2-(5-Bromo­pent­yl)-4-chloro-5-[2-(4-meth­oxy­phen­yl)ethyl­amino]­pyridazin-3(2H)-one

Hai-Quan Wang; Wang-Zhong Chen; Wen-Hua Chen; Bao-Min Xi

doi:10.1107/S1600536810030102

. 2010 Aug 4;66(Pt 9):o2215. doi: 10.1107/S1600536810030102

2-(5-Bromopentyl)-4-chloro-5-[2-(4-methoxyphenyl)ethylamino]pyridazin-3(2H)-one

Hai-Quan Wang ^a, Wang-Zhong Chen ^a, Wen-Hua Chen ^a, Bao-Min Xi ^a,^*

PMCID: PMC3008024 PMID: 21588586

Abstract

The asymmetric unit of the title compound, C₁₈H₂₃BrClN₃O₂, consists of two molecules which exhibit different conformations of the pentyl chains [C—C—C—C torsion angles of −60.4 (4) and 175.8 (3)°]. The crysal packing exhibits a chain structure, generated through the O atom of the pyridazinone forming a hydrogen bond with the N—H group of an adjacent molecule.

Related literature

The title compound is an intermediate in the synthesis of Alpha1-AR antagonists. For the biological applications of Alpha1-AR antagonists, see: Guderman et al. (1995 ▶); Cavalli et al. (1997 ▶); Pallavicini et al. (2006 ▶). For similar phenylpiperazinepyridazinone derivatives synthesized as potential Alpha1-AR antagonists, see: Xi et al. (2006 ▶).

Experimental

Crystal data

C₁₈H₂₃BrClN₃O₂
M _r = 428.75
Triclinic,
a = 9.7728 (14) Å
b = 12.6178 (19) Å
c = 15.500 (2) Å
α = 94.803 (2)°
β = 96.380 (2)°
γ = 91.035 (2)°
V = 1892.1 (5) Å³
Z = 4
Mo Kα radiation
μ = 2.33 mm⁻¹
T = 110 K
0.35 × 0.15 × 0.1 mm

Data collection

Rigaku Mercury diffractometer
Absorption correction: multi-scan (REQAB; Jacobson, 1998 ▶) T _min = 0.933, T _max = 0.975
15893 measured reflections
8131 independent reflections
6225 reflections with I > 2σ(I)
R _int = 0.036

Refinement

R[F ² > 2σ(F ²)] = 0.044
wR(F ²) = 0.143
S = 0.99
8131 reflections
453 parameters
H-atom parameters constrained
Δρ_max = 1.39 e Å⁻³
Δρ_min = −0.88 e Å⁻³

Data collection: CrystalClear (Rigaku/MSC, 2001 ▶); cell refinement: CrystalClear; data reduction: CrystalStructure (Rigaku/MSC, 2004 ▶); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEPII (Johnson, 1976 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810030102/ez2210sup1.cif

e-66-o2215-sup1.cif^{(30.3KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810030102/ez2210Isup2.hkl

e-66-o2215-Isup2.hkl^{(397.7KB, 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
N3—H3⋯O3ⁱ	0.88	2.11	2.796 (3)	135
N6—H6⋯O1ⁱⁱ	0.88	2.06	2.815 (3)	143

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

Acknowledgments

This work was supported by the National Natural Science Foundation of China (No. 30600776).

supplementary crystallographic information

Comment

Alpha1-adrenoceptors (Alpha1-AR) are members of the super family of seven transmembrane G protein coupled receptors (GPCR) (Guderman et al., 1995) and regulate several important physiological processes. In recent years, the search for new alpha1-AR antagonists has intensified due to their therapeutic potential in the treatment of hypertension (Cavalli et al., 1997) and benign prostatic hypertrophy (Pallavicini et al., 2006). In the course of our studies on phenylpiperazinepyridazinone derivatives as potential Alpha1-AR antagonists, we have synthesized a range of compounds (Xi et al., 2006) which show good blocking activities toward Alpha1-AR. Phenylpiperazinepyridazinone derivatives are a type of Alpha1-AR antagonist; the title compound is a key intermediate in the synthesis of phenylpiperazinepyridazinone derivatives.

The asymmetric unit of the title compound consists of two molecules which differ from one another crystallographically. The largest difference between the two molecules is in the conformations of the pentyl chains, indicated by the C2-C3-C4-C5 and C20-C21-C22-C23 torsion angles of -60.4 (4)° and 175.8 (3)°, respectively. The molecules contain pyridazinone and benzene rings, which are orientated at angles of 13.28 (17)° and 23.34 (14)° with respect to each other in the two molecules. The one dimensional chain structure found in the crystal packing is formed through intermolecular N—H···O hydrogen bonds.

Experimental

A mixture of 5-(4-methoxyphenethylamino)-4-chloropyridazin-3(2H)-one (0.3 g), K₂CO₃ (0.22 g), 1,5-dibromopentane(0.34 g), and acetone (16 ml) were heated to reflux of the solvent for 10 h. After cooling, the resulting precipitate was filtered off and filtrate was evaporated. The residue was chromatographed on silica gel with petroleum-ethyl acetate (3:2 with TEA) as eluent to give the title compound (0.169 g, 36.7%). Crystals suitable for X-ray analysis were obtained from the slow evaporation of a chloroform solution (m.p. 355–356 K).