Crystal structure of 2-benzylamino-4-(4-methoxyphenyl)-6,7,8,9-tetrahydro-5H-cyclohepta[b]pyridine-3-carbonitrile

The title compound comprises a 2-aminopyridine ring fused with a cycloheptane ring, which adopts a chair conformation. In the crystal, molecules are linked via pairs of N—H⋯Nnitrile hydrogen bonds, forming inversion dimers which enclose (14) ring motifs

The title compound, C 25 H 25 N 3 O, comprises a 2-aminopyridine ring fused with a cycloheptane ring, which adopts a chair conformation. The central pyridine ring (r.m.s. deviation = 0.013 Å ) carries three substituents, viz. a benzylamino group, a methoxyphenyl ring and a carbonitrile group. The N atom of the carbonitrile group is significantly displaced [by 0.2247 (1) Å ] from the plane of the pyridine ring, probably due to steric crowding involving the adjacent substituents. The phenyl and benzene rings are inclined to one another by 58.91 (7) and to the pyridine ring by 76.68 (7) and 49.80 (6) , respectively. In the crystal, inversion dimers linked by pairs of N-HÁ Á ÁN nitrile hydrogen bonds generate R 2 2 (14) loops. The dimers are linked by C-HÁ Á Á and slipped parallelinteractions [centroid-centroid distance = 3.6532 (3) Å ] into a three-dimensional structure.

Chemical context
The pyridine nucleus is prevalent in numerous natural products and extremely important in the chemistry of biological systems (Bringmann et al., 2004). 3-Cyanopyridine or pyridine-3-carbonitrile derivatives attract particular attention for their wide-spectrum biological activity along with their importance and utility as intermediates in the preparation of a variety of heterocyclic compounds (Shishoo et al., 1983;Doe et al., 1990). 3-Cyanopyridines with different alkyl and aryl/ heteroaryl groups have been found to have a number of biological properties including antitubercular, antimicrobial, anticancer, A2A adenosine receptor antagonists (Mantri et al., 2008), antihypertensive (Krauze et al., 1985), antihistaminic (Quintela et al., 1997), anti-inflammatory, analgesic and antipyretic (Manna et al., 1999) properties. Our interest in the preparation of pharmacologically active 3-cyanopyridines led us to synthesise the title compound and the X-ray crystal structure determination was undertaken in order to establish its conformation.

Structural commentary
The molecular structure of the title compound is shown in Fig. 1. The pyridine ring is connected to a benzene ring by a -CH 2 -NH 2 -chain. The cycloheptane ring adopts a chair conformation with puckering parameters Q2 = 0.4634 (15) Å , '2 = 304.24 (18) and Q3 = 0.6481 (16) Å and '3 = 284.37 (12) . The phenyl (C22-C27) and benzene (C31-C36) rings are inclined to one another by 58.91 (7) and to the pyridine (N3/C2-C6) ring by 76.68 (7) and 49.80 (6) , respectively. The N atom of the carbonitrile group, N1, is significantly displaced by 0.2247 (1) Å from the plane of the pyridine ring, perhaps due to steric crowding. The shortening of the C-N distance [C5-N3 = 1.3390 (14) Å ] and the opening of the N3-C5-C4 angle to 124.47 (10) may be attributed to the size of the substituent at C1, and correlates well with the values observed in a similar structure (Ç elik et al., 2013). There is conjugation between the donor (NH) and the acceptor (CN) groups via the C2-C6 bond. Thus the C6-N2 distance of 1.3502 (14) Å is shorter than the average conjugated C-N single bond, 1.370 (1) Å , found in the Cambridge Structural Database (Version 5.35; Groom & Allen, 2014). Steric hindrances rotate the benzene ring out of the plane of the central pyridine ring by 49.80 (6) . This twist may be due to the non-bonded interactions between one of the ortho H atoms of the benzene ring and atom H7B of the cycloheptane ring. As a result of theconjugation of atom O1, the O1-C34 bond length of 1.3618 (15) Å is significantly shorter than the O1-C37 distance of 1.410 (2) Å . An enlargement of bond angle [C33-C34-O1 = 124.34 (13) ] on one side and a narrowing of bond angle [C35-C34-O1 = 116.29 (12) ] on the other side of the benzene ring may be due to the steric repulsion between the aromatic rings and the methyl group, as found in a similar structure (Tokuno et al., 1986).

Figure 2
Partial packing diagram for the title compound, viewed along the c axis. Dashed lines represent intermolecular hydrogen bonds and C-HÁ Á Á contacts (see Table 1 for details; H atoms not involved in hydrogen bonding have been omitted for clarity).
which are inclined to the plane of the central pyridine ring by 49.80 (6) and 76.68 (7) , respectively. In the related structure (Ç elik et al., 2013), the 4-bromophenyl ring is almost coplanar with the pyridine ring, making a dihedral angle of 8.27 (16) while the 4-methoxyphenyl ring is inclined to the pyridine ring by 58.63 (15) , compared with 49.80 (6) in the title compound.

Synthesis and crystallization
A mixture of cycloheptanone (1 mmol), 4-methoxy aldehyde (1 mmol) and malononitrile (1 mmol) and benzylamine (1mmol) was taken in ethanol (10 ml) to which p-TSA (1.0 mmol) was added. The reaction mixture was heated under reflux for 2-3 h. On completion of the reaction, checked by thin-layer chromatography (TLC), the mixture was poured into crushed ice and extracted with ethyl acetate. The excess solvent was removed under vacuum and the residue was subjected to column chromatography using petroleum ether/ ethyl acetate mixture (97:3 v/v) as eluent to afford pure product. The product was recrystallized from ethyl acetate, affording colourless crystals of the title compound. (m.p. 415 K; yield 75%).

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 2. The NH and C-bound H atoms were placed in calculated positions and allowed to ride on their carrier atoms: N-H = 0.86 and C-H = 0.93-0.97 Å , with U iso (H) = 1.5U eq (C) for methyl H atoms and 1.2U eq (N,C) for other H atoms. The DELU restraint was applied. 0.14, À0.13 Computer programs: APEX2 and SAINT (Bruker, 2004), SHELXS97 and SHELXL2014 (Sheldrick, 2008) and PLATON (Spek, 2009).