1-[2-(4-Nitrophenyl)-5-(5-phenyl-1,2-oxazol-3-yl)-1,2,3,4-tetrahydroquinolin-4-yl]pyrrolidin-2-one

The title compound, (I) C₂₈H₂₄N₄O₄, is the trans diastereo­isomer of the compound 1-[2-(4-nitro­phen­yl)-6-(5-phenyl-3-isoxazol­yl)-1,2,3,4-tetra­hydro-4-quinolin­yl]-2-pyrrolidinone monohydrate, (II) [Gutierrez et al. (2011). Acta Cryst. E67, o175–o176]. The most obvious differences between the diastereo­isomers are the dihedral angles between the isoxazole ring and the benzene and phenyl rings [47.0 (2); 56.4 (2) and 33.3 (2); 11.0 (2)°, respectively, for (II) 75.4 (2) and 5.8 (3), respectively, for (I)]. In the crystal of (I), the mol­ecules are linked by N—H...O inter­actions into a chain along [001] with graph-set notation C(8).

Key indicators

• Single-crystal X-ray study
• T = 293 K
• Mean [sigma](C-C) = 0.007 Å
• R factor = 0.075
• wR factor = 0.162
• Data-to-parameter ratio = 9.6

checkCIF/PLATON results

No syntax errors found



Alert level C
PLAT220_ALERT_2_C Large Non-Solvent    O     Ueq(max)/Ueq(min) ...       3.03 Ratio
PLAT222_ALERT_3_C Large Non-Solvent    H    Uiso(max)/Uso(min) ...       6.41 Ratio
PLAT241_ALERT_2_C Check High      Ueq as Compared to Neighbors for         C6
PLAT242_ALERT_2_C Check Low       Ueq as Compared to Neighbors for         N1
PLAT242_ALERT_2_C Check Low       Ueq as Compared to Neighbors for         C1
PLAT245_ALERT_2_C U(iso) H2N     Smaller than U(eq) N2      by ...       0.03 AngSq
PLAT334_ALERT_2_C Small Average Benzene  C-C Dist. C1     -C6            1.37 Ang.
PLAT340_ALERT_3_C Low Bond Precision on  C-C Bonds (x 1000) Ang ..          7
PLAT910_ALERT_3_C Missing # of FCF Reflections Below Th(Min) .....          4
PLAT152_ALERT_1_C The Supplied and Calc. Volume s.u. Differ by ...         19 Units
PLAT950_ALERT_1_C Reported and Calculated Hmax Values Differ by ..          4

Alert level G
REFLT03_ALERT_1_G ALERT: Expected hkl max differ from CIF values
           From the CIF: _diffrn_reflns_theta_max           27.46
           From the CIF: _reflns_number_total               3144
           From the CIF: _diffrn_reflns_limit_ max hkl    0.   26.   13.
           From the CIF: _diffrn_reflns_limit_ min hkl  -22.    0.  -13.
           TEST1: Expected hkl limits for theta max
           Calculated maximum hkl   26.   26.   13.
           Calculated minimum hkl  -26.  -26.  -13.
REFLT03_ALERT_4_G Please check that the estimate of the number of Friedel pairs is
            correct. If it is not, please give the correct count in the
            _publ_section_exptl_refinement section of the submitted CIF.
           From the CIF: _diffrn_reflns_theta_max           27.46
           From the CIF: _reflns_number_total               3144
           Count of symmetry unique reflns         3142
           Completeness (_total/calc)            100.06%
           TEST3: Check Friedels for noncentro structure
           Estimate of Friedel pairs measured         2
           Fraction of Friedel pairs measured     0.001
           Are heavy atom types Z>Si present         no
PLAT199_ALERT_1_G Check the Reported _cell_measurement_temperature        293 K
PLAT200_ALERT_1_G Check the Reported   _diffrn_ambient_temperature        293 K
PLAT605_ALERT_4_G Structure Contains Solvent Accessible VOIDS of .     452.00 A   3 
PLAT791_ALERT_4_G Note: The Model has Chirality at C7     (Verify)          R
PLAT791_ALERT_4_G Note: The Model has Chirality at C9     (Verify)          S
PLAT981_ALERT_1_G No non-zero f" Anomalous Scattering Values Found          ?

   0 ALERT level A = In general: serious problem
   0 ALERT level B = Potentially serious problem
  11 ALERT level C = Check and explain
   8 ALERT level G = General alerts; check

   6 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   6 ALERT type 2 Indicator that the structure model may be wrong or deficient
   3 ALERT type 3 Indicator that the structure quality may be low
   4 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

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S1. Comment

Nitrogen containing heterocycles are indispensable structural units for medicinal chemists (Sankaran et al., 2010). Compounds possessing the quinoline system have wide applications as drugs and pharmaceuticals and also occur as the structural framework in some natural products (Kalita et al., 2006). They also have several pharmacological activities as anti-breast cancer (Shi et al., 2008), selective PDE4 inhibition (Lunniss et al., 2009), immuno modulatory (He et al., 2005), and antimycobacterial agents (Eswaran et al., 2010), among others.

Quinoline and its derivatives represent a major class of heterocycles, and a number of preparations have been known since the late 1800's. The quinoline skeleton is often used for the design of many synthetic compounds with diverse pharmacological properties. Several syntheses of quinolines are known, but due to their importance, the development of new synthetic approaches remains an active research area (Kouznetsov et al., 2005).

The isoxazoles form a relevant group of biologically active compounds with a wide range of applications, including Hsp90 super chaperone complex inhibitors (Taldone et al., 2008), tau aggregation inhibitors for treatment of Alzheimer's disease (Narlawar et al., 2008), mycobacterium tuberculosis pantothenate synthetase inhibitors (Velaparthi et al., 2008) and neuronal nicotinic acetylcholine receptor agonists (Rizzi et al., 2008).

A considerable number of methods to synthesize substituted isoxazoles have been published including approaches based on intramolecular cycloadditions, condensations, and intramolecular cyclizations of amino acids. These methods sometime suffer in their versatility, convenience and yield (Lautens & Roy, 2000). The isoxazole ring can be synthetized by 1, 3-dipolar cyclo-addition reactions between a nitrile oxide and an alkyne, that reaction may be catalyzed by copper(II). Cycloaddition reactions are among the most useful reactions in synthetic and mechanistic organic chemistry (Broggini et al., 2005).

Isoxazoles have a rich chemistry because of their easy reductive cleavage and susceptibility to ring transformations (Kotera et al., 1970). Depending on the substitution patterns, isoxazoles can be used as reagents for the imino-Diels-Alder condensation between anilines, aldehydes and electron-rich alkenes to generate tetrahydroquinolines with different selected substitution patterns.

Due to these facts, the combination of the two heterocyclic rings into a new chemical entity is of interest, as no examples are known in the chemical literature to date.

Many molecules widely used today consist of fusions of rings; an example is the case of penicillins, where incorporation of an isoxazole ring led to the formation of stable derivatives which catalyzed the degradation of gastric acid levels (flucloxacillin and cloxacillin).

We report here the crystal structure of a novel synthetic derivative cis quinoline-isoxazole prepared by imino Diels-Alder cyclo-addition, Scheme 1.

The structure of the title compound, (I) C₂₈H₂₄N₄O₄, has hexagonal (P6₁) symmetry and is the trans diastereoisomer of the compound 1-[2-(4-nitrophenyl)-6-(5-phenyl-3-isoxazolyl)-1,2,3,4-tetrahydro-4-quinolinyl]-2-pyrrolidinone-dihydrate, (II) (Gutierrez et al., 2011), so the pyrrolidinone fragment is trans oriented respect to 4-nitrophenyl fragment [C7—C8—C9—N4 torsion angle 85.59 (4)°; -175.(2) (4)° for (II) (mean)]. The most obvious differences between both diastereoisomers are the torsion angles between the isoxazole ring and the benzene and phenyl rings [47.0 (2); 56.4 (2) and 33.3 (2); 11.0 (2)° for (II) 75.4 (2) and 5.8 (3) for (I)]. In both diastereoisomers the six-membered heterocyclic ring has a half-boat conformation (Q_T= 0.477 (5) Å, θ = 47.7 (5)° ϕ= 76.3 (7)°), Cremer & Pople, 1975. In the crystal, molecules are linked by N— H··· O interactions into chains with graph-set notation C(8) along [001], Fig. 2, Bernstein et al., 1995.

Related literature

For details of nitrogen-containing heterocyclic compounds, see: Sankaran et al. (2010) and for their pharmacological activity, see: Shi et al. (2008); Lunniss et al. (2009); He et al. (2005); Eswaran et al. (2010). For reactions of isoxazoles, see: Taldone et al. (2008); Narlawar et al. (2008); Velaparthi et al. (2008); Rizzi et al. (2008); Lautens & Roy (2000); Broggini et al. (2005); Kotera et al. (1970). For applications of compounds possessing the quinoline system as drugs and pharmaceuticals, see: Kalita et al. (2006). For syntheses of quinolines, see: Kouznetsov et al. (2005). For the trans diastereoisomer of the title compound, see: Gutierrez et al. (2011). For graph-set motifs see: Bernstein et al. (1995) and for puckering parameters, see: Cremer & Pople (1975)

S2. Experimental

A mixture of 3-(3-aminophenyl)-5-phenylisoxazole (2.8 mmol) 3 and 4-nitrobenzaldehyde (3.4 mmol) 1 in anhydrous CH₃CN (15 mL) was stirred at room temperature for 30 min. BiCl₃ (2.0 mmol) was added. Over a period of 20 min, a solution the N-vinyl.2-pyrrolidone (NVP) (5.5 mmol) 4 in CH₃CN (10 ml) was added dropwise. The resulting mixture was stirred for 10–14 h. After completion of the reaction as indicated by TLC, the reaction mixture was diluted with water (30 mL) and extracted with ethyl acetate (3×15 mL). The organic layer was separated and dried (Na₂SO₄),concentrated in vacuum and the resulting product was purified by column chromatography (silica gel) using PE and EtOAc mixtures. Obtained for derivatives trans and cis Quinoline-Isoxazole 5 and (I), see Figure 3. Solid crystalline mp 130 - 132 °C; RMN-¹H(CDCl₃), 400 MHz, δ): 8.24 (2H, d, J = 8.0); 7.81 (2H, d, J= 8.0); 7.60 (1H, d, J = 8.0); 7.27(2H, dd, J = 8.0 and 4.0); 7.17 (1H,t, J = 8.0); 6.97 (1H, d, J = 8.0); 6.89 (2H, d, J = 8.0); 6.78 (1H, d, J = 8.0); 6.62 (1H, s); 5.35 (1H, s); 4.59 (1H, dd, J = 12.0 and 1.0); 4.41 (1H, br. s);2.39 (2H, m); 1.97 (2H, m); 1.62 (2H, s). RMN-¹³H (CDCl₃),400 MHz, δ): 174.68, 169.95, 162.48, 150.61, 147.65, 145.15, 130.87, 129.31, 128.98, 127.47,127.27, 125.95, 125.04, 124.61, 119.61, 116.32, 115.27, 99.89, 52.54, 47.51,46.22, 37.37, 31.36, 18.56. MS m/z (EI): 480. Anal. Calcd. for C₂₈H₂₄N₄O₄: C, 69.99; H,5.03;N, 11.66. Found: C, 69.89; H, 5.01; N, 11.77.

S3. Refinement

The SQUEEZE function of PLATON (Spek, 2009) was used to eliminate the contribution of electron density in the solvent region from the intensity data, and a solvent-free model was employed for the final refinement. The volume which is accessible for potential solvent molecules was calculated to be 452.0 ų and the total electron count per cell was calculated to be 15. Note that the calculated density, the F(000) value, the molecular weight and the formula are given without taking into account the results obtained with the SQUEEZE option in PLATON (Spek, 2009). Therefore, the solvent-free model and intensity data were used for the final results reported here.

The absolute configuration of the two stereogenic centres could not be established by the Flack parameter (Flack, 1983) and Friedel opposites were merged.

The position of the N2 H atom was refined freely with isotropic displacement parameters. All other H atoms were placed in geometrically idealized positions (C—H = 0.93–0.97 Å) and constrained to ride on their parent atoms with U_iso(H) = 1.2U_eq(C).

Computing details

Data collection: COLLECT (Nonius, 2000); cell refinement: DENZO-SMN (Otwinowski & Minor, 1997); data reduction: DENZO-SMN (Otwinowski & Minor, 1997); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997) & PLATON (Spek, 2009); software used to prepare material for publication: WinGX (Farrugia, 1999).

Figures

	Fig. 1. The structure of (I), showing the atom-numbering scheme. Displacement ellipsoids are plotted at the 30% probability level.
	Fig. 2. A view of (I), showing the mono-dimensional framework constructed via N—H···O hydrogen bonds. Hydrogen bonds are depicted as dashed lines [symmetry-code:(i) y, -x + y, z - 1/6.]
	Fig. 3. The preparation of the title compound.

1-[2-(4-Nitrophenyl)-5-(5-phenyl-1,2-oxazol-3-yl)-1,2,3,4-tetrahydroquinolin- 4-yl]pyrrolidin-2-one

Crystal data

C28H24N4O4	Dx = 1.229 Mg m^−3
Mr = 480.51	Mo Kα radiation, λ = 0.71073 Å
Hexagonal, P61	Cell parameters from 2728 reflections
Hall symbol: P 61	θ = 2.8–27.5°
a = 20.753 (3) Å	µ = 0.08 mm^−1
c = 10.446 (2) Å	T = 293 K
V = 3896.2 (11) Å^3	Prismatic, orange
Z = 6	0.20 × 0.20 × 0.18 mm
F(000) = 1512

Data collection

Nonius KappaCCD area-detector diffractometer	2646 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.026
Graphite monochromator	θmax = 27.5°, θmin = 2.8°
ϕ scans, and ω scans with κ offsets	h = −22→0
5951 measured reflections	k = 0→26
3144 independent reflections	l = −13→13

Refinement

Refinement on F^2	Primary atom site location: structure-invariant direct methods
Least-squares matrix: full	Secondary atom site location: difference Fourier map
R[F^2 > 2σ(F^2)] = 0.075	Hydrogen site location: inferred from neighbouring sites
wR(F^2) = 0.162	H atoms treated by a mixture of independent and constrained refinement
S = 1.22	w = 1/[σ^2(Fo^2) + (0.0755P)^2 + 0.8624P] where P = (Fo^2 + 2Fc^2)/3
3144 reflections	(Δ/σ)max = 0.010
329 parameters	Δρmax = 0.32 e Å^−3
1 restraint	Δρmin = −0.24 e Å^−3

Special details

Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is used for estimating s.u.'s 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 > 2σ(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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Ų)

	x	y	z	Uiso*/Ueq
O1	0.2019 (3)	−0.0999 (3)	0.6005 (5)	0.1165 (18)
O2	0.1082 (3)	−0.1080 (3)	0.5004 (7)	0.147 (3)
O3	0.54683 (17)	0.55998 (14)	0.2252 (3)	0.0485 (7)
O4	0.36115 (17)	0.42435 (19)	0.2789 (3)	0.0607 (8)
N1	0.1743 (3)	−0.0784 (3)	0.5205 (5)	0.0880 (15)
N2	0.43438 (18)	0.19821 (17)	0.2011 (4)	0.0456 (8)
N3	0.5569 (2)	0.49764 (18)	0.2257 (4)	0.0492 (8)
N4	0.36641 (16)	0.33963 (17)	0.1463 (3)	0.0388 (7)
C1	0.2234 (3)	−0.0115 (2)	0.4445 (5)	0.0631 (12)
C2	0.2982 (3)	0.0205 (3)	0.4559 (5)	0.0637 (12)
H2	0.3186	−0.0002	0.5098	0.076*
C3	0.3433 (2)	0.0833 (2)	0.3881 (5)	0.0597 (12)
H3	0.3946	0.1050	0.3963	0.072*
C4	0.3145 (2)	0.1154 (2)	0.3075 (4)	0.0489 (10)
C5	0.2376 (3)	0.0806 (3)	0.2964 (7)	0.0855 (19)
H5	0.2168	0.1006	0.2416	0.103*
C6	0.1916 (3)	0.0171 (3)	0.3647 (7)	0.091 (2)
H6	0.1401	−0.0057	0.3568	0.109*
C7	0.3612 (2)	0.1867 (2)	0.2334 (5)	0.0471 (9)
H7	0.3351	0.1839	0.1535	0.057*
C8	0.3719 (2)	0.25488 (19)	0.3085 (4)	0.0404 (8)
H8A	0.3237	0.2483	0.3310	0.048*
H8B	0.3985	0.2591	0.3873	0.048*
C9	0.41529 (18)	0.32633 (18)	0.2308 (4)	0.0337 (7)
H9	0.4378	0.3677	0.2918	0.040*
C10	0.47821 (18)	0.32842 (19)	0.1526 (4)	0.0335 (7)
C11	0.4825 (2)	0.26296 (19)	0.1383 (4)	0.0379 (8)
C12	0.5384 (2)	0.2653 (2)	0.0586 (4)	0.0451 (10)
H12	0.5428	0.2231	0.0502	0.054*
C13	0.5865 (2)	0.3290 (2)	−0.0069 (4)	0.0499 (10)
H13	0.6217	0.3289	−0.0618	0.060*
C14	0.5826 (2)	0.3935 (2)	0.0088 (4)	0.0439 (9)
H14	0.6151	0.4365	−0.0357	0.053*
C15	0.53053 (19)	0.39350 (19)	0.0906 (4)	0.0345 (8)
C16	0.53036 (18)	0.46432 (19)	0.1164 (4)	0.0355 (8)
C17	0.5044 (2)	0.5032 (2)	0.0404 (4)	0.0393 (8)
H17	0.4844	0.4914	−0.0417	0.047*
C18	0.51507 (19)	0.56076 (19)	0.1134 (4)	0.0374 (8)
C19	0.4969 (2)	0.6206 (2)	0.0963 (4)	0.0401 (8)
C20	0.4578 (2)	0.6207 (2)	−0.0102 (4)	0.0456 (9)
H20	0.4425	0.5828	−0.0704	0.055*
C21	0.4409 (2)	0.6770 (3)	−0.0284 (5)	0.0552 (11)
H21	0.4141	0.6767	−0.0999	0.066*
C22	0.4643 (3)	0.7329 (3)	0.0603 (6)	0.0655 (14)
H22	0.4544	0.7714	0.0476	0.079*
C23	0.5015 (4)	0.7325 (3)	0.1657 (6)	0.0790 (17)
H23	0.5157	0.7701	0.2262	0.095*
C24	0.5191 (3)	0.6767 (3)	0.1855 (5)	0.0671 (14)
H24	0.5454	0.6773	0.2579	0.080*
C25	0.3392 (3)	0.3060 (3)	0.0210 (5)	0.0674 (14)
H25A	0.3053	0.2529	0.0290	0.081*
H25B	0.3802	0.3141	−0.0341	0.081*
C26	0.2998 (3)	0.3441 (4)	−0.0316 (6)	0.0799 (16)
H26A	0.3271	0.3753	−0.1038	0.096*
H26B	0.2503	0.3076	−0.0602	0.096*
C27	0.2955 (3)	0.3900 (3)	0.0734 (5)	0.0704 (14)
H27A	0.2446	0.3694	0.1028	0.085*
H27B	0.3135	0.4407	0.0446	0.085*
C28	0.3444 (2)	0.3884 (2)	0.1797 (4)	0.0474 (10)
H2N	0.4315 (16)	0.1573 (18)	0.174 (3)	0.017 (8)*

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
O1	0.113 (4)	0.106 (3)	0.110 (4)	0.039 (3)	0.008 (3)	0.058 (3)
O2	0.088 (3)	0.109 (4)	0.173 (6)	−0.005 (3)	−0.006 (4)	0.069 (4)
O3	0.0723 (18)	0.0384 (13)	0.0401 (15)	0.0317 (13)	−0.0135 (14)	−0.0066 (12)
O4	0.0657 (18)	0.086 (2)	0.0577 (19)	0.0587 (18)	−0.0052 (16)	−0.0198 (18)
N1	0.079 (3)	0.063 (3)	0.090 (4)	0.011 (2)	0.004 (3)	0.018 (3)
N2	0.0506 (18)	0.0267 (15)	0.062 (2)	0.0212 (14)	0.0040 (17)	−0.0034 (15)
N3	0.067 (2)	0.0429 (17)	0.0464 (19)	0.0341 (16)	−0.0109 (18)	−0.0027 (16)
N4	0.0363 (15)	0.0475 (16)	0.0394 (17)	0.0262 (14)	−0.0005 (14)	−0.0013 (14)
C1	0.066 (3)	0.040 (2)	0.064 (3)	0.012 (2)	0.001 (2)	0.007 (2)
C2	0.070 (3)	0.061 (3)	0.063 (3)	0.035 (2)	0.004 (3)	0.016 (2)
C3	0.052 (2)	0.057 (2)	0.068 (3)	0.026 (2)	−0.002 (2)	0.014 (2)
C4	0.046 (2)	0.0338 (18)	0.058 (3)	0.0127 (16)	−0.001 (2)	0.0012 (19)
C5	0.059 (3)	0.070 (3)	0.111 (5)	0.020 (2)	−0.008 (3)	0.038 (4)
C6	0.056 (3)	0.068 (3)	0.117 (5)	0.008 (3)	−0.013 (3)	0.029 (4)
C7	0.046 (2)	0.0363 (19)	0.055 (2)	0.0175 (16)	−0.0023 (19)	0.0047 (18)
C8	0.0396 (18)	0.0416 (19)	0.043 (2)	0.0225 (16)	0.0057 (17)	0.0045 (17)
C9	0.0337 (16)	0.0332 (17)	0.0379 (18)	0.0194 (14)	0.0005 (15)	−0.0010 (15)
C10	0.0337 (17)	0.0359 (17)	0.0354 (18)	0.0207 (15)	−0.0041 (15)	−0.0050 (15)
C11	0.0400 (18)	0.0380 (18)	0.044 (2)	0.0260 (16)	−0.0081 (17)	−0.0073 (17)
C12	0.042 (2)	0.044 (2)	0.059 (3)	0.0297 (18)	−0.007 (2)	−0.016 (2)
C13	0.0383 (19)	0.059 (2)	0.056 (3)	0.0276 (19)	0.008 (2)	−0.012 (2)
C14	0.0369 (18)	0.043 (2)	0.050 (2)	0.0181 (16)	0.0077 (18)	−0.0001 (19)
C15	0.0344 (17)	0.0341 (17)	0.0376 (18)	0.0192 (14)	−0.0063 (15)	−0.0017 (15)
C16	0.0317 (17)	0.0348 (17)	0.0365 (19)	0.0139 (14)	0.0064 (15)	0.0058 (15)
C17	0.0493 (19)	0.0404 (18)	0.0315 (19)	0.0249 (16)	0.0008 (16)	0.0012 (16)
C18	0.0385 (18)	0.0345 (18)	0.0376 (19)	0.0170 (15)	0.0034 (16)	0.0050 (15)
C19	0.047 (2)	0.0351 (18)	0.042 (2)	0.0236 (16)	0.0096 (17)	0.0055 (16)
C20	0.053 (2)	0.047 (2)	0.041 (2)	0.0287 (19)	0.0041 (19)	0.0014 (18)
C21	0.065 (3)	0.063 (3)	0.053 (2)	0.044 (2)	0.002 (2)	0.010 (2)
C22	0.093 (4)	0.055 (3)	0.070 (3)	0.053 (3)	0.012 (3)	0.010 (3)
C23	0.120 (5)	0.063 (3)	0.076 (4)	0.061 (3)	−0.020 (4)	−0.025 (3)
C24	0.101 (4)	0.057 (3)	0.059 (3)	0.051 (3)	−0.025 (3)	−0.017 (2)
C25	0.078 (3)	0.086 (3)	0.058 (3)	0.055 (3)	−0.024 (3)	−0.020 (3)
C26	0.083 (4)	0.119 (5)	0.059 (3)	0.067 (4)	−0.022 (3)	−0.011 (3)
C27	0.075 (3)	0.096 (4)	0.069 (3)	0.064 (3)	−0.008 (3)	0.000 (3)
C28	0.042 (2)	0.062 (2)	0.051 (2)	0.035 (2)	0.0038 (19)	0.005 (2)

Geometric parameters (Å, º)

O1—N1	1.217 (6)	C11—C12	1.409 (6)
O2—N1	1.209 (7)	C12—C13	1.375 (6)
O3—C18	1.344 (5)	C12—H12	0.9300
O3—N3	1.410 (4)	C13—C14	1.390 (6)
O4—C28	1.221 (5)	C13—H13	0.9300
N1—C1	1.477 (6)	C14—C15	1.378 (5)
N2—C11	1.375 (5)	C14—H14	0.9300
N2—C7	1.454 (5)	C15—C16	1.496 (5)
N2—H2N	0.87 (3)	C16—C17	1.416 (5)
N3—C16	1.306 (5)	C17—C18	1.339 (5)
N4—C28	1.349 (5)	C17—H17	0.9300
N4—C25	1.457 (6)	C18—C19	1.477 (5)
N4—C9	1.472 (4)	C19—C20	1.378 (6)
C1—C2	1.353 (7)	C19—C24	1.379 (6)
C1—C6	1.370 (7)	C20—C21	1.390 (6)
C2—C3	1.362 (6)	C20—H20	0.9300
C2—H2	0.9300	C21—C22	1.370 (7)
C3—C4	1.381 (6)	C21—H21	0.9300
C3—H3	0.9300	C22—C23	1.346 (8)
C4—C5	1.389 (6)	C22—H22	0.9300
C4—C7	1.514 (6)	C23—C24	1.394 (7)
C5—C6	1.378 (8)	C23—H23	0.9300
C5—H5	0.9300	C24—H24	0.9300
C6—H6	0.9300	C25—C26	1.497 (7)
C7—C8	1.534 (5)	C25—H25A	0.9700
C7—H7	0.9800	C25—H25B	0.9700
C8—C9	1.527 (5)	C26—C27	1.486 (8)
C8—H8A	0.9700	C26—H26A	0.9700
C8—H8B	0.9700	C26—H26B	0.9700
C9—C10	1.523 (5)	C27—C28	1.515 (7)
C9—H9	0.9800	C27—H27A	0.9700
C10—C15	1.398 (5)	C27—H27B	0.9700
C10—C11	1.413 (5)
C18—O3—N3	108.2 (3)	C12—C13—H13	119.9
O2—N1—O1	123.8 (5)	C14—C13—H13	119.9
O2—N1—C1	117.2 (5)	C15—C14—C13	119.8 (4)
O1—N1—C1	119.0 (5)	C15—C14—H14	120.1
C11—N2—C7	117.3 (3)	C13—C14—H14	120.1
C11—N2—H2N	117 (2)	C14—C15—C10	121.1 (3)
C7—N2—H2N	111.2 (19)	C14—C15—C16	119.9 (3)
C16—N3—O3	105.4 (3)	C10—C15—C16	118.9 (3)
C28—N4—C25	113.3 (3)	N3—C16—C17	111.6 (3)
C28—N4—C9	120.7 (3)	N3—C16—C15	118.0 (3)
C25—N4—C9	126.0 (3)	C17—C16—C15	130.4 (3)
C2—C1—C6	121.6 (4)	C18—C17—C16	104.4 (3)
C2—C1—N1	119.8 (5)	C18—C17—H17	127.8
C6—C1—N1	118.6 (5)	C16—C17—H17	127.8
C1—C2—C3	119.6 (5)	C17—C18—O3	110.3 (3)
C1—C2—H2	120.2	C17—C18—C19	133.0 (4)
C3—C2—H2	120.2	O3—C18—C19	116.6 (3)
C2—C3—C4	121.5 (4)	C20—C19—C24	119.5 (4)
C2—C3—H3	119.3	C20—C19—C18	119.9 (4)
C4—C3—H3	119.3	C24—C19—C18	120.7 (4)
C3—C4—C5	117.5 (4)	C19—C20—C21	120.5 (4)
C3—C4—C7	124.3 (4)	C19—C20—H20	119.7
C5—C4—C7	118.2 (4)	C21—C20—H20	119.7
C6—C5—C4	121.4 (5)	C22—C21—C20	119.2 (4)
C6—C5—H5	119.3	C22—C21—H21	120.4
C4—C5—H5	119.3	C20—C21—H21	120.4
C1—C6—C5	118.4 (5)	C23—C22—C21	120.6 (4)
C1—C6—H6	120.8	C23—C22—H22	119.7
C5—C6—H6	120.8	C21—C22—H22	119.7
N2—C7—C4	112.6 (3)	C22—C23—C24	121.0 (5)
N2—C7—C8	108.0 (3)	C22—C23—H23	119.5
C4—C7—C8	111.5 (4)	C24—C23—H23	119.5
N2—C7—H7	108.2	C19—C24—C23	119.1 (5)
C4—C7—H7	108.2	C19—C24—H24	120.4
C8—C7—H7	108.2	C23—C24—H24	120.4
C9—C8—C7	111.5 (3)	N4—C25—C26	105.1 (4)
C9—C8—H8A	109.3	N4—C25—H25A	110.7
C7—C8—H8A	109.3	C26—C25—H25A	110.7
C9—C8—H8B	109.3	N4—C25—H25B	110.7
C7—C8—H8B	109.3	C26—C25—H25B	110.7
H8A—C8—H8B	108.0	H25A—C25—H25B	108.8
N4—C9—C10	109.5 (3)	C27—C26—C25	107.0 (4)
N4—C9—C8	112.0 (3)	C27—C26—H26A	110.3
C10—C9—C8	113.2 (3)	C25—C26—H26A	110.3
N4—C9—H9	107.3	C27—C26—H26B	110.3
C10—C9—H9	107.3	C25—C26—H26B	110.3
C8—C9—H9	107.3	H26A—C26—H26B	108.6
C15—C10—C11	119.2 (3)	C26—C27—C28	105.7 (4)
C15—C10—C9	121.1 (3)	C26—C27—H27A	110.6
C11—C10—C9	119.6 (3)	C28—C27—H27A	110.6
N2—C11—C12	119.9 (3)	C26—C27—H27B	110.6
N2—C11—C10	121.7 (3)	C28—C27—H27B	110.6
C12—C11—C10	118.4 (3)	H27A—C27—H27B	108.7
C13—C12—C11	121.2 (3)	O4—C28—N4	125.3 (4)
C13—C12—H12	119.4	O4—C28—C27	126.7 (4)
C11—C12—H12	119.4	N4—C28—C27	108.0 (4)
C12—C13—C14	120.2 (3)
C18—O3—N3—C16	−0.6 (4)	C12—C13—C14—C15	0.2 (6)
O2—N1—C1—C2	−174.9 (7)	C13—C14—C15—C10	−4.0 (6)
O1—N1—C1—C2	6.3 (8)	C13—C14—C15—C16	174.8 (4)
O2—N1—C1—C6	5.8 (9)	C11—C10—C15—C14	4.8 (5)
O1—N1—C1—C6	−173.0 (6)	C9—C10—C15—C14	−173.0 (3)
C6—C1—C2—C3	0.9 (8)	C11—C10—C15—C16	−174.0 (3)
N1—C1—C2—C3	−178.4 (5)	C9—C10—C15—C16	8.2 (5)
C1—C2—C3—C4	0.1 (8)	O3—N3—C16—C17	1.5 (4)
C2—C3—C4—C5	−1.0 (8)	O3—N3—C16—C15	−177.6 (3)
C2—C3—C4—C7	177.5 (5)	C14—C15—C16—N3	−103.9 (4)
C3—C4—C5—C6	1.1 (10)	C10—C15—C16—N3	74.9 (4)
C7—C4—C5—C6	−177.5 (6)	C14—C15—C16—C17	77.0 (5)
C2—C1—C6—C5	−0.8 (10)	C10—C15—C16—C17	−104.2 (5)
N1—C1—C6—C5	178.5 (6)	N3—C16—C17—C18	−1.9 (4)
C4—C5—C6—C1	−0.2 (11)	C15—C16—C17—C18	177.2 (4)
C11—N2—C7—C4	−177.3 (4)	C16—C17—C18—O3	1.4 (4)
C11—N2—C7—C8	−53.8 (5)	C16—C17—C18—C19	−176.3 (4)
C3—C4—C7—N2	29.5 (6)	N3—O3—C18—C17	−0.6 (4)
C5—C4—C7—N2	−152.0 (5)	N3—O3—C18—C19	177.6 (3)
C3—C4—C7—C8	−92.1 (5)	C17—C18—C19—C20	4.0 (6)
C5—C4—C7—C8	86.4 (6)	O3—C18—C19—C20	−173.6 (3)
N2—C7—C8—C9	59.0 (4)	C17—C18—C19—C24	−175.8 (5)
C4—C7—C8—C9	−176.8 (3)	O3—C18—C19—C24	6.6 (6)
C28—N4—C9—C10	−133.2 (3)	C24—C19—C20—C21	0.4 (6)
C25—N4—C9—C10	44.6 (5)	C18—C19—C20—C21	−179.4 (4)
C28—N4—C9—C8	100.4 (4)	C19—C20—C21—C22	0.6 (6)
C25—N4—C9—C8	−81.8 (5)	C20—C21—C22—C23	−1.7 (8)
C7—C8—C9—N4	85.5 (4)	C21—C22—C23—C24	1.9 (9)
C7—C8—C9—C10	−38.9 (4)	C20—C19—C24—C23	−0.2 (8)
N4—C9—C10—C15	63.8 (4)	C18—C19—C24—C23	179.5 (5)
C8—C9—C10—C15	−170.5 (3)	C22—C23—C24—C19	−0.9 (9)
N4—C9—C10—C11	−114.0 (4)	C28—N4—C25—C26	4.4 (6)
C8—C9—C10—C11	11.8 (5)	C9—N4—C25—C26	−173.5 (4)
C7—N2—C11—C12	−153.3 (4)	N4—C25—C26—C27	−8.6 (7)
C7—N2—C11—C10	27.5 (6)	C25—C26—C27—C28	9.5 (7)
C15—C10—C11—N2	177.3 (3)	C25—N4—C28—O4	−178.7 (4)
C9—C10—C11—N2	−4.9 (5)	C9—N4—C28—O4	−0.7 (6)
C15—C10—C11—C12	−1.9 (5)	C25—N4—C28—C27	1.6 (5)
C9—C10—C11—C12	175.9 (3)	C9—N4—C28—C27	179.6 (4)
N2—C11—C12—C13	179.0 (4)	C26—C27—C28—O4	173.3 (5)
C10—C11—C12—C13	−1.8 (6)	C26—C27—C28—N4	−7.0 (6)
C11—C12—C13—C14	2.7 (6)

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2N···O4^i	0.87 (3)	1.99 (3)	2.859 (6)	180 (5)

Symmetry code: (i) y, −x+y, z−1/6.