2-(4-Fluoro­phen­yl)-N-{4-[6-(4-fluoro­phen­yl)-2,3-dihydro­imidazo[2,1-b][1,3]thia­zol-5-yl]pyridin-2-yl}acetamide

Roland Selig; Dieter Schollmeyer; Wolfgang Albrecht; Stefan Laufer

doi:10.1107/S1600536810012766

. 2010 Apr 21;66(Pt 5):o1132. doi: 10.1107/S1600536810012766

2-(4-Fluorophenyl)-N-{4-[6-(4-fluorophenyl)-2,3-dihydroimidazo[2,1-b][1,3]thiazol-5-yl]pyridin-2-yl}acetamide

Roland Selig ^a, Dieter Schollmeyer ^b, Wolfgang Albrecht ^c, Stefan Laufer ^a,^*

PMCID: PMC2979114 PMID: 21579181

Abstract

In the crystal structure of the title compound, C₂₄H₁₈F₂N₄OS, the imidazole system makes dihedral angles of 34.3 (1) and 43.9 (1)°, respectively, with the directly attached 4-fluorophenyl and pyridine rings. The crystal structure is stabilized by intermolecular N—H⋯N hydrogen bonding and by an intramolecular C—H⋯O hydrogen interaction. The F atom of the 2-(4-fluorophenyl) group is disordered over two positions with site-occupancy factors of 0.75 and 0.25.

Related literature

For related compounds and their biological relevance, see: Ziegler et al. (2009 ▶).

Experimental

Crystal data

C₂₄H₁₈F₂N₄OS
M _r = 448.48
Monoclinic,
a = 4.9179 (3) Å
b = 23.592 (1) Å
c = 18.4834 (9) Å
β = 91.523 (2)°
V = 2143.8 (2) Å³
Z = 4
Mo Kα radiation
μ = 0.19 mm⁻¹
T = 173 K
0.35 × 0.16 × 0.08 mm

Data collection

Bruker SMART APEXII diffractometer
10277 measured reflections
4846 independent reflections
4129 reflections with I > 2σ(I)
R _int = 0.028

Refinement

R[F ² > 2σ(F ²)] = 0.038
wR(F ²) = 0.090
S = 1.03
4846 reflections
298 parameters
2 restraints
H-atom parameters constrained
Δρ_max = 0.23 e Å⁻³
Δρ_min = −0.20 e Å⁻³
Absolute structure: Flack (1983 ▶), 2197 Friedel pairs
Flack parameter: 0.07 (6)

Data collection: APEX2 (Bruker, 2006 ▶); cell refinement: SAINT (Bruker, 2006 ▶); data reduction: SAINT; program(s) used to solve structure: SIR97 (Altomare et al., 1999 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: PLATON (Spek, 2009 ▶); software used to prepare material for publication: PLATON.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810012766/im2189sup1.cif

e-66-o1132-sup1.cif^{(22.7KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810012766/im2189Isup2.hkl

e-66-o1132-Isup2.hkl^{(237.4KB, hkl)}

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
N13—H13⋯N6ⁱ	0.97	2.02	2.980 (2)	171
C8—H8⋯O15	0.95	2.24	2.845 (3)	120

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Symmetry code: (i) Inline graphic .

Acknowledgments

The authors would like to thank the Federal Ministry of Education and Research, Germany, Merckle GmbH, Ulm, Germany, and Fonds der Chemischen Industrie, Germany, for their generous support of this work.

supplementary crystallographic information

Comment

SKF86002 was an early lead compound of many imidazole based p38 MAP kinase inhibitors. A further improvement of these inhibitors was the modification of the pyridyl moiety by substitution with amines in C-2 position of the pyridine. This donor acceptor system can interact with hinge region/MET109 by bidentate hydrogen bonding. Additional interactions of the attached residues with the hydrophobic region II strongly increases potency of these compounds (Ziegler et al. 2009).

The imidazole system of the title compound 2-(4-fluorophenyl)-N-{4-[6-(4-fluorophenyl)-2,3-dihydroimidazo[2,1-b][1,3] thiazol-5-yl]-pyridin-2-yl}acetamide, C₂₄H₁₈F₂N₄OS, makes dihedral angles of 34.3 (1)° and 43.9 (1)° with the directly attached 4-fluorophenyl and the pyridine rings, respectively. The crystal structure is characterized by an intermolecular hydrogen bond N13—H13···N6 (2.02 Å). The molecular conformation is stabilized by an intramolecular C8—H8···O15 (2.24 Å) interaction. The flourine atom F1 is disordered over two positions with s.o.f 0.75:0.25.

Experimental

4-fluorphenylacetic acid (296 mg) was dissolved in 3 ml N-methylpyrrolidinone. After addition of 332 mg of carbonyldiimidazole the mixture was stirred for 1 h at room temperature. 200 mg 4-[6-(4-fluorophenyl)-2,3-dihydroimidazo[2,1-b][1,3]thiazol-5-yl]pyridin-2-amine was added and the reaction mixture was heated to 383 K for 19 h. The reaction mixture was quenched with a solution of concentrated sodium hydrogen carbonate and extracted with ethylacetate. The crude product was purified by flash chromatography (eluent: ethylacetate/hexane 2/1) to yield 155 mg (54%) of the title compound. Crystals suitable for X-ray analysis were obtained by slow crystallization from methanol at room temperature.