PMCCPMCCPMCC

Search tips
Search criteria 

Advanced

 
Logo of actaeInternational Union of Crystallographysearchopen accessarticle submissionjournal home pagethis article
 
Acta Crystallogr Sect E Struct Rep Online. 2009 June 1; 65(Pt 6): o1344.
Published online 2009 May 20. doi:  10.1107/S1600536809018285
PMCID: PMC2969533

4-[3-(4-Fluoro­phen­yl)quinoxalin-2-yl]-N-isopropyl­pyridin-2-amine

Abstract

In the crystal structure of the title compound, C22H19FN4, the quinoxaline system makes dihedral angles of 32.07 (13) and 69.64 (13)° with the 4-fluoro­phenyl and pyridine rings, respectively. The 4-fluoro­phenyl ring makes a dihedral angle of 71.77 (16)° with the pyridine ring. The crystal structure is stabilized by inter­molecular N—H(...)N hydrogen bonding.

Related literature

For chinoxaline derivatives and their biological activity, see: He et al. (2003 [triangle]); Kim et al. (2004 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o1344-scheme1.jpg

Experimental

Crystal data

  • C22H19FN4
  • M r = 358.41
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o1344-efi1.jpg
  • a = 17.230 (9) Å
  • b = 5.386 (3) Å
  • c = 19.123 (10) Å
  • β = 96.114 (13)°
  • V = 1764.4 (16) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.09 mm−1
  • T = 173 K
  • 0.4 × 0.06 × 0.03 mm

Data collection

  • Bruker SMART CCD diffractometer
  • Absorption correction: none
  • 20392 measured reflections
  • 4217 independent reflections
  • 1201 reflections with I > 2σ(I)
  • R int = 0.236

Refinement

  • R[F 2 > 2σ(F 2)] = 0.049
  • wR(F 2) = 0.123
  • S = 0.74
  • 4217 reflections
  • 247 parameters
  • H-atom parameters constrained
  • Δρmax = 0.23 e Å−3
  • Δρmin = −0.22 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/S1600536809018285/bt2957sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809018285/bt2957Isup2.hkl

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

supplementary crystallographic information

Comment

Functionalized quinoxaline derivatives are well known in pharmaceutical industry. They have been shown to possess antibacterial activity (Kim et al. 2004) and as PDGF-R tyrosine kinase inhibitor (He et al. 2003).

The title compound, 4-(3-(4-fluorophenyl)quinoxalin-2-yl)-N- isopropylpyridin-2-amine (I), was prepared in the course of our studies on 2-(2-alkylaminopyridin-4-yl)-3-(4-fluorophenyl)quinoxalines as potent p38 mitogen-activated protein (MAP) kinase inhibitors.

The analysis of the crystal structure of compound I is shown in Figure 1. As might be expected the 4-fluorophenyl, the pyridine ring as well as the quinoxaline ring are planar. The quinoxaline ring makes dihedral angles of 32.07 (13)° and 69.64 (13)° to the 4-fluorophenyl ring and the pyridine ring, respectively. The 4-fluorophenyl ring makes dihedral angles of 71.77 (16)° to the pyridine ring.

The crystal packing (Figure 2) shows that N17—H17 of the imidazole ring forms an intermolecular N–H···N hydrogen bond to pyridine (N14) resulting in a dimer. The length of the hydrogen bond is 2.16Å (Table 1).

Experimental

tert-Butyl 4-(3-(4-fluorophenyl)quinoxalin-2-yl)pyridin-2-yl(isopropyl)carbamate (120 mg, 0.26 mmol) was dissolved in DCM (2 ml), treated with trifluoroacetic acid (2 ml) and stirred for 16 h at 298 K. The reaction mixture was cooled to 273 K and neutralized with 1 N aqueous NaOH-solution to pH 12. Ethyl acetate was added and the organic layer was washed with water, dried over sodium sulfate and the solvent was removed under reduced pressure. The crude product was purified by flash-chromatography (silica gel, petroleum ether - ethyl acetate 4–1 to 2–1) to yield the title compound I (78 mg, 84%) as a colourless solid. The compound was recrystalized from dimethylsulfoxide.

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). They 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). The hydrogen atom attached to N17 was located in difference Fourier maps and freely refined.

Figures

Fig. 1.
View of compound I. Displacement ellipsoids are drawn at the 50% probability level. H atoms are depicted as circles of arbitrary size.
Fig. 2.
Part of the crystal packing of compound I. The hydrogen bond is shown with dashed lines. View along b axis.

Crystal data

C22H19FN4F(000) = 752
Mr = 358.41Dx = 1.349 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ynCell parameters from 934 reflections
a = 17.230 (9) Åθ = 2.2–19.5°
b = 5.386 (3) ŵ = 0.09 mm1
c = 19.123 (10) ÅT = 173 K
β = 96.114 (13)°Needle, colourless
V = 1764.4 (16) Å30.4 × 0.06 × 0.03 mm
Z = 4

Data collection

Bruker SMART CCD diffractometer1201 reflections with I > 2σ(I)
Radiation source: sealed TubeRint = 0.236
graphiteθmax = 28.0°, θmin = 1.5°
CCD scansh = −22→21
20392 measured reflectionsk = −7→6
4217 independent reflectionsl = −25→25

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.049H-atom parameters constrained
wR(F2) = 0.123w = 1/[σ2(Fo2) + (0.03P)2] where P = (Fo2 + 2Fc2)/3
S = 0.74(Δ/σ)max < 0.001
4217 reflectionsΔρmax = 0.23 e Å3
247 parametersΔρmin = −0.22 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: 0.0111 (10)

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
F10.32320 (13)−0.2743 (4)0.12436 (11)0.0534 (7)
N10.64239 (16)0.7424 (5)0.21100 (13)0.0280 (7)
C20.5913 (2)0.5582 (6)0.20994 (17)0.0247 (9)
C30.5637 (2)0.4311 (6)0.14642 (17)0.0247 (9)
N40.59317 (17)0.4791 (5)0.08672 (14)0.0286 (8)
C50.6482 (2)0.6633 (6)0.08760 (18)0.0261 (9)
C60.6806 (2)0.7247 (7)0.02532 (18)0.0354 (9)
H60.66760.6298−0.01620.043*
C70.7308 (2)0.9216 (7)0.02466 (19)0.0391 (10)
H70.75230.9632−0.01760.047*
C80.7511 (2)1.0634 (7)0.08587 (19)0.0360 (10)
H80.78531.20100.08430.043*
C90.7220 (2)1.0048 (6)0.14717 (18)0.0320 (10)
H90.73621.09940.18850.038*
C100.6703 (2)0.8013 (6)0.14864 (18)0.0288 (9)
C110.5688 (2)0.4924 (6)0.28109 (17)0.0266 (9)
C120.5957 (2)0.2739 (6)0.31406 (17)0.0283 (9)
H120.62290.15310.28990.034*
C130.5814 (2)0.2386 (6)0.38249 (17)0.0299 (9)
H130.60230.09340.40560.036*
N140.54053 (16)0.3921 (5)0.41920 (13)0.0260 (7)
C150.50848 (19)0.5941 (6)0.38430 (17)0.0259 (9)
C160.5247 (2)0.6521 (6)0.31639 (17)0.0271 (9)
H160.50540.80160.29460.033*
N170.46189 (16)0.7389 (5)0.42120 (13)0.0289 (7)
H170.45660.66230.46850.035*
C180.4038 (2)0.9131 (6)0.38765 (17)0.0309 (9)
H180.43041.02660.35640.037*
C190.3386 (2)0.7750 (7)0.34280 (18)0.0419 (10)
H19A0.31280.65980.37260.063*
H19B0.36090.68180.30570.063*
H19C0.30040.89490.32140.063*
C200.3708 (2)1.0676 (6)0.44350 (17)0.0374 (10)
H20A0.34270.95960.47350.056*
H20B0.33471.19170.42100.056*
H20C0.41341.15160.47220.056*
C210.4997 (2)0.2437 (6)0.14209 (16)0.0255 (8)
C220.4995 (2)0.0513 (6)0.09329 (17)0.0301 (9)
H220.54020.04180.06360.036*
C230.4409 (2)−0.1263 (6)0.08723 (18)0.0356 (10)
H230.4414−0.25980.05480.043*
C240.3825 (2)−0.1020 (7)0.1296 (2)0.0360 (10)
C250.3785 (2)0.0856 (7)0.17772 (18)0.0347 (10)
H250.33650.09520.20600.042*
C260.4380 (2)0.2604 (7)0.18368 (17)0.0321 (9)
H260.43670.39280.21640.039*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
F10.0456 (16)0.0392 (14)0.0736 (16)−0.0154 (12)−0.0022 (12)0.0043 (13)
N10.0310 (19)0.0222 (16)0.0312 (17)0.0018 (16)0.0047 (14)0.0014 (15)
C20.025 (2)0.020 (2)0.030 (2)0.0058 (17)0.0039 (18)0.0025 (18)
C30.027 (2)0.022 (2)0.026 (2)0.0052 (17)0.0060 (18)−0.0013 (18)
N40.0292 (19)0.0244 (18)0.0325 (18)0.0068 (15)0.0053 (15)0.0005 (14)
C50.028 (2)0.024 (2)0.027 (2)0.0018 (17)0.0059 (18)0.0003 (17)
C60.037 (3)0.033 (2)0.037 (2)0.005 (2)0.0078 (19)−0.002 (2)
C70.038 (3)0.040 (3)0.040 (3)0.007 (2)0.012 (2)0.011 (2)
C80.031 (3)0.030 (2)0.047 (2)0.0018 (18)0.005 (2)0.004 (2)
C90.029 (2)0.029 (2)0.038 (2)0.0020 (18)0.0052 (19)0.0032 (18)
C100.028 (2)0.027 (2)0.032 (2)0.0022 (18)0.0067 (18)0.0028 (18)
C110.026 (2)0.025 (2)0.029 (2)−0.0075 (17)0.0027 (18)−0.0067 (18)
C120.033 (2)0.021 (2)0.030 (2)0.0001 (18)0.0025 (18)−0.0038 (18)
C130.032 (2)0.020 (2)0.039 (2)0.0047 (19)0.0096 (19)0.0011 (19)
N140.0308 (19)0.0169 (16)0.0307 (17)−0.0021 (15)0.0051 (15)−0.0004 (14)
C150.026 (2)0.022 (2)0.030 (2)−0.0021 (18)0.0031 (18)−0.0024 (18)
C160.035 (2)0.018 (2)0.028 (2)−0.0004 (16)0.0027 (19)−0.0013 (16)
N170.0362 (19)0.0258 (17)0.0254 (16)0.0099 (15)0.0060 (14)0.0040 (15)
C180.032 (2)0.025 (2)0.035 (2)−0.0007 (19)0.0040 (19)−0.0001 (18)
C190.037 (3)0.046 (3)0.042 (2)0.001 (2)0.001 (2)−0.002 (2)
C200.041 (3)0.029 (2)0.044 (2)0.0097 (19)0.014 (2)0.0001 (19)
C210.029 (2)0.0200 (19)0.0268 (19)0.0030 (19)0.0021 (17)0.0039 (18)
C220.033 (2)0.024 (2)0.033 (2)0.0069 (18)0.0013 (19)0.0042 (19)
C230.041 (3)0.021 (2)0.043 (2)0.0047 (19)−0.006 (2)−0.0029 (18)
C240.035 (3)0.026 (2)0.045 (2)−0.011 (2)−0.003 (2)0.009 (2)
C250.031 (3)0.037 (2)0.035 (2)0.003 (2)0.0031 (19)0.006 (2)
C260.031 (2)0.033 (2)0.032 (2)0.001 (2)0.0004 (18)−0.0017 (19)

Geometric parameters (Å, °)

F1—C241.376 (4)C15—N171.368 (4)
N1—C21.325 (4)C15—C161.393 (4)
N1—C101.370 (4)C16—H160.9500
C2—C31.431 (4)N17—C181.469 (4)
C2—C111.497 (4)N17—H171.0071
C3—N41.324 (4)C18—C201.512 (4)
C3—C211.491 (4)C18—C191.532 (4)
N4—C51.371 (4)C18—H181.0000
C5—C101.402 (4)C19—H19A0.9800
C5—C61.407 (4)C19—H19B0.9800
C6—C71.370 (5)C19—H19C0.9800
C6—H60.9500C20—H20A0.9800
C7—C81.410 (4)C20—H20B0.9800
C7—H70.9500C20—H20C0.9800
C8—C91.360 (4)C21—C221.394 (4)
C8—H80.9500C21—C261.397 (4)
C9—C101.414 (4)C22—C231.386 (5)
C9—H90.9500C22—H220.9500
C11—C161.372 (4)C23—C241.363 (4)
C11—C121.391 (4)C23—H230.9500
C12—C131.370 (4)C24—C251.373 (4)
C12—H120.9500C25—C261.387 (4)
C13—N141.334 (4)C25—H250.9500
C13—H130.9500C26—H260.9500
N14—C151.362 (4)
C2—N1—C10117.0 (3)C15—C16—H16120.2
N1—C2—C3122.1 (3)C15—N17—C18123.3 (3)
N1—C2—C11113.5 (3)C15—N17—H17110.1
C3—C2—C11124.3 (3)C18—N17—H17122.1
N4—C3—C2121.0 (3)N17—C18—C20109.5 (3)
N4—C3—C21115.7 (3)N17—C18—C19111.1 (3)
C2—C3—C21123.2 (3)C20—C18—C19110.7 (3)
C3—N4—C5117.3 (3)N17—C18—H18108.5
N4—C5—C10121.4 (3)C20—C18—H18108.5
N4—C5—C6119.7 (3)C19—C18—H18108.5
C10—C5—C6118.8 (3)C18—C19—H19A109.5
C7—C6—C5119.9 (3)C18—C19—H19B109.5
C7—C6—H6120.1H19A—C19—H19B109.5
C5—C6—H6120.1C18—C19—H19C109.5
C6—C7—C8120.8 (3)H19A—C19—H19C109.5
C6—C7—H7119.6H19B—C19—H19C109.5
C8—C7—H7119.6C18—C20—H20A109.5
C9—C8—C7120.6 (4)C18—C20—H20B109.5
C9—C8—H8119.7H20A—C20—H20B109.5
C7—C8—H8119.7C18—C20—H20C109.5
C8—C9—C10119.2 (4)H20A—C20—H20C109.5
C8—C9—H9120.4H20B—C20—H20C109.5
C10—C9—H9120.4C22—C21—C26118.8 (3)
N1—C10—C5120.8 (3)C22—C21—C3119.3 (3)
N1—C10—C9118.5 (3)C26—C21—C3121.9 (3)
C5—C10—C9120.7 (3)C23—C22—C21121.2 (3)
C16—C11—C12118.8 (3)C23—C22—H22119.4
C16—C11—C2120.6 (3)C21—C22—H22119.4
C12—C11—C2120.4 (3)C24—C23—C22117.4 (3)
C13—C12—C11117.7 (3)C24—C23—H23121.3
C13—C12—H12121.1C22—C23—H23121.3
C11—C12—H12121.1C23—C24—C25124.2 (4)
N14—C13—C12125.1 (3)C23—C24—F1118.8 (4)
N14—C13—H13117.4C25—C24—F1117.0 (4)
C12—C13—H13117.4C24—C25—C26117.7 (4)
C13—N14—C15116.5 (3)C24—C25—H25121.1
N14—C15—N17115.6 (3)C26—C25—H25121.1
N14—C15—C16121.6 (3)C25—C26—C21120.6 (4)
N17—C15—C16122.7 (3)C25—C26—H26119.7
C11—C16—C15119.7 (3)C21—C26—H26119.7
C11—C16—H16120.2
C10—N1—C2—C3−2.4 (5)C2—C11—C12—C13171.9 (3)
C10—N1—C2—C11175.3 (3)C11—C12—C13—N143.4 (5)
N1—C2—C3—N45.8 (5)C12—C13—N14—C152.5 (5)
C11—C2—C3—N4−171.7 (3)C13—N14—C15—N17175.2 (3)
N1—C2—C3—C21−172.7 (3)C13—N14—C15—C16−6.9 (5)
C11—C2—C3—C219.9 (5)C12—C11—C16—C150.6 (5)
C2—C3—N4—C5−3.1 (5)C2—C11—C16—C15−176.1 (3)
C21—C3—N4—C5175.4 (3)N14—C15—C16—C115.5 (5)
C3—N4—C5—C10−2.2 (5)N17—C15—C16—C11−176.8 (3)
C3—N4—C5—C6−179.0 (3)N14—C15—N17—C18−160.1 (3)
N4—C5—C6—C7174.8 (3)C16—C15—N17—C1822.0 (5)
C10—C5—C6—C7−2.1 (5)C15—N17—C18—C20−172.2 (3)
C5—C6—C7—C80.4 (5)C15—N17—C18—C1965.2 (4)
C6—C7—C8—C91.0 (6)N4—C3—C21—C2231.4 (5)
C7—C8—C9—C10−0.7 (5)C2—C3—C21—C22−150.1 (3)
C2—N1—C10—C5−2.9 (5)N4—C3—C21—C26−146.0 (3)
C2—N1—C10—C9177.0 (3)C2—C3—C21—C2632.5 (5)
N4—C5—C10—N15.5 (5)C26—C21—C22—C23−2.2 (5)
C6—C5—C10—N1−177.7 (3)C3—C21—C22—C23−179.7 (3)
N4—C5—C10—C9−174.4 (3)C21—C22—C23—C241.6 (5)
C6—C5—C10—C92.4 (5)C22—C23—C24—C25−0.3 (6)
C8—C9—C10—N1179.1 (3)C22—C23—C24—F1179.5 (3)
C8—C9—C10—C5−1.0 (5)C23—C24—C25—C26−0.3 (5)
N1—C2—C11—C1669.2 (4)F1—C24—C25—C26179.9 (3)
C3—C2—C11—C16−113.1 (4)C24—C25—C26—C21−0.3 (5)
N1—C2—C11—C12−107.4 (4)C22—C21—C26—C251.5 (5)
C3—C2—C11—C1270.3 (5)C3—C21—C26—C25178.9 (3)
C16—C11—C12—C13−4.8 (5)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
N17—H17···N14i1.012.163.137 (4)162

Symmetry codes: (i) −x+1, −y+1, −z+1.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: BT2957).

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.
  • Bruker (2006). APEX2 and SAINT Bruker AXS Inc., Madison, Wisconsin, USA.
  • He, W., Myers, M. R., Hanney, B., Spada, A. P., Bilder, G., Galzcinski, H., Amin, D., Needle, S., Page, K., Jayyosi, Z. & Perrone, M. H. (2003). Bioorg. Med. Chem. Lett.13, 3097–3100. [PubMed]
  • Kim, Y. B., Kim, Y. H., Park, J. Y. & Kim, S. K. (2004). Bioorg. Med. Chem. Lett.14, 541–544. [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