Crystal structure of (1′S,2′S,3S)-1′-benzoyl-2′-(4-methoxyphenyl)-1-methyl-2′,5′,6′,10b′-tetrahydro-1′H-spiro[indoline-3,3′-pyrrolo[2,1-a]isoquinolin]-2-one

The synthesis and crystal structure of the spiro title compound is presented.


Chemical context
Spiro frameworks are often utilized in drug design as a result of their three-dimensionality and structural diversity, which provide a framework for the attachment of pharmaceutically relevant active sites (Kobayashi et al., 1991). The spiropyrrolidine structural motif is present in numerous naturally occurring and pharmacologically important alkaloids. The spiro-pyrrolidine-indolin-2-one framework in particular is found in a number of alkaloids of biological significance (Hilton et al., 2000). Some of these compounds have been used as antimicrobial and antitumour agents (Sundar et al., 2011), or have analgesic (Crooks & Sommerville, 1982) and antiinfluenza properties (Stylianakis et al., 2003). Taking into account the significance of spiro compounds in this context, the single-crystal X-ray structure of the title compound, 1, was determined. ISSN 2056-9890

Supramolecular features
In the crystal packing of 1, there are no classical hydrogen bonds orinteractions between the various rings of adjacent molecules. There are, however, different weak C-HÁ Á ÁO close contacts for the two disorder components (Table 1). For the major component, there is a close contact between translation-related molecules, C33-H33BÁ Á ÁO2 i , of 3.490 (5) Å [symmetry code: (i) x + 1, y, z], while for the minor component there is a close contact between glide-related molecules, C4-H4Á Á ÁO3 ii , of 3.559 (6) Å [symmetry code: (ii) x À 1, Ày + 1 2 , z À 1 2 ]. For the major component, these generate C(11) chains (Bernstein et al., 1995) that propagate parallel to the a axis (Fig. 2).

Database survey
A search in the Cambridge Structural Database (CSD, version 5.39, update August 2018;Groom et al., 2016) using pyrrolidine as the search fragment produced over 11600 hits. For the core spiro-pyrrolidine/N-methyl pyrrolidone fragment, the yield was a more modest 88 hits. These 88 structures show many different substitution patterns. The four structures with the most features in common with 1 are probably RAQCIY (Du et al., 2017), IFETAR (Guo et al., 2018), DOHMEV (Boudriga et al., 2019), and KIFRID (Zhang et al., 2018), though none of these are especially similar to 1.

Synthesis and crystallization
In a 50 mL round-bottom flask, 1-methylisatin (0.5 mmol) was dissolved in toluene (5 mL) followed by the addition of 1,2,3,4-tetrahydroisoquinoline (0.5 mmol) and the mixture was stirred at room temperature for half an hour. After that, (E)-3-(4-methoxyphenyl)-1-phenylprop-2-en-1-one (0.5 mmol) was added to the reaction mixture and stirring was continued at 383 K for 10 h. The reaction was monitored for the formation of the product by TLC at regular intervals. Soon after the formation of the product, the reaction mixture was concentrated under reduced pressure and extracted with ethyl  Table 1 Hydrogen-bond geometry (Å , ). Symmetry codes: (i) x þ 1; y; z; (ii) x À 1; Ày þ 1 2 ; z À 1 2 .

Figure 2
The crystal packing of the title compound, showing the C(11) chain (major disorder component only) running parallel to the a axis. Hydrogen bonds are shown as dotted lines. Only the H atoms on groups involved in the hydrogen bonding are included.

Figure 1
A view of the title compound showing the atom-labelling scheme. Displacement ellipsoids are drawn at the 30% probability level. For the sake of clarity, the minor component of disorder of the methoxyphenyl group is not shown.
acetate/water (v/v = 75:25). The organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum to yield the crude product, which was purified by column chromatography using ethyl acetate/n-hexane (3:17) as eluent. 0.2g of the compound were dissolved in ethanol and the solution was kept undisturbed in the open air for one week. After five days, crystals started to appear and were separated carefully.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. Hydrogen 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. The occupancies of the disorder group of the methoxy phenyl moiety were initially allowed to ride then it was fixed and refined. The benzene rings were refined as rigid hexagons with C-C distances of 1.39 Å . The other bond lengths of the major and the minor components were made similar using similarity restraints with an s.u. of 0.01 Å . The positions of the methoxyphenyl moiety (C30/O3/ C33) atoms are disordered over two positions with site occupancy factors of 0.638 (6) and 0.362 (6), respectively. Acta Cryst. (2020). E76, 1548-1550 research communications  Data collection: APEX2 (Bruker, 2008); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2018/3 (Sheldrick, 2015); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012) and Mercury (Macrae et al., 2020); software used to prepare material for publication: SHELXL97 (Sheldrick, 2008) and PLATON (Spek, 2020).

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.