organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 67| Part 2| February 2011| Pages o308-o309

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

aInstituto de Quimica de Recursos Naturales, Universidad de Talca, Casilla 747, Talca, Chile, bDepartamento de Química, Facultad de Ciencias Básicas, Universidad de Antofagasta, Casilla 170, Antofagasta - Chile, and cInstituto de Bio-Orgánica 'Antonio González', Universidad de La Laguna, Astrofísico Francisco Sánchez N°2, La Laguna, Tenerife, Spain.
*Correspondence e-mail: ivanbritob@yahoo.com

(Received 20 December 2010; accepted 24 December 2010; online 8 January 2011)

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[Gutierrez, M., Vallejos, G., Fernández, C., Cárdenas, A. & Brito, I. (2011). Acta Cryst. E67, o175-o176.]). 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).

Related literature

For details of nitro­gen-containing heterocyclic compounds, see: Sankaran et al. (2010[Sankaran, M., Kumarasamy, C., Chokkalingam, U. & Mohan, P. S. (2010). Bioorg. Med. Chem. Lett. 20, 7147-7151.]) and for their pharmacological activity, see: Shi et al. (2008[Shi, A., Nguyen, T. A., Battina, K. S., Rana, S., Takemoto, J. D., Chiang, K. P. & Hua, D. (2008). Bioorg. Med. Chem. Lett. 18, 3364-3368.]); Lunniss et al. (2009[Lunniss, J. C., Cooper, W. J. A., Eldred, D. C., Kranz, M., Lindvall, M., Lucas, S. F., Neu, M., Preston, A., Ranshaw, E. L., Redgrave, J. A., Robinson, E. J., Shimpley, J. T., Solanke, E. Y., Somers, O. D. & Wiseman, O. J. (2009). Bioorg. Med. Chem. Lett. 19, 1380-1385.]); He et al. (2005[He, F.-J., Yun, L.-H., Yang, R.-F., Xiao, Z.-Y., Cheng, J.-P., Zhou, W.-X. & Zhang, Y.-X. (2005). Bioorg. Med. Chem. Lett. 15, 2980-2985.]); Eswaran et al. (2010[Eswaran, S., Adhikari, V. A., Pal, K. N. & Chowdhury, H. I. (2010). Bioorg. Med. Chem. 20, 1040-1044.]). For reactions of isoxazoles, see: Taldone et al. (2008[Taldone, T., Gozman, A., Maharaj, R. & Chiosis, G. (2008). Curr. Opin. Pharmacol. 8, 370-374.]); Narlawar et al. (2008[Narlawar, R., Pickhardt, M., Leuchtenberger, S., Baumann, K., Krause, S., Dyrks, T., Weggen, S., Mandelkow, E. & Schmidt, B. (2008). Chem. Med. Chem. 3, 165-172.]); Velaparthi et al. (2008[Velaparthi, S., Brunsteiner, M., Uddin, R., Wan, B., Franzblau, S. G. & Petukhov, P. A. (2008). J. Med. Chem. 51, 1999-2002.]); Rizzi et al. (2008[Rizzi, L., Dallanoce, C., Matera, C., Magrone, P., Pucci, L., Gotti, C., Clementi, F. & De Amici, M. (2008). Bioorg. Med. Chem. Lett. 18, 4651-4654.]); Lautens & Roy (2000[Lautens, M. & Roy, A. (2000). Org. Lett. 2, 555-557.]); Broggini et al. (2005[Broggini, G., Chiesa, K., De Marchi, I., Martinelli, M., Pilati, T. & Zecchi, G. (2005). Tetrahedron, 61, 3525-3531.]); Kotera et al. (1970[Kotera, K., Takano, Y., Matsuura, A. & Kitahonoki, K. (1970). Tetrahedron, 26, 539-556.]). For applications of compounds possessing the quinoline system as drugs and pharmaceuticals, see: Kalita et al. (2006[Kalita, P., Baruah, B. & Bhuyan, P. (2006). Tetrahedron Lett. 47, 7779-7782.]). For syntheses of quinolines, see: Kouznetsov et al. (2005[Kouznetsov, V. V., Vargas, L. Y. & Melendez, C. C. (2005). Curr. Org. Chem. 9, 141-161.]). For the trans diastereoisomer of the title compound, see: Gutierrez et al. (2011[Gutierrez, M., Vallejos, G., Fernández, C., Cárdenas, A. & Brito, I. (2011). Acta Cryst. E67, o175-o176.]). For graph-set motifs see: Bernstein et al. (1995[Bernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl. 34, 1555-1573.]) and for puckering parameters, see: Cremer & Pople (1975[Cremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354-1358.])

[Scheme 1]

Experimental

Crystal data
  • C28H24N4O4

  • Mr = 480.51

  • Hexagonal, P 61

  • a = 20.753 (3) Å

  • c = 10.446 (2) Å

  • V = 3896.2 (11) Å3

  • Z = 6

  • Mo Kα radiation

  • μ = 0.08 mm−1

  • T = 293 K

  • 0.20 × 0.20 × 0.18 mm

Data collection
  • Nonius KappaCCD area-detector diffractometer

  • 5951 measured reflections

  • 3144 independent reflections

  • 2646 reflections with I > 2σ(I)

  • Rint = 0.026

Refinement
  • R[F2 > 2σ(F2)] = 0.075

  • wR(F2) = 0.162

  • S = 1.22

  • 3144 reflections

  • 329 parameters

  • 1 restraint

  • H atoms treated by a mixture of independent and constrained refinement

  • Δρmax = 0.32 e Å−3

  • Δρmin = −0.24 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
N2—H2N⋯O4i 0.87 (3) 1.99 (3) 2.859 (6) 180 (5)
Symmetry code: (i) [y, -x+y, z-{\script{1\over 6}}].

Data collection: COLLECT (Nonius, 2000[Nonius (2000). COLLECT. Nonius BV, Delft, The Netherlands.]); cell refinement: DENZO-SMN (Otwinowski & Minor, 1997[Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307-326. New York; Academic Press.]); data reduction: DENZO-SMN; program(s) used to solve structure: SIR97 (Altomare et al., 1999[Altomare, A., Burla, M. C., Camalli, M., Cascarano, G. L., Giacovazzo, C., Guagliardi, A., Moliterni, A. G. G., Polidori, G. & Spagna, R. (1999). J. Appl. Cryst. 32, 115-119.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997[Farrugia, L. J. (1997). J. Appl. Cryst. 30, 565.]) and PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]); software used to prepare material for publication: WinGX (Farrugia, 1999[Farrugia, L. J. (1999). J. Appl. Cryst. 32, 837-838.]).

Supporting information


Comment top

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 (QT= 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 top

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)

Experimental top

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.

Refinement top

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 Å3 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 Uiso(H) = 1.2Ueq(C).

Computing details top

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 top
[Figure 1] Fig. 1. The structure of (I), showing the atom-numbering scheme. Displacement ellipsoids are plotted at the 30% probability level.
[Figure 2] 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.]
[Figure 3] 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 top
Crystal data top
C28H24N4O4Dx = 1.229 Mg m3
Mr = 480.51Mo Kα radiation, λ = 0.71073 Å
Hexagonal, P61Cell parameters from 2728 reflections
Hall symbol: P 61θ = 2.8–27.5°
a = 20.753 (3) ŵ = 0.08 mm1
c = 10.446 (2) ÅT = 293 K
V = 3896.2 (11) Å3Prismatic, orange
Z = 60.20 × 0.20 × 0.18 mm
F(000) = 1512
Data collection top
Nonius KappaCCD area-detector
diffractometer
2646 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.026
Graphite monochromatorθmax = 27.5°, θmin = 2.8°
ϕ scans, and ω scans with κ offsetsh = 220
5951 measured reflectionsk = 026
3144 independent reflectionsl = 1313
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.075Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.162H atoms treated by a mixture of independent and constrained refinement
S = 1.22 w = 1/[σ2(Fo2) + (0.0755P)2 + 0.8624P]
where P = (Fo2 + 2Fc2)/3
3144 reflections(Δ/σ)max = 0.010
329 parametersΔρmax = 0.32 e Å3
1 restraintΔρmin = 0.24 e Å3
Crystal data top
C28H24N4O4Z = 6
Mr = 480.51Mo Kα radiation
Hexagonal, P61µ = 0.08 mm1
a = 20.753 (3) ÅT = 293 K
c = 10.446 (2) Å0.20 × 0.20 × 0.18 mm
V = 3896.2 (11) Å3
Data collection top
Nonius KappaCCD area-detector
diffractometer
2646 reflections with I > 2σ(I)
5951 measured reflectionsRint = 0.026
3144 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0751 restraint
wR(F2) = 0.162H atoms treated by a mixture of independent and constrained refinement
S = 1.22Δρmax = 0.32 e Å3
3144 reflectionsΔρmin = 0.24 e Å3
329 parameters
Special details top

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 (Å2) top
xyzUiso*/Ueq
O10.2019 (3)0.0999 (3)0.6005 (5)0.1165 (18)
O20.1082 (3)0.1080 (3)0.5004 (7)0.147 (3)
O30.54683 (17)0.55998 (14)0.2252 (3)0.0485 (7)
O40.36115 (17)0.42435 (19)0.2789 (3)0.0607 (8)
N10.1743 (3)0.0784 (3)0.5205 (5)0.0880 (15)
N20.43438 (18)0.19821 (17)0.2011 (4)0.0456 (8)
N30.5569 (2)0.49764 (18)0.2257 (4)0.0492 (8)
N40.36641 (16)0.33963 (17)0.1463 (3)0.0388 (7)
C10.2234 (3)0.0115 (2)0.4445 (5)0.0631 (12)
C20.2982 (3)0.0205 (3)0.4559 (5)0.0637 (12)
H20.31860.00020.50980.076*
C30.3433 (2)0.0833 (2)0.3881 (5)0.0597 (12)
H30.39460.10500.39630.072*
C40.3145 (2)0.1154 (2)0.3075 (4)0.0489 (10)
C50.2376 (3)0.0806 (3)0.2964 (7)0.0855 (19)
H50.21680.10060.24160.103*
C60.1916 (3)0.0171 (3)0.3647 (7)0.091 (2)
H60.14010.00570.35680.109*
C70.3612 (2)0.1867 (2)0.2334 (5)0.0471 (9)
H70.33510.18390.15350.057*
C80.3719 (2)0.25488 (19)0.3085 (4)0.0404 (8)
H8A0.32370.24830.33100.048*
H8B0.39850.25910.38730.048*
C90.41529 (18)0.32633 (18)0.2308 (4)0.0337 (7)
H90.43780.36770.29180.040*
C100.47821 (18)0.32842 (19)0.1526 (4)0.0335 (7)
C110.4825 (2)0.26296 (19)0.1383 (4)0.0379 (8)
C120.5384 (2)0.2653 (2)0.0586 (4)0.0451 (10)
H120.54280.22310.05020.054*
C130.5865 (2)0.3290 (2)0.0069 (4)0.0499 (10)
H130.62170.32890.06180.060*
C140.5826 (2)0.3935 (2)0.0088 (4)0.0439 (9)
H140.61510.43650.03570.053*
C150.53053 (19)0.39350 (19)0.0906 (4)0.0345 (8)
C160.53036 (18)0.46432 (19)0.1164 (4)0.0355 (8)
C170.5044 (2)0.5032 (2)0.0404 (4)0.0393 (8)
H170.48440.49140.04170.047*
C180.51507 (19)0.56076 (19)0.1134 (4)0.0374 (8)
C190.4969 (2)0.6206 (2)0.0963 (4)0.0401 (8)
C200.4578 (2)0.6207 (2)0.0102 (4)0.0456 (9)
H200.44250.58280.07040.055*
C210.4409 (2)0.6770 (3)0.0284 (5)0.0552 (11)
H210.41410.67670.09990.066*
C220.4643 (3)0.7329 (3)0.0603 (6)0.0655 (14)
H220.45440.77140.04760.079*
C230.5015 (4)0.7325 (3)0.1657 (6)0.0790 (17)
H230.51570.77010.22620.095*
C240.5191 (3)0.6767 (3)0.1855 (5)0.0671 (14)
H240.54540.67730.25790.080*
C250.3392 (3)0.3060 (3)0.0210 (5)0.0674 (14)
H25A0.30530.25290.02900.081*
H25B0.38020.31410.03410.081*
C260.2998 (3)0.3441 (4)0.0316 (6)0.0799 (16)
H26A0.32710.37530.10380.096*
H26B0.25030.30760.06020.096*
C270.2955 (3)0.3900 (3)0.0734 (5)0.0704 (14)
H27A0.24460.36940.10280.085*
H27B0.31350.44070.04460.085*
C280.3444 (2)0.3884 (2)0.1797 (4)0.0474 (10)
H2N0.4315 (16)0.1573 (18)0.174 (3)0.017 (8)*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.113 (4)0.106 (3)0.110 (4)0.039 (3)0.008 (3)0.058 (3)
O20.088 (3)0.109 (4)0.173 (6)0.005 (3)0.006 (4)0.069 (4)
O30.0723 (18)0.0384 (13)0.0401 (15)0.0317 (13)0.0135 (14)0.0066 (12)
O40.0657 (18)0.086 (2)0.0577 (19)0.0587 (18)0.0052 (16)0.0198 (18)
N10.079 (3)0.063 (3)0.090 (4)0.011 (2)0.004 (3)0.018 (3)
N20.0506 (18)0.0267 (15)0.062 (2)0.0212 (14)0.0040 (17)0.0034 (15)
N30.067 (2)0.0429 (17)0.0464 (19)0.0341 (16)0.0109 (18)0.0027 (16)
N40.0363 (15)0.0475 (16)0.0394 (17)0.0262 (14)0.0005 (14)0.0013 (14)
C10.066 (3)0.040 (2)0.064 (3)0.012 (2)0.001 (2)0.007 (2)
C20.070 (3)0.061 (3)0.063 (3)0.035 (2)0.004 (3)0.016 (2)
C30.052 (2)0.057 (2)0.068 (3)0.026 (2)0.002 (2)0.014 (2)
C40.046 (2)0.0338 (18)0.058 (3)0.0127 (16)0.001 (2)0.0012 (19)
C50.059 (3)0.070 (3)0.111 (5)0.020 (2)0.008 (3)0.038 (4)
C60.056 (3)0.068 (3)0.117 (5)0.008 (3)0.013 (3)0.029 (4)
C70.046 (2)0.0363 (19)0.055 (2)0.0175 (16)0.0023 (19)0.0047 (18)
C80.0396 (18)0.0416 (19)0.043 (2)0.0225 (16)0.0057 (17)0.0045 (17)
C90.0337 (16)0.0332 (17)0.0379 (18)0.0194 (14)0.0005 (15)0.0010 (15)
C100.0337 (17)0.0359 (17)0.0354 (18)0.0207 (15)0.0041 (15)0.0050 (15)
C110.0400 (18)0.0380 (18)0.044 (2)0.0260 (16)0.0081 (17)0.0073 (17)
C120.042 (2)0.044 (2)0.059 (3)0.0297 (18)0.007 (2)0.016 (2)
C130.0383 (19)0.059 (2)0.056 (3)0.0276 (19)0.008 (2)0.012 (2)
C140.0369 (18)0.043 (2)0.050 (2)0.0181 (16)0.0077 (18)0.0001 (19)
C150.0344 (17)0.0341 (17)0.0376 (18)0.0192 (14)0.0063 (15)0.0017 (15)
C160.0317 (17)0.0348 (17)0.0365 (19)0.0139 (14)0.0064 (15)0.0058 (15)
C170.0493 (19)0.0404 (18)0.0315 (19)0.0249 (16)0.0008 (16)0.0012 (16)
C180.0385 (18)0.0345 (18)0.0376 (19)0.0170 (15)0.0034 (16)0.0050 (15)
C190.047 (2)0.0351 (18)0.042 (2)0.0236 (16)0.0096 (17)0.0055 (16)
C200.053 (2)0.047 (2)0.041 (2)0.0287 (19)0.0041 (19)0.0014 (18)
C210.065 (3)0.063 (3)0.053 (2)0.044 (2)0.002 (2)0.010 (2)
C220.093 (4)0.055 (3)0.070 (3)0.053 (3)0.012 (3)0.010 (3)
C230.120 (5)0.063 (3)0.076 (4)0.061 (3)0.020 (4)0.025 (3)
C240.101 (4)0.057 (3)0.059 (3)0.051 (3)0.025 (3)0.017 (2)
C250.078 (3)0.086 (3)0.058 (3)0.055 (3)0.024 (3)0.020 (3)
C260.083 (4)0.119 (5)0.059 (3)0.067 (4)0.022 (3)0.011 (3)
C270.075 (3)0.096 (4)0.069 (3)0.064 (3)0.008 (3)0.000 (3)
C280.042 (2)0.062 (2)0.051 (2)0.035 (2)0.0038 (19)0.005 (2)
Geometric parameters (Å, º) top
O1—N11.217 (6)C11—C121.409 (6)
O2—N11.209 (7)C12—C131.375 (6)
O3—C181.344 (5)C12—H120.9300
O3—N31.410 (4)C13—C141.390 (6)
O4—C281.221 (5)C13—H130.9300
N1—C11.477 (6)C14—C151.378 (5)
N2—C111.375 (5)C14—H140.9300
N2—C71.454 (5)C15—C161.496 (5)
N2—H2N0.87 (3)C16—C171.416 (5)
N3—C161.306 (5)C17—C181.339 (5)
N4—C281.349 (5)C17—H170.9300
N4—C251.457 (6)C18—C191.477 (5)
N4—C91.472 (4)C19—C201.378 (6)
C1—C21.353 (7)C19—C241.379 (6)
C1—C61.370 (7)C20—C211.390 (6)
C2—C31.362 (6)C20—H200.9300
C2—H20.9300C21—C221.370 (7)
C3—C41.381 (6)C21—H210.9300
C3—H30.9300C22—C231.346 (8)
C4—C51.389 (6)C22—H220.9300
C4—C71.514 (6)C23—C241.394 (7)
C5—C61.378 (8)C23—H230.9300
C5—H50.9300C24—H240.9300
C6—H60.9300C25—C261.497 (7)
C7—C81.534 (5)C25—H25A0.9700
C7—H70.9800C25—H25B0.9700
C8—C91.527 (5)C26—C271.486 (8)
C8—H8A0.9700C26—H26A0.9700
C8—H8B0.9700C26—H26B0.9700
C9—C101.523 (5)C27—C281.515 (7)
C9—H90.9800C27—H27A0.9700
C10—C151.398 (5)C27—H27B0.9700
C10—C111.413 (5)
C18—O3—N3108.2 (3)C12—C13—H13119.9
O2—N1—O1123.8 (5)C14—C13—H13119.9
O2—N1—C1117.2 (5)C15—C14—C13119.8 (4)
O1—N1—C1119.0 (5)C15—C14—H14120.1
C11—N2—C7117.3 (3)C13—C14—H14120.1
C11—N2—H2N117 (2)C14—C15—C10121.1 (3)
C7—N2—H2N111.2 (19)C14—C15—C16119.9 (3)
C16—N3—O3105.4 (3)C10—C15—C16118.9 (3)
C28—N4—C25113.3 (3)N3—C16—C17111.6 (3)
C28—N4—C9120.7 (3)N3—C16—C15118.0 (3)
C25—N4—C9126.0 (3)C17—C16—C15130.4 (3)
C2—C1—C6121.6 (4)C18—C17—C16104.4 (3)
C2—C1—N1119.8 (5)C18—C17—H17127.8
C6—C1—N1118.6 (5)C16—C17—H17127.8
C1—C2—C3119.6 (5)C17—C18—O3110.3 (3)
C1—C2—H2120.2C17—C18—C19133.0 (4)
C3—C2—H2120.2O3—C18—C19116.6 (3)
C2—C3—C4121.5 (4)C20—C19—C24119.5 (4)
C2—C3—H3119.3C20—C19—C18119.9 (4)
C4—C3—H3119.3C24—C19—C18120.7 (4)
C3—C4—C5117.5 (4)C19—C20—C21120.5 (4)
C3—C4—C7124.3 (4)C19—C20—H20119.7
C5—C4—C7118.2 (4)C21—C20—H20119.7
C6—C5—C4121.4 (5)C22—C21—C20119.2 (4)
C6—C5—H5119.3C22—C21—H21120.4
C4—C5—H5119.3C20—C21—H21120.4
C1—C6—C5118.4 (5)C23—C22—C21120.6 (4)
C1—C6—H6120.8C23—C22—H22119.7
C5—C6—H6120.8C21—C22—H22119.7
N2—C7—C4112.6 (3)C22—C23—C24121.0 (5)
N2—C7—C8108.0 (3)C22—C23—H23119.5
C4—C7—C8111.5 (4)C24—C23—H23119.5
N2—C7—H7108.2C19—C24—C23119.1 (5)
C4—C7—H7108.2C19—C24—H24120.4
C8—C7—H7108.2C23—C24—H24120.4
C9—C8—C7111.5 (3)N4—C25—C26105.1 (4)
C9—C8—H8A109.3N4—C25—H25A110.7
C7—C8—H8A109.3C26—C25—H25A110.7
C9—C8—H8B109.3N4—C25—H25B110.7
C7—C8—H8B109.3C26—C25—H25B110.7
H8A—C8—H8B108.0H25A—C25—H25B108.8
N4—C9—C10109.5 (3)C27—C26—C25107.0 (4)
N4—C9—C8112.0 (3)C27—C26—H26A110.3
C10—C9—C8113.2 (3)C25—C26—H26A110.3
N4—C9—H9107.3C27—C26—H26B110.3
C10—C9—H9107.3C25—C26—H26B110.3
C8—C9—H9107.3H26A—C26—H26B108.6
C15—C10—C11119.2 (3)C26—C27—C28105.7 (4)
C15—C10—C9121.1 (3)C26—C27—H27A110.6
C11—C10—C9119.6 (3)C28—C27—H27A110.6
N2—C11—C12119.9 (3)C26—C27—H27B110.6
N2—C11—C10121.7 (3)C28—C27—H27B110.6
C12—C11—C10118.4 (3)H27A—C27—H27B108.7
C13—C12—C11121.2 (3)O4—C28—N4125.3 (4)
C13—C12—H12119.4O4—C28—C27126.7 (4)
C11—C12—H12119.4N4—C28—C27108.0 (4)
C12—C13—C14120.2 (3)
C18—O3—N3—C160.6 (4)C12—C13—C14—C150.2 (6)
O2—N1—C1—C2174.9 (7)C13—C14—C15—C104.0 (6)
O1—N1—C1—C26.3 (8)C13—C14—C15—C16174.8 (4)
O2—N1—C1—C65.8 (9)C11—C10—C15—C144.8 (5)
O1—N1—C1—C6173.0 (6)C9—C10—C15—C14173.0 (3)
C6—C1—C2—C30.9 (8)C11—C10—C15—C16174.0 (3)
N1—C1—C2—C3178.4 (5)C9—C10—C15—C168.2 (5)
C1—C2—C3—C40.1 (8)O3—N3—C16—C171.5 (4)
C2—C3—C4—C51.0 (8)O3—N3—C16—C15177.6 (3)
C2—C3—C4—C7177.5 (5)C14—C15—C16—N3103.9 (4)
C3—C4—C5—C61.1 (10)C10—C15—C16—N374.9 (4)
C7—C4—C5—C6177.5 (6)C14—C15—C16—C1777.0 (5)
C2—C1—C6—C50.8 (10)C10—C15—C16—C17104.2 (5)
N1—C1—C6—C5178.5 (6)N3—C16—C17—C181.9 (4)
C4—C5—C6—C10.2 (11)C15—C16—C17—C18177.2 (4)
C11—N2—C7—C4177.3 (4)C16—C17—C18—O31.4 (4)
C11—N2—C7—C853.8 (5)C16—C17—C18—C19176.3 (4)
C3—C4—C7—N229.5 (6)N3—O3—C18—C170.6 (4)
C5—C4—C7—N2152.0 (5)N3—O3—C18—C19177.6 (3)
C3—C4—C7—C892.1 (5)C17—C18—C19—C204.0 (6)
C5—C4—C7—C886.4 (6)O3—C18—C19—C20173.6 (3)
N2—C7—C8—C959.0 (4)C17—C18—C19—C24175.8 (5)
C4—C7—C8—C9176.8 (3)O3—C18—C19—C246.6 (6)
C28—N4—C9—C10133.2 (3)C24—C19—C20—C210.4 (6)
C25—N4—C9—C1044.6 (5)C18—C19—C20—C21179.4 (4)
C28—N4—C9—C8100.4 (4)C19—C20—C21—C220.6 (6)
C25—N4—C9—C881.8 (5)C20—C21—C22—C231.7 (8)
C7—C8—C9—N485.5 (4)C21—C22—C23—C241.9 (9)
C7—C8—C9—C1038.9 (4)C20—C19—C24—C230.2 (8)
N4—C9—C10—C1563.8 (4)C18—C19—C24—C23179.5 (5)
C8—C9—C10—C15170.5 (3)C22—C23—C24—C190.9 (9)
N4—C9—C10—C11114.0 (4)C28—N4—C25—C264.4 (6)
C8—C9—C10—C1111.8 (5)C9—N4—C25—C26173.5 (4)
C7—N2—C11—C12153.3 (4)N4—C25—C26—C278.6 (7)
C7—N2—C11—C1027.5 (6)C25—C26—C27—C289.5 (7)
C15—C10—C11—N2177.3 (3)C25—N4—C28—O4178.7 (4)
C9—C10—C11—N24.9 (5)C9—N4—C28—O40.7 (6)
C15—C10—C11—C121.9 (5)C25—N4—C28—C271.6 (5)
C9—C10—C11—C12175.9 (3)C9—N4—C28—C27179.6 (4)
N2—C11—C12—C13179.0 (4)C26—C27—C28—O4173.3 (5)
C10—C11—C12—C131.8 (6)C26—C27—C28—N47.0 (6)
C11—C12—C13—C142.7 (6)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N2—H2N···O4i0.87 (3)1.99 (3)2.859 (6)180 (5)
Symmetry code: (i) y, x+y, z1/6.

Experimental details

Crystal data
Chemical formulaC28H24N4O4
Mr480.51
Crystal system, space groupHexagonal, P61
Temperature (K)293
a, c (Å)20.753 (3), 10.446 (2)
V3)3896.2 (11)
Z6
Radiation typeMo Kα
µ (mm1)0.08
Crystal size (mm)0.20 × 0.20 × 0.18
Data collection
DiffractometerNonius KappaCCD area-detector
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
5951, 3144, 2646
Rint0.026
(sin θ/λ)max1)0.649
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.075, 0.162, 1.22
No. of reflections3144
No. of parameters329
No. of restraints1
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.32, 0.24

Computer programs: COLLECT (Nonius, 2000), DENZO-SMN (Otwinowski & Minor, 1997), SIR97 (Altomare et al., 1999), SHELXL97 (Sheldrick, 2008), ORTEP-3 for Windows (Farrugia, 1997) & PLATON (Spek, 2009), WinGX (Farrugia, 1999).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N2—H2N···O4i0.87 (3)1.99 (3)2.859 (6)180 (5)
Symmetry code: (i) y, x+y, z1/6.
 

Acknowledgements

LAS thanks FONDECYT (project No. 1100481) and PBCT ADI-38. We also thank the Spanish Research Council (CSIC) for providing us with a free-of-charge licence for the CSD system.

References

First citationAltomare, A., Burla, M. C., Camalli, M., Cascarano, G. L., Giacovazzo, C., Guagliardi, A., Moliterni, A. G. G., Polidori, G. & Spagna, R. (1999). J. Appl. Cryst. 32, 115–119.  Web of Science CrossRef CAS IUCr Journals
First citationBernstein, J., Davis, R. E., Shimoni, L. & Chang, N.-L. (1995). Angew. Chem. Int. Ed. Engl. 34, 1555–1573.  CrossRef CAS Web of Science
First citationBroggini, G., Chiesa, K., De Marchi, I., Martinelli, M., Pilati, T. & Zecchi, G. (2005). Tetrahedron, 61, 3525–3531.  Web of Science CSD CrossRef CAS
First citationCremer, D. & Pople, J. A. (1975). J. Am. Chem. Soc. 97, 1354–1358.  CrossRef CAS Web of Science
First citationEswaran, S., Adhikari, V. A., Pal, K. N. & Chowdhury, H. I. (2010). Bioorg. Med. Chem. 20, 1040–1044.  CrossRef CAS
First citationFarrugia, L. J. (1997). J. Appl. Cryst. 30, 565.  CrossRef IUCr Journals
First citationFarrugia, L. J. (1999). J. Appl. Cryst. 32, 837–838.  CrossRef CAS IUCr Journals
First citationGutierrez, M., Vallejos, G., Fernández, C., Cárdenas, A. & Brito, I. (2011). Acta Cryst. E67, o175–o176.  Web of Science CrossRef IUCr Journals
First citationHe, F.-J., Yun, L.-H., Yang, R.-F., Xiao, Z.-Y., Cheng, J.-P., Zhou, W.-X. & Zhang, Y.-X. (2005). Bioorg. Med. Chem. Lett. 15, 2980–2985.  Web of Science CrossRef PubMed CAS
First citationKalita, P., Baruah, B. & Bhuyan, P. (2006). Tetrahedron Lett. 47, 7779–7782.  Web of Science CrossRef CAS
First citationKotera, K., Takano, Y., Matsuura, A. & Kitahonoki, K. (1970). Tetrahedron, 26, 539–556.  CrossRef CAS
First citationKouznetsov, V. V., Vargas, L. Y. & Melendez, C. C. (2005). Curr. Org. Chem. 9, 141–161.  Web of Science CrossRef CAS
First citationLautens, M. & Roy, A. (2000). Org. Lett. 2, 555–557.  Web of Science CrossRef PubMed CAS
First citationLunniss, J. C., Cooper, W. J. A., Eldred, D. C., Kranz, M., Lindvall, M., Lucas, S. F., Neu, M., Preston, A., Ranshaw, E. L., Redgrave, J. A., Robinson, E. J., Shimpley, J. T., Solanke, E. Y., Somers, O. D. & Wiseman, O. J. (2009). Bioorg. Med. Chem. Lett. 19, 1380–1385.  Web of Science CrossRef PubMed CAS
First citationNarlawar, R., Pickhardt, M., Leuchtenberger, S., Baumann, K., Krause, S., Dyrks, T., Weggen, S., Mandelkow, E. & Schmidt, B. (2008). Chem. Med. Chem. 3, 165–172.  Web of Science CrossRef PubMed CAS
First citationNonius (2000). COLLECT. Nonius BV, Delft, The Netherlands.
First citationOtwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307–326. New York; Academic Press.
First citationRizzi, L., Dallanoce, C., Matera, C., Magrone, P., Pucci, L., Gotti, C., Clementi, F. & De Amici, M. (2008). Bioorg. Med. Chem. Lett. 18, 4651–4654.  Web of Science CrossRef PubMed CAS
First citationSankaran, M., Kumarasamy, C., Chokkalingam, U. & Mohan, P. S. (2010). Bioorg. Med. Chem. Lett. 20, 7147–7151.  Web of Science CrossRef CAS PubMed
First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals
First citationShi, A., Nguyen, T. A., Battina, K. S., Rana, S., Takemoto, J. D., Chiang, K. P. & Hua, D. (2008). Bioorg. Med. Chem. Lett. 18, 3364–3368.  Web of Science CrossRef PubMed CAS
First citationSpek, A. L. (2009). Acta Cryst. D65, 148–155.  Web of Science CrossRef CAS IUCr Journals
First citationTaldone, T., Gozman, A., Maharaj, R. & Chiosis, G. (2008). Curr. Opin. Pharmacol. 8, 370–374.  Web of Science CrossRef PubMed CAS
First citationVelaparthi, S., Brunsteiner, M., Uddin, R., Wan, B., Franzblau, S. G. & Petukhov, P. A. (2008). J. Med. Chem. 51, 1999–2002.  Web of Science CrossRef PubMed CAS

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 67| Part 2| February 2011| Pages o308-o309
Follow Acta Cryst. E
Sign up for e-alerts
Follow Acta Cryst. on Twitter
Follow us on facebook
Sign up for RSS feeds