3-(5-Chloro­naphthalene-1-sulfonamido)-2-(2-hy­droxy­eth­yl)-4,5,6,7-tetra­hydro-2H-pyrazolo­[4,3-c]pyridin-5-ium chloride

Xiao-Guang Bai; Hong-Tao Liu; Yu-Cheng Wang; Ju-Xian Wang

doi:10.1107/S1600536811012967

. 2011 Apr 13;67(Pt 5):o1103. doi: 10.1107/S1600536811012967

3-(5-Chloronaphthalene-1-sulfonamido)-2-(2-hydroxyethyl)-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridin-5-ium chloride

Xiao-Guang Bai ^a, Hong-Tao Liu ^a, Yu-Cheng Wang ^a, Ju-Xian Wang ^a,^*

PMCID: PMC3089121 PMID: 21754421

Abstract

In the cation of the title compound, C₁₈H₂₀ClN₄O₃S⁺·Cl⁻, the tetrahydropyridinium ring assumes a half-chair conformation. The dihedral angle between the pyrazole ring and the naphthalene ring system is 75.19 (6)°. In the crystal, ions are linked into a three-dimensional network by N—H⋯O, N—H⋯Cl and O—H⋯Cl hydrogen bonds and weak π–π stacking interactions with centroid–centroid distances of 3.608 (2) Å.

Related literature

For general background to potential anticancer kinase inhibitors, see: Fancelli et al. (2005 ▶); Gadekar et al. (1968 ▶). For a related structure, see: Brehm (1982 ▶).

Experimental

Crystal data

C₁₈H₂₀ClN₄O₃S⁺·Cl⁻
M _r = 443.34
Monoclinic,
a = 14.790 (3) Å
b = 10.432 (2) Å
c = 13.155 (3) Å
β = 103.84 (3)°
V = 1970.9 (7) Å³
Z = 4
Mo Kα radiation
μ = 0.46 mm⁻¹
T = 294 K
0.25 × 0.20 × 0.18 mm

Data collection

Rigaku SCXmini diffractometer
19975 measured reflections
4511 independent reflections
3748 reflections with I > 2σ(I)
R _int = 0.036

Refinement

R[F ² > 2σ(F ²)] = 0.041
wR(F ²) = 0.097
S = 1.08
4511 reflections
258 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.33 e Å⁻³
Δρ_min = −0.33 e Å⁻³

Data collection: CrystalClear (Rigaku, 2005 ▶); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: SHELXTL/PC (Sheldrick, 2008 ▶); software used to prepare material for publication: SHELXTL/PC.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536811012967/rz2578sup1.cif

e-67-o1103-sup1.cif^{(22KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811012967/rz2578Isup2.hkl

e-67-o1103-Isup2.hkl^{(221KB, hkl)}

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1⋯Cl2	0.80 (2)	2.47 (2)	3.261 (2)	170 (2)
N3—H3B⋯O3ⁱ	0.90	1.97	2.814 (3)	155
N3—H3A⋯Cl2ⁱⁱ	0.90	2.26	3.1060 (19)	156
O3—H3C⋯Cl2ⁱⁱⁱ	0.82	2.30	3.1151 (18)	172

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Symmetry codes: (i) Inline graphic ; (ii) ; (iii) .

Acknowledgments

This work was supported by the National Natural Science Foundation (81072577).

supplementary crystallographic information

Comment

As part of our ongoing project aimed at the development of potential anticancer kinase inhibitors (Fancelli et al., 2005; Gadekar et al., 1968), we have synthesized the title compound and report its crystal structure herein.

In the title compound (Fig. 1) bond lengths and angles have normal values. The dihedral angle between the planes of the pyrazole ring and the naphthalene ring system is 75.19 (6)°. As already observed in the related compound 2-methyl-4,5,6,7-tetrahydro-pyrazolo(3,4-c)pyridin-3-ol monohydrate (Brehm, 1982) the tetrahydropyridinium ring assumes a half-chair conformation, with atom C15 displaced by 0.665 (2) Å from the mean plane through the C12/C13/C14/C16/N3 atoms. The crystal structure (Fig. 2) is stabilized by N—H···O, N—H···Cl and O—H···Cl hydrogen bonds (Table 1) and by weak π···π stacking interactions occurring between centrosymmetrically related C5—C10 rings (centroid-to-centroid distance = 3.608 (2) Å).

Experimental

A mixture of tert-butyl 3-cyano-4-oxopiperidine-1-carboxylate (22.4 g, 100 mmol) and 2-hydroxyethylhydrazine (7.76 g, 100 mmol) in ethanol was stirred at room temperature for 24 h and concentrated by evaporation, then crystallized in AcOEt and petroleum ether (5:1 v/v) to give tert-butyl 3-amino-2-(2-hydroxyethyl)-6,7-dihydro-2H-pyrazolo[4,3-c]pyridine-5(4H)-carboxylate as a yellow solid (13.5 g, one-step yield: 72%). A mixture of a portion (4.0 g, 14.2 mmol) of the material so obtained, azabenzene (10 ml) and dry acetonitrile was stirred at room temperature for 10 min and then a solution of 5-chloronaphthalene-1-sulfonyl chloride (3.7 g, 14.2 mmol) in dry acetonitrile (100 ml) was slowly added dropwise, stirred for 2 additional hours and concentrated by evaporation. The residue was purified by flash chromatography to give 3.9 g of tert-butyl 3-(1-chloronaphthalene-5-sulfonamido)-2-(2-hydroxyethyl)-6,7-dihydro-2H-pyrazolo[4,3-c]pyridine-5(4H)-carboxylate as a slightly yellow solid (one-step yield: 54%). Then, dry HCl gas was bubbled in a solution of the material so obtained (3.0 g, 5.9 mmol) in dry DCM (100 ml) for 3 h to get a white solid of the title compound (one-step yield:98%). Colourless block crystals suitable for X-ray diffraction were obtained in 5 days by slow evaporation of a methanol solution.