tert-Butyl 3-(8-bromo-4H,10H-1,2-oxazolo[4,3-c][1]benzoxepin-10-yl)-2-methyl-1H-indole-1-carboxylate

In the title compound, C25H23BrN2O4, the seven-membered ring adopts a twisted-boat conformation. The indole ring system is planar within 0.021 (2) Å and the ester group [–C(=O)—O—C–] is almost coplanar with it [dihedral angle = 3.0 (2)°]. The conformation of the ester group is influenced by intramolecular C—H⋯O interactions. In the crystal structure, molecules are linked into chains along the b axis by C—H⋯N hydrogen bonds.


Comment
Nitrogen and oxygen containing heterocycles are ubiquitous substructures in myriad of biologically active natural products and small-molecule pharmaceuticals (Furstner, 2003;Liddell, 2002). The nitrile oxide cycloaddition is a useful method to prepare heterocyclic compounds (Caramella & Grunanger, 1984). Isoxazole, the cycloadduct of nitrile oxide, is regarded as a versatile synthetic precursor for γ-amino alcohols and β-hydroxy ketones. Isoxazoles are found in some natural products, such as ibotenic acid. Ibotenic acid is naturally occurring in mushrooms Amanita muscaria and Amanita pantherina. Ibotenic acid is a powerful neurotoxin that is used as a brain-lesioning agent and has shown to be highly neurotoxic when injected directly into the brains of mice and rats. Isoxazoles also form the basis for a number of drugs, including the COX-2 inhibitor valdecoxib. Valdecoxib is a prescription drug used in the treatment of osteoarthritis, rheumatoid arthritis, painful menstruation and menstrual symptoms (Stormer et al., 2004;Erdelyi et al., 2008).
Atom C11 in the molecule at (x,y,z) acts as donar to atom N1 at (x, 1+y, z), forming a chain running along the b axis (1.0 mmol) and N,N-dimethyl-4-aminopyridine (0.2 mmol) were dissolved in toluene (5 ml). Di-tert-butyl dicarbonate (2.5 mmol) in toluene (5 ml) was added in portions over a period of 0.5 h at 363 K to the nitroalkane solution and the reaction was allowed to proceed for a further 2 h. The mixture was evaporated and the product was purified by column chromatography using ethyl acetate-petroleum ether (2:8) as eluent. Single crystals appeared from the same eluent mixture.
supplementary materials sup-2 Refinement H atoms were positioned geometrically (C-H = 0.93-0.98 Å) and allowed to ride on their parent atoms, with U iso (H) = 1.5U eq (C) for methyl H and 1.2U eq (C) for other H atoms.

Special details
Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds involving l.s. planes.
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 > 2sigma(F 2 ) is used only for calculating R-factors(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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq