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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 [sigma](C-C) = 0.002 Å
Disorder in main residue
R = 0.039
wR = 0.103
Data-to-parameter ratio = 16.8
Details
Open access

Dabigatran etexilate tetrahydrate

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-H...O hydrogen bond present. In the crystal, the water molecules are involved in the formation of O-H...O, O-H...N and N-H...O 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[Nagarakanti, R. & Ellis, C. R. (2012). Clin. Ther. 34, 2051-2060.]); Van Ryn et al. (2010[Van Ryn, J., Stangier, J., Haertter, S., Liesenfeld, K. H., Wienen, W., Feuring, M. & Clemens, A. (2010). Thromb. Haemost. 103, 1116-1127.]).

[Scheme 1]

Experimental

Crystal data
  • C34H41N7O5·4H2O

  • Mr = 699.80

  • Triclinic, [P \overline 1]

  • a = 9.1140 (13) Å

  • b = 10.9700 (14) Å

  • c = 18.3830 (17) Å

  • [alpha] = 88.51 (1)°

  • [beta] = 85.455 (9)°

  • [gamma] = 83.034 (12)°

  • V = 1818.4 (4) Å3

  • Z = 2

  • Mo K[alpha] radiation

  • [mu] = 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[Rigaku/MSC (2009). CrystalClear. Rigaku/MSC, The Woodlands, Texas, USA.]) Tmin = 0.980, Tmax = 0.983

  • 23569 measured reflections

  • 8627 independent reflections

  • 5187 reflections with I > 2[sigma](I)

  • Rint = 0.036

Refinement
  • R[F2 > 2[sigma](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

  • [Delta][rho]max = 0.42 e Å-3

  • [Delta][rho]min = -0.37 e Å-3

Table 1
Hydrogen-bond geometry (Å, °)

D-H...A D-H H...A D...A D-H...A
N1-H1...O7i 0.896 (17) 1.980 (18) 2.8468 (16) 162.5 (15)
N1-H2...O1 0.902 (15) 1.931 (16) 2.6281 (16) 132.7 (13)
O6-H8...N5 0.912 (19) 1.88 (2) 2.7938 (16) 176.3 (16)
O6-H16...O3ii 0.84 (2) 2.00 (2) 2.8373 (15) 172.1 (18)
O7-H17...O8 0.861 (19) 1.954 (19) 2.8061 (16) 170.2 (18)
O7-H18...O9 0.881 (18) 1.871 (19) 2.7513 (15) 176.5 (17)
O9-H20...N2 0.93 (2) 2.00 (2) 2.9226 (16) 168.8 (19)
O9-H20...O2 0.93 (2) 2.43 (2) 3.1126 (14) 129.6 (16)
O9-H24...N7iii 0.844 (19) 2.050 (19) 2.8918 (16) 175.5 (18)
O8-H25...O6 0.84 (2) 2.04 (2) 2.8689 (17) 171 (2)
O8-H32...O6iii 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[Rigaku/MSC (2009). CrystalClear. Rigaku/MSC, The Woodlands, Texas, USA.]); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); 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.  [CrossRef] [ChemPort] [PubMed]
Rigaku/MSC (2009). CrystalClear. Rigaku/MSC, The Woodlands, Texas, USA.
Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.  [CrossRef] [details]
Van Ryn, J., Stangier, J., Haertter, S., Liesenfeld, K. H., Wienen, W., Feuring, M. & Clemens, A. (2010). Thromb. Haemost. 103, 1116-1127.  [ISI] [CrossRef] [ChemPort] [PubMed]


Acta Cryst (2012). E68, o3385  [ doi:10.1107/S1600536812046673 ]

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