Ethyl 2-[5-(4-chlorophenyl)-1-(4-fluorophenyl)-1H-pyrazol-3-yl]-4-methylthiazole-5-carboxylate

In the title compound, C22H17ClFN3O2S, the pyrazole ring is approximately planar with a maximum deviation of 0.001 (4) Å and makes dihedral angles of 4.95 (19), 35.78 (18) and 54.73 (18)° with the thiazole, fluorobenzene and chlorobenzene rings, respectively. In the crystal, intermolecular C—H⋯O hydrogen bonds link the molecules into chains along the a axis.

In the title compound, C 22 H 17 ClFN 3 O 2 S, the pyrazole ring is approximately planar with a maximum deviation of 0.001 (4) Å and makes dihedral angles of 4.95 (19), 35.78 (18) and 54.73 (18) with the thiazole, fluorobenzene and chlorobenzene rings, respectively. In the crystal, intermolecular C-HÁ Á ÁO hydrogen bonds link the molecules into chains along the a axis.

Related literature
For background to pyrazole derivatives and their antimicrobial activity, see: Ragavan et al. (2009Ragavan et al. ( , 2010. For bondlength data, see: Allen et al. (1987). For a related structure, see: Loh et al. (2010). For the stability of the temperature controller used in the data collection, see: Cosier & Glazer (1986 Table 1 Hydrogen-bond geometry (Å , ).

Comment
Antibacterial and antifungal activities of azoles are most widely studied and some of them are in clinical practice as antimicrobial agents. However, the azole-resistant strains had led to the development of new antimicrobial compounds. In particular pyrazole derivatives are extensively studied and used as antimicrobial agents. Pyrazole is an important class of heterocyclic compounds and many pyrazole derivatives are reported to have a broad spectrum of biological properties, such as anti-inflammatory, antifungal, herbicidal, anti-tumour, cytotoxic, molecular modelling and antiviral activities. Pyrazole derivatives also act as anti-angiogenic agents, A3 adenosine receptor antagonists, neuropeptide YY5 receptor antagonists, kinase inhibitor for treatment of type 2 diabetes, hyperlipidemia, obesity and thrombopiotinmimetics. Recently urea derivatives of pyrazoles have been reported as potent inhibitors of p38 kinase. Since the high electronegativity of halogens (particularly chlorine and fluorine) in the aromatic part of the drug molecules play an important role in enhancing their biological activity, we are interested to have 4-fluoro or 4-chloro substitution in the aryls of 1,5-diaryl pyrazoles. As part of our on-going research aiming the synthesis of new antimicrobial compounds, we have reported the synthesis of novel pyrazole derivatives and their microbial activities (Ragavan et al., 2009;. The title compound consists of four rings, namely pyrazole (C1-C3/N1/N2), thiazole (C4/N3/C5/C6/S1), fluorophenyl (C11-C16/F1) and chlorophenyl (C17-C22/Cl1) rings (Fig. 1). The pyrazole ring is approximately planar with a maximum deviation of 0.001 (4) Å at atom C1 and makes dihedral angles of 4.95 (19), 35.78 (18) and 54.73 (18)° with the thiazole, fluorophenyl and chlorophenyl rings, respectively. Bond lengths (Allen et al., 1987) and angles are within the normal ranges and are comparable to the related structure (Loh et al., 2010).
In the crystal packing ( Fig. 2), intermolecular C15-H15A···O2 hydrogen bonds link the molecules into one-dimensional chains along the a axis.

Experimental
The compound has been synthesized using the method available in the literature  and recrystallized using the ethanol-chloroform 1:1 mixture. Yield: 81%. M.p.: 411.3-413 K.

Refinement
All H atoms were positioned geometrically with the bond length of C-H being 0.93 to 0.97 Å and were refined using a riding model, with U iso (H) = 1.2 or 1.5 U eq (C). A rotating group model was applied to the methyl groups.

Special details
Experimental. The crystal was placed in the cold stream of an Oxford Cryosystems Cobra open-flow nitrogen cryostat (Cosier & Glazer, 1986) operating at 100.0 (1) K. Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating Rfactors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.