A new solvate of afatinib, a specific inhibitor of the ErbB family of tyrosine kinases

Zeller, M.; Araujo, G.L.B. de; Parker, T.; Singh Rai, A.; Byrn, S.R.

doi:10.1107/S2056989017002626

research communications

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ISSN: 2056-9890

Volume 73| Part 3| March 2017| Pages 417-422

https://doi.org/10.1107/S2056989017002626

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A new solvate of afatinib, a specific inhibitor of the ErbB family of tyrosine kinases

Matthias Zeller,^a ^* Gabriel Lima Barros de Araujo,^b Trev Parker,^c Amrinder Singh Rai ^c and Stephen R. Byrn ^c

^aDepartment of Chemistry, Purdue University, 560 Oval Dr., W. Lafayette, IN 47907-2084, USA, ^bFaculty of Pharmaceutical Sciences, Department of Pharmacy, University of Sao Paulo, Sao Paulo, SP, Brazil, and ^cDepartment of Industrial and Physical Pharmacy, Purdue University, West Lafayette, Indiana, USA
^*Correspondence e-mail: zeller4@purdue.edu

Edited by H. Stoeckli-Evans, University of Neuchâtel, Switzerland (Received 6 February 2017; accepted 15 February 2017; online 21 February 2017)

Afatinib (systematic name: N-{4-(3-chloro-4-fluoroanilino)-7-[(tetrahydrofuran-3-yl)oxy]quinazolin-6-yl}-4-(dimethylamino)but-2-enamide), is a specific inhibitor of the ErbB family of tyrosine kinases. The free base form crystallizes from acetonitrile as a mixed water–acetonitrile solvent, C₂₄H₂₅ClFN₅O₃·0.25C₂H₃N·2H₂O. It crystallizes with two independent molecules (A and B) in the asymmetric unit of the chiral space group P42₁2, but exhibits close to perfect pseudo-inversion symmetry, emulating P4/ncc that relates the two molecules to each other. Exact inversion symmetry is however broken by swapping of oxygen and CH₂ moieties of the outer tetrahydrofuranyl substituents of the two independent molecules. This can, in turn, be traced back to C—H⋯N and C—H⋯O interactions of the acetonitrile solvent molecules with the tetrahydrofuran oxygen and CH₂ units. In the crystal, neighboring molecules are connected via N—H⋯O hydrogen bonds between the secondary amine and the amide keto O atom. Additional hydrogen bonds are formed through the water solvent molecules, which are engaged in O—H⋯O and O—H⋯N hydrogen bonds connecting to the dimethylamino N atom, the amide keto O atom, and one of the quinazoline N atoms of a neighboring molecule, leading to an intricate three-dimensional hydrogen-bonded superstructure. There are two types of channels stretching along the direction of the c axis; one along the fourfold rotational axis, occupied by acetonitrile solvent molecules situated on that axis, and parallel channels which are not occupied by any solvent.

Keywords: crystal structure; pseudo-symmetry; pseudo-inversion center; ErbB tyrosine kinase inhibitor; hydrogen bonding.

CCDC reference: 1532940

1. Chemical context

Afatinib is an orally administered antitumor drug used for the treatment of patients with metastatic nonsmall cell lung carcinoma (Keating, 2014 ). This drug is an irreversible specific inhibitor of ErbB family of tyrosine kinases, comprising EGFR (ErbB1), HER2 (ErbB2), and HER4 (ErbB4) (Hirsh, 2011 ; Keating, 2014). It is marketed as a dimaleate salt (Giotrif, Boehringer–Ingelheim Pharma GmbH, Ingelheim, Germany) and is reported to present polymorphism as a free base and in its salt forms, as well as an ethanol solvate (Gidwani et al., 2012 ; Jiadeng, 2016 ). However, to the best of our knowledge no single-crystal structure has been described so far for any of the reported crystal forms. Herein, we describe an acetonitrile–water solvent structure of afatinib free base obtained via vapor diffusion experiments.

2. Structural commentary

Crystals of free base afatinib were obtained from an acetonitrile solution through vapor diffusion of hexanes. The compound crystallized in a tetragonal setting, space group P42₁2, as a mixed water–acetonitrile solvent with two molecules of water and one-quarter molecule of acetonitrile per formula unit of afatinib (Fig. 1). Two crystallographically independent molecules (A and B) of afatinib are present, and both exhibit disorder of its tetrahydrofuran-3-yloxy units, with a disorder ratio of 0.718 (9):0.282 (9) for molecule A and 0.787 (5):0.213 (5) for molecule B. The type of disorder differs slightly between the two molecules (see Fig. 2 and §5, Refinement).

Figure 1
The molecular structure of the title compound, showing the atom labeling. Displacement ellipsoids are drawn at the 50% probability level. Dashed lines indicate minor disordered moieties C and D of the tetrahydrofuran-3-yloxy units. C-atom labels of the disordered moieties have been omitted for clarity.

Figure 2
View of the two disordered tetrahydrofuran-3-yloxy moieties, with 50% probability displacement ellipsoids. Dashed lines indicate minor disordered moieties C and D.

The two independent molecules (A and B) are related by a pseudo-inversion center with close to centrosymmetric P4/ncc symmetry. After inversion, the two molecules are nearly superimposable with only very minor deviations for the aromatic core, the chlorofluoroaniline substituent and the (dimethylamino)but-2-enamide unit (see Fig. 3 for the molecular overlay). Focusing only on the two major moieties exact inversion symmetry is broken solely by the positions of the tetrahydrofuran (THF) O atoms, which are swapped with a CH₂ group between the two molecules. Associated with the different positions of O and CH₂ moieties, and possibly providing an explanation for this observation, is an ordering of the acetonitrile solvent molecules. Acetonitrile molecules related by pseudo-inversion do not as expected point in opposite directions, but are co-parallel with each other. The CH₃CN molecules are located in channels surrounded by the tetrahydrofuranyl units, and they interact with molecules A and B in opposite ways. The methyl ends of both CH₃CN molecules form C—H⋯O hydrogen bonds with the O atoms of the major moieties of molecule B, capping a tetramer of THF units on both sides. The nitrogen ends of the acetonitrile units, on the other hand, act as acceptors of weak C—H⋯N hydrogen bonds (Fig. 4 and Table 1). The methyl and nitrogen ends of the linear molecules are related by the pseudo-inversion operation. The different polarity of the two ends, one an hydrogen-bond donor, the other an hydrogen-bond acceptor, can thus be seen as an immediate cause for the swapping of oxygen and the CH₂ groups, which are also hydrogen-bond donors and acceptors, so that an attractive rather than repulsive interaction is maintained. Exact inversion symmetry is also broken by the different disorder patterns for the tetrahydrofuran-3-yloxy units substituents (see §5, Refinement, and Fig. 2 for details). The absence of inversion symmetry is further evidenced by the value of the absolute structure parameter for racemic twinning, which refined to 0.02 (1), indicating a chiral or noncentrosymmetric space group incompatible with centrosymmetric P4/ncc symmetry.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N4A—H4A1⋯O4Bⁱ	0.88	1.94	2.804 (5)	166
N3A—H3A⋯O2Aⁱⁱ	0.88	2.22	3.088 (5)	167
O4A—H4C⋯N5A	0.85 (5)	1.97 (5)	2.816 (6)	173 (4)
O4A—H4D⋯O5A	0.86 (5)	1.91 (5)	2.759 (6)	169 (5)
O5A—H5C⋯O2A	0.85 (3)	2.00 (4)	2.844 (4)	174 (5)
O5A—H5D⋯N1Bⁱⁱ	0.83 (5)	1.98 (5)	2.775 (6)	161 (5)
C4A—H4A⋯O2Aⁱⁱ	0.95	2.31	3.246 (6)	168
C16A—H16A⋯O4Bⁱ	0.95	2.41	3.183 (6)	139
C22A—H22A⋯O3Aⁱⁱⁱ	0.99	2.40	3.353 (13)	162
C24A—H24A⋯O5Bⁱ	0.99	2.50	3.388 (14)	150
N4B—H4B1⋯O4A^iv	0.88	1.96	2.820 (5)	167
N3B—H3B⋯O2B^v	0.88	2.26	3.123 (5)	166
O4B—H4E⋯N5B	0.87 (5)	1.95 (5)	2.811 (5)	175 (6)
O4B—H4F⋯O5B	0.86 (4)	1.91 (4)	2.756 (5)	169 (4)
O5B—H5E⋯O2B	0.85 (4)	1.98 (3)	2.828 (4)	173 (5)
O5B—H5F⋯N1A^v	0.86 (4)	1.95 (4)	2.794 (5)	169 (5)
C4B—H4B⋯O2B^v	0.95	2.34	3.280 (6)	169
C16B—H16B⋯O4A^iv	0.95	2.42	3.197 (6)	139
C22B—H22D⋯O5A^iv	0.99	2.43	3.160 (8)	130
C24B—H24D⋯O3B^vi	0.99	2.57	3.455 (9)	149
Symmetry codes: (i) $[x+{\script{1\over 2}}, -y+{\script{1\over 2}}, -z-1]$ ; (ii) -y+1, -x+1, -z; (iii) $[y+{\script{1\over 2}}, -x+{\script{3\over 2}}, z]$ ; (iv) $[x-{\script{1\over 2}}, -y+{\script{1\over 2}}, -z]$ ; (v) -y+1, -x+1, -z-1; (vi) $[y+{\script{1\over 2}}, -x+{\script{1\over 2}}, z]$ .

Figure 3
Least-squares overlay of molecule A (blue) on inverted molecule B (green). O atoms of the tetrahydrofuran-3-yloxy units are shown as red spheres to illustrate the absence of inversion symmetry in the title structure. The r.m.s. deviation is 0.6892 Å.

Figure 4
View of the interactions of the acetonitrile solvent molecules with the tetrahydrofuranyl units of molecules A and B. The remaining sections of molecules A and B have been omitted for clarity. Acetonitrile molecules are located on a fourfold rotation axis hence and the H atoms are fourfold disordered. C—H⋯N and C—H⋯O hydrogen bonds are indicated as green dashed lines and the H⋯N and H⋯O distances (Å) are given (see Table 1

Bond lengths and angles in both molecules are unexceptional and in the expected ranges. The central quinazoline cores of the molecules are nearly planar, with maximum deviations of 0.073 (5) Å for atoms C5A and C5B in molecules A and B, respectively. The but-2-enamide units are all-trans and also nearly planar (r.m.s. deviations are 0.046 Å for molecule A and 0.042 Å for molecule B, for all non-H atoms including the directly neighboring quinazoline C atom). Their mean planes are inclined to the quinazoline ring by 47.8 (2) and 47.3 (2)° in molecules A and B, respectively. The chlorofluoroaniline rings are also twisted out of the mean plane of the quinazoline ring by 36.6 (2) and 36.9 (1)° for molecules A and B, respectively.

The simulated powder pattern of the acetonitrile–water solvate reported here does not agree with any of the free base forms of afatinib A–D reported in the literature (Gidwani et al., 2012).

3. Supramolecular features

In the crystal of the title compound, neighboring molecules are connected via N—H⋯O hydrogen bonds between the secondary amine and the amide keto O atom (see Table 1 for details). Molecules are connected through pairwise hydrogen bonds, graph-set motif R₂²18, to their symmetry-related counterparts, creating twofold rotation symmetric dimers of A and B molecules, respectively (Fig. 5). Individual A–A and B–B dimers are arranged in infinite stacks along the c-axis direction through π-stacking interactions between the quinazoline units, and through weaker and more tilted π-stacking interactions between the annulated and the fluorochloro benzene rings (Fig. 6). Individual stacking interactions between the quinazoline units are across the pseudo-inversion centers, forming close to centrosymmetric pairs of A–B dimers, with an interplanar angle between quinazoline units of only 1.24 (11)°. The centroid to centroid distance between the pyrimidine rings of the A and B molecules is 3.442 (2) Å, the perpendicular distances between the two rings are 3.3144 (18) and 3.3113 (17) Å, with a slippage between the rings of 0.937 Å. The distance between annulated and chlorofluorobenzene rings is at 3.827 (3) Å substantially larger, and the slippage is 1.506 Å. The stacks created along the c-axis direction are further stabilized via hydrogen bonds involving the solvent water molecules. The O5 water molecule hydrogen bonds to the N1 atom of the quinazoline unit, connecting every second molecule in the infinite stacks, and the O4 water molecule hydrogen bonds to the dimethylamine N atom and water molecule O5, thus bridging the two ends of the dimethylaminobut-2-enamide units, giving the stacks additional support and stiffness (see Table 1 for details).

Figure 5
Hydrogen-bonded twofold rotation dimer of A molecules, in two oblique views.

Figure 6
Stacks along the c-axis direction connected through hydrogen bonds (blue dashed lines) and π–π stacking interactions (green dashed lines). (a) Side view with distances (Å) between ring centroids (red spheres) involved in π–π stacking. (b) Top view down the c axis. Colour code: molecule A blue, molecule B green.

The four parallel stacks within each unit cell are interdigitating with each other, and are also connected through another hydrogen bond facilitated by the water molecule, which acts as a hydrogen-bonding acceptor for the amide N—H group. Additional weaker C—H⋯N and C—H⋯O interactions (Table 1) also contribute to the structure and lattice stability (see Table 1 for details). In combination, these interactions lead to an intricate three-dimensional superstructure facilitated by hydrogen bonding, π-stacking and interdigitation of molecule side arms (Fig. 7). In between the connected infinite stacks there remains some void space in the form of channels that stretch along the c-axis direction. Two different types of channels are found: channels along the fourfold rotational axis that are occupied by the acetonitrile solvent molecules, with the solvent molecules situated on that axis, and another set of parallel channels that stretch directly along the c-axis direction and are not occupied by any solvent.

Figure 7
Crystal packing viewed along the a axis, showing the interdigitation of parallel stacks along the c-axis direction (see Fig. 4

) and the hydrogen bonds (dashed lines) connecting them, as well as acetonitrile occupied and empty channels at the A- and B-faces and the center of the unit cell, respectively.

4. Synthesis and crystallization

High-purity afatinib free base (>99%) was acquired from LC Labs and high-purity solvents (acetonitrile and hexanes) were procured from Sigma–Aldrich (Sigma–Aldrich, St Louis, MO, USA). Crystals suitable for single X-ray diffraction studies were obtained by vapor diffusion (Spingler et al., 2012 ), where afatinib free base was solubilized in acetonitrile and exposed to vapor of hexanes in a closed system.

5. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. The structure exhibits pseudo-inversion symmetry emulating the space group P4/ncc, with two independent molecules, indicated by label suffixes A and B, in the asymmetric unit that are nearly related by a pseudo-inversion center. Exact inversion symmetry is not realized, as evidenced by the BASF value for racemic twinning, which refined to 0.02 (1). Exact inversion symmetry is broken by flipping of the THF ring, exchanging O and CH₂ units, and by a different disorder pattern for the tetrahydrofuranyl substituents of the two independent molecules.

Table 2
Experimental details

Crystal data
Chemical formula	2C₂₄H₂₅ClFN₅O₃·0.5C₂H₃N·4H₂O
M_r	1064.47
Crystal system, space group	Tetragonal, P42₁2
Temperature (K)	100
a, c (Å)	26.2427 (4), 15.1639 (3)
V (Å³)	10443.1 (4)
Z	8
Radiation type	Cu Kα
μ (mm⁻¹)	1.75
Crystal size (mm)	0.35 × 0.15 × 0.11

Data collection
Diffractometer	Rigaku Rapid II curved image plate
Absorption correction	Multi-scan (SCALEPACK; Otwinowski & Minor, 1997 )
T_min, T_max	0.681, 0.831
No. of measured, independent and observed [I > 2σ(I)] reflections	50059, 9958, 7679
R_int	0.056
(sin θ/λ)_max (Å⁻¹)	0.617

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.049, 0.122, 1.03
No. of reflections	9958
No. of parameters	797
No. of restraints	414
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.30, −0.40
Absolute structure	Flack x determined using 2765 quotients [(I⁺)−(I⁻)]/[(I⁺)+(I⁻)] (Parsons et al., 2013 )
Absolute structure parameter	0.02 (1)
Computer programs: HKL-3000 (Otwinowski & Minor, 1997), SHELXS97 (Sheldrick, 2008 ), SHELXL2016 (Sheldrick, 2015), SHELXLE (Hübschle et al., 2011 ), Mercury (Macrae et al., 2008 ) and publCIF (Westrip, 2010 ).

For the first molecule, suffix A, the two disordered moieties differ mostly by the position of the tetrahydrofuranyl O atom, which forms the flap of the THF's envelope conformation, and is bent to opposite sides for the two moieties. The ether O atom and the THF C atoms are only slightly shifted between the two disordered moieties. For molecule B, the disorder is more pronounced and extends to the ether oxygen atom. The THF ring is mirror imaged between the two disordered units, swapping the positions of the O atom with that of a methylene group and shifting the two units against each other.

All four THF moieties were restrained to have similar geometries (SAME commands of SHELXL2016; Sheldrick, 2015 ), and U_ij components of the anisotropic displacement parameters were restrained to be similar for disordered atoms closer to each other than 1.7 Å (SIMU commands of SHELXL2016; Sheldrick, 2015). The occupancy ratio refined to 0.718 (9):0.282 (9) for moieties A and C, and to 0.787 (5):0.213 (5) for moieties B and D.

The water H atoms were located in difference Fourier maps and refined with a distance restraint of O—H = 0.84 (2) Å, and C- and N-bound H atoms were placed in calculated positions and treated as riding, with C—H = 0.95–0.99 Å and N—H = 0.88 Å, and with U_iso(H) = 1.5U_eq(O,C-methyl) and 1.2U_eq(C,N) for other H atoms. Acetonitrile molecules are located on fourfold axes and the H atoms are fourfold disordered by symmetry.

Supporting information

CCDC reference: 1532940

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S2056989017002626/su5351sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989017002626/su5351Isup2.hkl

checkCIF report

Computing details top

Data collection: HKL-3000 (Otwinowski & Minor, 1997); cell refinement: HKL-3000 (Otwinowski & Minor, 1997); data reduction: HKL-3000 (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2016 (Sheldrick, 2015) and SHELXLE (Hübschle et al., 2011); molecular graphics: Mercury (Macrae et al., 2008); software used to prepare material for publication: publCIF (Westrip, 2010).

N-{4-(3-Chloro-4-fluoroanilino)-7-[(tetrahydrofuran-3-yl)oxy]quinazolin-6-yl}-4-(dimethylamino)but-2-enamide–acetonitrile–water (2/1/8) top

Crystal data top

2C₂₄H₂₅ClFN₅O₃·0.5C₂H₃N·4H₂O	D_x = 1.354 Mg m⁻³
M_r = 1064.47	Cu Kα radiation, λ = 1.54178 Å
Tetragonal, P42₁2	Cell parameters from 50059 reflections
a = 26.2427 (4) Å	θ = 3.4–72.1°
c = 15.1639 (3) Å	µ = 1.75 mm⁻¹
V = 10443.1 (4) Å³	T = 100 K
Z = 8	Needle, colorless
F(000) = 4472	0.35 × 0.15 × 0.11 mm

Data collection top

Rigaku Rapid II curved image plate diffractometer	9958 independent reflections
Radiation source: microfocus X-ray tube	7679 reflections with I > 2σ(I)
Laterally graded multilayer (Goebel) mirror monochromator	R_int = 0.056
ω scans	θ_max = 72.1°, θ_min = 3.4°
Absorption correction: multi-scan (SCALEPACK; Otwinowski & Minor, 1997)	h = −32→29
T_min = 0.681, T_max = 0.831	k = −26→32
50059 measured reflections	l = −17→18

Refinement top

Refinement on F²	Hydrogen site location: mixed
Least-squares matrix: full	H atoms treated by a mixture of independent and constrained refinement
R[F² > 2σ(F²)] = 0.049	w = 1/[σ²(F_o²) + (0.043P)² + 7.7055P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.122	(Δ/σ)_max < 0.001
S = 1.03	Δρ_max = 0.30 e Å⁻³
9958 reflections	Δρ_min = −0.40 e Å⁻³
797 parameters	Extinction correction: (SHELXL2016; Sheldrick, 2015), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
414 restraints	Extinction coefficient: 0.00033 (4)
Primary atom site location: structure-invariant direct methods	Absolute structure: Flack x determined using 2765 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
Secondary atom site location: difference Fourier map	Absolute structure parameter: 0.02 (1)

Special details top

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.

Refinement. The structure exhibits pseudo-inversion symmetry emulating the space group P4/ncc. Exact inversion symmetry is not realized (BASF value for racemic twinning 0.020 (10)).

Two tetrahydrofuran rings (related by pseudo-inversion) are disordered in differing ways. For one the ring is inverted at the oxygen. For the other the ring is mirror imaged swapping the position of the oxygen atom. All four moieties were restrained to have similar geometries, and Uij components of ADPs were restrained to be similar for disordered atoms closer to each other than 1.7 Angstrom. Occupancy ratios refined to 0.718 (9) to 0.282 (9) for moieties A and C, and to 0.787 (5) to 0.213 (5) for moieties B and D.

Water H atom O-H bond lengths were restrained to 0.84 (2) Angstrom.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq	Occ. (<1)
Cl1A	0.54599 (6)	0.23028 (6)	0.07047 (8)	0.0360 (4)
F1A	0.53997 (14)	0.11926 (14)	0.0581 (2)	0.0539 (11)
N1A	0.75215 (15)	0.32939 (16)	−0.2041 (2)	0.0181 (9)
N2A	0.69450 (16)	0.27266 (17)	−0.1303 (2)	0.0203 (10)
N3A	0.72103 (16)	0.19492 (16)	−0.0728 (2)	0.0184 (10)
H3A	0.746818	0.173820	−0.066170	0.022*
C1A	0.7073 (2)	0.3151 (2)	−0.1742 (3)	0.0201 (12)
H1A	0.680162	0.338100	−0.185363	0.024*
C2A	0.7321 (2)	0.24006 (19)	−0.1137 (3)	0.0168 (11)
C3A	0.78385 (19)	0.25115 (19)	−0.1379 (3)	0.0170 (12)
C4A	0.82582 (19)	0.22136 (19)	−0.1152 (3)	0.0153 (11)
H4A	0.820572	0.190478	−0.083829	0.018*
N4A	0.91692 (16)	0.20715 (16)	−0.1080 (2)	0.0166 (10)
H4A1	0.941274	0.200066	−0.145975	0.020*
C5A	0.87443 (19)	0.2355 (2)	−0.1371 (3)	0.0165 (11)
N5A	1.04992 (17)	0.12854 (18)	0.1606 (3)	0.0254 (11)
C6A	0.88205 (19)	0.2798 (2)	−0.1896 (3)	0.0166 (11)
C7A	0.84157 (19)	0.31025 (19)	−0.2122 (3)	0.0170 (11)
H7A	0.846941	0.340077	−0.246439	0.020*
C8A	0.79197 (19)	0.2972 (2)	−0.1844 (2)	0.0148 (11)
C9A	0.6739 (2)	0.1778 (2)	−0.0399 (3)	0.0202 (12)
C10A	0.6657 (2)	0.1251 (2)	−0.0379 (3)	0.0286 (13)
H10A	0.691093	0.102591	−0.059468	0.034*
C11A	0.6204 (3)	0.1056 (2)	−0.0044 (4)	0.0401 (16)
H11A	0.614608	0.069887	−0.003718	0.048*
C12A	0.5843 (2)	0.1383 (2)	0.0276 (4)	0.0350 (15)
C13A	0.5921 (2)	0.1902 (2)	0.0279 (3)	0.0271 (13)
C14A	0.6371 (2)	0.2107 (2)	−0.0059 (3)	0.0218 (12)
H14A	0.642506	0.246471	−0.005889	0.026*
O2A	0.89023 (13)	0.20073 (14)	0.03517 (19)	0.0215 (8)
C15A	0.92164 (19)	0.1904 (2)	−0.0238 (3)	0.0185 (12)
C16A	0.96642 (19)	0.1581 (2)	−0.0071 (3)	0.0193 (12)
H16A	0.990825	0.153465	−0.052699	0.023*
C17A	0.9736 (2)	0.1354 (2)	0.0697 (3)	0.0226 (13)
H17A	0.948054	0.139789	0.113545	0.027*
C18A	1.0186 (2)	0.1035 (2)	0.0928 (3)	0.0273 (14)
H18A	1.006874	0.069948	0.114942	0.033*
H18B	1.039407	0.097553	0.039344	0.033*
C19A	1.0761 (2)	0.1733 (2)	0.1246 (4)	0.0365 (15)
H19A	1.101101	0.162373	0.080490	0.055*
H19B	1.093584	0.191439	0.172349	0.055*
H19C	1.051144	0.196023	0.096980	0.055*
C20A	1.0865 (2)	0.0933 (2)	0.1990 (4)	0.0406 (15)
H20A	1.109638	0.081026	0.152897	0.061*
H20B	1.068379	0.064377	0.225073	0.061*
H20C	1.106198	0.110843	0.244765	0.061*
O1A	0.93145 (13)	0.28774 (13)	−0.2136 (2)	0.0206 (8)
C21A	0.9410 (6)	0.3289 (5)	−0.2758 (17)	0.022 (2)	0.718 (9)
H21A	0.915222	0.328831	−0.324386	0.027*	0.718 (9)
C22A	0.9429 (4)	0.3805 (5)	−0.2302 (6)	0.028 (2)	0.718 (9)
H22A	0.913750	0.402123	−0.248009	0.034*	0.718 (9)
H22B	0.942657	0.376599	−0.165226	0.034*	0.718 (9)
C23A	0.9922 (4)	0.4027 (4)	−0.2612 (6)	0.035 (2)	0.718 (9)
H23A	0.987716	0.420478	−0.318291	0.042*	0.718 (9)
H23B	1.005922	0.427143	−0.217496	0.042*	0.718 (9)
O3A	1.0252 (2)	0.3599 (2)	−0.2706 (4)	0.0374 (16)	0.718 (9)
C24A	0.9951 (6)	0.3219 (4)	−0.3124 (14)	0.028 (2)	0.718 (9)
H24A	1.008122	0.287436	−0.298384	0.034*	0.718 (9)
H24B	0.995381	0.326476	−0.377212	0.034*	0.718 (9)
C21C	0.9418 (16)	0.3249 (13)	−0.281 (5)	0.024 (3)	0.282 (9)
H21C	0.919160	0.318416	−0.332591	0.029*	0.282 (9)
C22C	0.9382 (9)	0.3802 (12)	−0.2548 (16)	0.026 (3)	0.282 (9)
H22E	0.907338	0.395998	−0.280376	0.031*	0.282 (9)
H22F	0.936849	0.383724	−0.189820	0.031*	0.282 (9)
C23C	0.9853 (9)	0.4050 (8)	−0.2906 (15)	0.032 (3)	0.282 (9)
H23E	0.975859	0.433007	−0.331212	0.039*	0.282 (9)
H23F	1.005744	0.419462	−0.241821	0.039*	0.282 (9)
O3C	1.0136 (5)	0.3679 (5)	−0.3358 (10)	0.037 (3)	0.282 (9)
C24C	0.9974 (16)	0.3185 (9)	−0.309 (4)	0.029 (3)	0.282 (9)
H24E	1.018320	0.306284	−0.258484	0.035*	0.282 (9)
H24F	1.000348	0.293884	−0.357681	0.035*	0.282 (9)
O4A	0.99752 (15)	0.18082 (17)	0.2950 (2)	0.0274 (9)
H4C	1.011 (2)	0.164 (2)	0.253 (3)	0.041*
H4D	0.9765 (17)	0.2009 (18)	0.269 (3)	0.041*
O5A	0.92301 (15)	0.23351 (18)	0.2047 (2)	0.0360 (10)
H5C	0.912 (2)	0.226 (2)	0.154 (2)	0.054*
H5D	0.8972 (16)	0.246 (2)	0.228 (4)	0.054*
N6A	0.500000	0.000000	0.0706 (10)	0.100 (5)
C25A	0.500000	0.000000	−0.0068 (10)	0.065 (5)
C26A	0.500000	0.000000	−0.1044 (10)	0.096 (6)
H26A	0.470993	−0.018658	−0.125464	0.144*	0.25
H26B	0.530662	−0.015792	−0.125464	0.144*	0.25
H26C	0.498346	0.034450	−0.125464	0.144*	0.25
Cl1B	0.95744 (6)	0.26892 (6)	−0.55731 (8)	0.0386 (4)
F1B	0.96334 (12)	0.37984 (13)	−0.5399 (2)	0.0437 (9)
N1B	0.74716 (16)	0.16513 (17)	−0.3001 (2)	0.0194 (10)
N2B	0.80584 (16)	0.22306 (17)	−0.3705 (2)	0.0202 (10)
N3B	0.77931 (16)	0.30174 (16)	−0.4234 (2)	0.0167 (9)
H3B	0.753408	0.322621	−0.430670	0.020*
C1B	0.7923 (2)	0.1797 (2)	−0.3279 (3)	0.0211 (12)
H1B	0.819331	0.156553	−0.316512	0.025*
C2B	0.7685 (2)	0.25621 (19)	−0.3862 (3)	0.0167 (11)
C3B	0.71662 (19)	0.24443 (19)	−0.3633 (3)	0.0143 (11)
C4B	0.67449 (19)	0.27542 (19)	−0.3855 (3)	0.0170 (11)
H4B	0.679762	0.306750	−0.415510	0.020*
N4B	0.58392 (16)	0.28961 (16)	−0.3930 (2)	0.0197 (10)
H4B1	0.559066	0.295893	−0.355643	0.024*
C5B	0.6261 (2)	0.2604 (2)	−0.3638 (3)	0.0175 (11)
N5B	0.45204 (17)	0.37462 (18)	−0.6582 (2)	0.0253 (11)
C6B	0.6177 (2)	0.2159 (2)	−0.3129 (3)	0.0223 (12)
C7B	0.6581 (2)	0.1847 (2)	−0.2923 (3)	0.0204 (12)
H7B	0.652526	0.154174	−0.260097	0.024*
C8B	0.7077 (2)	0.1982 (2)	−0.3191 (3)	0.0183 (12)
C9B	0.8275 (2)	0.3199 (2)	−0.4520 (3)	0.0176 (11)
C10B	0.8359 (2)	0.3723 (2)	−0.4483 (3)	0.0208 (11)
H10B	0.810418	0.394157	−0.424751	0.025*
C11B	0.8815 (2)	0.3928 (2)	−0.4789 (3)	0.0274 (13)
H11B	0.887333	0.428497	−0.476902	0.033*
C12B	0.9179 (2)	0.3606 (2)	−0.5119 (3)	0.0285 (13)
C13B	0.9105 (2)	0.3082 (2)	−0.5159 (3)	0.0243 (12)
C14B	0.8650 (2)	0.2880 (2)	−0.4860 (3)	0.0214 (12)
H14B	0.859325	0.252258	−0.488762	0.026*
O2B	0.61156 (13)	0.29856 (14)	−0.53473 (19)	0.0209 (8)
C15B	0.58026 (19)	0.3081 (2)	−0.4757 (3)	0.0170 (11)
C16B	0.53511 (19)	0.3408 (2)	−0.4920 (3)	0.0202 (12)
H16B	0.510440	0.344796	−0.446629	0.024*
C17B	0.5283 (2)	0.36465 (19)	−0.5681 (3)	0.0206 (12)
H17B	0.553618	0.360544	−0.612326	0.025*
C18B	0.4836 (2)	0.3974 (2)	−0.5888 (3)	0.0272 (14)
H18C	0.462781	0.402146	−0.534975	0.033*
H18D	0.495562	0.431380	−0.608348	0.033*
C19B	0.4253 (2)	0.3290 (2)	−0.6251 (3)	0.0325 (14)
H19D	0.405129	0.313979	−0.672842	0.049*
H19E	0.402741	0.338744	−0.576490	0.049*
H19F	0.450346	0.304135	−0.604111	0.049*
C20B	0.4154 (2)	0.4119 (2)	−0.6936 (4)	0.0407 (15)
H20D	0.396854	0.396662	−0.743090	0.061*
H20E	0.433746	0.442196	−0.713900	0.061*
H20F	0.391252	0.421513	−0.647204	0.061*
O1B	0.56935 (19)	0.2103 (2)	−0.2827 (3)	0.0193 (12)	0.787 (5)
C21B	0.5595 (2)	0.1713 (3)	−0.2175 (4)	0.0215 (14)	0.787 (5)
H21B	0.588006	0.168742	−0.173961	0.026*	0.787 (5)
C22B	0.5094 (2)	0.1847 (3)	−0.1725 (4)	0.0226 (14)	0.787 (5)
H22C	0.509418	0.173841	−0.109982	0.027*	0.787 (5)
H22D	0.502461	0.221710	−0.175706	0.027*	0.787 (5)
C23B	0.4716 (3)	0.1550 (3)	−0.2253 (5)	0.0273 (15)	0.787 (5)
H23C	0.440105	0.148926	−0.190939	0.033*	0.787 (5)
H23D	0.462678	0.173237	−0.280321	0.033*	0.787 (5)
O3B	0.49710 (19)	0.10754 (19)	−0.2447 (3)	0.0357 (13)	0.787 (5)
C24B	0.5490 (3)	0.1204 (3)	−0.2617 (5)	0.0354 (17)	0.787 (5)
H24C	0.555014	0.122991	−0.325968	0.042*	0.787 (5)
H24D	0.571903	0.093880	−0.237446	0.042*	0.787 (5)
O1D	0.5663 (7)	0.1987 (7)	−0.3159 (11)	0.025 (4)	0.213 (5)
C21D	0.5525 (7)	0.1519 (9)	−0.2718 (12)	0.026 (3)	0.213 (5)
H21E	0.570895	0.122722	−0.299762	0.032*	0.213 (5)
C22D	0.5634 (7)	0.1525 (10)	−0.1741 (12)	0.030 (3)	0.213 (5)
H22G	0.586501	0.180850	−0.158334	0.036*	0.213 (5)
H22H	0.578862	0.119913	−0.154763	0.036*	0.213 (5)
C23D	0.5114 (7)	0.1598 (9)	−0.1336 (12)	0.029 (3)	0.213 (5)
H23G	0.510087	0.144714	−0.073751	0.035*	0.213 (5)
H23H	0.502886	0.196451	−0.129409	0.035*	0.213 (5)
O3D	0.4770 (6)	0.1344 (8)	−0.1910 (11)	0.032 (3)	0.213 (5)
C24D	0.4952 (7)	0.1431 (10)	−0.2782 (12)	0.030 (3)	0.213 (5)
H24G	0.478318	0.173350	−0.304025	0.036*	0.213 (5)
H24H	0.487987	0.113276	−0.316080	0.036*	0.213 (5)
O4B	0.50270 (15)	0.32327 (17)	−0.7952 (2)	0.0268 (9)
H4E	0.489 (2)	0.340 (2)	−0.752 (3)	0.040*
H4F	0.5294 (15)	0.3086 (19)	−0.774 (3)	0.040*
O5B	0.58067 (15)	0.27400 (17)	−0.7083 (2)	0.0304 (9)
H5E	0.589 (2)	0.284 (2)	−0.657 (2)	0.046*
H5F	0.6065 (16)	0.262 (2)	−0.736 (3)	0.046*
N6B	1.000000	0.500000	−0.4494 (7)	0.073 (4)
C25B	1.000000	0.500000	−0.5259 (8)	0.039 (3)
C26B	1.000000	0.500000	−0.6212 (7)	0.046 (3)
H26D	1.029352	0.481890	−0.642284	0.069*	0.25
H26E	1.001008	0.534475	−0.642284	0.069*	0.25
H26F	0.969640	0.483635	−0.642284	0.069*	0.25

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1A	0.0283 (8)	0.0446 (9)	0.0350 (6)	0.0075 (7)	0.0128 (6)	0.0002 (6)
F1A	0.040 (2)	0.046 (2)	0.076 (2)	−0.0179 (18)	0.0315 (19)	0.0005 (19)
N1A	0.016 (2)	0.020 (2)	0.0188 (17)	0.0039 (18)	0.0012 (16)	0.0001 (17)
N2A	0.019 (3)	0.022 (3)	0.0201 (18)	0.004 (2)	−0.0011 (17)	0.0057 (18)
N3A	0.015 (2)	0.020 (2)	0.0203 (17)	0.001 (2)	0.0018 (17)	0.0050 (17)
C1A	0.023 (3)	0.019 (3)	0.018 (2)	0.005 (2)	0.000 (2)	0.000 (2)
C2A	0.017 (3)	0.020 (3)	0.0126 (18)	0.002 (2)	−0.0013 (19)	−0.0014 (18)
C3A	0.017 (3)	0.019 (3)	0.015 (2)	0.002 (2)	0.0008 (19)	0.0001 (18)
C4A	0.017 (3)	0.018 (3)	0.0109 (19)	0.001 (2)	−0.0007 (18)	−0.0006 (18)
N4A	0.014 (2)	0.020 (2)	0.0154 (17)	0.0072 (19)	0.0011 (16)	0.0038 (16)
C5A	0.017 (3)	0.017 (3)	0.0150 (19)	0.007 (2)	0.0028 (18)	0.0031 (19)
N5A	0.020 (3)	0.029 (3)	0.028 (2)	0.006 (2)	−0.0035 (19)	0.009 (2)
C6A	0.015 (3)	0.017 (3)	0.018 (2)	0.004 (2)	0.0012 (19)	−0.0011 (19)
C7A	0.019 (3)	0.016 (3)	0.017 (2)	−0.002 (2)	−0.0002 (19)	0.0025 (18)
C8A	0.013 (3)	0.016 (3)	0.0152 (19)	0.003 (2)	−0.0012 (18)	−0.0030 (18)
C9A	0.019 (3)	0.026 (3)	0.0152 (19)	−0.004 (2)	0.001 (2)	0.002 (2)
C10A	0.032 (3)	0.020 (3)	0.034 (2)	0.001 (3)	0.010 (2)	−0.005 (2)
C11A	0.044 (4)	0.025 (4)	0.051 (3)	−0.012 (3)	0.019 (3)	−0.003 (3)
C12A	0.027 (3)	0.034 (4)	0.044 (3)	−0.010 (3)	0.018 (3)	0.003 (3)
C13A	0.019 (3)	0.037 (4)	0.025 (2)	0.001 (3)	0.007 (2)	0.001 (2)
C14A	0.023 (3)	0.026 (3)	0.016 (2)	−0.001 (2)	0.001 (2)	0.001 (2)
O2A	0.018 (2)	0.028 (2)	0.0180 (14)	0.0041 (17)	0.0020 (14)	0.0017 (15)
C15A	0.015 (3)	0.020 (3)	0.020 (2)	0.001 (2)	−0.001 (2)	0.001 (2)
C16A	0.020 (3)	0.023 (3)	0.0157 (19)	0.008 (2)	0.001 (2)	0.001 (2)
C17A	0.017 (3)	0.030 (3)	0.021 (2)	0.004 (3)	0.002 (2)	0.004 (2)
C18A	0.027 (3)	0.031 (4)	0.024 (2)	0.011 (3)	−0.003 (2)	0.005 (2)
C19A	0.021 (3)	0.047 (4)	0.041 (3)	0.000 (3)	0.002 (3)	0.019 (3)
C20A	0.033 (4)	0.044 (4)	0.045 (3)	0.009 (3)	−0.010 (3)	0.017 (3)
O1A	0.0143 (19)	0.022 (2)	0.0254 (16)	0.0020 (16)	0.0037 (14)	0.0069 (15)
C21A	0.017 (4)	0.023 (4)	0.027 (4)	−0.002 (3)	0.006 (3)	0.009 (4)
C22A	0.027 (4)	0.022 (4)	0.035 (4)	0.000 (3)	0.000 (3)	0.003 (4)
C23A	0.023 (4)	0.032 (4)	0.050 (5)	−0.003 (3)	−0.002 (4)	−0.002 (4)
O3A	0.023 (3)	0.031 (3)	0.058 (3)	−0.001 (2)	−0.001 (2)	−0.006 (3)
C24A	0.023 (4)	0.030 (4)	0.031 (4)	0.003 (3)	0.007 (3)	0.006 (3)
C21C	0.022 (6)	0.021 (6)	0.028 (6)	0.002 (6)	0.005 (6)	0.005 (6)
C22C	0.021 (6)	0.022 (6)	0.035 (7)	0.005 (5)	0.000 (6)	0.009 (6)
C23C	0.024 (6)	0.030 (6)	0.043 (7)	0.002 (5)	−0.001 (6)	0.006 (6)
O3C	0.025 (5)	0.035 (5)	0.050 (5)	−0.003 (5)	0.012 (5)	0.004 (5)
C24C	0.022 (6)	0.030 (6)	0.035 (6)	0.000 (6)	0.008 (6)	0.004 (6)
O4A	0.024 (2)	0.036 (3)	0.0221 (16)	−0.0015 (18)	−0.0012 (17)	0.0049 (16)
O5A	0.025 (2)	0.061 (3)	0.0220 (17)	0.013 (2)	0.0019 (16)	−0.0072 (19)
N6A	0.108 (9)	0.108 (9)	0.084 (10)	0.000	0.000	0.000
C25A	0.068 (8)	0.068 (8)	0.060 (9)	0.000	0.000	0.000
C26A	0.110 (10)	0.110 (10)	0.067 (10)	0.000	0.000	0.000
Cl1B	0.0316 (8)	0.0372 (9)	0.0470 (7)	0.0096 (7)	0.0191 (6)	0.0103 (6)
F1B	0.026 (2)	0.044 (2)	0.0611 (19)	−0.0100 (16)	0.0132 (16)	0.0082 (17)
N1B	0.018 (3)	0.022 (2)	0.0182 (17)	0.0003 (19)	−0.0031 (16)	0.0021 (17)
N2B	0.016 (2)	0.021 (3)	0.0237 (19)	0.0019 (19)	0.0009 (17)	0.0036 (18)
N3B	0.014 (2)	0.015 (2)	0.0209 (17)	−0.0010 (19)	0.0018 (16)	0.0016 (17)
C1B	0.016 (3)	0.022 (3)	0.025 (2)	0.003 (2)	−0.002 (2)	0.007 (2)
C2B	0.018 (3)	0.019 (3)	0.0125 (18)	0.001 (2)	−0.0006 (19)	−0.0004 (18)
C3B	0.016 (3)	0.014 (3)	0.013 (2)	0.000 (2)	−0.0005 (18)	−0.0001 (17)
C4B	0.018 (3)	0.016 (3)	0.017 (2)	−0.001 (2)	−0.0005 (19)	0.0025 (19)
N4B	0.015 (2)	0.028 (3)	0.0164 (17)	0.005 (2)	0.0022 (17)	0.0016 (17)
C5B	0.019 (3)	0.018 (3)	0.015 (2)	0.004 (2)	−0.0008 (19)	−0.0008 (19)
N5B	0.022 (3)	0.031 (3)	0.0231 (19)	0.007 (2)	−0.0067 (19)	0.0055 (19)
C6B	0.018 (3)	0.026 (3)	0.023 (2)	−0.005 (2)	0.003 (2)	0.005 (2)
C7B	0.019 (3)	0.022 (3)	0.020 (2)	0.001 (2)	0.002 (2)	0.005 (2)
C8B	0.021 (3)	0.019 (3)	0.0145 (19)	0.004 (2)	0.0005 (19)	0.0056 (19)
C9B	0.018 (3)	0.018 (3)	0.017 (2)	−0.002 (2)	0.0013 (19)	0.0031 (19)
C10B	0.019 (3)	0.020 (3)	0.024 (2)	−0.003 (2)	−0.0003 (19)	0.0019 (19)
C11B	0.029 (3)	0.020 (3)	0.033 (2)	−0.007 (2)	0.003 (2)	0.003 (2)
C12B	0.023 (3)	0.033 (4)	0.030 (2)	−0.009 (3)	0.004 (2)	0.004 (2)
C13B	0.026 (3)	0.023 (3)	0.024 (2)	0.005 (2)	0.003 (2)	0.005 (2)
C14B	0.024 (3)	0.020 (3)	0.020 (2)	−0.001 (2)	0.001 (2)	0.002 (2)
O2B	0.015 (2)	0.030 (2)	0.0173 (14)	0.0087 (16)	0.0007 (14)	−0.0002 (15)
C15B	0.012 (3)	0.020 (3)	0.019 (2)	−0.001 (2)	−0.0009 (19)	0.000 (2)
C16B	0.016 (3)	0.024 (3)	0.020 (2)	0.004 (2)	0.001 (2)	0.000 (2)
C17B	0.020 (3)	0.019 (3)	0.023 (2)	0.004 (2)	−0.005 (2)	−0.003 (2)
C18B	0.027 (3)	0.030 (4)	0.024 (2)	0.011 (3)	−0.003 (2)	−0.001 (2)
C19B	0.024 (3)	0.036 (4)	0.038 (3)	0.002 (3)	−0.007 (3)	0.009 (3)
C20B	0.037 (4)	0.043 (4)	0.042 (3)	0.016 (3)	−0.014 (3)	0.009 (3)
O1B	0.013 (2)	0.023 (3)	0.022 (3)	0.001 (2)	0.006 (2)	0.008 (2)
C21B	0.019 (3)	0.022 (3)	0.024 (3)	0.002 (3)	−0.002 (2)	0.010 (3)
C22B	0.020 (3)	0.026 (3)	0.022 (3)	−0.002 (3)	0.000 (2)	0.005 (2)
C23B	0.023 (3)	0.028 (4)	0.032 (3)	−0.004 (3)	0.003 (3)	−0.003 (3)
O3B	0.029 (3)	0.025 (3)	0.053 (3)	−0.006 (2)	0.008 (2)	−0.004 (2)
C24B	0.026 (4)	0.033 (4)	0.047 (3)	0.002 (3)	0.014 (3)	0.000 (3)
O1D	0.025 (6)	0.023 (7)	0.027 (7)	0.001 (6)	0.007 (6)	0.006 (6)
C21D	0.019 (5)	0.027 (5)	0.033 (5)	−0.003 (5)	0.005 (5)	0.005 (5)
C22D	0.023 (6)	0.033 (6)	0.035 (6)	−0.005 (6)	0.000 (6)	0.006 (6)
C23D	0.024 (6)	0.032 (6)	0.031 (6)	−0.003 (6)	−0.004 (6)	0.001 (6)
O3D	0.024 (6)	0.036 (6)	0.036 (6)	−0.005 (5)	0.001 (5)	0.003 (5)
C24D	0.022 (6)	0.031 (6)	0.037 (6)	−0.001 (5)	−0.002 (5)	0.005 (5)
O4B	0.019 (2)	0.039 (3)	0.0230 (16)	−0.0001 (18)	−0.0041 (17)	−0.0031 (16)
O5B	0.021 (2)	0.047 (3)	0.0224 (17)	0.0058 (19)	−0.0002 (15)	−0.0103 (17)
N6B	0.086 (7)	0.086 (7)	0.048 (7)	0.000	0.000	0.000
C25B	0.037 (5)	0.037 (5)	0.043 (6)	0.000	0.000	0.000
C26B	0.050 (5)	0.050 (5)	0.039 (6)	0.000	0.000	0.000

Geometric parameters (Å, º) top

Cl1A—C13A	1.729 (6)	F1B—C12B	1.362 (6)
F1A—C12A	1.349 (6)	N1B—C1B	1.315 (6)
N1A—C1A	1.315 (6)	N1B—C8B	1.380 (6)
N1A—C8A	1.377 (6)	N2B—C2B	1.332 (6)
N2A—C2A	1.329 (6)	N2B—C1B	1.355 (6)
N2A—C1A	1.340 (6)	N3B—C2B	1.351 (6)
N3A—C2A	1.368 (6)	N3B—C9B	1.420 (6)
N3A—C9A	1.407 (6)	N3B—H3B	0.8800
N3A—H3A	0.8800	C1B—H1B	0.9500
C1A—H1A	0.9500	C2B—C3B	1.439 (7)
C2A—C3A	1.437 (7)	C3B—C8B	1.407 (6)
C3A—C4A	1.394 (6)	C3B—C4B	1.413 (7)
C3A—C8A	1.415 (6)	C4B—C5B	1.369 (7)
C4A—C5A	1.369 (6)	C4B—H4B	0.9500
C4A—H4A	0.9500	N4B—C15B	1.348 (5)
N4A—C15A	1.356 (5)	N4B—C5B	1.417 (6)
N4A—C5A	1.411 (6)	N4B—H4B1	0.8800
N4A—H4A1	0.8800	C5B—C6B	1.418 (7)
C5A—C6A	1.424 (6)	N5B—C18B	1.466 (6)
N5A—C20A	1.454 (7)	N5B—C20B	1.472 (7)
N5A—C19A	1.467 (6)	N5B—C19B	1.474 (6)
N5A—C18A	1.472 (6)	C6B—O1B	1.358 (7)
C6A—O1A	1.363 (5)	C6B—C7B	1.375 (7)
C6A—C7A	1.373 (6)	C6B—O1D	1.424 (17)
C7A—C8A	1.411 (7)	C7B—C8B	1.410 (7)
C7A—H7A	0.9500	C7B—H7B	0.9500
C9A—C14A	1.396 (7)	C9B—C14B	1.390 (7)
C9A—C10A	1.399 (7)	C9B—C10B	1.396 (7)
C10A—C11A	1.389 (8)	C10B—C11B	1.391 (7)
C10A—H10A	0.9500	C10B—H10B	0.9500
C11A—C12A	1.367 (8)	C11B—C12B	1.370 (7)
C11A—H11A	0.9500	C11B—H11B	0.9500
C12A—C13A	1.378 (8)	C12B—C13B	1.391 (8)
C13A—C14A	1.393 (7)	C13B—C14B	1.383 (7)
C14A—H14A	0.9500	C14B—H14B	0.9500
O2A—C15A	1.246 (6)	O2B—C15B	1.241 (5)
C15A—C16A	1.471 (7)	C15B—C16B	1.483 (7)
C16A—C17A	1.322 (6)	C16B—C17B	1.325 (6)
C16A—H16A	0.9500	C16B—H16B	0.9500
C17A—C18A	1.491 (7)	C17B—C18B	1.489 (7)
C17A—H17A	0.9500	C17B—H17B	0.9500
C18A—H18A	0.9900	C18B—H18C	0.9900
C18A—H18B	0.9900	C18B—H18D	0.9900
C19A—H19A	0.9800	C19B—H19D	0.9800
C19A—H19B	0.9800	C19B—H19E	0.9800
C19A—H19C	0.9800	C19B—H19F	0.9800
C20A—H20A	0.9800	C20B—H20D	0.9800
C20A—H20B	0.9800	C20B—H20E	0.9800
C20A—H20C	0.9800	C20B—H20F	0.9800
O1A—C21C	1.43 (6)	O1B—C21B	1.445 (7)
O1A—C21A	1.456 (19)	C21B—C24B	1.520 (9)
C21A—C22A	1.522 (12)	C21B—C22B	1.521 (8)
C21A—C24A	1.534 (10)	C21B—H21B	1.0000
C21A—H21A	1.0000	C22B—C23B	1.495 (8)
C22A—C23A	1.495 (10)	C22B—H22C	0.9900
C22A—H22A	0.9900	C22B—H22D	0.9900
C22A—H22B	0.9900	C23B—O3B	1.444 (8)
C23A—O3A	1.426 (9)	C23B—H23C	0.9900
C23A—H23A	0.9900	C23B—H23D	0.9900
C23A—H23B	0.9900	O3B—C24B	1.427 (8)
O3A—C24A	1.423 (15)	C24B—H24C	0.9900
C24A—H24A	0.9900	C24B—H24D	0.9900
C24A—H24B	0.9900	O1D—C21D	1.445 (19)
C21C—C22C	1.51 (2)	C21D—C22D	1.508 (19)
C21C—C24C	1.53 (2)	C21D—C24D	1.524 (19)
C21C—H21C	1.0000	C21D—H21E	1.0000
C22C—C23C	1.497 (19)	C22D—C23D	1.509 (19)
C22C—H22E	0.9900	C22D—H22G	0.9900
C22C—H22F	0.9900	C22D—H22H	0.9900
C23C—O3C	1.403 (18)	C23D—O3D	1.420 (18)
C23C—H23E	0.9900	C23D—H23G	0.9900
C23C—H23F	0.9900	C23D—H23H	0.9900
O3C—C24C	1.43 (2)	O3D—C24D	1.424 (18)
C24C—H24E	0.9900	C24D—H24G	0.9900
C24C—H24F	0.9900	C24D—H24H	0.9900
O4A—H4C	0.87 (3)	O4B—H4E	0.87 (3)
O4A—H4D	0.86 (3)	O4B—H4F	0.86 (3)
O5A—H5C	0.84 (3)	O5B—H5E	0.85 (3)
O5A—H5D	0.84 (3)	O5B—H5F	0.85 (3)
N6A—C25A	1.174 (17)	N6B—C25B	1.161 (14)
C25A—C26A	1.48 (2)	C25B—C26B	1.444 (14)
C26A—H26A	0.9600	C26B—H26D	0.9600
C26A—H26B	0.9600	C26B—H26E	0.9600
C26A—H26C	0.9600	C26B—H26F	0.9600
C26A—H26Aⁱ	0.9600	C26B—H26D^iv	0.9600
C26A—H26Aⁱⁱ	0.9600	C26B—H26D^v	0.9600
C26A—H26Aⁱⁱⁱ	0.9600	C26B—H26D^vi	0.9600
C26A—H26Bⁱ	0.9600	C26B—H26E^iv	0.9600
C26A—H26Bⁱⁱ	0.9600	C26B—H26E^v	0.9600
C26A—H26Bⁱⁱⁱ	0.9600	C26B—H26E^vi	0.9600
C26A—H26Cⁱ	0.9599	C26B—H26F^iv	0.9599
C26A—H26Cⁱⁱ	0.9599	C26B—H26F^v	0.9599
C26A—H26Cⁱⁱⁱ	0.9599	C26B—H26F^vi	0.9599
Cl1B—C13B	1.725 (5)

C1A—N1A—C8A	115.3 (4)	C2B—N2B—C1B	116.1 (4)
C2A—N2A—C1A	116.2 (4)	C2B—N3B—C9B	127.7 (5)
C2A—N3A—C9A	128.6 (5)	C2B—N3B—H3B	116.2
C2A—N3A—H3A	115.7	C9B—N3B—H3B	116.2
C9A—N3A—H3A	115.7	N1B—C1B—N2B	129.3 (5)
N1A—C1A—N2A	129.3 (5)	N1B—C1B—H1B	115.3
N1A—C1A—H1A	115.3	N2B—C1B—H1B	115.3
N2A—C1A—H1A	115.3	N2B—C2B—N3B	119.8 (5)
N2A—C2A—N3A	119.1 (5)	N2B—C2B—C3B	120.9 (5)
N2A—C2A—C3A	121.5 (4)	N3B—C2B—C3B	119.3 (5)
N3A—C2A—C3A	119.4 (5)	C8B—C3B—C4B	118.7 (5)
C4A—C3A—C8A	118.9 (5)	C8B—C3B—C2B	117.2 (5)
C4A—C3A—C2A	124.8 (5)	C4B—C3B—C2B	124.0 (4)
C8A—C3A—C2A	116.3 (4)	C5B—C4B—C3B	120.2 (5)
C5A—C4A—C3A	121.6 (5)	C5B—C4B—H4B	119.9
C5A—C4A—H4A	119.2	C3B—C4B—H4B	119.9
C3A—C4A—H4A	119.2	C15B—N4B—C5B	122.8 (4)
C15A—N4A—C5A	122.5 (4)	C15B—N4B—H4B1	118.6
C15A—N4A—H4A1	118.7	C5B—N4B—H4B1	118.6
C5A—N4A—H4A1	118.7	C4B—C5B—N4B	119.6 (5)
C4A—C5A—N4A	121.2 (4)	C4B—C5B—C6B	120.7 (5)
C4A—C5A—C6A	119.2 (5)	N4B—C5B—C6B	119.6 (5)
N4A—C5A—C6A	119.6 (4)	C18B—N5B—C20B	111.0 (4)
C20A—N5A—C19A	110.4 (4)	C18B—N5B—C19B	110.8 (4)
C20A—N5A—C18A	111.4 (4)	C20B—N5B—C19B	110.6 (4)
C19A—N5A—C18A	111.1 (4)	O1B—C6B—C7B	125.4 (5)
O1A—C6A—C7A	125.5 (5)	O1B—C6B—C5B	114.8 (5)
O1A—C6A—C5A	114.1 (4)	C7B—C6B—C5B	119.7 (5)
C7A—C6A—C5A	120.4 (5)	C7B—C6B—O1D	123.2 (9)
C6A—C7A—C8A	119.9 (5)	C5B—C6B—O1D	113.0 (9)
C6A—C7A—H7A	120.1	C6B—C7B—C8B	119.8 (5)
C8A—C7A—H7A	120.1	C6B—C7B—H7B	120.1
N1A—C8A—C7A	119.1 (4)	C8B—C7B—H7B	120.1
N1A—C8A—C3A	121.2 (5)	N1B—C8B—C3B	121.2 (5)
C7A—C8A—C3A	119.7 (5)	N1B—C8B—C7B	118.4 (4)
C14A—C9A—C10A	119.7 (5)	C3B—C8B—C7B	120.4 (5)
C14A—C9A—N3A	122.8 (5)	C14B—C9B—C10B	119.8 (5)
C10A—C9A—N3A	117.4 (5)	C14B—C9B—N3B	122.8 (5)
C11A—C10A—C9A	120.3 (5)	C10B—C9B—N3B	117.3 (5)
C11A—C10A—H10A	119.8	C11B—C10B—C9B	120.2 (5)
C9A—C10A—H10A	119.8	C11B—C10B—H10B	119.9
C12A—C11A—C10A	119.4 (6)	C9B—C10B—H10B	119.9
C12A—C11A—H11A	120.3	C12B—C11B—C10B	119.0 (5)
C10A—C11A—H11A	120.3	C12B—C11B—H11B	120.5
F1A—C12A—C11A	119.2 (6)	C10B—C11B—H11B	120.5
F1A—C12A—C13A	119.6 (5)	F1B—C12B—C11B	119.7 (5)
C11A—C12A—C13A	121.3 (5)	F1B—C12B—C13B	118.4 (5)
C12A—C13A—C14A	120.4 (5)	C11B—C12B—C13B	121.8 (5)
C12A—C13A—Cl1A	119.9 (4)	C14B—C13B—C12B	119.1 (5)
C14A—C13A—Cl1A	119.7 (4)	C14B—C13B—Cl1B	120.5 (4)
C13A—C14A—C9A	118.9 (5)	C12B—C13B—Cl1B	120.4 (4)
C13A—C14A—H14A	120.5	C13B—C14B—C9B	120.1 (5)
C9A—C14A—H14A	120.5	C13B—C14B—H14B	120.0
O2A—C15A—N4A	123.0 (5)	C9B—C14B—H14B	120.0
O2A—C15A—C16A	122.0 (4)	O2B—C15B—N4B	123.4 (5)
N4A—C15A—C16A	114.9 (4)	O2B—C15B—C16B	121.7 (4)
C17A—C16A—C15A	121.6 (5)	N4B—C15B—C16B	114.9 (4)
C17A—C16A—H16A	119.2	C17B—C16B—C15B	121.7 (4)
C15A—C16A—H16A	119.2	C17B—C16B—H16B	119.2
C16A—C17A—C18A	124.9 (5)	C15B—C16B—H16B	119.2
C16A—C17A—H17A	117.5	C16B—C17B—C18B	124.2 (5)
C18A—C17A—H17A	117.5	C16B—C17B—H17B	117.9
N5A—C18A—C17A	110.8 (5)	C18B—C17B—H17B	117.9
N5A—C18A—H18A	109.5	N5B—C18B—C17B	111.1 (4)
C17A—C18A—H18A	109.5	N5B—C18B—H18C	109.4
N5A—C18A—H18B	109.5	C17B—C18B—H18C	109.4
C17A—C18A—H18B	109.5	N5B—C18B—H18D	109.4
H18A—C18A—H18B	108.1	C17B—C18B—H18D	109.4
N5A—C19A—H19A	109.5	H18C—C18B—H18D	108.0
N5A—C19A—H19B	109.5	N5B—C19B—H19D	109.5
H19A—C19A—H19B	109.5	N5B—C19B—H19E	109.5
N5A—C19A—H19C	109.5	H19D—C19B—H19E	109.5
H19A—C19A—H19C	109.5	N5B—C19B—H19F	109.5
H19B—C19A—H19C	109.5	H19D—C19B—H19F	109.5
N5A—C20A—H20A	109.5	H19E—C19B—H19F	109.5
N5A—C20A—H20B	109.5	N5B—C20B—H20D	109.5
H20A—C20A—H20B	109.5	N5B—C20B—H20E	109.5
N5A—C20A—H20C	109.5	H20D—C20B—H20E	109.5
H20A—C20A—H20C	109.5	N5B—C20B—H20F	109.5
H20B—C20A—H20C	109.5	H20D—C20B—H20F	109.5
C6A—O1A—C21C	118.2 (19)	H20E—C20B—H20F	109.5
C6A—O1A—C21A	116.7 (8)	C6B—O1B—C21B	118.4 (5)
O1A—C21A—C22A	111.8 (16)	O1B—C21B—C24B	110.6 (6)
O1A—C21A—C24A	107.7 (13)	O1B—C21B—C22B	107.4 (5)
C22A—C21A—C24A	103.9 (9)	C24B—C21B—C22B	104.1 (5)
O1A—C21A—H21A	111.0	O1B—C21B—H21B	111.5
C22A—C21A—H21A	111.0	C24B—C21B—H21B	111.5
C24A—C21A—H21A	111.0	C22B—C21B—H21B	111.5
C23A—C22A—C21A	103.4 (7)	C23B—C22B—C21B	102.3 (5)
C23A—C22A—H22A	111.1	C23B—C22B—H22C	111.3
C21A—C22A—H22A	111.1	C21B—C22B—H22C	111.3
C23A—C22A—H22B	111.1	C23B—C22B—H22D	111.3
C21A—C22A—H22B	111.1	C21B—C22B—H22D	111.3
H22A—C22A—H22B	109.0	H22C—C22B—H22D	109.2
O3A—C23A—C22A	104.5 (7)	O3B—C23B—C22B	104.5 (5)
O3A—C23A—H23A	110.8	O3B—C23B—H23C	110.8
C22A—C23A—H23A	110.8	C22B—C23B—H23C	110.8
O3A—C23A—H23B	110.8	O3B—C23B—H23D	110.8
C22A—C23A—H23B	110.8	C22B—C23B—H23D	110.8
H23A—C23A—H23B	108.9	H23C—C23B—H23D	108.9
C24A—O3A—C23A	105.0 (8)	C24B—O3B—C23B	106.0 (5)
O3A—C24A—C21A	105.6 (11)	O3B—C24B—C21B	107.5 (5)
O3A—C24A—H24A	110.6	O3B—C24B—H24C	110.2
C21A—C24A—H24A	110.6	C21B—C24B—H24C	110.2
O3A—C24A—H24B	110.6	O3B—C24B—H24D	110.2
C21A—C24A—H24B	110.6	C21B—C24B—H24D	110.2
H24A—C24A—H24B	108.7	H24C—C24B—H24D	108.5
O1A—C21C—C22C	117 (4)	C6B—O1D—C21D	119.5 (15)
O1A—C21C—C24C	108 (4)	O1D—C21D—C22D	113.5 (19)
C22C—C21C—C24C	103.6 (18)	O1D—C21D—C24D	110.3 (17)
O1A—C21C—H21C	109.4	C22D—C21D—C24D	104.5 (13)
C22C—C21C—H21C	109.4	O1D—C21D—H21E	109.4
C24C—C21C—H21C	109.4	C22D—C21D—H21E	109.4
C23C—C22C—C21C	105.9 (16)	C24D—C21D—H21E	109.4
C23C—C22C—H22E	110.6	C21D—C22D—C23D	103.3 (14)
C21C—C22C—H22E	110.6	C21D—C22D—H22G	111.1
C23C—C22C—H22F	110.6	C23D—C22D—H22G	111.1
C21C—C22C—H22F	110.6	C21D—C22D—H22H	111.1
H22E—C22C—H22F	108.7	C23D—C22D—H22H	111.1
O3C—C23C—C22C	108.2 (15)	H22G—C22D—H22H	109.1
O3C—C23C—H23E	110.0	O3D—C23D—C22D	105.4 (14)
C22C—C23C—H23E	110.0	O3D—C23D—H23G	110.7
O3C—C23C—H23F	110.0	C22D—C23D—H23G	110.7
C22C—C23C—H23F	110.0	O3D—C23D—H23H	110.7
H23E—C23C—H23F	108.4	C22D—C23D—H23H	110.7
C23C—O3C—C24C	109.3 (17)	H23G—C23D—H23H	108.8
O3C—C24C—C21C	105 (2)	C23D—O3D—C24D	106.3 (14)
O3C—C24C—H24E	110.7	O3D—C24D—C21D	107.2 (14)
C21C—C24C—H24E	110.7	O3D—C24D—H24G	110.3
O3C—C24C—H24F	110.7	C21D—C24D—H24G	110.3
C21C—C24C—H24F	110.7	O3D—C24D—H24H	110.3
H24E—C24C—H24F	108.8	C21D—C24D—H24H	110.3
H4C—O4A—H4D	104 (5)	H24G—C24D—H24H	108.5
H5C—O5A—H5D	101 (6)	H4E—O4B—H4F	107 (5)
N6A—C25A—C26A	180.0	H5E—O5B—H5F	110 (5)
C25A—C26A—H26A	109.5	N6B—C25B—C26B	180.0
C25A—C26A—H26B	109.5	C25B—C26B—H26D	109.5
H26A—C26A—H26B	109.5	C25B—C26B—H26E	109.5
C25A—C26A—H26C	109.5	H26D—C26B—H26E	109.5
H26A—C26A—H26C	109.5	C25B—C26B—H26F	109.5
H26B—C26A—H26C	109.5	H26D—C26B—H26F	109.5
C25A—C26A—H26Aⁱ	109.471 (1)	H26E—C26B—H26F	109.5
C25A—C26A—H26Aⁱⁱ	109.5	C25B—C26B—H26D^iv	109.469 (1)
C25A—C26A—H26Aⁱⁱⁱ	109.471 (1)	C25B—C26B—H26D^v	109.469 (1)
C25A—C26A—H26Bⁱ	109.5	C25B—C26B—H26D^vi	109.469 (2)
H26Aⁱ—C26A—H26Bⁱ	109.5	C25B—C26B—H26E^iv	109.467 (2)
C25A—C26A—H26Bⁱⁱ	109.471 (1)	H26D^iv—C26B—H26E^iv	109.5
H26Aⁱⁱ—C26A—H26Bⁱⁱ	109.5	C25B—C26B—H26E^v	109.467 (1)
C25A—C26A—H26Bⁱⁱⁱ	109.471 (1)	H26D^v—C26B—H26E^v	109.5
H26Aⁱⁱⁱ—C26A—H26Bⁱⁱⁱ	109.5	C25B—C26B—H26E^vi	109.467 (1)
C25A—C26A—H26Cⁱ	109.473 (1)	H26D^vi—C26B—H26E^vi	109.5
H26Aⁱ—C26A—H26Cⁱ	109.5	C25B—C26B—H26F^iv	109.470 (1)
H26Bⁱ—C26A—H26Cⁱ	109.5	H26D^iv—C26B—H26F^iv	109.5
C25A—C26A—H26Cⁱⁱ	109.5	H26E^iv—C26B—H26F^iv	109.5
H26Aⁱⁱ—C26A—H26Cⁱⁱ	109.5	C25B—C26B—H26F^v	109.470 (2)
H26Bⁱⁱ—C26A—H26Cⁱⁱ	109.5	H26D^v—C26B—H26F^v	109.5
C25A—C26A—H26Cⁱⁱⁱ	109.5	H26E^v—C26B—H26F^v	109.5
H26Aⁱⁱⁱ—C26A—H26Cⁱⁱⁱ	109.5	C25B—C26B—H26F^vi	109.470 (1)
H26Bⁱⁱⁱ—C26A—H26Cⁱⁱⁱ	109.5	H26D^vi—C26B—H26F^vi	109.5
C1B—N1B—C8B	115.2 (4)	H26E^vi—C26B—H26F^vi	109.5

C8A—N1A—C1A—N2A	−3.0 (7)	C1B—N2B—C2B—N3B	175.9 (4)
C2A—N2A—C1A—N1A	0.3 (7)	C1B—N2B—C2B—C3B	−3.6 (6)
C1A—N2A—C2A—N3A	−176.9 (4)	C9B—N3B—C2B—N2B	2.0 (7)
C1A—N2A—C2A—C3A	3.0 (6)	C9B—N3B—C2B—C3B	−178.6 (4)
C9A—N3A—C2A—N2A	−3.6 (7)	N2B—C2B—C3B—C8B	3.9 (6)
C9A—N3A—C2A—C3A	176.5 (4)	N3B—C2B—C3B—C8B	−175.6 (4)
N2A—C2A—C3A—C4A	173.4 (4)	N2B—C2B—C3B—C4B	−173.7 (4)
N3A—C2A—C3A—C4A	−6.6 (7)	N3B—C2B—C3B—C4B	6.9 (6)
N2A—C2A—C3A—C8A	−3.4 (6)	C8B—C3B—C4B—C5B	0.2 (6)
N3A—C2A—C3A—C8A	176.5 (4)	C2B—C3B—C4B—C5B	177.7 (4)
C8A—C3A—C4A—C5A	−0.2 (7)	C3B—C4B—C5B—N4B	−174.6 (4)
C2A—C3A—C4A—C5A	−177.0 (4)	C3B—C4B—C5B—C6B	5.2 (7)
C3A—C4A—C5A—N4A	175.0 (4)	C15B—N4B—C5B—C4B	43.7 (7)
C3A—C4A—C5A—C6A	−4.5 (7)	C15B—N4B—C5B—C6B	−136.0 (5)
C15A—N4A—C5A—C4A	−45.2 (7)	C4B—C5B—C6B—O1B	168.8 (5)
C15A—N4A—C5A—C6A	134.4 (5)	N4B—C5B—C6B—O1B	−11.5 (7)
C4A—C5A—C6A—O1A	−174.7 (4)	C4B—C5B—C6B—C7B	−6.5 (7)
N4A—C5A—C6A—O1A	5.8 (6)	N4B—C5B—C6B—C7B	173.2 (4)
C4A—C5A—C6A—C7A	5.1 (7)	C4B—C5B—C6B—O1D	−164.5 (9)
N4A—C5A—C6A—C7A	−174.4 (4)	N4B—C5B—C6B—O1D	15.2 (10)
O1A—C6A—C7A—C8A	178.8 (4)	O1B—C6B—C7B—C8B	−172.3 (5)
C5A—C6A—C7A—C8A	−1.0 (7)	C5B—C6B—C7B—C8B	2.4 (7)
C1A—N1A—C8A—C7A	−178.5 (4)	O1D—C6B—C7B—C8B	158.1 (9)
C1A—N1A—C8A—C3A	2.3 (6)	C1B—N1B—C8B—C3B	−1.4 (6)
C6A—C7A—C8A—N1A	177.1 (4)	C1B—N1B—C8B—C7B	179.2 (4)
C6A—C7A—C8A—C3A	−3.8 (6)	C4B—C3B—C8B—N1B	176.5 (4)
C4A—C3A—C8A—N1A	−176.4 (4)	C2B—C3B—C8B—N1B	−1.2 (6)
C2A—C3A—C8A—N1A	0.6 (6)	C4B—C3B—C8B—C7B	−4.2 (6)
C4A—C3A—C8A—C7A	4.4 (6)	C2B—C3B—C8B—C7B	178.1 (4)
C2A—C3A—C8A—C7A	−178.6 (4)	C6B—C7B—C8B—N1B	−177.8 (4)
C2A—N3A—C9A—C14A	−31.5 (7)	C6B—C7B—C8B—C3B	2.9 (7)
C2A—N3A—C9A—C10A	151.7 (5)	C2B—N3B—C9B—C14B	32.6 (7)
C14A—C9A—C10A—C11A	1.7 (8)	C2B—N3B—C9B—C10B	−149.8 (4)
N3A—C9A—C10A—C11A	178.6 (5)	C14B—C9B—C10B—C11B	0.4 (7)
C9A—C10A—C11A—C12A	−0.8 (9)	N3B—C9B—C10B—C11B	−177.3 (4)
C10A—C11A—C12A—F1A	178.5 (5)	C9B—C10B—C11B—C12B	−0.5 (7)
C10A—C11A—C12A—C13A	−0.5 (9)	C10B—C11B—C12B—F1B	−178.2 (4)
F1A—C12A—C13A—C14A	−178.0 (5)	C10B—C11B—C12B—C13B	0.2 (8)
C11A—C12A—C13A—C14A	1.0 (9)	F1B—C12B—C13B—C14B	178.7 (4)
F1A—C12A—C13A—Cl1A	2.0 (8)	C11B—C12B—C13B—C14B	0.3 (8)
C11A—C12A—C13A—Cl1A	−179.0 (5)	F1B—C12B—C13B—Cl1B	−1.2 (7)
C12A—C13A—C14A—C9A	−0.1 (7)	C11B—C12B—C13B—Cl1B	−179.6 (4)
Cl1A—C13A—C14A—C9A	179.9 (4)	C12B—C13B—C14B—C9B	−0.4 (7)
C10A—C9A—C14A—C13A	−1.2 (7)	Cl1B—C13B—C14B—C9B	179.5 (4)
N3A—C9A—C14A—C13A	−177.9 (4)	C10B—C9B—C14B—C13B	0.1 (7)
C5A—N4A—C15A—O2A	−3.5 (8)	N3B—C9B—C14B—C13B	177.6 (4)
C5A—N4A—C15A—C16A	175.4 (4)	C5B—N4B—C15B—O2B	4.9 (8)
O2A—C15A—C16A—C17A	5.0 (8)	C5B—N4B—C15B—C16B	−175.8 (4)
N4A—C15A—C16A—C17A	−173.9 (5)	O2B—C15B—C16B—C17B	−5.6 (8)
C15A—C16A—C17A—C18A	−178.0 (5)	N4B—C15B—C16B—C17B	175.2 (5)
C20A—N5A—C18A—C17A	166.2 (4)	C15B—C16B—C17B—C18B	179.2 (5)
C19A—N5A—C18A—C17A	−70.3 (5)	C20B—N5B—C18B—C17B	−166.4 (5)
C16A—C17A—C18A—N5A	112.2 (6)	C19B—N5B—C18B—C17B	70.3 (6)
C7A—C6A—O1A—C21C	−12 (2)	C16B—C17B—C18B—N5B	−113.4 (6)
C5A—C6A—O1A—C21C	167 (2)	C7B—C6B—O1B—C21B	6.0 (8)
C7A—C6A—O1A—C21A	−6.8 (11)	C5B—C6B—O1B—C21B	−168.9 (5)
C5A—C6A—O1A—C21A	173.0 (10)	C6B—O1B—C21B—C24B	−86.5 (7)
C6A—O1A—C21A—C22A	81.6 (14)	C6B—O1B—C21B—C22B	160.5 (5)
C6A—O1A—C21A—C24A	−164.8 (10)	O1B—C21B—C22B—C23B	93.5 (6)
O1A—C21A—C22A—C23A	128.0 (11)	C24B—C21B—C22B—C23B	−23.8 (7)
C24A—C21A—C22A—C23A	12.1 (18)	C21B—C22B—C23B—O3B	38.2 (6)
C21A—C22A—C23A—O3A	−33.6 (13)	C22B—C23B—O3B—C24B	−38.4 (7)
C22A—C23A—O3A—C24A	43.4 (10)	C23B—O3B—C24B—C21B	22.5 (7)
C23A—O3A—C24A—C21A	−35.0 (15)	O1B—C21B—C24B—O3B	−113.5 (6)
O1A—C21A—C24A—O3A	−105.5 (13)	C22B—C21B—C24B—O3B	1.6 (7)
C22A—C21A—C24A—O3A	13.2 (19)	C7B—C6B—O1D—C21D	19 (2)
C6A—O1A—C21C—C22C	75 (4)	C5B—C6B—O1D—C21D	176.1 (14)
C6A—O1A—C21C—C24C	−168 (2)	C6B—O1D—C21D—C22D	59 (2)
O1A—C21C—C22C—C23C	133 (3)	C6B—O1D—C21D—C24D	175.9 (15)
C24C—C21C—C22C—C23C	15 (5)	O1D—C21D—C22D—C23D	104 (2)
C21C—C22C—C23C—O3C	1 (4)	C24D—C21D—C22D—C23D	−16 (2)
C22C—C23C—O3C—C24C	−19 (3)	C21D—C22D—C23D—O3D	33 (2)
C23C—O3C—C24C—C21C	28 (5)	C22D—C23D—O3D—C24D	−37 (2)
O1A—C21C—C24C—O3C	−150 (4)	C23D—O3D—C24D—C21D	27 (3)
C22C—C21C—C24C—O3C	−26 (6)	O1D—C21D—C24D—O3D	−128 (2)
C8B—N1B—C1B—N2B	1.9 (7)	C22D—C21D—C24D—O3D	−5 (3)
C2B—N2B—C1B—N1B	0.7 (7)

Symmetry codes: (i) −x+1, −y, z; (ii) −y+1/2, x−1/2, z; (iii) y+1/2, −x+1/2, z; (iv) −x+2, −y+1, z; (v) −y+3/2, x−1/2, z; (vi) y+1/2, −x+3/2, z.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N4A—H4A1···O4B^vii	0.88	1.94	2.804 (5)	166
N3A—H3A···O2A^viii	0.88	2.22	3.088 (5)	167
O4A—H4C···N5A	0.85 (5)	1.97 (5)	2.816 (6)	173 (4)
O4A—H4D···O5A	0.86 (5)	1.91 (5)	2.759 (6)	169 (5)
O5A—H5C···O2A	0.85 (3)	2.00 (4)	2.844 (4)	174 (5)
O5A—H5D···N1B^viii	0.83 (5)	1.98 (5)	2.775 (6)	161 (5)
C4A—H4A···O2A^viii	0.95	2.31	3.246 (6)	168
C16A—H16A···O4B^vii	0.95	2.41	3.183 (6)	139
C22A—H22A···O3A^vi	0.99	2.40	3.353 (13)	162
C24A—H24A···O5B^vii	0.99	2.50	3.388 (14)	150
N4B—H4B1···O4A^ix	0.88	1.96	2.820 (5)	167
N3B—H3B···O2B^x	0.88	2.26	3.123 (5)	166
O4B—H4E···N5B	0.87 (5)	1.95 (5)	2.811 (5)	175 (6)
O4B—H4F···O5B	0.86 (4)	1.91 (4)	2.756 (5)	169 (4)
O5B—H5E···O2B	0.85 (4)	1.98 (3)	2.828 (4)	173 (5)
O5B—H5F···N1A^x	0.86 (4)	1.95 (4)	2.794 (5)	169 (5)
C4B—H4B···O2B^x	0.95	2.34	3.280 (6)	169
C16B—H16B···O4A^ix	0.95	2.42	3.197 (6)	139
C22B—H22D···O5A^ix	0.99	2.43	3.160 (8)	130
C24B—H24D···O3Bⁱⁱⁱ	0.99	2.57	3.455 (9)	149

Symmetry codes: (iii) y+1/2, −x+1/2, z; (vi) y+1/2, −x+3/2, z; (vii) x+1/2, −y+1/2, −z−1; (viii) −y+1, −x+1, −z; (ix) x−1/2, −y+1/2, −z; (x) −y+1, −x+1, −z−1.

Acknowledgements

The authors acknowledge funding for this work provided by the Sao Paulo Research Foundation (FAPESP) (grant Nos. 2015/15456-5 and 2015/05685-7).

References

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Volume 73| Part 3| March 2017| Pages 417-422

https://doi.org/10.1107/S2056989017002626

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research communications\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

A new solvate of afatinib, a specific inhibitor of the ErbB family of tyrosine kinases

1. Chemical context

2. Structural commentary

3. Supra­molecular features

4. Synthesis and crystallization

5. Refinement

Supporting information

Acknowledgements

References

research communications

3. Supramolecular features