3-Bromo-propyl 2-(2-chloro-phen-yl)-2-(4,5,6,7-tetra-hydro-thieno[3,2-c]pyridin-5-yl)acetate.

Abstract

In the crystal structure of the title compound, C(18)H(19)BrClNO(2)S, weak C-H⋯O inter-actions help to establish the packing.

Full text

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3-Bromopropyl 2-(2-chlorophenyl)-2-
(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-
5-yl)acetate
Ji-Fang Chen,aYing Liu,b* Jing-Yang Wangband Deng-Ke
Liub
aMaterials Science and Engineering, Tianjin Polytechnic University, Tianjin 300160,
People’s Republic of China, andbTianjin Institute of Pharmaceutical Research,
Tianjin 300193, People’s Republic of China
Correspondence e-mail: liudk@tjipr.com
Received 14 October 2010; accepted 17 December 2010
Key indicators: single-crystal X-ray study; T = 113 K; mean ?(C–C) = 0.003 A ˚;
R factor = 0.035; wR factor = 0.097; data-to-parameter ratio = 16.3.
In the crystal structure of the title compound, C18H19BrCl-
NO2S, weak C—H???O interactions help to establish the
packing.
Related literature
The title compound is a derivative of the antiplatelet agent
clopidogrel [systematic name (+)-(S)-methyl 2-(2-chloro
phenyl)-2-(6,7-dihydrothieno[3,2-c]pyridin-5(4H)-yl)acetate].
For background to the bioactivity and applications of clopi-
dogrel, see: Muller et al. (2003); Savi et al. (1994); Sharis et al.
(1998). For the synthesis of other derivatives with thienopyr-
idine, see: Aubert et al. (1985); Bouisset & Radisson (1991);
Savi et al. (1992); Bipin et al. (2002); Eric & Hiralal (1989); Liu
et al. (2008); Silva (2004).
Experimental
Crystal data
C18H19BrClNO2S
Mr= 428.76
Monoclinic, P21=n
a = 8.5707 (17) A˚
b = 18.414 (4) A˚
c = 12.206 (2) A˚
? = 106.89 (3)?
V = 1843.3 (7) A˚3
Z = 4
Cu K? radiation
? = 5.52 mm?1
T = 113 K
0.22 ? 0.18 ? 0.14 mm
Data collection
Rigaku Saturn diffractometer
Absorption correction: multi-scan
(CrystalClear; Rigaku, 2005)
Tmin= 0.377, Tmax= 0.512
18506 measured reflections
3546 independent reflections
3220 reflections with I > 2?(I)
Rint= 0.055
Refinement
R[F2> 2?(F2)] = 0.035
wR(F2) = 0.097
S = 1.04
3546 reflections
217 parameters
H-atom parameters constrained
??max= 0.34 e A˚?3
??min= ?0.69 e A˚?3
Table 1
Hydrogen-bond geometry (A˚,?).
D—H???A
C2—H2???O1i
C7—H7A???O1
C8—H8???Cl1
C16—H16B???Br1
Symmetry code: (i) x ?1
D—HH???AD???AD—H???A
0.95
0.99
1.00
0.99
2.43
2.50
2.58
2.91
3.340 (3)
3.103 (3)
3.110 (2)
3.323 (3)
161
119
113
106
2;?y þ3
2;z ?1
2.
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,
SHELXTL (Sheldrick, 2008); software used to prepare material for
publication: CrystalStructure (Rigaku/MSC, 2005).
2008); moleculargraphics:
The authors thank Mr Hai-Bin Song of Nankai University,
for the X-ray crystallographic determination and for helpful
suggestions.
Supplementary data and figures for this paper are available from the
IUCr electronic archives (Reference: RK2241).
References
Aubert, D., Ferrand, C. & Maffrand, J. P. (1985). US Patent 4 529 596.
Bipin, P., Bhushan, L. V. & Bhushan, L. B. (2002). WO Patent 02/059128 A2.
Bouisset, M. & Radisson, J. (1991). US Patent 5 036 156.
Eric, L. & Hiralal, N. K. (1989). Eur. Patent 0 342 118 A1.
Liu, D. K., Liu, Y., Liu, M., Zhang, S. J., Cheng, D., Jin, L. Y., Xu, W. R. & Liu,
C. X. (2008). CN Patent 101284838A.
Muller, I., Besta, F., Schulz, C., Li, Z., Massberg, S. & Gawaz, M. (2003).
Circulation, 108, 2195–2197.
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.
Savi, P., Herbert, J. M., Pflieger, A. M., Dol, F., Delebassee, D., Combalbert, J.,
Defreyn, G. & Maffrand, J. P. (1992). Biochem. Pharmacol. 44, 527–532.
Sharis, P. J., Cannon, C. P. & Loscalzo, J. (1998). Ann. Intern. Med. 129, 394–
405.
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.
Silva, R. A. (2004). WO Patent 2004/094374 A2.
organic compounds
Acta Cryst. (2011). E67, o221doi:10.1107/S1600536810053134 Chen et al.
o221
Acta Crystallographica Section E
Structure Reports
Online
ISSN 1600-5368

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supplementary materials

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supplementary materials
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Acta Cryst. (2011). E67, o221 [ doi:10.1107/S1600536810053134 ]
3-Bromopropyl 2-(2-chlorophenyl)-2-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl)acetate
J.-F. Chen, Y. Liu, J.-Y. Wang and D.-K. Liu
Comment
Clopidogrel is an oral, thienopyridine class antiplatelet agent used to inhibit blood clots in coronary artery disease, peripher-
al vascular disease, and cerebrovascular disease (Muller et al., 2003; Aubert et al., 1985; Bipin et al., 2002; Bouisset &
Radisson, 1991; Eric & Hiralal, 1989; Liu et al., 2008; Silva 2004; Savi et al., 1992; Savi et al., 1994; Sharis et al., 1998).
The molecular structure of the title compound (Fig. 1), a derivative of clopidogrel, is reported here.
As shown in Fig. 1, there is a chiral carbon (C8) in the compound, and the benzene ring, the ester chain and the thien-
opyridine group are all linked to C8 and a molecular chiral center is formed. The thiophene ring of the thienopyridine group
forms a plane and the C9–C14 benzen ring forms another plane. The dihedral angle formed between them is 65.46 (9)°. The
packing molecules in crystal is consolidated by weak C—H···O, C—H···Cl and C—H···Br interactions.
Experimental
The title compound was prepared according to the literature (Aubert et al., 1985). A mixture of α–bromo(2–chloro)phenyl
acetic acid (5 g, 20 mmol), 3–bromo–1–propanol (20 g, 144 mmol) and p–toluenesulfonic acid (1.0 g, 5.8 mmol) in toluene
(50 ml) was refluxed for 2 h. The reaction mixture was washed with saturated sodium bicarbonate (100 ml) and then with
distilled water (50 ml), dried with sodium sulfate and evaporated, to give colourless oil (98% yield). The colourless oil
obtained above, K2CO3 (36 mmol) and 4,5,6,7–tetrahydro thieno[3,2–c] pyridin (22 mmol) in toluene (50 ml) were stirred
at room temperature for 3 h. After removing the insoluble solid by filtration, the filtrate was concentrated and separated by
flash chromatography to provide the target compound (yield 87%). Colourless single crystals were grown from a solution
of petroleum ether and ethyl acetate (1:1 v/v).
Refinement
All the H atoms were positioned geometrically and refined as riding atoms, with C—H = 1.00Å for methine, 0.99Å for
methylene and C—H = 0.95Å for the other groups with Uiso(H) = 1.2Ueq(C).
Figures
Fig. 1. The molecular structure of title compound with the atom numbering scheme. Dis-
placement ellipsoids are drawn at the 50% probability level. H atoms are presented as a small
spheres of arbitrary radius.

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3-Bromopropyl 2-(2-chlorophenyl)-2-(4,5,6,7- tetrahydrothieno[3,2-c]pyridin-5-yl)acetate
Crystal data
C18H19BrClNO2S
F(000) = 872
Dx = 1.545 Mg m−3
Cu Kα radiation, λ = 1.54187 Å
Cell parameters from 2390 reflections
θ = 27.5–72.3°
µ = 5.52 mm−1
T = 113 K
Prism, colourless
Mr = 428.76
Monoclinic, P21/n
Hall symbol: -P 2yn
a = 8.5707 (17) Å
b = 18.414 (4) Å
c = 12.206 (2) Å
β = 106.89 (3)°
V = 1843.3 (7) Å3
Z = 4
0.22 × 0.18 × 0.14 mm
Data collection
Rigaku Saturn
diffractometer
Radiation source: fine-focus sealed tube
multilayer
Detector resolution: 14.63 pixels mm-1
ω scans
Absorption correction: multi-scan
(CrystalClear; Rigaku, 2005)
Tmin = 0.377, Tmax = 0.512
18506 measured reflections
3546 independent reflections
3220 reflections with I > 2σ(I)
Rint = 0.055
θmax = 72.5°, θmin = 4.5°
h = −10→10
k = −22→22
l = −14→11
Refinement
Refinement on F2
Primary atom site location: structure-invariant direct
methods
Secondary atom site location: difference Fourier map
Hydrogen site location: inferred from neighbouring
sites
Least-squares matrix: full
R[F2 > 2σ(F2)] = 0.035
wR(F2) = 0.097
H-atom parameters constrained
S = 1.04
w = 1/[σ2(Fo2) + (0.0543P)2 + 1.1251P]
where P = (Fo2 + 2Fc2)/3
(Δ/σ)max = 0.001
Δρmax = 0.34 e Å−3
Δρmin = −0.69 e Å−3
3546 reflections
217 parameters
0 restraints
Special details
Geometry. All s.u.'s (except the s.u. in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The
cell s.u.'s are taken into account individually in the estimation of s.u.'s in distances, angles and torsion angles; correlations between

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supplementary materials
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s.u.'s in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell s.u.'s is
used for estimating s.u.'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, convention-
al 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)
x
0.70621 (4)
0.63184 (7)
0.70637 (7)
0.7341 (2)
0.57129 (19)
0.7310 (2)
0.5719 (3)
0.5313
0.5302 (3)
0.4566
0.6102 (2)
0.7094 (3)
0.8122 (3)
0.9276
0.8052
0.7515 (3)
0.6459
0.8306
0.5925 (3)
0.5879
0.4892
0.6982 (2)
0.5998
0.8421 (3)
0.8233 (3)
0.9545 (3)
0.9384
1.1084 (3)
1.1986
1.1313 (3)
1.2378
0.9995 (3)
1.0166
0.6710 (3)
0.5484 (4)
0.4978
0.6545
0.4393 (3)
y
0.800075 (19)
0.55788 (3)
0.51762 (3)
0.75560 (8)
0.72271 (8)
0.60648 (9)
0.58635 (13)
0.5965
0.62460 (12)
0.6644
0.59768 (11)
0.54013 (11)
0.50420 (12)
0.5188
0.4508
0.52699 (11)
0.5030
0.5112
0.62862 (11)
0.6823
0.6113
0.62768 (11)
0.6012
0.61285 (11)
0.58555 (11)
0.57802 (12)
0.5594
0.59798 (13)
0.5940
0.62372 (14)
0.6360
0.63170 (12)
0.6503
0.70946 (11)
0.79869 (12)
0.8250
0.8217
0.80103 (14)
z
0.63501 (3)
0.47473 (5)
−0.19215 (5)
0.22244 (14)
0.32887 (14)
0.15415 (15)
−0.2481 (2)
−0.3276
−0.16565 (19)
−0.1807
−0.05354 (18)
−0.05401 (18)
0.05215 (19)
0.0665
0.0430
0.15262 (18)
0.1464
0.2252
0.05604 (18)
0.0509
0.0679
0.26063 (17)
0.2680
0.36541 (18)
0.46718 (19)
0.5653 (2)
0.6338
0.5619 (2)
0.6287
0.4615 (2)
0.4589
0.3643 (2)
0.2961
0.26505 (19)
0.3521 (2)
0.2798
0.3907
0.4279 (2)
Uiso*/Ueq
0.04494 (13)
0.02681 (15)
0.02410 (14)
0.0255 (3)
0.0229 (3)
0.0160 (3)
0.0247 (5)
0.030*
0.0215 (4)
0.026*
0.0173 (4)
0.0186 (4)
0.0212 (4)
0.025*
0.025*
0.0190 (4)
0.023*
0.023*
0.0190 (4)
0.023*
0.023*
0.0168 (4)
0.020*
0.0181 (4)
0.0205 (4)
0.0263 (5)
0.032*
0.0300 (5)
0.036*
0.0310 (5)
0.037*
0.0245 (5)
0.029*
0.0185 (4)
0.0314 (6)
0.038*
0.038*
0.0340 (6)
Br1
Cl1
S1
O1
O2
N1
C1
H1
C2
H2
C3
C4
C5
H5A
H5B
C6
H6A
H6B
C7
H7A
H7B
C8
H8
C9
C10
C11
H11
C12
H12
C13
H13
C14
H14
C15
C16
H16A
H16B
C17