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

The title compounds, C15H19N4O+·Cl- and C15H19N4O+·Cl-·H2O, obtained in attempts to synthesize metal complexes using tetra-hydro-indazole as a ligand, were characterized by NMR, IR and X-ray diffraction techniques. The partially saturated ring in the tetra-hydro-indazole core adopts a sofa conformation. An intra-molecular N-H⋯N hydrogen bond formed by the protonated amino group and the N atom of the pyridyl substituent is found in the first structure. In the hydro-chloride, the organic moieties are linked by two N-H⋯Cl- hydrogen bonds, forming a C(4) graph-set. In the hydrate crystal, a Cl- anion and a water mol-ecule assemble the moieties into infinite bands showing hydrogen-bond patterns with graph sets C(6), R64(12) and R42(8). Organic moieties form π-π stacked supra-molecular structures running along the b axis in both structures.

Chemical context

Tetra­hydro­indazoles can be regarded as annulated pyrazole analogs (Ansari et al., 2017 ▸) or as partially saturated indazoles (Gaikwad et al., 2015 ▸). In either of these categories they play an important role in medicinal chemistry. Tetra­hydro­indazoles are reported to be peripherally selective cannabinoid-1 receptor inverse agonists (Matthews et al., 2016 ▸), sigma-2 receptor ligands(Wu et al., 2015 ▸), and inter­leukin-2 inducible T-cell kinase inhibitors (Burch et al., 2015 ▸; Heifetz et al., 2016 ▸). Heterocyclic compounds containing a tetra­hydro­indazole core have been researched as anti­viral agents (Bassyouni et al., 2016 ▸) and compounds with anti­oxidant properties (Polo et al., 2016 ▸). With appropriate side-chain decorations, they also possess COX-2 inhibitory activity (Abdel-Rahman et al., 2012 ▸) and can inhibit bacterial type II topoisomerases (Wiener et al., 2007 ▸). The latter has led to the development of compounds with both anti­tumor and anti­microbial activity (Faidallah et al., 2013 ▸), including novel anti­tuberculosis agents (Guo et al., 2010 ▸).

The broad application spectrum of tetra­hydro­indazoles has led to the development of synthetic methodologies. Thus, traditional approaches using a combination of either α,β-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—H⋯N hydrogen bond formed by the protonated amino group and nitro­gen atom of pyridyl substituent is found in 1 (Table 1 ▸).

Figure 1

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.

Figure 2

ORTEP view of the asymmetric unit of 2 showing the atom-numbering scheme and 50% probability displacement ellipsoids. The intra­molecular hydrogen bonds are shown with dashed lines.

Table 1

Hydrogen-bond geometry (Å, °) for (1)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1N1⋯N2	0.97 (2)	2.42 (2)	2.928 (2)	112 (2)
N1—H2N1⋯Cl1i	0.97 (2)	2.08 (2)	3.034 (2)	168 (2)
N1—H3N1⋯Cl1ii	0.93 (2)	2.27 (2)	3.188 (2)	167 (2)

Symmetry codes: (i) ; (ii) .

Supra­molecular features

In the crystal of compound 1, the organic moieties are linked by two types of N—H⋯Cl− 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 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− anion and a water mol­ecule (Table 2 ▸). Each Cl− anion and water mol­ecule takes part in three inter­molecular hydrogen bonds. The organic cations are bridged by a pair of Cl− 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), (12) and (8). The packing of 2 is shown in Fig. 4 ▸.

Figure 3

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

Table 2

Hydrogen-bond geometry (Å, °) for (2)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
O1W—H1W⋯Cl1i	0.80 (3)	2.39 (3)	3.185 (2)	176 (3)
O1W—H2W⋯Cl1	0.94 (3)	2.31 (3)	3.247 (2)	179 (2)
N1—H1N1⋯Cl1ii	0.85 (2)	2.40 (2)	3.228 (2)	165 (2)
N1—H3N1⋯O1W	0.95 (2)	1.85 (3)	2.775 (2)	162 (2)

Symmetry codes: (i) ; (ii) .

Figure 4

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

In the crystal of 1, the organic moieties form stacks running along the b axis which are stabilized by π–π inter­actions (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 π–π-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 5

View of stacks of organic moieties in the crystal structure of 1. H atoms and chloride anions are not shown for clarity.

Figure 6

View of stacks of organic moieties in the crystal structure of 2. H atoms, chloride anions and water mol­ecules are not shown for clarity.

Database survey

A search of the Cambridge Structural Database (Version 5.38; Groom et al., 2016 ▸) for the 3,6,6-trimethyl-4-oxo-4,5,6,7-tetra­hydro-1H-indazole core revealed five structurally close compounds: UXAQUG, UXARAN, UXARER, UXARIV, UXAROB (Strakova et al., 2011 ▸). These compounds differ from compounds 1 and 2 by the substituents at the positions of atoms N3 and C5. In all examples, the partially saturated ring in the indazole fragment adopts a sofa conformation. 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.

7-Amino-3,6,6-trimethyl-1-(pyridin-2-yl)-1,5,6,7-tetra­hydro-4 -indazol-4-one (4): Gaseous H2 was bubbled for 10 min. through a solution/suspension of compound 3 (0.80 g, 2.7 mmol) and 10% Pd/C (80 mg) in a mixture of EtOH (10 mL) and THF (2 mL). The resulting reaction mixture was stirred under an H2 atmosphere at standard temperature and pressure for 3 h (TLC control). The catalyst was filtered through a celite pad and the filtrate was evaporated to dryness. The resulting amorphous solid was dried under reduced pressure to yield amine 4 (0.71 g, 97%) as a colorless powder. M.p. 390–392 K; R f = 0.14 (Hex:EtOAc:Et3N = 8:1:0.5). IR (KBr), υ (cm−1): 3360, 3295, 3055, 2985, 2955, 2945, 2930, 2890, 2865, 1670, 1590, 1575, 1540, 1465, 1455, 1285, 1250, 1145, 1085, 1075, 1035, 995. 1H NMR (CDCl3, 300 MHz) δ (ppm): 8.48 [m, 1H, H-C(Py)], 7.99 [d, J = 8.3 Hz, 1H, H-C(Py)], 7.87 [m, 1H, H-C(Py)], 7.26 [m, 1H, H-C(Py)], 4.27 (s, 1H, H-C7), 2.82 (d, J = 16.8 Hz, 1H, Ha-C5), 2.54 (s, 3H, H3C-C3), 2.18 (d, J = 16.8 Hz, 1H, Hb-C5), 2.08 (bs, 2H, H2N-C7) 1.26, 1.02 (2s, 6H, H3C-C6).13C NMR (75.5 MHz, CDCl3), δ (ppm): 194.1, 153.9, 152.4, 150.4, 148.0, 139.1, 122.1, 116.5, 115.9, 53.8, 47.8, 38.4, 27.3, 26.6, 13.7. Analysis calculated: (C15H18N4O) C, 66.64; H, 6.71; N, 20.73. Found: C, 66.56; H, 6.68; N, 20.74.

3,6,6-Trimethyl-4-oxo-1-(pyridin-2-yl)-4,5,6,7-tetra­hydro-1 -indazol-7-aminium n class="Chemical">chloride (1): A solution of CoCl2·6H2O (24 mg, 0.1 mmol) in ethanol (2 mL) was added to a solution of amine 4 (27 mg, 0.1 mmol) in ethanol (2 mL). The resulting reaction mixture was maturated at ambient temperature for 24 h. Then a part of it (1.2 mL) was transferred into an NMR tube and Et2O (0.8 mL) was added carefully on the top of the ethanol solution. After two days, colorless crystals of 1 were collected form the wall of the NMR tube. The product was characterized spectroscopically in its hydrate form (see below).

3,6,6-Trimethyl-4-oxo-1-(pyridin-2-yl)-4,5,6,7-tetra­hydro-1 -indazol-7-aminium chloride hydrate (2): A solution of HCl in EtOAc (0.5 M, 1.48 mL, 0.74 mmol, 1.0 equiv.) was added to a solution of amine 4 (0.20 g, 0.74 mmol, 1.0 equiv.) in EtOAc (2 mL) at ambient temperature. The resulting precipitate was filtered and washed on the filter with DCM. The the crude product was crystallized from water to obtain colorless crystals of 2 (195 mg, 81%) suitable for X-ray analysis. M.p. 543 K (decomp.); IR (KBr), υ (cm−1): 3430 (br.s), 3145, 3100, 3035, 2965, 2880, 2750, 2575, 1955 (br.s), 1685, 1600, 1545, 1520, 1490, 1465, 1450, 1400, 1375, 1360, 1295, 1245, 1140, 1045, 1000, 955. 1H NMR (300MHz, D2O), δ (ppm): δ 8.55 [m, 1H, H-C(Py)], 8.12 [m,1H,H-C (Py)], 7.90 [d, J = 8.3 Hz, 1H, H-C(Py)], 7.53 [m, 1H, H-C(Py)], 4.84 (s, 1H, H-C7), 3.00 (d, J =17.8 Hz, 1H, Ha-C5), 2.54 (s, 3H, H3C-C3), 2.45 (d, J = 17.8Hz,1H,Hb-C5), 1.36, 1.10 (2s, 6H, H3C-C6). 13C NMR (75.5 MHz, DMSO-d 6), δ (ppm):192.3, 151.4, 149.0, 148.0, 144.4, 140.1, 122.8, 118.0, 114.6, 51.4, 47.1, 37.2, 26.8, 25.4, 13.2. Analysis calculated: (C15H18N4O·HCl·H2O) C, 55.47; H, 6.52; N, 17.25. Found: C, 55.78; H,6.40; N, 17.29.

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 positions 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).

Table 3

Experimental details

	(1)	(2)
Crystal data
Chemical formula	C15H19N4O+·Cl−	C15H19N4O+·Cl−·H2O
M r	306.79	324.81
Crystal system, space group	Monoclinic, P21/c	Monoclinic, P21/c
Temperature (K)	190	190
a, b, c (Å)	13.5411 (4), 7.7421 (2), 19.2457 (5)	10.1855 (2), 7.4951 (2), 20.7961 (4)
β (°)	130.493 (2)	100.545 (1)
V (Å3)	1534.39 (8)	1560.79 (6)
Z	4	4
Radiation type	Mo Kα	Mo Kα
μ (mm−1)	0.25	0.26
Crystal size (mm)	0.38 × 0.32 × 0.15	0.42 × 0.25 × 0.14
Data collection
Diffractometer	Nonius KappaCCD	Nonius KappaCCD
No. of measured, independent and observed [I > 2σ(I)] reflections	5860, 3486, 2715	5549, 3552, 2874
R int	0.027	0.023
(sin θ/λ)max (Å−1)	0.649	0.654
Refinement
R[F 2 > 2σ(F 2)], wR(F 2), S	0.043, 0.101, 1.03	0.039, 0.102, 1.06
No. of reflections	3486	3552
No. of parameters	205	222
H-atom treatment	H atoms treated by a mixture of independent and constrained refinement	H atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å−3)	0.29, −0.25	0.29, −0.28

Computer programs: COLLECT (Bruker, 2004 ▸), SCALEPACK (Otwinowski & Minor, 1997 ▸), DENZO (Otwinowski & Minor, 1997 ▸), SIR2004 (Burla et al., 2005 ▸), SHELXL2017 (Sheldrick, 2015 ▸), ORTEP-3 for Windows (Farrugia, 2012 ▸) and publCIF (Westrip, 2010 ▸).

Crystal structure: contains datablock(s) 1, 2, global. DOI: 10.1107/S205698901701667X/eb2002sup1.cif

Structure factors: contains datablock(s) 1. DOI: 10.1107/S205698901701667X/eb20021sup2.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S205698901701667X/eb20021sup4.mol

Structure factors: contains datablock(s) 2. DOI: 10.1107/S205698901701667X/eb20022sup3.hkl

Click here for additional data file.

Supporting information file. DOI: 10.1107/S205698901701667X/eb20022sup5.mol

Click here for additional data file.

Supporting information file. DOI: 10.1107/S205698901701667X/eb20021sup6.cml

Click here for additional data file.

Supporting information file. DOI: 10.1107/S205698901701667X/eb20022sup7.cml

CCDC references: 1586488, 1586487

Additional supporting information: crystallographic information; 3D view; checkCIF report

C15H19N4O+·Cl−	F(000) = 648
Mr = 306.79	Dx = 1.328 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 13.5411 (4) Å	Cell parameters from 6801 reflections
b = 7.7421 (2) Å	θ = 1.0–27.5°
c = 19.2457 (5) Å	µ = 0.25 mm−1
β = 130.493 (2)°	T = 190 K
V = 1534.39 (8) Å3	Block, colourless
Z = 4	0.38 × 0.32 × 0.15 mm

Nonius KappaCCD diffractometer	Rint = 0.027
Radiation source: fine-focus sealed tube	θmax = 27.5°, θmin = 3.0°
CCD scans	h = −17→17
5860 measured reflections	k = −10→9
3486 independent reflections	l = −24→24
2715 reflections with I > 2σ(I)

Refinement on F2	0 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.043	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.101	w = 1/[σ2(Fo2) + (0.0363P)2 + 0.7495P] where P = (Fo2 + 2Fc2)/3
S = 1.03	(Δ/σ)max = 0.001
3486 reflections	Δρmax = 0.29 e Å−3
205 parameters	Δρmin = −0.25 e Å−3

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.

	x	y	z	Uiso*/Ueq
Cl1	0.63264 (4)	0.65297 (6)	0.33536 (3)	0.03342 (14)
O1	0.98736 (12)	−0.08281 (19)	0.66919 (8)	0.0361 (3)
N3	0.59725 (12)	0.17416 (17)	0.53425 (8)	0.0187 (3)
N4	0.65309 (13)	0.13670 (18)	0.62325 (9)	0.0219 (3)
C4	0.67526 (15)	0.1258 (2)	0.51633 (10)	0.0193 (3)
N2	0.41873 (13)	0.26763 (19)	0.38981 (9)	0.0230 (3)
C12	0.42625 (16)	0.3337 (2)	0.51532 (11)	0.0232 (4)
H12	0.471148	0.327724	0.577688	0.028*
C11	0.47588 (15)	0.2621 (2)	0.47773 (10)	0.0190 (3)
N1	0.55052 (14)	0.0192 (2)	0.35950 (9)	0.0220 (3)
C13	0.30686 (17)	0.4145 (2)	0.45593 (12)	0.0282 (4)
H13	0.267881	0.460408	0.477604	0.034*
C3	0.78494 (15)	0.0540 (2)	0.59559 (10)	0.0211 (3)
C6	0.78026 (16)	0.1295 (2)	0.44709 (11)	0.0246 (4)
C15	0.30553 (16)	0.3529 (2)	0.33478 (12)	0.0276 (4)
H15	0.265092	0.362741	0.273282	0.033*
C8	0.88681 (16)	−0.0231 (2)	0.59948 (11)	0.0244 (4)
C5	0.65109 (15)	0.1485 (2)	0.42887 (10)	0.0207 (3)
H5	0.616867	0.265008	0.405413	0.025*
C2	0.76718 (16)	0.0664 (2)	0.66070 (11)	0.0224 (4)
C10	0.75046 (18)	0.1108 (3)	0.35558 (12)	0.0325 (4)
H10A	0.830139	0.113448	0.366104	0.049*
H10B	0.695686	0.204248	0.315864	0.049*
H10C	0.706960	0.002985	0.327613	0.049*
C14	0.24569 (17)	0.4268 (2)	0.36430 (13)	0.0297 (4)
H14	0.166419	0.483251	0.323640	0.036*
C7	0.85647 (16)	−0.0288 (2)	0.50865 (11)	0.0253 (4)
H7A	0.806434	−0.132217	0.476113	0.030*
H7B	0.937384	−0.037310	0.520035	0.030*
C1	0.85803 (17)	0.0141 (3)	0.75907 (11)	0.0312 (4)
H1A	0.809647	−0.005846	0.778844	0.047*
H1B	0.920174	0.104542	0.795200	0.047*
H1C	0.902572	−0.089806	0.766326	0.047*
C9	0.86206 (17)	0.2931 (2)	0.49510 (13)	0.0301 (4)
H9A	0.815252	0.391477	0.456570	0.045*
H9B	0.942494	0.281965	0.507027	0.045*
H9C	0.879617	0.308100	0.551734	0.045*
H1N1	0.487 (2)	0.000 (3)	0.3670 (14)	0.046 (6)*
H2N1	0.503 (2)	0.062 (3)	0.2980 (16)	0.054 (7)*
H3N1	0.584 (2)	−0.088 (3)	0.3627 (14)	0.042 (6)*

	U11	U22	U33	U12	U13	U23
Cl1	0.0363 (3)	0.0353 (3)	0.0225 (2)	0.0052 (2)	0.01632 (19)	−0.00482 (19)
O1	0.0235 (7)	0.0442 (8)	0.0281 (6)	0.0113 (6)	0.0113 (6)	0.0038 (6)
N3	0.0190 (7)	0.0211 (7)	0.0168 (6)	0.0005 (6)	0.0119 (5)	0.0004 (6)
N4	0.0244 (7)	0.0234 (7)	0.0184 (6)	−0.0002 (6)	0.0141 (6)	0.0012 (6)
C4	0.0189 (8)	0.0186 (8)	0.0210 (7)	−0.0011 (6)	0.0132 (7)	−0.0020 (7)
N2	0.0207 (7)	0.0263 (7)	0.0216 (7)	0.0011 (6)	0.0136 (6)	0.0027 (6)
C12	0.0272 (9)	0.0200 (8)	0.0268 (8)	0.0003 (7)	0.0195 (7)	0.0005 (7)
C11	0.0189 (8)	0.0157 (8)	0.0232 (8)	−0.0015 (6)	0.0140 (7)	−0.0004 (7)
N1	0.0204 (7)	0.0266 (8)	0.0191 (7)	0.0023 (6)	0.0129 (6)	−0.0013 (6)
C13	0.0299 (9)	0.0235 (9)	0.0400 (10)	0.0021 (8)	0.0267 (8)	−0.0010 (8)
C3	0.0187 (8)	0.0209 (8)	0.0194 (7)	−0.0011 (7)	0.0105 (6)	−0.0019 (7)
C6	0.0218 (8)	0.0297 (9)	0.0264 (8)	0.0031 (7)	0.0176 (7)	0.0007 (8)
C15	0.0230 (8)	0.0299 (9)	0.0252 (8)	0.0022 (8)	0.0136 (7)	0.0063 (8)
C8	0.0203 (8)	0.0213 (8)	0.0254 (8)	−0.0005 (7)	0.0122 (7)	−0.0016 (7)
C5	0.0205 (8)	0.0220 (8)	0.0212 (7)	0.0022 (7)	0.0143 (7)	0.0010 (7)
C2	0.0214 (8)	0.0212 (8)	0.0201 (8)	−0.0022 (7)	0.0114 (7)	−0.0010 (7)
C10	0.0285 (9)	0.0455 (12)	0.0315 (9)	0.0064 (9)	0.0230 (8)	0.0043 (9)
C14	0.0224 (9)	0.0245 (9)	0.0379 (10)	0.0048 (7)	0.0176 (8)	0.0055 (8)
C7	0.0198 (8)	0.0281 (9)	0.0290 (9)	0.0042 (7)	0.0163 (7)	−0.0020 (8)
C1	0.0291 (9)	0.0364 (11)	0.0205 (8)	0.0007 (8)	0.0127 (8)	0.0025 (8)
C9	0.0251 (9)	0.0299 (10)	0.0390 (10)	0.0022 (8)	0.0224 (8)	0.0014 (8)

O1—C8	1.223 (2)	C6—C10	1.537 (2)
N3—C4	1.360 (2)	C6—C7	1.544 (2)
N3—N4	1.3811 (18)	C6—C5	1.552 (2)
N3—C11	1.424 (2)	C15—C14	1.380 (3)
N4—C2	1.325 (2)	C15—H15	0.9300
C4—C3	1.378 (2)	C8—C7	1.515 (2)
C4—C5	1.502 (2)	C5—H5	0.9800
N2—C11	1.328 (2)	C2—C1	1.496 (2)
N2—C15	1.341 (2)	C10—H10A	0.9600
C12—C13	1.383 (2)	C10—H10B	0.9600
C12—C11	1.383 (2)	C10—H10C	0.9600
C12—H12	0.9300	C14—H14	0.9300
N1—C5	1.509 (2)	C7—H7A	0.9700
N1—H1N1	0.97 (2)	C7—H7B	0.9700
N1—H2N1	0.97 (2)	C1—H1A	0.9600
N1—H3N1	0.93 (2)	C1—H1B	0.9600
C13—C14	1.381 (3)	C1—H1C	0.9600
C13—H13	0.9300	C9—H9A	0.9600
C3—C2	1.424 (2)	C9—H9B	0.9600
C3—C8	1.459 (2)	C9—H9C	0.9600
C6—C9	1.535 (3)
C4—N3—N4	111.53 (12)	C3—C8—C7	114.43 (14)
C4—N3—C11	129.76 (13)	C4—C5—N1	109.18 (13)
N4—N3—C11	118.61 (12)	C4—C5—C6	110.02 (13)
C2—N4—N3	105.47 (13)	N1—C5—C6	111.99 (13)
N3—C4—C3	106.66 (13)	C4—C5—H5	108.5
N3—C4—C5	127.76 (14)	N1—C5—H5	108.5
C3—C4—C5	125.56 (14)	C6—C5—H5	108.5
C11—N2—C15	116.33 (14)	N4—C2—C3	110.63 (14)
C13—C12—C11	116.96 (15)	N4—C2—C1	120.64 (15)
C13—C12—H12	121.5	C3—C2—C1	128.72 (16)
C11—C12—H12	121.5	C6—C10—H10A	109.5
N2—C11—C12	125.07 (15)	C6—C10—H10B	109.5
N2—C11—N3	114.67 (13)	H10A—C10—H10B	109.5
C12—C11—N3	120.26 (14)	C6—C10—H10C	109.5
C5—N1—H1N1	110.3 (13)	H10A—C10—H10C	109.5
C5—N1—H2N1	110.9 (14)	H10B—C10—H10C	109.5
H1N1—N1—H2N1	106.3 (18)	C15—C14—C13	118.12 (16)
C5—N1—H3N1	114.2 (13)	C15—C14—H14	120.9
H1N1—N1—H3N1	107.5 (19)	C13—C14—H14	120.9
H2N1—N1—H3N1	107.3 (19)	C8—C7—C6	114.06 (14)
C14—C13—C12	119.76 (16)	C8—C7—H7A	108.7
C14—C13—H13	120.1	C6—C7—H7A	108.7
C12—C13—H13	120.1	C8—C7—H7B	108.7
C4—C3—C2	105.68 (14)	C6—C7—H7B	108.7
C4—C3—C8	121.68 (14)	H7A—C7—H7B	107.6
C2—C3—C8	132.55 (15)	C2—C1—H1A	109.5
C9—C6—C10	108.51 (15)	C2—C1—H1B	109.5
C9—C6—C7	109.37 (14)	H1A—C1—H1B	109.5
C10—C6—C7	110.59 (14)	C2—C1—H1C	109.5
C9—C6—C5	108.97 (14)	H1A—C1—H1C	109.5
C10—C6—C5	109.35 (13)	H1B—C1—H1C	109.5
C7—C6—C5	110.02 (14)	C6—C9—H9A	109.5
N2—C15—C14	123.68 (16)	C6—C9—H9B	109.5
N2—C15—H15	118.2	H9A—C9—H9B	109.5
C14—C15—H15	118.2	C6—C9—H9C	109.5
O1—C8—C3	123.57 (16)	H9A—C9—H9C	109.5
O1—C8—C7	121.97 (15)	H9B—C9—H9C	109.5
C4—N3—N4—C2	0.69 (18)	N3—C4—C5—N1	−74.7 (2)
C11—N3—N4—C2	−176.00 (14)	C3—C4—C5—N1	107.05 (18)
N4—N3—C4—C3	0.27 (18)	N3—C4—C5—C6	162.06 (16)
C11—N3—C4—C3	176.49 (15)	C3—C4—C5—C6	−16.2 (2)
N4—N3—C4—C5	−178.26 (15)	C9—C6—C5—C4	−74.59 (17)
C11—N3—C4—C5	−2.0 (3)	C10—C6—C5—C4	166.95 (14)
C15—N2—C11—C12	1.4 (2)	C7—C6—C5—C4	45.31 (18)
C15—N2—C11—N3	−178.55 (14)	C9—C6—C5—N1	163.80 (14)
C13—C12—C11—N2	1.1 (3)	C10—C6—C5—N1	45.35 (19)
C13—C12—C11—N3	−178.92 (15)	C7—C6—C5—N1	−76.29 (16)
C4—N3—C11—N2	14.7 (2)	N3—N4—C2—C3	−1.36 (18)
N4—N3—C11—N2	−169.29 (14)	N3—N4—C2—C1	177.90 (15)
C4—N3—C11—C12	−165.27 (16)	C4—C3—C2—N4	1.55 (19)
N4—N3—C11—C12	10.7 (2)	C8—C3—C2—N4	−174.86 (17)
C11—C12—C13—C14	−2.6 (3)	C4—C3—C2—C1	−177.64 (17)
N3—C4—C3—C2	−1.05 (18)	C8—C3—C2—C1	6.0 (3)
C5—C4—C3—C2	177.52 (15)	N2—C15—C14—C13	1.0 (3)
N3—C4—C3—C8	175.84 (15)	C12—C13—C14—C15	1.7 (3)
C5—C4—C3—C8	−5.6 (3)	O1—C8—C7—C6	−145.62 (17)
C11—N2—C15—C14	−2.5 (3)	C3—C8—C7—C6	36.1 (2)
C4—C3—C8—O1	177.45 (17)	C9—C6—C7—C8	62.12 (18)
C2—C3—C8—O1	−6.6 (3)	C10—C6—C7—C8	−178.44 (14)
C4—C3—C8—C7	−4.4 (2)	C5—C6—C7—C8	−57.54 (19)
C2—C3—C8—C7	171.59 (17)

D—H···A	D—H	H···A	D···A	D—H···A
C12—H12···Cl1i	0.93	2.80	3.4470 (17)	127
C14—H14···O1ii	0.93	2.44	3.277 (2)	150
C7—H7A···Cl1iii	0.97	2.71	3.6401 (18)	160
C1—H1B···O1iv	0.96	2.60	3.503 (2)	156
N1—H1N1···N4v	0.97 (2)	2.29 (2)	3.218 (2)	161 (2)
N1—H1N1···N2	0.97 (2)	2.42 (2)	2.928 (2)	112 (2)
N1—H2N1···Cl1vi	0.97 (2)	2.08 (2)	3.034 (2)	168 (2)
N1—H3N1···Cl1iii	0.93 (2)	2.27 (2)	3.188 (2)	167 (2)

C15H19N4O+·Cl−·H2O	F(000) = 688
Mr = 324.81	Dx = 1.382 Mg m−3
Monoclinic, P21/c	Mo Kα radiation, λ = 0.71073 Å
a = 10.1855 (2) Å	Cell parameters from 8626 reflections
b = 7.4951 (2) Å	θ = 1.0–27.5°
c = 20.7961 (4) Å	µ = 0.26 mm−1
β = 100.545 (1)°	T = 190 K
V = 1560.79 (6) Å3	Block, colourless
Z = 4	0.42 × 0.25 × 0.14 mm

Nonius KappaCCD diffractometer	Rint = 0.023
Radiation source: fine-focus sealed tube	θmax = 27.7°, θmin = 3.6°
CCD scans	h = −13→13
5549 measured reflections	k = −9→9
3552 independent reflections	l = −27→26
2874 reflections with I > 2σ(I)

Refinement on F2	0 restraints
Least-squares matrix: full	Hydrogen site location: mixed
R[F2 > 2σ(F2)] = 0.039	H atoms treated by a mixture of independent and constrained refinement
wR(F2) = 0.102	w = 1/[σ2(Fo2) + (0.0426P)2 + 0.794P] where P = (Fo2 + 2Fc2)/3
S = 1.06	(Δ/σ)max < 0.001
3552 reflections	Δρmax = 0.29 e Å−3
222 parameters	Δρmin = −0.28 e Å−3

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.

	x	y	z	Uiso*/Ueq
Cl1	0.06154 (4)	0.62526 (6)	0.39636 (2)	0.02975 (13)
O1	0.45919 (12)	−0.12171 (17)	0.26173 (5)	0.0286 (3)
N2	0.33632 (13)	0.28400 (18)	0.51823 (6)	0.0210 (3)
O1W	−0.00940 (13)	0.25508 (19)	0.46352 (7)	0.0328 (3)
N3	0.48296 (12)	0.17260 (17)	0.45521 (6)	0.0159 (3)
N1	0.18153 (14)	0.01688 (19)	0.43612 (7)	0.0183 (3)
N4	0.61172 (12)	0.13967 (18)	0.44629 (6)	0.0196 (3)
C5	0.24311 (14)	0.1376 (2)	0.39147 (7)	0.0155 (3)
H5	0.223932	0.261303	0.401963	0.019*
C12	0.57141 (16)	0.3394 (2)	0.55440 (8)	0.0219 (3)
H12	0.658465	0.326736	0.547312	0.026*
C11	0.46319 (15)	0.2686 (2)	0.51150 (7)	0.0174 (3)
C4	0.39179 (14)	0.1150 (2)	0.40322 (7)	0.0153 (3)
C6	0.18454 (15)	0.1060 (2)	0.31807 (7)	0.0176 (3)
C10	0.03220 (16)	0.0870 (2)	0.30801 (8)	0.0246 (4)
H10A	0.009876	−0.020414	0.328751	0.037*
H10B	−0.003916	0.081667	0.262056	0.037*
H10C	−0.004705	0.187831	0.326935	0.037*
C9	0.21584 (16)	0.2703 (2)	0.27933 (8)	0.0227 (3)
H9A	0.180810	0.375246	0.296617	0.034*
H9B	0.175456	0.256460	0.234144	0.034*
H9C	0.310786	0.282002	0.283039	0.034*
C3	0.46350 (15)	0.0404 (2)	0.35966 (7)	0.0166 (3)
C8	0.39804 (16)	−0.0515 (2)	0.30028 (7)	0.0192 (3)
C15	0.31230 (18)	0.3783 (2)	0.56960 (8)	0.0270 (4)
H15	0.224058	0.395222	0.574240	0.032*
C7	0.24693 (16)	−0.0608 (2)	0.29224 (7)	0.0213 (3)
H7A	0.223032	−0.164981	0.315275	0.026*
H7B	0.209284	−0.075806	0.246229	0.026*
C14	0.4120 (2)	0.4514 (2)	0.61590 (8)	0.0299 (4)
H14	0.391561	0.513786	0.651450	0.036*
C13	0.54279 (19)	0.4297 (2)	0.60821 (8)	0.0280 (4)
H13	0.611825	0.475897	0.639260	0.034*
C2	0.59994 (15)	0.0631 (2)	0.38810 (7)	0.0196 (3)
C1	0.72083 (17)	0.0203 (3)	0.36008 (9)	0.0295 (4)
H1A	0.799516	0.046429	0.391767	0.044*
H1B	0.720784	0.090854	0.321550	0.044*
H1C	0.720059	−0.104005	0.348878	0.044*
H1W	−0.026 (3)	0.288 (4)	0.4977 (14)	0.063 (9)*
H2W	0.012 (3)	0.362 (4)	0.4440 (13)	0.066 (8)*
H1N1	0.1557 (19)	−0.083 (3)	0.4188 (9)	0.024 (5)*
H2N1	0.244 (2)	−0.009 (3)	0.4766 (11)	0.036 (5)*
H3N1	0.112 (2)	0.080 (3)	0.4513 (11)	0.049 (7)*

	U11	U22	U33	U12	U13	U23
Cl1	0.0343 (2)	0.0261 (2)	0.0301 (2)	−0.00602 (18)	0.00909 (17)	−0.00145 (17)
O1	0.0328 (7)	0.0360 (7)	0.0182 (6)	0.0076 (5)	0.0077 (5)	−0.0040 (5)
N2	0.0237 (7)	0.0214 (7)	0.0185 (6)	0.0011 (6)	0.0053 (5)	−0.0027 (6)
O1W	0.0343 (7)	0.0287 (7)	0.0385 (8)	0.0014 (6)	0.0152 (6)	−0.0051 (6)
N3	0.0144 (6)	0.0174 (6)	0.0156 (6)	−0.0002 (5)	0.0018 (5)	0.0000 (5)
N1	0.0185 (7)	0.0208 (7)	0.0162 (6)	−0.0037 (6)	0.0045 (5)	−0.0014 (6)
N4	0.0140 (6)	0.0226 (7)	0.0222 (7)	0.0005 (5)	0.0036 (5)	0.0019 (6)
C5	0.0155 (7)	0.0168 (7)	0.0143 (7)	−0.0016 (6)	0.0026 (5)	0.0007 (6)
C12	0.0250 (8)	0.0171 (7)	0.0211 (8)	−0.0021 (6)	−0.0029 (6)	0.0022 (6)
C11	0.0226 (8)	0.0141 (7)	0.0147 (7)	−0.0004 (6)	0.0018 (6)	0.0019 (6)
C4	0.0164 (7)	0.0153 (7)	0.0138 (7)	−0.0017 (6)	0.0022 (5)	0.0020 (6)
C6	0.0156 (7)	0.0224 (8)	0.0140 (7)	−0.0015 (6)	0.0003 (5)	0.0008 (6)
C10	0.0177 (8)	0.0332 (9)	0.0216 (8)	−0.0044 (7)	−0.0002 (6)	−0.0003 (7)
C9	0.0221 (8)	0.0251 (9)	0.0193 (7)	−0.0006 (7)	−0.0004 (6)	0.0054 (7)
C3	0.0185 (7)	0.0171 (7)	0.0146 (7)	0.0000 (6)	0.0039 (6)	0.0017 (6)
C8	0.0262 (8)	0.0180 (7)	0.0139 (7)	0.0015 (6)	0.0045 (6)	0.0031 (6)
C15	0.0344 (9)	0.0263 (9)	0.0222 (8)	0.0030 (7)	0.0100 (7)	−0.0024 (7)
C7	0.0244 (8)	0.0229 (8)	0.0163 (7)	−0.0042 (7)	0.0033 (6)	−0.0034 (6)
C14	0.0506 (12)	0.0225 (9)	0.0173 (7)	−0.0006 (8)	0.0079 (7)	−0.0035 (7)
C13	0.0427 (11)	0.0181 (8)	0.0189 (8)	−0.0055 (7)	−0.0061 (7)	−0.0014 (7)
C2	0.0183 (8)	0.0210 (8)	0.0201 (7)	0.0016 (6)	0.0054 (6)	0.0036 (6)
C1	0.0205 (8)	0.0392 (11)	0.0310 (9)	0.0027 (8)	0.0109 (7)	0.0000 (8)

O1—C8	1.2207 (19)	C6—C7	1.543 (2)
N2—C11	1.330 (2)	C10—H10A	0.9600
N2—C15	1.340 (2)	C10—H10B	0.9600
O1W—H1W	0.80 (3)	C10—H10C	0.9600
O1W—H2W	0.94 (3)	C9—H9A	0.9600
N3—C4	1.3601 (18)	C9—H9B	0.9600
N3—N4	1.3800 (17)	C9—H9C	0.9600
N3—C11	1.4196 (19)	C3—C2	1.418 (2)
N1—C5	1.5127 (19)	C3—C8	1.464 (2)
N1—H1N1	0.85 (2)	C8—C7	1.519 (2)
N1—H2N1	0.98 (2)	C15—C14	1.378 (3)
N1—H3N1	0.95 (2)	C15—H15	0.9300
N4—C2	1.325 (2)	C7—H7A	0.9700
C5—C4	1.499 (2)	C7—H7B	0.9700
C5—C6	1.5522 (19)	C14—C13	1.380 (3)
C5—H5	0.9800	C14—H14	0.9300
C12—C13	1.384 (2)	C13—H13	0.9300
C12—C11	1.390 (2)	C2—C1	1.491 (2)
C12—H12	0.9300	C1—H1A	0.9600
C4—C3	1.382 (2)	C1—H1B	0.9600
C6—C10	1.534 (2)	C1—H1C	0.9600
C6—C9	1.537 (2)
C11—N2—C15	116.89 (14)	H10B—C10—H10C	109.5
H1W—O1W—H2W	103 (3)	C6—C9—H9A	109.5
C4—N3—N4	111.34 (12)	C6—C9—H9B	109.5
C4—N3—C11	129.57 (13)	H9A—C9—H9B	109.5
N4—N3—C11	118.90 (12)	C6—C9—H9C	109.5
C5—N1—H1N1	113.5 (13)	H9A—C9—H9C	109.5
C5—N1—H2N1	111.4 (12)	H9B—C9—H9C	109.5
H1N1—N1—H2N1	106.9 (18)	C4—C3—C2	105.85 (13)
C5—N1—H3N1	108.9 (15)	C4—C3—C8	122.00 (13)
H1N1—N1—H3N1	112.7 (19)	C2—C3—C8	132.00 (14)
H2N1—N1—H3N1	102.9 (18)	O1—C8—C3	123.26 (15)
C2—N4—N3	105.71 (12)	O1—C8—C7	122.43 (14)
C4—C5—N1	110.64 (12)	C3—C8—C7	114.23 (13)
C4—C5—C6	109.76 (12)	N2—C15—C14	123.21 (17)
N1—C5—C6	112.59 (12)	N2—C15—H15	118.4
C4—C5—H5	107.9	C14—C15—H15	118.4
N1—C5—H5	107.9	C8—C7—C6	113.45 (13)
C6—C5—H5	107.9	C8—C7—H7A	108.9
C13—C12—C11	116.49 (16)	C6—C7—H7A	108.9
C13—C12—H12	121.8	C8—C7—H7B	108.9
C11—C12—H12	121.8	C6—C7—H7B	108.9
N2—C11—C12	124.81 (14)	H7A—C7—H7B	107.7
N2—C11—N3	114.70 (13)	C15—C14—C13	118.40 (16)
C12—C11—N3	120.48 (14)	C15—C14—H14	120.8
N3—C4—C3	106.48 (13)	C13—C14—H14	120.8
N3—C4—C5	128.05 (13)	C14—C13—C12	120.12 (16)
C3—C4—C5	125.34 (13)	C14—C13—H13	119.9
C10—C6—C9	107.73 (13)	C12—C13—H13	119.9
C10—C6—C7	110.38 (13)	N4—C2—C3	110.57 (13)
C9—C6—C7	109.20 (12)	N4—C2—C1	120.48 (14)
C10—C6—C5	110.21 (12)	C3—C2—C1	128.90 (15)
C9—C6—C5	108.27 (12)	C2—C1—H1A	109.5
C7—C6—C5	110.96 (12)	C2—C1—H1B	109.5
C6—C10—H10A	109.5	H1A—C1—H1B	109.5
C6—C10—H10B	109.5	C2—C1—H1C	109.5
H10A—C10—H10B	109.5	H1A—C1—H1C	109.5
C6—C10—H10C	109.5	H1B—C1—H1C	109.5
H10A—C10—H10C	109.5
C4—N3—N4—C2	0.70 (17)	N3—C4—C3—C2	−1.90 (16)
C11—N3—N4—C2	−174.73 (13)	C5—C4—C3—C2	174.12 (14)
C15—N2—C11—C12	1.5 (2)	N3—C4—C3—C8	174.09 (13)
C15—N2—C11—N3	−178.02 (14)	C5—C4—C3—C8	−9.9 (2)
C13—C12—C11—N2	1.0 (2)	C4—C3—C8—O1	−178.45 (15)
C13—C12—C11—N3	−179.50 (14)	C2—C3—C8—O1	−3.6 (3)
C4—N3—C11—N2	9.7 (2)	C4—C3—C8—C7	−1.5 (2)
N4—N3—C11—N2	−175.82 (13)	C2—C3—C8—C7	173.30 (16)
C4—N3—C11—C12	−169.86 (15)	C11—N2—C15—C14	−2.8 (2)
N4—N3—C11—C12	4.6 (2)	O1—C8—C7—C6	−148.01 (15)
N4—N3—C4—C3	0.81 (17)	C3—C8—C7—C6	35.01 (18)
C11—N3—C4—C3	175.62 (14)	C10—C6—C7—C8	179.76 (13)
N4—N3—C4—C5	−175.06 (14)	C9—C6—C7—C8	61.51 (16)
C11—N3—C4—C5	−0.3 (2)	C5—C6—C7—C8	−57.76 (16)
N1—C5—C4—N3	−72.98 (19)	N2—C15—C14—C13	1.5 (3)
C6—C5—C4—N3	162.17 (14)	C15—C14—C13—C12	1.2 (3)
N1—C5—C4—C3	111.88 (16)	C11—C12—C13—C14	−2.3 (2)
C6—C5—C4—C3	−13.0 (2)	N3—N4—C2—C3	−1.93 (17)
C4—C5—C6—C10	167.33 (13)	N3—N4—C2—C1	175.62 (15)
N1—C5—C6—C10	43.61 (17)	C4—C3—C2—N4	2.45 (18)
C4—C5—C6—C9	−75.07 (15)	C8—C3—C2—N4	−172.97 (15)
N1—C5—C6—C9	161.21 (13)	C4—C3—C2—C1	−174.84 (17)
C4—C5—C6—C7	44.75 (16)	C8—C3—C2—C1	9.7 (3)
N1—C5—C6—C7	−78.96 (15)

D—H···A	D—H	H···A	D···A	D—H···A
C12—H12···Cl1i	0.93	2.90	3.7006 (17)	145
C14—H14···O1ii	0.93	2.41	3.244 (2)	149
O1W—H1W···Cl1iii	0.80 (3)	2.39 (3)	3.185 (2)	176 (3)
O1W—H2W···Cl1	0.94 (3)	2.31 (3)	3.247 (2)	179 (2)
N1—H1N1···Cl1iv	0.85 (2)	2.40 (2)	3.228 (2)	165 (2)
N1—H2N1···N4v	0.98 (2)	2.20 (2)	3.1475 (19)	164 (2)
N1—H3N1···O1W	0.95 (2)	1.85 (3)	2.775 (2)	162 (2)