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Acta Crystallogr Sect E Struct Rep Online. 2010 May 1; 66(Pt 5): o1100.
Published online 2010 April 17. doi:  10.1107/S1600536810013450
PMCID: PMC2979018

N-[3-(5-Oxo-10,11-dihydro-5H-dibenzo[a,d]cyclo­hepten-2-ylamino)phen­yl]furan-3-carboxamide

Abstract

In the title compound, C26H20N2O3, the two aromatic rings of the tricyclic unit are oriented at a dihedral angle of 54.53 (9)°. The crystal structure displays inter­molecular N—H(...)O hydrogen bonding.

Related literature

For palladium-catalyzed amination reactions of aryl halides with anilines, see: Jensen et al. (2004 [triangle]); Grasa et al. (2001 [triangle]). For p38 inhibitors based on dibenzosuberones, see: Laufer et al. (2006 [triangle]).

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Object name is e-66-o1100-scheme1.jpg

Experimental

Crystal data

  • C26H20N2O3
  • M r = 408.44
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-o1100-efi1.jpg
  • a = 10.7691 (7) Å
  • b = 21.746 (1) Å
  • c = 8.8666 (6) Å
  • β = 101.934 (2)°
  • V = 2031.6 (2) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.09 mm−1
  • T = 173 K
  • 0.30 × 0.20 × 0.10 mm

Data collection

  • Bruker SMART APEXII diffractometer
  • 22214 measured reflections
  • 4856 independent reflections
  • 3347 reflections with I > 2σ(I)
  • R int = 0.044

Refinement

  • R[F 2 > 2σ(F 2)] = 0.050
  • wR(F 2) = 0.115
  • S = 0.99
  • 4856 reflections
  • 280 parameters
  • H-atom parameters constrained
  • Δρmax = 0.24 e Å−3
  • Δρmin = −0.30 e Å−3

Data collection: APEX2 (Bruker, 2006 [triangle]); cell refinement: SAINT (Bruker, 2006 [triangle]); data reduction: SAINT; program(s) used to solve structure: SIR97 (Altomare et al., 1999 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: PLATON (Spek, 2009 [triangle]); software used to prepare material for publication: PLATON.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810013450/im2187sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810013450/im2187Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

supplementary crystallographic information

Comment

p38 mitogen activated protein (MAP) kinase is a key enzyme in inflammatory diseases as it is involved in the biosynthesis of proinflammatory cytokines such as TNF-α and IL-1β (Laufer et al. 2006). Small molecule p38 inhibitors suppress the production of these cytokines and therefore p38 is an attractive and promising drug target for novel anti-inflammatory therapeutics (Laufer et al. 2006). Recently, we designed and synthesized a series of p38 inhibitors based on dibenzosuberones (Laufer et al. 2006). The title compound was prepared in the course of our studies on dibenzo[a,d]cycloheptan-5-ones as potent p38 MAP kinase inhibitors.

The structure of the title compound, at 173 (2) K has monoclinic (P21/c) symmetry. In the molecule (Fig.1), rings A (C1—C4, C14, C15) and B (C6—C11) are, of course, planar and they are oriented at a dihedral angle of A/B = 54.53 (9)°. The intramolecular C21—H21···O26 (2.66 Å) interaction stabilizes the conformation of the molecule. In the crystal structure the hydrogen bonds N17—H17···O16 (2.90 Å) and N24—H24···O26 (2.84 Å) link the molecule into double layers.

Experimental

For the preparation of the title compound a mixture of 500 mg (2.1 mmol) 2-chloro-10,11-dihydro-5H-dibenzo[a,d][7]annulen-5-one, 420 mg (2.1 mmol) N-(3-aminophenyl)-3-furamide, 940 mg (8.4 mmol) KOtert-Bu, 90 mg (0.19 mmol) 2-(dicyclohexylphosphino)-2'-, 4'-, 6'-triisopropylbiphenyl and 20 mg (0.09 mmol) Pd(OAc)2 in 3 ml absolute tert-butanol and 7 ml absolute toluol was stirred for 4 h at 363 K under an atmosphere of argon. The mixture was diluted with water and then extracted with ethyl acetate. The extracts were combined, washed with saturated saline solution, dried over Na2SO4 and then evaporated under reduced pressure. The residue was purified by flash chromatography (SiO2 60, n-hexane / ethyl acetate 3 + 2) (yield: 17.2 %). Crystals of the title compound were obtained by slow evaporation of a methanol / diethyl ether solution at room temperature.

Refinement

Hydrogen atoms attached to carbons were placed at calculated positions with C—H = 0.95 Å (aromatic) or 0.98–0.99 Å (sp3 C-atom). Hydrogen atoms attached to N17 and N24 were located in diff. Fourier maps. All H atoms were refined in the riding-model approximation with isotropic displacement parameters (set at 1.2–1.5 times of the Ueq of the parent atom).

Figures

Fig. 1.
View of compound I. Displacement ellipsoids are drawn at the 50% probability level.
Fig. 2.
Part of the crystal packing showing the supramoleculare structure. View along the a-axis.

Crystal data

C26H20N2O3F(000) = 856
Mr = 408.44Dx = 1.335 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71069 Å
Hall symbol: -P 2ybcCell parameters from 3910 reflections
a = 10.7691 (7) Åθ = 2.5–25.8°
b = 21.746 (1) ŵ = 0.09 mm1
c = 8.8666 (6) ÅT = 173 K
β = 101.934 (2)°Plate, yellow
V = 2031.6 (2) Å30.30 × 0.20 × 0.10 mm
Z = 4

Data collection

Bruker SMART APEXII diffractometer3347 reflections with I > 2σ(I)
Radiation source: sealed TubeRint = 0.044
graphiteθmax = 27.9°, θmin = 1.9°
CCD scanh = −14→14
22214 measured reflectionsk = −28→28
4856 independent reflectionsl = −11→11

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.050Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.115H-atom parameters constrained
S = 0.99w = 1/[σ2(Fo2) + (0.0358P)2 + 1.2737P] where P = (Fo2 + 2Fc2)/3
4856 reflections(Δ/σ)max < 0.001
280 parametersΔρmax = 0.24 e Å3
0 restraintsΔρmin = −0.30 e Å3

Special details

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > 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)

xyzUiso*/Ueq
C10.33786 (17)0.51791 (8)0.78886 (19)0.0268 (4)
C20.35431 (17)0.55527 (8)0.92028 (19)0.0282 (4)
H20.37140.59790.91310.034*
C30.34553 (17)0.52992 (8)1.05935 (19)0.0278 (4)
H30.35790.55591.14740.033*
C40.31908 (16)0.46745 (8)1.07779 (18)0.0255 (4)
C50.30193 (18)0.45074 (8)1.23480 (19)0.0293 (4)
C60.23344 (17)0.39443 (8)1.26987 (19)0.0306 (4)
C70.15301 (19)0.40150 (10)1.3739 (2)0.0394 (5)
H70.14350.44091.41660.047*
C80.0873 (2)0.35182 (12)1.4151 (3)0.0521 (6)
H80.03190.35721.48470.063*
C90.1023 (2)0.29455 (11)1.3551 (3)0.0528 (6)
H90.05720.26031.38340.063*
C100.1828 (2)0.28669 (10)1.2539 (2)0.0420 (5)
H100.19320.24691.21410.050*
C110.24914 (18)0.33624 (8)1.2092 (2)0.0323 (4)
C120.3358 (2)0.32699 (8)1.0986 (2)0.0359 (4)
H12A0.34300.28251.07880.043*
H12B0.42150.34251.14580.043*
C130.2882 (2)0.36007 (8)0.9458 (2)0.0345 (4)
H13A0.33160.34220.86800.041*
H13B0.19640.35140.91180.041*
C140.30687 (17)0.42898 (8)0.94687 (19)0.0269 (4)
C150.31629 (17)0.45534 (8)0.80680 (19)0.0272 (4)
H150.30760.42940.71890.033*
O160.33648 (14)0.48724 (6)1.34167 (14)0.0397 (3)
N170.34715 (16)0.53956 (6)0.64489 (16)0.0325 (4)
H170.35300.51030.57920.039*
C180.36701 (17)0.60072 (8)0.60389 (18)0.0279 (4)
C190.29900 (17)0.64925 (8)0.65027 (18)0.0269 (4)
H190.23920.64150.71310.032*
C200.31876 (17)0.70897 (8)0.60449 (18)0.0267 (4)
C210.40671 (18)0.72084 (8)0.5136 (2)0.0312 (4)
H210.42300.76190.48630.037*
C220.47030 (18)0.67210 (9)0.4632 (2)0.0344 (4)
H220.52800.67980.39760.041*
C230.45104 (18)0.61242 (8)0.5069 (2)0.0321 (4)
H230.49500.57940.47090.039*
N240.24633 (15)0.75736 (6)0.65095 (15)0.0291 (3)
H240.22550.75220.74440.035*
C250.18520 (17)0.80036 (8)0.55246 (18)0.0262 (4)
O260.18260 (14)0.79914 (6)0.41345 (14)0.0400 (3)
C270.12282 (16)0.85057 (8)0.61918 (19)0.0265 (4)
C280.04935 (19)0.89762 (9)0.5342 (2)0.0392 (5)
H280.02800.90080.42500.047*
C290.01532 (18)0.93667 (9)0.6332 (2)0.0373 (4)
H29−0.03510.97240.60590.045*
O300.06443 (17)0.91741 (7)0.78210 (18)0.0579 (4)
C310.1293 (2)0.86527 (9)0.7692 (2)0.0451 (5)
H310.17370.84190.85400.054*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C10.0327 (9)0.0268 (9)0.0223 (8)0.0032 (7)0.0090 (7)0.0015 (7)
C20.0391 (10)0.0206 (8)0.0256 (8)−0.0007 (7)0.0085 (7)0.0008 (7)
C30.0372 (10)0.0252 (9)0.0212 (8)0.0037 (7)0.0066 (7)−0.0032 (7)
C40.0328 (9)0.0227 (8)0.0222 (8)0.0043 (7)0.0087 (7)0.0015 (6)
C50.0394 (10)0.0263 (9)0.0238 (8)0.0076 (8)0.0103 (7)0.0019 (7)
C60.0350 (10)0.0349 (10)0.0222 (8)0.0031 (8)0.0062 (7)0.0055 (7)
C70.0417 (11)0.0512 (12)0.0266 (9)0.0012 (9)0.0099 (8)0.0027 (8)
C80.0502 (13)0.0741 (17)0.0365 (11)−0.0102 (12)0.0191 (10)0.0075 (11)
C90.0576 (14)0.0616 (15)0.0399 (12)−0.0216 (12)0.0118 (10)0.0123 (11)
C100.0523 (13)0.0376 (11)0.0346 (10)−0.0071 (9)0.0056 (9)0.0092 (8)
C110.0367 (10)0.0314 (10)0.0277 (9)0.0010 (8)0.0042 (8)0.0079 (7)
C120.0489 (12)0.0223 (9)0.0389 (10)0.0044 (8)0.0146 (9)0.0030 (8)
C130.0557 (12)0.0220 (9)0.0299 (9)−0.0011 (8)0.0186 (9)−0.0022 (7)
C140.0319 (9)0.0230 (8)0.0274 (9)0.0016 (7)0.0099 (7)0.0002 (7)
C150.0372 (10)0.0232 (9)0.0227 (8)0.0004 (7)0.0095 (7)−0.0048 (7)
O160.0678 (10)0.0308 (7)0.0232 (6)0.0006 (7)0.0153 (6)−0.0017 (5)
N170.0580 (10)0.0222 (7)0.0210 (7)0.0026 (7)0.0165 (7)−0.0009 (6)
C180.0394 (10)0.0263 (9)0.0184 (8)0.0003 (8)0.0072 (7)0.0013 (7)
C190.0374 (10)0.0285 (9)0.0161 (7)−0.0002 (7)0.0083 (7)0.0009 (6)
C200.0358 (10)0.0267 (9)0.0170 (7)0.0007 (7)0.0042 (7)−0.0009 (6)
C210.0388 (10)0.0268 (9)0.0293 (9)−0.0033 (8)0.0097 (8)0.0021 (7)
C220.0375 (10)0.0358 (10)0.0337 (10)0.0002 (8)0.0163 (8)0.0032 (8)
C230.0400 (10)0.0297 (9)0.0294 (9)0.0051 (8)0.0137 (8)−0.0007 (7)
N240.0469 (9)0.0267 (8)0.0162 (7)0.0040 (7)0.0123 (6)0.0019 (6)
C250.0347 (9)0.0259 (9)0.0191 (8)−0.0048 (7)0.0083 (7)0.0001 (7)
O260.0628 (9)0.0406 (8)0.0188 (6)0.0125 (7)0.0136 (6)0.0047 (5)
C270.0316 (9)0.0249 (9)0.0236 (8)−0.0032 (7)0.0070 (7)0.0018 (7)
C280.0436 (11)0.0396 (11)0.0331 (10)0.0046 (9)0.0046 (9)0.0084 (8)
C290.0349 (10)0.0269 (10)0.0503 (12)0.0082 (8)0.0093 (9)0.0054 (8)
O300.0789 (12)0.0513 (10)0.0456 (9)0.0208 (9)0.0179 (8)−0.0055 (7)
C310.0696 (15)0.0386 (11)0.0267 (10)0.0212 (11)0.0087 (9)−0.0009 (8)

Geometric parameters (Å, °)

C1—N171.384 (2)C14—C151.391 (2)
C1—C151.395 (2)C15—H150.9500
C1—C21.401 (2)N17—C181.407 (2)
C2—C31.372 (2)N17—H170.8739
C2—H20.9500C18—C191.394 (2)
C3—C41.405 (2)C18—C231.395 (2)
C3—H30.9500C19—C201.390 (2)
C4—C141.415 (2)C19—H190.9500
C4—C51.487 (2)C20—C211.389 (2)
C5—O161.233 (2)C20—N241.421 (2)
C5—C61.495 (3)C21—C221.385 (3)
C6—C71.398 (3)C21—H210.9500
C6—C111.399 (3)C22—C231.382 (3)
C7—C81.382 (3)C22—H220.9500
C7—H70.9500C23—H230.9500
C8—C91.377 (3)N24—C251.354 (2)
C8—H80.9500N24—H240.9089
C9—C101.381 (3)C25—O261.2274 (19)
C9—H90.9500C25—C271.469 (2)
C10—C111.395 (3)C27—C311.356 (2)
C10—H100.9500C27—C281.412 (2)
C11—C121.501 (3)C28—C291.326 (3)
C12—C131.525 (3)C28—H280.9500
C12—H12A0.9900C29—O301.382 (2)
C12—H12B0.9900C29—H290.9500
C13—C141.512 (2)O30—C311.349 (2)
C13—H13A0.9900C31—H310.9500
C13—H13B0.9900
N17—C1—C15118.86 (15)C15—C14—C13115.93 (15)
N17—C1—C2123.30 (16)C4—C14—C13125.51 (15)
C15—C1—C2117.79 (15)C14—C15—C1123.27 (15)
C3—C2—C1119.60 (16)C14—C15—H15118.4
C3—C2—H2120.2C1—C15—H15118.4
C1—C2—H2120.2C1—N17—C18127.17 (14)
C2—C3—C4123.15 (16)C1—N17—H17113.4
C2—C3—H3118.4C18—N17—H17118.7
C4—C3—H3118.4C19—C18—C23119.41 (16)
C3—C4—C14117.59 (15)C19—C18—N17121.48 (15)
C3—C4—C5114.38 (14)C23—C18—N17118.99 (15)
C14—C4—C5127.98 (15)C20—C19—C18119.97 (16)
O16—C5—C4119.09 (16)C20—C19—H19120.0
O16—C5—C6116.80 (15)C18—C19—H19120.0
C4—C5—C6123.85 (15)C21—C20—C19120.47 (16)
C7—C6—C11119.61 (17)C21—C20—N24120.79 (15)
C7—C6—C5116.52 (17)C19—C20—N24118.74 (15)
C11—C6—C5123.83 (16)C22—C21—C20119.14 (16)
C8—C7—C6120.6 (2)C22—C21—H21120.4
C8—C7—H7119.7C20—C21—H21120.4
C6—C7—H7119.7C23—C22—C21121.02 (17)
C9—C8—C7119.8 (2)C23—C22—H22119.5
C9—C8—H8120.1C21—C22—H22119.5
C7—C8—H8120.1C22—C23—C18119.89 (16)
C8—C9—C10120.2 (2)C22—C23—H23120.1
C8—C9—H9119.9C18—C23—H23120.1
C10—C9—H9119.9C25—N24—C20123.20 (14)
C9—C10—C11121.1 (2)C25—N24—H24119.6
C9—C10—H10119.5C20—N24—H24115.3
C11—C10—H10119.5O26—C25—N24122.68 (16)
C10—C11—C6118.66 (18)O26—C25—C27120.20 (16)
C10—C11—C12120.43 (17)N24—C25—C27117.10 (14)
C6—C11—C12120.91 (16)C31—C27—C28105.22 (16)
C11—C12—C13112.11 (16)C31—C27—C25129.44 (16)
C11—C12—H12A109.2C28—C27—C25125.17 (16)
C13—C12—H12A109.2C29—C28—C27108.14 (17)
C11—C12—H12B109.2C29—C28—H28125.9
C13—C12—H12B109.2C27—C28—H28125.9
H12A—C12—H12B107.9C28—C29—O30109.57 (17)
C14—C13—C12116.24 (16)C28—C29—H29125.2
C14—C13—H13A108.2O30—C29—H29125.2
C12—C13—H13A108.2C31—O30—C29106.05 (15)
C14—C13—H13B108.2O30—C31—C27111.01 (17)
C12—C13—H13B108.2O30—C31—H31124.5
H13A—C13—H13B107.4C27—C31—H31124.5
C15—C14—C4118.53 (15)
N17—C1—C2—C3−178.94 (17)C4—C14—C15—C10.3 (3)
C15—C1—C2—C3−1.7 (3)C13—C14—C15—C1−177.81 (17)
C1—C2—C3—C4−0.7 (3)N17—C1—C15—C14179.27 (17)
C2—C3—C4—C142.9 (3)C2—C1—C15—C141.9 (3)
C2—C3—C4—C5−174.59 (17)C15—C1—N17—C18179.19 (17)
C3—C4—C5—O16−14.7 (2)C2—C1—N17—C18−3.6 (3)
C14—C4—C5—O16168.12 (18)C1—N17—C18—C19−45.9 (3)
C3—C4—C5—C6159.21 (16)C1—N17—C18—C23138.03 (19)
C14—C4—C5—C6−18.0 (3)C23—C18—C19—C20−2.4 (3)
O16—C5—C6—C735.6 (2)N17—C18—C19—C20−178.41 (16)
C4—C5—C6—C7−138.42 (18)C18—C19—C20—C21−0.5 (3)
O16—C5—C6—C11−142.16 (18)C18—C19—C20—N24178.77 (15)
C4—C5—C6—C1143.8 (3)C19—C20—C21—C222.9 (3)
C11—C6—C7—C8−1.1 (3)N24—C20—C21—C22−176.33 (16)
C5—C6—C7—C8−178.99 (18)C20—C21—C22—C23−2.5 (3)
C6—C7—C8—C90.9 (3)C21—C22—C23—C18−0.4 (3)
C7—C8—C9—C100.0 (3)C19—C18—C23—C222.8 (3)
C8—C9—C10—C11−0.7 (3)N17—C18—C23—C22178.94 (17)
C9—C10—C11—C60.5 (3)C21—C20—N24—C2547.7 (2)
C9—C10—C11—C12−179.72 (19)C19—C20—N24—C25−131.59 (18)
C7—C6—C11—C100.4 (3)C20—N24—C25—O263.6 (3)
C5—C6—C11—C10178.11 (17)C20—N24—C25—C27−175.05 (15)
C7—C6—C11—C12−179.36 (17)O26—C25—C27—C31−169.7 (2)
C5—C6—C11—C12−1.7 (3)N24—C25—C27—C319.0 (3)
C10—C11—C12—C13114.25 (19)O26—C25—C27—C284.7 (3)
C6—C11—C12—C13−66.0 (2)N24—C25—C27—C28−176.57 (17)
C11—C12—C13—C1475.8 (2)C31—C27—C28—C29−0.6 (2)
C3—C4—C14—C15−2.7 (2)C25—C27—C28—C29−176.09 (17)
C5—C4—C14—C15174.47 (17)C27—C28—C29—O300.4 (2)
C3—C4—C14—C13175.28 (17)C28—C29—O30—C310.0 (2)
C5—C4—C14—C13−7.6 (3)C29—O30—C31—C27−0.3 (3)
C12—C13—C14—C15153.30 (17)C28—C27—C31—O300.6 (2)
C12—C13—C14—C4−24.7 (3)C25—C27—C31—O30175.83 (18)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N17—H17···O16i0.872.142.900 (2)146
N24—H24···O26ii0.912.002.839 (2)153
C21—H21···O210.952.662.937 (2)97

Symmetry codes: (i) x, y, z−1; (ii) x, −y+3/2, z+1/2.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: IM2187).

References

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Articles from Acta Crystallographica Section E: Structure Reports Online are provided here courtesy of International Union of Crystallography