Dabigatran etexilate tetra­hydrate

Liu, H.-Q.; Zhang, W.-G.; Cai, Z.-Q.; Xu, W.-R.; Shen, X.-P.

doi:10.1107/S1600536812046673

Volume 68
Part 12
Page o3385
December 2012

Received 3 November 2012
Accepted 12 November 2012
Online 17 November 2012

Key indicators
Single-crystal X-ray study
T = 113 K
Mean (C-C) = 0.002 Å
Disorder in main residue
R = 0.039
wR = 0.103
Data-to-parameter ratio = 16.8
Details

Dabigatran etexilate tetrahydrate

Hong-Qiang Liu,^a,^b Wei-Guang Zhang,^a,^b Zhi-Qiang Cai,^a Wei-Ren Xu ^a and Xiu-Ping Shen ^a ^*

^aState Key Laboratory of Drug Delivery Technology and Pharmacokinetics, Tianjin Centre for New Drug Safety Assessment and Research, Tianjin 300193, People's Republic of China, and ^bGraduate School, Tianjin University of Traditional Chinese Medicine, Tianjin 300193, People's Republic of China
Correspondence e-mail: xiupingshen@yahoo.com

In the title compound, C₃₄H₄₁N₇O₅·4H₂O (systematic name: ethyl 3-{[2-({4-[(Z)-amino(hexyloxycarbonylimino)methyl]anilino}methyl)-1-methylbenzimidazole-5-carbonyl]pyridin-2-ylamino}propanoate tetrahydrate), the benzene and pyridine rings form dihedral angles of 5.4 (1) and 43.8 (1)°, respectively, with the benzimidazole mean plane. The terminal butyl group is disordered over two conformations in a 0.756 (10):0.244 (10) ratio. There is an intramolecular N-HO hydrogen bond present. In the crystal, the water molecules are involved in the formation of O-HO, O-HN and N-HO hydrogen bonds, which link the components into layers parallel to the ab plane.

Related literature

For background to the anticoagulant drug dabigatran etexilate, see: Nagarakanti & Ellis (2012); Van Ryn et al. (2010).

Experimental

Crystal data

C₃₄H₄₁N₇O₅·4H₂O
M_r = 699.80
Triclinic, $[P \overline 1]$
a = 9.1140 (13) Å
b = 10.9700 (14) Å
c = 18.3830 (17) Å
= 88.51 (1)°
= 85.455 (9)°
= 83.034 (12)°
V = 1818.4 (4) Å³
Z = 2
Mo K radiation
= 0.09 mm^-1
T = 113 K
0.22 × 0.20 × 0.18 mm

Data collection

Rigaku Saturn 724 CCD area-detector diffractometer
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2009) T_min = 0.980, T_max = 0.983
23569 measured reflections
8627 independent reflections
5187 reflections with I > 2(I)
R_int = 0.036

Refinement

R[F² > 2(F²)] = 0.039
wR(F²) = 0.103
S = 0.96
8627 reflections
513 parameters
40 restraints
H atoms treated by a mixture of independent and constrained refinement
_max = 0.42 e Å^-3
_min = -0.37 e Å^-3

Table 1
Hydrogen-bond geometry (Å, °)

D-HA	D-H	HA	DA	D-HA
N1-H1O7ⁱ	0.896 (17)	1.980 (18)	2.8468 (16)	162.5 (15)
N1-H2O1	0.902 (15)	1.931 (16)	2.6281 (16)	132.7 (13)
O6-H8N5	0.912 (19)	1.88 (2)	2.7938 (16)	176.3 (16)
O6-H16O3ⁱⁱ	0.84 (2)	2.00 (2)	2.8373 (15)	172.1 (18)
O7-H17O8	0.861 (19)	1.954 (19)	2.8061 (16)	170.2 (18)
O7-H18O9	0.881 (18)	1.871 (19)	2.7513 (15)	176.5 (17)
O9-H20N2	0.93 (2)	2.00 (2)	2.9226 (16)	168.8 (19)
O9-H20O2	0.93 (2)	2.43 (2)	3.1126 (14)	129.6 (16)
O9-H24N7ⁱⁱⁱ	0.844 (19)	2.050 (19)	2.8918 (16)	175.5 (18)
O8-H25O6	0.84 (2)	2.04 (2)	2.8689 (17)	171 (2)
O8-H32O6ⁱⁱⁱ	0.94 (2)	1.89 (2)	2.8291 (17)	175.3 (17)
Symmetry codes: (i) x-1, y, z; (ii) -x+1, -y+2, -z+2; (iii) -x+1, -y+1, -z+2.

Data collection: CrystalClear (Rigaku/MSC, 2009); 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: SHELXTL.

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: CV5357 ).

References

Nagarakanti, R. & Ellis, C. R. (2012). Clin. Ther. 34, 2051-2060.
Rigaku/MSC (2009). CrystalClear. Rigaku/MSC, The Woodlands, Texas, USA.
Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.
Van Ryn, J., Stangier, J., Haertter, S., Liesenfeld, K. H., Wienen, W., Feuring, M. & Clemens, A. (2010). Thromb. Haemost. 103, 1116-1127.

organic compounds