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ISSN: 2056-9890

Ring-expansion synthesis and crystal structure of di­methyl 4-ethyl-1,4,5,6,7,8-hexa­hydro­azonino[5,6-b]indole-2,3-di­carboxyl­ate

aInstitute of Chemistry, Vietnam Academy of Science and Technology, 18 Hoang Quoc Viet, Hanoi, Vietnam, bGraduate University of Science and Technology, 18 Hoang Quoc Viet, Hanoi, Vietnam, cOrganic Chemistry Department, Peoples' Friendship University of Russia, 6 Miklukho-Maklaya St., Moscow 117198, Russian Federation, dInorganic Chemistry Department, Peoples' Friendship University of Russia, 6 Miklukho-Maklaya St., Moscow 117198, Russian Federation, eNational Research Centre "Kurchatov Institute", 1 Acad. Kurchatov Sq., Moscow 123182, Russian Federation, fInorganic Chemistry Department, Peoples' Friendship University of Russia, 6 Miklukho-Maklay St., Moscow 117198, Russian Federation, and gX-Ray Structural Centre, A.N. Nesmeyanov Institute of Organoelement Compounds, Russian Academy of Sciences, 28 Vavilov St., B–334, Moscow 119991, Russian Federation
*Correspondence e-mail: ngvtuyen@hotmail.com

Edited by W. T. A. Harrison, University of Aberdeen, Scotland (Received 16 December 2016; accepted 31 January 2017; online 7 February 2017)

The title compound, C20H24N2O4, is the product of a ring-expansion reaction from a seven-membered hexa­hydro­azepine to a nine-membered azonine. The azonine ring of the mol­ecule adopts a chair–boat conformation. In the crystal, mol­ecules are linked by bifurcated N—H⋯(O,O) hydrogen bonds, generating [010] zigzag chains. The title compound shows inhibitory activity against acetyl­cholinesterase and butyrylcholinesterase, and might be considered as a candidate for the design of new types of anti-Alzheimer's drugs.

1. Chemical context

The azonine moiety has long been known as a building block of natural alkaloids (Neuss et al., 1959[Neuss, N., Gorman, M., Svoboda, G. H., Maciak, G. & Beer, C. T. (1959). J. Am. Chem. Soc. 81, 4754-4755.], 1962[Neuss, N., Gorman, M., Boaz, H. E. & Cone, N. J. (1962). J. Am. Chem. Soc. 84, 1509-1510.]; Uprety & Bhakuni, 1975[Uprety, H. & Bhakuni, D. S. (1975). Tetrahedron Lett. 16, 1201-1204.]). Azonine derivatives are known to act as ligands towards different receptors, thus demonstrating diverse types of biological activity (Magnus et al., 1987[Magnus, P., Ladlow, M. & Elliott, J. (1987). J. Am. Chem. Soc. 109, 7929-7930.]; Kuehne, Bornman et al., 2003[Kuehne, M. E., Bornmann, W. G., Markó, I., Qin, Y., LeBoulluec, K. L., Frasier, D. A., Xu, F., Mulamba, T., Ensinger, C. L., Borman, L. S., Huot, A. E., Exon, C., Bizzarro, F. T., Cheung, J. B. & Bane, S. L. (2003). Org. Biomol. Chem. 1, 2120-2136.]; Kuehne, He et al., 2003[Kuehne, M., He, L., Jokiel, P., Pace, C. J., Fleck, M. W., Maisonneuve, I. M., Glick, S. D. & Bidlack, J. M. (2003). J. Med. Chem. 46, 2716-2730.]; Afsah et al., 2009[Afsah, E. M., Fadda, A. A., Bondock, S. & Hammouda, M. M. (2009). Z. Naturforsch. Teil B, 64, 415-422.]; Rostom, 2010[Rostom, S. A. F. (2010). Arch. Pharm. Chem. Life Sci. 343, 73-80.]; Tanaka et al., 2014[Tanaka, Y., Gamo, K., Oyama, T., Ohashi, M., Waki, M., Matsuno, K., Matsuura, N., Tokiwa, H. & Miyachi, H. (2014). Bioorg. Med. Chem. Lett. 24, 4001-4005.]; Soldi et al., 2015[Soldi, R., Horrigan, S. K., Cholody, M. W., Padia, J., Sorna, V., Bearss, J., Gilcrease, G., Bhalla, K., Verma, A., Vankayalapati, H. & Sharma, S. (2015). J. Med. Chem. 58, 5854-5862.]; Hartman & Kuduk, 2016[Hartman, G. D. & Kuduk, S. (2016). Patent US2016/272599A1, Novira Therapeutics, Inc., USA.]).

The direct synthesis of such systems from acyclic precursors is difficult due to thermodynamic and kinetic limitations and hence the search for novel and efficient synthetic routes to medium-sized rings has attracted appreciable attention in recent years. Earlier, we elaborated a ring-expansion reaction from a six-membered tetra­hydro­pyridine ring to an eight-membered azocine ring under the action of activated alkynes applicable to fused tetra­hydro­pyridines (Voskressensky et al., 2004[Voskressensky, L. G., Borisova, T. N., Kulikova, L. N., Varlamov, A. V., Catto, M., Altomare, C. & Carotti, A. (2004). Eur. J. Org. Chem. pp. 3128-3135.]; Voskressensky, Borisova et al., 2006[Voskressensky, L. G., Borisova, T. N., Kostenev, I. S., Kulikova, L. N. & Varlamov, A. V. (2006). Tetrahedron Lett. 47, 999-1001.]).

Herewith, we report on the synthesis of nine-membered azonine ring from a seven-membered hexa­hydro­azepine precursor using a similar reaction. More specifically, the initial 2-ethyl-1,2,3,4,5,6-hexa­hydro­azepino[4,3-b]indole in a methanol solution at room temperature under the action of dimethyl acetyl­enedi­carboxyl­ate undergoes a series of tandem transformations involving the hexa­hydro­azepine ring giving rise to azonino­indole (I)[link] and 3-meth­oxy­methyl-substituted indole (II) (Fig. 1[link]).

[Figure 1]
Figure 1
The synthesis of dimethyl 4-ethyl-1,4,5,6,7,8-hexa­hydro­azonino[5,6-b]indole-2,3-di­carboxyl­ate, (I)[link], in methanol.

The title compound (I)[link] has been tested in vitro for acetyl­cholinesterase and butyrylcholinesterase inhibition and demonstrated the inhibitor activity of 33.1 µM and 89.1 µM against acetyl­cholinesterase and butyrylcholinesterase, respectively. Thus, azonino­indoles might be considered as candidates for the design of new types of anti-Alzheimer's drugs.

[Scheme 1]

2. Structural commentary

The title compound (I)[link] is the product of the ring expansion described above. Its mol­ecular structure is unambiguously confirmed by the X-ray diffraction study (Fig. 2[link]).

[Figure 2]
Figure 2
The mol­ecular structure of (I)[link]. Displacement ellipsoids are drawn at the 50% probability level. H atoms are shown as small spheres of arbitrary radius.

The nine-membered azonine ring of the mol­ecule adopts a chair–boat conformation (the basal planes are C5–C6/C7A–C12B and N4–C5/C1–C12B, respectively). It should be noted that the analogous nine-membered azonine ring in the related compound methyl 4-ethyl-11-methyl-1,4,5,6,7,8-hexa­hydro­azonino [5,6-b]indole-2-carboxyl­ate adopts a twisted boat conformation (Voskressensky, Akbulatov et al., 2006[Voskressensky, L. G., Akbulatov, S. V., Borisova, T. N. & Varlamov, A. V. (2006). Tetrahedron, 62, 12392-12397.]). The C2=C3 and C3—N4 bond lengths [1.361 (2) and 1.401 (2) Å, respectively] in (I)[link] indicate the presence of conjugation within the enamine C2=C3—N4 fragment. The substituent planes at the C2=C3 double bond are twisted by 18.12 (13)°, presumably due to steric reasons. The N4 nitro­gen atom has a trigonal-pyramidal configuration (sum of the bond angles is 345.5°). The inter­planar angle between the carboxyl­ate substituents is 59.74 (6)°.

3. Supra­molecular features

In the crystal, mol­ecules of (I)[link] form zigzag chains propagating in the [010] direction by bifurcated N—H⋯(O,O) hydrogen-bonding inter­actions (Table 1[link]) which are further packed in stacks toward [100] (Fig. 3[link]).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
N8—H8⋯O1i 0.891 (17) 2.234 (18) 3.0690 (18) 155.7 (14)
N8—H8⋯O3i 0.891 (17) 2.546 (16) 3.1029 (16) 121.2 (12)
Symmetry code: (i) [-x+1, y+{\script{1\over 2}}, -z+{\script{3\over 2}}].
[Figure 3]
Figure 3
The crystal packing of (I)[link], viewed along the crystallographic a axis. Dashed and dotted lines indicate the bifurcated N—H⋯(O,O) hydrogen bonds.

4. Synthesis and crystallization

Dimethyl acetyl­enedi­carboxyl­ate (170 mg, 1.2 mmol) was added to 2-ethyl-1,2,3,4,5,6-hexa­hydro­azepino[4,3-b]indole (214 mg, 1 mmol) dissolved in methanol (10 ml). The reaction mixture was stirred for 2 h at room temperature and the progress of the reaction monitored by TLC. Then, the solvent was removed in vacuo and the residue was chromatographed over silica with ethyl­acetate:hexane as eluent to yield the target azonino­indole (I)[link] (23%) and 3-meth­oxy­methyl­indole (II). Colourless prisms of (I)[link] were grown by slow evaporation of an ethyl­acetate:hexane solution, m.p. 428–430 K. NMR 1H [CDCl3, δ (ppm), J (Hz)]: 1.03 (t, 3H, J = 7.2, CH3CH2), 1.77 (m, 2H, 6-CH2), 2.76 (q, 2H, J = 7.2, CH3CH2), 2.83 (m, 2H, 7-CH2), 3.08 (m, 2H, 5-CH2), 4.03 (s, 2H, 1-CH2), 3.75 (s, 3H, CO2CH3), 3.77 (s, 3H, CO2CH3), 7.09 (m, 2H, CH), 7.26 (d, 1H, J = 7.6, CH), 7.50 (d, 1H, J = 7.6, CH), 7.83 (br.s, 1H, NH). NMR 13C [DMSO-d6, δ (ppm), J (Hz)]: 15.2 (CH3), 22.6 (CH2), 24.0 (CH2), 27.0 (CH2), 44.5 (CH2), 52.2 (CH3), 52.3 (CH3), 55.6 (CH2), 108.3 (C), 111.0 (CH), 117.8 (CH), 118.7 (CH), 120.5 (CH), 124.4 (?), 128.1 (C), 135.3 (C), 135.6 (C), 151.1 (C), 166.3 (C), 169.3 (C). IR (KBr): ν (cm−1) = 1670, 3379. Found (%): C, 67.40; H, 6.79; N, 7.86. C20H24N2O4. Calculated (%): C, 67.30; H, 7.06; N, 8.00. Mass-spectrometry, m/z [Irel(%)]: 356 [M+] (60), 327 (10), 297 (60), 267 (30), 252 (10), 237 (30), 226 (10), 209 (20), 180 (30), 168 (40), 156 (60), 143 (45), 128 (20), 115 (20), 77 (10), 58 (100), 45 (30).

5. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2[link]. The amino-H atom was localized in Fourier syntheses and its position freely refined. The C-bound H atoms were placed in calculated positions with C—H = 0.95 Å (aryl-H), 0.96 Å (methyl-H), and 0.98 Å (methyl­ene-H) and refined in the riding-model approximation with the constraint Uiso(H) = 1.5Ueq(C) for the methyl groups and 1.2Ueq(C or N) for all other H atoms.

Table 2
Experimental details

Crystal data
Chemical formula C20H24N2O4
Mr 356.41
Crystal system, space group Monoclinic, P21/c
Temperature (K) 100
a, b, c (Å) 8.5900 (17), 10.450 (2), 20.670 (4)
β (°) 98.45 (3)
V3) 1835.3 (6)
Z 4
Radiation type Synchrotron, λ = 0.96990 Å
μ (mm−1) 0.19
Crystal size (mm) 0.20 × 0.08 × 0.05
 
Data collection
Diffractometer Rayonix SX165 CCD
Absorption correction Multi-scan (SCALA; Evans, 2006[Evans, P. (2006). Acta Cryst. D62, 72-82.])
Tmin, Tmax 0.960, 0.990
No. of measured, independent and observed [I > 2σ(I)] reflections 20559, 3894, 3123
Rint 0.068
(sin θ/λ)max−1) 0.641
 
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.046, 0.122, 1.01
No. of reflections 3894
No. of parameters 242
H-atom treatment H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3) 0.34, −0.24
Computer programs: Automar (MarXperts, 2015[MarXperts (2015). Automar. MarXperts GmbH, Norderstedt, Germany.]), iMosflm (Battye et al., 2011[Battye, T. G. G., Kontogiannis, L., Johnson, O., Powell, H. R. & Leslie, A. G. W. (2011). Acta Cryst. D67, 271-281.]) and SHELXTL (Sheldrick, 2015[Sheldrick, G. M. (2015). Acta Cryst. C71, 3-8.]).

Supporting information


Computing details top

Data collection: Automar (MarXperts, 2015); cell refinement: iMosflm (Battye et al., 2011); data reduction: iMosflm (Battye et al., 2011); program(s) used to solve structure: SHELXTL (Sheldrick, 2015); program(s) used to refine structure: SHELXTL (Sheldrick, 2015); molecular graphics: SHELXTL (Sheldrick, 2015); software used to prepare material for publication: SHELXTL (Sheldrick, 2015).

Dimethyl 4-ethyl-1,4,5,6,7,8-hexahydroazonino[5,6-b]indole-2,3-dicarboxylate top
Crystal data top
C20H24N2O4F(000) = 760
Mr = 356.41Dx = 1.290 Mg m3
Monoclinic, P21/cSynchrotron radiation, λ = 0.96990 Å
a = 8.5900 (17) ÅCell parameters from 600 reflections
b = 10.450 (2) Åθ = 3.8–38.0°
c = 20.670 (4) ŵ = 0.19 mm1
β = 98.45 (3)°T = 100 K
V = 1835.3 (6) Å3Prism, colourless
Z = 40.20 × 0.08 × 0.05 mm
Data collection top
Rayonix SX165 CCD
diffractometer
3123 reflections with I > 2σ(I)
/f scanRint = 0.068
Absorption correction: multi-scan
(Scala; Evans, 2006)
θmax = 38.5°, θmin = 3.8°
Tmin = 0.960, Tmax = 0.990h = 1010
20559 measured reflectionsk = 1312
3894 independent reflectionsl = 2626
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.046H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.122 w = 1/[σ2(Fo2) + (0.0484P)2 + 0.484P]
where P = (Fo2 + 2Fc2)/3
S = 1.01(Δ/σ)max = 0.001
3894 reflectionsΔρmax = 0.34 e Å3
242 parametersΔρmin = 0.24 e Å3
0 restraintsExtinction correction: SHELXL, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: difference Fourier mapExtinction coefficient: 0.0139 (16)
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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top
xyzUiso*/Ueq
O10.63858 (11)0.12498 (9)0.59679 (5)0.0243 (3)
O20.85193 (11)0.25114 (9)0.61630 (4)0.0223 (3)
O30.27706 (12)0.17391 (10)0.54825 (5)0.0265 (3)
O40.45470 (11)0.26071 (9)0.49055 (4)0.0224 (3)
C10.68135 (16)0.46000 (13)0.65876 (6)0.0200 (3)
H1A0.79160.46410.65010.024*
H1B0.62780.53850.64020.024*
C20.60249 (16)0.34538 (13)0.62131 (6)0.0186 (3)
C30.44674 (16)0.34394 (13)0.59639 (6)0.0187 (3)
N40.33815 (13)0.42675 (11)0.61889 (5)0.0201 (3)
C50.30356 (16)0.39814 (14)0.68573 (6)0.0217 (3)
H5A0.38990.34520.70880.026*
H5B0.20550.34710.68210.026*
C60.28472 (17)0.51732 (14)0.72650 (6)0.0245 (3)
H6A0.25980.49090.76980.029*
H6B0.19500.56840.70460.029*
C70.43311 (17)0.60151 (14)0.73627 (6)0.0240 (3)
H7A0.44870.63910.69370.029*
H7B0.41790.67260.76640.029*
C7A0.57725 (16)0.52745 (13)0.76366 (6)0.0210 (3)
N80.61170 (14)0.50489 (12)0.83032 (5)0.0225 (3)
H80.5647 (19)0.5452 (16)0.8602 (8)0.027*
C8A0.74364 (16)0.42812 (14)0.84258 (6)0.0216 (3)
C90.82348 (17)0.38193 (14)0.90185 (6)0.0256 (3)
H90.78910.40190.94230.031*
C100.95495 (18)0.30578 (15)0.89926 (7)0.0287 (4)
H101.01100.27230.93870.034*
C111.00664 (17)0.27727 (15)0.83940 (7)0.0274 (3)
H111.09760.22560.83910.033*
C120.92688 (17)0.32340 (14)0.78055 (7)0.0237 (3)
H120.96270.30350.74040.028*
C12A0.79257 (16)0.39984 (13)0.78146 (6)0.0200 (3)
C12B0.68382 (16)0.46324 (13)0.73182 (6)0.0196 (3)
C130.69611 (15)0.23057 (13)0.60961 (6)0.0188 (3)
C140.94677 (17)0.13776 (14)0.60964 (7)0.0262 (3)
H14A0.91750.10120.56590.039*
H14B0.92820.07440.64260.039*
H14C1.05840.16130.61590.039*
C150.38326 (16)0.24798 (13)0.54379 (6)0.0196 (3)
C160.41346 (18)0.16510 (15)0.44026 (7)0.0284 (4)
H16A0.46190.18720.40170.043*
H16B0.29880.16220.42830.043*
H16C0.45170.08120.45680.043*
C170.19643 (16)0.46212 (14)0.57286 (6)0.0230 (3)
H17A0.12680.51550.59590.028*
H17B0.13800.38350.55750.028*
C180.23772 (18)0.53519 (15)0.51430 (7)0.0291 (4)
H18A0.14090.55900.48560.044*
H18B0.30250.48110.49010.044*
H18C0.29650.61270.52930.044*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0240 (6)0.0204 (6)0.0279 (5)0.0006 (4)0.0022 (4)0.0029 (4)
O20.0184 (5)0.0221 (6)0.0265 (5)0.0014 (4)0.0033 (4)0.0013 (4)
O30.0249 (6)0.0291 (6)0.0250 (5)0.0061 (4)0.0027 (4)0.0020 (4)
O40.0268 (6)0.0254 (6)0.0151 (4)0.0018 (4)0.0037 (4)0.0034 (4)
C10.0205 (7)0.0204 (7)0.0190 (6)0.0003 (5)0.0024 (5)0.0005 (5)
C20.0210 (7)0.0206 (7)0.0143 (6)0.0001 (5)0.0027 (5)0.0003 (5)
C30.0230 (7)0.0186 (7)0.0144 (6)0.0011 (5)0.0026 (5)0.0003 (5)
N40.0205 (6)0.0236 (7)0.0157 (5)0.0033 (5)0.0007 (4)0.0000 (4)
C50.0217 (7)0.0253 (8)0.0181 (6)0.0012 (6)0.0036 (5)0.0002 (5)
C60.0252 (8)0.0287 (8)0.0196 (6)0.0047 (6)0.0030 (5)0.0025 (6)
C70.0279 (8)0.0237 (8)0.0199 (6)0.0047 (6)0.0024 (5)0.0035 (5)
C7A0.0259 (8)0.0192 (7)0.0172 (6)0.0017 (6)0.0012 (5)0.0020 (5)
N80.0248 (7)0.0265 (7)0.0161 (5)0.0015 (5)0.0024 (5)0.0031 (5)
C8A0.0234 (7)0.0213 (7)0.0194 (6)0.0045 (6)0.0005 (5)0.0005 (5)
C90.0273 (8)0.0294 (9)0.0190 (6)0.0067 (6)0.0003 (5)0.0009 (6)
C100.0297 (8)0.0283 (8)0.0248 (7)0.0048 (6)0.0066 (6)0.0052 (6)
C110.0237 (8)0.0237 (8)0.0324 (8)0.0006 (6)0.0033 (6)0.0004 (6)
C120.0230 (8)0.0232 (8)0.0240 (6)0.0033 (6)0.0000 (5)0.0022 (5)
C12A0.0218 (7)0.0181 (7)0.0190 (6)0.0053 (5)0.0010 (5)0.0014 (5)
C12B0.0212 (7)0.0182 (7)0.0187 (6)0.0017 (5)0.0004 (5)0.0018 (5)
C130.0210 (7)0.0226 (8)0.0126 (6)0.0007 (5)0.0015 (5)0.0008 (5)
C140.0235 (8)0.0254 (8)0.0301 (7)0.0049 (6)0.0051 (6)0.0011 (6)
C150.0204 (7)0.0219 (7)0.0158 (6)0.0034 (5)0.0006 (5)0.0008 (5)
C160.0307 (8)0.0338 (9)0.0195 (6)0.0007 (7)0.0004 (6)0.0102 (6)
C170.0203 (7)0.0265 (8)0.0210 (6)0.0032 (6)0.0011 (5)0.0013 (5)
C180.0276 (8)0.0320 (9)0.0266 (7)0.0043 (6)0.0001 (6)0.0070 (6)
Geometric parameters (Å, º) top
O1—C131.2221 (16)C7A—N81.3862 (16)
O2—C131.3426 (17)N8—C8A1.3813 (19)
O2—C141.4558 (17)N8—H80.891 (17)
O3—C151.2101 (17)C8A—C91.3991 (18)
O4—C151.3431 (17)C8A—C12A1.4198 (19)
O4—C161.4478 (16)C9—C101.389 (2)
C1—C12B1.5077 (18)C9—H90.9500
C1—C21.5292 (18)C10—C111.407 (2)
C1—H1A0.9900C10—H100.9500
C1—H1B0.9900C11—C121.3916 (19)
C2—C31.3612 (19)C11—H110.9500
C2—C131.4838 (19)C12—C12A1.406 (2)
C3—N41.4010 (18)C12—H120.9500
C3—C151.5201 (18)C12A—C12B1.4432 (18)
N4—C171.4776 (16)C14—H14A0.9800
N4—C51.4857 (17)C14—H14B0.9800
C5—C61.526 (2)C14—H14C0.9800
C5—H5A0.9900C16—H16A0.9800
C5—H5B0.9900C16—H16B0.9800
C6—C71.537 (2)C16—H16C0.9800
C6—H6A0.9900C17—C181.517 (2)
C6—H6B0.9900C17—H17A0.9900
C7—C7A1.4988 (19)C17—H17B0.9900
C7—H7A0.9900C18—H18A0.9800
C7—H7B0.9900C18—H18B0.9800
C7A—C12B1.378 (2)C18—H18C0.9800
C13—O2—C14115.04 (11)C8A—C9—H9121.3
C15—O4—C16115.27 (11)C9—C10—C11121.25 (13)
C12B—C1—C2117.68 (11)C9—C10—H10119.4
C12B—C1—H1A107.9C11—C10—H10119.4
C2—C1—H1A107.9C12—C11—C10121.14 (14)
C12B—C1—H1B107.9C12—C11—H11119.4
C2—C1—H1B107.9C10—C11—H11119.4
H1A—C1—H1B107.2C11—C12—C12A119.00 (14)
C3—C2—C13117.09 (12)C11—C12—H12120.5
C3—C2—C1122.54 (13)C12A—C12—H12120.5
C13—C2—C1120.35 (11)C12—C12A—C8A118.76 (12)
C2—C3—N4122.20 (12)C12—C12A—C12B134.28 (13)
C2—C3—C15120.48 (12)C8A—C12A—C12B106.96 (12)
N4—C3—C15117.29 (11)C7A—C12B—C12A106.86 (11)
C3—N4—C17117.81 (11)C7A—C12B—C1125.23 (12)
C3—N4—C5114.73 (11)C12A—C12B—C1127.89 (13)
C17—N4—C5113.00 (11)O1—C13—O2122.15 (13)
N4—C5—C6113.66 (12)O1—C13—C2123.62 (12)
N4—C5—H5A108.8O2—C13—C2114.19 (12)
C6—C5—H5A108.8O2—C14—H14A109.5
N4—C5—H5B108.8O2—C14—H14B109.5
C6—C5—H5B108.8H14A—C14—H14B109.5
H5A—C5—H5B107.7O2—C14—H14C109.5
C5—C6—C7112.73 (12)H14A—C14—H14C109.5
C5—C6—H6A109.0H14B—C14—H14C109.5
C7—C6—H6A109.0O3—C15—O4124.48 (12)
C5—C6—H6B109.0O3—C15—C3124.24 (12)
C7—C6—H6B109.0O4—C15—C3111.20 (11)
H6A—C6—H6B107.8O4—C16—H16A109.5
C7A—C7—C6112.15 (12)O4—C16—H16B109.5
C7A—C7—H7A109.2H16A—C16—H16B109.5
C6—C7—H7A109.2O4—C16—H16C109.5
C7A—C7—H7B109.2H16A—C16—H16C109.5
C6—C7—H7B109.2H16B—C16—H16C109.5
H7A—C7—H7B107.9N4—C17—C18111.88 (12)
C12B—C7A—N8109.40 (12)N4—C17—H17A109.2
C12B—C7A—C7129.87 (12)C18—C17—H17A109.2
N8—C7A—C7120.47 (13)N4—C17—H17B109.2
C8A—N8—C7A109.31 (12)C18—C17—H17B109.2
C8A—N8—H8126.1 (10)H17A—C17—H17B107.9
C7A—N8—H8123.8 (10)C17—C18—H18A109.5
N8—C8A—C9130.12 (13)C17—C18—H18B109.5
N8—C8A—C12A107.45 (11)H18A—C18—H18B109.5
C9—C8A—C12A122.43 (14)C17—C18—H18C109.5
C10—C9—C8A117.42 (13)H18A—C18—H18C109.5
C10—C9—H9121.3H18B—C18—H18C109.5
C12B—C1—C2—C389.83 (16)C9—C8A—C12A—C120.5 (2)
C12B—C1—C2—C1391.39 (15)N8—C8A—C12A—C12B0.01 (15)
C13—C2—C3—N4161.42 (12)C9—C8A—C12A—C12B179.83 (13)
C1—C2—C3—N419.8 (2)N8—C7A—C12B—C12A1.40 (15)
C13—C2—C3—C1516.67 (18)C7—C7A—C12B—C12A175.38 (14)
C1—C2—C3—C15162.15 (12)N8—C7A—C12B—C1177.49 (12)
C2—C3—N4—C17152.39 (13)C7—C7A—C12B—C13.5 (2)
C15—C3—N4—C1729.46 (17)C12—C12A—C12B—C7A178.33 (15)
C2—C3—N4—C570.79 (17)C8A—C12A—C12B—C7A0.85 (15)
C15—C3—N4—C5107.36 (13)C12—C12A—C12B—C12.8 (3)
C3—N4—C5—C6141.33 (12)C8A—C12A—C12B—C1178.00 (13)
C17—N4—C5—C679.77 (14)C2—C1—C12B—C7A96.28 (16)
N4—C5—C6—C759.93 (15)C2—C1—C12B—C12A82.37 (18)
C5—C6—C7—C7A53.56 (15)C14—O2—C13—O12.25 (17)
C6—C7—C7A—C12B91.06 (18)C14—O2—C13—C2175.79 (10)
C6—C7—C7A—N882.35 (15)C3—C2—C13—O121.88 (18)
C12B—C7A—N8—C8A1.44 (16)C1—C2—C13—O1159.27 (12)
C7—C7A—N8—C8A176.09 (12)C3—C2—C13—O2160.11 (11)
C7A—N8—C8A—C9178.94 (14)C1—C2—C13—O218.73 (16)
C7A—N8—C8A—C12A0.87 (15)C16—O4—C15—O39.14 (18)
N8—C8A—C9—C10179.83 (14)C16—O4—C15—C3174.08 (11)
C12A—C8A—C9—C100.0 (2)C2—C3—C15—O3124.43 (15)
C8A—C9—C10—C110.6 (2)N4—C3—C15—O353.76 (18)
C9—C10—C11—C120.6 (2)C2—C3—C15—O458.78 (16)
C10—C11—C12—C12A0.1 (2)N4—C3—C15—O4123.03 (12)
C11—C12—C12A—C8A0.5 (2)C3—N4—C17—C1862.97 (17)
C11—C12—C12A—C12B179.58 (15)C5—N4—C17—C18159.50 (12)
N8—C8A—C12A—C12179.34 (12)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N8—H8···O1i0.891 (17)2.234 (18)3.0690 (18)155.7 (14)
N8—H8···O3i0.891 (17)2.546 (16)3.1029 (16)121.2 (12)
Symmetry code: (i) x+1, y+1/2, z+3/2.
 

Acknowledgements

The work was supported by the Ministry of Education and Science of the Russian Federation (the Agreement number 02.a03.21.0008 of June 24, 2016).

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