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COMMUNICATIONS
ISSN: 2056-9890

4-(4-Fluoro­phen­yl)-2-methyl-3-(1-oxy-4-pyridyl)isoxazol-5(2H)-one

aInstitute of Pharmacy, Department of Pharmaceutical and Medicinal Chemistry, Eberhard-Karls-University Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany, and bDepartment of Organic Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14, D-55099 Mainz, Germany
*Correspondence e-mail: stefan.laufer@uni-tuebingen.de

(Received 6 November 2007; accepted 11 December 2007; online 23 January 2008)

The crystal structure of the title compound, C15H11FN2O3, was determined as part of a study on the biological activity of isoxazolone derivatives as p38 mitogen-activated protein kinase (MAPK) inhibitors. The dihedral angles between rings are isoxazole/benzene = 55.0 (3)°, isoxazole/pyridine = 33.8 (2)° and benzene/pyridine = 58.1 (2)°.

Related literature

Isoxazolones as potent inhibitors of p38 MAP kinases were first described by Laughlin et al. (2005[Laughlin, S. K., Clark, M. P., Djung, J. F., Golebiowski, A., Brugel, T. A., Sabat, M., Bookland, R. G., Laufersweiler, M. J., VanRens, J. C., Townes, J. A., De, B., Hsieh, L. C., Xu, S. C., Walter, R. L., Mekel, M. J., et al. (2005). Bioorg. Med. Chem. Lett. 15, 2399-2403.]). For related literature, see: Adams et al. (1998[Adams, J. L., Boehm, J. C., Kassis, S., Gorycki, P. D., Webb, E. F., Hall, R., Sorenson, M., Lee, J. C., Ayrton, A., Griswold, D. E. & Gallagher, T. F. (1998). Bioorg. Med. Chem. Lett. 8, 3111-3116.]); Clark et al. (2002[Clark, M. P., Djung, J. F., Laughlin, S. K. & Tullis, J. (2002). WO 02/094 266 A1. Is this a patent?.]); De Laszlo et al. (1998[De Laszlo, S. E., Visco, D., Agarwal, L., Chang, L., Chin, J., Croft, G., Forsyth, A., Fletcher, D., Frantz, B., Hacker, C., Hanlon, W., Harper, C., Kostura, M., Li, B., Luell, S., et al. (1998). Bioorg. Med. Chem. Lett. 8, 2689-2694.]); Foster et al. (2000[Foster, M. L., Halley, F. & Souness, J. E. (2000). Drug News Perspect. 13, 488-497.]); Laufer & Wagner (2002[Laufer, S. & Wagner, G. K. (2002). J. Med. Chem. 45, 2733-2740.]); Laufer et al. (2006[Laufer, S., Margutti, S. & Fritz, M. D. (2006). J. Med. Chem. 1, 197-207.]); Ohkawa et al. (2001[Ohkawa, S., Naruo, K., Miwatashi, S. & Kimura, H. (2001). Patent No. WO 2 001 074 811.]); Revesz et al. (2000[Revesz, L., Di Padova, F. E., Buhl, T., Feifel, R., Gram, H., Hiestand, P., Manning, U. & Zimmerlin, A. G. (2000). Bioorg. Med. Chem. Lett. 10, 1261-1264.]); Wang et al. (1998[Wang, Z., Canagarajah, B. J., Boehm, J. C., Kassisa, S., Cobb, M. H., Young, P. R., Abdel-Meguid, S., Adams, J. L. & Goldsmith, E. J. (1998). Structure, 6, 1117-1128.]).

[Scheme 1]

Experimental

Crystal data
  • C15H11FN2O3

  • Mr = 286.26

  • Tetragonal, P 43 21 2

  • a = 10.0828 (6) Å

  • c = 25.257 (5) Å

  • V = 2567.6 (6) Å3

  • Z = 8

  • Cu Kα radiation

  • μ = 0.97 mm−1

  • T = 193 (2) K

  • 0.40 × 0.20 × 0.10 mm

Data collection
  • Enraf–Nonius CAD-4 diffractometer

  • Absorption correction: multi-scan (MULABS; Blessing, 1995[Blessing, R. H. (1995). Acta Cryst. A51, 33-38.]) Tmin = 0.60, Tmax = 0.88

  • 5114 measured reflections

  • 1488 independent reflections

  • 1129 reflections with I > 2σ(I)

  • Rint = 0.081

  • 3 standard reflections frequency: 60 min intensity decay: 5%

Refinement
  • R[F2 > 2σ(F2)] = 0.068

  • wR(F2) = 0.192

  • S = 1.00

  • 1488 reflections

  • 191 parameters

  • H-atom parameters constrained

  • Δρmax = 0.45 e Å−3

  • Δρmin = −0.34 e Å−3

Data collection: CAD-4 Software (Enraf–Nonius, 1989[Enraf-Nonius (1989). CAD-4 Software. Version 5.0. Enraf-Nonius, Delft, The Netherlands.]); cell refinement: CAD-4 Software; data reduction: CORINC (Dräger & Gattow, 1971[Dräger, M. & Gattow, G. (1971). Acta Chem. Scand. 25, 761-762.]); program(s) used to solve structure: SIR92 (Altomare et al., 1994[Altomare, A., Cascarano, G., Giacovazzo, C., Guagliardi, A., Burla, M. C., Polidori, G. & Camalli, M. (1994). J. Appl. Cryst. 27, 435-436.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997[Sheldrick, G. M. (1997). SHELXL97. University of Göttingen, Germany.]); molecular graphics: PLATON (Spek, 2003[Spek, A. L. (2003). J. Appl. Cryst. 36, 7-13.]); software used to prepare material for publication: SHELXL97.

Supporting information


Comment top

Compound (II) (Fig. 2) was prepared in the course of our study on isoxazolones derivatives bearing the typical vicinal 4-pyridyl and 4-fluorophenyl pharmacophores of MAP Kinase inhibitors. Isoxazolones are described in the literature as inhibitors for p38 MAP Kinase (Laughlin et al., 2005; Clark et al., 2002).

The prototypical pyridinylimidazole SB 203580 is one of the best studied p38 inhibitors reported until now. Figure 1 shows the most important interactions between the ATP binding sites of p38 kinase and the imidazole inhibitor SB203580 (Wang et al., 1998). The 4-fluorophenyl ring of SB203580 occupies a hydrophobic back pocket, enhancing selectivity. Vicinal to this interaction site, the 4-pyridinyl ring forms a hydrogen bond from the backbone NH group of Met 109 of p38 MAP Kinase (Fig. 1).

However, certain liver toxicities, such as increased liver size and increased cytochrome P450 induction, have been reported (Foster et al., 2000; Adams et al., 1998). In light of this potential toxicity and the risks associated with developing human drugs, a continuing need exists for potent new small-molecule inhibitors of cytokine production with improved pharmacokinetic and safety profiles.

Several research groups have undertaken studies in which the imidazole ring was replaced by other 5- or 6- membered heterocycles (Laufer & Wagner, 2002; De Laszlo et al., 1998; Laufer et al., 2006; Revesz et al., 2000; Ohkawa et al., 2001). Replacement of the core heterocycle represents a strategy to dissect inhibition of p38 from interferences with cytochrome P450 (CYP450).

Accordingly, and based on the research published by Laughlin et al. (2005), we plan to prepare derivatives of isoxazolones in order to obtain more accurate and comparable information about this class of compounds as p38 MAP Kinase inhibitors in terms of biological activity.

The data presented here show the isoxazolone system is almost planar (Fig. 2). It is oriented at a dihedral angle of 55.0 (3)° to the fluorophenyl ring and 33.8 (2)° to the oxy-pyridine system. There are no significant intermolecular interactions.

Related literature top

Isoxazolones as potent inhibitors of p38 MAP kinases were first described by Laughlin et al. (2005). For related literature, see: Adams et al. (1998); Clark et al. (2002); De Laszlo et al. (1998); Foster et al. (2000); Laufer & Wagner (2002); Laufer et al. (2006); Ohkawa et al. (2001); Revesz et al. (2000); Wang et al. (1998).

Experimental top

For the synthesis of 2-(4-fluorophenyl)-3-oxo-3-pyridin-4-yl-N-oxide-propionic acid ethyl ester (see Fig. 3), to a suspension of 10 g (72 mmol) of isonicotinic acid N-oxide in 15 ml of DMF, 19.7 g (121 mmol) of CDI were added. The reaction mixture was stirred at 298 K for 1 h. The limpid solution was then cooled at 273 K and 13.3 g (72 mmol) of (4-fluorophenyl)acetic acid ethyl ester and 4.1 g (168 mmol) of NaH were added. The reaction mixture was stirred at 273 K for 15 min, then the temperature was raised to 298 K and kept under vigorous stirring for 4 h. The reaction mixture was then poured into water/ice, the pH adjusted to 6, and the solution extracted with ethyl acetate. The combined organic layers were then collected, dried over Na2SO4 and concentrated under vacuum, affording an oil that was chromatographed over SiO2 using acetone as eluent, yielding 80% of 2-(4-fluorophenyl)-3-oxo-3-pyridin-4-yl-N-oxide-propionic acid ethyl ester.

For the synthesis of (I), a suspension of 1.0 g (3.3 mmol) of 2-(4-fluorophenyl)-3-oxo-3-pyridin-4-yl-N-oxide-propionic acid ethyl ester and 0.3 g (4.0 mmol) of hydroxylamine hydrochloride in 0.5 ml of H2O was warmed to 353 K. 3 ml of MeOH were added and the resulting solution refluxed for 4 h. The reaction mixture was then cooled to 298 K and stored at 277 K overnight, whereupon a yellow solid precipitated, yielding 83% of (I).

For the synthesis of (II), a suspension of 0.71 g (2.6 mmol) of (I) in 1 ml of DMF was added to 0.620 ml (4.5 mmol) of Et3N and refluxed for 2 h. The reaction mixture was then cooled to 298 K, added to 0.231 ml (3.75 mmol) of iodomethane and stirred at 298 K for 2 h. Ethyl acetate was then added and the resulting precipitate separated by filtration and then crystalized from MeOH, yielding 40% of (II).

Refinement top

Hydrogen atoms attached to carbon were placed at calculated positions with C—H = 0.95 Å (aromatic) or 0.99–1.00 Å (sp3 C). All H atoms were refined with Ueq = 1.2 or 1.5 times Ueq of the parent atom).

Computing details top

Data collection: CAD-4 Software (Enraf–Nonius, 1989); cell refinement: CAD-4 Software (Enraf–Nonius, 1989); data reduction: CORINC (Dräger & Gattow, 1971); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: SHELXL97 (Sheldrick, 1997).

Figures top
[Figure 1] Fig. 1. Schematic drawing of important interactions between the prototypical pyridin-4-yl imidazole inhibitor SB 203580 and the ATP binding site of p38.
[Figure 2] Fig. 2. PLATON (Spek, 2003) view of (II). Displacement ellipsoids are drawn at the 50% probability level. H atoms are depicted as circles of arbitrary size.
[Figure 3] Fig. 3. Synthesis of (II).
4-(4-Fluorophenyl)-2-methyl-3-(1-oxy-4-pyridyl)isoxazol-5(2H)-one top
Crystal data top
C15H11FN2O3Dx = 1.481 Mg m3
Mr = 286.26Cu Kα radiation, λ = 1.54178 Å
Tetragonal, P43212Cell parameters from 25 reflections
Hall symbol: P 4nw 2abwθ = 20–32°
a = 10.0828 (6) ŵ = 0.97 mm1
c = 25.257 (5) ÅT = 193 K
V = 2567.6 (6) Å3Block, yellow
Z = 80.40 × 0.20 × 0.10 mm
F(000) = 1184
Data collection top
Enraf–Nonius CAD-4
diffractometer
1129 reflections with I > 2σ(I)
Radiation source: rotating anodeRint = 0.081
Graphite monochromatorθmax = 69.8°, θmin = 4.7°
θ/2ω scansh = 1212
Absorption correction: multi-scan
(MULABS; Blessing, 1995)
k = 1212
Tmin = 0.60, Tmax = 0.88l = 2330
5114 measured reflections3 standard reflections every 60 min
1488 independent reflections intensity decay: 5%
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)] = 0.068Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.192H-atom parameters constrained
S = 1.00 w = 1/[σ2(Fo2) + (0.149P)2]
where P = (Fo2 + 2Fc2)/3
1488 reflections(Δ/σ)max < 0.001
191 parametersΔρmax = 0.45 e Å3
0 restraintsΔρmin = 0.34 e Å3
Crystal data top
C15H11FN2O3Z = 8
Mr = 286.26Cu Kα radiation
Tetragonal, P43212µ = 0.97 mm1
a = 10.0828 (6) ÅT = 193 K
c = 25.257 (5) Å0.40 × 0.20 × 0.10 mm
V = 2567.6 (6) Å3
Data collection top
Enraf–Nonius CAD-4
diffractometer
1129 reflections with I > 2σ(I)
Absorption correction: multi-scan
(MULABS; Blessing, 1995)
Rint = 0.081
Tmin = 0.60, Tmax = 0.883 standard reflections every 60 min
5114 measured reflections intensity decay: 5%
1488 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0680 restraints
wR(F2) = 0.192H-atom parameters constrained
S = 1.00Δρmax = 0.45 e Å3
1488 reflectionsΔρmin = 0.34 e Å3
191 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. Friedel Pairs merged (MERG 3 instruction). 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
C10.4167 (4)0.0719 (4)0.3006 (2)0.0248 (11)
C20.3537 (4)0.1885 (4)0.2905 (2)0.0231 (10)
N30.2782 (4)0.1781 (4)0.24613 (17)0.0272 (10)
O40.2804 (4)0.0427 (3)0.23076 (16)0.0346 (9)
C50.3701 (5)0.0233 (5)0.2641 (2)0.0302 (11)
C60.1515 (5)0.2379 (6)0.2342 (2)0.0366 (13)
H6A0.08060.18550.25050.055*
H6B0.13870.24030.19580.055*
H6C0.14930.32840.24830.055*
O70.3926 (4)0.1402 (4)0.25595 (18)0.0409 (10)
C80.5231 (4)0.0446 (4)0.3400 (2)0.0262 (11)
C90.6393 (5)0.1185 (5)0.3410 (2)0.0290 (11)
H90.64990.18960.31670.035*
C100.7405 (5)0.0908 (5)0.3767 (3)0.0348 (13)
H100.81980.14150.37740.042*
C110.7207 (5)0.0138 (5)0.4112 (2)0.0300 (12)
C120.6096 (5)0.0891 (5)0.4118 (2)0.0315 (12)
H120.60000.15980.43640.038*
C130.5100 (5)0.0603 (5)0.3757 (3)0.0313 (12)
H130.43180.11280.37520.038*
F140.8198 (3)0.0417 (3)0.44649 (16)0.0477 (10)
C150.3631 (4)0.3142 (4)0.31988 (19)0.0198 (10)
C160.3580 (4)0.4384 (4)0.2958 (2)0.0253 (11)
H160.34480.44380.25860.030*
C170.3714 (5)0.5514 (5)0.3240 (2)0.0265 (11)
H170.36550.63470.30660.032*
N180.3934 (4)0.5467 (4)0.37729 (18)0.0253 (9)
C190.3954 (5)0.4264 (5)0.4021 (2)0.0270 (11)
H190.40760.42280.43940.032*
C200.3804 (4)0.3122 (4)0.3746 (2)0.0254 (10)
H200.38170.22980.39290.030*
O210.4120 (4)0.6544 (3)0.40417 (17)0.0395 (10)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0148 (19)0.020 (2)0.039 (3)0.0011 (17)0.0004 (19)0.000 (2)
C20.022 (2)0.021 (2)0.027 (3)0.0009 (17)0.0007 (19)0.0004 (19)
N30.033 (2)0.0243 (18)0.025 (2)0.0040 (17)0.0053 (18)0.0087 (17)
O40.0338 (19)0.0286 (17)0.041 (2)0.0032 (15)0.0063 (17)0.0105 (16)
C50.025 (2)0.022 (2)0.043 (3)0.0028 (19)0.004 (2)0.004 (2)
C60.036 (3)0.041 (3)0.033 (3)0.010 (2)0.011 (2)0.002 (2)
O70.040 (2)0.0289 (18)0.053 (3)0.0000 (15)0.002 (2)0.0161 (18)
C80.019 (2)0.017 (2)0.042 (3)0.0062 (17)0.002 (2)0.005 (2)
C90.026 (2)0.018 (2)0.042 (3)0.0040 (17)0.002 (2)0.002 (2)
C100.024 (2)0.028 (2)0.053 (4)0.002 (2)0.004 (2)0.013 (2)
C110.025 (2)0.024 (2)0.041 (3)0.0109 (19)0.010 (2)0.012 (2)
C120.035 (3)0.023 (2)0.037 (3)0.007 (2)0.002 (2)0.001 (2)
C130.022 (2)0.023 (2)0.048 (3)0.001 (2)0.001 (2)0.000 (2)
F140.0400 (17)0.0448 (18)0.058 (2)0.0099 (15)0.0234 (17)0.0034 (17)
C150.0172 (19)0.0174 (19)0.025 (3)0.0021 (15)0.0003 (18)0.0017 (18)
C160.025 (2)0.022 (2)0.028 (3)0.0062 (18)0.000 (2)0.003 (2)
C170.029 (2)0.020 (2)0.030 (3)0.0014 (18)0.003 (2)0.006 (2)
N180.0232 (19)0.0212 (19)0.031 (3)0.0019 (15)0.0016 (17)0.0046 (18)
C190.030 (2)0.025 (2)0.026 (3)0.0051 (19)0.002 (2)0.000 (2)
C200.025 (2)0.018 (2)0.033 (3)0.0015 (18)0.002 (2)0.0027 (19)
O210.049 (2)0.0213 (17)0.048 (3)0.0046 (15)0.0001 (19)0.0107 (17)
Geometric parameters (Å, º) top
C1—C21.360 (6)C10—H100.950
C1—C51.412 (7)C11—C121.354 (7)
C1—C81.489 (7)C11—F141.368 (6)
C2—N31.359 (6)C12—C131.388 (7)
C2—C151.472 (6)C12—H120.950
N3—O41.419 (5)C13—H130.950
N3—C61.444 (6)C15—C161.393 (6)
O4—C51.403 (6)C15—C201.394 (7)
C5—O71.218 (6)C16—C171.350 (7)
C6—H6A0.980C16—H160.950
C6—H6B0.980C17—N181.364 (7)
C6—H6C0.980C17—H170.950
C8—C91.389 (6)N18—O211.293 (5)
C8—C131.395 (7)N18—C191.366 (6)
C9—C101.391 (8)C19—C201.352 (7)
C9—H90.950C19—H190.950
C10—C111.382 (8)C20—H200.950
C2—C1—C5108.0 (4)C12—C11—F14118.8 (5)
C2—C1—C8128.4 (4)C12—C11—C10123.7 (5)
C5—C1—C8123.5 (4)F14—C11—C10117.5 (5)
N3—C2—C1110.5 (4)C11—C12—C13118.3 (5)
N3—C2—C15121.2 (4)C11—C12—H12120.9
C1—C2—C15128.3 (5)C13—C12—H12120.9
C2—N3—O4106.9 (4)C12—C13—C8121.0 (5)
C2—N3—C6129.5 (4)C12—C13—H13119.5
O4—N3—C6111.0 (4)C8—C13—H13119.5
C5—O4—N3107.6 (4)C16—C15—C20116.8 (4)
O7—C5—O4118.6 (5)C16—C15—C2123.5 (4)
O7—C5—C1134.9 (5)C20—C15—C2119.7 (4)
O4—C5—C1106.5 (4)C17—C16—C15121.6 (5)
N3—C6—H6A109.5C17—C16—H16119.2
N3—C6—H6B109.5C15—C16—H16119.2
H6A—C6—H6B109.5C16—C17—N18120.5 (4)
N3—C6—H6C109.5C16—C17—H17119.7
H6A—C6—H6C109.5N18—C17—H17119.7
H6B—C6—H6C109.5O21—N18—C17120.8 (4)
C9—C8—C13118.4 (5)O21—N18—C19120.2 (4)
C9—C8—C1121.4 (5)C17—N18—C19119.0 (4)
C13—C8—C1120.2 (4)C20—C19—N18121.3 (5)
C8—C9—C10121.5 (5)C20—C19—H19119.4
C8—C9—H9119.2N18—C19—H19119.4
C10—C9—H9119.2C19—C20—C15120.7 (4)
C11—C10—C9117.2 (5)C19—C20—H20119.6
C11—C10—H10121.4C15—C20—H20119.6
C9—C10—H10121.4
C5—C1—C2—N35.8 (6)C8—C9—C10—C110.2 (8)
C8—C1—C2—N3170.2 (5)C9—C10—C11—C120.0 (8)
C5—C1—C2—C15176.1 (4)C9—C10—C11—F14180.0 (4)
C8—C1—C2—C157.9 (8)F14—C11—C12—C13179.7 (5)
C1—C2—N3—O47.4 (5)C10—C11—C12—C130.3 (8)
C15—C2—N3—O4174.4 (4)C11—C12—C13—C80.9 (8)
C1—C2—N3—C6144.7 (5)C9—C8—C13—C121.1 (8)
C15—C2—N3—C637.1 (7)C1—C8—C13—C12178.5 (5)
C2—N3—O4—C56.0 (5)N3—C2—C15—C1633.2 (7)
C6—N3—O4—C5151.9 (4)C1—C2—C15—C16144.7 (5)
N3—O4—C5—O7176.3 (5)N3—C2—C15—C20148.1 (5)
N3—O4—C5—C12.5 (5)C1—C2—C15—C2034.1 (7)
C2—C1—C5—O7179.6 (6)C20—C15—C16—C171.0 (6)
C8—C1—C5—O74.1 (10)C2—C15—C16—C17177.8 (5)
C2—C1—C5—O41.9 (6)C15—C16—C17—N181.5 (7)
C8—C1—C5—O4174.4 (4)C16—C17—N18—O21177.0 (4)
C2—C1—C8—C954.3 (8)C16—C17—N18—C193.1 (7)
C5—C1—C8—C9121.2 (5)O21—N18—C19—C20177.9 (4)
C2—C1—C8—C13128.4 (6)C17—N18—C19—C202.2 (7)
C5—C1—C8—C1356.1 (7)N18—C19—C20—C150.3 (7)
C13—C8—C9—C100.7 (8)C16—C15—C20—C191.9 (7)
C1—C8—C9—C10178.1 (5)C2—C15—C20—C19176.9 (4)

Experimental details

Crystal data
Chemical formulaC15H11FN2O3
Mr286.26
Crystal system, space groupTetragonal, P43212
Temperature (K)193
a, c (Å)10.0828 (6), 25.257 (5)
V3)2567.6 (6)
Z8
Radiation typeCu Kα
µ (mm1)0.97
Crystal size (mm)0.40 × 0.20 × 0.10
Data collection
DiffractometerEnraf–Nonius CAD-4
diffractometer
Absorption correctionMulti-scan
(MULABS; Blessing, 1995)
Tmin, Tmax0.60, 0.88
No. of measured, independent and
observed [I > 2σ(I)] reflections
5114, 1488, 1129
Rint0.081
(sin θ/λ)max1)0.609
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.068, 0.192, 1.00
No. of reflections1488
No. of parameters191
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å3)0.45, 0.34

Computer programs: CAD-4 Software (Enraf–Nonius, 1989), CORINC (Dräger & Gattow, 1971), SIR92 (Altomare et al., 1994), SHELXL97 (Sheldrick, 1997), PLATON (Spek, 2003).

 

Acknowledgements

The authors thank the EU–Craft Program, Project Macrocept (FP6) for funding.

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