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Acta Crystallogr Sect E Struct Rep Online. 2010 December 1; 66(Pt 12): o3213.
Published online 2010 November 17. doi:  10.1107/S1600536810046908
PMCID: PMC3011544

2-Chloro­ethyl 2-(2-chloro­phen­yl)-2-(4,5,6,7-tetrahydro­thieno[3,2-c]pyridin-5-yl)acetate

Abstract

The mol­ecular packing of the title compound, C17H17Cl2NO2S, is stabilized by weak C—H(...)O and C—H(...)Cl inter­actions. The ester chain is almost planar with a mean deviation of 0.0605 Å and makes dihedral angles of 71.60 (4) and 74.70 (8)° with the benzene ring and the thio­phene ring, respectively. The benzene and thio­phene rings make a dihedral angle of 84.22 (7)°.

Related literature

The title compound is a derivative of clopidogrel. For background to the bioactivity and applications of the anti­platelet agent clopidogrel, see, for example, Gurbel & Tantry (2007 [triangle]); Muller et al. (2003 [triangle]); Savi et al. (1994 [triangle]); Sharis et al. (1998 [triangle]). For the synthesis of other derivatives with thienopyridine, see: Aubert et al. (1985 [triangle]); Bipin et al. (2002 [triangle]); Bouisset & Radisson (1991 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-66-o3213-scheme1.jpg

Experimental

Crystal data

  • C17H17Cl2NO2S
  • M r = 370.28
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-66-o3213-efi1.jpg
  • a = 9.689 (1) Å
  • b = 11.2670 (12) Å
  • c = 15.5670 (16) Å
  • β = 100.509 (8)°
  • V = 1670.9 (3) Å3
  • Z = 4
  • Cu Kα radiation
  • μ = 4.73 mm−1
  • T = 113 K
  • 0.26 × 0.24 × 0.20 mm

Data collection

  • Rigaku Saturn diffractometer
  • Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005 [triangle]) T min = 0.373, T max = 0.451
  • 18109 measured reflections
  • 3203 independent reflections
  • 2974 reflections with I > 2σ(I)
  • R int = 0.065

Refinement

  • R[F 2 > 2σ(F 2)] = 0.037
  • wR(F 2) = 0.107
  • S = 1.09
  • 3203 reflections
  • 210 parameters
  • H-atom parameters constrained
  • Δρmax = 0.55 e Å−3
  • Δρmin = −0.50 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: SHELXTL (Sheldrick, 2008 [triangle]); 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/S1600536810046908/fk2029sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536810046908/fk2029Isup2.hkl

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

Acknowledgments

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

supplementary crystallographic information

Comment

Clopidogrel, a thienopyridine class inhibitor of P2Y12 ADP platelet receptor, has been found to be particularly useful in the treatment of coronary artery disease, peripheral vascular disease, and cerebrovascular disease (Aubert et al., 1985; Bipin et al., 2002; Bouisset & Radisson, 1991; Muller et al., 2003; Savi, et al.,1994; Gurbel & Tantry, 2007; Sharis et al., 1998). The crystal structure of the title compound, 2-Chloroethyl 2-(2-chlorophenyl)-2-(6,7-dihydro thieno[3,2-c]pyridin-5(4H)-yl)acetate (I), a derivative of clopidogrel, is reported here.

As shown in Fig. 1, the benzene ring, the ester chain and the thienopyridine group are all linked to C8 and a molecular chiral center is formed. The ester chain(C15/C16/C17/O1/O2/Cl2) is almost planar, the mean deviation from the plane is 0.0605 Å. The dihedral angles formed between the benzene ring plane (A), the ester chain plane (B) and the thiophene ring plane (C) are 71.60 (4) ° (A/B), 74.70 (8) ° (B/C) and 84.22 (7) ° (A/C), respectively. The packing is consolidated by C—H···O and C—H···Cl interactions, see Table 1.

Experimental

(I) was prepared from α-bromo(2-chloro)phenyl acetic acid and 4,5,6,7-tetrahydro thieno[3,2-c] pyridin by esterification and substitution reaction. Colourless crystals (m.p. 91.8–92.8°C) were obtained in a yield of 93.7%. Single crystals were grown from hexane-ethyl acetate (1:1) solution.

Refinement

All the H atoms were positioned geometrically and refined as riding atoms, with C8—H8=1.00 Å, C—H=0.95Å (for the other CH groups), and 0.99Å (CH2), Uiso = 1.2Ueq(C).

Figures

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

Crystal data

C17H17Cl2NO2SF(000) = 768
Mr = 370.28Dx = 1.472 Mg m3
Monoclinic, P21/nCu Kα radiation, λ = 1.54187 Å
Hall symbol: -P 2ynCell parameters from 2162 reflections
a = 9.689 (1) Åθ = 27.6–72.0°
b = 11.2670 (12) ŵ = 4.73 mm1
c = 15.5670 (16) ÅT = 113 K
β = 100.509 (8)°Prism, colorless
V = 1670.9 (3) Å30.26 × 0.24 × 0.20 mm
Z = 4

Data collection

Rigaku Saturn diffractometer3203 independent reflections
Radiation source: fine-focus sealed tube2974 reflections with I > 2σ(I)
multilayerRint = 0.065
Detector resolution: 14.63 pixels mm-1θmax = 72.6°, θmin = 4.9°
ω scansh = −11→11
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005)k = −13→13
Tmin = 0.373, Tmax = 0.451l = −19→15
18109 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)] = 0.037H-atom parameters constrained
wR(F2) = 0.107w = 1/[σ2(Fo2) + (0.0633P)2 + 0.6161P] where P = (Fo2 + 2Fc2)/3
S = 1.09(Δ/σ)max = 0.001
3203 reflectionsΔρmax = 0.55 e Å3
210 parametersΔρmin = −0.50 e Å3
0 restraintsExtinction correction: SHELXL, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0023 (4)

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
Cl10.04822 (5)0.57741 (4)0.11386 (3)0.02277 (16)
Cl20.76621 (5)0.81053 (4)0.43330 (3)0.02378 (16)
S1−0.27359 (5)0.25362 (4)0.37037 (3)0.02083 (16)
O10.32239 (15)0.54792 (13)0.45403 (9)0.0225 (3)
O20.39640 (14)0.66198 (12)0.35279 (9)0.0174 (3)
N10.08010 (16)0.47629 (13)0.32205 (10)0.0130 (3)
C1−0.1656 (2)0.13256 (17)0.36824 (13)0.0210 (4)
H1−0.19590.05240.36850.025*
C2−0.0317 (2)0.16624 (17)0.36612 (13)0.0179 (4)
H20.04320.11200.36560.022*
C3−0.01587 (19)0.29199 (16)0.36478 (12)0.0144 (4)
C4−0.13725 (19)0.35097 (16)0.36683 (12)0.0153 (4)
C5−0.1531 (2)0.48332 (16)0.36218 (13)0.0176 (4)
H5A−0.20340.51130.40830.021*
H5B−0.20850.50660.30480.021*
C6−0.0070 (2)0.53980 (16)0.37471 (13)0.0169 (4)
H6A−0.01540.62420.35680.020*
H6B0.03760.53640.43720.020*
C70.11670 (19)0.35649 (16)0.35549 (14)0.0175 (4)
H7A0.18030.36130.41290.021*
H7B0.16570.31300.31460.021*
C80.19666 (18)0.54645 (15)0.30224 (12)0.0139 (4)
H80.15490.62210.27560.017*
C90.26203 (18)0.48536 (15)0.23238 (12)0.0132 (4)
C100.19866 (18)0.49132 (16)0.14532 (12)0.0143 (4)
C110.2530 (2)0.43267 (17)0.08043 (13)0.0175 (4)
H110.20700.43750.02120.021*
C120.3751 (2)0.36703 (16)0.10307 (13)0.0179 (4)
H120.41270.32610.05920.021*
C130.44201 (19)0.36086 (16)0.18876 (13)0.0164 (4)
H130.52680.31710.20390.020*
C140.38540 (19)0.41882 (15)0.25317 (13)0.0155 (4)
H140.43140.41310.31240.019*
C150.31009 (19)0.58238 (15)0.37984 (13)0.0160 (4)
C160.5174 (2)0.69884 (17)0.41623 (13)0.0188 (4)
H16A0.56750.62930.44580.023*
H16B0.48920.75170.46080.023*
C170.6085 (2)0.76441 (17)0.36247 (14)0.0202 (4)
H17A0.55770.83450.33420.024*
H17B0.63160.71180.31620.024*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
Cl10.0140 (2)0.0368 (3)0.0168 (3)0.00997 (17)0.00123 (19)0.00264 (18)
Cl20.0144 (3)0.0303 (3)0.0259 (3)−0.00757 (16)0.0018 (2)0.00000 (18)
S10.0121 (3)0.0269 (3)0.0237 (3)−0.00480 (16)0.0040 (2)0.00486 (18)
O10.0192 (7)0.0317 (7)0.0173 (8)−0.0060 (6)0.0050 (6)0.0020 (6)
O20.0138 (6)0.0248 (7)0.0131 (7)−0.0073 (5)0.0014 (5)0.0002 (5)
N10.0113 (7)0.0173 (7)0.0119 (8)−0.0005 (6)0.0062 (6)0.0000 (6)
C10.0235 (10)0.0211 (9)0.0194 (11)−0.0054 (7)0.0063 (8)0.0003 (7)
C20.0217 (10)0.0208 (9)0.0126 (10)−0.0013 (7)0.0065 (8)0.0001 (7)
C30.0136 (9)0.0210 (9)0.0090 (9)−0.0004 (7)0.0033 (7)0.0018 (7)
C40.0141 (9)0.0241 (9)0.0079 (9)−0.0021 (7)0.0027 (7)0.0012 (7)
C50.0148 (9)0.0225 (9)0.0174 (10)0.0024 (7)0.0077 (8)0.0037 (7)
C60.0154 (9)0.0186 (8)0.0191 (10)0.0005 (7)0.0100 (8)−0.0004 (7)
C70.0101 (8)0.0171 (8)0.0262 (11)0.0005 (6)0.0058 (8)0.0031 (7)
C80.0111 (8)0.0172 (8)0.0143 (9)−0.0011 (6)0.0049 (7)−0.0002 (7)
C90.0093 (8)0.0167 (8)0.0143 (9)−0.0025 (6)0.0044 (7)0.0013 (6)
C100.0103 (8)0.0205 (8)0.0123 (10)−0.0005 (6)0.0026 (7)0.0007 (7)
C110.0135 (9)0.0243 (9)0.0145 (10)−0.0015 (7)0.0020 (7)−0.0003 (7)
C120.0169 (9)0.0207 (9)0.0174 (10)0.0008 (7)0.0068 (8)−0.0030 (7)
C130.0131 (9)0.0204 (9)0.0161 (10)0.0024 (7)0.0036 (7)0.0001 (7)
C140.0114 (9)0.0190 (9)0.0159 (10)−0.0006 (6)0.0023 (7)0.0013 (7)
C150.0124 (9)0.0183 (9)0.0188 (11)−0.0002 (6)0.0068 (8)−0.0017 (7)
C160.0137 (9)0.0262 (10)0.0162 (10)−0.0057 (7)0.0024 (8)−0.0035 (7)
C170.0140 (9)0.0240 (9)0.0222 (11)−0.0049 (7)0.0022 (8)−0.0004 (8)

Geometric parameters (Å, °)

Cl1—C101.7450 (18)C6—H6B0.9900
Cl2—C171.791 (2)C7—H7A0.9900
S1—C11.723 (2)C7—H7B0.9900
S1—C41.7256 (18)C8—C91.520 (2)
O1—C151.204 (2)C8—C151.532 (3)
O2—C151.345 (2)C8—H81.0000
O2—C161.449 (2)C9—C101.384 (3)
N1—C81.457 (2)C9—C141.398 (3)
N1—C61.466 (2)C10—C111.389 (3)
N1—C71.467 (2)C11—C121.385 (3)
C1—C21.358 (3)C11—H110.9500
C1—H10.9500C12—C131.374 (3)
C2—C31.426 (3)C12—H120.9500
C2—H20.9500C13—C141.390 (3)
C3—C41.356 (3)C13—H130.9500
C3—C71.506 (2)C14—H140.9500
C4—C51.499 (3)C16—C171.515 (3)
C5—C61.532 (3)C16—H16A0.9900
C5—H5A0.9900C16—H16B0.9900
C5—H5B0.9900C17—H17A0.9900
C6—H6A0.9900C17—H17B0.9900
C1—S1—C491.80 (9)C9—C8—C15110.57 (14)
C15—O2—C16116.73 (15)N1—C8—H8106.2
C8—N1—C6113.66 (14)C9—C8—H8106.2
C8—N1—C7115.33 (14)C15—C8—H8106.2
C6—N1—C7112.16 (14)C10—C9—C14117.43 (17)
C2—C1—S1111.44 (15)C10—C9—C8120.70 (16)
C2—C1—H1124.3C14—C9—C8121.85 (17)
S1—C1—H1124.3C9—C10—C11122.00 (17)
C1—C2—C3112.55 (17)C9—C10—Cl1120.04 (14)
C1—C2—H2123.7C11—C10—Cl1117.94 (15)
C3—C2—H2123.7C12—C11—C10119.25 (19)
C4—C3—C2113.01 (17)C12—C11—H11120.4
C4—C3—C7121.62 (16)C10—C11—H11120.4
C2—C3—C7125.23 (16)C13—C12—C11120.25 (18)
C3—C4—C5124.61 (16)C13—C12—H12119.9
C3—C4—S1111.19 (14)C11—C12—H12119.9
C5—C4—S1124.14 (14)C12—C13—C14119.86 (17)
C4—C5—C6108.82 (15)C12—C13—H13120.1
C4—C5—H5A109.9C14—C13—H13120.1
C6—C5—H5A109.9C13—C14—C9121.20 (18)
C4—C5—H5B109.9C13—C14—H14119.4
C6—C5—H5B109.9C9—C14—H14119.4
H5A—C5—H5B108.3O1—C15—O2123.85 (18)
N1—C6—C5109.83 (15)O1—C15—C8127.06 (17)
N1—C6—H6A109.7O2—C15—C8109.08 (15)
C5—C6—H6A109.7O2—C16—C17104.11 (16)
N1—C6—H6B109.7O2—C16—H16A110.9
C5—C6—H6B109.7C17—C16—H16A110.9
H6A—C6—H6B108.2O2—C16—H16B110.9
N1—C7—C3108.85 (15)C17—C16—H16B110.9
N1—C7—H7A109.9H16A—C16—H16B109.0
C3—C7—H7A109.9C16—C17—Cl2108.60 (15)
N1—C7—H7B109.9C16—C17—H17A110.0
C3—C7—H7B109.9Cl2—C17—H17A110.0
H7A—C7—H7B108.3C16—C17—H17B110.0
N1—C8—C9110.25 (14)Cl2—C17—H17B110.0
N1—C8—C15116.67 (15)H17A—C17—H17B108.4
C4—S1—C1—C20.79 (17)N1—C8—C9—C1078.1 (2)
S1—C1—C2—C3−0.9 (2)C15—C8—C9—C10−151.36 (16)
C1—C2—C3—C40.6 (2)N1—C8—C9—C14−100.15 (19)
C1—C2—C3—C7−175.08 (19)C15—C8—C9—C1430.3 (2)
C2—C3—C4—C5−177.23 (17)C14—C9—C10—C110.9 (3)
C7—C3—C4—C5−1.3 (3)C8—C9—C10—C11−177.49 (16)
C2—C3—C4—S10.0 (2)C14—C9—C10—Cl1−177.49 (13)
C7—C3—C4—S1175.86 (15)C8—C9—C10—Cl14.1 (2)
C1—S1—C4—C3−0.42 (16)C9—C10—C11—C12−0.6 (3)
C1—S1—C4—C5176.78 (17)Cl1—C10—C11—C12177.76 (14)
C3—C4—C5—C6−12.0 (3)C10—C11—C12—C13−0.5 (3)
S1—C4—C5—C6171.12 (14)C11—C12—C13—C141.3 (3)
C8—N1—C6—C5157.57 (15)C12—C13—C14—C9−1.0 (3)
C7—N1—C6—C5−69.4 (2)C10—C9—C14—C130.0 (3)
C4—C5—C6—N144.8 (2)C8—C9—C14—C13178.30 (16)
C8—N1—C7—C3−174.85 (15)C16—O2—C15—O15.7 (3)
C6—N1—C7—C352.9 (2)C16—O2—C15—C8−175.09 (14)
C4—C3—C7—N1−18.0 (3)N1—C8—C15—O19.3 (3)
C2—C3—C7—N1157.41 (17)C9—C8—C15—O1−117.7 (2)
C6—N1—C8—C9−167.86 (15)N1—C8—C15—O2−169.92 (14)
C7—N1—C8—C960.6 (2)C9—C8—C15—O263.05 (18)
C6—N1—C8—C1565.0 (2)C15—O2—C16—C17167.79 (15)
C7—N1—C8—C15−66.6 (2)O2—C16—C17—Cl2−177.94 (12)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C7—H7a···O10.992.533.140 (2)120.0
C8—H8···Cl11.002.593.042 (2)107

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: FK2029).

References

  • Aubert, D., Ferrand, C. & Maffrand, J. P. (1985). US. Patent 4 529 596.
  • Bipin, P., Bhushan, L. B. & Bhushan, L. V. (2002). WO Patent 02/059128 A2.
  • Bouisset, M. & Radisson, J. (1991). US Patent 5 036 156.
  • Gurbel, P. A. & Tantry, U. S. (2007). Thromb. Res.120 , 311–321. [PubMed]
  • Muller, I., Besta, F., Schulz, C., Li, Z., Massberg, S. & Gawaz, M. (2003). Circulation 108, 2195–2197. [PubMed]
  • Rigaku/MSC (2005). CrystalClear and CrystalStructure Rigaku/MSC Inc., The Woodlands, Texas, USA.
  • Savi, P., Combalbert, J., Gaich, C., Rouchon, M. C., Maffrand, J. P., Berger, Y. & Herbert, J. M. (1994). Thromb. Haemost.72, 313–317. [PubMed]
  • Sharis, P. J., Cannon, C. P. & Loscalzo, J. (1998). Ann. Intern. Med.129, 394–405. [PubMed]
  • Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. [PubMed]

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