Crystal structure of 3,6,6-trimethyl-4-oxo-1-(pyridin-2-yl)-4,5,6,7-tetrahydro-1H-indazol-7-aminium chloride and its monohydrate

In the title compounds 1 and 2, the organic moieties adopt flattened conformations stabilized by an intramolecular N—H⋯N hydrogen bonds formed by the protonated amino group and the N atom of the pyridyl substituent. In 1, the organic moieties are linked with two N—H⋯Cl−-type hydrogen bonds, forming a C(4) graph-set. In its monohydrate, 2, the Cl− anion and a water molecule assemble the moieties into infinite bands showing hydrogen-bond patterns with graph sets C(6), (12) and (8). Both crystals display π–π stacked supramolecular structures running along the b axis.

The title compounds, C 15 H 19 N 4 O + ÁCl À and C 15 H 19 N 4 O + ÁCl À ÁH 2 O, obtained in attempts to synthesize metal complexes using tetrahydroindazole as a ligand, were characterized by NMR, IR and X-ray diffraction techniques. The partially saturated ring in the tetrahydroindazole core adopts a sofa conformation. An intramolecular N-HÁ Á ÁN hydrogen bond formed by the protonated amino group and the N atom of the pyridyl substituent is found in the first structure. In the hydrochloride, the organic moieties are linked by two N-HÁ Á ÁCl À hydrogen bonds, forming a C(4) graph-set. In the hydrate crystal, a Cl À anion and a water molecule assemble the moieties into infinite bands showing hydrogen-bond patterns with graph sets C(6), R 6 4 (12) and R 4 2 (8). Organic moieties formstacked supramolecular structures running along the b axis in both structures.
The broad application spectrum of tetrahydroindazoles has led to the development of synthetic methodologies. Thus, traditional approaches using a combination of either ,unsaturated ketones (Nakhai & Bergman, 2009) or dicarbonyl compounds (Murugavel et al., 2010), or tricarbonyl compounds (Kim et al., 2010;Scala et al., 2015) with hydrazines have been significantly updated and improved. In addition, the microwave-assisted synthesis of tetrahydroindazoles has been reported (Silva et al., 2006;Polo et al., 2016). It is interesting to note that compounds possessing free NH-functionality in the pyrazole ring have been studied thoroughly for their tautomeric equilibria (Claramunt et al., 2006). Additionally, tetrahydroindazolones substituted with 2-aminobenzamides have been studied as fluorescent probes (Jia et al., 2012). Other studies on side-chain modifications include the synthesis of polyfluoroalkyl-substituted analogs (Khlebnikova et al., 2012), triazole-functionalized tetrahydroindazolones (Strakova et al., 2009) and their conjugation with biologically active natural products such as lupane triterpenoids (Khlebnicova et al., 2017). Among other synthetic approaches, the Ritter reaction provides a fast entry into structural modifications and is applicable to obtain a combinatorial library of compounds (Turks et al., 2012). Combinatorial chemistry methodology has been reported for the construction of tetrahydroindazolones in enantiomerically pure pairs (Song et al., 2012). Also, enantiomerically pure 7-amino-tetrahydroindazolones (Strakova et al., 2011) have been obtained. For these reasons, we were interested in the synthesis of 7-amino-3,6,6-trimethyl-1-(pyridin-2-yl)-1,5,6,7-tetrahydro-4H-indazol-4-one for use as a starting material for further structural modifications. Herein, the structures of the corresponding hydrochloride 1 and its hydrate 2 are reported.

Structural commentary
Figs. 1 and 2 show the asymmetric units of the hydrochloride (1) and its hydrate (2) with the symmetry-independent hydrogen bonds. The geometry and conformation of the organic cation in compounds 1 and 2 are substantially similar. The pyrazole ring is planar within an r.m.s. deviation of the fitted atoms of 0.0059 Å in 1 and 0.0092 Å in 2. In both structures, the partially saturated ring adopts a sofa conformation. The distance of atom C6 from the mean plane formed by atoms C3-C5/C7/C8 (r.m.s. deviation of fitted atoms = 0.0495 Å in 1 and 0.0558 Å in 2) is 0.639 (2) Å in 1 and 0.642 (2) Å in 2. The dihedral angle between the latter plane and pyrazole ring is 5.79 (6) in 1 and 6.48 (4) in 2. On the other hand, the dihedral angle between the pyrazole ring and its pyridyl substituent is 11.91 (6) [torsion angle N4-N3-C11-C12 = 10.7 (2) ] in 1 and 7.22 (5) [torsion angle N4-N3-C11-C12 = 4.6 (2) ] in 2. An intramolecular N-HÁ Á ÁN hydrogen bond formed by the protonated amino group and nitrogen atom of pyridyl substituent is found in 1 (Table 1).

Supramolecular features
In the crystal of compound 1, the organic moieties are linked by two types of N-HÁ Á ÁCl À hydrogen bonds into infinite chains along the b-axis direction (Table 1). According to Etter (1990), the hydrogen-bond pattern in 1 can be described by a    ORTEP view of the asymmetric unit of 1 showing the atom-numbering scheme and 50% probability displacement ellipsoids. The intramolecular hydrogen bond is shown with dashed lines. C(4) graph set. The packing of 1 is shown in Fig. 3. In the structure of 2, in addition to participating in an intramolecular hydrogen bond, the protonated amino group also forms two intermolecular hydrogen bonds with the Cl À anion and a water molecule (Table 2). Each Cl À anion and water molecule takes part in three intermolecular hydrogen bonds. The organic cations are bridged by a pair of Cl À anions and a water molecule, thus assembling the moieties into infinite bands running along the b-axis direction. The hydrogen-bond pattern can be described by graph sets C(6), R 4 6 (12) and R 2 4 (8). The packing of 2 is shown in Fig. 4.
In the crystal of 1, the organic moieties form stacks running along the b axis which are stabilized byinteractions (Fig. 5). The distance between the centroids of the pyridine and pyrazole rings of adjacent molecules is 3.585 (2) Å . The shortest contact is 3.239 (2) Å between atoms N2 and N4 of two inversion-related molecules (Fig. 5). In the crystal of 2, the organic moieties also form --stacked supramolecular structures running along the b-axis direction (Fig. 6). The distance between the centroids of the pyridine rings of adjacent molecules is 3.748 (2) Å . The shortest contact is 3.170 (2) Å between the N3 atoms of two inversion-related molecules (Fig. 6).

Figure 3
The crystal packing of compound 1, viewed along the a axis. The hydrogen bonds are shown as dashed lines (see Table 1).

Figure 4
The crystal packing of compound 2, viewed along the c axis. The hydrogen bonds are shown as dashed lines (see Table 2).

Figure 5
View of stacks of organic moieties in the crystal structure of 1. H atoms and chloride anions are not shown for clarity.
However, the phenyl ring at the position N3 forms much larger dihedral angles with the pyrazole ring than with the pyridyl substituent in the structures reported here.

Synthesis and crystallization
The synthesis of the title compounds is depicted in the reaction scheme below. The 7-aminotetrahydroindazolone derivative 4 was prepared by an analogy of the procedure published by Strakova et al. (2011) from the known precursor 3 (Strakova et al., 2009). In our attempts to synthesize metal complexes with ligand 4, we obtained the hydrochloride salt 1 in its anhydrous form. It can be explained by the acidity of cobalt chloride hexahydrate, which was used in the selected experiment. This prompted us to develop a preparative synthesis of the hydrochloride salt. This was achieved by the formation and precipitation of crude hydrochloride in ethyl acetate solution. Its crystallization from water provided the hydrochloride hydrate 2.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 3. Hydrogen atoms bonded to heteroatoms were refined isotropically. Other H atoms were included in the refinement at geometrically calculated posi-tions with C-H = 0.95-0.99Å and treated as riding with U iso (H) = 1.2U eq (C) or 1.5U eq (C-methyl).

3,6,6-Trimethyl-4-oxo-1-(pyridin-2-yl)-4,5,6,7-tetrahydro-1H-indazol-7-aminium chloride (1)
Crystal data 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.