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Acta Crystallogr Sect E Struct Rep Online. 2010 March 1; 66(Pt 3): o680–o681.
Published online 2010 February 20. doi:  10.1107/S1600536810005805
PMCID: PMC2983536

2-Ethyl-6-(2-pyrid­yl)-5,6,6a,11b-tetra­hydro-7H-indeno[2,1-c]quinoline

Abstract

The title compound, C23H22N2, was obtained using the three-component imino Diels–Alder reaction via a one-pot condensation between anilines, α-pyridine­carboxy­aldehyde and indene using BF3·OEt2 as the catalyst. The mol­ecular structure reveals the cis-form as the unique diastereoisomer. The crystal structure comprises one-dimensional zigzag ribbons connected via N—H(...)N hydrogen bonds. C—H(...)π inter­actions also occur.

Related literature

For background to polycyclic quinoline derivatives, see: Denny & Baguley (2003 [triangle]); Gelderblom & Sparreboom (2006 [triangle]). For the biological activity of quinolines, see: Ewesuedo et al. (2001 [triangle]); Ishida & Asao (2002 [triangle]); Kouznetsov et al. (2006 [triangle]); Li et al. (2006 [triangle]); Ohyama et al. (1999 [triangle]); Priel et al. (1991 [triangle]); Twelves et al. (1999 [triangle]); Martínez & Chacón-García (2005 [triangle]); Pommier (2006 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-0o680-scheme1.jpg

Experimental

Crystal data

  • C23H22N2
  • M r = 326.43
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-0o680-efi1.jpg
  • a = 13.241 (4) Å
  • b = 15.801 (4) Å
  • c = 8.789 (2) Å
  • β = 101.168 (6)°
  • V = 1804.0 (8) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.07 mm−1
  • T = 293 K
  • 0.30 × 0.28 × 0.26 mm

Data collection

  • Rigaku AFC7S Mercury diffractometer
  • Absorption correction: multi-scan (Jacobson, 1998 [triangle]) T min = 0.971, T max = 0.981
  • 20284 measured reflections
  • 3688 independent reflections
  • 2420 reflections with I > 2σ(I)
  • R int = 0.044
  • Standard reflections: 0

Refinement

  • R[F 2 > 2σ(F 2)] = 0.058
  • wR(F 2) = 0.157
  • S = 1.07
  • 3688 reflections
  • 226 parameters
  • H-atom parameters constrained
  • Δρmax = 0.25 e Å−3
  • Δρmin = −0.20 e Å−3

Data collection: CrystalClear (Rigaku, 2002 [triangle]); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXTL-NT (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXTL-NT; molecular graphics: SHELXTL-NT and DIAMOND (Brandenburg, 1998 [triangle]); software used to prepare material for publication: SHELXTL-NT and PLATON (Spek, 2009 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I. DOI: 10.1107/S1600536810005805/tk2615sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810005805/tk2615Isup2.hkl

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

Acknowledgments

The authors are grateful for financial support from the Colombian Institute for Science and Research (COLCIENCIAS-CENIVAM, grant No. 432–2004) and FONACIT-MCT Venezuela (project: LAB-199700821). ARRB also thanks COLCIENCIAS for a fellowship.

supplementary crystallographic information

Comment

Within the quinoline family, polycyclic analogues are the most relevant compounds due to their broad potential as antitumoral agents (Gelderblom & Sparreboom, 2006; Denny & Baguley, 2003). Since the discovery of camptothecin, a natural topopisomerase (topo) I inhibitor (Pommier, 2006; Priel et al., 1991), a constant search for new compounds with the ability for inhibit the topoisomerases I/II enzymes has been undertaken (Li et al., 2006; Martínez & Chacón-García, 2005). The compound (6-[2-(dimethylamino)ethylamino]-3-hydroxy-7H-indeno[2,1-c] quinolin-7-one dihydrochloride (known as TAS-103) presents potent cytotoxicity in different leukemia lines (Twelves et al., 1999; Ohyama et al., 1999). The exhibited anti-cancer activity is due to its ability to function as a dual inhibitor of both topo I/II, and it has been investigated in clinical studies in recent years (Ewesuedo et al., 2001; Ishida & Asao, 2002).

In our preliminary studies of TAS-103 analogues, we have developed the synthesis (using the imino Diels Alder reaction) and studied the biological activity of the 6-α-pyridinyl- tetrahydro)indeno[2,1-c]quinolines (Kouznetsov et al., 2006). It was found that these compounds were active against MCF-7, H-460 and SF-268 cancer cell lines making them potential anti-cancer agents (Kouznetsov et al., 2006).

In order to obtain detailed information on its molecular conformation and the stereochemistry of the reaction, in this contribution, the molecular structure of the title compound, (I), is described. The structural analysis indicated (I) exists in the cis-form as a unique regio- and diastereo-isomer (Fig. 1). The tetrahydropyridine ring adopts a half-chair conformation and the indene ring displays an envelope configuration. The crystal packing of (I) consists of one-dimensional zigzag ribbons that run along the c direction and linked via N—H···N hydrogen bonding interactions (Fig. 2 & Table 1).

Experimental

A mixture of aryl amine (3.6 mmol) and α-pyridinecarboxyaldehyde (4.0 mmol) in anhydrous CH3CN (15 ml) was stirred at room temperature for 30 min after which BF3.OEt2 (3.6 mmol) was added. Over a period of 20 min, an acetonitrile solution (10 ml) of indene (4.0 mmol) was added dropwise. The resulting mixture was stirred at 343 K for 5 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 x 15 ml). The organic layer was separated and dried (Na2SO4), concentrated in vacuo, and the resulting product was purified by column chromatography (silica gel, petroleum ether: EtOAc) to afford pure (I) as a colorless solid, mp 424–425 K (yield 43%). This compound was recrystallized by slow evaporation from the solvent mixture, hexane-ethyl acetate.

Refinement

All H atoms were placed in geometrically idealized positions and constrained to ride on their parent atoms, with C—H distances of 0.93 (aromatic) and 0.96 Å (methyl), and with Uiso(H) = 1.5 (1.2 for aromatic-H atoms) times Ueq(C). The low completeness ratio is due to the experimental setup whereby the equipment has a χ circle and an added area detector (four-circle diffractometer modified with a CCD). This precludes the collection of some regions of reciprocal lattice space and lowers the completeness. In order to compensate, additional redundant data were measured.

Figures

Fig. 1.
Molecular structure of (I) showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 50% probability level. H atoms are represented by circles of arbitrary size.
Fig. 2.
View of a one-dimensional ribbon aligned along the c axis, generated by N—H···N hydrogen bonds. Intermolecular hydrogen bonds are indicated by dashed lines. H atoms not involved in hydrogen bonding have been omitted for ...

Crystal data

C23H22N2F(000) = 696
Mr = 326.43Dx = 1.202 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 11041 reflections
a = 13.241 (4) Åθ = 1.6–27.7°
b = 15.801 (4) ŵ = 0.07 mm1
c = 8.789 (2) ÅT = 293 K
β = 101.168 (6)°Block, yellow
V = 1804.0 (8) Å30.30 × 0.28 × 0.26 mm
Z = 4

Data collection

Rigaku AFC7S Mercury diffractometer3688 independent reflections
Radiation source: Normal-focus sealed tube2420 reflections with I > 2σ(I)
graphiteRint = 0.044
ω scansθmax = 28.0°, θmin = 2.0°
Absorption correction: multi-scan (Jacobson, 1998)h = −15→15
Tmin = 0.971, Tmax = 0.981k = −18→20
20284 measured 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)] = 0.058Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.157H-atom parameters constrained
S = 1.07w = 1/[σ2(Fo2) + (0.0698P)2 + 0.2578P] where P = (Fo2 + 2Fc2)/3
3688 reflections(Δ/σ)max < 0.001
226 parametersΔρmax = 0.25 e Å3
0 restraintsΔρmin = −0.20 e Å3

Special details

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)

xyzUiso*/Ueq
N10.02307 (11)0.64024 (9)0.43799 (17)0.0490 (4)
H1N−0.01920.65890.35650.059*
N2−0.13358 (12)0.73555 (10)0.68890 (19)0.0562 (4)
C10.00785 (13)0.68474 (11)0.5771 (2)0.0460 (4)
H10.02420.74470.56680.055*
C20.07995 (13)0.64878 (11)0.7193 (2)0.0458 (4)
H20.07410.68450.80840.055*
C30.05427 (14)0.55713 (11)0.7591 (2)0.0528 (5)
H3A0.00730.55630.83110.063*
H3B0.02370.52610.66630.063*
C40.15662 (15)0.52035 (11)0.8317 (2)0.0499 (5)
C50.17744 (17)0.44613 (13)0.9155 (2)0.0636 (6)
H50.12400.41270.93660.076*
C60.2788 (2)0.42241 (15)0.9675 (3)0.0744 (7)
H60.29340.37211.02230.089*
C70.35794 (19)0.47219 (16)0.9391 (3)0.0766 (7)
H70.42570.45550.97530.092*
C80.33764 (16)0.54720 (14)0.8568 (2)0.0653 (6)
H80.39150.58110.83870.078*
C90.23611 (14)0.57118 (11)0.8019 (2)0.0485 (5)
C100.19475 (13)0.64765 (11)0.7040 (2)0.0456 (4)
H100.22920.69920.74950.055*
C110.20897 (13)0.63816 (10)0.5372 (2)0.0434 (4)
C120.30732 (15)0.63126 (11)0.5033 (2)0.0523 (5)
H120.36360.63650.58450.063*
C130.32582 (15)0.61707 (12)0.3557 (2)0.0540 (5)
C140.24015 (16)0.60999 (12)0.2362 (2)0.0545 (5)
H140.24940.59970.13560.065*
C150.14227 (14)0.61795 (11)0.2647 (2)0.0485 (5)
H150.08640.61280.18280.058*
C160.12446 (13)0.63354 (10)0.4138 (2)0.0427 (4)
C170.43476 (17)0.60998 (15)0.3268 (3)0.0731 (7)
H17A0.48020.59430.42300.088*
H17B0.43710.56490.25260.088*
C180.4737 (2)0.6887 (2)0.2677 (5)0.1291 (13)
H18A0.54270.67980.25200.194*
H18B0.47340.73340.34160.194*
H18C0.43030.70400.17100.194*
C19−0.10323 (13)0.67742 (11)0.5962 (2)0.0459 (4)
C20−0.16803 (15)0.61310 (12)0.5276 (2)0.0562 (5)
H20−0.14460.57310.46500.067*
C21−0.26739 (16)0.60932 (13)0.5534 (3)0.0620 (6)
H21−0.31200.56690.50820.074*
C22−0.29921 (16)0.66882 (15)0.6463 (3)0.0667 (6)
H22−0.36600.66800.66500.080*
C23−0.23034 (16)0.73019 (14)0.7117 (3)0.0667 (6)
H23−0.25250.77030.77550.080*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
N10.0429 (9)0.0609 (9)0.0431 (9)0.0008 (7)0.0077 (7)−0.0047 (7)
N20.0480 (10)0.0581 (10)0.0636 (11)0.0033 (7)0.0136 (8)−0.0097 (8)
C10.0445 (11)0.0427 (9)0.0513 (11)−0.0007 (7)0.0103 (8)−0.0045 (8)
C20.0460 (11)0.0466 (10)0.0451 (10)−0.0006 (7)0.0091 (8)−0.0094 (8)
C30.0511 (12)0.0547 (11)0.0533 (11)−0.0027 (8)0.0122 (9)0.0011 (9)
C40.0565 (12)0.0515 (11)0.0408 (10)0.0000 (8)0.0067 (8)−0.0038 (8)
C50.0707 (15)0.0608 (13)0.0563 (12)−0.0049 (10)0.0051 (11)0.0056 (10)
C60.0868 (18)0.0677 (14)0.0625 (14)0.0120 (13)−0.0013 (13)0.0099 (11)
C70.0646 (16)0.0928 (17)0.0676 (15)0.0176 (13)0.0005 (12)0.0117 (13)
C80.0509 (13)0.0838 (15)0.0593 (13)0.0032 (10)0.0056 (10)0.0078 (11)
C90.0475 (12)0.0563 (11)0.0402 (10)0.0008 (8)0.0050 (8)−0.0065 (8)
C100.0439 (11)0.0461 (10)0.0461 (10)−0.0033 (7)0.0066 (8)−0.0066 (8)
C110.0439 (11)0.0418 (9)0.0445 (10)−0.0030 (7)0.0086 (8)−0.0019 (7)
C120.0436 (12)0.0595 (12)0.0526 (12)−0.0034 (8)0.0065 (9)−0.0006 (9)
C130.0498 (12)0.0606 (12)0.0540 (12)0.0000 (8)0.0164 (10)0.0008 (9)
C140.0591 (13)0.0595 (12)0.0478 (11)−0.0007 (9)0.0178 (10)−0.0022 (9)
C150.0489 (12)0.0524 (11)0.0430 (10)−0.0017 (8)0.0060 (9)−0.0009 (8)
C160.0423 (11)0.0394 (9)0.0471 (10)−0.0024 (7)0.0107 (8)−0.0004 (7)
C170.0557 (14)0.0962 (17)0.0727 (15)0.0020 (11)0.0255 (12)−0.0024 (13)
C180.085 (2)0.129 (3)0.188 (4)−0.0048 (18)0.064 (2)0.038 (3)
C190.0462 (11)0.0439 (10)0.0474 (10)0.0035 (8)0.0083 (8)−0.0001 (8)
C200.0514 (12)0.0529 (11)0.0651 (13)−0.0019 (8)0.0134 (10)−0.0089 (9)
C210.0496 (13)0.0631 (13)0.0738 (15)−0.0089 (9)0.0129 (11)−0.0028 (11)
C220.0467 (12)0.0813 (15)0.0751 (15)−0.0015 (11)0.0192 (11)−0.0010 (12)
C230.0532 (14)0.0742 (14)0.0765 (15)0.0050 (10)0.0218 (11)−0.0149 (11)

Geometric parameters (Å, °)

N1—C161.403 (2)C10—H100.9800
N1—C11.458 (2)C11—C121.395 (3)
N1—H1N0.8700C11—C161.401 (2)
N2—C231.337 (2)C12—C131.384 (3)
N2—C191.340 (2)C12—H120.9300
C1—C191.517 (2)C13—C141.393 (3)
C1—C21.528 (2)C13—C171.516 (3)
C1—H10.9800C14—C151.373 (3)
C2—C31.543 (2)C14—H140.9300
C2—C101.552 (2)C15—C161.397 (2)
C2—H20.9800C15—H150.9300
C3—C41.499 (3)C17—C181.479 (3)
C3—H3A0.9700C17—H17A0.9700
C3—H3B0.9700C17—H17B0.9700
C4—C51.384 (3)C18—H18A0.9600
C4—C91.389 (3)C18—H18B0.9600
C5—C61.383 (3)C18—H18C0.9600
C5—H50.9300C19—C201.390 (3)
C6—C71.371 (3)C20—C211.379 (3)
C6—H60.9300C20—H200.9300
C7—C81.387 (3)C21—C221.364 (3)
C7—H70.9300C21—H210.9300
C8—C91.390 (3)C22—C231.378 (3)
C8—H80.9300C22—H220.9300
C9—C101.522 (2)C23—H230.9300
C10—C111.521 (2)
C16—N1—C1117.08 (14)C12—C11—C16118.00 (17)
C16—N1—H1N112.5C12—C11—C10120.53 (16)
C1—N1—H1N110.8C16—C11—C10121.44 (16)
C23—N2—C19117.16 (17)C13—C12—C11123.67 (18)
N1—C1—C19110.52 (14)C13—C12—H12118.2
N1—C1—C2109.93 (14)C11—C12—H12118.2
C19—C1—C2110.28 (14)C12—C13—C14116.96 (18)
N1—C1—H1108.7C12—C13—C17121.04 (18)
C19—C1—H1108.7C14—C13—C17122.00 (18)
C2—C1—H1108.7C15—C14—C13120.98 (18)
C1—C2—C3113.82 (14)C15—C14—H14119.5
C1—C2—C10113.60 (14)C13—C14—H14119.5
C3—C2—C10105.75 (14)C14—C15—C16121.60 (17)
C1—C2—H2107.8C14—C15—H15119.2
C3—C2—H2107.8C16—C15—H15119.2
C10—C2—H2107.8C15—C16—C11118.71 (17)
C4—C3—C2103.86 (15)C15—C16—N1119.70 (16)
C4—C3—H3A111.0C11—C16—N1121.53 (16)
C2—C3—H3A111.0C18—C17—C13113.9 (2)
C4—C3—H3B111.0C18—C17—H17A108.8
C2—C3—H3B111.0C13—C17—H17A108.8
H3A—C3—H3B109.0C18—C17—H17B108.8
C5—C4—C9120.69 (18)C13—C17—H17B108.8
C5—C4—C3128.74 (18)H17A—C17—H17B107.7
C9—C4—C3110.56 (16)C17—C18—H18A109.5
C6—C5—C4119.1 (2)C17—C18—H18B109.5
C6—C5—H5120.5H18A—C18—H18B109.5
C4—C5—H5120.5C17—C18—H18C109.5
C7—C6—C5120.8 (2)H18A—C18—H18C109.5
C7—C6—H6119.6H18B—C18—H18C109.5
C5—C6—H6119.6N2—C19—C20122.16 (17)
C6—C7—C8120.5 (2)N2—C19—C1115.24 (15)
C6—C7—H7119.8C20—C19—C1122.56 (16)
C8—C7—H7119.8C21—C20—C19119.26 (18)
C7—C8—C9119.4 (2)C21—C20—H20120.4
C7—C8—H8120.3C19—C20—H20120.4
C9—C8—H8120.3C22—C21—C20118.92 (19)
C4—C9—C8119.61 (19)C22—C21—H21120.5
C4—C9—C10111.27 (16)C20—C21—H21120.5
C8—C9—C10129.09 (18)C21—C22—C23118.6 (2)
C11—C10—C9111.60 (14)C21—C22—H22120.7
C11—C10—C2113.02 (14)C23—C22—H22120.7
C9—C10—C2102.20 (14)N2—C23—C22123.90 (19)
C11—C10—H10109.9N2—C23—H23118.1
C9—C10—H10109.9C22—C23—H23118.1
C2—C10—H10109.9

Hydrogen-bond geometry (Å, °)

Cg4 is the centroid of the C4–C9 ring.
D—H···AD—HH···AD···AD—H···A
N1—H1N···N2i0.872.533.345 (2)157
C20—H20···N10.932.512.825 (3)100
C14—H14···Cg4ii0.932.743.611 (2)153

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: TK2615).

References

  • Brandenburg, K. (1998). DIAMOND Crystal Impact GbR, Bonn, Germany.
  • Denny, W. A. & Baguley, B. C. (2003). Curr. Top. Med. Chem.3, 339–353. [PubMed]
  • Ewesuedo, R. B., Iyer, L., Das, S., Koenig, A., Mani, S., Vogelzang, N. J., Schilsky, R. L., Brenckman, W. & Ratain, M. J. (2001). J. Clin. Oncol.19, 2084–2090. [PubMed]
  • Gelderblom, H. & Sparreboom, A. (2006). In Drugs Affecting of Tumours, edited by H. M. Pinedo & C. H. Smorenburg, pp. 83–100. Switzerland: Birkhuser Vergal.
  • Ishida, K. & Asao, T. (2002). Biochim. Biophys. Acta, 1587, 155–163. [PubMed]
  • Jacobson, R. (1998). Private communication to the Rigaku Corporation, Tokyo, Japan.
  • Kouznetsov, V. V., Ochoa Puentes, C., Zachinno, S. A., Gupta, M., Romero, B. A. R., Sortino, M., Vásquez, Y., Bahsas, A. & Amaro-Luis, J. (2006). Lett. Org. Chem.3, 300–304.
  • Li, Q.-Y., Zu, Y.-G., Shi, R.-Z. & Yao, L.-P. (2006). Curr. Med. Chem.13, 2021–2039. [PubMed]
  • Martínez, R. & Chacón-García, L. (2005). Curr. Med. Chem.12, 127–151. [PubMed]
  • Ohyama, T., Li, Y., Utsugi, T., Irie, S., Yamada, Y. & Sato, T. (1999). Jpn J. Cancer Res.44, 691–698. [PubMed]
  • Pommier, Y. (2006). Nat. Rev. Cancer, 6, 789–802. [PubMed]
  • Priel, E., Showalter, S. D., Roberts, M., Oroszlan, S. & Blair, D. G. (1991). J. Virol.65, 4137–4141. [PMC free article] [PubMed]
  • Rigaku (2002). CrystalClear Rigaku Corporation, Tokyo, Japan.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Spek, A. L. (2009). Acta Cryst. D65, 148–155. [PMC free article] [PubMed]
  • Twelves, C. J., Gardner, C., Flavin, A., Sludden, J., Dennis, I., de Bono, J., Beale, P., Vasey, P., Hutchison, C., Macham, M. A., Rodríguez, A., Judson, I. & Bleehen, N. M. (1999). Br. J. Cancer, 80, 1786–1791. [PMC free article] [PubMed]

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