Crystal structure, Hirshfeld surface analysis and DFT calculations of 7-bromo-2,3-di­hydro­pyrrolo[2,1-b]quinazolin-9(1H)-one

Tojiboev, A.; Elmuradov, B.; Kattaev, N.; Abdurazakov, A.; Nasrullayev, A.; Tashkhodjaev, B.

doi:10.1107/S2056989022007800

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ISSN: 2056-9890

Volume 78| Part 9| September 2022| Pages 885-889

https://doi.org/10.1107/S2056989022007800

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Crystal structure, Hirshfeld surface analysis and DFT calculations of 7-bromo-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one

Akmaljon Tojiboev,^a,^b ^* Burkhon Elmuradov,^c Nuritdin Kattaev,^b Asqar Abdurazakov,^c Azizbek Nasrullayev ^d and Bakhodir Tashkhodjaev ^c

^aUniversity of Geological Sciences, Olimlar street, 64, Mirzo Ulugbek district, Tashkent, Uzbekistan, ^bDepartment of Chemistry, National University of Uzbekistan named after Mirzo Ulugbek, Tashkent, Uzbekistan, ^cS. Yunusov Institute of Chemistry of Plant Substances, Academy of Sciences of Uzbekistan, Tashkent, Uzbekistan, and ^dDepartment of Organic Synthesis and Bioorganic Chemistry, Samarkand State University, Samarkand, Uzbekistan
^*Correspondence e-mail: a_tojiboev@yahoo.com

Edited by M. Weil, Vienna University of Technology, Austria (Received 13 July 2022; accepted 2 August 2022; online 9 August 2022)

The molecular structure of the title compound, C₁₁H₉BrN₂O, is almost planar. The benzene and pyrimidine rings are essentially coplanar, with r.m.s. deviations of 0.0130 Å, and the largest displacement is for the flap atom of the dihydropyrrole moiety [0.154 (7) Å]. Hirshfeld surface analyses revealed that the crystal packing is dominated by H⋯H, Br⋯H/H⋯Br and O⋯H/H⋯O interactions, and Br⋯Br interactions in the crystal structure are also observed. Theoretical calculations using density functional theory (DFT) with the B3LYP functional basis set gave numerical parameters for the frontier molecular orbitals.

Keywords: crystal structure; 7-bromo-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one; Hirshfeld surface analysis; DFT.

CCDC reference: 2194365

1. Chemical context

Quinazolines are of significant interest for their various biological properties (Rajput et al., 2012 ; Ramesh et al., 2012 ; Khan et al., 2014 ; Ajani et al., 2016 ). This class of compounds is considered as an attractive target for medicinal chemists, because quinazoline and its derivatives are the scaffold of several potent antitumor drugs, for example the well-known erlotinib and gefitinib (Sordella et al., 2004 ; Raymond et al., 2000 ). Besides these two drugs, the Food and Drug Administration (FDA) has approved some other quinazolines as effective anticancer drugs, viz. lapatinib and vandetanib. In general, the reported biological activities of quinazolines include antibacterial, anti-inflammatory, CNS depressant, anticonvulsant, antifungal, antimalarial, anticancer properties, which make them interesting for the pharmaceutical industry (Ajani et al., 2015 ).

In this context, synthetic analogues of the tricyclic quinazoline-9-one-7-bromo-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one have been synthesized, amongst them the title compound with a bromine atom in position 7. In comparison with a reported literature procedure (Shakhidoyatov, 1983 ), this compound is now obtained in higher yields (80–88%). For this purpose, condensation of 2-amino-5-brombenzoic acid with appropriate pyrrolidin-2-one was used whereas in the literature (Shakhidoyatov, 1983), 2-amino-5-brombenzoic acid was added to the corresponding lactam mixture with a condensing agent (POCl₃) at room temperature (293–298 K) and the reaction products separated by extraction after the reaction mixture was reduced to pH = 9–10 with NH₄OH. As distinguished from the reported procedure, we carried out these reactions by cooling in an ice bath at a much lower temperature (273–275 K) and for a relatively longer period of time. The reaction products were finally separated by cold NH₄OH at pH = 10–11. In general, the interactions of 7-bromo-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one with aldehydes are well-studied (Abdurazakov et al., 2007 ).

Here, we report the molecular and crystal structures as well as Hirshfeld surface analysis and the frontier molecular orbitals calculated by density functional theory (DFT) with the B3LYP functional basis set.

2. Structural commentary

The molecular structure of the title compound is shown in Fig. 1. The molecule is almost planar. In particular, the benzene and pyrimidine rings are essentially coplanar, with an r.m.s. deviations of 0.0130 Å from planarity. The remaining atoms of the dihydropyrrole ring are slightly displaced from these planes, with deviations of −0.060 (5) Å for C1, −0.154 (7) Å for flap atom C2, and 0.060 (6) Å for C3. The acyclic C7—Br1 bond length 1.900 (3) Å is consistent with the data for other Br-substituted tricyclic quinazolinone derivatives (Mukarramov et al., 2009 ; Tozhiboev et al., 2007a ; D'yakonov et al., 1992 ; Okmanov et al., 2009 ; Pereira et al., 2005 ).

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

3. Supramolecular features

In the crystal, molecules participate in centrosymmetric halogen-bonding dimers with Br⋯Br intermolecular contacts of 3.5961 (5) Å, which is shorter than the sum of van der Waals radii (Bondi et al., 1964 ) of two bromine atoms (3.66 Å). The C7—Br⋯Br angle amounts to 166.70 (14)°. The molecules also engage in weak C7—Br⋯Cg interactions, with Br⋯Cg1(2 − x, 1 − y, 1 − z) = 3.6428 (15) Å, forming a layered network (Fig. 2). Additional π–π stacking (Fig. 3) occurs between the aromatic rings of neighbouring molecules, with the distance between the centroids Cg2⋯Cg2ⁱ being 3.9969 (14) Å [symmetry code: (i) 1 − x, 1 − y, 1 − z] and a ring slippage of 1.569 Å, and Cg2⋯Cg3ⁱⁱ being 3.7513 (16) Å [symmetry code: (ii) 2 − x, 1 − y, 1 − z] and a ring slippage of 1.194 Å. Both short intermolecular contacts help to stack parallel molecules along [100]. The resulting two-dimensional network extends parallel to (002), with neighbouring layers linked through C1—H1B⋯N4 short intermolecular contacts, H1B⋯N4(x, $[{1\over 2}]$ − y, $[{1\over 2}]$ + z) = 2.73 Å, C1—H1B⋯N4(x, $[{1\over 2}]$ − y, $[{1\over 2}]$ + z) = 169°, to form the full three-dimensional structure (Fig. 4).

Figure 2
The packing of the title compound in a view perpendicular to (002). Intermolecular Br⋯Br contacts and C—Br⋯Cg1 are shown as red and green dashed lines, respectively. Cg1 is the centroid of the C1–C3/C3A/N10 ring.

Figure 3
The packing of the title compound in a view approximately along [001], showing stacking between adjacent molecules in terms of Cg2⋯Cg2 (blue dashed lines) and Cg2⋯Cg3 (red dashed lines) interactions. Cg2 is the centroid (blue sphere) of the pyrimidine ring and Cg3 is the centroid (red sphere) of the benzene ring. H atoms are omitted for clarity.

Figure 4
Packing of the title compound along [100], with intermolecular C—H⋯N contacts shown as light-blue dashed lines.

4. Hirshfeld surface analysis

In order to quantify the intermolecular interactions in the crystal of the title compound, a Hirshfeld surface (HS) analysis (Spackman et al., 2009 ) was performed and associated two-dimensional fingerprint plots (McKinnon et al., 2007 ) were generated with the program CrystalExplorer (Spackman et al., 2021 ). The HS mapped over d_norm is depicted in Fig. 5, which shows the most prominent intermolecular interactions as red spots corresponding to the Br⋯Br, C—H⋯O and N—H⋯O contacts. The two-dimensional fingerprint plot for all contacts is given in Fig. 6a. H⋯H contacts are responsible for the largest contribution (37.2%) to the Hirshfeld surface (Fig. 6b). Besides these contacts, Br⋯H/H⋯Br (19.6%), O⋯H/H⋯O (11.3%), N⋯H/H⋯N (8.1%) and C⋯H/H⋯C (6.9%) interactions contribute significantly to the total Hirshfeld surface; their decomposed fingerprint plots are shown in Fig. 6c–f. The contributions of further contacts are only minor and amount to N⋯C/C⋯N (3.5%), O⋯C/C⋯O (2.0%), Br⋯C/C⋯Br (0.9%), Br⋯Br (0.8%), O⋯N/N⋯O (0.5%) and Br⋯N/N⋯Br (0.3%).

Figure 5
The Hirshfeld surface of the title compound mapped over d_norm, showing the close contacts.

Figure 6
A view of the two-dimensional fingerprint plots for the title compound, showing (a) all interactions, and delineated into (b) H⋯H, (c) Br⋯H/H⋯Br, (d) O⋯H/H⋯O, (e) N⋯H/H⋯N and (f) C⋯H/H⋯C interactions. The d_i and d_e values are the closest internal and external distances (in A°) from given points on the Hirshfeld surface contacts.

5. Frontier molecular orbitals

DFT was used to calculate the frontier molecular orbitals (FMOs, Fig. 7), which give important details of how a molecule interacts with other species, for example in terms of molecular reactivity and the ability of a molecule to absorb light. From the highest occupied molecular orbital (HOMO) electrons can be donated to the lowest unoccupied molecular orbital (LUMO). Moreover, the energy of the HOMO is directly related to the ionization potential, while the LUMO energy is directly related to the electron affinity, and the resulting energy difference (or energy gap) between HOMO and LUMO gives information about the stability of a molecule. In the case where the energy gap is small, the molecule is highly polarizable and has a high chemical reactivity. By using the HOMO and LUMO energy values of a molecule, its electronegativity (c), chemical hardness (h) and chemical softness (s) can be calculated as follows: c = (I + A)/2; h = (I - A)/2; s = 1/2h, where I and A are the ionization potential and electron affinity, respectively, where I = –E_HOMO and A = –E_LUMO (Pir et al., 2014 ; Azizov et al., 2021 ).

Figure 7
The frontier molecular orbitals (HOMO-LUMO) and the resulting band gap of the title molecule.

E_HOMO and E_LUMO, electronegativity (c), hardness (h), potential (m), electrophilicity (w) and softness (s) for the title molecule were calculated at the DFT/B3LYP level using the 6-311++G(d,p) basis set (Table 1). The values of h and s are significant for the evaluation of both reactivity and stability. The electron transition from the HOMO to the LUMO energy level is shown in Fig. 7. The energy band gap [ΔE = E_LUMO − E_HOMO] of the molecule is 4.8208 eV, the frontier molecular orbital energies E_HOMO and E_LUMO being −6.4559 and −1.6351 eV, respectively. The high value of the band gap (4,8208 eV) indicates the relatively high stability of the title molecule.

Table 1
Calculated parameters of the title molecule calculated at the B3LYP/6–311++G(d,p) level

Parameters	DFT/B3LYP
Total energy TE (a.u.)	−3183.662028
E_HOMO (eV)	−6.4559
E_LUMO (eV)	−1.6351
Energy gap, ΔE (eV)	4.8208
Dipole moment, μ (Debye)	4.6478
Ionization potential, I (eV)	6.4559
Electron affinity, A	1.6351
Electronegativity, χ	4.0455
Hardness, η	2.4104
Electrophilicity index, ω	3.3949
Softness, σ	0.2074

6. Database survey

A search in the Cambridge Structural Database (CSD, version 2022; Groom et al., 2016 ) gave four matches of molecules containing the 2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one moiety with a similar conformation to that in the title structure: deoxyvasicinone (TEFGEQ; Turgunov et al., 1995 ), deoxyvasicinonium chloride (TEFGIU; Turgunov et al., 1995), bis(deoxyvasicinonium) tetrachloridocobaltate(II) (TEFGOA; Turgunov et al., 1995) and 4-oxo-2,3-tetramethylene-3,4-dihydroquinazolinium 2,3-tetramethylene-3,4-dihydroquinazol-4-one hemikis(oxalate) oxalic acid solvate (TITGUZ; Tozhiboev et al., 2007b ). A search for compounds substituted in position 7 of 2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one moiety gave only two hits: N-(9-oxo-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazolin-7-yl)propanamide sesquihydrate (GABJAX; Elmuradov et al., 2016 ) and 3b-hydroxy-7-methoxy-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one monohydrate (HIHLIT; Magotra et al., 1996 ). Comparing the listed structures with that of the title compound gave analogous complanarities of the benzene and pyrimidine rings. In the case of structures TEFGEQ, GABJAX and HIHLIT they have also similarities regarding π–π stacking interactions.

7. Synthesis and crystallization

The reaction scheme to yield the title compound is shown in Fig. 8. To a mixture of 4.32 g (20 mmol) 2-amino-5-bromobenzoic acid and 2.72 g (32 mmol) pyrrolidin-2-one, 21.8 g (13 ml) (d = 1.675) (0.142 mol) of phosphoroxychloride were added dropwise over 1 h at 273–275 K. The reaction mixture was then heated at 368–371 K for 2 h, it was subsequently cooled and finally poured over ice. The temperature of the mixture was kept at around 273–275 K. When the reaction mixture was completely decomposed, it was brought to pH = 10–11 with 25%_wt ammonium hydroxide solution. The light-yellow precipitate was filtered off, dried and recrystallized from methanol. The yield of the product was 4.35 g (82%), m.p. 431–433 K (literature, m.p. = 430–431 K; Shakhidoyatov, 1983).

Figure 8
The reaction scheme of the title compound.

¹H NMR (400 Mz, CDCl₃, δ, ppm): 8.4 (1H, d, J = 2.4, H-8), 7.8 (1H, dd, J = 2.4, J = 8.8, H-6), 7.5 (1H, d, J = 8.8, H-5), 4.2 (2H, q, J = 7.2, H-1), 3.18 (2H, t, J = 7.6, H-3), 2.31 (2H, m, H-2).

8. Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2. H atoms attached to C were positioned geometrically, with C—H = 0.93 Å (for aromatic) or C—H = 0.97 Å (for methylene H atoms), and were refined with U_iso(H) = 1.2U_eq(C).

Table 2
Experimental details

Crystal data
Chemical formula	C₁₁H₉BrN₂O
M_r	265.11
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	296
a, b, c (Å)	7.5654 (3), 11.4972 (2), 12.1025 (3)
β (°)	105.583 (3)
V (Å³)	1013.99 (5)
Z	4
Radiation type	Cu Kα
μ (mm⁻¹)	5.30
Crystal size (mm)	0.45 × 0.10 × 0.10

Data collection
Diffractometer	XtaLAB Synergy, Single source at home/near, HyPix3000
Absorption correction	Multi-scan (CrysAlis PRO; Rigaku OD, 2020 $[Rigaku OD (2020). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]$ )
T_min, T_max	0.400, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	9036, 1959, 1770
R_int	0.035
(sin θ/λ)_max (Å⁻¹)	0.615

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.036, 0.099, 1.08
No. of reflections	1959
No. of parameters	137
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.61, −0.56
Computer programs: CrysAlis PRO (Rigaku OD, 2020 $[Rigaku OD (2020). CrysAlis PRO. Rigaku Oxford Diffraction, Yarnton, England.]$ ), SHELXS (Sheldrick, 2008 ), SHELXL (Sheldrick, 2015 ), PLATON (Spek, 2020 ) and publCIF (Westrip, 2010 ).

Supporting information

CCDC reference: 2194365

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2056989022007800/wm5655sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989022007800/wm5655Isup3.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989022007800/wm5655Isup3.cml

checkCIF report

Computing details top

Data collection: CrysAlis PRO (Rigaku OD, 2020); cell refinement: CrysAlis PRO (Rigaku OD, 2020); data reduction: CrysAlis PRO (Rigaku OD, 2020); program(s) used to solve structure: SHELXS (Sheldrick, 2008); program(s) used to refine structure: SHELXL (Sheldrick, 2015); molecular graphics: PLATON (Spek, 2020); software used to prepare material for publication: publCIF (Westrip, 2010).

7-Bromo-2,3-dihydropyrrolo[2,1-b]quinazolin-9(1H)-one top

Crystal data top

C₁₁H₉BrN₂O	F(000) = 528
M_r = 265.11	D_x = 1.737 Mg m⁻³
Monoclinic, P2₁/c	Cu Kα radiation, λ = 1.54184 Å
a = 7.5654 (3) Å	Cell parameters from 5905 reflections
b = 11.4972 (2) Å	θ = 3.8–71.3°
c = 12.1025 (3) Å	µ = 5.30 mm⁻¹
β = 105.583 (3)°	T = 296 K
V = 1013.99 (5) Å³	Prismatic, colourless
Z = 4	0.45 × 0.10 × 0.10 mm

Data collection top

XtaLAB Synergy, Single source at home/near, HyPix3000 diffractometer	1959 independent reflections
Radiation source: micro-focus sealed X-ray tube	1770 reflections with I > 2σ(I)
Detector resolution: 10.0000 pixels mm^-1	R_int = 0.035
ω scans	θ_max = 71.5°, θ_min = 5.4°
Absorption correction: multi-scan (CrysAlisPro; Rigaku OD, 2020)	h = −9→9
T_min = 0.400, T_max = 1.000	k = −14→13
9036 measured reflections	l = −14→14

Refinement top

Refinement on F²	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F² > 2σ(F²)] = 0.036	w = 1/[σ²(F_o²) + (0.0459P)² + 0.6636P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.099	(Δ/σ)_max = 0.005
S = 1.08	Δρ_max = 0.61 e Å⁻³
1959 reflections	Δρ_min = −0.56 e Å⁻³
137 parameters	Extinction correction: SHELXL-2018/3 (Sheldrick 2015), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
0 restraints	Extinction coefficient: 0.0045 (4)

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
Br	0.90737 (5)	0.85845 (3)	0.51410 (4)	0.0772 (2)
O	0.6024 (3)	0.46212 (19)	0.28785 (15)	0.0704 (6)
C1	0.5525 (4)	0.2291 (2)	0.3474 (2)	0.0524 (6)
H1A	0.615715	0.217862	0.288281	0.063*
H1B	0.424182	0.245293	0.311148	0.063*
C2	0.5725 (5)	0.1238 (3)	0.4234 (3)	0.0646 (8)
H2A	0.660804	0.070068	0.406688	0.077*
H2B	0.455714	0.084094	0.411100	0.077*
C3	0.6385 (5)	0.1665 (2)	0.5467 (2)	0.0573 (7)
H3A	0.541287	0.160567	0.584874	0.069*
H3B	0.742854	0.121317	0.589288	0.069*
C3A	0.6916 (4)	0.2907 (2)	0.53807 (19)	0.0428 (5)
N4	0.7726 (4)	0.35675 (17)	0.62262 (17)	0.0503 (5)
C4A	0.8027 (3)	0.4710 (2)	0.59434 (19)	0.0424 (5)
C5	0.8937 (4)	0.5471 (2)	0.6820 (2)	0.0569 (7)
H5	0.932797	0.519968	0.757050	0.068*
C6	0.9258 (4)	0.6610 (2)	0.6588 (2)	0.0554 (7)
H6	0.986151	0.710837	0.717397	0.066*
C7	0.8667 (4)	0.7005 (2)	0.5464 (2)	0.0490 (6)
C8	0.7793 (4)	0.6286 (2)	0.4582 (2)	0.0486 (6)
H8	0.742035	0.656476	0.383367	0.058*
C8A	0.7471 (3)	0.5135 (2)	0.48227 (19)	0.0403 (5)
C9	0.6560 (3)	0.4355 (2)	0.38867 (19)	0.0451 (5)
N10	0.6368 (3)	0.32406 (18)	0.42522 (15)	0.0405 (4)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
Br	0.0940 (3)	0.0341 (2)	0.1020 (4)	−0.00671 (14)	0.0235 (2)	0.00799 (14)
O	0.1104 (17)	0.0553 (12)	0.0345 (9)	0.0020 (11)	0.0007 (10)	0.0064 (8)
C1	0.0651 (16)	0.0489 (15)	0.0402 (12)	−0.0045 (12)	0.0089 (11)	−0.0130 (11)
C2	0.090 (2)	0.0478 (16)	0.0519 (16)	−0.0179 (15)	0.0121 (15)	−0.0119 (12)
C3	0.088 (2)	0.0401 (13)	0.0432 (13)	−0.0170 (13)	0.0171 (13)	−0.0026 (11)
C3A	0.0572 (14)	0.0365 (12)	0.0347 (11)	−0.0038 (10)	0.0121 (10)	0.0004 (9)
N4	0.0768 (15)	0.0375 (12)	0.0338 (10)	−0.0096 (9)	0.0099 (10)	−0.0008 (8)
C4A	0.0548 (13)	0.0338 (12)	0.0377 (11)	−0.0018 (10)	0.0110 (10)	0.0000 (9)
C5	0.0807 (19)	0.0420 (14)	0.0412 (12)	−0.0082 (13)	0.0047 (12)	−0.0026 (11)
C6	0.0657 (16)	0.0411 (13)	0.0557 (15)	−0.0073 (12)	0.0100 (13)	−0.0097 (11)
C7	0.0530 (14)	0.0315 (12)	0.0638 (15)	0.0004 (10)	0.0177 (12)	0.0019 (11)
C8	0.0595 (15)	0.0385 (13)	0.0476 (13)	0.0059 (10)	0.0142 (11)	0.0086 (10)
C8A	0.0473 (12)	0.0363 (12)	0.0375 (11)	0.0042 (9)	0.0116 (9)	0.0011 (9)
C9	0.0571 (14)	0.0407 (13)	0.0354 (11)	0.0060 (10)	0.0090 (10)	0.0027 (9)
N10	0.0515 (11)	0.0373 (10)	0.0317 (9)	−0.0017 (8)	0.0093 (8)	−0.0033 (8)

Geometric parameters (Å, º) top

Br—C7	1.900 (3)	C3A—N10	1.371 (3)
O—C9	1.217 (3)	N4—C4A	1.392 (3)
C1—N10	1.471 (3)	C4A—C8A	1.396 (3)
C1—C2	1.503 (4)	C4A—C5	1.404 (3)
C1—H1A	0.9700	C5—C6	1.375 (4)
C1—H1B	0.9700	C5—H5	0.9300
C2—C3	1.522 (4)	C6—C7	1.389 (4)
C2—H2A	0.9700	C6—H6	0.9300
C2—H2B	0.9700	C7—C8	1.371 (4)
C3—C3A	1.494 (4)	C8—C8A	1.391 (3)
C3—H3A	0.9700	C8—H8	0.9300
C3—H3B	0.9700	C8A—C9	1.464 (3)
C3A—N4	1.290 (3)	C9—N10	1.376 (3)

N10—C1—C2	104.5 (2)	N4—C4A—C5	118.8 (2)
N10—C1—H1A	110.8	C8A—C4A—C5	118.3 (2)
C2—C1—H1A	110.8	C6—C5—C4A	121.1 (2)
N10—C1—H1B	110.8	C6—C5—H5	119.4
C2—C1—H1B	110.8	C4A—C5—H5	119.4
H1A—C1—H1B	108.9	C5—C6—C7	118.9 (2)
C1—C2—C3	107.0 (2)	C5—C6—H6	120.6
C1—C2—H2A	110.3	C7—C6—H6	120.6
C3—C2—H2A	110.3	C8—C7—C6	121.8 (2)
C1—C2—H2B	110.3	C8—C7—Br	119.1 (2)
C3—C2—H2B	110.3	C6—C7—Br	119.1 (2)
H2A—C2—H2B	108.6	C7—C8—C8A	119.0 (2)
C3A—C3—C2	105.3 (2)	C7—C8—H8	120.5
C3A—C3—H3A	110.7	C8A—C8—H8	120.5
C2—C3—H3A	110.7	C8—C8A—C4A	120.8 (2)
C3A—C3—H3B	110.7	C8—C8A—C9	119.6 (2)
C2—C3—H3B	110.7	C4A—C8A—C9	119.6 (2)
H3A—C3—H3B	108.8	O—C9—N10	121.4 (2)
N4—C3A—N10	125.3 (2)	O—C9—C8A	125.6 (2)
N4—C3A—C3	125.9 (2)	N10—C9—C8A	112.97 (19)
N10—C3A—C3	108.8 (2)	C3A—N10—C9	123.4 (2)
C3A—N4—C4A	115.8 (2)	C3A—N10—C1	113.1 (2)
N4—C4A—C8A	122.9 (2)	C9—N10—C1	123.41 (19)

N10—C1—C2—C3	9.8 (4)	C5—C4A—C8A—C8	−0.7 (4)
C1—C2—C3—C3A	−11.4 (4)	N4—C4A—C8A—C9	−1.2 (4)
C2—C3—C3A—N4	−172.4 (3)	C5—C4A—C8A—C9	178.5 (2)
C2—C3—C3A—N10	8.8 (3)	C8—C8A—C9—O	−0.4 (4)
N10—C3A—N4—C4A	0.9 (4)	C4A—C8A—C9—O	−179.6 (3)
C3—C3A—N4—C4A	−177.8 (3)	C8—C8A—C9—N10	178.8 (2)
C3A—N4—C4A—C8A	1.0 (4)	C4A—C8A—C9—N10	−0.3 (3)
C3A—N4—C4A—C5	−178.7 (3)	N4—C3A—N10—C9	−2.6 (4)
N4—C4A—C5—C6	−179.6 (3)	C3—C3A—N10—C9	176.2 (2)
C8A—C4A—C5—C6	0.7 (4)	N4—C3A—N10—C1	178.4 (3)
C4A—C5—C6—C7	0.0 (5)	C3—C3A—N10—C1	−2.7 (3)
C5—C6—C7—C8	−0.7 (4)	O—C9—N10—C3A	−178.6 (3)
C5—C6—C7—Br	179.0 (2)	C8A—C9—N10—C3A	2.1 (3)
C6—C7—C8—C8A	0.8 (4)	O—C9—N10—C1	0.3 (4)
Br—C7—C8—C8A	−179.02 (19)	C8A—C9—N10—C1	−179.0 (2)
C7—C8—C8A—C4A	−0.1 (4)	C2—C1—N10—C3A	−4.5 (3)
C7—C8—C8A—C9	−179.2 (2)	C2—C1—N10—C9	176.5 (2)
N4—C4A—C8A—C8	179.6 (2)

Calculated parameters of the title molecule calculated at the B3LYP/6-311++G(d,p) level top

Parameters	DFT/B3LYP
Total energy TE (a.u.)	-3183.662028
E_HOMO (eV)	-6.4559
E_LUMO (eV)	-1.6351
Energy gap, ΔE (eV)	4.8208
Dipole moment, µ (Debye)	4.6478
Ionization potential, I (eV)	6.4559
Electron affinity, A	1.6351
Electronegativity, χ	4.0455
Hardness, η	2.4104
Electrophilicity index, ω	3.3949
Softness, σ	0.2074

Acknowledgements

The authors thank the Institute of Bioorganic Chemistry of Academy Sciences of Uzbekistan, Tashkent, Uzbekistan for providing the single-crystal XRD facility.

Funding information

Funding for this research was provided by: the Ministry of Innovative Development of Uzbekistan (grant No. F-FA-2021-408 "Study of the laws of introducing of pharmacophore fragments into the molecule on the basis of modern cross-coupling and heterocyclization reactions").

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