N-tert-Butyl-2-[4-(dimethyl­amino)­phen­yl]imidazo[1,2-a]pyrazin-3-amine

Zeenat Fatima; Thothadri Srinivasan; Suman Koorathota; Sathiah Thennarasu; Devadasan Velmurugan

doi:10.1107/S1600536813007861

. 2013 Mar 28;69(Pt 4):o612–o613. doi: 10.1107/S1600536813007861

N-tert-Butyl-2-[4-(dimethylamino)phenyl]imidazo[1,2-a]pyrazin-3-amine

Zeenat Fatima ^a, Thothadri Srinivasan ^a, Suman Koorathota ^b, Sathiah Thennarasu ^b, Devadasan Velmurugan ^a,^*

PMCID: PMC3629650 PMID: 23634137

Abstract

In the title compound, C₁₈H₂₃N₅, the imidazole ring makes a dihedral angles of 3.96 (8) and 19.02 (8)°, respectively, with the pyrazine and benzene rings while the dihedral angle between the pyrazine and benzene rings is 16.96 (7)°. In the crystal, molecules are linked via N—H⋯N hydrogen bonds, forming chains along [010]. These chains are linked by C—H⋯N hydrogen bonds, forming two-dimensional networks lying parallel to (001).

Related literature

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 ongoing structural studies of heterocyclic N-containing derivatives, see: Nasir et al. (2010 ▶). For background to the fluorescence properties of compounds related to the title compound, 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 a related structure, see: Ouzidan et al. (2011 ▶).

Experimental

Crystal data

C₁₈H₂₃N₅
M _r = 309.41
Orthorhombic,
a = 12.1746 (11) Å
b = 13.9614 (13) Å
c = 20.2985 (19) Å
V = 3450.2 (6) Å³
Z = 8
Mo Kα radiation
μ = 0.07 mm⁻¹
T = 293 K
0.30 × 0.25 × 0.20 mm

Data collection

Bruker SMART APEXII area-detector diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2008 ▶) T _min = 0.978, T _max = 0.985
18314 measured reflections
4157 independent reflections
2964 reflections with I > 2σ(I)
R _int = 0.043

Refinement

R[F ² > 2σ(F ²)] = 0.049
wR(F ²) = 0.148
S = 1.03
4157 reflections
218 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.32 e Å⁻³
Δρ_min = −0.25 e Å⁻³

Data collection: APEX2 (Bruker, 2008 ▶); cell refinement: SAINT (Bruker, 2008 ▶); data reduction: SAINT; 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 and PLATON (Spek, 2009 ▶).

Supplementary Material

Click here for additional data file.^{(27.2KB, cif)}

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S1600536813007861/su2577sup1.cif

e-69-0o612-sup1.cif^{(27.2KB, cif)}

Click here for additional data file.^{(199.7KB, hkl)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536813007861/su2577Isup2.hkl

e-69-0o612-Isup2.hkl^{(199.7KB, hkl)}

Click here for additional data file.^{(6.4KB, cml)}

Supplementary material file. DOI: 10.1107/S1600536813007861/su2577Isup3.cml

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N3—H3⋯N1ⁱ	0.873 (18)	2.201 (18)	3.0361 (18)	160.0 (14)
C11—H11⋯N4ⁱⁱ	0.93	2.53	3.428 (2)	162

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Symmetry codes: (i) Inline graphic ; (ii) .

Acknowledgments

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

supplementary crystallographic information

Comment

The pyrazine ring system is a useful structural element in medicinal chemistry and has found broad applications in drug development which can be used as antiproliferative agents (Dubinina et al., 2006), potent CXCR3 antagonists (Du et al., 2009),CB1 antagonists (Ellsworth et al., 2007) and c-Src inhibitory (Mukaiyama et al., 2007). On-going structural studies of heterocyclic N-containing derivatives (Nasir et al., 2010) are also 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 has been 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/N4/C3/C5/C6) makes a dihedral angle of 3.96 (8)° with the pyrazine ring (N1/N2/C1-C4) and a dihedral angle of 19.02 (8)° with the benzene ring (C7-C12). The dihedral angle between the pyrazine ring and the benzene ring is 16.96 (7)°.The dimethylamine group (N5/C14/C15) attached with the benzene ring makes a dihedral angle of 8.84 (11)°.

In the crystal, molecules are linked via N-H···N hydrogen bonds forming chains along [010]. These chains are linked by C—H···N hydrogen bonds forming two-dimensional networks lying parallel to (001); see Table 1 and Fig. 2 for details.

Experimental

2-aminoamidine (1.0 mmol) was placed in an oven-dried round bottom flask, dissolved in EtOH (5.0 mL) and stirred at room temperature. 4-N,N-dimethyl benzaldehyde (1.0 mmol), isocyanide (1.0 mmol) and Iodine (2.0 mol%) were added sequentially and the mixture stirred at room temperature for one hour. Progress of the reaction was monitored by TLC. When finished 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: 2% EtOAc in hexane). Colourless block-like crystals, suitable for X-ray diffraction analysis, were obtained by slow evaporation of a solution of the title compound in ethanol at room temperature [M.p: 478 - 480 K; IR (KBr, cm^-1): 3259 (NH)]