Darifenacin hydrobromide

In the title compound {systematic name: (S)-3-[(aminocarbonyl)diphenylmethyl]-1-[2-(2,3-dihydrobenzofuran-5-yl)ethyl]pyrrolidinium bromide}, C28H31N2O2 +·Br−, the pyrrolidine rings adopts an envelope conformation. The two phenyl rings make a dihedral angle of 72.5 (1)°. The four coplanar atoms of the pyrrolidine ring makes dihedral angles of 33.1 (2) and 82.8 (2)° with the two phenyl rings. The molecular conformation is influenced by a C—H⋯O interaction. In the crystal packing, there are two N—H⋯Br hydrogen bonds running in opposite directions. They appear to form C(10) and C(9) chain motifs in the unit cell. In addition, the molecular packing is further stabilized by C—H⋯Br and C—H⋯O hydrogen bonds. The C atom bonded to the benzofuran ring system is disordered in a 0.66:0.34 ratio.

In the title compound {systematic name: (S)-3-[(aminocarbonyl)diphenylmethyl]-1-[2-(2,3-dihydrobenzofuran-5-yl)ethyl]pyrrolidinium bromide}, C 28 H 31 N 2 O 2 + ÁBr À , the pyrrolidine rings adopts an envelope conformation. The two phenyl rings make a dihedral angle of 72.5 (1) . The four coplanar atoms of the pyrrolidine ring makes dihedral angles of 33.1 (2) and 82.8 (2) with the two phenyl rings. The molecular conformation is influenced by a C-HÁ Á ÁO interaction. In the crystal packing, there are two N-HÁ Á ÁBr hydrogen bonds running in opposite directions. They appear to form C(10) and C(9) chain motifs in the unit cell. In addition, the molecular packing is further stabilized by C-HÁ Á ÁBr and C-HÁ Á ÁO hydrogen bonds. The C atom bonded to the benzofuran ring system is disordered in a 0.66:0.34 ratio.

Comment
Darifenacin is a selective muscarinic M3-receptor antagonist that has been evaluated in clinical trials in patients with overative bladder syndrome using a controlled-release formulation (Chapple, 2004;Croom & Keating, 2004;Haab et al., 2004;Levin et al., 2008). As no crystal structure of the title compound has yet been published, we have undertaken the singlecrystal X-ray diffraction study and report here its results.
The X-ray study confirmed the molecular structure and atomic connectivity for (I), as illustrated in Fig. 1. The bond length of C12-O1 [1.222 (5) Å] confirms the double bond character for amide group, as evidenced by Allen et al. (1987). The C-N and C--O bond lengths in the pyrrolidine and furan rings are comparable to the related literature values (Selvanayagam et al., 2005).
The dihedral angle between the fused benzene and furan rings of the benzofuran system is 4.6 (2)°. The best plane of the pyrrolidine ring and benzofuran system make a dihedral angle of 44.5 (2)°. Two phenyl rings (A and B) are oriented with a dihedral angle of 72.5 (2)°. These two phenyl rings make a dihedral angle of 33.1 (2) and 82.8 (2)°, respectively with pyrroldine ring.
An intramolecular C-H···O interaction is observed in (I) ( Table 2). In the crystal packing, the H1 and H2NB atoms bonded to N1 and N2 forms a strong N-H···Br hydrogen bonds which leads a C(10) and C(9) chain motif in the unit cell running in the opposite directions ( Fig. 2). In addition to this the molecular packing is further stabilized by strong C-H···Br hydrogen bonds and C-H···O interactions (Table 2).

Experimental
In order to obtain crystals suitable for X-ray study, darifenacin hydrobromide was dissolved in a methanol-water solution (80:20v/v); the solvents were then allowed to evaporate slowly.

Refinement
Atoms H2NA and H2NB were located from a difference Fourier map; the remaining H atoms were positioned geometrically and were treated as riding on their parent C and N atoms with C-H distances of 0.93-0.97 Å, N-H distance of 0.91 Å supplementary materials sup-2 and with U iso = 1.2U eq (C or N) for other H. Atom C20 was found to be disordered over two positions. The occupancies were kept fixed at 0.34 and 0.66 during the last cycles of refinement. Fig. 1. The structure and atom-numbering scheme for (I); displacement ellipsoids are drawn at the 30% probability level. For the sake of clarity, H atoms, not involved in hydrogen bonds, have been omitted.