Synthesis and crystal structure of ethyl 2-{[4-amino-5-cyano-6-(3,4-di­meth­oxy­phen­yl)pyrimidin-2-yl]sulfan­yl}acetate

Abuzahra, M.M.; Zaghary, W.A.; Ahmed, N.S.; Khedr, M.A.; Haffez, H.R.S.; Elgemeie, G.H.; Jones, P.G.

doi:10.1107/S2056989026010352

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ISSN: 2056-9890

Volume 82| Part 11| November 2026| Pages 1313-1316

https://doi.org/10.1107/S2056989026010352

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Synthesis and crystal structure of ethyl 2-{[4-amino-5-cyano-6-(3,4-dimethoxyphenyl)pyrimidin-2-yl]sulfanyl}acetate

Manar M. Abuzahra,^a Wafaa A. Zaghary,^a Nesreen S. Ahmed,^b Mohammed A. Khedr,^a Hesham R. S. Haffez,^c Galal H. Elgemeie ^d and Peter G. Jones ^e ^*

^aPharmaceutical Chemistry Deapartment, Faculty of Pharmacy, Capital University, Helwan, Egypt, ^bTherapeutic Chemistry Department, National Research Centre, Dokki, Cairo, Egypt, ^cBiochemistry and Molecular Biology, Faculty of Pharmacy, Capital University, Helwan, Egypt, ^dChemistry Department, Faculty of Science, Capital University, Helwan, Egypt, and ^eInstitut für Anorganische und Analytische Chemie, Technische Universität Braunschweig, Hagenring 30, D-38106 Braunschweig, Germany
^*Correspondence e-mail: [email protected]

Edited by C. Schulzke, Universität Greifswald, Germany (Received 7 September 2026; accepted 6 October 2026; online 20 October 2026)

In the title compound, C₁₇H₁₈N₄O₄S, the pyrimidine and phenyl rings subtend an interplanar angle of 30.05 (5)°. The ring angle at the C atom between the N atoms is very wide at 129.32 (11)° and the angles at the ring N atoms are narrow [115.58 (10) and 115.98 (10)°]. The molecules are linked by two classical hydrogen bonds with the amine group as donor, namely N—H⋯N≡C and N—H⋯O=C, via an inversion centre and a 2₁ screw axis, respectively. There are also short contacts of 3.6006 (7) Å between the centroids of pairs of pyrimidine rings across inversion centres.

Keywords: crystal structure; pyrimidine; hydrogen bond; ester; acetate.

CCDC reference: 2593312

1. Chemical context

In medicinal chemistry, pyrimidines are an important class of nitrogen-containing heterocycles. As components of nucleic acids, they are necessarily constituents of every cell, and thus of all biological living matter. They are also present in many other naturally occurring molecules, such as vitamins, coenzymes and uric acids. Various pyrimidine scaffolds have been designed and used by chemists to produce innovative medicaments with a range of pharmacological activities (Luo et al., 2026 ). There are many clinically approved drugs containing pyrimidine in their structures; some examples are 5-fluorouracil and Gemcitabine as anticancer, Zidovudine and Stavudine as anti-HIV, Buspirone as anti-anxiety, and Trimethoprim, Sulfadiazine and Sulfadoxine as antimicrobial agents (Sahu et al., 2016 ; Stolarczyk et al., 2018 ). One significant family of pyrimidines consists of 2-thiopyrimidine (2-TP) and its derivatives, also well known as 2-mercaptopyrimidine compounds, in which the S atom replaces the O atom of uridine-based systems. 2-TP derivatives have found a wide range of applications in the preparation of cardiotonic drugs and anticancer, antitubercular, anti-inflammatory and antibacterial agents (Lamie et al., 2020 ; El-serwy et al., 2019 ). They have attracted the attention of chemists and biochemists who wish to develop the range of potentially therapeutic compounds bearing thiopyrimidine scaffolds (Sondhi et al., 2005 ; Rabeh et al., 2026 ).

We have recently described various synthetic approaches to the synthesis of purine and pyrimidine analogs (Abu-Zaied et al., 2020 ; Abu-Zaied et al., 2021 ). In the majority of biochemical reactions, several derivatives of these ring structures are regarded as crucial antimetabolites (Khedr et al., 2022 ; Khedr et al., 2023 ). As a continuation of these studies of the synthesis of biologically active antimetabolic agents (Elgemeie et al., 2019 ; Elgemeie et al., 2022 ), the current study reports the synthesis of ethyl 2-{[4-amino-5-cyano-6-(3,4-dimethoxyphenyl)pyrimidin-2-yl]sulfanyl}acetate, 4, by reacting the pyrimidine-2-thiol derivative 3 with ethyl chloroacetate (Fig. 1). The crystal structure was determined to confirm the nature of 4, and is reported here.

Figure 1
The synthesis of compound 4.

2. Structural commentary

The molecule of compound 4 in the crystal is shown in Fig. 2, with selected molecular dimensions in Table 1. Both rings are essentially planar, with r.m.s. deviations of 0.010 and 0.013 Å for the pyrimidine and phenyl ring, respectively. The only substituent lying significantly out-of-plane is C7 [by 0.221 (2) Å]. The interplanar angle is 30.05 (5)°. The ring angle at C2 is the widest at 129.32 (11)°, associated with a narrow angle N3—C2—S1 of 112.01 (8)° at the planar centre C2. The narrowest ring angles are those at the N atoms [115.58 (10) and 115.98 (10)°]. The bond length S1—C2 is significantly shorter than S1—C8, consistent with the different hybridizations of the C atoms; similar considerations apply to C5—C7 being shorter than C6—C21. The NH₂ group is planar, with the N atom lying an insignificant 0.003 (9) Å out of the plane of its substituents. The atom sequence C8—C9—O2—C10—C11 of the side chain displays an extended conformation.

Table 1
Selected geometric parameters (Å, °)

S1—C2	1.7619 (12)	N3—C4	1.3473 (15)
S1—C8	1.7987 (12)	C4—C5	1.4335 (15)
N1—C2	1.3348 (14)	C5—C6	1.3980 (16)
N1—C6	1.3508 (15)	C5—C7	1.4250 (16)
C2—N3	1.3323 (15)	C6—C21	1.4801 (15)

C2—S1—C8	101.07 (6)	N3—C4—C5	119.76 (10)
C2—N1—C6	115.58 (10)	C6—C5—C4	118.35 (10)
N3—C2—N1	129.32 (11)	N1—C6—C5	120.76 (10)
C2—N3—C4	115.98 (10)

C8—S1—C2—N1	−13.64 (10)	C8—C9—O2—C10	−179.59 (9)
C2—S1—C8—C9	−69.51 (9)	C11—C10—O2—C9	−174.39 (10)
S1—C8—C9—O2	144.75 (8)

Figure 2
The molecule of compound 4 in the crystal. Displacement ellipsoids represent 50% probability levels.

3. Supramolecular features

The main intermolecular contacts are the classical hydrogen bonds from the H atoms of the amino group, H021 and H022, to the acceptors N4 and O1 of adjacent molecules, via an inversion centre and the 2₁ screw axis, respectively (Table 2, which also includes some borderline weak hydrogen bonds). Fig. 3 shows the infinite chains of molecules parallel to the b axis formed by the contact H022⋯O1. It also shows (implicitly) the short contacts between pairs of pyrimidine rings connected by inversion, with a centroid-to-centroid distance of 3.6006 (7) Å and an offset of 1.2 Å (symmetry operator: −x + 2, −y + 1, −z + 1) for the pair involving the reference molecule.

Table 2
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H021⋯N4ⁱ	0.862 (19)	2.201 (19)	3.0368 (15)	163.4 (16)
N2—H022⋯O1ⁱⁱ	0.879 (19)	2.139 (19)	2.9942 (13)	164.0 (16)
C8—H8A⋯N4ⁱⁱⁱ	0.99	2.67	3.4693 (16)	138
C11—H11A⋯O3^iv	0.98	2.52	3.1459 (15)	122
C27—H27B⋯S1^v	0.98	2.95	3.6836 (12)	133
Symmetry codes: (i) ; (ii) $[-x+2, y+{\script{1\over 2}}, -z+{\script{3\over 2}}]$ ; (iii) ; (iv) $[-x+1, y-{\script{1\over 2}}, -z+{\script{1\over 2}}]$ ; (v) .

Figure 3
Two chains of molecules of compound 4, running vertically, linked by the hydrogen bonds N2⋯H022—O1 (thick dashed lines). The view direction is perpendicular to the bc plane, in the region a ≃ 0.75. Atom names indicate the asymmetric unit. H atoms not involved in these interactions are omitted for clarity.

The combination of inversion and 2₁ symmetry for the two hydrogen bonds means that the overall packing is three-dimensional rather than a ribbon or layer structure. The second packing diagram (Fig. 4) is therefore a projection showing the combination of both hydrogen bonds.

Figure 4
A projection of the three-dimensional packing of compound 4 parallel to the b axis, showing linkages via both classical hydrogen bonds (thick dashed lines). Atom names indicate the asymmetric unit. H atoms not involved in these interactions are omitted for clarity.

4. Database survey

Searches were conducted using the Cambridge Structural Database (CSD, Version 6.01, update November 2025; Groom et al., 2016 ) and the ConQuest routine (Version 2025.3.1; Bruno et al., 2002 ), and were restricted to non-disordered `organic' structures.

A general search for pyrimidine systems with no further annelation gave 2950 hits. The angle at C2 was consistently and significantly larger than 120°, with a mean angle of 126.9 (17)° for 3782 values. A search restricted to the substitution pattern of compound 4 (S at C2, N at C4, CN at C5 and C at C6) gave just two hits: 4-[4-(7-chloroquinolin-4-yl)piperazin-1-yl]-2-(methylsulfanyl)-6-phenylpyrimidine-5-carbonitrile (refcode HUKRUC; Kaur et al., 2015 ) and 2-[(4-chlorobenzyl)sulfanyl]-4-(2-methylpropyl)-6-[3-(trifluoromethyl)anilino]pyrimidine-5-carbonitrile (XAZLUH; El-Emam et al., 2012 ). However, neither of these can be regarded as closely similar to 4, thus underlining its novel nature.

5. Synthesis and crystallization

A mixture of compound 3 (1 mmol) and ethyl chloroacetate (1.2 mmol) in acetonitrile containing a few drops of triethylamine was stirred at room temperature for 48 h. The precipitate thus formed was filtered off and washed with ethanol to give the desired compound 4, as a buff powder, which was recrystallized from acetonitrile to give pale-yellow crystals (isolated single crystals are effectively colourless) in 65% yield.

M.p. 453–455 K; IR (KBr, ν cm⁻¹): 3470, 3347 (NH₂) 2206 (CN), 1736, (C=O); ¹H NMR (DMSO-d₆, 500 MHz): δ (ppm) 1.11 (t, J = 7.0 Hz, 3H, CH₂CH₃), 3.84 (s, 3H, OCH₃), 3.85 (s, 3H, OCH₃), 4.03 (s, 2H, S-CH₂), 4.07 (q, J = 7.0 Hz, 2H, CH₂CH₃), 7.12 (d, J = 8.5 Hz, 1H, Ar-H), 7.54 (d, J = 2.0 Hz, 1H, Ar-H), 7.57 (d, J = 8.5 Hz, 1H, Ar-H), 8.03 (br s, 2H, NH₂, D₂O-exchangeable); ¹³C NMR (DMSO-d₆, 150 MHz): δ (ppm) 14.4 (CH₂CH₃), 33.5 (S—CH₂), 56.2 (2OCH₃), 61.6 (CH₂CH₃), 82.3, 111.6, 112.4, 117.1, 122.6, 128.2, 148.8, 152.0, 164.1, 166.7, 169.4 (C=O ester), 172.4. Analysis calculated (%) for C₁₇H₁₈N₄O₄S: C 54.53, H 4.85, N 14.96, S 8.56; found: C 54.54, H 5.13, N 14.85, S 8.74.

6. Refinement

Details of data collection and structure refinement are summarized in Table 3. H atoms of the NH₂ group were refined freely. Methyl groups were refined as idealized rigid groups allowed to rotate but not tip, with C—H = 0.98 Å and H—C—H = 109.5°. Other H atoms were refined using a riding model, with aromatic C—H = 0.95 Å and methylene C—H = 0.99 Å. The U_iso(H) values were fixed at 1.5U_eq of the parent C atoms for the methyl groups and 1.2U_eq for the other H atoms. Two badly fitting reflections (Δ/σ > 8) were omitted from the refinement.

Table 3
Experimental details

Crystal data
Chemical formula	C₁₇H₁₈N₄O₄S
M_r	374.41
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	100
a, b, c (Å)	13.4276 (5), 8.2128 (3), 16.6201 (7)
β (°)	110.762 (5)
V (Å³)	1713.80 (13)
Z	4
Radiation type	Cu Kα
μ (mm⁻¹)	1.97
Crystal size (mm)	0.14 × 0.05 × 0.03

Data collection
Diffractometer	Rigaku XtaLAB Synergy
Absorption correction	Multi-scan (CrysAlis PRO; Rigaku OD, 2026 )
T_min, T_max	0.763, 1.000
No. of measured, independent and observed [I > 2σ(I)] reflections	78100, 3747, 3512
R_int	0.044
θ values (°)	θ_max = 81.6, θ_min = 3.5
(sin θ/λ)_max (Å⁻¹)	0.642

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.030, 0.079, 1.09
No. of reflections	3747
No. of parameters	246
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement
Δρ_max, Δρ_min (e Å⁻³)	0.33, −0.27
Computer programs: CrysAlis PRO (Rigaku OD, 2026), SHELXT (Sheldrick, 2015a ), SHELXL2019 (Sheldrick, 2015b ), XP (Bruker, 1998 ) and publCIF (Westrip, 2010 ).

Supporting information

CCDC reference: 2593312

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S2056989026010352/yz2085sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989026010352/yz2085Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989026010352/yz2085Isup3.cml

checkCIF report

Computing details top

Ethyl 2-{[4-amino-5-cyano-6-(3,4-dimethoxyphenyl)pyrimidin-2-yl]sulfanyl}acetate top

Crystal data top

C₁₇H₁₈N₄O₄S	F(000) = 784
M_r = 374.41	D_x = 1.451 Mg m⁻³
Monoclinic, P2₁/c	Cu Kα radiation, λ = 1.54184 Å
a = 13.4276 (5) Å	Cell parameters from 44633 reflections
b = 8.2128 (3) Å	θ = 3.5–80.1°
c = 16.6201 (7) Å	µ = 1.97 mm⁻¹
β = 110.762 (5)°	T = 100 K
V = 1713.80 (13) Å³	Prism, colourless
Z = 4	0.14 × 0.05 × 0.03 mm

Data collection top

Rigaku XtaLAB Synergy diffractometer	3747 independent reflections
Radiation source: micro-focus sealed X-ray tube, PhotonJet (Cu) X-ray Source	3512 reflections with I > 2σ(I)
Mirror monochromator	R_int = 0.044
Detector resolution: 10.0000 pixels mm^-1	θ_max = 81.6°, θ_min = 3.5°
ω scans	h = −16→17
Absorption correction: multi-scan (CrysAlis PRO; Rigaku OD, 2026)	k = −10→10
T_min = 0.763, T_max = 1.000	l = −21→21
78100 measured reflections

Refinement top

Refinement on F²	Primary atom site location: dual
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.030	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.079	w = 1/[σ²(F_o²) + (0.038P)² + 0.7704P] where P = (F_o² + 2F_c²)/3
S = 1.09	(Δ/σ)_max = 0.001
3747 reflections	Δρ_max = 0.33 e Å⁻³
246 parameters	Δρ_min = −0.27 e Å⁻³
0 restraints

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

	x	y	z	U_iso*/U_eq
S1	0.94829 (2)	0.20843 (4)	0.67241 (2)	0.01892 (9)
N1	0.84359 (8)	0.39055 (12)	0.53524 (6)	0.0170 (2)
C2	0.92716 (9)	0.38561 (14)	0.60876 (7)	0.0165 (2)
N3	1.00361 (7)	0.49571 (12)	0.64206 (6)	0.0171 (2)
C4	0.99444 (9)	0.63454 (14)	0.59681 (7)	0.0167 (2)
C5	0.90500 (9)	0.65719 (14)	0.51876 (7)	0.0162 (2)
C6	0.83380 (9)	0.52791 (14)	0.48834 (7)	0.0160 (2)
C7	0.88980 (9)	0.81410 (14)	0.47967 (7)	0.0172 (2)
C8	0.82267 (9)	0.10613 (14)	0.62413 (8)	0.0194 (2)
H8A	0.805412	0.098954	0.561170	0.023*
H8B	0.828418	−0.006128	0.647040	0.023*
C9	0.73379 (9)	0.19453 (14)	0.64200 (7)	0.0167 (2)
C10	0.55229 (9)	0.26761 (15)	0.58683 (8)	0.0209 (2)
H10A	0.564619	0.386653	0.591305	0.025*
H10B	0.542433	0.229385	0.640011	0.025*
C11	0.45556 (10)	0.22845 (19)	0.50957 (8)	0.0292 (3)
H11A	0.467709	0.261922	0.457205	0.044*
H11B	0.393828	0.286890	0.513533	0.044*
H11C	0.442029	0.110989	0.507580	0.044*
C21	0.74471 (9)	0.53373 (14)	0.40457 (7)	0.0161 (2)
C22	0.75448 (9)	0.62478 (14)	0.33607 (7)	0.0159 (2)
H22	0.819795	0.677987	0.342878	0.019*
C23	0.67021 (9)	0.63755 (14)	0.25914 (7)	0.0160 (2)
C24	0.57304 (9)	0.55837 (13)	0.24843 (7)	0.0156 (2)
C25	0.56457 (9)	0.46370 (14)	0.31507 (7)	0.0177 (2)
H25	0.500013	0.407833	0.307827	0.021*
C26	0.65032 (9)	0.45039 (14)	0.39242 (7)	0.0179 (2)
H26	0.644264	0.383860	0.437216	0.021*
C27	0.76480 (10)	0.82281 (16)	0.20173 (8)	0.0217 (2)
H27A	0.755218	0.884562	0.149059	0.033*
H27B	0.827392	0.752223	0.214699	0.033*
H27C	0.775101	0.898458	0.249615	0.033*
C28	0.38928 (9)	0.52854 (16)	0.16163 (8)	0.0225 (2)
H28A	0.338779	0.564480	0.105858	0.034*
H28B	0.368932	0.574936	0.207907	0.034*
H28C	0.388298	0.409430	0.164783	0.034*
O1	0.74353 (7)	0.26372 (12)	0.70858 (5)	0.02394 (19)
O2	0.64265 (6)	0.18454 (11)	0.57556 (5)	0.02001 (18)
O3	0.67237 (6)	0.72523 (11)	0.18981 (5)	0.02081 (19)
O4	0.49428 (6)	0.58233 (10)	0.17089 (5)	0.01874 (18)
N2	1.06917 (8)	0.74770 (14)	0.62655 (7)	0.0207 (2)
H021	1.0695 (14)	0.837 (2)	0.5990 (11)	0.033 (4)*
H022	1.1204 (14)	0.733 (2)	0.6765 (12)	0.030 (4)*
N4	0.87969 (8)	0.94458 (13)	0.45245 (6)	0.0220 (2)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
S1	0.01518 (14)	0.02360 (15)	0.01707 (14)	0.00250 (10)	0.00460 (11)	0.00545 (10)
N1	0.0160 (4)	0.0198 (5)	0.0144 (4)	0.0012 (4)	0.0043 (4)	0.0008 (4)
C2	0.0156 (5)	0.0214 (6)	0.0139 (5)	0.0034 (4)	0.0068 (4)	0.0004 (4)
N3	0.0150 (4)	0.0231 (5)	0.0133 (4)	0.0014 (4)	0.0052 (3)	0.0012 (4)
C4	0.0159 (5)	0.0226 (6)	0.0124 (5)	0.0005 (4)	0.0062 (4)	−0.0016 (4)
C5	0.0152 (5)	0.0202 (5)	0.0130 (5)	0.0020 (4)	0.0049 (4)	0.0000 (4)
C6	0.0150 (5)	0.0191 (5)	0.0139 (5)	0.0030 (4)	0.0052 (4)	−0.0009 (4)
C7	0.0138 (5)	0.0232 (6)	0.0133 (5)	−0.0011 (4)	0.0032 (4)	−0.0037 (4)
C8	0.0190 (5)	0.0182 (5)	0.0208 (5)	0.0002 (4)	0.0069 (4)	0.0003 (4)
C9	0.0165 (5)	0.0165 (5)	0.0162 (5)	−0.0019 (4)	0.0046 (4)	0.0021 (4)
C10	0.0173 (6)	0.0254 (6)	0.0194 (5)	0.0023 (5)	0.0058 (5)	−0.0026 (5)
C11	0.0200 (6)	0.0403 (8)	0.0224 (6)	0.0054 (5)	0.0014 (5)	−0.0069 (5)
C21	0.0159 (5)	0.0162 (5)	0.0147 (5)	0.0024 (4)	0.0036 (4)	−0.0011 (4)
C22	0.0137 (5)	0.0175 (5)	0.0156 (5)	0.0004 (4)	0.0040 (4)	−0.0017 (4)
C23	0.0164 (5)	0.0172 (5)	0.0141 (5)	0.0010 (4)	0.0049 (4)	−0.0007 (4)
C24	0.0142 (5)	0.0157 (5)	0.0145 (5)	0.0012 (4)	0.0020 (4)	−0.0020 (4)
C25	0.0165 (5)	0.0165 (5)	0.0193 (5)	−0.0018 (4)	0.0052 (4)	−0.0013 (4)
C26	0.0199 (5)	0.0173 (5)	0.0157 (5)	0.0000 (4)	0.0052 (4)	0.0005 (4)
C27	0.0175 (5)	0.0256 (6)	0.0211 (6)	−0.0054 (5)	0.0056 (4)	0.0014 (5)
C28	0.0131 (5)	0.0272 (6)	0.0232 (6)	−0.0034 (5)	0.0015 (4)	0.0016 (5)
O1	0.0190 (4)	0.0330 (5)	0.0179 (4)	0.0016 (4)	0.0042 (3)	−0.0049 (4)
O2	0.0161 (4)	0.0250 (4)	0.0172 (4)	0.0013 (3)	0.0038 (3)	−0.0031 (3)
O3	0.0166 (4)	0.0282 (5)	0.0146 (4)	−0.0054 (3)	0.0019 (3)	0.0041 (3)
O4	0.0131 (4)	0.0228 (4)	0.0162 (4)	−0.0025 (3)	0.0002 (3)	0.0016 (3)
N2	0.0183 (5)	0.0260 (5)	0.0139 (5)	−0.0042 (4)	0.0011 (4)	0.0019 (4)
N4	0.0216 (5)	0.0219 (5)	0.0198 (5)	−0.0010 (4)	0.0040 (4)	0.0001 (4)

Geometric parameters (Å, º) top

S1—C2	1.7619 (12)	C11—H11C	0.9800
S1—C8	1.7987 (12)	C21—C26	1.3908 (16)
N1—C2	1.3348 (14)	C21—C22	1.4066 (16)
N1—C6	1.3508 (15)	C22—C23	1.3786 (15)
C2—N3	1.3323 (15)	C22—H22	0.9500
N3—C4	1.3473 (15)	C23—O3	1.3677 (13)
C4—N2	1.3279 (16)	C23—C24	1.4115 (16)
C4—C5	1.4335 (15)	C24—O4	1.3609 (13)
C5—C6	1.3980 (16)	C24—C25	1.3905 (16)
C5—C7	1.4250 (16)	C25—C26	1.3930 (16)
C6—C21	1.4801 (15)	C25—H25	0.9500
C7—N4	1.1522 (16)	C26—H26	0.9500
C8—C9	1.5136 (16)	C27—O3	1.4309 (14)
C8—H8A	0.9900	C27—H27A	0.9800
C8—H8B	0.9900	C27—H27B	0.9800
C9—O1	1.2091 (15)	C27—H27C	0.9800
C9—O2	1.3288 (14)	C28—O4	1.4328 (14)
C10—O2	1.4608 (14)	C28—H28A	0.9800
C10—C11	1.5023 (17)	C28—H28B	0.9800
C10—H10A	0.9900	C28—H28C	0.9800
C10—H10B	0.9900	N2—H021	0.862 (19)
C11—H11A	0.9800	N2—H022	0.879 (19)
C11—H11B	0.9800

C2—S1—C8	101.07 (6)	C26—C21—C22	119.06 (10)
C2—N1—C6	115.58 (10)	C26—C21—C6	120.78 (10)
N3—C2—N1	129.32 (11)	C22—C21—C6	120.16 (10)
N3—C2—S1	112.01 (8)	C23—C22—C21	120.65 (10)
N1—C2—S1	118.62 (9)	C23—C22—H22	119.7
C2—N3—C4	115.98 (10)	C21—C22—H22	119.7
N2—C4—N3	118.49 (10)	O3—C23—C22	124.46 (10)
N2—C4—C5	121.75 (11)	O3—C23—C24	115.54 (10)
N3—C4—C5	119.76 (10)	C22—C23—C24	120.00 (10)
C6—C5—C7	123.56 (10)	O4—C24—C25	125.43 (10)
C6—C5—C4	118.35 (10)	O4—C24—C23	115.22 (10)
C7—C5—C4	117.94 (10)	C25—C24—C23	119.35 (10)
N1—C6—C5	120.76 (10)	C24—C25—C26	120.31 (10)
N1—C6—C21	116.78 (10)	C24—C25—H25	119.8
C5—C6—C21	122.46 (10)	C26—C25—H25	119.8
N4—C7—C5	176.29 (12)	C21—C26—C25	120.53 (10)
C9—C8—S1	111.62 (8)	C21—C26—H26	119.7
C9—C8—H8A	109.3	C25—C26—H26	119.7
S1—C8—H8A	109.3	O3—C27—H27A	109.5
C9—C8—H8B	109.3	O3—C27—H27B	109.5
S1—C8—H8B	109.3	H27A—C27—H27B	109.5
H8A—C8—H8B	108.0	O3—C27—H27C	109.5
O1—C9—O2	123.95 (11)	H27A—C27—H27C	109.5
O1—C9—C8	124.61 (10)	H27B—C27—H27C	109.5
O2—C9—C8	111.43 (10)	O4—C28—H28A	109.5
O2—C10—C11	107.23 (10)	O4—C28—H28B	109.5
O2—C10—H10A	110.3	H28A—C28—H28B	109.5
C11—C10—H10A	110.3	O4—C28—H28C	109.5
O2—C10—H10B	110.3	H28A—C28—H28C	109.5
C11—C10—H10B	110.3	H28B—C28—H28C	109.5
H10A—C10—H10B	108.5	C9—O2—C10	115.26 (9)
C10—C11—H11A	109.5	C23—O3—C27	117.04 (9)
C10—C11—H11B	109.5	C24—O4—C28	117.51 (9)
H11A—C11—H11B	109.5	C4—N2—H021	122.7 (12)
C10—C11—H11C	109.5	C4—N2—H022	119.3 (11)
H11A—C11—H11C	109.5	H021—N2—H022	118.1 (16)
H11B—C11—H11C	109.5

C6—N1—C2—N3	−1.24 (17)	N1—C6—C21—C22	−149.74 (10)
C6—N1—C2—S1	−178.13 (8)	C5—C6—C21—C22	30.48 (16)
C8—S1—C2—N3	168.96 (8)	C26—C21—C22—C23	2.90 (17)
C8—S1—C2—N1	−13.64 (10)	C6—C21—C22—C23	−176.82 (10)
N1—C2—N3—C4	2.13 (17)	C21—C22—C23—O3	179.04 (10)
S1—C2—N3—C4	179.18 (8)	C21—C22—C23—C24	−0.22 (16)
C2—N3—C4—N2	−179.21 (10)	O3—C23—C24—O4	−0.95 (14)
C2—N3—C4—C5	1.14 (15)	C22—C23—C24—O4	178.37 (10)
N2—C4—C5—C6	175.43 (11)	O3—C23—C24—C25	178.65 (10)
N3—C4—C5—C6	−4.93 (15)	C22—C23—C24—C25	−2.03 (16)
N2—C4—C5—C7	−8.73 (16)	O4—C24—C25—C26	−178.87 (10)
N3—C4—C5—C7	170.91 (10)	C23—C24—C25—C26	1.57 (17)
C2—N1—C6—C5	−2.96 (15)	C22—C21—C26—C25	−3.37 (17)
C2—N1—C6—C21	177.25 (9)	C6—C21—C26—C25	176.35 (10)
C7—C5—C6—N1	−169.69 (10)	C24—C25—C26—C21	1.15 (17)
C4—C5—C6—N1	5.90 (16)	O1—C9—O2—C10	1.39 (16)
C7—C5—C6—C21	10.08 (17)	C8—C9—O2—C10	−179.59 (9)
C4—C5—C6—C21	−174.33 (10)	C11—C10—O2—C9	−174.39 (10)
C2—S1—C8—C9	−69.51 (9)	C22—C23—O3—C27	−6.61 (16)
S1—C8—C9—O1	−36.23 (15)	C24—C23—O3—C27	172.68 (10)
S1—C8—C9—O2	144.75 (8)	C25—C24—O4—C28	10.82 (16)
N1—C6—C21—C26	30.55 (15)	C23—C24—O4—C28	−169.61 (10)
C5—C6—C21—C26	−149.23 (11)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H021···N4ⁱ	0.862 (19)	2.201 (19)	3.0368 (15)	163.4 (16)
N2—H022···O1ⁱⁱ	0.879 (19)	2.139 (19)	2.9942 (13)	164.0 (16)
N2—H022···S1ⁱⁱ	0.879 (19)	2.973 (17)	3.4465 (11)	115.7 (13)
C8—H8A···N4ⁱⁱⁱ	0.99	2.67	3.4693 (16)	138
C11—H11A···O3^iv	0.98	2.52	3.1459 (15)	122
C27—H27B···S1^v	0.98	2.95	3.6836 (12)	133

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

Acknowledgements

The authors acknowledge support by the Open Access Publication Funds of the Technical University of Braunschweig.

References

Abu-Zaied, M. A., Elgemeie, G. H. & Mahmoud, N. M. (2021). ACS Omega 6, 16890–16904. CAS Google Scholar
Abu-Zaied, M. A., Mahmoud, N. M. & Elgemeie, G. H. (2020). ACS Omega 5, 20042–20050. CAS Google Scholar
Bruker (1998). XP. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Bruno, I. J., Cole, J. C., Edgington, P. R., Kessler, M., Macrae, C. F., McCabe, P., Pearson, J. & Taylor, R. (2002). Acta Cryst. B58, 389–397. Web of Science CrossRef CAS IUCr Journals Google Scholar
El-Emam, A. A., Al-Deeb, O. A., El-Brollosy, N. R., Ng, S. W. & Tiekink, E. R. T. (2012). Acta Cryst. E68, o2059–o2060. CrossRef IUCr Journals Google Scholar
Elgemeie, G. H., Azzam, R. A. & Elsayed, R. E. (2019). Med. Chem. Res. 28, 1099–1131. Web of Science CrossRef CAS Google Scholar
Elgemeie, G. H., Azzam, R. A., Zaghary, W. A., Khedr, M. A. & Elsherif, G. E. (2022). Curr. Pharm. Des. 28, 3374–3403. Web of Science CrossRef CAS PubMed Google Scholar
El–serwy, W. S., Mohamed, H. S., El–serwy, W. S., Mohamed, N. A., Kassem, E. M. M., Nossier, E. S. & Shalaby, A. S. G. (2019). J. Heterocycl. Chem. 56, 2027–2035. CAS 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
Kaur, H., Balzarini, J., de Kock, C., Smith, P. J., Chibale, K. & Singh, K. (2015). Eur. J. Med. Chem. 101, 52–62. CrossRef CAS Google Scholar
Khedr, M. A., Zaghary, W. A., Elsherif, G. E., Azzam, R. A. & Elgemeie, G. H. (2022). Nucleosides Nucleotides Nucleic Acids 41, 643–670. CrossRef CAS Google Scholar
Khedr, M. A., Zaghary, W. A., Elsherif, G. E., Azzam, R. A. & Elgemeie, G. H. (2023). Nucleosides Nucleotides Nucleic Acids 42, 77–104. CrossRef CAS Google Scholar
Lamie, P. F. & Philoppes, J. N. (2020). J. Enzyme Inhib. Med. Chem. 35, 864–879. CrossRef CAS Google Scholar
Luo, M., Jiang, S., Ma, Y. & Zhao, P. (2026). Future Med. Chem. 18, 1783–1796. CrossRef CAS Google Scholar
Rabeh, R. M., Kassab, A. E., Hassan, R. A. & Shahin, I. G. (2026). RSC Adv. 16, 16976–16992. CrossRef CAS Google Scholar
Rigaku OD (2026). CrysAlis PRO. Rigaku Oxford Diffraction Ltd, Yarnton, Oxfordshire, England. Google Scholar
Sahu, M., Kumar, S., Aharwal, R. P. & Sandhu, S. S. (2016). Int. J. Pharm. Pharm. Sci. 8, 38. CrossRef 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
Sondhi, S. M., Goyal, R. N., Lahoti, A. M., Singh, N., Shukla, R. & Raghubir, R. (2005). Bioorg. Med. Chem. 13, 3185–3195. CrossRef CAS Google Scholar
Stolarczyk, M., Bryndal, I., Matera-Witkiewicz, A., Lis, T., Królewska-Golińska, K., Cieślak, M., Kaźmierczak-Barańska, J. & Cieplik, J. (2018). Acta Cryst. C74, 1138–1145. Web of Science CSD CrossRef IUCr Journals Google Scholar
Westrip, S. P. (2010). J. Appl. Cryst. 43, 920–925. Web of Science CrossRef CAS IUCr Journals Google Scholar

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