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Acta Crystallogr Sect E Struct Rep Online. 2009 October 1; 65(Pt 10): o2512.
Published online 2009 September 26. doi:  10.1107/S1600536809037295
PMCID: PMC2970199

2-(4-Fluoro­phen­yl)-3-(4-pyrid­yl)pyrido[2,3-b]pyrazine

Abstract

In the crystal structure of the title compound, C18H11FN4, the pyridopyrazine system makes dihedral angles of 45.51 (7) and 44.75 (7)° with the attached 4-fluoro­phenyl ring and the pyridine ring, respectively. The 4-fluoro­phenyl ring makes a dihedral angle of 54.54 (8)° with the pyridine ring. The pyridine ring part of the pyridopyrazine ring and the pyrazine ring of two c-glide-plane-related mol­ecules form π–π inter­actions. The angle between the planes is 2.09 (7)° and the distance between the centroids is 3.557 (1)Å.

Related literature

For preparation of pyridopyrazines under microwave conditions, see: Zhao et al. (2004 [triangle]).

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Object name is e-65-o2512-scheme1.jpg

Experimental

Crystal data

  • C18H11FN4
  • M r = 302.31
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o2512-efi1.jpg
  • a = 17.222 (9) Å
  • b = 11.2199 (12) Å
  • c = 7.329 (4) Å
  • β = 91.80 (3)°
  • V = 1415.4 (10) Å3
  • Z = 4
  • Cu Kα radiation
  • μ = 0.80 mm−1
  • T = 193 K
  • 0.64 × 0.51 × 0.06 mm

Data collection

  • Enraf–Nonius CAD-4 diffractometer
  • Absorption correction: numerical (CORINC; Dräger & Gattow, 1971 [triangle]) T min = 0.675, T max = 0.949
  • 2766 measured reflections
  • 2677 independent reflections
  • 2309 reflections with I > 2σ(I)
  • R int = 0.029
  • 3 standard reflections frequency: 60 min intensity decay: 2%

Refinement

  • R[F 2 > 2σ(F 2)] = 0.046
  • wR(F 2) = 0.134
  • S = 1.07
  • 2677 reflections
  • 209 parameters
  • H-atom parameters constrained
  • Δρmax = 0.22 e Å−3
  • Δρmin = −0.24 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.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809037295/nc2158sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809037295/nc2158Isup2.hkl

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

supplementary crystallographic information

Comment

The title compound, 2-(4-fluorophenyl)-3-(pyridin-4-yl)pyrido[3,2-b]pyrazine (II), was prepared in the course of our studies on pyridin-4-yl-substituted pyridopyrazines as potent p38 mitogen-activated protein (MAP) kinase inhibitors.

The microwave-assisted reaction of 1-(4-fluorophenyl)-2-(pyridin-4-yl)ethane-1,2-dione and 2,3-diaminopyridine yields two regioisomers, 3-(4-fluorophenyl)-2-(pyridin-4-yl)pyrido[2,3-b]pyrazine (I) and 2-(4-fluorophenyl)-3-(pyridin-4-yl)pyrido[3,2-b]pyrazine (II) (Figure I). The isomers were separated by flash-chromatography. To identify the two regioisomers x-ray analysis was used. In this article we present the x-ray data of the last eluted isomer II.

As might be expected the 4-fluorophenyl, the pyridine ring as well as the pyridopyrazine ring are planar (Figure 2). The pyridopyrazine ring makes dihedral angles of 45.51 (7)° and 44.75 (7)° to the 4-fluorophenyl ring and the pyridine ring, respectively. The 4-fluorophenyl ring makes a dihedral angle of 54.54 (8)° to the pyridine ring. The pyridine ring part of the pyridopyrazine ring and the pyrazine ring of two by c-glide plane related molecules forms π-π interactions. The angle between the planes is 2.09 (7)° and the distance of the centroids 3.557 (1) Å.

Experimental

1-(4-Fluorophenyl)-2-(pyridin-4-yl)ethane-1,2-dione (113 mg, 0.5 mmol), and 2,3-diaminopyridine (54 mg, 0.5 mmol), and methanol/glacial acetic acid (2 ml, 9:1, V:V) were combined in a reaction vial. The reaction vessel was heated in a microwave reactor for 5 min at 433 K (initial power 250 W), after which a stream of compressed air cooled the reaction vessel to r.t. The solvent was removed under reduced pressure and the residue was purified by flash-chromatography (silica gel, petroleum ether/ethyl acetate 1–4 to 0–1) to yield 65 mg (43%) of II as a colorless solid. Suitable crystals of compound II for X-ray were obtained by slow evaporation at 298 K of a solution of n-hexane - diethyl ether (2–1).

Refinement

Hydrogen atoms attached to carbons were placed at calculated positions with C—H = 0.95 Å (aromatic C-atom). All H atoms were refined in the riding-model approximation with isotropic displacement parameters (set at 1.2 times of the Ueq of the parent atom).

Figures

Fig. 1.
Synthesis of I and II.
Fig. 2.
View of compound II. Displacement ellipsoids are drawn at the 50% probability level.

Crystal data

C18H11FN4F(000) = 624
Mr = 302.31Dx = 1.419 Mg m3
Monoclinic, P21/cCu Kα radiation, λ = 1.54178 Å
Hall symbol: -P 2ybcCell parameters from 25 reflections
a = 17.222 (9) Åθ = 35–50°
b = 11.2199 (12) ŵ = 0.80 mm1
c = 7.329 (4) ÅT = 193 K
β = 91.80 (3)°Plate, yellow
V = 1415.4 (10) Å30.64 × 0.51 × 0.06 mm
Z = 4

Data collection

Enraf–Nonius CAD-4 diffractometer2309 reflections with I > 2σ(I)
Radiation source: rotating anodeRint = 0.029
graphiteθmax = 70.1°, θmin = 2.6°
ω/2θ scansh = 0→20
Absorption correction: numerical (CORINC; Dräger & Gattow, 1971)k = 0→13
Tmin = 0.675, Tmax = 0.949l = −8→8
2766 measured reflections3 standard reflections every 60 min
2677 independent reflections intensity decay: 2%

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.046H-atom parameters constrained
wR(F2) = 0.134w = 1/[σ2(Fo2) + (0.0797P)2 + 0.3717P] where P = (Fo2 + 2Fc2)/3
S = 1.07(Δ/σ)max < 0.001
2677 reflectionsΔρmax = 0.22 e Å3
209 parametersΔρmin = −0.24 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: 0.0012 (4)

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
C10.30818 (9)0.56244 (13)0.5692 (2)0.0294 (4)
N20.37936 (8)0.58947 (12)0.62301 (19)0.0323 (3)
C30.39843 (9)0.70720 (14)0.6323 (2)0.0317 (4)
N40.47243 (8)0.73360 (13)0.6904 (2)0.0386 (4)
C50.48914 (10)0.84780 (17)0.7036 (2)0.0419 (4)
H50.54050.86830.74320.050*
C60.43761 (11)0.94200 (16)0.6641 (2)0.0409 (4)
H60.45391.02230.67950.049*
C70.36428 (10)0.91673 (14)0.6039 (2)0.0362 (4)
H70.32830.97860.57500.043*
C80.34280 (9)0.79530 (14)0.5851 (2)0.0307 (4)
N90.27022 (8)0.76613 (11)0.52296 (18)0.0312 (3)
C100.25245 (9)0.65216 (13)0.5120 (2)0.0291 (3)
C110.28858 (9)0.43306 (14)0.5734 (2)0.0315 (4)
C120.22105 (10)0.39077 (15)0.6474 (2)0.0386 (4)
H120.18370.44450.69300.046*
C130.20869 (11)0.26876 (16)0.6541 (3)0.0420 (4)
H130.16190.24120.70480.050*
N140.25842 (9)0.18762 (13)0.5938 (2)0.0435 (4)
C150.32369 (11)0.22990 (15)0.5235 (2)0.0402 (4)
H150.36020.17410.48010.048*
C160.34126 (10)0.34977 (14)0.5101 (2)0.0344 (4)
H160.38850.37490.45850.041*
C170.17368 (9)0.62393 (13)0.4370 (2)0.0293 (3)
C180.16111 (9)0.53902 (13)0.3005 (2)0.0333 (4)
H180.20360.49450.25710.040*
C190.08724 (10)0.51921 (15)0.2280 (3)0.0398 (4)
H190.07860.46140.13480.048*
C200.02664 (10)0.58435 (16)0.2928 (3)0.0410 (4)
C210.03648 (10)0.66822 (17)0.4283 (3)0.0446 (4)
H21−0.00660.71120.47240.054*
C220.11058 (10)0.68841 (15)0.4987 (2)0.0379 (4)
H220.11870.74720.59060.046*
F23−0.04531 (7)0.56622 (13)0.21986 (18)0.0642 (4)

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
C10.0316 (8)0.0300 (8)0.0268 (8)0.0022 (6)0.0028 (6)0.0011 (6)
N20.0312 (7)0.0329 (7)0.0329 (7)0.0013 (5)0.0011 (5)0.0018 (5)
C30.0319 (8)0.0350 (8)0.0283 (8)−0.0016 (6)0.0036 (6)−0.0013 (6)
N40.0326 (7)0.0447 (8)0.0384 (8)−0.0024 (6)−0.0008 (6)−0.0001 (6)
C50.0346 (9)0.0514 (10)0.0397 (10)−0.0121 (7)0.0005 (7)−0.0046 (8)
C60.0436 (10)0.0399 (9)0.0396 (10)−0.0126 (7)0.0097 (8)−0.0075 (7)
C70.0384 (9)0.0304 (8)0.0403 (10)−0.0025 (6)0.0081 (7)−0.0029 (7)
C80.0312 (8)0.0312 (8)0.0299 (8)−0.0019 (6)0.0055 (6)−0.0026 (6)
N90.0317 (7)0.0280 (7)0.0342 (7)0.0007 (5)0.0031 (5)−0.0007 (5)
C100.0311 (8)0.0279 (7)0.0284 (8)0.0009 (6)0.0040 (6)0.0000 (6)
C110.0338 (8)0.0305 (8)0.0298 (8)0.0012 (6)−0.0030 (6)0.0046 (6)
C120.0367 (9)0.0374 (9)0.0418 (10)0.0034 (7)0.0020 (7)0.0084 (7)
C130.0401 (9)0.0421 (9)0.0435 (10)−0.0070 (7)−0.0002 (7)0.0115 (8)
N140.0523 (9)0.0337 (7)0.0443 (9)−0.0024 (6)−0.0008 (7)0.0060 (6)
C150.0499 (10)0.0308 (8)0.0399 (10)0.0044 (7)0.0016 (8)0.0018 (7)
C160.0366 (8)0.0330 (8)0.0334 (9)0.0014 (6)−0.0008 (6)0.0029 (6)
C170.0312 (8)0.0257 (7)0.0311 (8)0.0005 (6)0.0016 (6)0.0029 (6)
C180.0365 (8)0.0282 (7)0.0352 (9)0.0005 (6)0.0013 (7)0.0009 (6)
C190.0453 (10)0.0345 (8)0.0394 (10)−0.0070 (7)−0.0033 (7)−0.0014 (7)
C200.0295 (8)0.0503 (10)0.0431 (10)−0.0074 (7)−0.0027 (7)0.0052 (8)
C210.0329 (9)0.0533 (10)0.0480 (11)0.0059 (7)0.0050 (8)−0.0022 (8)
C220.0358 (9)0.0388 (9)0.0393 (10)0.0027 (7)0.0016 (7)−0.0060 (7)
F230.0348 (6)0.0915 (10)0.0656 (8)−0.0096 (6)−0.0107 (5)−0.0054 (7)

Geometric parameters (Å, °)

C1—N21.311 (2)C12—H120.9500
C1—C101.444 (2)C13—N141.335 (2)
C1—C111.491 (2)C13—H130.9500
N2—C31.362 (2)N14—C151.338 (2)
C3—N41.363 (2)C15—C161.383 (2)
C3—C81.412 (2)C15—H150.9500
N4—C51.316 (2)C16—H160.9500
C5—C61.404 (3)C17—C221.393 (2)
C5—H50.9500C17—C181.393 (2)
C6—C71.355 (3)C18—C191.381 (2)
C6—H60.9500C18—H180.9500
C7—C81.417 (2)C19—C201.371 (3)
C7—H70.9500C19—H190.9500
C8—N91.357 (2)C20—F231.349 (2)
N9—C101.3167 (19)C20—C211.375 (3)
C10—C171.482 (2)C21—C221.380 (2)
C11—C121.383 (2)C21—H210.9500
C11—C161.392 (2)C22—H220.9500
C12—C131.386 (2)
N2—C1—C10122.18 (14)C13—C12—H12120.5
N2—C1—C11115.41 (13)N14—C13—C12124.13 (17)
C10—C1—C11122.41 (14)N14—C13—H13117.9
C1—N2—C3117.45 (14)C12—C13—H13117.9
N2—C3—N4116.60 (14)C13—N14—C15116.18 (15)
N2—C3—C8120.38 (15)N14—C15—C16124.10 (17)
N4—C3—C8123.01 (15)N14—C15—H15118.0
C5—N4—C3115.75 (15)C16—C15—H15118.0
N4—C5—C6125.61 (16)C15—C16—C11118.86 (16)
N4—C5—H5117.2C15—C16—H16120.6
C6—C5—H5117.2C11—C16—H16120.6
C7—C6—C5119.09 (16)C22—C17—C18118.88 (15)
C7—C6—H6120.5C22—C17—C10118.89 (14)
C5—C6—H6120.5C18—C17—C10122.15 (14)
C6—C7—C8118.08 (16)C19—C18—C17120.45 (16)
C6—C7—H7121.0C19—C18—H18119.8
C8—C7—H7121.0C17—C18—H18119.8
N9—C8—C3121.61 (14)C20—C19—C18118.86 (16)
N9—C8—C7119.96 (14)C20—C19—H19120.6
C3—C8—C7118.43 (15)C18—C19—H19120.6
C10—N9—C8117.69 (13)F23—C20—C19118.82 (17)
N9—C10—C1120.54 (14)F23—C20—C21118.69 (17)
N9—C10—C17116.01 (13)C19—C20—C21122.49 (16)
C1—C10—C17123.44 (13)C20—C21—C22118.28 (17)
C12—C11—C16117.74 (15)C20—C21—H21120.9
C12—C11—C1122.42 (15)C22—C21—H21120.9
C16—C11—C1119.75 (15)C21—C22—C17121.02 (16)
C11—C12—C13118.99 (16)C21—C22—H22119.5
C11—C12—H12120.5C17—C22—H22119.5
C10—C1—N2—C33.3 (2)N2—C1—C11—C16−43.4 (2)
C11—C1—N2—C3−176.00 (14)C10—C1—C11—C16137.36 (16)
C1—N2—C3—N4179.30 (14)C16—C11—C12—C13−0.4 (2)
C1—N2—C3—C80.0 (2)C1—C11—C12—C13−176.96 (16)
N2—C3—N4—C5−178.11 (15)C11—C12—C13—N140.3 (3)
C8—C3—N4—C51.2 (2)C12—C13—N14—C150.0 (3)
C3—N4—C5—C60.3 (3)C13—N14—C15—C16−0.3 (3)
N4—C5—C6—C7−1.3 (3)N14—C15—C16—C110.2 (3)
C5—C6—C7—C80.6 (3)C12—C11—C16—C150.2 (2)
N2—C3—C8—N9−2.6 (2)C1—C11—C16—C15176.82 (15)
N4—C3—C8—N9178.18 (15)N9—C10—C17—C22−45.2 (2)
N2—C3—C8—C7177.49 (15)C1—C10—C17—C22135.38 (17)
N4—C3—C8—C7−1.8 (2)N9—C10—C17—C18131.58 (16)
C6—C7—C8—N9−179.16 (15)C1—C10—C17—C18−47.8 (2)
C6—C7—C8—C30.8 (2)C22—C17—C18—C19−0.1 (2)
C3—C8—N9—C101.6 (2)C10—C17—C18—C19−176.90 (15)
C7—C8—N9—C10−178.43 (15)C17—C18—C19—C20−0.1 (2)
C8—N9—C10—C11.6 (2)C18—C19—C20—F23179.01 (16)
C8—N9—C10—C17−177.79 (13)C18—C19—C20—C21−0.5 (3)
N2—C1—C10—N9−4.3 (2)F23—C20—C21—C22−178.31 (17)
C11—C1—C10—N9174.95 (15)C19—C20—C21—C221.2 (3)
N2—C1—C10—C17175.07 (14)C20—C21—C22—C17−1.3 (3)
C11—C1—C10—C17−5.7 (2)C18—C17—C22—C210.8 (3)
N2—C1—C11—C12133.14 (17)C10—C17—C22—C21177.73 (16)
C10—C1—C11—C12−46.1 (2)

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: NC2158).

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.
  • Dräger, M. & Gattow, G. (1971). Acta Chem. Scand.25, 761–762.
  • Enraf–Nonius (1989). CAD-4 Software Enraf–Nonius, Delft, The Netherlands.
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]
  • Spek, A. L. (2009). Acta Cryst. D65, 148–155. [PMC free article] [PubMed]
  • Zhao, Z., Wisnoski, D. D., Wolkenberg, S. E., Leister, W. H., Wang, Y. & Lindsley, C. W. (2004). Tetrahedron Lett.45, 4873–4876.

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