
O18—C6—C7—C8 | −179.53 (15) | C14'—C15'—C16'—C17' | −4 (6) |
C5—C6—C7—C8 | 1.2 (3) | C15'—C16'—C17'—C12' | 11 (6) |
O28—C7—C8—C9 | 179.02 (15) | C13'—C12'—C17'—C16' | −11 (4) |
C6—C7—C8—C9 | −0.7 (2) | N11—C12'—C17'—C16' | −161 (4) |
C2—N1—C9—C10 | −0.5 (2) | C5—C6—O18—C19 | −1.1 (2) |
C2—N1—C9—C8 | 179.41 (16) | C7—C6—O18—C19 | 179.61 (14) |
C7—C8—C9—N1 | 179.62 (15) | C6—O18—C19—C20 | 174.33 (14) |
C7—C8—C9—C10 | −0.5 (2) | O18—C19—C20—C21 | 166.04 (15) |
N1—C9—C10—C5 | −178.89 (15) | C19—C20—C21—N22 | 54.0 (2) |
C8—C9—C10—C5 | 1.2 (2) | C20—C21—N22—C27 | 54.86 (19) |
N1—C9—C10—C4 | 1.4 (2) | C20—C21—N22—C23 | 174.57 (15) |
C8—C9—C10—C4 | −178.49 (15) | C27—N22—C23—C24 | −54.7 (2) |
C6—C5—C10—C9 | −0.7 (2) | C21—N22—C23—C24 | −176.76 (17) |
C6—C5—C10—C4 | 178.92 (16) | N22—C23—C24—O25 | 57.9 (2) |
N3—C4—C10—C9 | −1.7 (2) | C23—C24—O25—C26 | −59.2 (2) |
N11—C4—C10—C9 | 177.61 (15) | C24—O25—C26—C27 | 60.6 (2) |
N3—C4—C10—C5 | 178.60 (16) | C21—N22—C27—C26 | 173.58 (15) |
N11—C4—C10—C5 | −2.1 (3) | C23—N22—C27—C26 | 54.74 (19) |
N3—C4—N11—C12 | −0.6 (3) | O25—C26—C27—N22 | −59.3 (2) |
C10—C4—N11—C12 | −179.94 (18) | C8—C7—O28—C29 | −3.9 (2) |
N3—C4—N11—C12' | −3.5 (12) | C6—C7—O28—C29 | 175.88 (15) |
C10—C4—N11—C12' | 177.1 (11) | O31—C32—C33—C34 | 41.3 (3) |
C4—N11—C12—C17 | −29.1 (3) | O30—C32—C33—C34 | −140.79 (17) |
C4—N11—C12—C13 | 153.23 (19) | C32—C33—C34—C35' | −160.0 (6) |
C17—C12—C13—C14 | −1.3 (3) | C32—C33—C34—C35 | −174.15 (19) |
N11—C12—C13—C14 | 176.4 (2) | C33—C34—C35—C36 | 179.3 (2) |
C12—C13—C14—C15 | 0.1 (3) | C34—C35—C36—C37 | 179.9 (2) |
C12—C13—C14—Cl1 | 178.38 (17) | C35—C36—C37—C38 | −178.5 (2) |
C13—C14—C15—F1 | −177 (2) | C36—C37—C38—C39 | −177.9 (2) |
Cl1—C14—C15—F1 | 5 (2) | C37—C38—C39—C40 | −69.0 (3) |
C13—C14—C15—C16 | 1.2 (4) | C33—C34—C35'—C36' | 169.2 (6) |
Cl1—C14—C15—C16 | −177.0 (2) | C34—C35'—C36'—C37' | 179.8 (8) |
F1—C15—C16—C17 | 176.9 (19) | C35'—C36'—C37'—C38' | −67.5 (11) |
C14—C15—C16—C17 | −1.3 (4) | C36'—C37'—C38'—C39' | −169.1 (9) |
C15—C16—C17—C12 | 0.1 (4) | C37'—C38'—C39'—C40 | −179.1 (9) |
C13—C12—C17—C16 | 1.2 (3) | C38'—C39'—C40—O42 | −103.4 (10) |
N11—C12—C17—C16 | −176.4 (2) | C38'—C39'—C40—O41 | 60.0 (11) |
C4—N11—C12'—C13' | 158.5 (10) | C38—C39—C40—O42 | −99.5 (3) |
C4—N11—C12'—C17' | −49 (5) | C38—C39—C40—O41 | 83.0 (3) |
C17'—C12'—C13'—C14' | 5 (2) |
D—H···A | D—H | H···A | D···A | D—H···A |
N11—H11···O42i | 0.84 (2) | 2.20 (2) | 3.025 (2) | 169.6 (18) |
O41—H41···N22ii | 1.01 | 1.78 | 2.6566 (19) | 144 |
O30—H30···N1 | 0.99 (3) | 1.65 (3) | 2.6135 (19) | 166 (2) |
C5—H5···O42i | 0.95 | 2.25 | 3.194 (2) | 170 |
C2—H2···F1iii | 0.95 | 2.15 | 3.07 (3) | 163 |
C2—H2···F1′iii | 0.95 | 2.32 | 3.253 (3) | 166 |
C29—H29B···O18iv | 0.98 | 2.65 | 3.6101 (19) | 167 |
C23—H23B···O25v | 0.99 | 2.57 | 3.220 (2) | 123 |
C27—H27B···F1vi | 0.99 | 2.71 | 3.68 (4) | 166 |
C39—H39A···O30vii | 0.99 | 2.50 | 3.255 (4) | 133 |
C21—H21B···O31viii | 0.99 | 2.29 | 3.234 (2) | 160 |
C13—H13···O30ix | 0.95 | 2.39 | 3.139 (3) | 135 |
C13′—H13′···O30ix | 0.95 | 2.53 | 3.268 (3) | 135 |
Cg2···Cg2viii | 3.5358 (11) | 0 (1) | ||
Cg2···Cg3viii | 3.7909 (11) | 1 (1) | ||
Cg2···Cg3ix | 3.7530 (11) | 1 (1) | ||
Cg3···Cg3viii | 3.7934 (11) | 0 (1) |
Symmetry codes: (i) x−1/2, −y+3/2, z−1/2; (ii) x+1/2, −y+3/2, z+1/2; (iii) −x, −y+2, −z+1; (iv) −x+2, −y+1, −z+1; (v) −x+3/2, y−1/2, −z+1/2; (vi) x+1, y, z; (vii) −x+3/2, y+1/2, −z+3/2; (viii) −x+1, −y+1, −z+1; (ix) −x+1, −y+2, −z+1. |
Acknowledgements
CPG thanks SERB, New Delhi, for a project fellowship. This work was funded by the Science and Engineering Research Board (SERB), New Delhi (grant No. EEQ/2018/001172).
Funding information
Funding for this research was provided by: Science and Engineering Research Board (SERB), New Delhi (grant No. EEQ/2018/001172 to Dr. Rajesh G. Gonnade).
References
Braga, D., Dichiarante, E., Palladino, G., Grepioni, F., Chierotti, M. R., Gobetto, R. & Pellegrino, L. (2010). CrystEngComm, 12, 3534–3536. Web of Science CSD CrossRef CAS Google Scholar
Braga, D., Giaffreda, S. L. & Grepioni, F. (2006). Chem. Commun. pp. 3877–3879. Web of Science CSD CrossRef Google Scholar
Bruker (2016). APEX3, SAINT-Plus and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Caspari, W. A. (1928). J. Chem. Soc. pp. 3235–3241. CSD CrossRef Google Scholar
Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854. Web of Science CrossRef CAS IUCr Journals Google Scholar
Fitton, A. & Goa, K. L. (1991). Drugs, 41, 780–798. CrossRef PubMed CAS Google Scholar
Gilday, J. P., Graham, A. S., Ymen, B. I. & Bohlin, M. (2005). US Patent US 2005/0209229 A1. Google Scholar
Gonnade, R. G. (2015). PCT Int. Appl. WO 2015/170345 A1. Google Scholar
Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179. Web of Science CrossRef IUCr Journals Google Scholar
Grzesiak, M., Nitek, W., Rafalska-Łasocha, A. & Łasocha, W. (2012). Z. Kristallogr. 227, 629–634. CrossRef CAS Google Scholar
Housty, J. & Hospital, M. (1967). Acta Cryst. 22, 288–295. CSD CAS Web of Science Google Scholar
Karki, S., Friščić, T. & Jones, W. (2009). CrystEngComm, 11, 470–481. Web of Science CSD CrossRef CAS Google Scholar
Kobayashi, K. & Hagiwara, K. (2013). Targ Oncol, 8, 27–33. CrossRef Google Scholar
Krueger, E. L., Sinha, A. S., Desper, J. & Aakeröy, C. B. (2017). CrystEngComm, 19, 4605–4614. CrossRef CAS Google Scholar
Macrae, C. F., Sovago, I., Cottrell, S. J., Galek, P. T. A., McCabe, P., Pidcock, E., Platings, M., Shields, G. P., Stevens, J. S., Towler, M. & Wood, P. A. (2020). J. Appl. Cryst. 53, 226–235. Web of Science CrossRef CAS IUCr Journals Google Scholar
Martins, I. C. B., Sardo, M., Santos, S. M., Fernandes, A., Antunes, A., André, V., Mafra, L. & Duarte, M. T. (2016). Cryst. Growth Des. 16, 154–166. CrossRef CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Sheldrick, G. M. (2015). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Spek, A. L. (2020). Acta Cryst. E76, 1–11. Web of Science CrossRef IUCr Journals Google Scholar
Thompson, L. J., Voguri, R. S., Male, L. & Tremayne, M. (2011). CrystEngComm, 13, 4188–4195. Web of Science CSD CrossRef CAS Google Scholar
Thorat, S. H., Patwadkar, M. V., Gonnade, R. G. & Vaidhyanathan, R. (2014). CrystEngComm, 16, 8638–8641. Web of Science CSD CrossRef CAS Google Scholar
Thorat, S. H., Sahu, S. K., Patwadkar, M. V., Badiger, M. V. & Gonnade, R. G. (2015). J. Pharm. Sci. 104, 4207–4216. Web of Science CSD CrossRef CAS PubMed Google Scholar
Tothadi, S. & Phadkule, A. (2019). CrystEngComm, 21, 2481–2484. CrossRef CAS Google Scholar
Westrip, S. P. (2010). J. Appl. Cryst. 43, 920–925. Web of Science CrossRef CAS IUCr Journals Google Scholar
Zhao, F.-H., Che, Y.-X. & Zheng, J.-M. (2012). Cryst. Growth Des. 12, 4712–4715. CrossRef CAS Google Scholar
This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.