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Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 72| Part 12| December 2016| Pages 1783-1785
https://doi.org/10.1107/S2056989016017734

Crystal structure of vilazodone hydro­chloride methanol monosolvate

CROSSMARK_Color_square_no_text.svg
Xiu-Rong Hu,a* Jia-Li Yeb and Jian-Ming Gua

aChemistry Department, Zhejiang University, Hangzhou 310028, People's Republic of China, and bCollege of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou 310053, People's Republic of China
*Correspondence e-mail: huxiurong@zju.edu.cn

Edited by D.-J. Xu, Zhejiang University (Yuquan Campus), China (Received 30 October 2016; accepted 7 November 2016; online 10 November 2016)

In the title compound, C26H28N5O2+·Cl−·CH3OH {systematic name: 4-(2-carbamoyl-1-benzo­furan-5-yl)-1-[4-(5-cyano-1H-indol-3-yl)but­yl]piperazin-1-ium chloride methanol monosolvate}, the protonated piperazine ring adopts a chair conformation. The indole ring plane is nearly perpendicular to the benzo­furan ring system, with a dihedral angle of 85.77 (2)°. In the crystal, the organic cations, Cl− anions and methanol solvent mol­ecules are linked by classical N—H⋯O and N—H⋯Cl hydrogen bonds, and weak C—H⋯O and C—H⋯π inter­actions into a three-dimensional supra­molecular architecture.

CCDC reference: 1439516

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1. Chemical context

Major depression disorder (MDD) currently ranks as the world's fourth greatest cause of illness and is expected to rank second by the year 2020 according to WHO studies (Murray & Lopez, 1996[Murray, C. J. & Lopez, A. D. (1996). Science, 274, 740-743.]). The title compound, viladozone hydro­chloride (marketed as Viibryd by Forest Pharmaceuticals), is a new treatment option for MDD. It was approved on January 21, 2011 by the FDA, licensed by Merck KGaA.

[Scheme 1]

Vilazodone hydro­chloride is a selective serotonin re-uptake inhibitor (SSRI) with properties that are most similar to those of citalopram, escitalopram (levapro), fluoveline, proxetin, and sertraline. The new drug differs from its predecessors by also acting as a partial agonist at serotonergic 5-HT1A receptors. The mechanism of the anti­depressant effect of vilazodone is thought to be related to its enhancement of serotonergic activity in the CNS through selective inhibition of serotonin re-uptake. Vilazodone binds with high affinity to the serotonin re-uptake site but not to the norepinephrine or dopamine re-uptake site. As a result, vilazodone potently and selectively inhibits the re-uptake of serotonin (Choi et al., 2012[Choi, E., Zmarlicka, M. & Ehret, M. J. (2012). Am. J. Health Syst. Pharm. 69, 1551-1557.]; Reed et al., 2012[Reed, C. R., Kajdasz, D. K., Whalen, H., Athanasiou, M. C., Gallipoli, S. & Thase, M. E. (2012). Curr. Med. Res. Opin. 28, 27-39.]; Schwartz & Singh, 2012[Schwartz, T. & Singh, M. (2012). Neuropsychiatr. Dis. Treat. pp. 123-139.]). Many patents and papers have been reported on the synthesis, polymorphism and bioavailability of this drug (Bathe et al., 2011[Bathe, A., Helfert, B., Neuenfeld, S., Kniel, H., Bartels, M., Rudolph, S. & Bothcher, H. (2011). US Patent 7981894.]; Heinrich & Böttcher, 2004[Heinrich, T. & Böttcher, H. (2004). Bioorg. Med. Chem. Lett. 14, 2681-2684.]; Leksic et al., 2013[Leksic, E., Pavlicia, D., Skalec, S. D., Dogan, J., Mrsic, N. & Pavlicic, D. (2013). WO Patent 2013078361.]; Lu et al., 2012[Lu, T.-X., Zhang, C. & Hu, C. (2012). Chin. J. Med. Chem. 22, 74-81.]) but up till now, its three-dimensional structure has not been reported. This work concerns the crystal structure of vilazodone hydro­chloride methanol solvate, (I)[link], studied at 275 K.

2. Structural commentary

The title compound combines indole-butyl-amine and chromenonyl piperazine structural elements in a single mol­ecular entity. The asymmetric unit of (I)[link] contains one protonated vilazodone cation, one Cl− anion and one methanol mol­ecule (Fig. 1[link]).

[Figure 1]
Figure 1
The mol­ecular structure of the title compound, showing the atom-labelling scheme and displacement ellipsoids at 40% probability level. H atoms are shown as small circles of arbitrary radii.

The expected proton transfer from hydro­chloric acid to atom N3 of piperazine occurs; the H atom on the piperazine N3 atom was located unequivocally in the electron-density map. The six-membered piperazine ring adopts a chair conformation. The electron-withdrawing cyano group at position 5 on the indole is twisted out of the mean plane of the indole unit, as indicated by the relevant torsion angles N1—C1—C2—C7 and N1—C1—C2—C3 [144.3 (2) and 34.0 (2)°, respectively]. The conformation of the cyano group is similar to that of other drugs containing nitrile groups, such as bicalutamide and Febuxostat (Hu & Gu, 2005[Hu, X.-R. & Gu, J.-M. (2005). Acta Cryst. E61, o3897-o3898.]; Jiang et al., 2011[Jiang, Q.-Y., Qian, J.-J., Gu, J.-M., Tang, G.-P. & Hu, X.-R. (2011). Acta Cryst. E67, o1232.]). The indole moiety is connected by an n-butyl linker to the piperazine ring. The conformation of the butyl chain is of some inter­est. Three C atoms of the butyl group (C10, C11 and C12) are coplanar with atom C9 of the indole, as confirmed by the C9—C10—C11—C12 torsion angle of 179.2 (2)°, meanwhile atoms C11, C12 and C13 are coplanar with piperazine atom N3. A dihedral angle of 80.9 (2)° is formed between the mean planes of N3/C11–C13 and C9–C12. The dihedral angle between the C9–C12 mean plane and the indole plane is 10.0 (2)°. The second piperazine N atom, N4, is bonded to the benzo­furan ring. The formamide group is almost coplanar with the connected benzo­furan ring, making a dihedral angle of 2.53 (2)°. The indole ring is almost perpendicular to the benzo­furan ring, as indicated by the dihedral angle of 85.77 (2)° between them.

3. Supra­molecular features

In the crystal, N3—H3A⋯Cl1, O3—H3B⋯Cl1 and N2—H2⋯O3i [symmetry code: (i) 1 − x, −y, 1 − z] hydrogen bonds (Table 1[link]), connect the Cl− ion to two neighbouring cations and a methanol mol­ecule, forming a mol­ecular dimer. Hydrogen bonds N5—H5A⋯Cl1ii [symmetry code: (ii) 1 − x, 2 − y, 2 − z] and N3—H3A⋯Cl1 link another two neighbouring cations and the Cl− anion into a mol­ecular sheet. As a result, 28-membered rings with the graph-set motif R44(28) are generated (Fig. 2[link]).

Table 1
Hydrogen-bond geometry (Å, °)

Cg5 is the centroid of the C18–C22 ring.
D—H⋯A D—H H⋯A D⋯A D—H⋯A
N2—H2⋯O3i 0.86 2.25 2.971 (3) 141
N3—H3A⋯Cl1 0.91 2.18 3.0787 (19) 172
N5—H5A⋯Cl1ii 0.86 2.42 3.250 (2) 162
N5—H5B⋯N1iii 0.86 2.33 3.151 (4) 160
O3—H3B⋯Cl1 0.82 2.38 3.195 (2) 171
C13—H13A⋯O2iv 0.97 2.33 3.272 (3) 164
C19—H19⋯O3v 0.93 2.55 3.348 (3) 144
C14—H14B⋯Cg5vi 0.97 2.48 3.393 (2) 156
Symmetry codes: (i) -x+1, -y, -z+1; (ii) -x, -y+2, -z+2; (iii) -x, -y+1, -z+1; (iv) x, y-1, z-1; (v) x-1, y, z; (vi) -x, -y+1, -z+2.
[Figure 2]
Figure 2
Part of the crystal packing of the title compound. Hydrogen bonds are shown as dashed lines. H atoms not involved in hydrogen bonding have been omitted for clarity.

4. Synthesis and crystallization

Vilazodone hydro­chloride was supplied by Hangzhou HEZE pharmaceutical Technology Co., Ltd. It was recrystallized from methanol solution, giving single crystals suitable for X-ray diffraction.

5. Refinement

Experimental details including the crystal data, data collection and refinement are summarized in Table 2[link]. The difference density indicated the presence of an H atom at atom N3, showing proton transfer from HCl to the amino group of the vilazodone ring. This H atom was placed in a calculated position with N—H = 0.91 Å and refined as riding with Uiso(H) = 1.2Ueq(N). All other H atoms were placed in calculated positions with O—H = 0.82, N—H = 0.86 and C—H = 0.93–0.98 Å, and included in the refinement in a riding model with Uiso(H) = 1.2 or 1.5Ueq(carrier atom).

Table 2
Experimental details

Crystal data
Chemical formula C26H28N5O2+·Cl−·CH4O
Mr 510.03
Crystal system, space group Triclinic, P[\overline{1}]
Temperature (K) 296
a, b, c (Å) 10.5572 (5), 11.0764 (4), 11.4408 (5)
α, β, γ (°) 104.622 (1), 97.327 (2), 90.695 (1)
V (Å3) 1282.57 (10)
Z 2
Radiation type Mo Kα
μ (mm−1) 0.19
Crystal size (mm) 0.50 × 0.46 × 0.38
 
Data collection
Diffractometer Rigaku R-AXIS RAPID/ZJUG
Absorption correction Multi-scan (ABSCOR; Higashi, 1995[Higashi, T. (1995). ABSCOR. Rigaku Corporation, Tokyo, Japan.])
Tmin, Tmax 0.91, 0.93
No. of measured, independent and observed [I > 2σ(I)] reflections 11090, 5000, 3865
Rint 0.044
(sin θ/λ)max (Å−1) 0.617
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.053, 0.154, 1.00
No. of reflections 5000
No. of parameters 328
H-atom treatment H-atom parameters constrained
Δρmax, Δρmin (e Å−3) 0.31, −0.43
Computer programs: PROCESS-AUTO (Rigaku, 2006[Rigaku (2006). PROCESS-AUTO. Rigaku Corporation, Tokyo, Japan.]), CrystalStructure (Rigaku, 2007[Rigaku (2007). CrystalStructure. Rigaku Corporation, Tokyo, Japan.]), SHELXS97 and SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]), ORTEP-3 for Windows and WinGX (Farrugia, 2012[Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849-854.]).

Supporting information

CCDC reference: 1439516

Crystal structure: contains datablocks global, I. DOI: https://doi.org/10.1107/S2056989016017734/xu5894sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989016017734/xu5894Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989016017734/xu5894Isup3.cml

checkCIF report


Computing details top

Data collection: PROCESS-AUTO (Rigaku, 2006); cell refinement: PROCESS-AUTO (Rigaku, 2006); data reduction: CrystalStructure (Rigaku, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: WinGX (Farrugia, 2012).

4-(2-Carbamoyl-1-benzofuran-5-yl)-1-[4-(5-cyano-1H-indol-3-yl)butyl]piperazin-1-ium chloride methanol monosolvate top
Crystal data top
C26H28N5O2+·Cl−·CH4OZ = 2
Mr = 510.03F(000) = 540
Triclinic, P1Dx = 1.321 Mg m−3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 10.5572 (5) ÅCell parameters from 9260 reflections
b = 11.0764 (4) Åθ = 3.1–27.4°
c = 11.4408 (5) ŵ = 0.19 mm−1
α = 104.622 (1)°T = 296 K
β = 97.327 (2)°Chunk, colorless
γ = 90.695 (1)°0.50 × 0.46 × 0.38 mm
V = 1282.57 (10) Å3
Data collection top
Rigaku R-AXIS RAPID/ZJUG
diffractometer		5000 independent reflections
Radiation source: rotating anode3865 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.044
Detector resolution: 10.00 pixels mm-1θmax = 26.0°, θmin = 3.1°
ω scansh = −12→13
Absorption correction: multi-scan
(ABSCOR; Higashi, 1995)		k = −13→13
Tmin = 0.91, Tmax = 0.93l = −14→14
11090 measured reflections
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.053H-atom parameters constrained
wR(F2) = 0.154 w = 1/[σ2(Fo2) + (0.0589P)2 + 0.9975P]
where P = (Fo2 + 2Fc2)/3
S = 1.00(Δ/σ)max < 0.001
5000 reflectionsΔρmax = 0.31 e Å−3
328 parametersΔρmin = −0.43 e Å−3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.096 (6)
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. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
C10.4328 (3)−0.1560 (3)−0.0343 (3)0.0527 (7)
C20.4157 (2)−0.2028 (2)0.0690 (2)0.0456 (6)
C30.4277 (3)−0.3323 (3)0.0575 (3)0.0540 (7)
H30.4489−0.3833−0.01460.065*
C40.4084 (3)−0.3835 (2)0.1517 (3)0.0523 (6)
H40.4165−0.46840.14480.063*
C50.3764 (2)−0.3039 (2)0.2580 (2)0.0428 (6)
C60.3641 (2)−0.1733 (2)0.2719 (2)0.0386 (5)
C70.3851 (2)−0.1233 (2)0.1752 (2)0.0422 (5)
H70.3788−0.03820.18190.051*
C80.3290 (2)−0.2199 (2)0.4438 (2)0.0454 (6)
H80.3117−0.21360.52270.054*
C90.3331 (2)−0.1218 (2)0.3923 (2)0.0400 (5)
C100.3143 (3)0.0136 (2)0.4511 (2)0.0467 (6)
H10A0.23620.03870.41090.056*
H10B0.38470.06390.43860.056*
C110.3065 (3)0.0404 (2)0.5869 (2)0.0473 (6)
H11A0.38410.01390.62650.057*
H11B0.2355−0.00950.59890.057*
C120.2892 (3)0.1776 (2)0.6494 (2)0.0483 (6)
H12A0.31730.19280.73620.058*
H12B0.34200.23050.61740.058*
C130.1509 (2)0.2113 (2)0.6295 (2)0.0424 (5)
H13A0.12230.19170.54250.051*
H13B0.09930.15970.66400.051*
C140.1686 (2)0.3853 (2)0.8187 (2)0.0401 (5)
H14A0.25990.37560.83510.048*
H14B0.12540.33110.85720.048*
C150.1392 (2)0.5194 (2)0.8736 (2)0.0390 (5)
H15A0.16240.53920.96140.047*
H15B0.19010.57440.84220.047*
C16−0.0349 (2)0.5071 (2)0.7125 (2)0.0413 (5)
H16A0.01260.56000.67600.050*
H16B−0.12510.52080.69520.050*
C17−0.0103 (2)0.3716 (2)0.6576 (2)0.0429 (5)
H17A−0.06200.31860.69050.051*
H17B−0.03520.35160.57000.051*
C18−0.0372 (2)0.6568 (2)0.91099 (19)0.0355 (5)
C19−0.1686 (2)0.6817 (2)0.8901 (2)0.0418 (5)
H19−0.22270.62310.83200.050*
C20−0.2185 (2)0.7889 (2)0.9523 (2)0.0445 (6)
H20−0.30440.80490.93620.053*
C21−0.1359 (2)0.8719 (2)1.0397 (2)0.0382 (5)
C22−0.0071 (2)0.8519 (2)1.0647 (2)0.0360 (5)
C230.0436 (2)0.7436 (2)0.9991 (2)0.0376 (5)
H230.13010.72961.01410.045*
C24−0.0552 (2)1.0322 (2)1.1871 (2)0.0398 (5)
C250.0438 (2)0.9582 (2)1.1613 (2)0.0411 (5)
H250.12800.97301.19860.049*
C26−0.0613 (3)1.1537 (2)1.2777 (2)0.0434 (6)
C270.5996 (3)0.6981 (3)0.6439 (3)0.0676 (8)
H27A0.56590.68320.55920.101*
H27B0.69080.71130.65370.101*
H27C0.56280.77080.68990.101*
Cl10.27357 (7)0.52925 (6)0.58111 (7)0.0569 (2)
N10.4448 (3)−0.1220 (3)−0.1192 (2)0.0661 (7)
N20.3540 (2)−0.32906 (18)0.3639 (2)0.0475 (5)
H20.3552−0.40150.37840.057*
N30.12773 (18)0.34606 (16)0.68429 (16)0.0348 (4)
H3A0.17400.39350.64910.042*
N40.00394 (18)0.54081 (17)0.84536 (17)0.0382 (4)
N5−0.1755 (2)1.20379 (19)1.2756 (2)0.0507 (5)
H5A−0.18581.27401.32580.061*
H5B−0.23881.16591.22400.061*
O1−0.16729 (16)0.98325 (15)1.11414 (15)0.0439 (4)
O20.0344 (2)1.20077 (18)1.34781 (18)0.0616 (5)
O30.5686 (2)0.5922 (2)0.6869 (2)0.0730 (6)
H3B0.49210.57310.66730.110*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0437 (14)0.0638 (17)0.0454 (15)0.0061 (12)0.0123 (11)0.0015 (13)
C20.0368 (12)0.0535 (14)0.0425 (13)0.0042 (11)0.0080 (10)0.0039 (11)
C30.0483 (15)0.0508 (15)0.0524 (16)0.0055 (12)0.0119 (12)−0.0086 (12)
C40.0533 (15)0.0368 (12)0.0602 (17)0.0061 (11)0.0097 (13)−0.0011 (11)
C50.0392 (12)0.0340 (11)0.0506 (14)0.0017 (10)0.0045 (10)0.0035 (10)
C60.0360 (12)0.0348 (11)0.0429 (13)0.0047 (9)0.0071 (10)0.0050 (9)
C70.0415 (13)0.0381 (12)0.0445 (13)0.0042 (10)0.0064 (10)0.0054 (10)
C80.0505 (14)0.0387 (12)0.0472 (14)0.0044 (11)0.0117 (11)0.0087 (10)
C90.0420 (12)0.0337 (11)0.0427 (13)0.0052 (10)0.0092 (10)0.0053 (9)
C100.0637 (16)0.0337 (12)0.0443 (14)0.0110 (11)0.0174 (12)0.0077 (10)
C110.0580 (16)0.0384 (12)0.0439 (14)0.0131 (11)0.0079 (11)0.0067 (10)
C120.0499 (15)0.0416 (13)0.0476 (14)0.0096 (11)0.0073 (11)−0.0001 (11)
C130.0510 (14)0.0320 (11)0.0404 (13)0.0038 (10)0.0081 (11)0.0009 (9)
C140.0455 (13)0.0399 (12)0.0325 (12)0.0075 (10)0.0036 (10)0.0051 (9)
C150.0384 (12)0.0412 (12)0.0325 (11)0.0080 (10)0.0004 (9)0.0024 (9)
C160.0430 (13)0.0402 (12)0.0355 (12)0.0082 (10)−0.0014 (10)0.0031 (9)
C170.0409 (13)0.0419 (12)0.0391 (13)0.0032 (10)−0.0010 (10)0.0008 (10)
C180.0354 (11)0.0383 (11)0.0327 (11)0.0056 (9)0.0051 (9)0.0084 (9)
C190.0377 (12)0.0437 (12)0.0391 (13)0.0030 (10)0.0017 (10)0.0033 (10)
C200.0338 (12)0.0493 (13)0.0471 (14)0.0101 (10)0.0031 (10)0.0074 (11)
C210.0397 (12)0.0361 (11)0.0386 (12)0.0087 (9)0.0071 (10)0.0077 (9)
C220.0366 (12)0.0364 (11)0.0353 (11)0.0051 (9)0.0076 (9)0.0082 (9)
C230.0331 (11)0.0399 (12)0.0377 (12)0.0050 (9)0.0052 (9)0.0059 (9)
C240.0466 (13)0.0366 (11)0.0347 (12)0.0041 (10)0.0045 (10)0.0070 (9)
C250.0420 (13)0.0401 (12)0.0386 (12)0.0056 (10)0.0037 (10)0.0060 (10)
C260.0579 (15)0.0357 (12)0.0367 (12)0.0063 (11)0.0100 (11)0.0078 (10)
C270.083 (2)0.0565 (17)0.0645 (19)0.0146 (16)0.0063 (16)0.0187 (14)
Cl10.0675 (5)0.0391 (3)0.0694 (5)0.0037 (3)0.0318 (4)0.0125 (3)
N10.0635 (16)0.0842 (18)0.0510 (14)0.0089 (13)0.0171 (12)0.0133 (13)
N20.0535 (13)0.0309 (10)0.0589 (13)0.0042 (9)0.0116 (10)0.0109 (9)
N30.0399 (10)0.0318 (9)0.0324 (10)0.0030 (8)0.0082 (8)0.0059 (7)
N40.0390 (10)0.0381 (10)0.0335 (10)0.0061 (8)0.0032 (8)0.0026 (8)
N50.0554 (13)0.0395 (11)0.0523 (13)0.0102 (10)0.0117 (10)0.0003 (9)
O10.0441 (9)0.0389 (9)0.0451 (10)0.0120 (7)0.0075 (7)0.0032 (7)
O20.0724 (13)0.0489 (11)0.0529 (11)0.0061 (10)−0.0041 (10)−0.0003 (9)
O30.0716 (14)0.0594 (13)0.0920 (17)0.0092 (11)0.0003 (13)0.0315 (12)
Geometric parameters (Å, º) top
C1—N11.147 (4)C15—H15B0.9700
C1—C21.435 (4)C16—N41.472 (3)
C2—C71.387 (3)C16—C171.513 (3)
C2—C31.416 (4)C16—H16A0.9700
C3—C41.373 (4)C16—H16B0.9700
C3—H30.9300C17—N31.495 (3)
C4—C51.393 (3)C17—H17A0.9700
C4—H40.9300C17—H17B0.9700
C5—N21.358 (3)C18—C231.393 (3)
C5—C61.424 (3)C18—N41.419 (3)
C6—C71.397 (3)C18—C191.419 (3)
C6—C91.432 (3)C19—C201.371 (3)
C7—H70.9300C19—H190.9300
C8—C91.363 (3)C20—C211.378 (3)
C8—N21.370 (3)C20—H200.9300
C8—H80.9300C21—O11.382 (3)
C9—C101.508 (3)C21—C221.385 (3)
C10—C111.520 (3)C22—C231.398 (3)
C10—H10A0.9700C22—C251.439 (3)
C10—H10B0.9700C23—H230.9300
C11—C121.531 (3)C24—C251.352 (3)
C11—H11A0.9700C24—O11.377 (3)
C11—H11B0.9700C24—C261.484 (3)
C12—C131.515 (4)C25—H250.9300
C12—H12A0.9700C26—O21.227 (3)
C12—H12B0.9700C26—N51.333 (3)
C13—N31.502 (3)C27—O31.431 (3)
C13—H13A0.9700C27—H27A0.9600
C13—H13B0.9700C27—H27B0.9600
C14—N31.493 (3)C27—H27C0.9600
C14—C151.512 (3)N2—H20.8600
C14—H14A0.9700N3—H3A0.9100
C14—H14B0.9700N5—H5A0.8600
C15—N41.459 (3)N5—H5B0.8600
C15—H15A0.9700O3—H3B0.8200
N1—C1—C2177.9 (3)N4—C16—H16A109.5
C7—C2—C3121.5 (2)C17—C16—H16A109.5
C7—C2—C1120.5 (2)N4—C16—H16B109.5
C3—C2—C1117.9 (2)C17—C16—H16B109.5
C4—C3—C2120.7 (2)H16A—C16—H16B108.1
C4—C3—H3119.6N3—C17—C16111.14 (18)
C2—C3—H3119.6N3—C17—H17A109.4
C3—C4—C5117.8 (2)C16—C17—H17A109.4
C3—C4—H4121.1N3—C17—H17B109.4
C5—C4—H4121.1C16—C17—H17B109.4
N2—C5—C4129.9 (2)H17A—C17—H17B108.0
N2—C5—C6107.5 (2)C23—C18—N4123.0 (2)
C4—C5—C6122.6 (2)C23—C18—C19118.9 (2)
C7—C6—C5118.6 (2)N4—C18—C19118.0 (2)
C7—C6—C9134.4 (2)C20—C19—C18122.4 (2)
C5—C6—C9107.0 (2)C20—C19—H19118.8
C2—C7—C6118.8 (2)C18—C19—H19118.8
C2—C7—H7120.6C19—C20—C21117.1 (2)
C6—C7—H7120.6C19—C20—H20121.5
C9—C8—N2111.1 (2)C21—C20—H20121.5
C9—C8—H8124.5C20—C21—O1126.2 (2)
N2—C8—H8124.5C20—C21—C22123.0 (2)
C8—C9—C6105.7 (2)O1—C21—C22110.7 (2)
C8—C9—C10127.3 (2)C21—C22—C23119.5 (2)
C6—C9—C10127.0 (2)C21—C22—C25105.5 (2)
C9—C10—C11113.6 (2)C23—C22—C25134.9 (2)
C9—C10—H10A108.8C18—C23—C22119.1 (2)
C11—C10—H10A108.8C18—C23—H23120.5
C9—C10—H10B108.8C22—C23—H23120.5
C11—C10—H10B108.8C25—C24—O1112.0 (2)
H10A—C10—H10B107.7C25—C24—C26131.2 (2)
C10—C11—C12114.8 (2)O1—C24—C26116.9 (2)
C10—C11—H11A108.6C24—C25—C22106.4 (2)
C12—C11—H11A108.6C24—C25—H25126.8
C10—C11—H11B108.6C22—C25—H25126.8
C12—C11—H11B108.6O2—C26—N5124.6 (2)
H11A—C11—H11B107.6O2—C26—C24120.2 (2)
C13—C12—C11111.4 (2)N5—C26—C24115.2 (2)
C13—C12—H12A109.3O3—C27—H27A109.5
C11—C12—H12A109.3O3—C27—H27B109.5
C13—C12—H12B109.3H27A—C27—H27B109.5
C11—C12—H12B109.3O3—C27—H27C109.5
H12A—C12—H12B108.0H27A—C27—H27C109.5
N3—C13—C12114.26 (19)H27B—C27—H27C109.5
N3—C13—H13A108.7C5—N2—C8108.8 (2)
C12—C13—H13A108.7C5—N2—H2125.6
N3—C13—H13B108.7C8—N2—H2125.6
C12—C13—H13B108.7C14—N3—C17109.46 (17)
H13A—C13—H13B107.6C14—N3—C13112.72 (17)
N3—C14—C15112.17 (18)C17—N3—C13110.61 (17)
N3—C14—H14A109.2C14—N3—H3A108.0
C15—C14—H14A109.2C17—N3—H3A108.0
N3—C14—H14B109.2C13—N3—H3A108.0
C15—C14—H14B109.2C18—N4—C15115.32 (18)
H14A—C14—H14B107.9C18—N4—C16116.13 (18)
N4—C15—C14111.40 (19)C15—N4—C16110.43 (18)
N4—C15—H15A109.3C26—N5—H5A120.0
C14—C15—H15A109.3C26—N5—H5B120.0
N4—C15—H15B109.3H5A—N5—H5B120.0
C14—C15—H15B109.3C24—O1—C21105.34 (17)
H15A—C15—H15B108.0C27—O3—H3B109.5
N4—C16—C17110.67 (19)
C7—C2—C3—C40.4 (4)O1—C21—C22—C250.1 (3)
C1—C2—C3—C4−177.9 (3)N4—C18—C23—C22−175.9 (2)
C2—C3—C4—C50.2 (4)C19—C18—C23—C220.5 (3)
C3—C4—C5—N2−179.1 (3)C21—C22—C23—C18−1.0 (3)
C3—C4—C5—C6−0.4 (4)C25—C22—C23—C18178.5 (2)
N2—C5—C6—C7178.9 (2)O1—C24—C25—C22−0.5 (3)
C4—C5—C6—C7−0.1 (4)C26—C24—C25—C22180.0 (2)
N2—C5—C6—C90.1 (3)C21—C22—C25—C240.2 (3)
C4—C5—C6—C9−178.9 (2)C23—C22—C25—C24−179.4 (2)
C3—C2—C7—C6−0.9 (4)C25—C24—C26—O2−2.5 (4)
C1—C2—C7—C6177.4 (2)O1—C24—C26—O2178.0 (2)
C5—C6—C7—C20.8 (3)C25—C24—C26—N5177.7 (2)
C9—C6—C7—C2179.1 (2)O1—C24—C26—N5−1.8 (3)
N2—C8—C9—C6−0.6 (3)C4—C5—N2—C8178.4 (3)
N2—C8—C9—C10−178.4 (2)C6—C5—N2—C8−0.5 (3)
C7—C6—C9—C8−178.2 (3)C9—C8—N2—C50.7 (3)
C5—C6—C9—C80.3 (3)C15—C14—N3—C17−53.8 (2)
C7—C6—C9—C10−0.5 (4)C15—C14—N3—C13−177.34 (19)
C5—C6—C9—C10178.1 (2)C16—C17—N3—C1455.1 (2)
C8—C9—C10—C117.9 (4)C16—C17—N3—C13179.89 (19)
C6—C9—C10—C11−169.3 (2)C12—C13—N3—C14−58.5 (3)
C9—C10—C11—C12179.2 (2)C12—C13—N3—C17178.6 (2)
C10—C11—C12—C1380.7 (3)C23—C18—N4—C15−1.8 (3)
C11—C12—C13—N3−177.70 (19)C19—C18—N4—C15−178.3 (2)
N3—C14—C15—N455.5 (3)C23—C18—N4—C16−133.3 (2)
N4—C16—C17—N3−58.2 (3)C19—C18—N4—C1650.3 (3)
C23—C18—C19—C200.9 (4)C14—C15—N4—C18168.90 (18)
N4—C18—C19—C20177.5 (2)C14—C15—N4—C16−57.0 (2)
C18—C19—C20—C21−1.6 (4)C17—C16—N4—C18−167.80 (19)
C19—C20—C21—O1−178.4 (2)C17—C16—N4—C1558.5 (2)
C19—C20—C21—C221.0 (4)C25—C24—O1—C210.6 (3)
C20—C21—C22—C230.3 (4)C26—C24—O1—C21−179.84 (19)
O1—C21—C22—C23179.77 (19)C20—C21—O1—C24179.0 (2)
C20—C21—C22—C25−179.3 (2)C22—C21—O1—C24−0.4 (2)
Hydrogen-bond geometry (Å, º) top
Cg5 is the centroid of the C18–C22 ring.
D—H···AD—HH···AD···AD—H···A
N2—H2···O3i0.862.252.971 (3)141
N3—H3A···Cl10.912.183.0787 (19)172
N5—H5A···Cl1ii0.862.423.250 (2)162
N5—H5B···N1iii0.862.333.151 (4)160
O3—H3B···Cl10.822.383.195 (2)171
C13—H13A···O2iv0.972.333.272 (3)164
C19—H19···O3v0.932.553.348 (3)144
C14—H14B···Cg5vi0.972.483.393 (2)156
Symmetry codes: (i) −x+1, −y, −z+1; (ii) −x, −y+2, −z+2; (iii) −x, −y+1, −z+1; (iv) x, y−1, z−1; (v) x−1, y, z; (vi) −x, −y+1, −z+2.
 

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ISSN: 2056-9890
Volume 72| Part 12| December 2016| Pages 1783-1785
https://doi.org/10.1107/S2056989016017734
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