1-( 2-Bromo-5-methoxyphenyl )-8-chloro-6-( 2-fluoro-phenyl )-4 H-1 , 2 , 4-triazolo [ 4 , 3-a ] [ 1 , 4 ] benzodiazepine

1,4-Benzodiazepine derivatives are widely used as daytime sedatives, tranquilizers, sleep inducers, anaesthetics, anticonvulsants and muscle relaxants (Block et al., 1989; Di Braccio et al., 2001; Hollister, 1983; Moroz, 2004). Five-atom heterocyclic fused benzodiazepine ring systems occupy a prominent place among drugs for treatment of central nervous system (CNS) disorders (Robol et al., 1996; Wang et al., 1999; Novelli et al., 1999; Evans et al., 2001).

The title compound, (I), C 23 H 15 BrClFN 4 O, (Fig. 1), which appears to have promising physiological properties, comparable with those of diazepam (Valium), is a structural analogue of well known CNS depressant drugs such as midazolam, (II), and alprazolam, C 17 H 13 ClN 4 , (III). To confirm the structural relationship of (I) to these drugs, its crystal structure is presented here.
The bond distances within the five-membered ring (Table 1) suggest that the C9-N3 and C16-N4 bonds have far more double-bond character than do N3-N4, C9-N2 and C16-N2, i.e. the canonical form shown in the scheme is probably the most significant contributor to the overall structure. The bond angle sums about atoms C7 (359.6 ), C9 (360.0 ), C16 (360.0 ) and N2 (359.7 ) suggest that all these atoms are well regarded as being sp 2 hybridized.
The seven-membered diazepine ring (C7/C11/C10/N2/C9/ C8/N1) in (I) is far from planar, and its shape approximates to a twist chair (Hendrickson, 1967) with a pseudo-twofold axis passing through C9 and the C7-C11 bond midpoint, if such a description is valid for a seven-membered ring containing multiple bonds. However, the pattern of the torsion angles of the seven-membered ring is also close to reflecting C s symmetry. In the structure of alprazolam dihydrate (Vega et al., 1999), a similar ring conformation was described as a boat. In this description applied to (I), atoms C7, C9, N1 and N2 form the bottom of the boat (r.m.s. deviation from the mean plane = 0.017 Å ), C8 the prow, and C10 and C11 the stern [deviations from the C7/C9/N1/N2 mean plane = 0.686 (3), 0.666 (3) and 0.698 (3) Å , respectively].
The crystal packing in (I), shown in Fig. 2, results in (101) sheets of molecules. Apart from a possible C-HÁ Á ÁN interaction (Table 2), which might help to provide coherence between adjacent (101) sheets, there are few significant intermolecular interactions in (I). Anystacking must be extremely weak, the smallest centroidÁ Á Ácentroid separation being 4.11 Å . No C-HÁ Á Á interactions were identified in a PLATON (Spek, 2003) analysis of (I).
H atoms were positioned geometrically (C-H = 0.95-0.99 Å ) and refined as riding, with U iso (H) = 1.2U eq (carrier) or 1.5U eq (methyl carrier). The methyl group was rotated to fit the electron density.
Data collection: COLLECT (Nonius, 1998); cell refinement: SCALEPACK (Otwinowski & Minor, 1997); data reduction: SCALEPACK, DENZO (Otwinowski & Minor, 1997) and SORTAV (Blessing, 1995); program(s) used to solve structure: SHELXS97 (Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 (Farrugia, 1997); software used to prepare material for publication: SHELXL97. 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 F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger.