Crystal structure and Hirshfeld surface analysis of 6-amino-8-(2,6-di­chloro­phen­yl)-1,3,4,8-tetra­hydro-2H-pyrido[1,2-a]pyrimidine-7,9-dicarbo­nitrile

Naghiyev, F.N.; Tereshina, T.A.; Khrustalev, V.N.; Akkurt, M.; Rzayev, R.M.; Akobirshoeva, A.A.; Mamedov, İ.G.

doi:10.1107/S2056989021003583

research communications

CRYSTALLOGRAPHIC
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ISSN: 2056-9890

Volume 77| Part 5| May 2021| Pages 516-521

https://doi.org/10.1107/S2056989021003583

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Crystal structure and Hirshfeld surface analysis of 6-amino-8-(2,6-dichlorophenyl)-1,3,4,8-tetrahydro-2H-pyrido[1,2-a]pyrimidine-7,9-dicarbonitrile

Farid N. Naghiyev,^a Tatiana A. Tereshina,^b Victor N. Khrustalev,^b,^c Mehmet Akkurt,^d Rovnag M. Rzayev,^e Anzurat A. Akobirshoeva ^f ^* and İbrahim G. Mamedov ^a

^aDepartment of Chemistry, Baku State University, Z. Khalilov str. 23, Az, 1148 Baku, Azerbaijan, ^bPeoples' Friendship University of Russia (RUDN University), Miklukho-Maklay St. 6, Moscow, 117198, Russian Federation, ^cN. D. Zelinsky Institute of Organic Chemistry RAS, Leninsky Prosp. 47, Moscow, 119991, Russian Federation, ^dDepartment of Physics, Faculty of Sciences, Erciyes University, 38039 Kayseri, Turkey, ^e"Composite Materials" Scientific Research Center, Azerbaijan State Economic University (UNEC), H. Aliyev str. 135, Az 1063, Baku, Azerbaijan, and ^fAcad. Sci. Republ. Tadzhikistan, Kh. Yu. Yusufbekov Pamir Biol. Inst., 1 Kholdorova St, Khorog 736002, Gbao, Tajikistan
^*Correspondence e-mail: anzurat2003@mail.ru

Edited by M. Weil, Vienna University of Technology, Austria (Received 17 March 2021; accepted 2 April 2021; online 9 April 2021)

In the molecular structure of the title compound, C₁₆H₁₃Cl₂N₅, the 1,4-dihydropyridine ring of the 1,3,4,8-tetrahydro-2H-pyrido[1,2-a]pyrimidine ring system adopts a screw-boat conformation, while the 1,3-diazinane ring is puckered. In the crystal, intermolecular N—H⋯N and C—H⋯N hydrogen bonds form molecular sheets parallel to the (110) and ( $[\overline{1}]$ 10) planes, crossing each other. Adjacent molecules are further linked by C—H⋯π interactions, which form zigzag chains propagating parallel to [100]. A Hirshfeld surface analysis indicates that the most significant contributions to the crystal packing are from N⋯H/H⋯N (28.4%), H⋯H (24.5%), C⋯H/H⋯C (21.4%) and Cl⋯H/H⋯Cl (16.1%) contacts.

Keywords: crystal structure; cycloaddition product; 1,3,4,8-tetrahydro-2H-pyrido[1,2-a]pyrimidine; Hirshfeld surface analysis.

CCDC reference: 2075706

1. Chemical context

Chemical transformations comprising carbon–carbon and carbon–heteroatom bond-formation reactions are fundamental tools in modern synthetic organic chemistry (Yadigarov et al., 2009 ; Abdelhamid et al., 2011 ; Khalilov et al., 2011 ; Yin et al., 2020 ). They are also used for the synthesis of valuable building blocks in medicinal chemistry, coordination chemistry and material science (Mahmoudi et al., 2017 , 2019 ; Viswanathan et al., 2019 ).

Pyrido[l,2-a]pyrimidines constitute a valuable class of heterocycles because many of them possess broad biological activities, such as monoamine oxidase inhibition, antihypertensive, insecticide, serotonergic antagonist, analgesic, anti-inflammatory, cytoprotective, bronchodilatory, phosphodiesterase-inhibitory, antithrombotic, antiallergic, antiatherosclerotic and hypoglycaemic activities, as well as antitumor effects (Hermecz & Mészáros, 1988 ; Ukrainets et al., 2018 ). The pyrido[1,2-a]pyrimidine motif is incorporated into the structure of some marketed drugs, including the antiasthmatic agent pemirolast, the tranquilizer pirenperone, the antiallergic agent ramastine, and the psychotropic agents risperidone and paliperidone (Awouters et al., 1986 ; Blaton et al., 1995 ; Yahata et al., 2006 ; Riva et al., 2011 ). Over recent decades, a number of synthetic protocols for the synthesis of pyrido[1,2-a]pyrimidines have been reported, and these approaches have focused on two-component reactions (Wu et al., 2003 ; Pryadeina et al., 2005 ). Multi-component reactions have developed as powerful tools for the design of complex molecules, natural products and drug-like molecules in a minimum number of synthetic steps (Abdelhamid et al., 2014 ; McLaughlin et al., 2014 ; Janssen et al., 2018 ).

As part of our studies on the chemistry of bridgehead nitrogen heterocycles, as well as taking into account our ongoing structural studies (Mamedov et al., 2013 ; Naghiyev et al., 2020a ,b ,c ; Naghiyev et al., 2021 ), we report here the crystal structure and Hirshfeld surface analysis of the title compound, C₁₆H₁₃Cl₂N₅, obtained by an efficient three-component synthetic protocol.

2. Structural commentary

In the molecular structure of the title compound, (Fig. 1), the 1,4-dihydropyridine ring (N5/C6–C9/C9A) of the 1,3,4,8-tetrahydro-2H-pyrido[1,2-a]pyrimidine ring system (N1/C2–C4/N5/C6–C9/C9A) adopts a screw-boat conformation with puckering parameters (Cremer & Pople, 1975 ) Q_T = 0.520 (3) Å, θ = 120.8 (3)° and φ = 270.4 (3)°, while the 1,3-diazinane ring (N1/C2–C4/N5/C9A) is puckered [Q_T = 0.160 (3) Å, θ = 75.2 (11)° and φ = 169.4 (10)°]. The dichlorophenyl ring (C11–C16) makes a dihedral angle of 80.82 (12)° with the mean plane of the 1,3,4,8-tetrahydro-2H-pyrido[1,2-a]pyrimidine ring system.

Figure 1
The molecular structure of the title compound. Displacement ellipsoids are drawn at the 50% probability level.

3. Supramolecular features

In the crystal, intermolecular N—H⋯N hydrogen bonds between the amine functions as donor groups and the nitrile N atoms as acceptor groups and intermolecular C—H⋯N hydrogen bonds lead to the formation of sheets extending parallel to (110) and ( $[\overline{1}]$ 10) (Table 1; Figs. 2, 3 and 4). These hydrogen-bonded sheets cross each other (Fig. 5). C—H⋯π interactions (Table 1), which form zigzag chains propagating parallel to [100] (Fig. 6), are also involved in the packing.

Table 1
Hydrogen-bond geometry (Å, °)

Cg3 is the centroid of the C11–C16 dichlorophenyl ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯N10ⁱ	0.85 (3)	2.43 (3)	3.152 (3)	143 (3)
N6—H6A⋯N17ⁱⁱ	0.85 (4)	2.17 (3)	2.927 (3)	149 (3)
N6—H6B⋯N10ⁱⁱⁱ	0.85 (4)	2.16 (4)	2.953 (3)	156 (3)
C4—H4B⋯N17^iv	0.99	2.59	3.440 (4)	144
C2—H2A⋯Cg3^iv	0.99	2.87	3.653 (3)	136
Symmetry codes: (i) $[x+{\script{1\over 2}}, -y+{\script{3\over 2}}, z+{\script{1\over 2}}]$ ; (ii) $[x-{\script{1\over 2}}, y-{\script{1\over 2}}, z]$ ; (iii) $[x, -y+1, z+{\script{1\over 2}}]$ ; (iv) $[x-{\script{1\over 2}}, -y+{\script{3\over 2}}, z+{\script{1\over 2}}]$ .

Figure 2
A view showing details of the intermolecular N—H⋯N and C—H⋯N hydrogen bonds in the unit cell of the title compound. The dichlorophenyl group and H atoms not involved in hydrogen bonding have been omitted for clarity. [Symmetry codes: (a) x, 1 − y, − $[{1\over 2}]$ + z; (b) x, 1 − y, $[{1\over 2}]$ + z; (c) − $[{1\over 2}]$ + x, − $[{1\over 2}]$ + y, z; (d) $[{1\over 2}]$ + x, $[{1\over 2}]$ + y, z; (e) − $[{1\over 2}]$ + x, $[{3\over 2}]$ − y, − $[{1\over 2}]$ + z; (f) − $[{1\over 2}]$ + x, $[{3\over 2}]$ − y, $[{1\over 2}]$ + z; (g) $[{1\over 2}]$ + x, $[{3\over 2}]$ − y, $[{1\over 2}]$ + z].

Figure 3
A view along [100] showing the intermolecular N—H⋯N and C—H⋯N hydrogen bonds of the title compound. The dichlorophenyl group and H atoms not involved in hydrogen bonding have been omitted for clarity.

Figure 4
A view along [010] showing the intermolecular N—H⋯N and C—H⋯N hydrogen bonds of the title compound. The dichlorophenyl group and H atoms not involved in hydrogen bonding have been omitted for clarity.

Figure 5
A view along [001] showing the intermolecular N—H⋯N and C—H⋯N hydrogen bonds of the title compound. The dichlorophenyl group and H atoms not involved in hydrogen bonding have been omitted for clarity.

Figure 6
A view along [010] showing the C—H⋯π interactions in the title compound.

4. Hirshfeld surface analysis

In order to visualize the intermolecular interactions in the crystal of the title compound, a Hirshfeld surface analysis (Spackman & Jayatilaka, 2009 ) was performed with CrystalExplorer17.5 (Turner et al., 2017 ). Fig. 7(a) and Fig. 7(b) show the front and back sides of the three-dimensional Hirshfeld surface of the title molecule plotted over d_norm in the range −0.4776 to +1.4517 a.u., using a `high standard' surface resolution colour-mapped over the normalized contact distance. The red, white and blue regions visible on the d_norm surfaces indicate contacts with distances shorter, longer and equal to the van der Waals separations. The red spots highlight the interatomic contacts, including the N—H⋯N and C—H⋯N hydrogen bonds.

Figure 7
(a) Front and (b) back sides of the three-dimensional Hirshfeld surface of the title compound plotted over d_norm in the range −0.4776 to +1.4517 a.u.

The overall two-dimensional fingerprint plot for the title compound and those delineated into N⋯H/H⋯N, H⋯H, C⋯H/H⋯C and Cl⋯H/H⋯Cl contacts are illustrated in Fig. 8. Numerical details of the various contacts are given in Table 2 and their percentage contributions to the Hirshfeld surfaces are collated in Table 3. N⋯H/H⋯N (28.4%), H⋯H (24.5%), C⋯H/H⋯C (21.4%) and Cl⋯H/H⋯Cl (16.1%) contribute significantly to the packing while Cl⋯C/C⋯Cl, Cl⋯Cl, Cl⋯N/N⋯Cl, C⋯N/N⋯C, C⋯C and N⋯N contacts have a negligible directional impact.

Table 2
Summary of short interatomic contacts (Å) in the title compound

Contact	Distance	Symmetry operation
H6B⋯N10	2.16	x, 1 − y, $[{1\over 2}]$ + z
H1⋯N10	2.43	$[{1\over 2}]$ + x, $[{3\over 2}]$ − y, $[{1\over 2}]$ + z
H4B⋯N17	2.59	− $[{1\over 2}]$ + x, $[{3\over 2}]$ − y, $[{1\over 2}]$ + z
H6A⋯N17	2.16	− $[{1\over 2}]$ + x, − $[{1\over 2}]$ + y, z
N10⋯H15	2.81	−1 + x, y, z
H3B⋯H13	2.57	x, y, 1 + z

Table 3
Percentage contributions of interatomic contacts to the Hirshfeld surface for the title compound

Contact	Percentage contribution
N⋯H/H⋯N	28.4
H⋯H	24.5
C⋯H/H⋯C	21.4
Cl⋯H/H⋯Cl	16.1
Cl⋯C/C⋯Cl	3.3
Cl⋯Cl	2.5
Cl⋯N/N⋯Cl	2.3
C⋯N/N⋯C	0.8
C⋯C	0.6
N⋯N	0.2

Figure 8
The two-dimensional fingerprint plots of the title compound, showing (a) all interactions, and delineated into (b) N⋯H/H⋯N, (c) H⋯H, (d) C⋯H/H⋯C and (f) Cl⋯H/H⋯Cl interactions [d_e and d_i represent the distances from a point on the Hirshfeld surface to the nearest atoms outside (external) and inside (internal) the surface, respectively].

The large number of N⋯H/H⋯N, H⋯H, C⋯H/H⋯C and Cl⋯H/H⋯Cl interactions suggest that van der Waals interactions and hydrogen bonding play the major roles in the crystal packing (Hathwar et al., 2015 ).

5. Database survey

Four related compounds, which have the 1,3,4,8-tetrahydro-2H-pyrido[1,2-a]pyrimidine ring system of the title compound, were found in a search of the Cambridge Structural Database (CSD version 5.42, update of November 2020; Groom et al., 2016 ): 9-(4-nitrobenzylidene)-8,9-dihydropyrido[2,3-d]pyrrolo[1,2-a]pyrimidin-5(7H)-one (refcode VAMBET; Khodjaniyazov & Ashurov, 2016 ), 11-(aminomethylidene)-8,9,10,11-tetrahydropyrido[2′,3′:4,5]pyrimido[1,2-a]azepin-5(7H)-one (HECLUZ; Khodjaniyazov et al., 2017 ), 7′-amino-1′H-spiro[cycloheptane-1,2′-pyrimido[4,5-d]pyrimidin]-4′(3′H)-one (LEGLIU; Chen et al., 2012 ) and 11-(2-oxopyrrolidin-1-ylmethyl)-1,2,3,4,5,6,11,11a-octahydropyrido[2,1-b]quinazolin-6-one dihydrate (KUTPEV; Samarov et al., 2010 ).

In the crystal of VAMBET, molecules are linked via C—H⋯O and C—H⋯N hydrogen bonds, forming layers parallel to (101). In the molecule of HECLUZ, the seven-membered pentamethylene ring adopts a twist-boat conformation. In the crystal, hydrogen bonds with 16-membered ring and three chain motifs are generated by N—H⋯N and N—H⋯O contacts. The amino group is located close to the nitrogen atoms, forming hydrogen bonds with R₂¹(4) and R₂²(12) graph-set motifs. This amino group also forms a hydrogen bond with the C=O oxygen atom of a molecule translated parallel to [100], which links the molecules into R₄⁴(16) rings. Hydrogen-bonded chains are formed along [100] by alternating R₂²(12) and R₄⁴(16) rings. These chains are stabilized by intermolecular π–π stacking interactions observed between the pyridine and pyrimidine rings. In LEGLIU, the molecular structure is built up from two fused six-membered rings and one seven-membered ring linked through a spiro C atom. The crystal packing is stabilized by intermolecular N—H⋯O hydrogen bonds between the two N—H groups and the ketone O atoms of the neighbouring molecules. In KUTPEV, water molecules are mutually O—H⋯O hydrogen bonded and form infinite chains propagating parallel to [010]. Neighbouring chains are linked by the quinazoline molecules by means of O—H⋯O=C hydrogen bonds, forming a two-dimensional network.

6. Synthesis and crystallization

To a dissolved mixture of 2-(2,6-dichlorobenzylidene)malononitrile (1.14 g; 5.1 mmol) and malononitrile (0.34 g; 5.2 mmol) in methanol (40 mL), 1,3-diaminopropane (0.38 g; 5.2 mmol) was added and was stirred at room temperature for 10 min. Then 25 mL of methanol were removed from the reaction mixture that was left overnight. The precipitated crystals were separated by filtration and recrystallized from ethanol (yield 78%; m.p. 541–542 K).

¹H NMR (300 MHz, DMSO-d₆): 1.89 (m, 2H, CH₂); 3.13 (m, 2H, CH₂); 3.67 (m, 2H, CH₂); 5.31 (s, 1H, CH-Ar); 6.14 (s, 2H, NH₂); 6.78 (s, 1H, NH); 7.25 (t, 1H, Ar-H, ³J_H–H = 7,9); 7.42 (d, 2H, 2Ar-H, ³J_H–H = 7,8). ¹³C NMR (75 MHz, DMSO-d₆): 22.30 (CH₂), 36.32 (Ar-CH), 38.62 (CH₂), 42.92 (CH₂), 51.70 (=C_quar), 55.06 (=C_quar), 121.61 (CN), 122.04 (CN), 129.56 (3CH_arom), 138.25 (3C_ar), 152.11 (=C_quar), 154.17 (=C_quar).

7. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 4. The C-bound H atoms were placed in calculated positions (C—H = 0.95–1.00 Å) and refined as riding with U_iso(H) = 1.2U_eq(C). All N-bound H atoms were located in a difference map [N1—H1 = 0.85 (3) Å, N6—H6A = 0.85 (4) Å and N6—H6B = 0.85 (4) Å] and they were refined with the constraint U_iso(H) = 1.2U_eq(N).

Table 4
Experimental details

Crystal data
Chemical formula	C₁₆H₁₃Cl₂N₅
M_r	346.21
Crystal system, space group	Monoclinic, Cc
Temperature (K)	100
a, b, c (Å)	8.6598 (2), 16.0275 (5), 11.6590 (3)
β (°)	90.7364 (9)
V (Å³)	1618.08 (8)
Z	4
Radiation type	Mo Kα
μ (mm⁻¹)	0.41
Crystal size (mm)	0.30 × 0.03 × 0.03

Data collection
Diffractometer	Bruker D8 QUEST PHOTON-III CCD
Absorption correction	Multi-scan (SADABS; Krause et al., 2015 )
T_min, T_max	0.880, 0.980
No. of measured, independent and observed [I > 2σ(I)] reflections	21346, 5861, 4528
R_int	0.064
(sin θ/λ)_max (Å⁻¹)	0.758

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.044, 0.090, 1.03
No. of reflections	5861
No. of parameters	217
No. of restraints	2
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.25, −0.32
Absolute structure	Flack x determined using 1774 quotients [(I⁺)−(I⁻)]/[(I⁺)+(I⁻)] (Parsons et al., 2013 ).
Absolute structure parameter	0.27 (3)
Computer programs: APEX3 (Bruker, 2018 ), SAINT (Bruker, 2013 ), SHELXT2014/5 (Sheldrick, 2015a ), SHELXL2018/3 (Sheldrick, 2015b ), ORTEP-3 for Windows (Farrugia, 2012 ) and PLATON (Spek, 2020 ).

Supporting information

CCDC reference: 2075706

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2056989021003583/wm5605sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989021003583/wm5605Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989021003583/wm5605Isup3.cml

checkCIF report

Computing details top

Data collection: APEX3 (Bruker, 2018); cell refinement: SAINT (Bruker, 2013); data reduction: SAINT (Bruker, 2013); program(s) used to solve structure: SHELXT2014/5 (Sheldrick, 2015a); program(s) used to refine structure: SHELXL2018/3 (Sheldrick, 2015b); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: PLATON (Spek, 2020).

6-Amino-8-(2,6-dichlorophenyl)-1,3,4,8-tetrahydro-2H-pyrido[1,2-a]pyrimidine-7,9-dicarbonitrile top

Crystal data top

C₁₆H₁₃Cl₂N₅	F(000) = 712
M_r = 346.21	D_x = 1.421 Mg m⁻³
Monoclinic, Cc	Mo Kα radiation, λ = 0.71073 Å
a = 8.6598 (2) Å	Cell parameters from 4611 reflections
b = 16.0275 (5) Å	θ = 2.5–32.2°
c = 11.6590 (3) Å	µ = 0.41 mm⁻¹
β = 90.7364 (9)°	T = 100 K
V = 1618.08 (8) Å³	Needle, colourless
Z = 4	0.30 × 0.03 × 0.03 mm

Data collection top

Bruker D8 QUEST PHOTON-III CCD diffractometer	4528 reflections with I > 2σ(I)
φ and ω scans	R_int = 0.064
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	θ_max = 32.6°, θ_min = 2.5°
T_min = 0.880, T_max = 0.980	h = −13→13
21346 measured reflections	k = −24→24
5861 independent reflections	l = −17→17

Refinement top

Refinement on F²	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.044	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.090	w = 1/[σ²(F_o²) + (0.0315P)² + 0.2854P] where P = (F_o² + 2F_c²)/3
S = 1.02	(Δ/σ)_max < 0.001
5861 reflections	Δρ_max = 0.25 e Å⁻³
217 parameters	Δρ_min = −0.32 e Å⁻³
2 restraints	Absolute structure: Flack x determined using 1774 quotients [(I⁺)-(I^-)]/[(I⁺)+(I^-)] (Parsons et al., 2013).
Primary atom site location: difference Fourier map	Absolute structure parameter: 0.27 (3)

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

	x	y	z	U_iso*/U_eq
Cl1	0.48473 (9)	0.76604 (6)	0.16871 (7)	0.0429 (2)
Cl2	0.69787 (9)	0.56058 (4)	0.51124 (7)	0.03080 (17)
N1	0.5635 (3)	0.75406 (14)	0.7250 (2)	0.0199 (5)
H1	0.604 (4)	0.801 (2)	0.709 (3)	0.024*
C2	0.5218 (3)	0.73373 (16)	0.8418 (2)	0.0207 (5)
H2A	0.4154	0.7528	0.8576	0.025*
H2B	0.5934	0.7611	0.8969	0.025*
C3	0.5326 (4)	0.63931 (17)	0.8531 (2)	0.0248 (6)
H3A	0.6392	0.6206	0.8373	0.030*
H3B	0.5064	0.6222	0.9321	0.030*
C4	0.4209 (3)	0.59988 (16)	0.7681 (2)	0.0218 (5)
H4A	0.4471	0.5401	0.7595	0.026*
H4B	0.3151	0.6033	0.7990	0.026*
N5	0.4232 (3)	0.64027 (13)	0.65394 (19)	0.0167 (4)
C6	0.3418 (3)	0.60234 (14)	0.5649 (2)	0.0163 (5)
N6	0.2511 (3)	0.53821 (15)	0.5930 (2)	0.0236 (5)
H6A	0.214 (4)	0.506 (2)	0.541 (3)	0.028*
H6B	0.238 (4)	0.522 (2)	0.661 (3)	0.028*
C7	0.3535 (3)	0.63028 (15)	0.4540 (2)	0.0155 (5)
C8	0.4667 (3)	0.69614 (15)	0.4164 (2)	0.0167 (5)
H8	0.4066	0.7379	0.3704	0.020*
C9	0.5266 (3)	0.74104 (16)	0.5222 (2)	0.0179 (5)
C9A	0.5062 (3)	0.71289 (15)	0.6322 (2)	0.0161 (5)
C10	0.2600 (3)	0.59393 (15)	0.3682 (2)	0.0147 (5)
N10	0.1851 (3)	0.56730 (13)	0.2941 (2)	0.0194 (5)
C11	0.5914 (3)	0.66149 (18)	0.3380 (3)	0.0200 (5)
C12	0.6051 (3)	0.6880 (2)	0.2246 (3)	0.0283 (6)
C13	0.7126 (4)	0.6549 (3)	0.1492 (3)	0.0375 (8)
H13	0.7167	0.6742	0.0723	0.045*
C14	0.8127 (4)	0.5940 (2)	0.1873 (3)	0.0383 (8)
H14	0.8869	0.5715	0.1367	0.046*
C15	0.8058 (3)	0.56565 (19)	0.2989 (3)	0.0314 (7)
H15	0.8746	0.5235	0.3254	0.038*
C16	0.6971 (3)	0.59938 (18)	0.3718 (3)	0.0240 (6)
C17	0.5995 (3)	0.81835 (17)	0.5040 (2)	0.0228 (6)
N17	0.6562 (4)	0.88151 (16)	0.4841 (2)	0.0362 (7)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Cl1	0.0391 (4)	0.0681 (6)	0.0215 (4)	−0.0012 (4)	0.0009 (3)	0.0190 (4)
Cl2	0.0305 (4)	0.0267 (3)	0.0353 (4)	0.0081 (3)	0.0050 (3)	0.0077 (3)
N1	0.0294 (12)	0.0147 (10)	0.0156 (11)	−0.0072 (9)	0.0006 (9)	0.0002 (8)
C2	0.0278 (14)	0.0215 (13)	0.0127 (12)	−0.0055 (10)	−0.0012 (10)	−0.0013 (10)
C3	0.0353 (16)	0.0207 (13)	0.0180 (14)	−0.0050 (11)	−0.0071 (12)	0.0033 (10)
C4	0.0328 (14)	0.0189 (12)	0.0136 (13)	−0.0088 (11)	−0.0029 (11)	0.0027 (9)
N5	0.0237 (11)	0.0145 (10)	0.0120 (10)	−0.0050 (8)	0.0000 (8)	0.0003 (7)
C6	0.0200 (12)	0.0127 (10)	0.0161 (12)	−0.0016 (9)	−0.0006 (9)	−0.0018 (9)
N6	0.0354 (13)	0.0211 (11)	0.0142 (11)	−0.0141 (10)	−0.0024 (10)	0.0009 (9)
C7	0.0179 (11)	0.0150 (11)	0.0137 (12)	−0.0006 (9)	0.0007 (9)	−0.0013 (9)
C8	0.0216 (13)	0.0135 (10)	0.0151 (12)	−0.0022 (9)	0.0001 (10)	0.0002 (9)
C9	0.0242 (13)	0.0149 (11)	0.0148 (13)	−0.0040 (9)	0.0029 (10)	−0.0025 (9)
C9A	0.0189 (12)	0.0131 (10)	0.0163 (12)	−0.0025 (9)	0.0001 (9)	−0.0007 (9)
C10	0.0179 (11)	0.0123 (10)	0.0140 (12)	0.0010 (9)	0.0034 (9)	0.0018 (8)
N10	0.0226 (11)	0.0193 (11)	0.0163 (12)	0.0030 (9)	−0.0013 (9)	−0.0016 (8)
C11	0.0220 (12)	0.0199 (11)	0.0181 (12)	−0.0082 (9)	0.0022 (10)	−0.0051 (9)
C12	0.0257 (15)	0.0417 (17)	0.0175 (15)	−0.0130 (13)	0.0008 (11)	−0.0018 (12)
C13	0.0281 (16)	0.067 (2)	0.0179 (15)	−0.0197 (16)	0.0048 (12)	−0.0117 (15)
C14	0.0248 (15)	0.053 (2)	0.038 (2)	−0.0131 (15)	0.0123 (13)	−0.0255 (16)
C15	0.0214 (14)	0.0300 (15)	0.043 (2)	−0.0064 (12)	0.0079 (13)	−0.0150 (14)
C16	0.0228 (14)	0.0229 (13)	0.0264 (15)	−0.0039 (10)	0.0037 (11)	−0.0039 (11)
C17	0.0329 (15)	0.0213 (12)	0.0144 (13)	−0.0073 (11)	0.0054 (11)	−0.0053 (10)
N17	0.064 (2)	0.0259 (12)	0.0189 (13)	−0.0208 (13)	0.0093 (12)	−0.0046 (10)

Geometric parameters (Å, º) top

Cl1—C12	1.749 (4)	N6—H6B	0.85 (4)
Cl2—C16	1.741 (3)	C7—C10	1.406 (4)
N1—C9A	1.355 (3)	C7—C8	1.509 (3)
N1—C2	1.451 (3)	C8—C9	1.514 (4)
N1—H1	0.85 (3)	C8—C11	1.529 (4)
C2—C3	1.522 (4)	C8—H8	1.0000
C2—H2A	0.9900	C9—C9A	1.373 (4)
C2—H2B	0.9900	C9—C17	1.408 (4)
C3—C4	1.514 (4)	C10—N10	1.155 (3)
C3—H3A	0.9900	C11—C12	1.395 (4)
C3—H3B	0.9900	C11—C16	1.405 (4)
C4—N5	1.481 (3)	C12—C13	1.392 (4)
C4—H4A	0.9900	C13—C14	1.375 (5)
C4—H4B	0.9900	C13—H13	0.9500
N5—C6	1.387 (3)	C14—C15	1.380 (5)
N5—C9A	1.393 (3)	C14—H14	0.9500
C6—N6	1.337 (3)	C15—C16	1.385 (4)
C6—C7	1.373 (4)	C15—H15	0.9500
N6—H6A	0.85 (4)	C17—N17	1.150 (3)

C9A—N1—C2	123.1 (2)	C7—C8—C9	108.2 (2)
C9A—N1—H1	114 (2)	C7—C8—C11	112.7 (2)
C2—N1—H1	121 (2)	C9—C8—C11	115.0 (2)
N1—C2—C3	106.8 (2)	C7—C8—H8	106.8
N1—C2—H2A	110.4	C9—C8—H8	106.8
C3—C2—H2A	110.4	C11—C8—H8	106.8
N1—C2—H2B	110.4	C9A—C9—C17	119.5 (2)
C3—C2—H2B	110.4	C9A—C9—C8	123.9 (2)
H2A—C2—H2B	108.6	C17—C9—C8	116.4 (2)
C4—C3—C2	108.7 (2)	N1—C9A—C9	122.4 (2)
C4—C3—H3A	110.0	N1—C9A—N5	116.5 (2)
C2—C3—H3A	110.0	C9—C9A—N5	121.1 (2)
C4—C3—H3B	110.0	N10—C10—C7	176.6 (3)
C2—C3—H3B	110.0	C12—C11—C16	114.7 (3)
H3A—C3—H3B	108.3	C12—C11—C8	121.7 (3)
N5—C4—C3	113.0 (2)	C16—C11—C8	123.5 (3)
N5—C4—H4A	109.0	C13—C12—C11	123.2 (3)
C3—C4—H4A	109.0	C13—C12—Cl1	115.9 (3)
N5—C4—H4B	109.0	C11—C12—Cl1	120.8 (2)
C3—C4—H4B	109.0	C14—C13—C12	119.3 (3)
H4A—C4—H4B	107.8	C14—C13—H13	120.3
C6—N5—C9A	119.3 (2)	C12—C13—H13	120.3
C6—N5—C4	117.9 (2)	C13—C14—C15	120.2 (3)
C9A—N5—C4	122.8 (2)	C13—C14—H14	119.9
N6—C6—C7	122.1 (2)	C15—C14—H14	119.9
N6—C6—N5	116.6 (2)	C14—C15—C16	119.2 (3)
C7—C6—N5	121.2 (2)	C14—C15—H15	120.4
C6—N6—H6A	120 (2)	C16—C15—H15	120.4
C6—N6—H6B	124 (2)	C15—C16—C11	123.3 (3)
H6A—N6—H6B	115 (3)	C15—C16—Cl2	116.0 (3)
C6—C7—C10	119.1 (2)	C11—C16—Cl2	120.6 (2)
C6—C7—C8	123.9 (2)	N17—C17—C9	176.9 (3)
C10—C7—C8	117.0 (2)

C9A—N1—C2—C3	46.5 (3)	C17—C9—C9A—N5	174.5 (3)
N1—C2—C3—C4	−60.3 (3)	C8—C9—C9A—N5	−1.8 (4)
C2—C3—C4—N5	43.2 (3)	C6—N5—C9A—N1	170.2 (2)
C3—C4—N5—C6	171.2 (2)	C4—N5—C9A—N1	−11.5 (4)
C3—C4—N5—C9A	−7.1 (4)	C6—N5—C9A—C9	−9.1 (4)
C9A—N5—C6—N6	−173.0 (2)	C4—N5—C9A—C9	169.2 (2)
C4—N5—C6—N6	8.6 (4)	C7—C8—C11—C12	116.4 (3)
C9A—N5—C6—C7	6.4 (4)	C9—C8—C11—C12	−118.9 (3)
C4—N5—C6—C7	−172.0 (2)	C7—C8—C11—C16	−61.5 (3)
N6—C6—C7—C10	4.1 (4)	C9—C8—C11—C16	63.2 (3)
N5—C6—C7—C10	−175.2 (2)	C16—C11—C12—C13	1.1 (4)
N6—C6—C7—C8	−173.2 (2)	C8—C11—C12—C13	−176.9 (3)
N5—C6—C7—C8	7.4 (4)	C16—C11—C12—Cl1	−179.0 (2)
C6—C7—C8—C9	−16.0 (3)	C8—C11—C12—Cl1	3.0 (4)
C10—C7—C8—C9	166.6 (2)	C11—C12—C13—C14	−1.0 (5)
C6—C7—C8—C11	112.3 (3)	Cl1—C12—C13—C14	179.1 (2)
C10—C7—C8—C11	−65.1 (3)	C12—C13—C14—C15	0.5 (5)
C7—C8—C9—C9A	13.2 (3)	C13—C14—C15—C16	−0.2 (5)
C11—C8—C9—C9A	−113.8 (3)	C14—C15—C16—C11	0.4 (4)
C7—C8—C9—C17	−163.2 (2)	C14—C15—C16—Cl2	−179.4 (2)
C11—C8—C9—C17	69.8 (3)	C12—C11—C16—C15	−0.8 (4)
C2—N1—C9A—C9	169.2 (3)	C8—C11—C16—C15	177.2 (3)
C2—N1—C9A—N5	−10.1 (4)	C12—C11—C16—Cl2	179.0 (2)
C17—C9—C9A—N1	−4.7 (4)	C8—C11—C16—Cl2	−3.1 (4)
C8—C9—C9A—N1	179.0 (3)

Hydrogen-bond geometry (Å, º) top

Cg3 is the centroid of the C11–C16 dichlorophenyl ring.

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···N10ⁱ	0.85 (3)	2.43 (3)	3.152 (3)	143 (3)
N6—H6A···N17ⁱⁱ	0.85 (4)	2.17 (3)	2.927 (3)	149 (3)
N6—H6B···N10ⁱⁱⁱ	0.85 (4)	2.16 (4)	2.953 (3)	156 (3)
C4—H4B···N17^iv	0.99	2.59	3.440 (4)	144
C2—H2A···Cg3^iv	0.99	2.87	3.653 (3)	136

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

Summary of short interatomic contacts (Å) in the title compound top

Contact	Distance	Symmetry operation
H6B···N10	2.16	x, 1 - y, 1/2 + z
H1···N10	2.43	1/2 + x, 3/2 - y, 1/2 + z
H4B···N17	2.59	-1/2 + x, 3/2 - y, 1/2 + z
H6A···N17	2.16	-1/2 + x, -1/2 + y, z
N10···H15	2.81	-1 + x, y, z
H3B···H13	2.57	x, y, 1 + z

Percentage contributions of interatomic contacts to the Hirshfeld surface for the title compound top

Contact	Percentage contribution
N···H/H···N	28.4
H···H	24.5
C···H/H···C	21.4
Cl···H/H···Cl	16.1
Cl···C/C···Cl	3.3
Cl···Cl	2.5
Cl···N/N···Cl	2.3
C···N/N···C	0.8
C···C	0.6
N···N	0.2

Acknowledgements

Authors contributions are as follows. Conceptualization, FNN and IGM; methodology, FNN and IGM; investigation, VNK, FNN, TAT and AAA; writing (original draft), MA and IGM; writing (review and editing of the manuscript), MA and IGM; visualization, MA, FNN and IGM; funding acquisition, VNK and FNN; resources, RMR, AAA and FNN; supervision, IGM and MA.

Funding information

This work was supported by Baku State University, and RUDN University Strategic Academic Leadership Program.

References

Abdelhamid, A. A., Mohamed, S. K., Khalilov, A. N., Gurbanov, A. V. & Ng, S. W. (2011). Acta Cryst. E67, o744. Web of Science CSD CrossRef IUCr Journals Google Scholar
Abdelhamid, A. A., Mohamed, S. K., Maharramov, A. M., Khalilov, A. N. & Allahverdiev, M. A. (2014). J. Saudi Chem. Soc. 18, 474–478. Web of Science CSD CrossRef Google Scholar
Awouters, F., Vermeire, J., Smeyers, F., Vermote, P., van Beek, R. & Niemegeers, C. J. E. (1986). Drug Dev. Res. 8, 95–102. CrossRef CAS Web of Science Google Scholar
Blaton, N. M., Peeters, O. M. & De Ranter, C. J. (1995). Acta Cryst. C51, 533–535. CSD CrossRef CAS Web of Science IUCr Journals Google Scholar
Bruker (2013). SAINT. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Bruker (2018). APEX3. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Chen, S., Shi, D., Liu, M. & Li, J. (2012). Acta Cryst. E68, o2546. CSD CrossRef IUCr Journals Google Scholar
Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354–1358. CrossRef CAS Web of Science Google Scholar
Farrugia, L. J. (2012). J. Appl. Cryst. 45, 849–854. Web of Science CrossRef CAS IUCr Journals Google Scholar
Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179. Web of Science CrossRef IUCr Journals Google Scholar
Hathwar, V. R., Sist, M., Jørgensen, M. R. V., Mamakhel, A. H., Wang, X., Hoffmann, C. M., Sugimoto, K., Overgaard, J. & Iversen, B. B. (2015). IUCrJ, 2, 563–574. Web of Science CSD CrossRef CAS PubMed IUCr Journals Google Scholar
Hermecz, I. & Mészáros, Z. (1988). Med. Res. Rev. 8, 203–230. CrossRef CAS PubMed Web of Science Google Scholar
Janssen, G. V., van den Heuvel, J. A. C., Megens, R. P., Benningshof, J. C. J. & Ovaa, H. (2018). Bioorg. Med. Chem. 26, 41–49. Web of Science CrossRef CAS PubMed Google Scholar
Khalilov, A. N., Abdelhamid, A. A., Gurbanov, A. V. & Ng, S. W. (2011). Acta Cryst. E67, o1146. Web of Science CSD CrossRef IUCr Journals Google Scholar
Khodjaniyazov, Kh. U. & Ashurov, J. M. (2016). Acta Cryst. E72, 452–455. Web of Science CSD CrossRef IUCr Journals Google Scholar
Khodjaniyazov, K. U., Makhmudov, U. S., Turgunov, K. K. & Elmuradov, B. Z. (2017). Acta Cryst. E73, 1497–1500. Web of Science CSD CrossRef IUCr Journals Google Scholar
Krause, L., Herbst-Irmer, R., Sheldrick, G. M. & Stalke, D. (2015). J. Appl. Cryst. 48, 3–10. Web of Science CSD CrossRef ICSD CAS IUCr Journals Google Scholar
Mahmoudi, G., Dey, L., Chowdhury, H., Bauzá, A., Ghosh, B. K., Kirillov, A. M., Seth, S. K., Gurbanov, A. V. & Frontera, A. (2017). Inorg. Chim. Acta, 461, 192–205. Web of Science CSD CrossRef CAS Google Scholar
Mahmoudi, G., Khandar, A. A., Afkhami, F. A., Miroslaw, B., Gurbanov, A. V., Zubkov, F. I., Kennedy, A., Franconetti, A. & Frontera, A. (2019). CrystEngComm, 21, 108–117. Web of Science CSD CrossRef CAS Google Scholar
Mamedov, I. G., Bayramov, M. R., Mamedova, Y. V. & Maharramov, A. M. (2013). Magn. Reson. Chem. 51, 234–239. Web of Science CrossRef CAS PubMed Google Scholar
McLaughlin, E. C., Norman, M. W., Ko Ko, T. & Stolt, I. (2014). Tetrahedron Lett. 55, 2609–2611. Web of Science CrossRef CAS Google Scholar
Naghiyev, F. N., Akkurt, M., Askerov, R. K., Mamedov, I. G., Rzayev, R. M., Chyrka, T. & Maharramov, A. M. (2020a). Acta Cryst. E76, 720–723. Web of Science CrossRef IUCr Journals Google Scholar
Naghiyev, F. N., Cisterna, J., Khalilov, A. N., Maharramov, A. M., Askerov, R. K., Asadov, K. A., Mamedov, I. G., Salmanli, K. S., Cárdenas, A. & Brito, I. (2020b). Molecules, 25, 2235. Web of Science CSD CrossRef Google Scholar
Naghiyev, F. N., Grishina, M. M., Khrustalev, V. N., Khalilov, A. N., Akkurt, M., Akobirshoeva, A. A. & Mamedov, İ. G. (2021). Acta Cryst. E77, 195–199. Web of Science CSD CrossRef IUCr Journals Google Scholar
Naghiyev, F. N., Mammadova, G. Z., Mamedov, I. G., Huseynova, A. T., Çelikesir, S. T., Akkurt, M. & Akobirshoeva, A. A. (2020c). Acta Cryst. E76, 1365–1368. Web of Science CSD CrossRef IUCr Journals Google Scholar
Parsons, S., Flack, H. D. & Wagner, T. (2013). Acta Cryst. B69, 249–259. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Pryadeina, M. V., Burgart, Y. V., Kodess, M. I. & Saloutin, V. I. (2005). Russ. Chem. Bull. 54, 2841–2845. Web of Science CrossRef CAS Google Scholar
Riva, R., Banfi, L., Castaldi, G., Ghislieri, D., Malpezzi, L., Musumeci, F., Tufaro, R. & Rasparini, M. (2011). Eur. J. Org. Chem. pp. 2319–2325. Web of Science CSD CrossRef Google Scholar
Samarov, Z. U., Okmanov, R. Y., Turgunov, K. K., Tashkhodjaev, B. & Shakhidoyatov, K. M. (2010). Acta Cryst. E66, o890. Web of Science CSD CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8. Web of Science CrossRef IUCr Journals Google Scholar
Spackman, M. A. & Jayatilaka, D. (2009). CrystEngComm, 11, 19–32. Web of Science CrossRef CAS Google Scholar
Spek, A. L. (2020). Acta Cryst. E76, 1–11. Web of Science CrossRef IUCr Journals Google Scholar
Turner, M. J., Mckinnon, J. J., Wolff, S. K., Grimwood, D. J., Spackman, P. R., Jayatilaka, D. & Spackman, M. A. (2017). CrystalExplorer17. University of Western Australia. Google Scholar
Ukrainets, I. V., Bereznyakova, N. L., Sim, G. & Davidenko, A. A. (2018). Pharm. Chem. J. 52, 601–605. Web of Science CSD CrossRef CAS Google Scholar
Viswanathan, A., Kute, D., Musa, A., Mani, S. K., Sipilä, V., Emmert-Streib, F., Zubkov, F. I., Gurbanov, A. V., Yli-Harja, O. & Kandhavelu, M. (2019). Eur. J. Med. Chem. 166, 291–303. Web of Science CrossRef CAS PubMed Google Scholar
Wu, Y.-J., He, H., Hu, S., Huang, Y., Scola, P. M., Grant-Young, K., Bertekap, R. L., Wu, D., Gao, Q., Li, Y., Klakouski, C. & Westphal, R. S. (2003). J. Med. Chem. 46, 4834–4837. Web of Science CSD CrossRef PubMed CAS Google Scholar
Yadigarov, R. R., Khalilov, A. N., Mamedov, I. G., Nagiev, F. N., Magerramov, A. M. & Allakhverdiev, M. A. (2009). Russ. J. Org. Chem. 45, 1856–1858. Web of Science CrossRef CAS Google Scholar
Yahata, H., Saito, M., Sendo, T., Itoh, Y., Uchida, M., Hirakawa, T., Nakano, H. & Oishi, R. (2006). Int. J. Cancer, 118, 2636–2638. Web of Science CrossRef PubMed CAS Google Scholar
Yin, J., Khalilov, A. N., Muthupandi, P., Ladd, R. & Birman, V. B. (2020). J. Am. Chem. Soc. 142, 60–63. Web of Science CSD CrossRef CAS PubMed Google Scholar

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