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Acta Crystallogr Sect E Struct Rep Online. 2010 February 1; 66(Pt 2): o451.
Published online 2010 January 27. doi:  10.1107/S1600536810002680
PMCID: PMC2979910

7-[4-(4-Fluoro­phen­yl)-2-methyl­sulfanyl-1H-imidazol-5-yl]tetra­zolo[1,5-a]pyridine

Abstract

The crystal structure of the title compound, C15H11FN6S, forms a three-dimensional network stabilized by π–π inter­actions between the imidazole core and the tetra­zole ring of the tetra­zolopyridine­unit; the centroid–centroid distance is 3.627 (1) Å. The crystal structure also displays bifurcated N—H(...)(N,N) hydrogen bonding and C—H(...)F inter­actions. The former involve the NH H atom of the imidazole core and the tetra­zolopyridine N atoms, while the latter involve a methyl H atom, of the methyl­sulfanyl group, and the 4-fluoro­phenyl F atom. In the mol­ecule, the imidazole ring makes dihedral angles of 40.45 (9) and 17.09 (8)°, respectively, with the 4-fluoro­phenyl ring and the tetra­zolopyridine ring mean plane.

Related literature

For the biological relevance and the development of p38 MAP kinase inhibitors, see: see: Peifer et al. (2006 [triangle]). For the preparation of 2-fluoro-4-[4-(4-fluoro­phen­yl)-2-(methyl­thio)-1H-imidazol-5-yl]pyridine, see: Laufer & Liedtke (2006 [triangle]). For the preparation of tetra­zolopyridines, see: Capelli et al. (2008 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-0o451-scheme1.jpg

Experimental

Crystal data

  • C15H11FN6S
  • M r = 326.36
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-0o451-efi1.jpg
  • a = 9.8342 (7) Å
  • b = 18.1908 (6) Å
  • c = 8.2374 (7) Å
  • β = 100.292 (3)°
  • V = 1449.89 (17) Å3
  • Z = 4
  • Cu Kα radiation
  • μ = 2.17 mm−1
  • T = 193 K
  • 0.30 × 0.20 × 0.10 mm

Data collection

  • Enraf–Nonius CAD-4 diffractometer
  • Absorption correction: ψ scan (CORINC; Dräger & Gattow, 1971 [triangle]) T min = 0.866, T max = 0.999
  • 5760 measured reflections
  • 2733 independent reflections
  • 2403 reflections with I > 2σ(I)
  • R int = 0.056
  • 3 standard reflections every 60 min intensity decay: 3%

Refinement

  • R[F 2 > 2σ(F 2)] = 0.038
  • wR(F 2) = 0.107
  • S = 1.06
  • 2733 reflections
  • 210 parameters
  • H-atom parameters constrained
  • Δρmax = 0.37 e Å−3
  • Δρmin = −0.30 e Å−3

Data collection: CAD-4 Software (Enraf–Nonius, 1989 [triangle]); cell refinement: CAD-4 Software; data reduction: CORINC (Dräger & Gattow, 1971 [triangle]); 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/S1600536810002680/su2158sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810002680/su2158Isup2.hkl

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

Acknowledgments

The authors would like to thank the Federal Ministry of Education and Research, Germany, Merckle GmbH, Ulm, Germany, and the Fonds der Chemischen Industrie, Germany, for their generous support of this work.

supplementary crystallographic information

Comment

Pyridylimidazoles like SB203580 are well known p38 MAP kinase inhibitors (Peifer et al., 2006). The function of the pyridine moiety is to accept a hydrogen bond from the backbone of Met109 in the Hinge region. In the course of our studies we have tried to modify this acceptor system by using the title tetrazolopyridine (Capelli et al., 2008).

The molecular structure of the title compound is given in Fig. 1, and the geometrical parameters are available in the Supplementary information and the archived CIF. The imidazole ring mean plane makes dihedral angles of 40.45 (9)° and 17.09 (8)° with the 4-fluorophenyl ring and the tetrazolopyridine ring mean plane, respectively.

The crystal structure displays asymmetric bifurcated N—H···N hydrogen bonds involving the tetrazolopyridine N-atoms and the NH H-atom of the the imidazole core (Table 1). There is also a C-H···F interaction involving the methylsulfanyl group and the 4-fluorophenyl F-atom (Table 1). The crystal structure of the title compound forms a three dimensional network stabilized by π-π interactions between the imidazole core and the tetrazole moiety of the tetrazolopyridine group; the centroid···centroid distance is 3.627 (1) Å (Table 1).

Experimental

A mixture of 300 mg 2-fluoro-4-[4-(4-fluorophenyl)-2-(methylthio)-1H-imidazol-5- yl]pyridine (Laufer & Liedtke, 2006) in anhydrous DMF with 100 mg sodium azide was heated at 353 K for 12 h. The solvent was then removed under reduced pressure and the residue was diluted with ethylacetate. The organic phase was washed with water and concentrated under reduced pressure. The residue was purified by flash chromatography with ethyl acetate/hexane (1/1) to yield 153 mg (47%) of the title compound. Crystals suitable for X-ray analysis were obtained by crystallization from methanol.

Refinement

The H atom attached to N10 was located in a difference Fourier map and refined with a distance restraint of 0.92 (2) Å and Uiso(H) = 1.2Ueq(N). The C-bound H-atoms were placed in calculated positions and refined in the riding-model approximation: C-H = 0.95 - 0.98 Å with Uiso(H) = k × Ueq(C), where k = 1.2 for H-aromatic and 1.5 for H-methyl.

Figures

Fig. 1.
A view of the molecular structure of the title compound. the displacement ellipsoids are drawn at the 50% probability level.

Crystal data

C15H11FN6SF(000) = 672
Mr = 326.36Dx = 1.495 Mg m3
Monoclinic, P21/cCu Kα radiation, λ = 1.54178 Å
Hall symbol: -P 2ybcCell parameters from 25 reflections
a = 9.8342 (7) Åθ = 65–70°
b = 18.1908 (6) ŵ = 2.17 mm1
c = 8.2374 (7) ÅT = 193 K
β = 100.292 (3)°Plate, colourless
V = 1449.89 (17) Å30.30 × 0.20 × 0.10 mm
Z = 4

Data collection

Enraf–Nonius CAD-4 diffractometer2403 reflections with I > 2σ(I)
Radiation source: rotating anodeRint = 0.056
graphiteθmax = 69.9°, θmin = 4.6°
ω/2θ scansh = −11→11
Absorption correction: ψ scan (CORINC; Dräger & Gattow, 1971)k = −22→22
Tmin = 0.866, Tmax = 0.999l = −10→0
5760 measured reflections3 standard reflections every 60 min
2733 independent reflections intensity decay: 3%

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.038H-atom parameters constrained
wR(F2) = 0.107w = 1/[σ2(Fo2) + (0.051P)2 + 0.5315P] where P = (Fo2 + 2Fc2)/3
S = 1.06(Δ/σ)max = 0.001
2733 reflectionsΔρmax = 0.37 e Å3
210 parametersΔρmin = −0.30 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: 0.0014 (2)

Special details

Geometry. Bond distances, angles etc. have been calculated using the rounded fractional coordinates. All su's are estimated from the variances of the (full) variance-covariance matrix. The cell esds are taken into account in the estimation of distances, angles and torsion angles
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
S200.84423 (5)0.32567 (2)0.15709 (8)0.0423 (2)
F190.09192 (12)0.08344 (6)0.37488 (16)0.0442 (4)
N10.29691 (15)0.61704 (7)0.31439 (19)0.0284 (4)
N20.18289 (15)0.63452 (8)0.3762 (2)0.0315 (4)
N30.12953 (15)0.57831 (8)0.4381 (2)0.0304 (4)
N3A0.21213 (13)0.52053 (7)0.41594 (17)0.0232 (4)
N80.62050 (14)0.39105 (8)0.25381 (18)0.0265 (4)
N100.61319 (14)0.26910 (7)0.24463 (18)0.0271 (4)
C40.20076 (17)0.44913 (9)0.4666 (2)0.0267 (5)
C50.29443 (17)0.40040 (9)0.4318 (2)0.0264 (5)
C60.40054 (16)0.42075 (8)0.3415 (2)0.0221 (4)
C70.41195 (16)0.49369 (9)0.2991 (2)0.0231 (4)
C7A0.31553 (16)0.54434 (9)0.3388 (2)0.0230 (4)
C90.68541 (17)0.33087 (9)0.2239 (2)0.0275 (5)
C110.49088 (16)0.29071 (9)0.2895 (2)0.0239 (5)
C120.49810 (16)0.36671 (9)0.2974 (2)0.0233 (5)
C130.38534 (16)0.23580 (9)0.3073 (2)0.0241 (5)
C140.24524 (17)0.24835 (9)0.2461 (2)0.0286 (5)
C150.14573 (18)0.19732 (10)0.2673 (2)0.0313 (5)
C160.18916 (19)0.13307 (9)0.3491 (2)0.0301 (5)
C170.32598 (19)0.11634 (9)0.4043 (2)0.0297 (5)
C180.42396 (18)0.16837 (9)0.3835 (2)0.0266 (5)
C210.8749 (2)0.42202 (11)0.1351 (3)0.0420 (7)
H40.129400.434700.523900.0320*
H50.290100.351000.468200.0320*
H70.483900.509300.243900.0280*
H100.645900.222700.232200.0320*
H140.217900.292800.188900.0340*
H150.050500.206300.226900.0380*
H170.352400.070400.455200.0360*
H180.519000.158200.421600.0320*
H21A0.802500.442700.050100.0630*
H21B0.965200.429100.102800.0630*
H21C0.873800.446900.240300.0630*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
S200.0311 (3)0.0261 (3)0.0757 (4)0.0036 (2)0.0258 (2)−0.0011 (2)
F190.0400 (6)0.0307 (6)0.0661 (8)−0.0095 (5)0.0210 (6)0.0042 (5)
N10.0261 (7)0.0188 (7)0.0413 (8)0.0027 (5)0.0087 (6)0.0029 (6)
N20.0264 (7)0.0217 (7)0.0478 (9)0.0046 (6)0.0104 (6)0.0033 (6)
N30.0264 (7)0.0230 (7)0.0436 (9)0.0066 (6)0.0112 (6)0.0017 (6)
N3A0.0207 (6)0.0193 (6)0.0304 (7)0.0018 (5)0.0066 (5)0.0006 (5)
N80.0218 (7)0.0208 (7)0.0377 (8)0.0005 (5)0.0073 (6)−0.0022 (6)
N100.0239 (7)0.0182 (6)0.0395 (8)0.0026 (5)0.0067 (6)−0.0020 (6)
C40.0273 (8)0.0208 (8)0.0342 (9)−0.0014 (6)0.0113 (7)0.0034 (7)
C50.0304 (8)0.0185 (8)0.0311 (9)−0.0003 (6)0.0076 (7)0.0027 (7)
C60.0209 (7)0.0192 (7)0.0255 (8)0.0000 (6)0.0019 (6)−0.0016 (6)
C70.0202 (7)0.0204 (7)0.0293 (8)−0.0014 (6)0.0059 (6)−0.0012 (6)
C7A0.0211 (7)0.0191 (7)0.0286 (8)−0.0018 (6)0.0037 (6)0.0000 (6)
C90.0219 (8)0.0219 (8)0.0390 (9)0.0005 (6)0.0062 (7)−0.0014 (7)
C110.0228 (8)0.0194 (8)0.0287 (8)0.0020 (6)0.0027 (6)−0.0015 (6)
C120.0221 (8)0.0198 (8)0.0275 (8)0.0007 (6)0.0031 (6)−0.0004 (6)
C130.0265 (8)0.0193 (8)0.0262 (8)0.0003 (6)0.0043 (6)−0.0028 (6)
C140.0283 (9)0.0198 (8)0.0364 (10)0.0018 (7)0.0022 (7)0.0005 (7)
C150.0246 (8)0.0256 (8)0.0432 (10)0.0009 (7)0.0044 (7)−0.0034 (8)
C160.0320 (9)0.0227 (8)0.0382 (9)−0.0057 (7)0.0133 (7)−0.0041 (7)
C170.0389 (10)0.0212 (8)0.0299 (9)0.0016 (7)0.0088 (7)0.0025 (7)
C180.0280 (8)0.0222 (8)0.0288 (8)0.0027 (6)0.0026 (7)−0.0005 (6)
C210.0417 (11)0.0295 (10)0.0608 (13)−0.0047 (8)0.0255 (10)−0.0009 (9)

Geometric parameters (Å, °)

S20—C91.7488 (18)C11—C121.385 (2)
S20—C211.793 (2)C11—C131.467 (2)
F19—C161.359 (2)C13—C181.399 (2)
N1—N21.350 (2)C13—C141.399 (2)
N1—C7A1.345 (2)C14—C151.382 (2)
N2—N31.295 (2)C15—C161.378 (2)
N3—N3A1.361 (2)C16—C171.375 (3)
N3A—C41.375 (2)C17—C181.383 (2)
N3A—C7A1.362 (2)C4—H40.9500
N8—C91.313 (2)C5—H50.9500
N8—C121.389 (2)C7—H70.9500
N10—C91.356 (2)C14—H140.9500
N10—C111.377 (2)C15—H150.9500
N10—H100.9200C17—H170.9500
C4—C51.346 (2)C18—H180.9500
C5—C61.434 (2)C21—H21A0.9800
C6—C71.382 (2)C21—H21B0.9800
C6—C121.464 (2)C21—H21C0.9800
C7—C7A1.402 (2)
C9—S20—C2198.90 (9)C11—C13—C14121.46 (15)
N2—N1—C7A105.98 (13)C11—C13—C18120.11 (15)
N1—N2—N3112.64 (14)C13—C14—C15121.26 (15)
N2—N3—N3A105.28 (14)C14—C15—C16117.82 (16)
N3—N3A—C4127.32 (14)F19—C16—C17118.39 (15)
N3—N3A—C7A109.28 (13)F19—C16—C15118.32 (16)
C4—N3A—C7A123.36 (14)C15—C16—C17123.28 (17)
C9—N8—C12104.82 (14)C16—C17—C18118.02 (15)
C9—N10—C11107.42 (13)C13—C18—C17121.08 (16)
C11—N10—H10129.00N3A—C4—H4121.00
C9—N10—H10123.00C5—C4—H4121.00
N3A—C4—C5117.50 (15)C4—C5—H5119.00
C4—C5—C6121.98 (15)C6—C5—H5119.00
C5—C6—C7118.59 (14)C6—C7—H7121.00
C5—C6—C12121.68 (14)C7A—C7—H7121.00
C7—C6—C12119.71 (14)C13—C14—H14119.00
C6—C7—C7A118.90 (15)C15—C14—H14119.00
N3A—C7A—C7119.48 (14)C14—C15—H15121.00
N1—C7A—N3A106.81 (14)C16—C15—H15121.00
N1—C7A—C7133.70 (15)C16—C17—H17121.00
S20—C9—N8126.57 (13)C18—C17—H17121.00
S20—C9—N10120.80 (12)C13—C18—H18119.00
N8—C9—N10112.59 (15)C17—C18—H18119.00
N10—C11—C12104.93 (14)S20—C21—H21A109.00
C12—C11—C13134.93 (15)S20—C21—H21B109.00
N10—C11—C13120.00 (14)S20—C21—H21C109.00
N8—C12—C11110.22 (14)H21A—C21—H21B109.00
C6—C12—C11130.65 (15)H21A—C21—H21C109.00
N8—C12—C6119.13 (14)H21B—C21—H21C109.00
C14—C13—C18118.41 (15)
C21—S20—C9—N8−3.16 (18)C5—C6—C12—C1118.8 (3)
C21—S20—C9—N10174.43 (15)C7—C6—C12—N816.8 (2)
N2—N1—C7A—C7178.07 (18)C7—C6—C12—C11−162.78 (17)
N2—N1—C7A—N3A−0.43 (18)C5—C6—C12—N8−161.63 (15)
C7A—N1—N2—N30.4 (2)C12—C6—C7—C7A178.46 (15)
N1—N2—N3—N3A−0.1 (2)C6—C7—C7A—N3A−0.9 (2)
N2—N3—N3A—C7A−0.15 (18)C6—C7—C7A—N1−179.22 (18)
N2—N3—N3A—C4177.50 (16)N10—C11—C12—N81.62 (18)
N3—N3A—C7A—N10.37 (18)N10—C11—C12—C6−178.74 (16)
N3—N3A—C4—C5−179.88 (15)C13—C11—C12—N8−173.91 (17)
C7A—N3A—C4—C5−2.5 (2)C13—C11—C12—C65.7 (3)
C4—N3A—C7A—C73.9 (2)N10—C11—C13—C14−136.99 (17)
N3—N3A—C7A—C7−178.39 (15)N10—C11—C13—C1841.5 (2)
C4—N3A—C7A—N1−177.39 (15)C12—C11—C13—C1438.0 (3)
C12—N8—C9—S20177.95 (13)C12—C11—C13—C18−143.46 (19)
C9—N8—C12—C11−1.15 (18)C11—C13—C14—C15−178.13 (15)
C12—N8—C9—N100.20 (19)C18—C13—C14—C153.3 (2)
C9—N8—C12—C6179.17 (15)C11—C13—C18—C17178.80 (15)
C9—N10—C11—C12−1.45 (18)C14—C13—C18—C17−2.6 (2)
C9—N10—C11—C13174.90 (15)C13—C14—C15—C16−0.8 (2)
C11—N10—C9—S20−177.08 (12)C14—C15—C16—F19178.12 (15)
C11—N10—C9—N80.82 (19)C14—C15—C16—C17−2.6 (3)
N3A—C4—C5—C6−1.7 (2)F19—C16—C17—C18−177.45 (15)
C4—C5—C6—C74.4 (2)C15—C16—C17—C183.3 (3)
C4—C5—C6—C12−177.10 (16)C16—C17—C18—C13−0.6 (2)
C5—C6—C7—C7A−3.0 (2)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N10—H10···N1i0.922.062.9703 (19)174
N10—H10···N2i0.922.603.423 (2)151
C7—H7···N80.952.532.847 (2)100
C21—H21B···F19ii0.982.443.286 (3)144

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

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: SU2158).

References

  • Altomare, A., Burla, M. C., Camalli, M., Cascarano, G. L., Giacovazzo, C., Guagliardi, A., Moliterni, A. G. G., Polidori, G. & Spagna, R. (1999). J. Appl. Cryst.32, 115–119.
  • Capelli, A., Giuliani, G., Anzini, M., Riitano, D., Giorgi, G. & Vomero, S. (2008). Bioorg. Med. Chem.16, 6850–6859. [PubMed]
  • Dräger, M. & Gattow, G. (1971). Acta Chem. Scand.25, 761–762.
  • Enraf–Nonius (1989). CAD-4 Software Enraf–Nonius, Delft, The Netherlands.
  • Laufer, S. & Liedtke, A. (2006). Tetrahedron Lett.47, 7199–7203.
  • Peifer, C., Wagner, G. & Laufer, S. (2006). Curr. Top. Med. Chem.6, 113–149. [PubMed]
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Spek, A. L. (2009). Acta Cryst. D65, 148–155. [PMC free article] [PubMed]

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