Crystal structure of ethyl 5′′-fluoro-2′′,3-dioxo-6′,7′,8′,8a’-tetrahydro-2′H,3H,5′H-dispiro[benzo[b]thiophene-2,1′-indolizine-3′,3′′-indoline]-2′-carboxylate

In the title compound, C25H23FN2O4S, the fused piperidine ring of the octahydroindolizine ring system adopts a chair conformation and the five-membered ring has a twisted conformation on the N—C(spiro) bond. The mean planes of the benzothiophene and indoline ring systems are inclined to the mean plane of the pyrrolidine ring by 83.1 (1) and 84.9 (1)°, respectively, and to each other by 29.37 (17)°. In the crystal, molecules are linked via pairs of N—H⋯O hydrogen bonds, forming inversion dimers with an R 2 2(8) ring motif. The dimers are linked via C—H⋯O hydrogen bonds, forming slabs lying parallel to (100). The packing between the slabs features a short [2.734 (2) Å] F⋯F contact.


S1. Comment
Indole-containing compounds are best known for their medicinal properties in the pharmaceutical industry. In modern times, analogs based on indole are significant players in a diverse array of markets such as dyes, plastics, agriculture, vitamin supplements, over-the-counterdrugs, flavour enhancers and perfumery (Barden, 2011). Several indole derivatives, such as Sunitinib, a tyrosine kinase inhibitor (Oudard et al., 2011), or Delavirdine a non-nucleoside reverse transcriptase inhibitor (Beale, 2011), are in clinical use. Spiroindoles are important heterocyclic compounds with diverse bioactivities (Aanandhi et al., 2008;Muthukumar et al., 2008).
The X-ray study confirmed the molecular structure and atomic connectivity for the title compound, as illustrated in Fig.   1. Pyridine ring adopts a chair conformation [puckering parameters q 2 = 0.069 (3) Å and π 2 = 303 (2)°]. The pyrrole ring adopts a twisted conformation with the lowest asymmetry parameters ΔC2(N1-C10) = 1.8 (2)°. The pyrrole ring system is oriented with a dihedral angles of 84.9 (1) and 83.1 (1)°, respectively with respect to the mean planes of benzothiophene ring and indole ring systems.
In the crystal, molecules are linked via N-H···O hydrogen bonds forming inversion dimers with an R 2 2 (8) ring motif (Table 1 and Fig. 2). The dimers are linked via C-H···O hydrogen bonds forming slabs lying parallel to (100); see Table   1 and Fig. 2. The slabs are linked by a short F···F i interaction [2.73482) Å, symmetry code: (i) -x, -y+2, -z] forming a three-dimensional structure.

S2. Experimental
A reaction mixture of (E)-ethyl 2-(3-oxobenzo[b]thiophen-2(3H)-ylidene)acetate (1.0 mmol), 5-Fluoroisatin (1.1 mmol) and pipecolic acid (1.1 mmol) was refluxed in methanol (20 ml) until completion of the reaction was evidenced by TLC analysis. After completion of the reaction the solvent was evaporated under reduced pressure. The crude reaction mixture was dissolved in dichloromethane (2 x 50 ml) and washed with water followed by brine solution. The organic layer was separated and dried over sodium sulfate. After filtration and evaporation of the organic solvent was carried out under reduced pressure. The product was separated by column chromatography using hexane and ethyl acetate (9:1) as an eluent to give a colorless solid. The product was dissolved in chloroform (3 ml) and heated for two minutes. The resulting solution was subjected to crystallization by slow evaporation of the solvent resulting in single crystals suitable for X-ray crystallographic studies.

S3. Refinement
The NH H atom was located in a difference Fourier map and freely refined. The C-bound 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 atoms and = 1.2U eq (C) for all other H atoms.

Figure 1
The molecular structure of the title compound, showing the atom labelling. Displacement ellipsoids are drawn at the 30% probability level.

Figure 2
A view along the b axis of the crystal packing of the title compound. Hydrogen bonds are shown as dashed lines (see Table 1 for details; H atoms not involved in these interactions have been omitted for clarity). where P = (F o 2 + 2F c 2 )/3 (Δ/σ) max = 0.001 Δρ max = 0.38 e Å −3 Δρ min = −0.24 e Å −3 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.