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Acta Crystallogr Sect E Struct Rep Online. 2010 November 1; 66(Pt 11): o2762.
Published online 2010 October 9. doi:  10.1107/S1600536810039085
PMCID: PMC3009028

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

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 [triangle]); Savi et al. (1994 [triangle]); Sharis et al. (1998 [triangle]). For the synthesis of other derivatives with thienopyridine, see: Cheng (2009 [triangle]).

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Object name is e-66-o2762-scheme1.jpg

Experimental

Crystal data

  • C19H22N4O3S
  • M r = 386.47
  • Triclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-o2762-efi1.jpg
  • 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 [triangle]) 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
  • Δρmax = 0.31 e Å−3
  • Δρmin = −0.26 e Å−3

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

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

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

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

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

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.

Refinement

All the H atoms were located on their parent atoms with C—H = 0.95 Å (aromatic CH) and 0.99 Å (CH2), Uiso = 1.2Ueq(C).

Figures

Fig. 1.
The molecular structure of (I), Displacement ellipsoids are drawn at the 50% probability level.

Crystal data

C19H22N4O3SZ = 2
Mr = 386.47F(000) = 408
Triclinic, P1Dx = 1.454 Mg m3
a = 6.1315 (7) ÅMo Kα radiation, λ = 0.71070 Å
b = 8.8552 (10) ÅCell parameters from 2732 reflections
c = 17.025 (2) Åθ = 1.2–27.9°
α = 84.101 (8)°µ = 0.21 mm1
β = 83.385 (9)°T = 113 K
γ = 74.635 (6)°Block, yellow
V = 882.87 (18) Å30.32 × 0.30 × 0.28 mm

Data collection

Rigaku Saturn CCD area-detector diffractometer4169 independent reflections
Radiation source: rotating anode3402 reflections with I > 2σ(I)
confocalRint = 0.025
Detector resolution: 7.31 pixels mm-1θmax = 27.9°, θmin = 1.2°
ω and [var phi] scansh = −8→8
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005)k = −11→11
Tmin = 0.935, Tmax = 0.943l = −22→21
10552 measured reflections

Refinement

Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.032H-atom parameters constrained
wR(F2) = 0.088w = 1/[σ2(Fo2) + (0.0455P)2 + 0.1626P] where P = (Fo2 + 2Fc2)/3
S = 1.08(Δ/σ)max = 0.001
4169 reflectionsΔρmax = 0.31 e Å3
245 parametersΔρmin = −0.26 e Å3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.019 (7)

Special details

Geometry. All e.s.d.'s (except the e.s.d. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell e.s.d.'s are taken into account individually in the estimation of e.s.d.'s in distances, angles and torsion angles; correlations between e.s.d.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell e.s.d.'s is used for estimating e.s.d.'s involving l.s. planes.
Refinement. Refinement of F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional R-factors R are based on F, with F set to zero for negative F2. The threshold expression of F2 > σ(F2) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F2 are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2)

xyzUiso*/Ueq
S10.30943 (5)0.92591 (3)−0.249539 (17)0.01923 (11)
O1−0.12392 (14)0.78988 (11)0.05647 (6)0.0249 (2)
O21.01128 (18)0.15750 (13)0.58507 (6)0.0376 (3)
O30.7589 (2)0.02733 (13)0.58411 (7)0.0451 (3)
N10.22099 (16)0.69145 (11)−0.00851 (6)0.0145 (2)
N20.32167 (16)0.71481 (11)0.16167 (6)0.0148 (2)
N30.44060 (16)0.56269 (11)0.31518 (6)0.0156 (2)
N40.8425 (2)0.13723 (14)0.55919 (7)0.0275 (3)
C10.0996 (2)0.85073 (14)−0.27522 (7)0.0208 (3)
H10.03700.8743−0.32490.025*
C20.0340 (2)0.75339 (14)−0.21584 (7)0.0183 (2)
H2−0.08040.7006−0.21930.022*
C30.15476 (19)0.73858 (13)−0.14760 (7)0.0147 (2)
C40.31018 (19)0.82610 (13)−0.15692 (7)0.0147 (2)
C50.45773 (19)0.83687 (14)−0.09431 (7)0.0162 (2)
H5A0.39910.9385−0.07000.019*
H5B0.61480.8302−0.11810.019*
C60.45572 (19)0.70088 (13)−0.03118 (7)0.0156 (2)
H6A0.54670.6011−0.05230.019*
H6B0.52450.71760.01600.019*
C70.1199 (2)0.64098 (14)−0.07174 (7)0.0163 (2)
H7A−0.04460.6535−0.05700.020*
H7B0.19160.5287−0.07920.020*
C80.08392 (19)0.77300 (13)0.04926 (7)0.0161 (2)
C90.1956 (2)0.83986 (14)0.10806 (7)0.0171 (2)
H9A0.30080.89810.07880.021*
H9B0.07750.91470.13960.021*
C100.4469 (2)0.78077 (14)0.21157 (7)0.0173 (2)
H10A0.33870.86070.24330.021*
H10B0.55150.83320.17750.021*
C110.5819 (2)0.65394 (14)0.26673 (7)0.0181 (2)
H11A0.70320.58200.23490.022*
H11B0.65560.70330.30220.022*
C120.2908 (2)0.51145 (14)0.26835 (7)0.0172 (2)
H12A0.18000.46850.30470.021*
H12B0.38240.42630.23580.021*
C130.1640 (2)0.64430 (14)0.21457 (7)0.0177 (2)
H13A0.06970.60390.18260.021*
H13B0.06150.72540.24710.021*
C140.5398 (2)0.45722 (13)0.37518 (7)0.0157 (2)
C150.7310 (2)0.47506 (14)0.40870 (7)0.0194 (3)
H150.79350.56080.38980.023*
C160.8282 (2)0.37062 (15)0.46814 (7)0.0212 (3)
H160.95790.38370.48950.025*
C170.7371 (2)0.24656 (14)0.49676 (7)0.0207 (3)
C180.5485 (2)0.22540 (14)0.46630 (7)0.0214 (3)
H180.48610.14040.48670.026*
C190.4521 (2)0.32864 (14)0.40612 (7)0.0194 (3)
H190.32370.31310.38490.023*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
S10.02648 (18)0.01618 (16)0.01532 (16)−0.00697 (12)−0.00135 (12)0.00086 (11)
O10.0145 (4)0.0317 (5)0.0297 (5)−0.0068 (4)0.0002 (4)−0.0080 (4)
O20.0329 (6)0.0445 (6)0.0350 (6)−0.0089 (5)−0.0162 (5)0.0104 (5)
O30.0627 (8)0.0347 (6)0.0444 (7)−0.0234 (6)−0.0272 (6)0.0207 (5)
N10.0127 (5)0.0165 (5)0.0148 (5)−0.0046 (4)−0.0031 (4)0.0004 (4)
N20.0149 (5)0.0158 (5)0.0154 (5)−0.0068 (4)−0.0027 (4)0.0006 (4)
N30.0160 (5)0.0161 (5)0.0164 (5)−0.0074 (4)−0.0027 (4)0.0005 (4)
N40.0324 (6)0.0252 (6)0.0230 (6)−0.0035 (5)−0.0069 (5)0.0023 (5)
C10.0269 (6)0.0191 (6)0.0169 (6)−0.0045 (5)−0.0062 (5)−0.0025 (5)
C20.0210 (6)0.0172 (5)0.0179 (6)−0.0049 (5)−0.0042 (5)−0.0045 (5)
C30.0148 (5)0.0117 (5)0.0166 (6)−0.0014 (4)−0.0016 (4)−0.0022 (4)
C40.0162 (5)0.0121 (5)0.0148 (5)−0.0021 (4)−0.0010 (4)−0.0009 (4)
C50.0141 (5)0.0165 (5)0.0187 (6)−0.0057 (4)−0.0020 (5)0.0008 (4)
C60.0116 (5)0.0170 (5)0.0178 (6)−0.0029 (4)−0.0033 (4)0.0013 (4)
C70.0182 (6)0.0163 (5)0.0163 (6)−0.0071 (4)−0.0048 (5)0.0006 (4)
C80.0167 (6)0.0136 (5)0.0178 (6)−0.0040 (4)−0.0037 (5)0.0020 (4)
C90.0185 (6)0.0149 (5)0.0184 (6)−0.0048 (4)−0.0021 (5)−0.0011 (4)
C100.0191 (6)0.0174 (5)0.0183 (6)−0.0092 (5)−0.0036 (5)−0.0006 (5)
C110.0168 (6)0.0203 (6)0.0199 (6)−0.0101 (5)−0.0026 (5)0.0008 (5)
C120.0171 (6)0.0182 (6)0.0191 (6)−0.0096 (5)−0.0036 (5)0.0010 (5)
C130.0144 (5)0.0198 (6)0.0202 (6)−0.0075 (4)−0.0016 (5)0.0004 (5)
C140.0166 (5)0.0151 (5)0.0148 (5)−0.0033 (4)0.0017 (4)−0.0037 (4)
C150.0205 (6)0.0202 (6)0.0191 (6)−0.0076 (5)−0.0021 (5)−0.0024 (5)
C160.0208 (6)0.0236 (6)0.0203 (6)−0.0060 (5)−0.0042 (5)−0.0039 (5)
C170.0245 (6)0.0190 (6)0.0162 (6)−0.0012 (5)−0.0023 (5)−0.0010 (5)
C180.0264 (7)0.0175 (6)0.0204 (6)−0.0069 (5)−0.0003 (5)−0.0003 (5)
C190.0204 (6)0.0190 (6)0.0199 (6)−0.0070 (5)−0.0025 (5)−0.0015 (5)

Geometric parameters (Å, °)

S1—C11.7127 (13)C6—H6B0.9900
S1—C41.7265 (12)C7—H7A0.9900
O1—C81.2362 (14)C7—H7B0.9900
O2—N41.2317 (16)C8—C91.5219 (16)
O3—N41.2327 (16)C9—H9A0.9900
N1—C81.3524 (16)C9—H9B0.9900
N1—C71.4638 (14)C10—C111.5160 (16)
N1—C61.4685 (14)C10—H10A0.9900
N2—C131.4628 (14)C10—H10B0.9900
N2—C101.4637 (14)C11—H11A0.9900
N2—C91.4690 (15)C11—H11B0.9900
N3—C141.3900 (15)C12—C131.5115 (16)
N3—C121.4662 (14)C12—H12A0.9900
N3—C111.4674 (14)C12—H12B0.9900
N4—C171.4491 (16)C13—H13A0.9900
C1—C21.3558 (18)C13—H13B0.9900
C1—H10.9500C14—C151.4125 (17)
C2—C31.4251 (16)C14—C191.4140 (16)
C2—H20.9500C15—C161.3746 (17)
C3—C41.3658 (16)C15—H150.9500
C3—C71.5051 (16)C16—C171.3818 (18)
C4—C51.5008 (16)C16—H160.9500
C5—C61.5311 (16)C17—C181.3833 (18)
C5—H5A0.9900C18—C191.3768 (17)
C5—H5B0.9900C18—H180.9500
C6—H6A0.9900C19—H190.9500
C1—S1—C492.11 (6)N2—C9—H9A109.4
C8—N1—C7119.36 (10)C8—C9—H9A109.4
C8—N1—C6123.35 (10)N2—C9—H9B109.4
C7—N1—C6113.03 (9)C8—C9—H9B109.4
C13—N2—C10107.24 (9)H9A—C9—H9B108.0
C13—N2—C9110.12 (9)N2—C10—C11111.11 (9)
C10—N2—C9109.88 (9)N2—C10—H10A109.4
C14—N3—C12117.17 (9)C11—C10—H10A109.4
C14—N3—C11117.63 (9)N2—C10—H10B109.4
C12—N3—C11112.57 (9)C11—C10—H10B109.4
O2—N4—O3122.75 (11)H10A—C10—H10B108.0
O2—N4—C17118.95 (11)N3—C11—C10112.67 (10)
O3—N4—C17118.30 (11)N3—C11—H11A109.1
C2—C1—S1111.59 (9)C10—C11—H11A109.1
C2—C1—H1124.2N3—C11—H11B109.1
S1—C1—H1124.2C10—C11—H11B109.1
C1—C2—C3112.85 (11)H11A—C11—H11B107.8
C1—C2—H2123.6N3—C12—C13112.06 (9)
C3—C2—H2123.6N3—C12—H12A109.2
C4—C3—C2112.58 (11)C13—C12—H12A109.2
C4—C3—C7121.64 (10)N3—C12—H12B109.2
C2—C3—C7125.77 (10)C13—C12—H12B109.2
C3—C4—C5124.49 (11)H12A—C12—H12B107.9
C3—C4—S1110.87 (9)N2—C13—C12110.96 (9)
C5—C4—S1124.63 (9)N2—C13—H13A109.4
C4—C5—C6108.25 (9)C12—C13—H13A109.4
C4—C5—H5A110.0N2—C13—H13B109.4
C6—C5—H5A110.0C12—C13—H13B109.4
C4—C5—H5B110.0H13A—C13—H13B108.0
C6—C5—H5B110.0N3—C14—C15121.43 (11)
H5A—C5—H5B108.4N3—C14—C19121.51 (11)
N1—C6—C5109.67 (9)C15—C14—C19117.06 (11)
N1—C6—H6A109.7C16—C15—C14121.21 (11)
C5—C6—H6A109.7C16—C15—H15119.4
N1—C6—H6B109.7C14—C15—H15119.4
C5—C6—H6B109.7C15—C16—C17119.90 (12)
H6A—C6—H6B108.2C15—C16—H16120.0
N1—C7—C3109.44 (9)C17—C16—H16120.0
N1—C7—H7A109.8C16—C17—C18120.89 (12)
C3—C7—H7A109.8C16—C17—N4119.13 (12)
N1—C7—H7B109.8C18—C17—N4119.98 (11)
C3—C7—H7B109.8C19—C18—C17119.43 (11)
H7A—C7—H7B108.2C19—C18—H18120.3
O1—C8—N1122.19 (11)C17—C18—H18120.3
O1—C8—C9120.27 (11)C18—C19—C14121.51 (11)
N1—C8—C9117.51 (10)C18—C19—H19119.2
N2—C9—C8111.26 (9)C14—C19—H19119.2
C4—S1—C1—C2−0.24 (10)C9—N2—C10—C11−179.10 (9)
S1—C1—C2—C30.11 (14)C14—N3—C11—C10−171.71 (10)
C1—C2—C3—C40.12 (15)C12—N3—C11—C1047.41 (13)
C1—C2—C3—C7179.31 (11)N2—C10—C11—N3−54.79 (13)
C2—C3—C4—C5178.37 (10)C14—N3—C12—C13170.61 (10)
C7—C3—C4—C5−0.85 (17)C11—N3—C12—C13−48.32 (13)
C2—C3—C4—S1−0.30 (13)C10—N2—C13—C12−62.45 (12)
C7—C3—C4—S1−179.52 (9)C9—N2—C13—C12178.02 (9)
C1—S1—C4—C30.31 (9)N3—C12—C13—N256.93 (13)
C1—S1—C4—C5−178.36 (10)C12—N3—C14—C15162.26 (10)
C3—C4—C5—C616.48 (15)C11—N3—C14—C1523.17 (16)
S1—C4—C5—C6−165.03 (8)C12—N3—C14—C19−18.64 (16)
C8—N1—C6—C5−87.64 (13)C11—N3—C14—C19−157.73 (11)
C7—N1—C6—C568.93 (12)N3—C14—C15—C16179.86 (11)
C4—C5—C6—N1−47.59 (12)C19—C14—C15—C160.72 (18)
C8—N1—C7—C3107.55 (12)C14—C15—C16—C17−0.80 (19)
C6—N1—C7—C3−50.05 (12)C15—C16—C17—C180.11 (19)
C4—C3—C7—N116.24 (15)C15—C16—C17—N4179.73 (11)
C2—C3—C7—N1−162.88 (11)O2—N4—C17—C16−0.17 (18)
C7—N1—C8—O19.29 (17)O3—N4—C17—C16179.92 (13)
C6—N1—C8—O1164.47 (11)O2—N4—C17—C18179.45 (12)
C7—N1—C8—C9−172.84 (9)O3—N4—C17—C18−0.46 (19)
C6—N1—C8—C9−17.67 (16)C16—C17—C18—C190.64 (19)
C13—N2—C9—C8−68.22 (12)N4—C17—C18—C19−178.97 (11)
C10—N2—C9—C8173.88 (9)C17—C18—C19—C14−0.72 (19)
O1—C8—C9—N2106.91 (12)N3—C14—C19—C18−179.10 (11)
N1—C8—C9—N2−71.00 (13)C15—C14—C19—C180.05 (18)
C13—N2—C10—C1161.22 (12)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C1—H1···O3i0.952.473.346 (2)154
C5—H5A···O1ii0.992.563.475 (2)153
C6—H6B···O1iii0.992.593.420 (2)142

Symmetry codes: (i) x−1, y+1, z−1; (ii) −x, −y+2, −z; (iii) x+1, y, z.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: KP2278).

References

  • Cheng, D. (2009). PhD thesis, Tianjin University, China.
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