1-[4-(4-Nitro­phen­yl)piperazin-1-yl]-2-(4,5,6,7-tetra­hydro­thieno[3,2-c]pyridin-5-yl)ethanone

Shuai Mu; Miao Yang; Deng-Ke Liu; Chang-Xiao Liu

doi:10.1107/S1600536810039085

. 2010 Oct 9;66(Pt 11):o2762. doi: 10.1107/S1600536810039085

1-[4-(4-Nitrophenyl)piperazin-1-yl]-2-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl)ethanone

Shuai Mu ^a, Miao Yang ^b, Deng-Ke Liu ^c,^*, Chang-Xiao Liu ^c

PMCID: PMC3009028 PMID: 21588964

Abstract

The title compound, C₁₉H₂₂N₄O₃S, comprises a thienopyridine moiety which is characteristic for antiplatelet agents of the clopidogrel class of compounds. In the crystal, inversion dimers are formed through pairs of C—H⋯O interactions. The benzene ring plane and the nitro plane are almost coplanar, with a dihedral angle of 0.83 (2)°. The piperazine ring adopts a chair conformation.

Related literature

For background to the bioactivity and applications of the antiplatelet agent clopidogrel, see, for example: Muller et al. (2003 ▶); Savi et al. (1994 ▶); Sharis et al. (1998 ▶). For the synthesis of other derivatives with thienopyridine, see: Cheng (2009 ▶).

Experimental

Crystal data

C₁₉H₂₂N₄O₃S
M _r = 386.47
Triclinic,
a = 6.1315 (7) Å
b = 8.8552 (10) Å
c = 17.025 (2) Å
α = 84.101 (8)°
β = 83.385 (9)°
γ = 74.635 (6)°
V = 882.87 (18) Å³
Z = 2
Mo Kα radiation
μ = 0.21 mm⁻¹
T = 113 K
0.32 × 0.30 × 0.28 mm

Data collection

Rigaku Saturn CCD area-detector diffractometer
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005 ▶) T _min = 0.935, T _max = 0.943
10552 measured reflections
4169 independent reflections
3402 reflections with I > 2σ(I)
R _int = 0.025

Refinement

R[F ² > 2σ(F ²)] = 0.032
wR(F ²) = 0.088
S = 1.08
4169 reflections
245 parameters
H-atom parameters constrained
Δρ_max = 0.31 e Å⁻³
Δρ_min = −0.26 e Å⁻³

Data collection: CrystalClear (Rigaku/MSC, 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: SHELXL97; software used to prepare material for publication: CrystalStructure (Rigaku/MSC, 2005 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536810039085/kp2278sup1.cif

e-66-o2762-sup1.cif^{(21.7KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810039085/kp2278Isup2.hkl

e-66-o2762-Isup2.hkl^{(204.3KB, 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
C1—H1⋯O3ⁱ	0.95	2.47	3.346 (2)	154
C5—H5A⋯O1ⁱⁱ	0.99	2.56	3.475 (2)	153
C6—H6B⋯O1ⁱⁱⁱ	0.99	2.59	3.420 (2)	142

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

Acknowledgments

The authors thank Mr Hai-Bin Song of Nankai University and Mr Zhi-Qiang Cai of Tianjin Institute of Pharmaceutical Research for their helpful suggestions.

supplementary crystallographic information

Comment

Clopidogrel is an oral, thienopyridine class antiplatelet agent used to inhibit blood clots in coronary artery disease, peripheral vascular disease, and cerebrovascular disease (Muller et al., 2003; Savi et al., 1994; Sharis et al., 1998). The crystal structure of the title compound (I), a derivative with thienopyridine, synthesised through the transformation of clopidogrel, is reported here.

The C14–C19 benzene ring plane and the nitro plane defined by O2/O3/N4 are almost coplanar, with a dihedral angle of 0.83° (Fig. 1). The piperazine ring shows a stable chair conformation. The bond angle in the ring ranges from 107.24–112.67°. The dihedrals formed between C10–C13 plane and C11/C12/N3 plane, C10–C13 plane and C10/C13/N2 plane are 43.32° and 55.40°, respectively. The packing is realised by C—H···O (Table 1) interactions leading to centrosymmetric dimers.

Experimental

2-Chloro-1-(4-(4-nitrophenyl)piperazin-1-yl)ethanone 4 g (0.014 mol) and anhydrous K₂CO₃ 7.7 g (0.056 mol) were dissolved in 40 ml toluene. The mixture was heated to 373 K. Then 2.2 g (0.015 mol) of 4,5,6,7-tetrahydrothieno[3,2-c] pyridine was added dropwise into the mixture, and stirred for 16 h under room temperature. K₂CO₃ was removed after filtration and the reaction solution was concentrated under reduced pressure to get yellow powder as a crude product. The powder was dissolved in a mixture of petroleum ether (20 ml) and acetone (4 ml) at 277 K, then white crystals were grown slowly.