The title compound was obtained via a two-step synthesis (Dimroth reaction and amidation) for anticancer activity screening and was selected from a 1H-1,2,3-triazole-4-carboxamide library. The cyclopropyl ring is oriented almost perpendicular to the benzene ring [dihedral angle = 87.9 (1)°], while the dihedral angle between the mean plane of the cyclopropyl ring and that of the triazole ring is 55.6 (1)°. In the crystal, the molecules are linked by O—H⋯O and C—H⋯N interactions into infinite ribbons propagating in the [001] direction, which are interconnected by weak C—H⋯O interactions into layers.
Keywords: crystal structure; 1,2,3-triazole; amide; 1,2,3-triazole-4-carboxamide; Hirshfeld surface analysis
Abstract
The title compound, C15H18N4O2, was obtained via a two-step synthesis (Dimroth reaction and amidation) for anticancer activity screening and was selected from a 1H-1,2,3-triazole-4-carboxamide library. The cyclopropyl ring is oriented almost perpendicular to the benzene ring [dihedral angle = 87.9 (1)°], while the dihedral angle between the mean plane of the cyclopropyl ring and that of the triazole ring is 55.6 (1)°. In the crystal, the molecules are linked by O—H⋯O and C—H⋯N interactions into infinite ribbons propagating in the [001] direction, which are interconnected by weak C—H⋯O interactions into layers. The intermolecular interactions were characterized via Hirshfeld surface analysis, which indicated that the largest fingerprint contact percentages are H⋯H (55.5%), N⋯H/H⋯N (15.4%), C⋯H/H⋯C (13.2%) and O⋯H/H⋯O (12.9%).
Chemical context
The 1,2,3-triazolyl-4-carboxamide motif is of great interest in drug discovery, especially in relation to anticancer and antimicrobial research. Besides the well-known drugs rufinamide and carboxyamidotriazole, several preclinical studies are ongoing. As an example of antitumour activity evaluations, libraries of 1,2,3-triazole-4-carboxamides containing podophyllotoxin (Reddy et al., 2018 ▸), 1-R-N-[(1-R-1H-1,2,3-triazol-4-yl)methyl]-1H-1,2,3-triazole-4-carboxamides (Elamari et al., 2013 ▸), 5-(trifluoromethyl)-1H-1,2,3-triazole-4-carboxamides (Wang et al., 2018 ▸; Zhou et al., 2014 ▸) and 1-benzyl-N-[2-(phenylamino)pyridin-3-yl]-1H-1,2,3-triazole-4-carboxamides (Prasad et al., 2019 ▸) have been tested. Several 1,4,5-trisubstituted 1,2,3-triazole-4-carboxamides showed high affinity in the nanomolar concentration range toward Hsp90 associated with cell proliferation inhibition (Taddei et al., 2014 ▸; Giannini et al., 2015 ▸). Moreover, 4-[4-(hydrazinecarbonyl)-5-methyl-1H-1,2,3-triazol-1-yl]benzenesulfonamide was found to act as a COX-2 inhibitor (Bekheit et al., 2021 ▸).
In our previous studies, new active compounds with a 1,2,3-triazolyl-4-carboxamide motif were reported (Shyyka et al., 2019 ▸; Pokhodylo, Shyyka, Finiuk & Stoika, 2020 ▸; Pokhodylo, Slyvka & Pavlyuk, 2020 ▸). Additionally, 1,2,3-triazolyl-4-carboxamide derivatives were found to be inhibitors of the Wnt/β-catenin signalling pathway (Obianom et al., 2019 ▸). In addition, compounds with this motif exhibited fungicidal (Wang et al., 2014 ▸), antiviral (Krajczyk et al., 2014 ▸) and antimicrobial (Pokhodylo et al., 2021 ▸; Jadhav et al., 2017 ▸) activities. The most convenient synthetic path to diverse 1H-1,2,3-triazole-4-carboxamides is a two-step synthesis involving the Dimroth reaction of organic azides with β-ketoesters (Pokhodylo & Obushak, 2019 ▸) followed by amidation of the resulting 1H-1,2,3-triazole-4-carboxylic acids.
Given the practical interest of 1-aryl-1H-1,2,3-triazole-4-carboxamides in anticancer and antimicrobial research, in the present paper, we report the molecular and crystal structure of the title compound C15H18N4O2, highlighting its molecular conformation and analysing the intermolecular interactions. The cyclopropyl substituent was selected as it meets the criteria of lead-oriented synthesis, increasing the number of sp
3-carbon atoms, but at the same time is conformationally restricted and occupies minimal volume among other C3-alkyl substituents. Moreover, the 5-cyclopropyltriazole fragment could appear as a bisected or perpendicular conformer.
Structural commentary
The title compound crystallizes in the monoclinic centrosymmetric space group P21/c, with one molecule in the asymmetric unit as shown in Fig. 1 ▸. The molecular structure possesses three conformational degrees of freedom due to free rotation about the C9—C10, C8—C11 and N1—C1 single bonds. The C10/N4/O1 amide group is turned slightly relative to the N1/N2/N3/C8/C9 triazole ring by 11.71 (4)°. Within the C11/C12/C13 cyclopropyl ring, the C—C bond lengths differ by an insignificant amount [C11—C12 = 1.488 (3), C11—C13 = 1.492 (3), C12—C13 = 1.471 (3) Å]. The cyclopropyl ring is oriented almost perpendicular to the C1–C6 benzene ring and the dihedral angle between these planes is 87.9 (1)°. The dihedral angle between the mean plane of the cyclopropyl ring and that of the triazole ring is 55.6 (1)°.
Figure 1.
The molecular structure of the title compound with displacement ellipsoids drawn at the 50% probability level.
A similar location of the cyclopropyl ring relative to the 1,2,3-triazole ring was also observed in 5-cyclopropyl-1-(3-methoxyphenyl)-1H-1,2,3-triazole-4-carboxylic acid (Pokhodylo et al., 2017 ▸), but in the structure of the related compound N-(4-chlorophenyl)-5-cyclopropyl-1-(4-methoxyphenyl)-1H-1,2,3-triazole-4-carboxamide (Pokhodylo & Slyvka et al., 2020 ▸), the cyclopropyl ring is close to coplanar with the aryl substituent. An intramolecular N4—H4⋯N3 close contact (H⋯N = 2.37 Å; N—H⋯N = 106°) is observed.
The dihedral angle between the tolyl and 1,2,3-triazole rings in the title compound is 32.75 (7)°, which is comparable with the corresponding angle in 5-cyclopropyl-1-(3-methoxyphenyl)-1H-1,2,3-triazole-4-carboxylic acid [39.1 (2)°] but lower than in the structure of 5-methyl-1-(4-nitrophenyl)-1H-1,2,3-triazol-4-ylphosphonate [45.36 (6)°] (Pokhodylo, Shykka, Goreshnik et al., 2020 ▸). Conversely, in the triazoles unsubstituted at the 5-position, [1-(3-bromo- or 4-fluorophenyl)-1H-1,2,3-triazol-4-yl]methyl methylphosphonate, these angle are 22.9 (3) and 15.7 (2)°, respectively (Pokhodylo, Shyyka et al., 2019 ▸).
Supramolecular features
As shown in Fig. 2 ▸ and Table 1 ▸, the extended structure of the title compound features a number of directional intermolecular interactions. The molecules are linked by O2—H2⋯O1i and C11—H11⋯N3ii (see Table 1 ▸ for symmetry codes) interactions into an infinite ribbon propagating in the [001] direction. The ribbons are interconnected by a weak C5—H5⋯O2iii interaction into layers (Fig. 3 ▸).
Figure 2.
The hydrogen-bonded ribbon in the title compound. Hydrogen bonds are shown as dashed lines. The symmetry codes are as in Table 1 ▸.
Table 1. Hydrogen-bond geometry (Å, °).
| D—H⋯A | D—H | H⋯A | D⋯A | D—H⋯A |
|---|---|---|---|---|
| O2—H2⋯O1i | 0.95 (3) | 1.78 (3) | 2.734 (2) | 177 (3) |
| C11—H11⋯N3ii | 0.98 | 2.61 | 3.391 (2) | 137 |
| C5—H5⋯O2iii | 0.93 | 2.66 | 3.564 (3) | 164 |
Symmetry codes: (i) x, -y+{\script{1\over 2}}, z-{\script{1\over 2}}; (ii) x, -y+{\script{1\over 2}}, z+{\script{1\over 2}}; (iii) -x+1, -y+1, -z+1.
Figure 3.
A view along the b-axis direction of the crystal packing of the title compound.
Hirshfeld surface analysis
The significant interactions among the molecules of the title compound can be visualized qualitatively through Hirshfeld surface analysis (Spackman & Jayatilaka, 2009 ▸). The mapping of the normalized contact distance (d norm) was performed using the CrystalExplorer software (Turner et al., 2017 ▸). The most prominent interactions (short contact areas) are indicated on the Hirshfeld surfaces in red, whereas long contacts are shown in blue. Fingerprint plots were produced to show the intermolecular surface bond distances with the regions highlighted for O⋯H/H⋯O and N⋯H/H⋯N interactions (Fig. 4 ▸). The contributions to the surface area for such contacts are 12.9% and 15.4%, respectively. The relatively low percentage of C⋯H/H⋯C contacts (13.2%) indicates the small contribution of C—H⋯π interactions for consolidating the crystal packing. The contribution to the surface area for H⋯H contacts is 55.5%.
Figure 4.
(a) Hirshfeld surface for the title compound mapped with d norm over the range −0.68 to 1.46 showing the O—H⋯O, C—H⋯N and C—H⋯O hydrogen-bonded contacts. Fingerprint plots resolved into (b) O⋯H/H⋯O and (c) N⋯H/H⋯N contacts. Neighbouring molecules associated with close contacts are also shown.
Database survey
The most closest related compounds containing a similar 1-aryl-1H-1,2,3-triazole-4-carboxamide skeleton to the title compound but with different substituents on the amide are: N-(4-chlorophenyl)-5-cyclopropyl-1-(4-methoxyphenyl)-1H-1,2,3-triazole-4-carboxamide (Pokhodylo & Slyvka et al., 2020 ▸), (S)-1-(4-chlorophenyl)-N-(1-hydroxy-3-phenylpropan-2-yl)-5-methyl-1H-1,2,3-triazole-4-carboxamide (I) [Cambridge Structural Database (Version 2021.1; Groom et al., 2016 ▸) refcode ZIPSEY; Shen et al., 2013 ▸], 1-(4-chlorophenyl)-5-methyl-N-[(3-phenyl-1,2-oxazol-5-yl)methyl]-1H-1,2,3-triazole-4-carboxamide (II) (LELHOB; Niu et al., 2013 ▸), (5-methyl-1-[8-(trifluoromethyl)quinolin-4-yl]-1H-1,2,3-triazol-4-yl)morpholino)methanone (III) (LOHWIP; Anuradha et al., 2008 ▸) and 1-(3-amino-5-(3-hydroxy-3-methylbut-1-yn-1-yl)phenyl)-N-butyl-1H-1,2,3-triazole-4-carboxamide (IV) (BEBJEZ; Li et al., 2012 ▸).
Compounds (I) and (II) crystallize in the monoclinic crystal system with space groups P21 and P21/c, respectively, while compounds (III) and (IV) crystallize in the triclinic space group P
. Structure (I) contains two crystallographically independent molecules, the hydroxyl groups of which participate in intermolecular O—H⋯O hydrogen bonds. In contrast to the molecular structure of title compound, the torsion angles between the phenyl rings and triazole rings in (I) are −45.2 (6)° (C5—C6—N1—N2) and 39.9 (6)° (C1′—C6′—N1′—N2′); the analogous value in (II) is 19.2 (2)°. In structure (II), the carboxamide groups connect neighbouring molecules into infinite chains by means of N—H⋯O hydrogen bonds. The molecules in structures (III) and (IV) are connected by N—H⋯O(oxazol) contacts. Similarly to (I) and (II), structure (III) contains a 5-methyl substituent at the triazole ring; as a result of the significant steric hindrance of 8-(trifluoromethyl)quinoline, the dihedral angle between the rings is 54.7°. The phenyl and triazole rings in (IV) are close to coplanar (7.5°), while the hydroxyl, carboxamide and amino groups participate in O—H⋯O and N—H⋯O hydrogen bonds. Finally, two copper(I) π-complexes of compositions [Cu(C12H13N5O)(NO3)]·0.5H2O and [Cu(C12H13N5O)(CF3COO)](C12H13N5O is N-allyl-5-amino-1-phenyl-1H-1,2,3-triazole-4-carboxamide) were obtained by electrochemical synthesis (ZEQTOG and ZEQTUM; Slyvka et al., 2012 ▸). Crystals of these compounds are monoclinic, space group C2/c: in both structures, the N-allyl-1H-1,2,3-triazole-4-carboxamide motif acts as a bridging chelating ligand and forms with the copper(I) atoms infinite chains containing [CuC4NO] seven-membered rings.
Synthesis and crystallization
5-Cyclopropyl-1-p-tolyl-1H-1,2,3-triazole-4-carboxylic acid (Pokhodylo et al., 2017 ▸) (1.22 g, 5.00 mmol) was added to a solution of 1,1′-carbonyldiimidazole (CDI, 0.81 g, 5.0 mmol) in dry acetonitrile (5 ml) and the mixture was kept for 30 min at 323 K. Then, 0.3 ml of 2-aminoethanol (0.31 g, 5.00 mmol) was added, and the mixture was heated at 343 K for 1 h. After cooling to room temperature, water (30 ml) was added. The precipitate was filtered off, washed with water on a filter, crystallized from diluted ethanol solution, and dried in air to give the title compound as colourless crystals, m.p. 396–397 K. The reaction scheme is shown in Fig. 5 ▸. IR (KBr, ν, cm−1): 1685 (C=O); 3370 (N—H). 1H NMR: (400 MHz, DMSO-d 6): δ = 0.85–0.91 (m, 2H, CH2), 0.98–1.02 (m, 2H, CH2), 1.95–1.99 (m, 1H, CH), 2.46 (c, 3H, CH3), 3.37 (q, J = 5.8 Hz, 2H, CH2N), 3.54 (q, J = 5.8 Hz, 2H, CH2O), 4.58 (t, J = 6.0, Hz, 1H, OH), 7.37 (d, J = 7.6 Hz, 2H, HAr-3,5), 7.43 (d, J = 7.6 Hz, 2H, HAr-2,6), 8.14 (t, J = 5.4 Hz, 1H, NH). 13C NMR: (101 MHz, DMSO-d 6): δ = 5.3 (CH), 8.2 (2 × CH2), 21.1 (CH3), 42.3 (CH2N), 59.5 (CH2O), 126.5 (2 × CHAr-2,6), 130.1 (2 × CHAr-3,5), 133.7 (CAr-1), 137.2 (CTriazole-4), 139.2 (CAr-4), 144.6 (CTriazole-5), 161.8 (C=O). MS, m/z = 287 (M ++1). Calculated for C15H18N4O2, (%): C 62.92; H 6.34, N 19.57. Found (%): C 62.83; H 6.57, N 19.32.
Figure 5.
Synthesis of 5-cyclopropyl-N-(2-hydroxyethyl)-1-(p-tolyl)-1H-1,2,3-triazole-4-carboxamide.
Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2 ▸. N-bound and O-bound H atoms were located in difference-Fourier maps and refined isotropically. C-bound H atoms were positioned geometrically and refined using a riding model, with C—H = 0.93–0.98 Å andU iso(H) = 1.2U eq(C) or 1.5U eq(C-methyl).
Table 2. Experimental details.
| Crystal data | |
| Chemical formula | C15H18N4O2 |
| M r | 286.33 |
| Crystal system, space group | Monoclinic, P21/c |
| Temperature (K) | 293 |
| a, b, c (Å) | 14.3158 (6), 8.3972 (3), 13.0871 (4) |
| β (°) | 108.040 (4) |
| V (Å3) | 1495.90 (10) |
| Z | 4 |
| Radiation type | Mo Kα |
| μ (mm−1) | 0.09 |
| Crystal size (mm) | 0.5 × 0.4 × 0.06 |
| Data collection | |
| Diffractometer | Oxford Diffraction Xcalibur3 CCD |
| Absorption correction | Multi-scan (CrysAlis RED; Oxford Diffraction, 2004 ▸) |
| Tmin, Tmax | 0.935, 0.988 |
| No. of measured, independent and observed [I > 2σ(I)] reflections | 8400, 2632, 1621 |
| R int | 0.032 |
| (sin θ/λ)max (Å−1) | 0.595 |
| Refinement | |
| R[F2 > 2σ(F 2)], wR(F 2), S | 0.047, 0.099, 1.05 |
| No. of reflections | 2632 |
| No. of parameters | 199 |
| H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
| Δρmax, Δρmin (e Å−3) | 0.14, −0.20 |
Supplementary Material
Crystal structure: contains datablock(s) I. DOI: 10.1107/S2056989021009774/hb7983sup1.cif
Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989021009774/hb7983Isup2.hkl
Supporting information file. DOI: 10.1107/S2056989021009774/hb7983Isup3.mol
Supporting information file. DOI: 10.1107/S2056989021009774/hb7983Isup4.cml
CCDC reference: 736128
Additional supporting information: crystallographic information; 3D view; checkCIF report
supplementary crystallographic information
Crystal data
| C15H18N4O2 | F(000) = 608 |
| Mr = 286.33 | Dx = 1.271 Mg m−3 |
| Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
| a = 14.3158 (6) Å | Cell parameters from 1679 reflections |
| b = 8.3972 (3) Å | θ = 2.9–26.4° |
| c = 13.0871 (4) Å | µ = 0.09 mm−1 |
| β = 108.040 (4)° | T = 293 K |
| V = 1495.90 (10) Å3 | Lamina, clear colourless |
| Z = 4 | 0.5 × 0.4 × 0.06 mm |
Data collection
| Oxford Diffraction Xcalibur3 CCD diffractometer | 1621 reflections with I > 2σ(I) |
| ω scans | Rint = 0.032 |
| Absorption correction: multi-scan (CrysAlis RED; Oxford Diffraction, 2004) | θmax = 25.0°, θmin = 2.9° |
| Tmin = 0.935, Tmax = 0.988 | h = −17→17 |
| 8400 measured reflections | k = −9→9 |
| 2632 independent reflections | l = −15→8 |
Refinement
| Refinement on F2 | Primary atom site location: dual |
| Least-squares matrix: full | Hydrogen site location: mixed |
| R[F2 > 2σ(F2)] = 0.047 | H atoms treated by a mixture of independent and constrained refinement |
| wR(F2) = 0.099 | w = 1/[σ2(Fo2) + (0.035P)2 + 0.180P] where P = (Fo2 + 2Fc2)/3 |
| S = 1.05 | (Δ/σ)max < 0.001 |
| 2632 reflections | Δρmax = 0.14 e Å−3 |
| 199 parameters | Δρmin = −0.20 e Å−3 |
| 0 restraints |
Special details
| Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes. |
| Refinement. 1. Fixed Uiso At 1.2 times of: All C(H) groups, All C(H,H) groups At 1.5 times of: All C(H,H,H) groups 2.a Ternary CH refined with riding coordinates: C11(H11) 2.b Secondary CH2 refined with riding coordinates: C12(H12A,H12B), C13(H13A,H13B), C14(H14A,H14B), C15(H15A,H15B) 2.c Aromatic/amide H refined with riding coordinates: C2(H2A), C3(H3), C5(H5), C6(H6) 2.d Idealised Me refined as rotating group: C7(H7A,H7B,H7C) |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)
| x | y | z | Uiso*/Ueq | ||
| O1 | 0.13456 (11) | 0.3294 (2) | 0.60427 (12) | 0.0974 (5) | |
| O2 | 0.06831 (14) | 0.3928 (2) | 0.21808 (14) | 0.1042 (6) | |
| H2 | 0.092 (2) | 0.318 (4) | 0.177 (3) | 0.171 (14)* | |
| N1 | 0.44653 (12) | 0.35154 (18) | 0.67420 (11) | 0.0570 (4) | |
| N2 | 0.43955 (13) | 0.3492 (2) | 0.56776 (12) | 0.0687 (5) | |
| N3 | 0.34622 (13) | 0.3512 (2) | 0.51377 (12) | 0.0680 (5) | |
| N4 | 0.14491 (15) | 0.3789 (3) | 0.44072 (15) | 0.0846 (6) | |
| H4 | 0.1840 (16) | 0.397 (3) | 0.4005 (17) | 0.090 (7)* | |
| C1 | 0.54283 (14) | 0.3518 (2) | 0.75104 (14) | 0.0573 (5) | |
| C2 | 0.56125 (17) | 0.2755 (2) | 0.84840 (16) | 0.0660 (6) | |
| H2A | 0.510965 | 0.223701 | 0.866145 | 0.079* | |
| C3 | 0.65554 (19) | 0.2771 (3) | 0.91933 (17) | 0.0755 (6) | |
| H3 | 0.667851 | 0.226965 | 0.985570 | 0.091* | |
| C4 | 0.73224 (17) | 0.3510 (3) | 0.89461 (18) | 0.0754 (6) | |
| C5 | 0.71121 (17) | 0.4244 (3) | 0.79535 (19) | 0.0768 (6) | |
| H5 | 0.761557 | 0.474207 | 0.776551 | 0.092* | |
| C6 | 0.61784 (16) | 0.4254 (2) | 0.72389 (17) | 0.0658 (5) | |
| H6 | 0.605361 | 0.475465 | 0.657611 | 0.079* | |
| C7 | 0.83533 (18) | 0.3513 (4) | 0.9729 (2) | 0.1156 (10) | |
| H7A | 0.853395 | 0.457928 | 0.997559 | 0.173* | |
| H7B | 0.880342 | 0.311663 | 0.937725 | 0.173* | |
| H7C | 0.837630 | 0.284323 | 1.033110 | 0.173* | |
| C8 | 0.35570 (14) | 0.3551 (2) | 0.68719 (14) | 0.0546 (5) | |
| C9 | 0.29293 (14) | 0.3532 (2) | 0.58406 (14) | 0.0583 (5) | |
| C10 | 0.18463 (16) | 0.3519 (2) | 0.54485 (16) | 0.0671 (5) | |
| C11 | 0.33673 (14) | 0.3634 (2) | 0.79130 (14) | 0.0616 (5) | |
| H11 | 0.329955 | 0.260032 | 0.823068 | 0.074* | |
| C12 | 0.27363 (19) | 0.4924 (3) | 0.81202 (17) | 0.0882 (7) | |
| H12A | 0.249069 | 0.572020 | 0.756496 | 0.106* | |
| H12B | 0.228996 | 0.465129 | 0.851979 | 0.106* | |
| C13 | 0.37951 (19) | 0.4924 (3) | 0.87037 (17) | 0.0791 (7) | |
| H13A | 0.399859 | 0.464995 | 0.946092 | 0.095* | |
| H13B | 0.419936 | 0.571906 | 0.850592 | 0.095* | |
| C14 | 0.03984 (18) | 0.3804 (3) | 0.38523 (18) | 0.0979 (8) | |
| H14A | 0.016031 | 0.489258 | 0.378087 | 0.117* | |
| H14B | 0.005972 | 0.321759 | 0.427025 | 0.117* | |
| C15 | 0.01844 (17) | 0.3080 (3) | 0.27817 (18) | 0.0946 (8) | |
| H15A | 0.039484 | 0.197635 | 0.285111 | 0.114* | |
| H15B | −0.051722 | 0.310769 | 0.241585 | 0.114* |
Atomic displacement parameters (Å2)
| U11 | U22 | U33 | U12 | U13 | U23 | |
| O1 | 0.0884 (11) | 0.1413 (16) | 0.0775 (10) | −0.0021 (10) | 0.0476 (9) | 0.0143 (9) |
| O2 | 0.1267 (15) | 0.1162 (15) | 0.0851 (12) | −0.0073 (11) | 0.0552 (11) | −0.0083 (10) |
| N1 | 0.0729 (11) | 0.0568 (10) | 0.0487 (9) | −0.0034 (8) | 0.0296 (8) | −0.0040 (8) |
| N2 | 0.0769 (13) | 0.0840 (13) | 0.0532 (10) | −0.0042 (10) | 0.0317 (9) | −0.0090 (9) |
| N3 | 0.0760 (13) | 0.0828 (13) | 0.0525 (9) | −0.0047 (10) | 0.0302 (9) | −0.0081 (8) |
| N4 | 0.0674 (13) | 0.1313 (18) | 0.0594 (12) | −0.0073 (11) | 0.0258 (10) | 0.0050 (11) |
| C1 | 0.0700 (14) | 0.0492 (12) | 0.0575 (12) | 0.0002 (10) | 0.0271 (11) | −0.0064 (10) |
| C2 | 0.0834 (17) | 0.0572 (13) | 0.0609 (13) | −0.0025 (11) | 0.0273 (12) | −0.0031 (10) |
| C3 | 0.0962 (19) | 0.0669 (15) | 0.0621 (13) | 0.0136 (13) | 0.0228 (14) | −0.0030 (11) |
| C4 | 0.0750 (16) | 0.0746 (15) | 0.0752 (15) | 0.0140 (13) | 0.0209 (12) | −0.0165 (13) |
| C5 | 0.0738 (17) | 0.0738 (16) | 0.0895 (17) | 0.0014 (12) | 0.0349 (14) | −0.0096 (13) |
| C6 | 0.0758 (15) | 0.0599 (13) | 0.0684 (13) | 0.0026 (11) | 0.0322 (12) | 0.0003 (10) |
| C7 | 0.0830 (19) | 0.155 (3) | 0.1007 (19) | 0.0267 (17) | 0.0160 (15) | −0.0231 (18) |
| C8 | 0.0729 (13) | 0.0448 (11) | 0.0535 (11) | −0.0021 (10) | 0.0304 (10) | −0.0007 (9) |
| C9 | 0.0719 (14) | 0.0575 (13) | 0.0538 (12) | −0.0048 (10) | 0.0315 (10) | −0.0014 (10) |
| C10 | 0.0796 (15) | 0.0702 (14) | 0.0591 (13) | −0.0042 (12) | 0.0328 (12) | −0.0001 (11) |
| C11 | 0.0893 (15) | 0.0516 (12) | 0.0536 (11) | −0.0055 (11) | 0.0364 (10) | −0.0003 (10) |
| C12 | 0.116 (2) | 0.0920 (18) | 0.0739 (15) | 0.0236 (15) | 0.0541 (15) | 0.0002 (12) |
| C13 | 0.116 (2) | 0.0663 (15) | 0.0657 (13) | −0.0099 (13) | 0.0447 (14) | −0.0104 (11) |
| C14 | 0.0787 (18) | 0.147 (2) | 0.0738 (15) | 0.0057 (15) | 0.0315 (13) | −0.0002 (15) |
| C15 | 0.0722 (16) | 0.125 (2) | 0.0884 (18) | −0.0097 (14) | 0.0268 (14) | −0.0072 (15) |
Geometric parameters (Å, º)
| O1—C10 | 1.224 (2) | C6—H6 | 0.9300 |
| O2—H2 | 0.95 (3) | C7—H7A | 0.9600 |
| O2—C15 | 1.408 (3) | C7—H7B | 0.9600 |
| N1—N2 | 1.3655 (19) | C7—H7C | 0.9600 |
| N1—C1 | 1.433 (2) | C8—C9 | 1.370 (2) |
| N1—C8 | 1.363 (2) | C8—C11 | 1.471 (2) |
| N2—N3 | 1.304 (2) | C9—C10 | 1.475 (3) |
| N3—C9 | 1.365 (2) | C11—H11 | 0.9800 |
| N4—H4 | 0.89 (2) | C11—C12 | 1.488 (3) |
| N4—C10 | 1.324 (3) | C11—C13 | 1.492 (3) |
| N4—C14 | 1.454 (3) | C12—H12A | 0.9700 |
| C1—C2 | 1.377 (3) | C12—H12B | 0.9700 |
| C1—C6 | 1.378 (3) | C12—C13 | 1.471 (3) |
| C2—H2A | 0.9300 | C13—H13A | 0.9700 |
| C2—C3 | 1.381 (3) | C13—H13B | 0.9700 |
| C3—H3 | 0.9300 | C14—H14A | 0.9700 |
| C3—C4 | 1.384 (3) | C14—H14B | 0.9700 |
| C4—C5 | 1.384 (3) | C14—C15 | 1.470 (3) |
| C4—C7 | 1.514 (3) | C15—H15A | 0.9700 |
| C5—H5 | 0.9300 | C15—H15B | 0.9700 |
| C5—C6 | 1.374 (3) | ||
| C15—O2—H2 | 108 (2) | N3—C9—C8 | 109.33 (17) |
| N2—N1—C1 | 117.80 (15) | N3—C9—C10 | 120.82 (17) |
| C8—N1—N2 | 110.87 (15) | C8—C9—C10 | 129.85 (16) |
| C8—N1—C1 | 131.32 (15) | O1—C10—N4 | 122.1 (2) |
| N3—N2—N1 | 106.95 (14) | O1—C10—C9 | 122.64 (19) |
| N2—N3—C9 | 109.13 (15) | N4—C10—C9 | 115.29 (17) |
| C10—N4—H4 | 119.3 (14) | C8—C11—H11 | 115.0 |
| C10—N4—C14 | 124.32 (19) | C8—C11—C12 | 119.99 (17) |
| C14—N4—H4 | 116.4 (14) | C8—C11—C13 | 121.51 (16) |
| C2—C1—N1 | 121.04 (18) | C12—C11—H11 | 115.0 |
| C2—C1—C6 | 120.41 (19) | C12—C11—C13 | 59.16 (14) |
| C6—C1—N1 | 118.51 (17) | C13—C11—H11 | 115.0 |
| C1—C2—H2A | 120.5 | C11—C12—H12A | 117.7 |
| C1—C2—C3 | 119.0 (2) | C11—C12—H12B | 117.7 |
| C3—C2—H2A | 120.5 | H12A—C12—H12B | 114.8 |
| C2—C3—H3 | 119.1 | C13—C12—C11 | 60.56 (14) |
| C2—C3—C4 | 121.9 (2) | C13—C12—H12A | 117.7 |
| C4—C3—H3 | 119.1 | C13—C12—H12B | 117.7 |
| C3—C4—C7 | 121.3 (2) | C11—C13—H13A | 117.7 |
| C5—C4—C3 | 117.5 (2) | C11—C13—H13B | 117.7 |
| C5—C4—C7 | 121.2 (2) | C12—C13—C11 | 60.28 (14) |
| C4—C5—H5 | 119.2 | C12—C13—H13A | 117.7 |
| C6—C5—C4 | 121.7 (2) | C12—C13—H13B | 117.7 |
| C6—C5—H5 | 119.2 | H13A—C13—H13B | 114.9 |
| C1—C6—H6 | 120.2 | N4—C14—H14A | 109.5 |
| C5—C6—C1 | 119.6 (2) | N4—C14—H14B | 109.5 |
| C5—C6—H6 | 120.2 | N4—C14—C15 | 110.52 (19) |
| C4—C7—H7A | 109.5 | H14A—C14—H14B | 108.1 |
| C4—C7—H7B | 109.5 | C15—C14—H14A | 109.5 |
| C4—C7—H7C | 109.5 | C15—C14—H14B | 109.5 |
| H7A—C7—H7B | 109.5 | O2—C15—C14 | 109.4 (2) |
| H7A—C7—H7C | 109.5 | O2—C15—H15A | 109.8 |
| H7B—C7—H7C | 109.5 | O2—C15—H15B | 109.8 |
| N1—C8—C9 | 103.70 (15) | C14—C15—H15A | 109.8 |
| N1—C8—C11 | 124.99 (17) | C14—C15—H15B | 109.8 |
| C9—C8—C11 | 131.29 (17) | H15A—C15—H15B | 108.3 |
| N1—N2—N3—C9 | −0.6 (2) | C2—C3—C4—C5 | 0.0 (3) |
| N1—C1—C2—C3 | 179.09 (16) | C2—C3—C4—C7 | −179.8 (2) |
| N1—C1—C6—C5 | −178.65 (17) | C3—C4—C5—C6 | 0.5 (3) |
| N1—C8—C9—N3 | −1.0 (2) | C4—C5—C6—C1 | 0.0 (3) |
| N1—C8—C9—C10 | 178.57 (19) | C6—C1—C2—C3 | 1.5 (3) |
| N1—C8—C11—C12 | 125.2 (2) | C7—C4—C5—C6 | −179.7 (2) |
| N1—C8—C11—C13 | 55.1 (3) | C8—N1—N2—N3 | 0.0 (2) |
| N2—N1—C1—C2 | −146.14 (17) | C8—N1—C1—C2 | 34.7 (3) |
| N2—N1—C1—C6 | 31.5 (2) | C8—N1—C1—C6 | −147.61 (19) |
| N2—N1—C8—C9 | 0.61 (19) | C8—C9—C10—O1 | −10.8 (3) |
| N2—N1—C8—C11 | −177.98 (16) | C8—C9—C10—N4 | 168.3 (2) |
| N2—N3—C9—C8 | 1.0 (2) | C8—C11—C12—C13 | −111.0 (2) |
| N2—N3—C9—C10 | −178.57 (17) | C8—C11—C13—C12 | 108.5 (2) |
| N3—C9—C10—O1 | 168.7 (2) | C9—C8—C11—C12 | −53.0 (3) |
| N3—C9—C10—N4 | −12.2 (3) | C9—C8—C11—C13 | −123.1 (2) |
| N4—C14—C15—O2 | −58.8 (3) | C10—N4—C14—C15 | −141.9 (2) |
| C1—N1—N2—N3 | −179.30 (16) | C11—C8—C9—N3 | 177.49 (18) |
| C1—N1—C8—C9 | 179.77 (18) | C11—C8—C9—C10 | −3.0 (3) |
| C1—N1—C8—C11 | 1.2 (3) | C14—N4—C10—O1 | −1.9 (3) |
| C1—C2—C3—C4 | −1.0 (3) | C14—N4—C10—C9 | 179.0 (2) |
| C2—C1—C6—C5 | −1.0 (3) |
Hydrogen-bond geometry (Å, º)
| D—H···A | D—H | H···A | D···A | D—H···A |
| O2—H2···O1i | 0.95 (3) | 1.78 (3) | 2.734 (2) | 177 (3) |
| C11—H11···N3ii | 0.98 | 2.61 | 3.391 (2) | 137 |
| C5—H5···O2iii | 0.93 | 2.66 | 3.564 (3) | 164 |
Symmetry codes: (i) x, −y+1/2, z−1/2; (ii) x, −y+1/2, z+1/2; (iii) −x+1, −y+1, −z+1.
Funding Statement
This work was funded by Ministry of Education and Science of Ukraine grant 0121U107777.
References
- Anuradha, N., Thiruvalluvar, A., Mahalinga, M. & Butcher, R. J. (2008). Acta Cryst. E64, o2375. [DOI] [PMC free article] [PubMed]
- Bekheit, M. S., Mohamed, H. A., Abdel-Wahab, B. F. & Fouad, M. A. (2021). Med. Chem. Res. 30, 1125–1138.
- Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341.
- Elamari, H., Slimi, R., Chabot, G. G., Quentin, L., Scherman, D. & Girard, C. (2013). Eur. J. Med. Chem. 60, 360–364. [DOI] [PubMed]
- Giannini, G. & Battistuzzi, G. (2015). Bioorg. Med. Chem. Lett. 25, 462–465. [DOI] [PubMed]
- Groom, C. R., Bruno, I. J., Lightfoot, M. P. & Ward, S. C. (2016). Acta Cryst. B72, 171–179. [DOI] [PMC free article] [PubMed]
- Jadhav, R. P., Raundal, H. N., Patil, A. A. & Bobade, V. D. (2017). J. Saudi Chem. Soc. 21, 152–159.
- Krajczyk, A., Kulinska, K., Kulinski, T., Hurst, B. L., Day, C. W., Smee, D. F., Ostrowski, T., Januszczyk, P. & Zeidler, J. (2014). Antivir. Chem. Chemother. 23, 161–171. [DOI] [PubMed]
- Li, Y.-J., Xu, L., Yang, W.-L., Liu, H.-B., Lai, S.-W., Che, C.-M. & Li, Y.-L. (2012). Chem. Eur. J. 18, 4782–4790. [DOI] [PubMed]
- Niu, T.-F., Lv, M.-F., Wang, L., Yi, W.-B. & Cai, C. (2013). Org. Biomol. Chem. 11, 1040–1048. [DOI] [PubMed]
- Obianom, O. N., Ai, Y., Li, Y., Yang, W., Guo, D., Yang, H., Sakamuru, S., Xia, M., Xue, F. & Shu, Y. (2019). J. Med. Chem. 62, 727–741. [DOI] [PMC free article] [PubMed]
- Oxford Diffraction (2004). CrysAlis CCD and CrysAlis RED. Oxford Diffraction, Yarnton, England.
- Pokhodylo, N., Manko, N., Finiuk, N., Klyuchivska, O., Matiychuk, V., Obushak, M. & Stoika, R. (2021). J. Mol. Struct. 2021 Art. 131146.
- Pokhodylo, N., Shyyka, O., Finiuk, N. & Stoika, R. (2020). Ukr. Biochem. J. 92, 23–32.
- Pokhodylo, N., Slyvka, Y. & Pavlyuk, V. (2020). Acta Cryst. E76, 756–760. [DOI] [PMC free article] [PubMed]
- Pokhodylo, N. T. & Obushak, M. D. (2019). Russ. J. Org. Chem. 55, 1241–1243.
- Pokhodylo, N. T., Shyyka, O. Ya., Goreshnik, E. A. & Obushak, M. D. (2020). ChemistrySelect, 5, 260–264.
- Pokhodylo, N. T., Shyyka, O. Ya., Matiychuk, V. S., Obushak, M. D. & Pavlyuk, V. V. (2017). ChemistrySelect, 2, 5871–5876.
- Pokhodylo, N. T., Shyyka, O. Ya., Tupychak, M. A., Slyvka, Yu. I. & Obushak, M. D. (2019). Chem. Heterocycl. Compd, 55, 374–378.
- Prasad, B., Lakshma Nayak, V., Srikanth, P. S., Baig, M. F., Subba Reddy, N. V., Babu, K. S. & Kamal, A. (2019). Bioorg. Chem. 83, 535–548. [DOI] [PubMed]
- Reddy, V. G., Bonam, S. R., Reddy, T. S., Akunuri, R., Naidu, V. G. M., Nayak, V. L., Bhargava, S. K., Kumar, H. S., Srihari, P. & Kamal, A. (2018). Eur. J. Med. Chem. 144, 595–611. [DOI] [PubMed]
- Sheldrick, G. M. (2015a). Acta Cryst. A71, 3–8.
- Sheldrick, G. M. (2015b). Acta Cryst. C71, 3–8.
- Shen, G.-L., Chen, Z.-B., Wu, Z.-F. & Dong, H.-S. (2013). J. Heterocycl. Chem. 50, 781–786.
- Shyyka, O. Ya., Pokhodylo, N. T. & Finiuk, N. S. (2019). Biopolym. Cell, 35, 321–330.
- Slyvka, Yu. I., Pavlyuk, A. V., Ardan, B. R., Pokhodilo, N. T., Goreshnik, E. A. & Demchenko, P. Yu. (2012). Russ. J. Inorg. Chem. 57, 815–821.
- Spackman, M. A. & Jayatilaka, D. (2009). CrystEngComm, 11, 19–32.
- Taddei, M., Ferrini, S., Giannotti, L., Corsi, M., Manetti, F., Giannini, G., Vesci, L., Milazzo, F. M., Alloatti, D., Guglielmi, M. B., Castorina, M., Cervoni, M. L., Barbarino, M., Foderà, R., Carollo, V., Pisano, C., Armaroli, S. & Cabri, W. (2014). J. Med. Chem. 57, 2258–2274. [DOI] [PubMed]
- Turner, M. J., Mckinnon, J. J., Wolff, S. K., Grimwood, D. J., Spackman, P. R., Jayatilaka, D. & Spackman, M. A. (2017). CrystalExplorer17. The University of Western Australia. http://hirshfeldsurface.net
- Wang, L., Xu, S., Liu, X., Chen, X., Xiong, H., Hou, S., Zou, W., Tang, Q., Zheng, P. & Zhu, W. (2018). Bioorg. Chem. 77, 370–380. [DOI] [PubMed]
- Wang, Z., Gao, Y., Hou, Y., Zhang, C., Yu, S. J., Bian, Q., Li, Z. M. & Zhao, W. G. (2014). Eur. J. Med. Chem. 86, 87–94. [DOI] [PubMed]
- Zhou, S., Liao, H., Liu, M., Feng, G., Fu, B., Li, R., Cheng, M., Zhao, Y. & Gong, P. (2014). Bioorg. Med. Chem. 22, 6438–6452. [DOI] [PubMed]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.
Supplementary Materials
Crystal structure: contains datablock(s) I. DOI: 10.1107/S2056989021009774/hb7983sup1.cif
Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989021009774/hb7983Isup2.hkl
Supporting information file. DOI: 10.1107/S2056989021009774/hb7983Isup3.mol
Supporting information file. DOI: 10.1107/S2056989021009774/hb7983Isup4.cml
CCDC reference: 736128
Additional supporting information: crystallographic information; 3D view; checkCIF report