Ethyl 8-amino-6-bromoimidazo[1,2-a]pyridine-2-carb­oxy­late

Siham Dahmani; Youssef Kandri Rodi; Santiago V Luis; El Mokhtar Essassi; Lahcen El Ammari

doi:10.1107/S1600536811017077

. 2011 May 11;67(Pt 6):o1390. doi: 10.1107/S1600536811017077

Ethyl 8-amino-6-bromoimidazo[1,2-a]pyridine-2-carboxylate

Siham Dahmani ^a,^*, Youssef Kandri Rodi ^a, Santiago V Luis ^b, El Mokhtar Essassi ^c, Lahcen El Ammari ^d

PMCID: PMC3120515 PMID: 21754778

Abstract

There are two independent molecules in the asymmetric unit of the title compound, C₁₀H₁₀BrN₃O₂, which are linked by N—H⋯O and C—H⋯O hydrogen bonds. The fused ring systems in both molecules are nearly planar with maximum deviations of 0.001 (3) and 0.029 (3) Å. All non-H atoms of the first molecule are approximately co-planar whereas in the second molecule, the ethyl group is almost perpendicular to the imidazo[1,2-a]pyridine system, the C—O—C—C torsion angles in the carboxylic acid ethyl group being −179.8 (4) and 112.1 (5)°, respectively.

Related literature

For the biological activity of imidazo[1,2-a]pyridine derivatives, see: Anderson et al. (2003 ▶); Trapani et al. (2003 ▶); Gueiffier et al. (1998 ▶); Mavel et al. (2002 ▶). For their pharmacological activity, see: Rival et al. (1992 ▶); Rupert et al. (2003 ▶); Katritzky et al. (2003 ▶).

Experimental

Crystal data

C₁₀H₁₀BrN₃O₂
M _r = 284.12
Monoclinic,
a = 8.366 (2) Å
b = 11.842 (3) Å
c = 22.743 (5) Å
β = 98.328 (6)°
V = 2229.3 (8) Å³
Z = 8
Mo Kα radiation
μ = 3.68 mm⁻¹
T = 292 K
0.44 × 0.19 × 0.17 mm

Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2009 ▶) T _min = 0.437, T _max = 0.535
13222 measured reflections
4555 independent reflections
3156 reflections with I > 2σ(I)
R _int = 0.032

Refinement

R[F ² > 2σ(F ²)] = 0.041
wR(F ²) = 0.116
S = 1.03
4555 reflections
291 parameters
H-atom parameters constrained
Δρ_max = 0.70 e Å⁻³
Δρ_min = −0.51 e Å⁻³

Data collection: APEX2 (Bruker, 2009 ▶); cell refinement: SAINT-Plus (Bruker, 2009 ▶); data reduction: SAINT-Plus; 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, 1997 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536811017077/dn2683sup1.cif

e-67-o1390-sup1.cif^{(27.2KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811017077/dn2683Isup2.hkl

e-67-o1390-Isup2.hkl^{(218.7KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811017077/dn2683Isup3.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—H3A⋯N5ⁱ	0.86	2.47	3.300 (4)	161
N3—H3B⋯O3ⁱⁱ	0.86	2.38	3.055 (5)	135
N6—H6B⋯O2	0.85	2.34	3.096 (4)	147
N6—H6A⋯O1ⁱⁱⁱ	0.86	2.58	3.183 (4)	129
N6—H6A⋯N2ⁱⁱⁱ	0.86	2.60	3.388 (4)	154
C5—H5⋯O4	0.93	2.26	3.074 (4)	146

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

supplementary crystallographic information

Comment

Imidazo[1,2-a]pyridine derivatives are important intermediates in organic synthesis, especially in the synthesis of biologically active and medicinally useful agents. For instance, they are widely used in the synthesis of cyclin- dependent kinases (CDK) inhibitors (Anderson et al., 2003), anticonvulsant agents, (Trapani et al., 2003) and antiviral agents (Gueiffier et al.,1998; Mavel et al.,2002).

Derivatives containing the imidazo[1,2-a]- pyridine ring system have been shown to possess a broad range of useful pharmacological activities, including antibacterial, (Rival et al., 1992) and anti-inflammatory properties (Rupert et al., 2003). Drug formulations containing imidazo[1,2-a]pyridines currently available on the market include alpidem (anxiolytic), zolpidem (hypnotic), and zolimidine (antiulcer) (Katritzky et al.,2003).

In this work, we report a novel and efficient method for the synthesis of 6-bromo-8-amino-imidazo[1,2-a]pyridine via the treatment of ethyl bromopyruvate with 5-bromo-2,3-diaminopyridine in the presence of NaHCO₃ in ethanol at reflux in 65% yield (scheme1).

The Plot of the two molecules building the asymmetric unit of the 8-Amino-6- bromo-imidazo[1,2-a]pyridin-2-carboxylic acid ethyl ester is shown in Fig.1. The two fused five and six-membered rings belonging to each molecule are nearly planar with the maximum deviation of -0.001 (3)Å from C7 and 0.029 (3)Å from C17. The dihedral angle between them is 26.06 (11)°. The ethyl group is almost perpendicular to the imidazo[1,2-a]pyridine system, in the second molecule, as indicated by the torsion angle C18–O3–C19–C20 of 112.1 (5)° (see Fig.2). The first molecule is approximately planar and the torsion angle C—O—C—C is in the range of -179.8 (4)°. In the crystal, the molecules are linked by intermolecular N—H···O and C—H···O hydrogen bonds building a three dimensionnal network (Table 1).

Experimental

A mixture of ethyl bromopyruvate (0.3 ml; 2.35 mmol), 5-bromo-2,3-diaminopyridine (0.5 g, 2.35 mmol) and NaHCO₃ (0.22 g, 2.35 mmol) in ethanol was stirred at reflux for the appropriate time. After completion of the reaction, as indicated by TLC, The solution was extracted with dichloromethane and the organic layer was dried over anhydrous Na₂SO₄. Evaporation of the solvent followed by recrystallization in hexane afforded yellow crystals of the title compound.