Crystal structure determination, Hirshfeld surface, crystal void, inter-molecular inter-action energy analyses, as well as DFT and energy framework calculations of 2-(4-oxo-4,5-di-hydro-1H-pyra-zolo[3,4-d]pyrimidin-1-yl)acetic acid.

In the title mol-ecule, C7H6N4O3, the bicyclic ring system is planar with the carb-oxy-methyl group inclined by 81.05 (5)° to this plane. In the crystal, corrugated layers parallel to (010) are generated by N-H⋯O, O-H⋯N and C-H⋯O hydrogen-bonding inter-actions. The layers are associated through C-H⋯π(ring) inter-actions. A Hirshfeld surface analysis indicates that the most important contributions to the crystal packing are from H⋯O/O⋯H (34.8%), H⋯N/N⋯H (19.3%) and H⋯H (18.1%) inter-actions. The volume of the crystal voids and the percentage of free space were calculated to be 176.30 Å3 and 10.94%, showing that there is no large cavity in the crystal packing. Computational methods revealed O-H⋯N, N-H⋯O and C-H⋯O hydrogen-bonding energies of 76.3, 55.2, 32.8 and 19.1 kJ mol-1, respectively. Evaluations of the electrostatic, dispersion and total energy frameworks indicate that the stabilization is dominated via dispersion energy contributions. Moreover, the optimized mol-ecular structure, using density functional theory (DFT) at the B3LYP/6-311G(d,p) level, was compared with the experimentally determined one. The HOMO-LUMO energy gap was determined and the mol-ecular electrostatic potential (MEP) surface was calculated at the B3LYP/6-31G level to predict sites for electrophilic and nucleophilic attacks. © Irrou et al. 2022.

Chemical context

The chemistry of heterocyclic compounds still receives increasing inter­est because of the therapeutic importance of most heterocyclic compounds, especially those with nitro­gen-containing heterocycles, which are of great inter­est as potential bioactive mol­ecules (Taia et al., 2020 ▸; Sebbar et al., 2016 ▸; El Ghayati et al., 2021 ▸; Dinakaran et al., 2012 ▸; Lahmidi et al., 2018 ▸; Hni et al., 2019 ▸). In this regard, pyrazolo­[3,4-d]pyrimidines are an important family of heterocyclic compounds, and their derivatives possess various pharmacological properties (Bakavoli et al., 2010 ▸; Severina et al., 2016 ▸), including their applications as anti-microbial (Holla et al., 2006 ▸; Bakavoli et al., 2010 ▸), anti-tumor (Kandeel et al., 2012 ▸), anti-inflammatory (El-Tombary, 2013 ▸), anti-oxidant (El-Mekabaty, 2015 ▸), anti-cancer (Gupta et al., 2008 ▸; Maher et al., 2019 ▸) and anti-convulsant (Severina et al., 2016 ▸) agents. Pyrazolo­pyrimidines can also be used in the treatment of Alzheimers’ disease (Zhang et al., 2018 ▸), and they have a powerful activity against herpes viruses (Gudmundsson et al., 2009 ▸) and human leukaemia (HL-60) (Song et al., 2011 ▸).

As a continuation of our research in this context, the title compound, (I), was synthesized by basic hydrolysis of the methyl ester of 2-(4-oxo-4, 5-di­hydro-1H-pyrazolo­[3,4-d]pyrimidin-1-yl)acetate. We report herein its synthesis, mol­ecular and crystal structures along with Hirshfeld surface analysis, crystal void and inter­molecular inter­action energies. Moreover, the optimized mol­ecular structure carried out at the B3LYP/6–311 G(d,p) level is compared with the experimentally determined structure, and energy framework as well as mol­ecular electrostatic potential (MEP) surface computations carried out at the B3LYP/6-31G level to predict the reactive sites for the electrophilic and nucleophilic attacks on (I) are presented.

Structural commentary

The pyrazolo­pyrimidine moiety is planar to within 0.0143 (10) Å (r.m.s deviation = 0.0082 Å) with the flap atom N1, which is part of the NH group, being the furthest from the mean plane. The plane of the carboxyl group is inclined to the above plane by 81.05 (5)°. There are no unusual bond lengths or inter­atomic angles in the mol­ecule (Fig. 1 ▸).

Figure 1

The title mol­ecule with displacement ellipsoids at the 30% probability level.

Supra­molecular features

In the crystal, inversion dimers are formed by N1—H1⋯O1 hydrogen bonds (Table 1 ▸) and are connected into sheets by complementary C5—H5⋯O1 hydrogen bonds (Table 1 ▸). Adjacent sheets are connected by O2—H2A⋯N2 and C6—C6A⋯O3 hydrogen bonds (Table 1 ▸) to form corrugated (010) layers with the component sheets alternately arranged parallel to (11 ) and ( 16) (Figs. 2 ▸ and 3 ▸). These corrugated layers are associated through C6—H6B⋯Cg1 inter­actions (Table 1 ▸ and Fig. 3 ▸).

Table 1

Hydrogen-bond geometry (Å, °)

Cg1 is the centroid of the C3/C4/C5/N4/N3 ring.

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯O1i	0.91	1.90	2.8094 (16)	175
O2—H2A⋯N2ii	0.87	1.85	2.7120 (14)	173
C5—H5⋯O1iii	0.93	2.33	3.2305 (18)	164
C6—H6A⋯O3iv	0.97	2.36	3.2436 (18)	152
C6—H6B⋯Cg1v	0.97	2.98	3.7387 (15)	136

Symmetry codes: (i) ; (ii) ; (iii) ; (iv) ; (v) .

Figure 2

View of the crystal packing along the b-axis direction with N—H⋯O, O—H⋯N and C—H⋯O hydrogen bonds shown, respectively, by light-blue, pink and black dashed lines. C—H⋯π(ring) inter­actions are shown by green dashed lines.

Figure 3

View of the crystal packing along the a-axis direction with N—H⋯O, O—H⋯N and C—H⋯O hydrogen bonds shown, respectively, by light-blue, pink and black dashed lines. C—H⋯π(ring) inter­actions are shown by green dashed lines.

Hirshfeld surface and crystal void analysis

In order to visualize the inter­molecular inter­actions in the crystal of (I), a Hirshfeld surface (HS) analysis (Hirshfeld, 1977 ▸) was carried out by using Crystal Explorer (Spackman et al., 2021 ▸). In the HS plotted over d norm (Fig. 4 ▸), the white surface indicates contacts with distances equal to the sum of van der Waals radii, and the red and blue colours indicate distances shorter or longer than the sum of the van der Waals radii, respectively (Venkatesan et al., 2016 ▸). The bright-red spots indicate sites of donor and/or acceptor inter­actions and they also appear as blue and red regions corresponding to positive (hydrogen bond donors) and negative (hydrogen bond acceptors) potentials on the HS mapped over electrostatic potential (Spackman et al., 2008 ▸; Jayatilaka et al., 2005 ▸), as shown in Fig. 5 ▸. The shape-index of the HS is a tool to visualize the presence of π–π stacking by the appearance of adjacent red and blue triangles. Fig. 5 ▸ clearly suggests that there are no significant π–π inter­actions in (I), as the above pattern is absent.

Figure 4

View of the three-dimensional Hirshfeld surface of the title compound, plotted over d norm in the range −0.6986 to 1.3450 a.u.

Figure 5

Hirshfeld surface of the title compound plotted over shape-index.

The overall two-dimensional fingerprint plot, Fig. 6 ▸ a, and those delineated into H⋯O/O⋯H, H⋯N/N⋯H, H⋯H, H⋯C/C⋯H, C⋯O/O⋯C, N⋯O/O⋯N, C⋯N/N⋯C, C⋯C and O⋯O contacts (McKinnon et al., 2007 ▸), and their relative contributions to the Hirshfeld surface, are illustrated in Fig. 6 ▸ b–j. The most important inter­action is H⋯O/O⋯H, contributing 34.8% to the overall crystal packing, which is shown in Fig. 6 ▸ b where the pair of spikes have tips at d e + d i = 1.81 Å. The pair of spikes in the fingerprint plot delineated into H⋯N/N⋯H contacts, Fig. 6 ▸ c, with a 19.3% contribution to the HS has a symmetric distribution of points with the tips at d e + d i = 1.74 Å. The H⋯H contacts contribute with 18.1% to the HS and are shown in Fig. 6 ▸ c as widely scattered points of high density due to the large hydrogen content of the mol­ecule with the tip at d e = d i = 1.28 Å. The high contribution of these inter­actions suggest that van der Waals inter­actions play the major role in the crystal packing (Hathwar et al., 2015 ▸). The presence of C—H⋯π inter­actions is shown by the pair of wings in the fingerprint plot delineated into H⋯C/C⋯H contacts with the tips at d e + d i = 2.93 Å (Fig. 6 ▸ e) with a 9.0% contribution to the HS. The C⋯O/O⋯C (Fig. 6 ▸ f), N⋯O/O⋯N (Fig. 6 ▸ g) and C⋯N/N⋯C (Fig. 6 ▸ h) contacts contribute with 6.7%, 5.9% and 3.1%, respectively, to the HS and the distributions of points appear with the tips at d e + d i = 2.95 Å, d e + d i = 3.15 Å and d e + d i = 3.38 Å. The C⋯C contacts, Fig. 6 ▸ i, with a 2.1% contribution to the HS, have a bullet-shaped distribution of points with the tip at d e = d i = 1.73 Å. Finally, the contribution of the O⋯O contacts (Fig. 6 ▸ j) to the HS is 1.0% with a low density of points.

Figure 6

The full two-dimensional fingerprint plots for the title compound, showing (a) all inter­actions, and delineated into (b) H⋯O/O⋯H, (c) H⋯N/N⋯H, (d) H⋯H, (e) H⋯C/C⋯H, (f) C⋯O/O⋯C, (g) N⋯O/O⋯N, (h) C⋯N/N⋯C, (i) C⋯C and (j) O⋯O inter­actions. The d i and d e values are the closest inter­nal and external distances (in Å) from given points on the Hirshfeld surface contacts.

The Hirshfeld surface representations with the function d norm plotted onto the surface are shown for the H⋯O/O⋯H, H⋯N/N⋯H, H⋯H and H⋯C/C⋯H inter­actions in Fig. 7 ▸ a–d, respectively.

Figure 7

The Hirshfeld surface representations with the function d norm plotted onto the surface for (a) H⋯O/O⋯H, (b) H⋯N/N⋯H, (c) H⋯H and (d) H⋯C/C⋯H inter­actions.

The strength of the crystal packing is important for determining the response to an applied mechanical force. If the crystal packing results in significant voids, then the mol­ecules are not tightly packed and a small amount of applied external mechanical force may easily break the crystal. To check the mechanical stability of the crystal, a void analysis was performed by adding up the electron densities of the spherically symmetric atoms contained in the asymmetric unit (Turner et al., 2011 ▸). The void surface is defined as an isosurface of the procrystal electron density and is calculated for the whole unit cell where the void surface meets the boundary of the unit cell and capping faces are generated to create an enclosed volume. The volume of the crystal voids (Fig. 8 ▸ a and b) and the percentage of free space in the unit cell are calculated as 176.30 Å3 and 10.94%, respectively. Thus, the crystal packing appears compact and the mechanical stability should be substantial.

Figure 8

Graphical views of voids in the crystal packing of (I) (a) along the a-axis direction and (b) along the b-axis direction.

Inter­action energy and energy framework calculations

The inter­molecular inter­action energies were calculated using a CE–B3LYP/6–31G(d,p) energy model available in Crystal Explorer (Spackman et al., 2021 ▸), where a cluster of mol­ecules is generated by applying crystallographic symmetry operations with respect to a selected central mol­ecule within the radius of 3.8 Å (Turner et al., 2014 ▸). The total inter­molecular energy (E tot) is the sum of electrostatic (E ele), polarization (E pol), dispersion (E dis) and exchange–repulsion (E rep) energies (Turner et al., 2015 ▸) with scale factors of 1.057, 0.740, 0.871 and 0.618, respectively (Mackenzie et al., 2017 ▸). Hydrogen-bonding inter­action energies (in kJ mol−1) were calculated to be −73.0 (E ele), −16.4 (E pol), −27.3 (E dis), 93.6 (E rep) and −55.2 (E tot) for N1—H1⋯O1 hydrogen-bonding inter­actions, −103.5 (E ele), −22.1 (E pol), −13.2 (E dis), 98.8 (E rep) and −76.3 (E tot) for O2—H2A⋯N2 hydrogen-bonding inter­actions, −12.2 (E ele), −2.9 (E pol), −34.4 (E dis), 19.9 (E rep) and −32.8 (E tot) for C5—H5⋯O1 hydrogen-bonding inter­actions, and −19.5 (E ele), −3.2 (E pol), −12.3 (E dis), 23.8 (E rep) and −19.0 (E tot) for C6—H6A⋯O3 hydrogen-bonding inter­actions.

Energy frameworks combine the calculation of inter­molecular inter­action energies with a graphical representation of their magnitude (Turner et al., 2015 ▸). Energies between mol­ecular pairs are represented as cylinders joining the centroids of pairs of mol­ecules with the cylinder radius proportional to the relative strength of the corresponding inter­action energy. Energy frameworks were constructed for E ele (red cylinders), E dis (green cylinders) and E tot (blue cylinders) (Fig. 9 ▸ a, b and c). The results indicate that the stabilization is dominated via dispersion energy contributions in (I).

Figure 9

The energy framework for a cluster of mol­ecules of (I) viewed down the a-axis direction (the b axis is vertical and the c axis is horizontal) showing (a) electrostatic energy, (b) dispersion energy and (c) total energy diagrams. The cylindrical radius is proportional to the relative strength of the corresponding energies and they were adjusted to the same scale factor of 80 with cut-off value of 5 kJ mol−1 within 1 × 1 × 1 unit cells.

DFT and Mol­ecular electrostatic potential (MEP) calculations

Density functional theory (DFT) using the standard B3LYP functional (Becke, 1993 ▸) and Pople’s basis set 6–31G(d,p) implemented in GAUSSIAN 09 (Frisch et al., 2009 ▸) was used to optimize the mol­ecular structure of (I) in the gas phase. The minimum was confirmed by frequency calculations, and the resulting optimized parameters (bond lengths and angles) agreed satisfactorily with the experimental structural data (Table 2 ▸). As a result, energies and other physico-chemical properties obtained from the optimized structure could be safely used to describe those of (I). The corresponding HOMO and LUMO energies were then used to estimate some parameters of global chemical reactivity, such as electronegativity (χ), hardness (η), ionization potential (I), electrophilicity (ω) and softness (σ) (Table 3 ▸). In addition, the mol­ecular electrostatic potential (MEP) map, and dipole moment (μ) of (I) were similarly calculated.

Table 2

Comparison of selected (X-ray and DFT) bond lengths and angles (Å, °)

	X-ray	B3LYP/6–311G(d,p)
O1=C1	1.2315 (17)	1.2450
O2—C7	1.3148 (17)	1.3767
O3=C7	1.2028 (17)	1.2273
N1—C2	1.3512 (18)	1.3749
N1—C1	1.3961 (18)	1.4047
N1—H1	0.9098	1.0128
N2=C2	1.3030 (18)	1.3131
N2—C3	1.3655 (17)	1.3742
N3—C3	1.3449 (17)	1.3605
N3—N4	1.3723 (16)	1.3955
N3—C6	1.4468 (17)	1.4417
C3=C4	1.3872 (19)	1.4048
N4=C5	1.3182 (19)	1.3412
C2—N1—C1	124.73 (11)	125.36
C2—N1—H1	121.4	120.93
C1—N1—H1	113.9	114.80
C2=N2—C3	112.91 (12)	113.46
C3—N3—N4	111.03 (11)	111.21
C3—N3—C6	128.49 (12)	128.12
N4—N3—C6	120.31 (11)	120.45
O1=C1—N1	120.51 (13)	120.02
O1=C1—C4	127.62 (13)	128.40
N2=C2—N1	124.94 (13)	124.12
O3=C7—O2	124.87 (13)	123.65
C2—N1—C1=O1	–176.82 (13)	–178.60
C3—N2—C2—N1	–0.6 (2)	–0.53
C1—N1—C2=N2	–1.4 (2)	–1.25
N4—N3—C3—N2	–178.88 (12)	–179.92

Table 3

Calculated energies

Total energy, TE (eV)	–19449.75
E HOMO (eV)	–6.66
E LUMO (eV)	–1.41
Gap, ΔE (eV)	5.25
Dipole moment, μ (Debye)	4.49
Ionization potential, I (eV)	6.66
Electron affinity, A	1.42
Electronegativity, χ	4.04
Hardness, η	2.62
Electrophilicity index, ω	3.11
Softness, σ	0.38
Fraction of electron transferred, ΔN	0.56

Minor differences between theory and experiment are likely due to optimized values being obtained in the isolated gas phase, neglecting inter­actions in the solid phase. Briefly, the average O2—C7 and N4—C5 bond lengths calculated at the DFT/B3LYP/6-31G(d,p) level are 1.3767 and 1.3412 Å, respectively, which is slightly higher than the experimental values of 1.3148 (17) and 1.3182 (19) Å, respectively. Moreover, the torsion angles N4—N3—C3—N2 = −179.92° and C3—N2—C2—N1 = −0.53° agree well with the experimental ones of −178.88 (12) and −0.6 (2)°.

The optimized frontier mol­ecular orbitals (HOMO and LUMO) are shown in Fig. 10 ▸. These orbitals play an important role in intra­molecular charge transfer (ICT). The topological characteristics of these levels are important for inter­preting kinetic stability and therefore potential chemical reactivity. The calculated energy band gap [ΔE = E LUMO – E HOMO] of the mol­ecule is 5.25 eV which indicates a hard mol­ecule with low polarizability and low chemical and biological activities but high kinetic stability. The LUMO is mainly centered on the plane extending over the whole aromatic ring system of (I). The numerical reactivity descriptors, which are mainly based on HOMO–LUMO energies, are summarized in Table 3 ▸. The ionization potential (I) is defined as the amount of energy required to remove an electron from a mol­ecule. The high ionization energy indicates also high stability and hence chemical inertness. Electron affinity (A) is defined as the energy released when an electron is added to a neutral mol­ecule. Therefore a large value indicates the tendency of the mol­ecule to retain its electrons. A negative chemical potential (μ) reflects mol­ecular stability while hardness (η) characterizes the resistance of the cloud of mol­ecular electrons to deformation during small disturbances. The overall electrophilicity index (ω) of a mol­ecule is a measure of its stabilization energy following the addition of an external electronic charge or its resistance to exchange electron(s) with the system (Parr et al., 1999 ▸). For (I), the ionization energy of 6.66 eV indicates high stability.

Figure 10

The optimized frontier molecular orbitals (HOMO and LUMO) with the energy band gap of (I).

The mol­ecular electrostatic potential (MEP) of the surface was calculated on the optimized B3LYP/6-31G (d,p) level using Gaussview software (Frisch et al., 2009 ▸). The MEP surface (Fig. 11 ▸) gives information about the reactive sites. The total electron density on which the electrostatic potential surface has been mapped is shown in Fig. 12 ▸ where a visual representation of chemically active sites and the comparative reactivity of atoms is also shown. The red regions denote the most negative electrostatic potential, the blue regions represent most positive electrostatic potential, and green regions represent the region of zero potential. Fig. 12 ▸ confirms the existence of inter­molecular N—H⋯O, O—H⋯N and—H⋯O hydrogen-bonding inter­actions.

Figure 11

MEP surfaces of (I) mapped at the B3LYP/6–311G level.

Figure 12

Contour surface of the electrostatic potential of (I).

Database survey

A search of the Cambridge Structural Database (CSD, updated March 2022; Groom et al., 2016 ▸) with the search fragment A (R = C—CH, C—C—OH; R′ = R" = variable; Fig. 13 ▸) yielded 11 hits. These included structures with R = t-Bu, R" = H, R′ = Ph (RULHEN; Liu et al., 2015 ▸), p-anis (QIBVIH; Tan et al., 2007 ▸); R" = H, R = i-Pr, R′ = cyclo­butane­carboxamido (QIBVON; Tan et al., 2007 ▸), R = n-Bu, R′ = benzamido (QIBWAA; Tan et al., 2007 ▸), R = 3-phenyl­propyl, R′ = CH3S (IFICUV; Avasthi et al., 2002 ▸), R = 2-chloro­ethyl, R′ = H (XAZRAT; Khazi et al., 2012 ▸); R = 1-β-D-ribo­furanosyl, R′ = H, R" = OMe (FOVHIH; Anderson et al., 1986 ▸), R′ = NH2, R" = H (YOMJIW; Ren et al., 2019 ▸); R = 2-de­oxy-β-d-erythro-pento­furanosyl, R′ = NH2, R" = Br (HIPPAX; Seela et al., 1999 ▸), R" = I (HIPPEB; Seela et al., 1999 ▸); R = 2-de­oxy-2-fluoro-β-d-arabino-furanosyl, R′ = NH2, R" = Br (EJEJUY; He et al., 2003 ▸). Like in (I), the pyrazolo­pyrimidine unit is essentially planar in these mol­ecules, but with the variety of substituents and the presence of different hydrogen-bonding inter­actions, the packings in the crystal are quite different.

Figure 13

The mol­ecular moiety used for the database search procedure.

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 4 ▸. Hydrogen atoms attached to carbon were placed in idealized positions while those attached to nitro­gen and to oxygen were placed in locations derived from a difference-Fourier map and their parameters adjusted to give N—H = 0.91 and O—H = 0.87 Å. All H atoms were included as riding contributions with isotropic displacement parameters tied to those of the attached atoms.

Table 4

Experimental details

Crystal data
Chemical formula	C7H6N4O3
M r	194.16
Crystal system, space group	Monoclinic, C2/c
Temperature (K)	296
a, b, c (Å)	15.3747 (4), 4.6699 (1), 23.0423 (5)
β (°)	103.122 (1)
V (Å3)	1611.20 (6)
Z	8
Radiation type	Cu Kα
μ (mm−1)	1.11
Crystal size (mm)	0.24 × 0.18 × 0.11
Data collection
Diffractometer	Bruker D8 VENTURE PHOTON 100 CMOS
Absorption correction	Multi-scan (SADABS; Krause et al., 2015 ▸)
T min, T max	0.81, 0.89
No. of measured, independent and observed [I > 2σ(I)] reflections	5850, 1598, 1503
R int	0.026
(sin θ/λ)max (Å−1)	0.625
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.048, 0.114, 1.16
No. of reflections	1598
No. of parameters	128
H-atom treatment	H-atom parameters constrained
Δρmax, Δρmin (e Å−3)	0.25, −0.33

Computer programs: APEX3 and SAINT (Bruker, 2016 ▸), SHELXT (Sheldrick, 2015a ▸), SHELXL (Sheldrick, 2015b ▸), DIAMOND (Brandenburg & Putz, 2012 ▸) and publCIF (Westrip, 2010 ▸).

Synthesis and crystallization

Ethyl 2-(4-oxo-4,5-di­hydro-1H-pyrazolo­[3,4-d]pyrimidin-1-yl)acetate (5 mmol) was dissolved in 10 ml of ethanol to which 10 ml of NaOH (aqueous, 10%wt) were added. The reaction mixture was stirred magnetically at room temperature for 4 h. After evaporation of ethanol and washing the aqueous phase with ethyl acetate, the mixture was acidified with an aqueous solution of HCl (3 N). The formed precipitate was filtered off and rinsed with ether. The crude product was recrystallized from ethanol to obtain colourless crystals of (I) in 72% yield.

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S2056989022008489/wm5656sup1.cif

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989022008489/wm5656Isup3.cdx

Click here for additional data file.

Supporting information file. DOI: 10.1107/S2056989022008489/wm5656Isup4.cml

Structure factors: contains datablock(s) I. DOI: 10.1107/S2056989022008489/wm5656Isup5.hkl

CCDC reference: 2203303

Additional supporting information: crystallographic information; 3D view; checkCIF report

C7H6N4O3	F(000) = 800
Mr = 194.16	Dx = 1.601 Mg m−3
Monoclinic, C2/c	Cu Kα radiation, λ = 1.54178 Å
a = 15.3747 (4) Å	Cell parameters from 5261 reflections
b = 4.6699 (1) Å	θ = 3.9–74.4°
c = 23.0423 (5) Å	µ = 1.11 mm−1
β = 103.122 (1)°	T = 296 K
V = 1611.20 (6) Å3	Block, colourless
Z = 8	0.24 × 0.18 × 0.11 mm

Bruker D8 VENTURE PHOTON 100 CMOS diffractometer	1598 independent reflections
Radiation source: INCOATEC IµS micro–focus source	1503 reflections with I > 2σ(I)
Mirror monochromator	Rint = 0.026
Detector resolution: 10.4167 pixels mm-1	θmax = 74.4°, θmin = 3.9°
ω scans	h = −16→18
Absorption correction: multi-scan (SADABS; Krause et al., 2015)	k = −5→5
Tmin = 0.81, Tmax = 0.89	l = −28→28
5850 measured reflections

Refinement on F2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.048	H-atom parameters constrained
wR(F2) = 0.114	w = 1/[σ2(Fo2) + (0.063P)2 + 0.6265P] where P = (Fo2 + 2Fc2)/3
S = 1.16	(Δ/σ)max < 0.001
1598 reflections	Δρmax = 0.25 e Å−3
128 parameters	Δρmin = −0.33 e Å−3
0 restraints	Extinction correction: SHELXL 2018/3 (Sheldrick, 2015b), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: dual	Extinction coefficient: 0.0304 (14)

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. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 2sigma(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger. H-atoms attached to carbon were placed in calculated positions (C—H = 0.95 - 0.99 Å) while those attached to nitrogen and to oxygen were placed in locations derived from a difference map and their parameters adjusted to give N—H = 0.91 and O—H = 0.87 Å. All were included as riding contributions with isotropic displacement parameters 1.2 - 1.5 times those of the attached atoms.

	x	y	z	Uiso*/Ueq
O1	0.39351 (7)	0.6126 (2)	0.49522 (5)	0.0517 (4)
H1	0.491406	0.298878	0.457379	0.078*
O2	0.17845 (7)	0.3011 (2)	0.24916 (4)	0.0474 (3)
H2A	0.169736	0.370596	0.213269	0.071*
O3	0.07906 (7)	−0.0274 (3)	0.20612 (5)	0.0586 (4)
N1	0.43440 (7)	0.2658 (3)	0.43684 (5)	0.0417 (3)
N2	0.33583 (7)	0.0013 (3)	0.36309 (5)	0.0397 (3)
N3	0.18190 (7)	0.1198 (3)	0.35967 (5)	0.0375 (3)
C1	0.37053 (9)	0.4290 (3)	0.45639 (6)	0.0389 (4)
C2	0.41582 (9)	0.0694 (3)	0.39270 (6)	0.0421 (4)
H2	0.463751	−0.024383	0.382697	0.051*
C3	0.27031 (9)	0.1489 (3)	0.38153 (5)	0.0353 (3)
C4	0.28199 (9)	0.3561 (3)	0.42577 (5)	0.0376 (3)
N4	0.13470 (8)	0.3040 (3)	0.38734 (5)	0.0435 (3)
C5	0.19481 (10)	0.4438 (3)	0.42717 (6)	0.0438 (4)
H5	0.181431	0.582221	0.452827	0.053*
C6	0.13600 (9)	−0.0569 (3)	0.31065 (6)	0.0410 (4)
H6A	0.076673	−0.099206	0.316240	0.049*
H6B	0.167753	−0.237123	0.311870	0.049*
C7	0.12731 (8)	0.0757 (3)	0.24955 (6)	0.0387 (4)

	U11	U22	U33	U12	U13	U23
O1	0.0478 (6)	0.0593 (7)	0.0440 (6)	−0.0021 (5)	0.0021 (4)	−0.0198 (5)
O2	0.0562 (6)	0.0484 (6)	0.0337 (5)	−0.0094 (5)	0.0024 (4)	0.0066 (4)
O3	0.0537 (7)	0.0787 (8)	0.0370 (6)	−0.0145 (6)	−0.0030 (5)	−0.0075 (5)
N1	0.0377 (6)	0.0487 (7)	0.0362 (6)	−0.0022 (5)	0.0031 (5)	−0.0063 (5)
N2	0.0409 (6)	0.0435 (6)	0.0333 (6)	−0.0011 (5)	0.0057 (5)	−0.0058 (5)
N3	0.0373 (6)	0.0434 (6)	0.0300 (6)	−0.0026 (5)	0.0040 (4)	−0.0002 (4)
C1	0.0435 (7)	0.0425 (7)	0.0293 (6)	−0.0021 (6)	0.0050 (5)	−0.0036 (5)
C2	0.0418 (7)	0.0470 (8)	0.0366 (7)	0.0006 (6)	0.0069 (6)	−0.0051 (6)
C3	0.0380 (7)	0.0392 (7)	0.0278 (6)	−0.0021 (5)	0.0056 (5)	0.0016 (5)
C4	0.0405 (7)	0.0425 (7)	0.0290 (6)	−0.0013 (5)	0.0062 (5)	−0.0019 (5)
N4	0.0415 (6)	0.0525 (7)	0.0364 (6)	0.0021 (5)	0.0087 (5)	−0.0001 (5)
C5	0.0452 (8)	0.0510 (8)	0.0348 (7)	0.0026 (6)	0.0081 (6)	−0.0050 (6)
C6	0.0418 (7)	0.0433 (8)	0.0348 (7)	−0.0092 (6)	0.0018 (5)	−0.0003 (5)
C7	0.0354 (7)	0.0446 (8)	0.0336 (7)	0.0004 (5)	0.0024 (5)	−0.0018 (5)

O1—C1	1.2315 (17)	N3—C6	1.4468 (17)
O2—C7	1.3148 (17)	C1—C4	1.4251 (18)
O2—H2A	0.8701	C2—H2	0.9300
O3—C7	1.2028 (17)	C3—C4	1.3872 (19)
N1—C2	1.3512 (18)	C4—C5	1.4090 (19)
N1—C1	1.3961 (18)	N4—C5	1.3182 (19)
N1—H1	0.9098	C5—H5	0.9300
N2—C2	1.3030 (18)	C6—C7	1.5160 (18)
N2—C3	1.3655 (17)	C6—H6A	0.9700
N3—C3	1.3449 (17)	C6—H6B	0.9700
N3—N4	1.3723 (16)
C7—O2—H2A	110.0	C3—C4—C5	104.74 (12)
C2—N1—C1	124.73 (11)	C3—C4—C1	118.71 (12)
C2—N1—H1	121.4	C5—C4—C1	136.54 (13)
C1—N1—H1	113.9	C5—N4—N3	105.83 (11)
C2—N2—C3	112.91 (12)	N4—C5—C4	111.12 (13)
C3—N3—N4	111.03 (11)	N4—C5—H5	124.4
C3—N3—C6	128.49 (12)	C4—C5—H5	124.4
N4—N3—C6	120.31 (11)	N3—C6—C7	114.60 (11)
O1—C1—N1	120.51 (13)	N3—C6—H6A	108.6
O1—C1—C4	127.62 (13)	C7—C6—H6A	108.6
N1—C1—C4	111.86 (11)	N3—C6—H6B	108.6
N2—C2—N1	124.94 (13)	C7—C6—H6B	108.6
N2—C2—H2	117.5	H6A—C6—H6B	107.6
N1—C2—H2	117.5	O3—C7—O2	124.87 (13)
N3—C3—N2	125.93 (12)	O3—C7—C6	121.10 (13)
N3—C3—C4	107.27 (12)	O2—C7—C6	113.99 (11)
N2—C3—C4	126.80 (12)
C2—N1—C1—O1	−176.82 (13)	O1—C1—C4—C3	177.49 (14)
C2—N1—C1—C4	2.4 (2)	N1—C1—C4—C3	−1.64 (18)
C3—N2—C2—N1	−0.6 (2)	O1—C1—C4—C5	−1.6 (3)
C1—N1—C2—N2	−1.4 (2)	N1—C1—C4—C5	179.24 (15)
N4—N3—C3—N2	−178.88 (12)	C3—N3—N4—C5	−0.97 (15)
C6—N3—C3—N2	−3.7 (2)	C6—N3—N4—C5	−176.57 (12)
N4—N3—C3—C4	0.92 (15)	N3—N4—C5—C4	0.64 (16)
C6—N3—C3—C4	176.06 (12)	C3—C4—C5—N4	−0.10 (16)
C2—N2—C3—N3	−179.00 (13)	C1—C4—C5—N4	179.09 (15)
C2—N2—C3—C4	1.2 (2)	C3—N3—C6—C7	−83.22 (17)
N3—C3—C4—C5	−0.49 (15)	N4—N3—C6—C7	91.53 (15)
N2—C3—C4—C5	179.30 (13)	N3—C6—C7—O3	−168.31 (14)
N3—C3—C4—C1	−179.86 (11)	N3—C6—C7—O2	13.70 (18)
N2—C3—C4—C1	−0.1 (2)

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1···O1i	0.91	1.90	2.8094 (16)	175
O2—H2A···N2ii	0.87	1.85	2.7120 (14)	173
C5—H5···O1iii	0.93	2.33	3.2305 (18)	164
C6—H6A···O3iv	0.97	2.36	3.2436 (18)	152
C6—H6B···Cg1v	0.97	2.98	3.7387 (15)	136