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

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 65| Part 1| January 2009| Pages o144-o145

Ethyl 4-{1-[(2,4-di­nitro­phen­yl)hydrazono]eth­yl}-5-(2-naphthyl­meth­oxy­meth­yl)isoxazole-3-carboxyl­ate

aCenter For Structural and Functional Neuroscience, Department of Biomedical & Pharmaceutical Sciences, University of Montana, Missoula, MT 59812, USA, and bDepartment of Chemistry, University of Idaho, Moscow, ID 83844-2343, USA
*Correspondence e-mail: nicholas.natale@umontana.edu

(Received 24 November 2008; accepted 9 December 2008; online 17 December 2008)

The title compound, C26H23N5O8, was prepared and its structure investigated to further develop a working hypothesis for the essential binding pharmacophore for ligands of the System Xc- transporter [Patel et al. (2004[Patel, S. A., Warren, B. A., Rhoderick, J. F. & Bridges, R. J. (2004). Neuropharmacology, 46, 273-284.]). Neuropharmacology, 46, 273–284]. The hydrazone group displays an E geometry and the isoxazole double bond and C=N group of the hydrazone are in an s-cis relationship. The secondary amino NH group forms an intra­molecular N—H⋯O hydrogen bond to a ring nitro group. There is a dihedral angle of 44.27 (5)° between the isoxazole plane and the hydrazone group plane.

Related literature

For a related structure, see: Burkhart et al. (1999[Burkhart, D. J., Vij, A. & Natale, N. R. (1999). J. Chem. Crystallogr. 29, 749-758.], 2001[Burkhart, D. J., Zhou, P., Blumenfeld, A., Twamley, B. & Natale, N. R. (2001). Tetrahedron, 57, 8039-8046.]). For general background, see: Davis et al. (1993[Davis, F. A., Reddy, R. T., Han, W. & Reddy, R. E. (1993). Pure Appl. Chem. 65, 633-640.]); Honore & Lauridsen (1980[Honore, T. & Lauridsen, J. (1980). Acta Chem. Scand. B, 34, 235-240.]); Krogsgaard-Larsen, Honore, Hansen, Curtis & Lodge (1980[Krogsgaard-Larsen, P., Honore, T., Hansen, J. J., Curtis, D. R. & Lodge, D. (1980). Nature (London), 284, 64-66.]); Natale et al. (2006[Natale, N. R., Magnusson, K. & Nelson, J. K. (2006). Curr. Top. Med. Chem. 6, 823-846.]); Patel et al. (2004[Patel, S. A., Warren, B. A., Rhoderick, J. F. & Bridges, R. J. (2004). Neuropharmacology, 46, 273-284.], 2006[Patel, S. A., Natale, N. R., Esslinger, C. S., Gajewski, M., Rhoderick, J. F., O'Brien, E., Gerdes, J. & Bridges, R. J. (2006). Soc. Neurosci. Abstr. 629.17/D66.]); Stables & Kupferberg (2008[Stables, J. P. & Kupferberg, H. J. (2008). www.ninds.nih.gov/funding/research/asp/addadd_review.pdf.]); Twamley et al. (2007[Twamley, B., Szabon-Watola, M., Sharma, S. & Natale, N. R. (2007). Acta Cryst. E63, o2258-o2260.]); Zhou & Natale (1998[Zhou, P. & Natale, N. R. (1998). Tetrahedron Lett. 39, 8249-8252.]).

[Scheme 1]

Experimental

Crystal data
  • C26H23N5O8

  • Mr = 533.49

  • Triclinic, [P \overline 1]

  • a = 7.0839 (6) Å

  • b = 12.176 (1) Å

  • c = 14.184 (2) Å

  • α = 90.581 (1)°

  • β = 95.925 (2)°

  • γ = 99.251 (2)°

  • V = 1200.7 (2) Å3

  • Z = 2

  • Mo Kα radiation

  • μ = 0.11 mm−1

  • T = 90 (2) K

  • 0.47 × 0.33 × 0.30 mm

Data collection
  • Bruker SMART APEX diffractometer

  • Absorption correction: multi-scan (SADABS; Bruker, 2007[Bruker (2007). SMART, SAINT-Plus and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]) Tmin = 0.949, Tmax = 0.971

  • 18560 measured reflections

  • 4357 independent reflections

  • 4009 reflections with I > 2σ(I)

  • Rint = 0.023

Refinement
  • R[F2 > 2σ(F2)] = 0.035

  • wR(F2) = 0.092

  • S = 1.02

  • 4357 reflections

  • 354 parameters

  • H-atom parameters constrained

  • Δρmax = 0.28 e Å−3

  • Δρmin = −0.23 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
N28—H28A⋯O37 0.88 1.96 2.6028 (14) 128

Data collection: SMART (Bruker, 2007[Bruker (2007). SMART, SAINT-Plus and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]); cell refinement: SAINT-Plus (Bruker, 2007[Bruker (2007). SMART, SAINT-Plus and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA.]); data reduction: SAINT-Plus; program(s) used to solve structure: XS in SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: XL in SHELXTL; molecular graphics: XP in SHELXTL; software used to prepare material for publication: publCIF (Westrip, 2009[Westrip, S. P. (2009). publCIF. In preparation.]).

Supporting information


Comment top

In the course of our continuing studies on the synthesis and structure activity relationships of analogs of AMPA (II) (see Figure 2; Krogsgaard-Larsen et al., 1980; Honore, & Lauridsen, 1980) for glutamate receptors and transporters (Natale et al., 2006), we have found that a simple isoxazole hydrazone (IIIb) (Burkhart et al., 1999) exhibited significant binding at the System Xc- transporter (SXc-) (Patel et al., 2004), and that this correlated with anticonvulsant activity in vivo (Stables & Kupferberg, 2008). Since the three dimensional structure of the SXc- is unsolved at this writing we have developed a preliminary pharmacophore model for ligand binding which indicates that lipophilic groups appear to be tolerated (Patel et al., 2006), which is also promising from the perspective of increasing the likelihood of delivering such ligands past the blood brain barrier. Therefore we carried out the synthesis of (Ia) and also examined its structure, see Figure 1. We had previously examined the structure of (IIIa), (see Figure 2) and found it adopted an s-trans-E geometry at the juncture between the isoxazole and the hydrazone double bond, respectively (Burkhart et al., 1999). The naphthyloxy analog (Ia) adopts a similar E-geometry at the C=N double bond, but an s-cis conformation at the C-4 bond between the isoxazole and the hydrazone. The observation that (Ib) exhibits no significant glutamate inhibition at SystemXc- represents a negative control in the Structure Activity Relationship. This raises interesting questions as to the relationship between conformation and geometry vis-a-vis biological effect, and this will be the subject of forthcoming manuscripts.

Related literature top

For related literature, see: Burkhart et al. (1999, 2001); Davis et al. (1993); Honore & Lauridsen (1980); Krogsgaard-Larsen, Honore, Hansen, Curtis & Lodge (1980); Natale et al. (2006); Patel et al. (2004, 2006); Stables & Kupferberg (2008); Twamley et al. (2007); Zhou & Natale (1998). It would be much more useful to readers if the "Related literature" section had some kind of simple sub-division, so that, instead of just "For related literature, see···" it said, for example, "For general background, see···. For related structures, see···.? etc. Please revise this section as indicated.

Experimental top

The title compound (Ia) was prepared from ethyl 5-methyl-4-(2,5,5-trimethyl-1,3-dioxan-2-yl)isoxazole-3-carboxylate (Zhou & Natale, 1998) via lateral metalation (Burkhart et al., 2001), and electrophilic quenching using the Davis oxaziridine (Davis et al., 1993), to the corresponding 5-methyl alcohol. This alcohol can also be prepared by bromination followed by nucleophilic substitution by water (Twamley et al., 2007). The title compound was obtained from the 5-methyl alcohol by Williamson ether synthesis, deprotection and hydrazone formation (Burkhart et al., 1999).

4-{1-[(2,4-Dinitro-phenyl)-hydrazono]-ethyl}-5-(naphthalen-2-ylmethoxymethyl)-\ isoxazole-3-carboxylic acid ethyl ester (Ia)

To a stirred solution of ethyl 5-(naphthalen-2-yl-methoxymethyl)-4-acetyl-isoxazole-3-carboxylate (0.650 g, 1.93 mmol), in 10 ml of THF, a solution of 12 ml (1.0 eq.) of reagent 2,4-DNP was added and the reaction mixture was monitored by TLC (ether/hexane as a mobile phase). During reaction the reddish precipitate formed which was separated and purified by column chromatography. The fast moving, major isomer was examined by crystallography. Yield 57% The major isomer, yellow crystals, m.p.= 105–107 °C, 1H NMR (deuteriochloroform): δ 1.45 (t, 3H, J=7.1 Hz), 2.34 (s, 3H), 4.48 (q, 2H, J=7.1 Hz), 4.77 (s, 2H), 4.83 (s, 2H), 7.42 (m, 3H), 7.56 (d, 1H, J=9.5 Hz), 7.80 (m, 4H), 8.03 (dd, 1H, J=2.4, 9.5 Hz), 9.00 (d, 1H, J=2.6 Hz), 9.99 (brs, 1H, NH). 13C NMR (500 MHz) δ 14.1, 17.3, 60.6, 62.7, 73.1, 116.0, 118.3, 123.2, 125.4, 126.3, 126.4, 127.0, 127.5, 127.6, 128.4, 129.8, 132.9, 133.0, 134.1, 138.6, 143.8, 144.2, 154.1, 159.8, 168.8. The minor isomer, 1H NMR (deuteriochloroform):δ 1.40 (t, 3H, J=7.1 Hz), 2.43 (s, 3H), 4.46 (q, 2H, J=7.1 Hz), 4.80 (s, 2H), 4.93 (s, 2H), 7.22 (d, 1H, J=9.5 Hz), 7.42 (m, 3H), 7.80 (m, 4H), 8.03 (dd, 1H, J=2.4, 9.5 Hz), 8.65 (d, 1H, J=2.6 Hz), 10.75 (brs, 1H, NH).

Refinement top

All other H atoms were positioned geometrically and refined using a riding model, with Uiso constrained to be 1.2Ueq (CHarom, CH2 = 0.95–0.99 Å) and 1.5Ueq (CH3 = 0.98Å) of the carrier atom.

Computing details top

Data collection: SMART (Bruker, 2007); cell refinement: SAINT-Plus (Bruker, 2007); data reduction: SAINT-Plus (Bruker, 2007); program(s) used to solve structure: XS in SHELXTL (Sheldrick, 2008); program(s) used to refine structure: XL in SHELXTL (Sheldrick, 2008); molecular graphics: XP in SHELXTL (Sheldrick, 2008); software used to prepare material for publication: publCIF (Westrip, 2009).

Figures top
[Figure 1] Fig. 1. Molecular Structure of (Ia), showing 30% probablility displacement ellipsoids.
[Figure 2] Fig. 2. Structure of the title Compound (Ia), corresponding carboxylic acid (Ib), the neurotransmitter AMPA (II), and previously reported simple analog (III).
Ethyl 4-{1-[(2,4-dinitrophenyl)hydrazono]ethyl}- 5-(2-naphthylmethoxymethyl)isoxazole-3-carboxylate top
Crystal data top
C26H23N5O8Z = 2
Mr = 533.49F(000) = 556
Triclinic, P1Dx = 1.476 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 7.0839 (6) ÅCell parameters from 6135 reflections
b = 12.176 (1) Åθ = 2.3–30.1°
c = 14.184 (2) ŵ = 0.11 mm1
α = 90.581 (1)°T = 90 K
β = 95.925 (2)°Needle, yellow
γ = 99.251 (2)°0.47 × 0.33 × 0.30 mm
V = 1200.7 (2) Å3
Data collection top
Bruker SMART APEX
diffractometer
4357 independent reflections
Radiation source: normal-focus sealed tube4009 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.023
Detector resolution: 8.3 pixels mm-1θmax = 25.3°, θmin = 2.2°
ω scansh = 88
Absorption correction: multi-scan
(SADABS; Bruker, 2007)
k = 1414
Tmin = 0.949, Tmax = 0.971l = 1717
18560 measured reflections
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)] = 0.035Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.092H-atom parameters constrained
S = 1.02 w = 1/[σ2(Fo2) + (0.0462P)2 + 0.5022P]
where P = (Fo2 + 2Fc2)/3
4357 reflections(Δ/σ)max < 0.001
354 parametersΔρmax = 0.28 e Å3
0 restraintsΔρmin = 0.23 e Å3
Crystal data top
C26H23N5O8γ = 99.251 (2)°
Mr = 533.49V = 1200.7 (2) Å3
Triclinic, P1Z = 2
a = 7.0839 (6) ÅMo Kα radiation
b = 12.176 (1) ŵ = 0.11 mm1
c = 14.184 (2) ÅT = 90 K
α = 90.581 (1)°0.47 × 0.33 × 0.30 mm
β = 95.925 (2)°
Data collection top
Bruker SMART APEX
diffractometer
4357 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2007)
4009 reflections with I > 2σ(I)
Tmin = 0.949, Tmax = 0.971Rint = 0.023
18560 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0350 restraints
wR(F2) = 0.092H-atom parameters constrained
S = 1.02Δρmax = 0.28 e Å3
4357 reflectionsΔρmin = 0.23 e Å3
354 parameters
Special details top

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'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 > σ(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
C10.86385 (19)0.87869 (12)0.65591 (10)0.0225 (3)
H1A0.84040.95310.64980.027*
C20.9219 (2)0.84176 (12)0.74301 (10)0.0243 (3)
H2A0.93960.89100.79670.029*
C30.95619 (18)0.73084 (12)0.75441 (10)0.0223 (3)
C41.0160 (2)0.68877 (14)0.84368 (10)0.0279 (3)
H4A1.03620.73630.89850.034*
C51.0451 (2)0.58036 (14)0.85179 (11)0.0300 (4)
H5A1.08350.55320.91210.036*
C61.01822 (19)0.50944 (13)0.77116 (11)0.0272 (3)
H6A1.03910.43460.77720.033*
C70.96224 (19)0.54760 (12)0.68412 (10)0.0230 (3)
H7A0.94570.49900.63010.028*
C80.92856 (18)0.65841 (11)0.67329 (10)0.0199 (3)
C90.86964 (18)0.69966 (11)0.58372 (9)0.0186 (3)
H9A0.85170.65170.52920.022*
C100.83807 (18)0.80712 (11)0.57424 (9)0.0187 (3)
C120.78057 (19)0.85335 (11)0.47991 (9)0.0199 (3)
H12A0.66160.88570.48270.024*
H12B0.88350.91300.46360.024*
O130.74889 (14)0.76632 (8)0.40973 (7)0.0234 (2)
C140.7541 (2)0.80387 (11)0.31558 (9)0.0210 (3)
H14A0.80400.74870.27720.025*
H14B0.84460.87490.31620.025*
C150.56224 (19)0.82104 (11)0.26945 (9)0.0183 (3)
O160.50754 (14)0.92145 (7)0.28170 (7)0.0218 (2)
N170.32990 (17)0.92234 (9)0.22939 (8)0.0214 (3)
C180.28435 (19)0.82377 (11)0.18738 (9)0.0178 (3)
C190.09928 (19)0.79318 (11)0.12615 (9)0.0183 (3)
O200.04690 (14)0.70128 (8)0.09134 (7)0.0255 (2)
O210.00088 (13)0.87728 (8)0.11528 (7)0.0221 (2)
C220.1807 (2)0.85128 (12)0.05412 (10)0.0248 (3)
H22A0.26440.78760.07920.030*
H22B0.15610.83100.01070.030*
C230.2763 (2)0.95228 (13)0.05216 (11)0.0303 (3)
H23A0.39830.93710.01120.045*
H23B0.19221.01480.02740.045*
H23C0.30120.97120.11660.045*
C240.42658 (18)0.75465 (11)0.21070 (9)0.0166 (3)
C250.43276 (18)0.63811 (11)0.18367 (9)0.0163 (3)
C260.4029 (2)0.59917 (11)0.08182 (9)0.0211 (3)
H26A0.29370.53810.07270.032*
H26B0.51900.57310.06470.032*
H26C0.37630.66090.04140.032*
N270.47840 (15)0.57795 (9)0.25405 (8)0.0166 (2)
N280.49202 (15)0.47000 (9)0.23163 (8)0.0169 (2)
H28A0.46520.44440.17270.020*
C290.54745 (17)0.40296 (10)0.30165 (9)0.0159 (3)
C300.56433 (18)0.29033 (10)0.28470 (9)0.0165 (3)
C310.62357 (18)0.22374 (11)0.35731 (10)0.0179 (3)
H31A0.63350.14820.34490.022*
C320.66733 (18)0.26928 (11)0.44716 (9)0.0184 (3)
C330.65367 (18)0.37992 (11)0.46714 (9)0.0186 (3)
H33A0.68440.40960.53010.022*
C340.59579 (18)0.44555 (11)0.39560 (9)0.0180 (3)
H34A0.58800.52110.40930.022*
N350.52605 (15)0.23912 (9)0.19029 (8)0.0186 (2)
O360.56216 (15)0.14538 (8)0.17852 (7)0.0263 (2)
O370.45844 (14)0.29207 (8)0.12397 (7)0.0222 (2)
N380.73724 (16)0.20206 (10)0.52367 (8)0.0215 (3)
O390.79957 (15)0.24887 (9)0.60029 (7)0.0288 (2)
O400.73174 (15)0.10215 (8)0.50788 (8)0.0292 (2)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0195 (7)0.0215 (7)0.0262 (7)0.0015 (5)0.0036 (6)0.0018 (6)
C20.0201 (7)0.0306 (8)0.0208 (7)0.0002 (6)0.0033 (5)0.0071 (6)
C30.0130 (6)0.0332 (8)0.0198 (7)0.0001 (6)0.0033 (5)0.0021 (6)
C40.0183 (7)0.0457 (9)0.0186 (7)0.0014 (6)0.0022 (5)0.0002 (6)
C50.0185 (7)0.0494 (10)0.0221 (7)0.0044 (6)0.0019 (6)0.0141 (7)
C60.0163 (7)0.0330 (8)0.0320 (8)0.0026 (6)0.0029 (6)0.0116 (6)
C70.0156 (6)0.0273 (7)0.0248 (7)0.0000 (5)0.0016 (5)0.0037 (6)
C80.0116 (6)0.0263 (7)0.0208 (7)0.0010 (5)0.0031 (5)0.0029 (5)
C90.0140 (6)0.0234 (7)0.0176 (7)0.0002 (5)0.0014 (5)0.0011 (5)
C100.0130 (6)0.0222 (7)0.0202 (7)0.0005 (5)0.0025 (5)0.0010 (5)
C120.0189 (6)0.0181 (7)0.0223 (7)0.0024 (5)0.0014 (5)0.0008 (5)
O130.0318 (5)0.0187 (5)0.0175 (5)0.0021 (4)0.0043 (4)0.0013 (4)
C140.0244 (7)0.0205 (7)0.0175 (7)0.0031 (5)0.0002 (5)0.0025 (5)
C150.0250 (7)0.0154 (6)0.0149 (6)0.0035 (5)0.0036 (5)0.0027 (5)
O160.0270 (5)0.0169 (5)0.0208 (5)0.0048 (4)0.0026 (4)0.0004 (4)
N170.0248 (6)0.0205 (6)0.0196 (6)0.0067 (5)0.0001 (5)0.0032 (5)
C180.0223 (7)0.0170 (6)0.0150 (6)0.0048 (5)0.0041 (5)0.0037 (5)
C190.0217 (7)0.0186 (7)0.0164 (6)0.0064 (5)0.0058 (5)0.0046 (5)
O200.0271 (5)0.0202 (5)0.0287 (6)0.0057 (4)0.0028 (4)0.0007 (4)
O210.0218 (5)0.0216 (5)0.0240 (5)0.0083 (4)0.0007 (4)0.0012 (4)
C220.0199 (7)0.0309 (8)0.0244 (7)0.0089 (6)0.0012 (6)0.0018 (6)
C230.0261 (8)0.0322 (8)0.0344 (8)0.0122 (6)0.0006 (6)0.0043 (7)
C240.0199 (6)0.0172 (6)0.0137 (6)0.0043 (5)0.0035 (5)0.0038 (5)
C250.0141 (6)0.0173 (6)0.0180 (6)0.0035 (5)0.0018 (5)0.0013 (5)
C260.0260 (7)0.0192 (7)0.0187 (7)0.0058 (5)0.0020 (5)0.0011 (5)
N270.0159 (5)0.0141 (5)0.0204 (6)0.0037 (4)0.0018 (4)0.0004 (4)
N280.0208 (6)0.0149 (5)0.0151 (5)0.0043 (4)0.0008 (4)0.0001 (4)
C290.0118 (6)0.0169 (6)0.0192 (6)0.0019 (5)0.0035 (5)0.0019 (5)
C300.0139 (6)0.0165 (6)0.0188 (7)0.0008 (5)0.0031 (5)0.0003 (5)
C310.0145 (6)0.0158 (6)0.0243 (7)0.0027 (5)0.0052 (5)0.0027 (5)
C320.0138 (6)0.0218 (7)0.0203 (7)0.0033 (5)0.0037 (5)0.0065 (5)
C330.0164 (6)0.0225 (7)0.0170 (7)0.0034 (5)0.0022 (5)0.0003 (5)
C340.0177 (6)0.0165 (6)0.0204 (7)0.0036 (5)0.0032 (5)0.0004 (5)
N350.0179 (6)0.0166 (6)0.0212 (6)0.0014 (4)0.0036 (4)0.0005 (4)
O360.0373 (6)0.0150 (5)0.0275 (5)0.0073 (4)0.0038 (4)0.0032 (4)
O370.0275 (5)0.0214 (5)0.0176 (5)0.0058 (4)0.0010 (4)0.0007 (4)
N380.0183 (6)0.0251 (6)0.0230 (6)0.0066 (5)0.0058 (5)0.0078 (5)
O390.0328 (6)0.0356 (6)0.0190 (5)0.0098 (5)0.0001 (4)0.0051 (4)
O400.0360 (6)0.0203 (5)0.0333 (6)0.0095 (4)0.0040 (5)0.0093 (4)
Geometric parameters (Å, º) top
C1—C21.365 (2)C19—O211.3300 (16)
C1—C101.4210 (19)O21—C221.4628 (16)
C1—H1A0.9500C22—C231.496 (2)
C2—C31.418 (2)C22—H22A0.9900
C2—H2A0.9500C22—H22B0.9900
C3—C41.420 (2)C23—H23A0.9800
C3—C81.420 (2)C23—H23B0.9800
C4—C51.373 (2)C23—H23C0.9800
C4—H4A0.9500C24—C251.4749 (18)
C5—C61.404 (2)C25—N271.2893 (17)
C5—H5A0.9500C25—C261.4991 (18)
C6—C71.366 (2)C26—H26A0.9800
C6—H6A0.9500C26—H26B0.9800
C7—C81.415 (2)C26—H26C0.9800
C7—H7A0.9500N27—N281.3700 (15)
C8—C91.4182 (19)N28—C291.3587 (17)
C9—C101.3682 (19)N28—H28A0.8800
C9—H9A0.9500C29—C341.4130 (19)
C10—C121.4998 (18)C29—C301.4160 (18)
C12—O131.4214 (16)C30—C311.3898 (18)
C12—H12A0.9900C30—N351.4524 (17)
C12—H12B0.9900C31—C321.3699 (19)
O13—C141.4181 (16)C31—H31A0.9500
C14—C151.4930 (19)C32—C331.3945 (19)
C14—H14A0.9900C32—N381.4596 (17)
C14—H14B0.9900C33—C341.3684 (18)
C15—O161.3554 (16)C33—H33A0.9500
C15—C241.3575 (19)C34—H34A0.9500
O16—N171.3950 (15)N35—O361.2227 (14)
N17—C181.3120 (17)N35—O371.2443 (14)
C18—C241.4291 (18)N38—O391.2282 (15)
C18—C191.4876 (19)N38—O401.2284 (15)
C19—O201.2047 (16)
C2—C1—C10120.75 (13)C19—O21—C22114.54 (11)
C2—C1—H1A119.6O21—C22—C23107.90 (12)
C10—C1—H1A119.6O21—C22—H22A110.1
C1—C2—C3120.89 (13)C23—C22—H22A110.1
C1—C2—H2A119.6O21—C22—H22B110.1
C3—C2—H2A119.6C23—C22—H22B110.1
C2—C3—C4122.80 (13)H22A—C22—H22B108.4
C2—C3—C8118.70 (13)C22—C23—H23A109.5
C4—C3—C8118.50 (13)C22—C23—H23B109.5
C5—C4—C3120.92 (14)H23A—C23—H23B109.5
C5—C4—H4A119.5C22—C23—H23C109.5
C3—C4—H4A119.5H23A—C23—H23C109.5
C4—C5—C6120.20 (14)H23B—C23—H23C109.5
C4—C5—H5A119.9C15—C24—C18103.34 (11)
C6—C5—H5A119.9C15—C24—C25125.47 (12)
C7—C6—C5120.32 (14)C18—C24—C25131.16 (12)
C7—C6—H6A119.8N27—C25—C24113.88 (11)
C5—C6—H6A119.8N27—C25—C26124.68 (12)
C6—C7—C8121.02 (14)C24—C25—C26121.28 (11)
C6—C7—H7A119.5C25—C26—H26A109.5
C8—C7—H7A119.5C25—C26—H26B109.5
C7—C8—C9121.98 (13)H26A—C26—H26B109.5
C7—C8—C3119.02 (13)C25—C26—H26C109.5
C9—C8—C3118.99 (13)H26A—C26—H26C109.5
C10—C9—C8121.36 (12)H26B—C26—H26C109.5
C10—C9—H9A119.3C25—N27—N28115.76 (11)
C8—C9—H9A119.3C29—N28—N27119.06 (11)
C9—C10—C1119.31 (12)C29—N28—H28A120.5
C9—C10—C12122.27 (12)N27—N28—H28A120.5
C1—C10—C12118.41 (12)N28—C29—C34120.13 (11)
O13—C12—C10109.06 (10)N28—C29—C30122.70 (12)
O13—C12—H12A109.9C34—C29—C30117.16 (12)
C10—C12—H12A109.9C31—C30—C29121.66 (12)
O13—C12—H12B109.9C31—C30—N35116.43 (11)
C10—C12—H12B109.9C29—C30—N35121.90 (11)
H12A—C12—H12B108.3C32—C31—C30118.64 (12)
C14—O13—C12114.09 (10)C32—C31—H31A120.7
O13—C14—C15113.35 (11)C30—C31—H31A120.7
O13—C14—H14A108.9C31—C32—C33121.72 (12)
C15—C14—H14A108.9C31—C32—N38119.48 (12)
O13—C14—H14B108.9C33—C32—N38118.76 (12)
C15—C14—H14B108.9C34—C33—C32119.63 (12)
H14A—C14—H14B107.7C34—C33—H33A120.2
O16—C15—C24109.91 (11)C32—C33—H33A120.2
O16—C15—C14118.15 (11)C33—C34—C29121.19 (12)
C24—C15—C14131.86 (12)C33—C34—H34A119.4
C15—O16—N17109.21 (10)C29—C34—H34A119.4
C18—N17—O16105.26 (10)O36—N35—O37122.13 (11)
N17—C18—C24112.27 (12)O36—N35—C30118.81 (11)
N17—C18—C19120.58 (12)O37—N35—C30119.06 (10)
C24—C18—C19127.11 (12)O39—N38—O40123.59 (11)
O20—C19—O21124.76 (12)O39—N38—C32118.01 (11)
O20—C19—C18122.48 (12)O40—N38—C32118.39 (11)
O21—C19—C18112.76 (11)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N28—H28A···O370.881.962.6028 (14)128

Experimental details

Crystal data
Chemical formulaC26H23N5O8
Mr533.49
Crystal system, space groupTriclinic, P1
Temperature (K)90
a, b, c (Å)7.0839 (6), 12.176 (1), 14.184 (2)
α, β, γ (°)90.581 (1), 95.925 (2), 99.251 (2)
V3)1200.7 (2)
Z2
Radiation typeMo Kα
µ (mm1)0.11
Crystal size (mm)0.47 × 0.33 × 0.30
Data collection
DiffractometerBruker SMART APEX
diffractometer
Absorption correctionMulti-scan
(SADABS; Bruker, 2007)
Tmin, Tmax0.949, 0.971
No. of measured, independent and
observed [I > 2σ(I)] reflections
18560, 4357, 4009
Rint0.023
(sin θ/λ)max1)0.600
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.035, 0.092, 1.02
No. of reflections4357
No. of parameters354
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.28, 0.23

Computer programs: SMART (Bruker, 2007), SAINT-Plus (Bruker, 2007), XS in SHELXTL (Sheldrick, 2008), XL in SHELXTL (Sheldrick, 2008), XP in SHELXTL (Sheldrick, 2008), publCIF (Westrip, 2009).

Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N28—H28A···O370.881.962.6028 (14)128
 

Footnotes

Formerly at Department Of Chemistry, University of Idaho, 83844-2343, USA.

Acknowledgements

The authors thank NIH for grants NS038444(NN), NINDS NS30570 (RJB), P20RR015583 (RJB, SP, NN), and the Malcolm and Carol Renfrew Scholarship (MIS, TR). The Bruker SMART APEX diffraction facility was established at the University of Idaho with the assistance of the NSF–EPSCoR program and the M. J. Murdock Charitable Trust, Vancouver, WA, USA.

References

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Volume 65| Part 1| January 2009| Pages o144-o145
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