N-(5-Ethylsulfanyl-1,3,4-thiadiazol-2-yl)-2-(4,5,6,7-tetrahydrothieno[3,2-c]pyri­din-5-yl)acetamide

Shuang Zhi; Shuai Mu; Ying Liu; Deng-Ke Liu

doi:10.1107/S1600536811017107

. 2011 May 25;67(Pt 6):o1490. doi: 10.1107/S1600536811017107

N-(5-Ethylsulfanyl-1,3,4-thiadiazol-2-yl)-2-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl)acetamide

Shuang Zhi ^a, Shuai Mu ^b, Ying Liu ^c,^*, Deng-Ke Liu ^c

PMCID: PMC3120429 PMID: 21754858

Abstract

In the title compound, C₁₃H₁₆N₄OS₃, a thienopyridinederivative, the tetrahydropyridine ring exhibits a half-chair conformation, and the folded conformation of the molecule is defined by the N—C—C—N torsion angle of −78.85 (16)°. The crystal packing features intermolecular C—H⋯N, N—H⋯N and C—H⋯O hydrogen bonds.

Related literature

The title compound is a potential antiplatelet agent. As irreversible P2Y12 antagonists, thienopyridines have proved the relevance of inhibiting signaling via the platelet-specific P2Y12 ADP receptor in the prevention of cardiovascular events, see: Iyengar (2009 ▶); Franchini & Mannucci, (2009 ▶); Van Giezen et al. (2009 ▶); Van Giezen & Humphries (2005 ▶). For a related structure, see: Chen et al. (2010 ▶). For the synthesis of the title compound, see: Liu et al. (2008 ▶).

Experimental

Crystal data

C₁₃H₁₆N₄OS₃
M _r = 340.48
Monoclinic,
a = 6.532 (4) Å
b = 9.788 (6) Å
c = 23.491 (15) Å
β = 95.524 (6)°
V = 1494.8 (16) Å³
Z = 4
Mo Kα radiation
μ = 0.50 mm⁻¹
T = 113 K
0.28 × 0.22 × 0.18 mm

Data collection

Rigaku Saturn CCD area-detector diffractometer
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005 ▶) T _min = 0.873, T _max = 0.916
12423 measured reflections
3545 independent reflections
2653 reflections with I > 2σ(I)
R _int = 0.036

Refinement

R[F ² > 2σ(F ²)] = 0.030
wR(F ²) = 0.079
S = 1.03
3545 reflections
195 parameters
1 restraint
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.44 e Å⁻³
Δρ_min = −0.23 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: SHELXTL (Sheldrick, 2008 ▶); software used to prepare material for publication: CrystalStructure (Rigaku/MSC, 2005 ▶).

Supplementary Material

Crystal structure: contains datablocks global, I. DOI: 10.1107/S1600536811017107/kp2327sup1.cif

e-67-o1490-sup1.cif^{(18.6KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536811017107/kp2327Isup2.hkl

e-67-o1490-Isup2.hkl^{(173.9KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536811017107/kp2327Isup3.cdx

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
C12—H12B⋯N1ⁱ	0.99	2.60	3.473 (3)	147
N2—H2⋯N3ⁱⁱ	0.89 (1)	2.02 (1)	2.902 (2)	171 (2)
C5—H5⋯O1ⁱⁱⁱ	0.95	2.46	3.279 (2)	145

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

Acknowledgments

The authors thank Mr Hai-Bin Song of Nankai University for the X-ray crystallographic determination and for helpful suggestions.

supplementary crystallographic information

Comment

As irreversible P2Y12 antagonists, the thienopyridines (e.g., clopidogrel and prasugrel) have been further proved the relevance of inhibiting signaling via the platelet-specific P2Y12 ADP receptor in the prevention of cardiovascular events (Iyengar, 2009; Van Giezen & Humphries, 2005; Franchini, et al., 2009). The structure of the title compound (I), a new derivative of thienopyridine, is presented here.

The tetrahydropyridine ring is in a half-chair conformation (Fig. 1). The thiadiazole ring plane (r.m.s. deviation 0.0020Å) and the acidamide plane (r.m.s. deviation 0.0074 Å) are almost coplanar, with a dihedral angle of 3.24 (9)°. The dihedral angles formed between the thiadiazole ring plane and the thiophene ring plane, the acidamide plane and the thiophene ring plane are 76.19 (6)° and 78.47 (7)° , respectively. Crystal packing is via hydrogen bonds C—H···N, N—H···N and C—H···O (Table 1, Fig. 2).

Experimental

Chloracetyl chloride was dropwised added into a mixture of 5-(ethylthio)-1,3,4-thiadiazol-2-amine, TEA and DMF at 268 K. After stirred for 3 h, the mixture was poured into cold water. 2-Chloro-N-(5-(ethylthio)-1,3,4-thiadiazol-2-yl)acetamide was precipitated as an intermediate. Then the intermediate, equimolar quantities thienopyridine salt and TEA were refluxed for 5 h in acetonitrile, and the product was obtained by silica gel column chromatography. Crystallisation of the obtained yellow solid from methanol afforded light-yellow crystals suitable for X-ray analysis.