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Acta Crystallogr Sect E Struct Rep Online. 2010 August 1; 66(Pt 8): o1999.
Published online 2010 July 14. doi:  10.1107/S1600536810026577
PMCID: PMC3007311

Ethyl 5-methyl­imidazo[1,2-a]pyridine-2-carboxyl­ate

Abstract

The title compound, C11H12N2O2, was synthesized from the reaction of 6-methyl­pyridin-2-amine and ethyl 3-bromo-2-oxopropionate. In the mol­ecular structure, the six- and five-membered rings are individually almost planar with r.m.s. deviations of 0.003 and 0.002 Å, respectively. The two rings are almost coplanar, the dihedral angle between their planes being 1.4 (3)°. Inter­molecular C—H(...)O and C—H(...)N hydrogen bonds are present in the crystal structure.

Related literature

For the biological properties of related compounds, see: Xia et al. (2005 [triangle]); Warshakoon et al. (2006 [triangle]); Imaeda et al. (2008 [triangle]). For the synthetic procedure, see: Xia et al. (2005 [triangle]). For bond-length data, see: Allen et al. (1987 [triangle]).

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Object name is e-66-o1999-scheme1.jpg

Experimental

Crystal data

  • C11H12N2O2
  • M r = 204.23
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-o1999-efi1.jpg
  • a = 17.164 (3) Å
  • b = 10.521 (2) Å
  • c = 13.759 (3) Å
  • β = 124.77 (3)°
  • V = 2041 (1) Å3
  • Z = 8
  • Mo Kα radiation
  • μ = 0.09 mm−1
  • T = 293 K
  • 0.30 × 0.20 × 0.10 mm

Data collection

  • Enraf–Nonius CAD-4 diffractometer
  • Absorption correction: ψ scan (North et al., 1968 [triangle]) T min = 0.973, T max = 0.991
  • 1923 measured reflections
  • 1859 independent reflections
  • 1360 reflections with I > 2σ(I)
  • R int = 0.028
  • 3 standard reflections every 200 reflections intensity decay: 1%

Refinement

  • R[F 2 > 2σ(F 2)] = 0.051
  • wR(F 2) = 0.152
  • S = 1.00
  • 1859 reflections
  • 137 parameters
  • H-atom parameters constrained
  • Δρmax = 0.24 e Å−3
  • Δρmin = −0.20 e Å−3

Data collection: CAD-4 EXPRESS (Enraf–Nonius, 1994 [triangle]); cell refinement: CAD-4 EXPRESS; data reduction: XCAD4 (Harms & Wocadlo, 1995 [triangle]); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: SHELXTL (Sheldrick, 2008 [triangle]); software used to prepare material for publication: SHELXL97.

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810026577/im2214sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810026577/im2214Isup2.hkl

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

Acknowledgments

The authors would like to thank Professor Hua-qin Wang of Nanjing University for the data collection.

supplementary crystallographic information

Comment

Imidazo[1,2a]pyridine derivatives are of great interest because of their chemical and pharmaceutical properties. Some derivatives play a key role in preparing hypoxia inducible factor 1α prolyl hydroxylase inhibitors. And HIF-1α is of great potential value for treating ischemic diseases (Warshakoon et al.,2006). Some can be used as a material for preparing a series of FXa inhibitors, which can be used to cure various kinds of thromboembolic diseases (Imaeda et al.,2008). Herein we report the crystal structure of the title compound, (I). The molecular structure of (I) is shown in Fig.1. In this structure ring A (C1/C2/C3/C4/N2/C7) is a planar six-mermbered ring and the mean deviation from plane is 0.0027 Å, ring B(C4/N1/C5/C6/N2) is a planar five-mermbered ring with a mean deviation from planarity of 0.0018 Å. The dihedral angle between A and B ring is 1.4 (3)°. In the crystal structure, intermolecular C—H···O and C—H···N hydrogen bonds (Table 1) link the molecules to form a trimeric unit (Fig. 2).

Experimental

6-Methyl-pyridin-2-ylamine (8 mmol) and 3-bromo-2-oxo-propionic acid ethyl ester (12 mmol) were added to 50 mL ethanol. The mixture was refluxed for 6 h and then the solvent was totally evaporated. Solid anhydrous KHCO3 was added until pH=8 had been reached. Set aside for 3 h led to the observation of a white, flocculent precipitate, which was filtered and dried (yield ca. 52.6%, Xia et al. (2005)). Crystals suitable for X-ray analysis were obtained by dissolving (I) (0.5 g) in ethyl acetate (20 ml) and evaporating the solvent slowly at room temperature for about 10 d.

Refinement

All H atoms were positioned geometrically, with C—H= 0.97, 0.96 and 0.93 Å for methylene, methyl and aromatic H atoms, respectively, and constrained to ride on their parent atoms, with Uiso(H)=xUeq(C), where x=1.5 for methyl H atoms and x=1.2 for all other H atoms.

Figures

Fig. 1.
A view of the molecular structure of (I). Displacement ellipsoids are drawn at the 50% probability level.
Fig. 2.
A packing diagram for (I). Dashed lines indicate an intermolecular C—H···N hydrogen bond and an intermolecular C—H···O hydrogen bond.

Crystal data

C11H12N2O2F(000) = 864
Mr = 204.23Dx = 1.329 Mg m3
Monoclinic, C2/cMelting point = 425–426 K
Hall symbol: -C 2ycMo Kα radiation, λ = 0.71073 Å
a = 17.164 (3) ÅCell parameters from 25 reflections
b = 10.521 (2) Åθ = 9–13°
c = 13.759 (3) ŵ = 0.09 mm1
β = 124.77 (3)°T = 293 K
V = 2041 (1) Å3Block, colorless
Z = 80.30 × 0.20 × 0.10 mm

Data collection

Enraf–Nonius CAD-4 diffractometer1360 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.028
graphiteθmax = 25.3°, θmin = 2.4°
ω/2θ scansh = −20→0
Absorption correction: ψ scan (North et al., 1968)k = −12→0
Tmin = 0.973, Tmax = 0.991l = −13→16
1923 measured reflections3 standard reflections every 200 reflections
1859 independent reflections intensity decay: 1%

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.051H-atom parameters constrained
wR(F2) = 0.152w = 1/[σ2(Fo2) + (0.1P)2] where P = (Fo2 + 2Fc2)/3
S = 1.00(Δ/σ)max < 0.001
1859 reflectionsΔρmax = 0.24 e Å3
137 parametersΔρmin = −0.20 e Å3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0117 (17)

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
N10.12866 (11)0.40243 (18)0.19751 (15)0.0466 (5)
O10.07064 (11)0.13738 (15)0.15389 (15)0.0602 (5)
C10.06679 (17)0.7803 (2)0.15626 (19)0.0523 (6)
H1B0.05020.86580.14520.063*
N20.02673 (11)0.56505 (15)0.13920 (13)0.0376 (4)
O2−0.07427 (10)0.20448 (14)0.09371 (13)0.0512 (5)
C20.16246 (17)0.7466 (3)0.2109 (2)0.0582 (6)
H2A0.20750.81020.23460.070*
C30.19016 (14)0.6232 (2)0.22978 (18)0.0527 (6)
H3A0.25370.60200.26650.063*
C40.12108 (13)0.5273 (2)0.19286 (17)0.0422 (5)
C50.03813 (14)0.3590 (2)0.14702 (17)0.0408 (5)
C6−0.02457 (13)0.45553 (19)0.11134 (16)0.0387 (5)
H6A−0.08960.44870.07510.046*
C7−0.00174 (15)0.6916 (2)0.11927 (17)0.0432 (5)
C8−0.10473 (15)0.7154 (2)0.05724 (19)0.0509 (6)
H8A−0.11640.80530.04800.076*
H8B−0.12600.68070.10280.076*
H8C−0.13850.6757−0.01920.076*
C90.01645 (14)0.2218 (2)0.13352 (17)0.0432 (5)
C10−0.10735 (16)0.0748 (2)0.0699 (2)0.0560 (6)
H10A−0.07010.02410.14120.067*
H10B−0.10110.03860.00980.067*
C11−0.20816 (17)0.0755 (3)0.0283 (2)0.0727 (8)
H11A−0.2321−0.00990.01140.109*
H11B−0.24430.1261−0.04210.109*
H11C−0.21340.11090.08870.109*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
N10.0347 (9)0.0568 (12)0.0450 (10)0.0026 (8)0.0208 (8)0.0007 (8)
O10.0514 (10)0.0524 (10)0.0734 (11)0.0127 (8)0.0335 (9)0.0054 (8)
C10.0589 (14)0.0472 (13)0.0525 (13)−0.0098 (11)0.0328 (11)−0.0024 (10)
N20.0335 (9)0.0460 (10)0.0347 (9)−0.0019 (7)0.0202 (7)−0.0025 (7)
O20.0443 (9)0.0417 (9)0.0654 (10)−0.0026 (6)0.0301 (8)−0.0048 (7)
C20.0540 (14)0.0666 (16)0.0554 (13)−0.0196 (12)0.0320 (11)−0.0058 (12)
C30.0362 (11)0.0717 (17)0.0488 (13)−0.0106 (10)0.0234 (10)−0.0027 (11)
C40.0330 (10)0.0564 (14)0.0360 (10)−0.0003 (9)0.0188 (8)−0.0004 (9)
C50.0365 (10)0.0492 (12)0.0365 (10)0.0012 (9)0.0207 (9)0.0003 (9)
C60.0327 (10)0.0457 (12)0.0372 (10)−0.0037 (9)0.0196 (8)−0.0020 (9)
C70.0474 (12)0.0466 (13)0.0387 (11)−0.0031 (10)0.0264 (9)−0.0024 (9)
C80.0498 (13)0.0447 (13)0.0588 (13)0.0022 (10)0.0313 (11)−0.0019 (10)
C90.0397 (11)0.0491 (13)0.0401 (11)0.0056 (9)0.0223 (9)0.0022 (9)
C100.0557 (14)0.0427 (13)0.0662 (15)−0.0034 (10)0.0327 (12)−0.0038 (11)
C110.0557 (15)0.0608 (17)0.092 (2)−0.0087 (12)0.0369 (15)−0.0109 (14)

Geometric parameters (Å, °)

N1—C41.318 (3)C3—H3A0.9300
N1—C51.369 (2)C5—C61.352 (3)
O1—C91.198 (2)C5—C91.475 (3)
C1—C71.353 (3)C6—H6A0.9300
C1—C21.407 (3)C7—C81.482 (3)
C1—H1B0.9300C8—H8A0.9600
N2—C61.366 (2)C8—H8B0.9600
N2—C71.391 (3)C8—H8C0.9600
N2—C41.401 (2)C10—C111.480 (3)
O2—C91.336 (2)C10—H10A0.9700
O2—C101.442 (3)C10—H10B0.9700
C2—C31.357 (4)C11—H11A0.9600
C2—H2A0.9300C11—H11B0.9600
C3—C41.412 (3)C11—H11C0.9600
C4—N1—C5104.84 (16)C1—C7—C8126.6 (2)
C7—C1—C2121.8 (2)N2—C7—C8116.43 (18)
C7—C1—H1B119.1C7—C8—H8A109.5
C2—C1—H1B119.1C7—C8—H8B109.5
C6—N2—C7130.90 (17)H8A—C8—H8B109.5
C6—N2—C4105.97 (16)C7—C8—H8C109.5
C7—N2—C4123.11 (16)H8A—C8—H8C109.5
C9—O2—C10116.01 (17)H8B—C8—H8C109.5
C3—C2—C1121.2 (2)O1—C9—O2124.2 (2)
C3—C2—H2A119.4O1—C9—C5126.1 (2)
C1—C2—H2A119.4O2—C9—C5109.67 (17)
C2—C3—C4119.0 (2)O2—C10—C11107.8 (2)
C2—C3—H3A120.5O2—C10—H10A110.2
C4—C3—H3A120.5C11—C10—H10A110.2
N1—C4—N2111.15 (17)O2—C10—H10B110.2
N1—C4—C3130.93 (19)C11—C10—H10B110.2
N2—C4—C3117.91 (19)H10A—C10—H10B108.5
C6—C5—N1111.79 (19)C10—C11—H11A109.5
C6—C5—C9126.71 (19)C10—C11—H11B109.5
N1—C5—C9121.48 (18)H11A—C11—H11B109.5
C5—C6—N2106.24 (17)C10—C11—H11C109.5
C5—C6—H6A126.9H11A—C11—H11C109.5
N2—C6—H6A126.9H11B—C11—H11C109.5
C1—C7—N2117.0 (2)
C7—C1—C2—C3−0.6 (3)C4—N2—C6—C5−0.42 (19)
C1—C2—C3—C40.4 (3)C2—C1—C7—N20.9 (3)
C5—N1—C4—N2−0.5 (2)C2—C1—C7—C8−177.8 (2)
C5—N1—C4—C3−179.0 (2)C6—N2—C7—C1−178.96 (19)
C6—N2—C4—N10.6 (2)C4—N2—C7—C1−1.2 (3)
C7—N2—C4—N1−177.71 (17)C6—N2—C7—C8−0.2 (3)
C6—N2—C4—C3179.30 (17)C4—N2—C7—C8177.64 (16)
C7—N2—C4—C31.0 (3)C10—O2—C9—O1−2.8 (3)
C2—C3—C4—N1177.8 (2)C10—O2—C9—C5176.75 (17)
C2—C3—C4—N2−0.6 (3)C6—C5—C9—O1171.5 (2)
C4—N1—C5—C60.2 (2)N1—C5—C9—O1−6.9 (3)
C4—N1—C5—C9178.87 (19)C6—C5—C9—O2−8.0 (3)
N1—C5—C6—N20.2 (2)N1—C5—C9—O2173.49 (16)
C9—C5—C6—N2−178.43 (18)C9—O2—C10—C11179.40 (18)
C7—N2—C6—C5177.67 (18)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C2—H2A···N1i0.932.593.461 (4)155
C3—H3A···O1i0.932.583.456 (4)157

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: IM2214).

References

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  • Enraf–Nonius (1989). CAD-4 EXPRESS Enraf–Nonius, Delft, The Netherlands.
  • Harms, K. & Wocadlo, S. (1995). XCAD4 University of Marburg, Germany.
  • Imaeda, Y., Kawasamoto, T., Tobisu, M., Konishi, N., Hiroe, K., Kawamura, M., Tanaka, T. & Kubo, K. (2008). Bioorg. Med. Chem.16, 3125–3140. [PubMed]
  • North, A. C. T., Phillips, D. C. & Mathews, F. S. (1968). Acta Cryst. A24, 351–359.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Warshakoon, N. C., Wu, S., Boyer, A., Kawamoto, R., Sheville, J., Renock, S., Xu, K., Pokross, M., Evdokimov, A. G., Walter, R. & Mekel, M. (2006). Bioorg. Med. Chem. Lett.16, 5598–5601. [PubMed]
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