1-[2-(4-Nitrophenyl)-5-(5-phenyl-1,2-oxazol-3-yl)-1,2,3,4-tetrahydroquinolin-4-yl]pyrrolidin-2-one

The title compound, (I) C28H24N4O4, is the trans diastereoisomer of the compound 1-[2-(4-nitrophenyl)-6-(5-phenyl-3-isoxazolyl)-1,2,3,4-tetrahydro-4-quinolinyl]-2-pyrrolidinone monohydrate, (II) [Gutierrez et al. (2011 ▶). Acta Cryst. E67, o175–o176]. The most obvious differences between the diastereoisomers are the dihedral angles between the isoxazole ring and the benzene and phenyl rings [47.0 (2); 56.4 (2) and 33.3 (2); 11.0 (2)°, respectively, for (II) 75.4 (2) and 5.8 (3), respectively, for (I)]. In the crystal of (I), the molecules are linked by N—H⋯O interactions into a chain along [001] with graph-set notation C(8).

Quinoline and its derivatives represent a major class of heterocycles, and a number of preparations have been known since the late 1800's. The quinoline skeleton is often used for the design of many synthetic compounds with diverse pharmacological properties. Several syntheses of quinolines are known, but due to their importance, the development of new synthetic approaches remains an active research area (Kouznetsov et al., 2005).
The isoxazoles form a relevant group of biologically active compounds with a wide range of applications, including Hsp90 super chaperone complex inhibitors (Taldone et al., 2008), tau aggregation inhibitors for treatment of Alzheimer's disease (Narlawar et al., 2008), mycobacterium tuberculosis pantothenate synthetase inhibitors (Velaparthi et al., 2008) and neuronal nicotinic acetylcholine receptor agonists (Rizzi et al., 2008).
A considerable number of methods to synthesize substituted isoxazoles have been published including approaches based on intramolecular cycloadditions, condensations, and intramolecular cyclizations of amino acids. These methods sometime suffer in their versatility, convenience and yield (Lautens & Roy, 2000). The isoxazole ring can be synthetized by 1, 3-dipolar cyclo-addition reactions between a nitrile oxide and an alkyne, that reaction may be catalyzed by copper(II). Cycloaddition reactions are among the most useful reactions in synthetic and mechanistic organic chemistry (Broggini et al., 2005).
Isoxazoles have a rich chemistry because of their easy reductive cleavage and susceptibility to ring transformations (Kotera et al., 1970). Depending on the substitution patterns, isoxazoles can be used as reagents for the imino-Diels-Alder condensation between anilines, aldehydes and electron-rich alkenes to generate tetrahydroquinolines with different selected substitution patterns.
Due to these facts, the combination of the two heterocyclic rings into a new chemical entity is of interest, as no examples are known in the chemical literature to date.
Many molecules widely used today consist of fusions of rings; an example is the case of penicillins, where incorporation of an isoxazole ring led to the formation of stable derivatives which catalyzed the degradation of gastric acid levels (flucloxacillin and cloxacillin).
We report here the crystal structure of a novel synthetic derivative cis quinoline-isoxazole prepared by imino Diels-Alder cyclo-addition, Scheme 1.

Refinement
The SQUEEZE function of PLATON (Spek, 2009) was used to eliminate the contribution of electron density in the solvent region from the intensity data, and a solvent-free model was employed for the final refinement. The volume which is accessible for potential solvent molecules was calculated to be 452.0 Å 3 and the total electron count per cell was calculated to be 15. Note that the calculated density, the F(000) value, the molecular weight and the formula are given without taking into account the results obtained with the SQUEEZE option in PLATON (Spek, 2009). Therefore, the solvent-free model and intensity data were used for the final results reported here.
The absolute configuration of the two stereogenic centres could not be established by the Flack parameter (Flack, 1983) and Friedel opposites were merged.
The position of the N2 H atom was refined freely with isotropic displacement parameters. All other H atoms were placed in geometrically idealized positions (C-H = 0.93-0.97 Å) and constrained to ride on their parent atoms with U iso (H) = 1.2U eq (C).  Fig. 1. The structure of (I), showing the atom-numbering scheme. Displacement ellipsoids are plotted at the 30% probability level.   (5)