supplementary materials


su2601 scheme

Acta Cryst. (2013). E69, o949-o950    [ doi:10.1107/S1600536813013640 ]

N-tert-Butyl-2-(2,6-dichlorophenyl)imidazo[1,2-a]pyrazin-3-amine

Z. Fatima, T. Srinivasan, S. Koorathota, S. Thennarasu and D. Velmurugan

Abstract top

In the title compound, C16H16Cl2N4, the imidazole ring mean plane makes a dihedral angle of 70.01 (1)° with the phenyl ring. The Cl atoms deviate by -0.0472 (6) and 0.0245 (8) Å from the plane of their attached benzene ring. In the crystal, molecules are linked via pairs of C-H...N hydrogen bonds, forming inversion dimers.

Comment top

The pyrazine ring system is a useful structural element in medicinal chemistry and has found broad applications in drug development such as antiproliferative agents (Dubinina et al., 2006), potent CXCR3 antagonists (Du et al., 2009), CB1 antagonists (Ellsworth et al., 2007) and c-Src inhibitors (Mukaiyama et al., 2007). On-going structural studies of heterocyclic N-containing derivatives (Nasir et al., 2010) are motivated by an investigation of their fluorescence properties (Kawai et al., 2001; Abdullah, 2005). For multidrug-resistant Tuberculosis (Dooley et al., 1992), antifungal and antimycobacterial activity (Banfi et al. 2006) and bactericidal effects (Jackson et al. 2000), the use of imidazole based compounds were reported. In view of the different applications of this class of compounds, we have undertaken a single-crystal structure determination of the title compound.

In the titled compound, Fig.1, the imidazole ring (N2/N3/C3/C5/C6) makes a dihedral angle of 1.06 (9)° with the pyrazine ring (N1/N3/C1-C4), and a dihedral angle of 70.01 (1)° with the phenyl ring (C7-C12). The dihedral angle between the pyrazine ring and the phenyl ring is 69.54 (1)°. The chlorine atoms Cl1 and Cl2 attached to the phenyl ring deviate by -0.0472 (6)Å and 0.0245 (8)Å.

In the crystal, molecules are linked via pairs of C—H···N hydrogen bonds forming inversion dimers (Table 1 and Fig.2).

Related literature top

For applications of the pyrazine ring system in drug development, see: Du et al. (2009); Dubinina et al. (2006); Ellsworth et al. (2007); Mukaiyama et al. (2007). For background to the fluorescence properties of related compounds, see: Kawai et al. (2001); Abdullah (2005). For general background to the use of imidazole derivatives as drugs, see: Dooley et al. (1992); Jackson et al. (2000); Banfi et al. (2006). For related structures, see: Ouzidan et al. (2011); Nasir et al. (2010).

Experimental top

2-aminopyrazine (1.0 mmol) was placed in oven-dried round bottom flask, dissolved in EtOH (5.0 mL) and stirred at room temperature. 2,6-dichlorobenzaldehyde (1.0 mmol), tert-butyl isocyanide (1.0 mmol) and Iodine (2.0 mol%) were added together and the mixture stirred, progress of the reaction was monitored by using TLC, at room temperature for one hour. The reaction mixture was concentrated under reduced pressure and the crude product was partitioned between EtOAc and water. The organic phase was separated, and the residual product in the aqueous phase was extracted with EtOAc (2 × 10 mL). The combined organic extract was dried over anhydrous Na2SO4, filtered, concentrated and purified using column chromatography (silica gel 60-120 mesh, elutent: 5% EtOAc in hexane).M.p: 421 - 423 k, IR (KBr, cm-1): 3353 (NH). After two weeks a colourless crystalline solid separated out. It was washed with a minimum amount of ethanol and then dried in a vacuum oven; a crystal was chosen for X-ray diffraction studies from this sample.

Refinement top

The H atoms were placed in calculated positions and refined as riding atoms: C—H = 0.93 and 0.96 Å for CH and CH3 H atoms, respectively, with Uiso(H) = 1.5Ueq(C-methyl) and = 1.2Ueq(C) for other H atoms.

Computing details top

Data collection: APEX2 (Bruker, 2008); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2009).

Figures top
[Figure 1] Fig. 1. The molecular structure of the title molecule, with atom labelling. Displacement ellipsoids are drawn at the 30% probability level.
[Figure 2] Fig. 2. The crystal packing of the title compound viewed along the a axis. The hydrogen bonds are sown as dashed lines (see Table 1 for details; H-atoms not involved in H-bonds have been excluded for clarity).
N-tert-Butyl-2-(2,6-dichlorophenyl)imidazo[1,2-a]pyrazin-3-amine top
Crystal data top
C16H16Cl2N4Z = 2
Mr = 335.23F(000) = 348
Triclinic, P1Dx = 1.336 Mg m3
Hall symbol: -P 1Mo Kα radiation, λ = 0.71073 Å
a = 8.1482 (4) ÅCell parameters from 3438 reflections
b = 9.8553 (5) Åθ = 1.8–26.5°
c = 11.5265 (6) ŵ = 0.39 mm1
α = 93.218 (2)°T = 293 K
β = 99.320 (3)°Block, colourless
γ = 113.026 (2)°0.30 × 0.25 × 0.20 mm
V = 833.31 (7) Å3
Data collection top
Bruker SMART APEXII area-detector
diffractometer
3438 independent reflections
Radiation source: fine-focus sealed tube2941 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.026
ω and φ scansθmax = 26.5°, θmin = 1.8°
Absorption correction: multi-scan
(SADABS; Bruker, 2008)
h = 1010
Tmin = 0.892, Tmax = 0.926k = 1212
12583 measured reflectionsl = 1414
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.040H-atom parameters constrained
wR(F2) = 0.120 w = 1/[σ2(Fo2) + (0.0616P)2 + 0.252P]
where P = (Fo2 + 2Fc2)/3
S = 1.05(Δ/σ)max < 0.001
3438 reflectionsΔρmax = 0.34 e Å3
203 parametersΔρmin = 0.40 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: 0.029 (4)
Crystal data top
C16H16Cl2N4γ = 113.026 (2)°
Mr = 335.23V = 833.31 (7) Å3
Triclinic, P1Z = 2
a = 8.1482 (4) ÅMo Kα radiation
b = 9.8553 (5) ŵ = 0.39 mm1
c = 11.5265 (6) ÅT = 293 K
α = 93.218 (2)°0.30 × 0.25 × 0.20 mm
β = 99.320 (3)°
Data collection top
Bruker SMART APEXII area-detector
diffractometer
3438 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2008)
2941 reflections with I > 2σ(I)
Tmin = 0.892, Tmax = 0.926Rint = 0.026
12583 measured reflectionsθmax = 26.5°
Refinement top
R[F2 > 2σ(F2)] = 0.040H-atom parameters constrained
wR(F2) = 0.120Δρmax = 0.34 e Å3
S = 1.05Δρmin = 0.40 e Å3
3438 reflectionsAbsolute structure: ?
203 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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) top
xyzUiso*/Ueq
C10.8515 (3)0.3445 (2)0.14305 (16)0.0590 (5)
H10.82780.39570.20440.071*
C20.8018 (2)0.3676 (2)0.04035 (15)0.0490 (4)
H20.74620.43270.03070.059*
C30.9215 (2)0.19622 (19)0.03479 (14)0.0428 (4)
C40.9674 (3)0.1803 (2)0.07708 (15)0.0573 (5)
H41.02380.11650.08940.069*
C50.8067 (2)0.29067 (17)0.16413 (13)0.0374 (3)
C60.8760 (2)0.19427 (17)0.21161 (13)0.0386 (3)
C70.8730 (2)0.15258 (17)0.33280 (13)0.0412 (4)
C80.9765 (2)0.25222 (19)0.43377 (14)0.0466 (4)
C90.9642 (3)0.2172 (2)0.54712 (16)0.0618 (5)
H91.03430.28720.61260.074*
C100.8473 (4)0.0779 (3)0.56200 (17)0.0737 (6)
H100.83780.05340.63810.088*
C110.7438 (4)0.0259 (2)0.46540 (18)0.0711 (6)
H110.66520.12060.47570.085*
C120.7582 (3)0.0125 (2)0.35278 (16)0.0543 (4)
C130.5310 (2)0.3227 (2)0.20642 (16)0.0529 (4)
C140.4269 (3)0.2237 (5)0.0930 (3)0.1323 (15)
H14A0.44060.28170.02820.198*
H14B0.30040.17680.09670.198*
H14C0.47270.14890.08110.198*
C150.4854 (5)0.4564 (4)0.2163 (4)0.1293 (15)
H15A0.55210.51830.29000.194*
H15B0.35720.42430.21370.194*
H15C0.51780.51180.15160.194*
C160.4855 (4)0.2406 (4)0.3101 (3)0.1010 (10)
H16A0.50250.14980.30060.151*
H16B0.36110.21800.31440.151*
H16C0.56390.30120.38170.151*
N10.9338 (2)0.2515 (2)0.16355 (13)0.0635 (4)
N20.9474 (2)0.13643 (16)0.13275 (12)0.0466 (3)
N30.83689 (17)0.29093 (14)0.04973 (11)0.0386 (3)
N40.72957 (19)0.38082 (15)0.20777 (13)0.0471 (3)
H4A0.79780.47190.23610.057*
Cl11.12956 (7)0.42849 (6)0.41790 (4)0.0670 (2)
Cl20.62201 (10)0.11935 (6)0.23322 (5)0.0897 (3)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0591 (11)0.0737 (12)0.0376 (9)0.0192 (9)0.0069 (8)0.0206 (8)
C20.0468 (9)0.0563 (10)0.0433 (9)0.0191 (8)0.0079 (7)0.0192 (7)
C30.0458 (8)0.0510 (9)0.0335 (8)0.0213 (7)0.0092 (6)0.0038 (6)
C40.0675 (12)0.0724 (12)0.0367 (9)0.0316 (10)0.0160 (8)0.0033 (8)
C50.0377 (7)0.0415 (7)0.0325 (7)0.0145 (6)0.0092 (6)0.0062 (6)
C60.0440 (8)0.0432 (8)0.0302 (7)0.0191 (6)0.0081 (6)0.0047 (6)
C70.0520 (9)0.0461 (8)0.0309 (7)0.0244 (7)0.0101 (6)0.0076 (6)
C80.0552 (10)0.0493 (9)0.0363 (8)0.0215 (8)0.0109 (7)0.0055 (7)
C90.0847 (14)0.0649 (11)0.0316 (8)0.0274 (10)0.0090 (8)0.0024 (8)
C100.1114 (18)0.0719 (13)0.0364 (10)0.0311 (13)0.0228 (11)0.0187 (9)
C110.1029 (17)0.0547 (11)0.0495 (11)0.0206 (11)0.0241 (11)0.0198 (9)
C120.0718 (12)0.0473 (9)0.0394 (9)0.0199 (8)0.0099 (8)0.0067 (7)
C130.0517 (10)0.0700 (11)0.0510 (10)0.0342 (9)0.0207 (8)0.0183 (9)
C140.0456 (13)0.225 (4)0.092 (2)0.0308 (19)0.0034 (13)0.041 (2)
C150.121 (3)0.123 (3)0.221 (4)0.095 (2)0.105 (3)0.087 (3)
C160.0738 (16)0.136 (2)0.113 (2)0.0448 (17)0.0477 (16)0.076 (2)
N10.0727 (11)0.0839 (12)0.0337 (8)0.0292 (9)0.0157 (7)0.0109 (7)
N20.0590 (8)0.0559 (8)0.0350 (7)0.0324 (7)0.0130 (6)0.0071 (6)
N30.0375 (6)0.0449 (7)0.0317 (6)0.0144 (5)0.0071 (5)0.0083 (5)
N40.0487 (8)0.0432 (7)0.0548 (8)0.0213 (6)0.0177 (6)0.0064 (6)
Cl10.0707 (3)0.0591 (3)0.0495 (3)0.0047 (2)0.0110 (2)0.0012 (2)
Cl20.1200 (5)0.0537 (3)0.0557 (3)0.0004 (3)0.0043 (3)0.0005 (2)
Geometric parameters (Å, º) top
C1—C21.347 (3)C9—H90.9300
C1—N11.362 (3)C10—C111.375 (3)
C1—H10.9300C10—H100.9300
C2—N31.376 (2)C11—C121.383 (3)
C2—H20.9300C11—H110.9300
C3—N21.327 (2)C12—Cl21.7307 (19)
C3—N31.378 (2)C13—N41.487 (2)
C3—C41.417 (2)C13—C141.494 (3)
C4—N11.304 (3)C13—C161.496 (3)
C4—H40.9300C13—C151.506 (3)
C5—C61.378 (2)C14—H14A0.9600
C5—N31.3800 (19)C14—H14B0.9600
C5—N41.388 (2)C14—H14C0.9600
C6—N21.3650 (19)C15—H15A0.9600
C6—C71.479 (2)C15—H15B0.9600
C7—C121.389 (2)C15—H15C0.9600
C7—C81.391 (2)C16—H16A0.9600
C8—C91.379 (2)C16—H16B0.9600
C8—Cl11.7383 (18)C16—H16C0.9600
C9—C101.370 (3)N4—H4A0.8600
C2—C1—N1124.75 (17)C11—C12—Cl2117.84 (15)
C2—C1—H1117.6C7—C12—Cl2119.48 (13)
N1—C1—H1117.6N4—C13—C14109.91 (16)
C1—C2—N3117.18 (17)N4—C13—C16111.05 (16)
C1—C2—H2121.4C14—C13—C16110.3 (3)
N3—C2—H2121.4N4—C13—C15106.32 (19)
N2—C3—N3111.51 (13)C14—C13—C15110.4 (3)
N2—C3—C4131.36 (16)C16—C13—C15108.7 (2)
N3—C3—C4117.12 (15)C13—C14—H14A109.5
N1—C4—C3122.75 (18)C13—C14—H14B109.5
N1—C4—H4118.6H14A—C14—H14B109.5
C3—C4—H4118.6C13—C14—H14C109.5
C6—C5—N3104.18 (13)H14A—C14—H14C109.5
C6—C5—N4134.65 (14)H14B—C14—H14C109.5
N3—C5—N4121.10 (13)C13—C15—H15A109.5
N2—C6—C5112.36 (13)C13—C15—H15B109.5
N2—C6—C7122.10 (13)H15A—C15—H15B109.5
C5—C6—C7125.53 (13)C13—C15—H15C109.5
C12—C7—C8115.75 (14)H15A—C15—H15C109.5
C12—C7—C6121.53 (14)H15B—C15—H15C109.5
C8—C7—C6122.64 (14)C13—C16—H16A109.5
C9—C8—C7122.83 (17)C13—C16—H16B109.5
C9—C8—Cl1117.98 (14)H16A—C16—H16B109.5
C7—C8—Cl1119.18 (12)C13—C16—H16C109.5
C10—C9—C8119.10 (18)H16A—C16—H16C109.5
C10—C9—H9120.4H16B—C16—H16C109.5
C8—C9—H9120.4C4—N1—C1117.39 (16)
C9—C10—C11120.58 (18)C3—N2—C6104.55 (13)
C9—C10—H10119.7C2—N3—C3120.81 (14)
C11—C10—H10119.7C2—N3—C5131.78 (14)
C10—C11—C12119.06 (19)C3—N3—C5107.39 (12)
C10—C11—H11120.5C5—N4—C13121.18 (14)
C12—C11—H11120.5C5—N4—H4A119.4
C11—C12—C7122.66 (17)C13—N4—H4A119.4
N1—C1—C2—N30.2 (3)C8—C7—C12—Cl2179.44 (13)
N2—C3—C4—N1178.52 (19)C6—C7—C12—Cl22.7 (2)
N3—C3—C4—N10.4 (3)C3—C4—N1—C10.2 (3)
N3—C5—C6—N20.31 (18)C2—C1—N1—C40.3 (3)
N4—C5—C6—N2176.49 (17)N3—C3—N2—C60.44 (19)
N3—C5—C6—C7178.54 (14)C4—C3—N2—C6179.42 (19)
N4—C5—C6—C74.7 (3)C5—C6—N2—C30.46 (19)
N2—C6—C7—C1271.1 (2)C7—C6—N2—C3178.43 (15)
C5—C6—C7—C12107.6 (2)C1—C2—N3—C30.8 (2)
N2—C6—C7—C8112.39 (19)C1—C2—N3—C5178.89 (16)
C5—C6—C7—C868.9 (2)N2—C3—N3—C2178.22 (14)
C12—C7—C8—C91.6 (3)C4—C3—N3—C20.9 (2)
C6—C7—C8—C9175.10 (17)N2—C3—N3—C50.26 (18)
C12—C7—C8—Cl1177.99 (13)C4—C3—N3—C5179.40 (15)
C6—C7—C8—Cl15.3 (2)C6—C5—N3—C2178.28 (16)
C7—C8—C9—C100.9 (3)N4—C5—N3—C20.9 (3)
Cl1—C8—C9—C10178.66 (18)C6—C5—N3—C30.03 (16)
C8—C9—C10—C110.2 (4)N4—C5—N3—C3177.31 (14)
C9—C10—C11—C120.5 (4)C6—C5—N4—C1387.5 (2)
C10—C11—C12—C70.3 (4)N3—C5—N4—C1396.14 (18)
C10—C11—C12—Cl2178.48 (19)C14—C13—N4—C540.2 (3)
C8—C7—C12—C111.3 (3)C16—C13—N4—C582.2 (2)
C6—C7—C12—C11175.48 (19)C15—C13—N4—C5159.7 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C4—H4···N2i0.932.623.500 (3)158
Symmetry code: (i) x+2, y, z.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C4—H4···N2i0.932.623.500 (3)158
Symmetry code: (i) x+2, y, z.
Acknowledgements top

The authors thank the TBI X-ray facility, CAS in Crystallography and Biophysics, University of Madras, India, for the data collection. ZF also thanks the UGC for a meritorious fellowship.

references
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