Supporting information
Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807030103/fb2049sup1.cif | |
Structure factor file (CIF format) https://doi.org/10.1107/S1600536807030103/fb2049Isup2.hkl |
CCDC reference: 655024
Preparation is depicted in Scheme 2. A solution of ethyl 3a-methyl-3-(4-nitrophenyl)-5-phenyl-3a,4-dihydro [1,2,4]triazolo[4,3-a][1,5]benzodiazepine-1-carboxylate (1) (0.65 mmol) and 4-methyl-N-phenylbenzohydrazonoyl chloride (2) (0.65 mmol) in dichloromethane (20 ml) was prepared; triethylamine (0.9 mmol) dissolved in dichloromethane (5 ml) was added dropwise. The mixture was stirred for 7 days at room temperature, washed several times with water. The aqueous phase was then extracted with dichloromethane (3 x 20 ml). The organic layer was dried over anhydrous sodium sulfate and then concentrated under reduced pressure. Then it was purified by chromatography on silica gel column (eluent: hexane/ethyl acetate), the isolated product was recrystallized from ethanol and the diastereoisomer 3X (RS/SR) was obtained in 50% yield. The diatereoisomer 3Y (RR/SS) was not isolated.
Melting point: 479–481 K. 1H NMR (CDCl3, δ, p.p.m.): 1.20 (t, 3H, CH3CH2O), 1.80 (s, 3H, CH3—C3a), 2.35 (s, 3H, CH3—Ar), 2.90, 3.70 (2 d, J = 15 Hz, 2H, CH2–4), 4.29 (m, 2H, CH3CH2O), 6.65- 7.73 (m, 22H, H—Ar). 13C NMR (CDCl3, δ, p.p.m.): 14.31 (CH3CH2O), 21.81 (CH3—Ar), 26.92 (CH3—C3a), 41.22 (CH2–C4), 62.42 (CH3CH2O), 85.93, 90.05 (C3a, C4a), 158.06 (C=O). Mass spectrum: m/z 678 (M+, 100%). Anal. calc. for C40H35N7O4: C, 70.90; H, 5.17; N, 14.48; found: C, 70.56; H, 5.47; N, 14.26%.
All the H atoms were found in a difference Fourier map. Nevertheless, the H atoms were refined using a riding model with Caryl—H = 0.93 Å, Cmethylene—H = 0.97 Å and Cmethyl—H = 0.96 Å. Uiso(H) = 1.2Ueq(C) except for Uiso(Hmethyl) = 1.5Ueq(Cmethyl).
Several benzodiazepine derivatives containing additional rings have proven to be of pharmacological interest (Sternbach, 1978; Bellantuono et al., 1980). For years, our research team is interested in the synthesis of such compounds by cyclization reactions onto 1,4-benzodiazepines (Benelbaghdadi et al., 1997) and 1,5-benzodiazepines (Baouid et al., 1994; Boudina et al., 2006). Within this context, we have studied the 1,3-dipolar cycloadditions of diarylnitrilimines with ethyl 3a-methyl-3-(4-nitrophenyl)-5-phenyl-3a,4-dihydro[1,2,4] triazolo[4,3-a][1,5]benzodiazepine-1-carboxylate (1) (Baouid et al., 1994).
From the spectral data (mass; 1H– 13C– NMR) possible diastereoisomers 3X or 3Y of the cycloadduct were established. In particular, the chemical shifts of 86 and 90 p.p.m. observed for the quaternary carbon atoms C8a and C9a have ruled out the formation of the alternative regioisomer that would be formed by a reverse addition of the dipolar compound (2) on C=N of the ethyl 3a-methyl-3-(4-nitrophenyl)-5-phenyl-3a,4-dihydro[1,2,4]triazolo[4,3-a] [1,5]benzodiazepine-1-carboxylate, (1). For the alternative regioisomer chemical shifts of about 50 p.p.m. would be expected (Begtrup et al. 1988). However, the NMR spectroscopic data (1H and 13C) did not allow to distinguish between the two diastereoisomers 3X (RS/SR) and 3Y (RR/SS).
On the other hand, the present crystallographic study has confirmed the formation of the (3X) trans diastereoisomer with its two asymmetric carbon atoms C8a and C9a displaying respective (RS,SR) absolute configurations. The 1,3-dipolar cycloaddition of diarylnitrilimine on ethyl 3a-methyl-3-(4-nitrophenyl)-5-phenyl-3a,4-dihydro[1,2,4]triazolo[4,3-a] [1,5]benzodiazepine-1-carboxylate, (1), is completely regio- and diastereoselective.
The molecule of the title compound (Scheme 1; Fig. 1) is composed of a tetracylic core formed by a benzodiazepine bicycle and two 5-membered rings (triazoles) that are differently substituted.
The 7-membered diazepine ring displays a boat conformation; the atoms N5, N13, C8a and C9a form the "bottom" of the boat. The atoms (C8a, C9, C9a) form the "prow" while (N5, N13, C13a, C4a) form the "stern". The angles between the best planes of the "bottom" and the "prow" and between the "bottom" and the "stern" equal to 47.5 (3) and 53.2 (2)°, respectively.
The bonds within the triazole rings are comparable with those reported in the literature for related compounds, as for example in 1-(2-Bromo-5-methoxyphenyl)-8-chloro-6-(2-fluorophenyl)- 4H-1,2,4-triazolo[4,3-a][1,4]benzodiazepine (Harrison et al., 2005).
For related literature, see: Baouid et al. (1994); Begtrup et al. (1988); Bellantuono et al. (1980); Benelbaghdadi et al. (1997); Boudina et al. (2006); Harrison et al. (2005); Sternbach (1978).
Data collection: CrysAlis CCD (Oxford Diffraction, 2004); cell refinement: CrysAlis CCD; data reduction: CrysAlis RED (Oxford Diffraction, 2004); program(s) used to solve structure: SHELXS97 (Sheldrick, 1990); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEP-3 for Windows (Version 1.075; Farrugia, 1997); software used to prepare material for publication: WinGX (Farrugia, 1999).
C40H35N7O4 | F(000) = 1424 |
Mr = 677.75 | Dx = 1.282 Mg m−3 |
Monoclinic, P21/c | Melting point = 479–481 K |
Hall symbol: -P2ybc | Mo Kα radiation, λ = 0.71073 Å |
a = 9.4951 (6) Å | Cell parameters from 6080 reflections |
b = 21.436 (1) Å | θ = 3.1–25.0° |
c = 18.885 (1) Å | µ = 0.09 mm−1 |
β = 114.011 (5)° | T = 293 K |
V = 3511.2 (4) Å3 | Parallelepiped, orange |
Z = 4 | 0.47 × 0.36 × 0.13 mm |
Oxford Diffraction Xcalibur CCD diffractometer | 4822 reflections with I > 2σ(I) |
Radiation source: fine-focus sealed tube | Rint = 0.058 |
Graphite monochromator | θmax = 32.4°, θmin = 3.1° |
ω scans | h = −14→13 |
59538 measured reflections | k = −31→31 |
6080 independent reflections | l = −25→25 |
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.077 | Hydrogen site location: difference Fourier map |
wR(F2) = 0.213 | H-atom parameters constrained |
S = 1.14 | w = 1/[σ2(Fo2) + (0.098P)2 + 1.8217P] where P = (Fo2 + 2Fc2)/3 |
6080 reflections | (Δ/σ)max = 0.001 |
463 parameters | Δρmax = 0.36 e Å−3 |
0 restraints | Δρmin = −0.27 e Å−3 |
136 constraints |
C40H35N7O4 | V = 3511.2 (4) Å3 |
Mr = 677.75 | Z = 4 |
Monoclinic, P21/c | Mo Kα radiation |
a = 9.4951 (6) Å | µ = 0.09 mm−1 |
b = 21.436 (1) Å | T = 293 K |
c = 18.885 (1) Å | 0.47 × 0.36 × 0.13 mm |
β = 114.011 (5)° |
Oxford Diffraction Xcalibur CCD diffractometer | 4822 reflections with I > 2σ(I) |
59538 measured reflections | Rint = 0.058 |
6080 independent reflections |
R[F2 > 2σ(F2)] = 0.077 | 0 restraints |
wR(F2) = 0.213 | H-atom parameters constrained |
S = 1.14 | Δρmax = 0.36 e Å−3 |
6080 reflections | Δρmin = −0.27 e Å−3 |
463 parameters |
Experimental. A reference frame was measured every 25 frames. No significant intensity decay was observed. |
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 F2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F2, conventional 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. All H atoms were placed in geometrically idealized positions via HFIX instructions and constrained to ride on their parent atoms, with Uiso(H) = 1.5Ueq(C) for methyl groups and Uiso(H) = 1.2Ueq for others hydrogen atoms. |
x | y | z | Uiso*/Ueq | ||
N13 | 0.8798 (3) | 0.64005 (11) | 0.73679 (13) | 0.0453 (6) | |
N10 | 0.9424 (3) | 0.73291 (11) | 0.70030 (13) | 0.0480 (6) | |
N8 | 0.6017 (3) | 0.59766 (11) | 0.52064 (13) | 0.0466 (6) | |
O15 | 0.7815 (3) | 0.43645 (12) | 0.63243 (16) | 0.0766 (7) | |
C19 | 0.5837 (3) | 0.61582 (14) | 0.44793 (16) | 0.0458 (7) | |
C9A | 0.8549 (3) | 0.67390 (12) | 0.66433 (15) | 0.0430 (6) | |
N11 | 1.0667 (3) | 0.71352 (12) | 0.76823 (14) | 0.0535 (6) | |
N5 | 0.6045 (3) | 0.58458 (12) | 0.63816 (14) | 0.0539 (6) | |
C12 | 1.0256 (3) | 0.66285 (14) | 0.79014 (16) | 0.0483 (7) | |
C9 | 0.6868 (3) | 0.68968 (13) | 0.61452 (16) | 0.0441 (6) | |
H9A | 0.6840 | 0.7157 | 0.5720 | 0.053* | |
H9B | 0.6482 | 0.7146 | 0.6457 | 0.053* | |
C30 | 1.0136 (3) | 0.58390 (14) | 0.64662 (19) | 0.0534 (7) | |
H30 | 1.0219 | 0.5676 | 0.6938 | 0.064* | |
C6 | 0.6678 (3) | 0.53484 (14) | 0.61605 (17) | 0.0496 (7) | |
C8A | 0.5740 (3) | 0.63483 (14) | 0.57988 (16) | 0.0487 (7) | |
C13A | 0.7580 (3) | 0.63447 (14) | 0.76182 (16) | 0.0492 (7) | |
N7 | 0.6638 (3) | 0.53876 (11) | 0.54741 (14) | 0.0503 (6) | |
N25 | 0.5507 (4) | 0.6741 (2) | 0.22816 (19) | 0.0823 (10) | |
C22 | 0.5580 (4) | 0.65315 (18) | 0.30281 (18) | 0.0616 (9) | |
C1 | 0.7694 (4) | 0.65645 (16) | 0.83336 (18) | 0.0610 (8) | |
H1 | 0.8577 | 0.6775 | 0.8660 | 0.073* | |
C29 | 0.9337 (3) | 0.63911 (13) | 0.61937 (16) | 0.0449 (7) | |
O27 | 0.5059 (4) | 0.72786 (19) | 0.20691 (18) | 0.1052 (11) | |
C35 | 0.9795 (4) | 0.77661 (14) | 0.65434 (17) | 0.0518 (7) | |
C24 | 0.5323 (4) | 0.67613 (15) | 0.41974 (18) | 0.0577 (8) | |
H24 | 0.5065 | 0.7040 | 0.4503 | 0.069* | |
C21 | 0.6053 (4) | 0.59292 (18) | 0.32795 (19) | 0.0644 (9) | |
H21 | 0.6282 | 0.5652 | 0.2962 | 0.077* | |
C36 | 1.1210 (4) | 0.77877 (17) | 0.65089 (19) | 0.0663 (9) | |
H36 | 1.1990 | 0.7518 | 0.6812 | 0.080* | |
O26 | 0.5892 (4) | 0.6378 (2) | 0.18951 (18) | 0.1127 (12) | |
C23 | 0.5198 (4) | 0.69428 (17) | 0.34791 (19) | 0.0639 (9) | |
H23 | 0.4856 | 0.7342 | 0.3298 | 0.077* | |
C14 | 0.7398 (4) | 0.48117 (16) | 0.6684 (2) | 0.0594 (9) | |
C41 | 1.1213 (3) | 0.62815 (15) | 0.85988 (17) | 0.0535 (7) | |
C32 | 1.0725 (4) | 0.57616 (19) | 0.5349 (2) | 0.0715 (10) | |
H32 | 1.1172 | 0.5548 | 0.5064 | 0.086* | |
C20 | 0.6181 (3) | 0.57443 (16) | 0.39974 (18) | 0.0548 (8) | |
H20 | 0.6499 | 0.5340 | 0.4167 | 0.066* | |
C46 | 1.0849 (5) | 0.56743 (16) | 0.8711 (2) | 0.0724 (10) | |
H46 | 0.9982 | 0.5484 | 0.8341 | 0.087* | |
C28 | 0.4078 (3) | 0.65696 (18) | 0.5526 (2) | 0.0638 (9) | |
H28A | 0.3959 | 0.6960 | 0.5259 | 0.096* | |
H28B | 0.3825 | 0.6622 | 0.5966 | 0.096* | |
H28C | 0.3401 | 0.6265 | 0.5181 | 0.096* | |
O18 | 0.7576 (4) | 0.48085 (13) | 0.73454 (16) | 0.0943 (9) | |
C34 | 0.9279 (3) | 0.66300 (15) | 0.54979 (17) | 0.0523 (7) | |
H34 | 0.8772 | 0.7005 | 0.5310 | 0.063* | |
C4 | 0.5049 (4) | 0.59495 (19) | 0.7373 (2) | 0.0729 (10) | |
H4 | 0.4151 | 0.5749 | 0.7045 | 0.087* | |
C37 | 0.8927 (6) | 0.85982 (17) | 0.5618 (2) | 0.0833 (12) | |
H37 | 0.8159 | 0.8874 | 0.5318 | 0.100* | |
C40 | 0.8653 (4) | 0.81866 (15) | 0.61064 (19) | 0.0628 (9) | |
H40 | 0.7707 | 0.8189 | 0.6145 | 0.075* | |
C33 | 0.9968 (4) | 0.63152 (18) | 0.5080 (2) | 0.0670 (10) | |
H33 | 0.9916 | 0.6480 | 0.4614 | 0.080* | |
C2 | 0.6489 (5) | 0.6469 (2) | 0.8558 (2) | 0.0775 (11) | |
H2 | 0.6571 | 0.6616 | 0.9037 | 0.093* | |
C31 | 1.0814 (4) | 0.55270 (17) | 0.6039 (2) | 0.0680 (10) | |
H31 | 1.1335 | 0.5154 | 0.6225 | 0.082* | |
C43 | 1.3423 (4) | 0.6215 (2) | 0.9816 (2) | 0.0785 (11) | |
H43 | 1.4301 | 0.6401 | 1.0184 | 0.094* | |
C42 | 1.2516 (4) | 0.65532 (18) | 0.91650 (19) | 0.0635 (9) | |
H42 | 1.2777 | 0.6962 | 0.9106 | 0.076* | |
C4A | 0.6243 (3) | 0.60306 (14) | 0.71428 (17) | 0.0523 (7) | |
C3 | 0.5176 (5) | 0.6162 (2) | 0.8082 (2) | 0.0849 (12) | |
H3 | 0.4377 | 0.6098 | 0.8239 | 0.102* | |
C45 | 1.1766 (6) | 0.53514 (19) | 0.9369 (2) | 0.0909 (13) | |
H45 | 1.1502 | 0.4944 | 0.9435 | 0.109* | |
C44 | 1.3065 (6) | 0.5615 (2) | 0.9933 (2) | 0.0891 (13) | |
C39 | 1.1476 (5) | 0.8209 (2) | 0.6026 (2) | 0.0913 (13) | |
H39 | 1.2439 | 0.8225 | 0.6008 | 0.110* | |
C17 | 1.0267 (6) | 0.3910 (3) | 0.7055 (3) | 0.1157 (18) | |
H17A | 1.0771 | 0.3516 | 0.7231 | 0.174* | |
H17B | 1.0629 | 0.4205 | 0.7473 | 0.174* | |
H17C | 1.0494 | 0.4060 | 0.6634 | 0.174* | |
C38 | 1.0331 (6) | 0.8603 (2) | 0.5573 (3) | 0.0998 (16) | |
H38 | 1.0506 | 0.8875 | 0.5233 | 0.120* | |
C16 | 0.8648 (5) | 0.3833 (2) | 0.6798 (3) | 0.0949 (14) | |
H16A | 0.8391 | 0.3794 | 0.7244 | 0.114* | |
H16B | 0.8330 | 0.3452 | 0.6496 | 0.114* | |
C47 | 1.4031 (8) | 0.5261 (3) | 1.0664 (3) | 0.144 (3) | |
H47A | 1.4097 | 0.4831 | 1.0539 | 0.215* | |
H47B | 1.3561 | 0.5289 | 1.1027 | 0.215* | |
H47C | 1.5047 | 0.5437 | 1.0890 | 0.215* |
U11 | U22 | U33 | U12 | U13 | U23 | |
N13 | 0.0399 (12) | 0.0537 (14) | 0.0384 (12) | −0.0037 (10) | 0.0119 (10) | 0.0001 (10) |
N10 | 0.0520 (14) | 0.0489 (14) | 0.0373 (12) | −0.0058 (11) | 0.0122 (11) | −0.0026 (10) |
N8 | 0.0472 (13) | 0.0500 (14) | 0.0382 (12) | −0.0023 (11) | 0.0129 (10) | −0.0002 (10) |
O15 | 0.0715 (16) | 0.0647 (15) | 0.0899 (18) | 0.0106 (12) | 0.0291 (14) | 0.0220 (13) |
C19 | 0.0350 (14) | 0.0573 (17) | 0.0407 (15) | −0.0116 (12) | 0.0108 (12) | −0.0036 (13) |
C9A | 0.0445 (15) | 0.0443 (15) | 0.0387 (14) | −0.0038 (12) | 0.0152 (12) | −0.0009 (11) |
N11 | 0.0525 (15) | 0.0591 (16) | 0.0418 (13) | −0.0064 (12) | 0.0119 (12) | −0.0063 (11) |
N5 | 0.0505 (14) | 0.0645 (16) | 0.0422 (13) | −0.0104 (12) | 0.0144 (11) | 0.0058 (12) |
C12 | 0.0461 (16) | 0.0525 (17) | 0.0422 (16) | −0.0015 (13) | 0.0137 (13) | −0.0031 (13) |
C9 | 0.0458 (15) | 0.0493 (16) | 0.0401 (14) | 0.0010 (12) | 0.0204 (12) | 0.0007 (12) |
C30 | 0.0425 (16) | 0.0569 (18) | 0.0592 (19) | −0.0051 (14) | 0.0191 (14) | −0.0073 (14) |
C6 | 0.0340 (14) | 0.0551 (18) | 0.0513 (18) | −0.0118 (12) | 0.0088 (13) | −0.0012 (14) |
C8A | 0.0428 (15) | 0.0590 (18) | 0.0435 (15) | −0.0052 (13) | 0.0169 (13) | 0.0008 (13) |
C13A | 0.0512 (17) | 0.0550 (17) | 0.0423 (16) | 0.0027 (13) | 0.0200 (13) | 0.0063 (13) |
N7 | 0.0420 (13) | 0.0521 (14) | 0.0485 (15) | −0.0095 (11) | 0.0098 (11) | 0.0021 (11) |
N25 | 0.0636 (19) | 0.129 (3) | 0.0521 (19) | −0.027 (2) | 0.0212 (16) | 0.006 (2) |
C22 | 0.0478 (18) | 0.091 (3) | 0.0426 (17) | −0.0173 (17) | 0.0153 (14) | 0.0058 (17) |
C1 | 0.064 (2) | 0.072 (2) | 0.0452 (17) | 0.0077 (16) | 0.0210 (16) | 0.0023 (15) |
C29 | 0.0354 (14) | 0.0509 (16) | 0.0479 (16) | −0.0096 (12) | 0.0165 (12) | −0.0086 (12) |
O27 | 0.107 (2) | 0.132 (3) | 0.076 (2) | −0.020 (2) | 0.0358 (17) | 0.0350 (19) |
C35 | 0.0597 (19) | 0.0485 (17) | 0.0443 (16) | −0.0127 (14) | 0.0182 (14) | −0.0082 (13) |
C24 | 0.0613 (19) | 0.0615 (19) | 0.0462 (17) | −0.0011 (15) | 0.0177 (15) | 0.0029 (14) |
C21 | 0.0565 (19) | 0.088 (3) | 0.0521 (19) | −0.0121 (18) | 0.0253 (16) | −0.0100 (18) |
C36 | 0.065 (2) | 0.076 (2) | 0.0543 (19) | −0.0186 (17) | 0.0199 (17) | −0.0001 (16) |
O26 | 0.114 (3) | 0.175 (3) | 0.0635 (18) | −0.018 (2) | 0.0513 (19) | −0.006 (2) |
C23 | 0.062 (2) | 0.071 (2) | 0.0493 (18) | −0.0096 (17) | 0.0131 (16) | 0.0110 (16) |
C14 | 0.0499 (18) | 0.059 (2) | 0.057 (2) | −0.0162 (15) | 0.0084 (15) | 0.0109 (16) |
C41 | 0.0475 (17) | 0.0626 (19) | 0.0445 (16) | 0.0044 (14) | 0.0126 (14) | −0.0033 (14) |
C32 | 0.058 (2) | 0.078 (2) | 0.091 (3) | −0.0171 (18) | 0.044 (2) | −0.034 (2) |
C20 | 0.0450 (16) | 0.0653 (19) | 0.0524 (18) | −0.0071 (14) | 0.0180 (14) | −0.0029 (15) |
C46 | 0.080 (2) | 0.058 (2) | 0.057 (2) | 0.0063 (17) | 0.0053 (18) | −0.0025 (16) |
C28 | 0.0415 (17) | 0.088 (2) | 0.060 (2) | 0.0027 (16) | 0.0188 (15) | 0.0089 (17) |
O18 | 0.125 (2) | 0.0802 (19) | 0.0605 (18) | −0.0032 (16) | 0.0206 (16) | 0.0145 (13) |
C34 | 0.0443 (16) | 0.0655 (19) | 0.0481 (17) | −0.0104 (14) | 0.0198 (14) | −0.0095 (14) |
C4 | 0.061 (2) | 0.102 (3) | 0.060 (2) | −0.0136 (19) | 0.0289 (18) | 0.0178 (19) |
C37 | 0.105 (3) | 0.060 (2) | 0.065 (2) | −0.012 (2) | 0.014 (2) | 0.0089 (18) |
C40 | 0.076 (2) | 0.0505 (18) | 0.0559 (19) | −0.0041 (16) | 0.0207 (17) | −0.0053 (15) |
C33 | 0.0561 (19) | 0.092 (3) | 0.060 (2) | −0.0223 (19) | 0.0308 (17) | −0.0215 (18) |
C2 | 0.087 (3) | 0.110 (3) | 0.0479 (19) | 0.021 (2) | 0.040 (2) | 0.0155 (19) |
C31 | 0.0472 (18) | 0.063 (2) | 0.097 (3) | −0.0027 (15) | 0.0322 (19) | −0.0198 (19) |
C43 | 0.060 (2) | 0.104 (3) | 0.052 (2) | 0.015 (2) | 0.0030 (17) | −0.0076 (19) |
C42 | 0.0533 (19) | 0.079 (2) | 0.0517 (19) | 0.0007 (16) | 0.0141 (16) | −0.0066 (16) |
C4A | 0.0506 (17) | 0.0612 (19) | 0.0450 (16) | −0.0048 (14) | 0.0194 (14) | 0.0089 (14) |
C3 | 0.072 (3) | 0.126 (4) | 0.074 (3) | 0.006 (2) | 0.046 (2) | 0.023 (2) |
C45 | 0.118 (4) | 0.062 (2) | 0.066 (2) | 0.020 (2) | 0.011 (2) | 0.0047 (19) |
C44 | 0.107 (3) | 0.077 (3) | 0.058 (2) | 0.035 (2) | 0.008 (2) | 0.000 (2) |
C39 | 0.083 (3) | 0.114 (3) | 0.074 (3) | −0.033 (3) | 0.029 (2) | 0.009 (2) |
C17 | 0.095 (4) | 0.145 (5) | 0.111 (4) | 0.035 (3) | 0.046 (3) | 0.062 (3) |
C38 | 0.113 (4) | 0.105 (3) | 0.071 (3) | −0.041 (3) | 0.027 (3) | 0.020 (2) |
C16 | 0.078 (3) | 0.078 (3) | 0.120 (4) | 0.008 (2) | 0.031 (3) | 0.047 (3) |
C47 | 0.170 (6) | 0.117 (4) | 0.078 (3) | 0.051 (4) | −0.017 (3) | 0.013 (3) |
N13—C13A | 1.421 (4) | C23—H23 | 0.9300 |
N13—C12 | 1.427 (4) | C14—O18 | 1.191 (4) |
N13—C9A | 1.480 (3) | C41—C46 | 1.385 (5) |
N10—N11 | 1.407 (3) | C41—C42 | 1.391 (4) |
N10—C35 | 1.416 (4) | C32—C31 | 1.367 (5) |
N10—C9A | 1.514 (3) | C32—C33 | 1.373 (5) |
N8—C19 | 1.369 (4) | C32—H32 | 0.9300 |
N8—N7 | 1.398 (3) | C20—H20 | 0.9300 |
N8—C8A | 1.482 (4) | C46—C45 | 1.378 (5) |
O15—C14 | 1.325 (4) | C46—H46 | 0.9300 |
O15—C16 | 1.466 (4) | C28—H28A | 0.9600 |
C19—C20 | 1.401 (4) | C28—H28B | 0.9600 |
C19—C24 | 1.408 (4) | C28—H28C | 0.9600 |
C9A—C9 | 1.525 (4) | C34—C33 | 1.388 (4) |
C9A—C29 | 1.534 (4) | C34—H34 | 0.9300 |
N11—C12 | 1.278 (4) | C4—C3 | 1.373 (6) |
N5—C6 | 1.370 (4) | C4—C4A | 1.380 (4) |
N5—C4A | 1.428 (4) | C4—H4 | 0.9300 |
N5—C8A | 1.482 (4) | C37—C38 | 1.370 (7) |
C12—C41 | 1.463 (4) | C37—C40 | 1.376 (5) |
C9—C8A | 1.545 (4) | C37—H37 | 0.9300 |
C9—H9A | 0.9700 | C40—H40 | 0.9300 |
C9—H9B | 0.9700 | C33—H33 | 0.9300 |
C30—C29 | 1.387 (4) | C2—C3 | 1.373 (6) |
C30—C31 | 1.392 (4) | C2—H2 | 0.9300 |
C30—H30 | 0.9300 | C31—H31 | 0.9300 |
C6—N7 | 1.284 (4) | C43—C44 | 1.372 (6) |
C6—C14 | 1.489 (4) | C43—C42 | 1.384 (5) |
C8A—C28 | 1.523 (4) | C43—H43 | 0.9300 |
C13A—C1 | 1.393 (4) | C42—H42 | 0.9300 |
C13A—C4A | 1.394 (4) | C3—H3 | 0.9300 |
N25—O26 | 1.220 (5) | C45—C44 | 1.381 (6) |
N25—O27 | 1.238 (5) | C45—H45 | 0.9300 |
N25—C22 | 1.454 (4) | C44—C47 | 1.514 (6) |
C22—C23 | 1.373 (5) | C39—C38 | 1.369 (7) |
C22—C21 | 1.386 (5) | C39—H39 | 0.9300 |
C1—C2 | 1.387 (5) | C17—C16 | 1.421 (6) |
C1—H1 | 0.9300 | C17—H17A | 0.9600 |
C29—C34 | 1.390 (4) | C17—H17B | 0.9600 |
C35—C36 | 1.373 (5) | C17—H17C | 0.9600 |
C35—C40 | 1.393 (5) | C38—H38 | 0.9300 |
C24—C23 | 1.369 (4) | C16—H16A | 0.9700 |
C24—H24 | 0.9300 | C16—H16B | 0.9700 |
C21—C20 | 1.370 (4) | C47—H47A | 0.9600 |
C21—H21 | 0.9300 | C47—H47B | 0.9600 |
C36—C39 | 1.377 (5) | C47—H47C | 0.9600 |
C36—H36 | 0.9300 | ||
C13A—N13—C12 | 118.8 (2) | C42—C41—C12 | 120.8 (3) |
C13A—N13—C9A | 120.2 (2) | C31—C32—C33 | 119.4 (3) |
C12—N13—C9A | 103.2 (2) | C31—C32—H32 | 120.3 |
N11—N10—C35 | 115.4 (2) | C33—C32—H32 | 120.3 |
N11—N10—C9A | 105.4 (2) | C21—C20—C19 | 120.6 (3) |
C35—N10—C9A | 120.4 (2) | C21—C20—H20 | 119.7 |
C19—N8—N7 | 118.8 (2) | C19—C20—H20 | 119.7 |
C19—N8—C8A | 128.0 (2) | C45—C46—C41 | 120.3 (4) |
N7—N8—C8A | 113.0 (2) | C45—C46—H46 | 119.8 |
C14—O15—C16 | 116.7 (3) | C41—C46—H46 | 119.8 |
N8—C19—C20 | 120.3 (3) | C8A—C28—H28A | 109.5 |
N8—C19—C24 | 121.5 (3) | C8A—C28—H28B | 109.5 |
C20—C19—C24 | 118.2 (3) | H28A—C28—H28B | 109.5 |
N13—C9A—N10 | 98.2 (2) | C8A—C28—H28C | 109.5 |
N13—C9A—C9 | 114.3 (2) | H28A—C28—H28C | 109.5 |
N10—C9A—C9 | 109.7 (2) | H28B—C28—H28C | 109.5 |
N13—C9A—C29 | 110.1 (2) | C33—C34—C29 | 120.8 (3) |
N10—C9A—C29 | 110.7 (2) | C33—C34—H34 | 119.6 |
C9—C9A—C29 | 113.0 (2) | C29—C34—H34 | 119.6 |
C12—N11—N10 | 107.1 (2) | C3—C4—C4A | 120.5 (4) |
C6—N5—C4A | 128.9 (3) | C3—C4—H4 | 119.7 |
C6—N5—C8A | 108.5 (2) | C4A—C4—H4 | 119.7 |
C4A—N5—C8A | 116.9 (2) | C38—C37—C40 | 120.1 (4) |
N11—C12—N13 | 113.5 (2) | C38—C37—H37 | 119.9 |
N11—C12—C41 | 124.3 (3) | C40—C37—H37 | 119.9 |
N13—C12—C41 | 122.0 (3) | C37—C40—C35 | 119.8 (4) |
C9A—C9—C8A | 117.6 (2) | C37—C40—H40 | 120.1 |
C9A—C9—H9A | 107.9 | C35—C40—H40 | 120.1 |
C8A—C9—H9A | 107.9 | C32—C33—C34 | 120.4 (3) |
C9A—C9—H9B | 107.9 | C32—C33—H33 | 119.8 |
C8A—C9—H9B | 107.9 | C34—C33—H33 | 119.8 |
H9A—C9—H9B | 107.2 | C3—C2—C1 | 120.9 (3) |
C29—C30—C31 | 120.5 (3) | C3—C2—H2 | 119.6 |
C29—C30—H30 | 119.8 | C1—C2—H2 | 119.6 |
C31—C30—H30 | 119.8 | C32—C31—C30 | 120.8 (3) |
N7—C6—N5 | 114.9 (3) | C32—C31—H31 | 119.6 |
N7—C6—C14 | 122.5 (3) | C30—C31—H31 | 119.6 |
N5—C6—C14 | 122.6 (3) | C44—C43—C42 | 121.9 (4) |
N8—C8A—N5 | 97.4 (2) | C44—C43—H43 | 119.0 |
N8—C8A—C28 | 112.9 (2) | C42—C43—H43 | 119.0 |
N5—C8A—C28 | 109.9 (2) | C43—C42—C41 | 120.1 (4) |
N8—C8A—C9 | 115.0 (2) | C43—C42—H42 | 120.0 |
N5—C8A—C9 | 110.3 (2) | C41—C42—H42 | 120.0 |
C28—C8A—C9 | 110.5 (3) | C4—C4A—C13A | 120.5 (3) |
C1—C13A—C4A | 118.6 (3) | C4—C4A—N5 | 119.5 (3) |
C1—C13A—N13 | 122.8 (3) | C13A—C4A—N5 | 119.7 (3) |
C4A—C13A—N13 | 118.5 (3) | C2—C3—C4 | 119.6 (3) |
C6—N7—N8 | 105.0 (2) | C2—C3—H3 | 120.2 |
O26—N25—O27 | 123.2 (4) | C4—C3—H3 | 120.2 |
O26—N25—C22 | 118.4 (4) | C46—C45—C44 | 121.8 (4) |
O27—N25—C22 | 118.4 (4) | C46—C45—H45 | 119.1 |
C23—C22—C21 | 121.1 (3) | C44—C45—H45 | 119.1 |
C23—C22—N25 | 118.9 (4) | C43—C44—C45 | 117.5 (4) |
C21—C22—N25 | 120.0 (4) | C43—C44—C47 | 121.3 (4) |
C2—C1—C13A | 119.9 (3) | C45—C44—C47 | 121.1 (5) |
C2—C1—H1 | 120.1 | C38—C39—C36 | 120.4 (4) |
C13A—C1—H1 | 120.1 | C38—C39—H39 | 119.8 |
C30—C29—C34 | 118.1 (3) | C36—C39—H39 | 119.8 |
C30—C29—C9A | 121.7 (3) | C16—C17—H17A | 109.5 |
C34—C29—C9A | 120.2 (3) | C16—C17—H17B | 109.5 |
C36—C35—C40 | 119.4 (3) | H17A—C17—H17B | 109.5 |
C36—C35—N10 | 123.0 (3) | C16—C17—H17C | 109.5 |
C40—C35—N10 | 117.6 (3) | H17A—C17—H17C | 109.5 |
C23—C24—C19 | 120.8 (3) | H17B—C17—H17C | 109.5 |
C23—C24—H24 | 119.6 | C39—C38—C37 | 120.1 (4) |
C19—C24—H24 | 119.6 | C39—C38—H38 | 120.0 |
C20—C21—C22 | 119.6 (3) | C37—C38—H38 | 120.0 |
C20—C21—H21 | 120.2 | C17—C16—O15 | 110.9 (3) |
C22—C21—H21 | 120.2 | C17—C16—H16A | 109.5 |
C35—C36—C39 | 120.0 (4) | O15—C16—H16A | 109.5 |
C35—C36—H36 | 120.0 | C17—C16—H16B | 109.5 |
C39—C36—H36 | 120.0 | O15—C16—H16B | 109.5 |
C24—C23—C22 | 119.6 (3) | H16A—C16—H16B | 108.0 |
C24—C23—H23 | 120.2 | C44—C47—H47A | 109.5 |
C22—C23—H23 | 120.2 | C44—C47—H47B | 109.5 |
O18—C14—O15 | 126.1 (3) | H47A—C47—H47B | 109.5 |
O18—C14—C6 | 122.1 (4) | C44—C47—H47C | 109.5 |
O15—C14—C6 | 111.8 (3) | H47A—C47—H47C | 109.5 |
C46—C41—C42 | 118.3 (3) | H47B—C47—H47C | 109.5 |
C46—C41—C12 | 120.9 (3) | ||
N7—N8—C19—C20 | 4.0 (4) | N13—C9A—C29—C34 | −178.9 (2) |
C8A—N8—C19—C20 | 178.9 (3) | N10—C9A—C29—C34 | −71.4 (3) |
N7—N8—C19—C24 | −175.4 (2) | C9—C9A—C29—C34 | 52.0 (3) |
C8A—N8—C19—C24 | −0.4 (4) | N11—N10—C35—C36 | 30.3 (4) |
C13A—N13—C9A—N10 | 105.0 (3) | C9A—N10—C35—C36 | −98.0 (3) |
C12—N13—C9A—N10 | −30.1 (2) | N11—N10—C35—C40 | −150.2 (3) |
C13A—N13—C9A—C9 | −11.0 (3) | C9A—N10—C35—C40 | 81.6 (3) |
C12—N13—C9A—C9 | −146.2 (2) | N8—C19—C24—C23 | 177.8 (3) |
C13A—N13—C9A—C29 | −139.4 (2) | C20—C19—C24—C23 | −1.5 (4) |
C12—N13—C9A—C29 | 85.5 (3) | C23—C22—C21—C20 | −1.7 (5) |
N11—N10—C9A—N13 | 34.7 (2) | N25—C22—C21—C20 | 177.3 (3) |
C35—N10—C9A—N13 | 167.3 (2) | C40—C35—C36—C39 | −2.1 (5) |
N11—N10—C9A—C9 | 154.3 (2) | N10—C35—C36—C39 | 177.4 (3) |
C35—N10—C9A—C9 | −73.1 (3) | C19—C24—C23—C22 | −0.1 (5) |
N11—N10—C9A—C29 | −80.5 (3) | C21—C22—C23—C24 | 1.7 (5) |
C35—N10—C9A—C29 | 52.2 (3) | N25—C22—C23—C24 | −177.3 (3) |
C35—N10—N11—C12 | −161.6 (2) | C16—O15—C14—O18 | −3.5 (5) |
C9A—N10—N11—C12 | −26.3 (3) | C16—O15—C14—C6 | 175.3 (3) |
N10—N11—C12—N13 | 5.7 (3) | N7—C6—C14—O18 | 171.9 (3) |
N10—N11—C12—C41 | −178.6 (3) | N5—C6—C14—O18 | −6.3 (5) |
C13A—N13—C12—N11 | −118.5 (3) | N7—C6—C14—O15 | −7.0 (4) |
C9A—N13—C12—N11 | 17.4 (3) | N5—C6—C14—O15 | 174.8 (3) |
C13A—N13—C12—C41 | 65.7 (4) | N11—C12—C41—C46 | −165.7 (3) |
C9A—N13—C12—C41 | −158.4 (3) | N13—C12—C41—C46 | 9.7 (5) |
N13—C9A—C9—C8A | −64.3 (3) | N11—C12—C41—C42 | 14.2 (5) |
N10—C9A—C9—C8A | −173.4 (2) | N13—C12—C41—C42 | −170.5 (3) |
C29—C9A—C9—C8A | 62.6 (3) | C22—C21—C20—C19 | 0.0 (5) |
C4A—N5—C6—N7 | −162.1 (3) | N8—C19—C20—C21 | −177.8 (3) |
C8A—N5—C6—N7 | −10.2 (3) | C24—C19—C20—C21 | 1.5 (4) |
C4A—N5—C6—C14 | 16.3 (4) | C42—C41—C46—C45 | −0.2 (6) |
C8A—N5—C6—C14 | 168.2 (2) | C12—C41—C46—C45 | 179.6 (4) |
C19—N8—C8A—N5 | 175.8 (2) | C30—C29—C34—C33 | 1.6 (4) |
N7—N8—C8A—N5 | −9.0 (3) | C9A—C29—C34—C33 | −179.1 (3) |
C19—N8—C8A—C28 | 60.5 (4) | C38—C37—C40—C35 | −1.3 (5) |
N7—N8—C8A—C28 | −124.3 (3) | C36—C35—C40—C37 | 3.1 (5) |
C19—N8—C8A—C9 | −67.7 (3) | N10—C35—C40—C37 | −176.5 (3) |
N7—N8—C8A—C9 | 107.5 (3) | C31—C32—C33—C34 | −1.0 (5) |
C6—N5—C8A—N8 | 10.7 (3) | C29—C34—C33—C32 | −0.2 (5) |
C4A—N5—C8A—N8 | 166.4 (2) | C13A—C1—C2—C3 | −0.2 (6) |
C6—N5—C8A—C28 | 128.5 (3) | C33—C32—C31—C30 | 0.7 (5) |
C4A—N5—C8A—C28 | −75.8 (3) | C29—C30—C31—C32 | 0.8 (5) |
C6—N5—C8A—C9 | −109.5 (3) | C44—C43—C42—C41 | −1.3 (6) |
C4A—N5—C8A—C9 | 46.2 (3) | C46—C41—C42—C43 | 0.9 (5) |
C9A—C9—C8A—N8 | −67.1 (3) | C12—C41—C42—C43 | −179.0 (3) |
C9A—C9—C8A—N5 | 41.8 (3) | C3—C4—C4A—C13A | −1.8 (5) |
C9A—C9—C8A—C28 | 163.5 (2) | C3—C4—C4A—N5 | −175.6 (3) |
C12—N13—C13A—C1 | 7.0 (4) | C1—C13A—C4A—C4 | 1.1 (5) |
C9A—N13—C13A—C1 | −121.4 (3) | N13—C13A—C4A—C4 | 178.1 (3) |
C12—N13—C13A—C4A | −169.8 (3) | C1—C13A—C4A—N5 | 174.9 (3) |
C9A—N13—C13A—C4A | 61.7 (4) | N13—C13A—C4A—N5 | −8.1 (4) |
N5—C6—N7—N8 | 4.0 (3) | C6—N5—C4A—C4 | −107.8 (4) |
C14—C6—N7—N8 | −174.4 (2) | C8A—N5—C4A—C4 | 102.3 (3) |
C19—N8—N7—C6 | 179.6 (2) | C6—N5—C4A—C13A | 78.3 (4) |
C8A—N8—N7—C6 | 3.9 (3) | C8A—N5—C4A—C13A | −71.6 (4) |
O26—N25—C22—C23 | 177.9 (3) | C1—C2—C3—C4 | −0.5 (6) |
O27—N25—C22—C23 | −2.0 (5) | C4A—C4—C3—C2 | 1.4 (6) |
O26—N25—C22—C21 | −1.1 (5) | C41—C46—C45—C44 | −0.1 (7) |
O27—N25—C22—C21 | 179.0 (3) | C42—C43—C44—C45 | 1.0 (7) |
C4A—C13A—C1—C2 | −0.1 (5) | C42—C43—C44—C47 | −177.4 (5) |
N13—C13A—C1—C2 | −177.0 (3) | C46—C45—C44—C43 | −0.3 (7) |
C31—C30—C29—C34 | −2.0 (4) | C46—C45—C44—C47 | 178.1 (5) |
C31—C30—C29—C9A | 178.8 (3) | C35—C36—C39—C38 | −0.7 (6) |
N13—C9A—C29—C30 | 0.4 (3) | C36—C39—C38—C37 | 2.5 (7) |
N10—C9A—C29—C30 | 107.8 (3) | C40—C37—C38—C39 | −1.5 (7) |
C9—C9A—C29—C30 | −128.8 (3) | C14—O15—C16—C17 | −96.1 (5) |
D—H···A | D—H | H···A | D···A | D—H···A |
C16—H16A···O18 | 0.97 | 2.34 | 2.708 (6) | 101 |
C20—H20···N7 | 0.93 | 2.42 | 2.751 (4) | 101 |
C30—H30···N13 | 0.93 | 2.40 | 2.779 (4) | 104 |
C46—H46···N13 | 0.93 | 2.61 | 2.938 (4) | 101 |
Experimental details
Crystal data | |
Chemical formula | C40H35N7O4 |
Mr | 677.75 |
Crystal system, space group | Monoclinic, P21/c |
Temperature (K) | 293 |
a, b, c (Å) | 9.4951 (6), 21.436 (1), 18.885 (1) |
β (°) | 114.011 (5) |
V (Å3) | 3511.2 (4) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.09 |
Crystal size (mm) | 0.47 × 0.36 × 0.13 |
Data collection | |
Diffractometer | Oxford Diffraction Xcalibur CCD |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 59538, 6080, 4822 |
Rint | 0.058 |
(sin θ/λ)max (Å−1) | 0.754 |
Refinement | |
R[F2 > 2σ(F2)], wR(F2), S | 0.077, 0.213, 1.14 |
No. of reflections | 6080 |
No. of parameters | 463 |
H-atom treatment | H-atom parameters constrained |
Δρmax, Δρmin (e Å−3) | 0.36, −0.27 |
Computer programs: CrysAlis CCD (Oxford Diffraction, 2004), CrysAlis CCD, CrysAlis RED (Oxford Diffraction, 2004), SHELXS97 (Sheldrick, 1990), SHELXL97 (Sheldrick, 1997), ORTEP-3 for Windows (Version 1.075; Farrugia, 1997), WinGX (Farrugia, 1999).
D—H···A | D—H | H···A | D···A | D—H···A |
C16—H16A···O18 | 0.97 | 2.34 | 2.708 (6) | 101 |
C20—H20···N7 | 0.93 | 2.42 | 2.751 (4) | 101 |
C30—H30···N13 | 0.93 | 2.40 | 2.779 (4) | 104 |
C46—H46···N13 | 0.93 | 2.61 | 2.938 (4) | 101 |
D—H···Cg | D—H | H···Cg | D···Cg | D—H···Cg |
C34—H34···Cg1i | 0.98 | 2.93 | 3.666 (5) | 121 |
C19—H19···Cg2ii | 0.93 | 2.86 | 3.697 (5) | 146 |
Symmetry codes: (i) x, y, z; (ii) x, 3/2-y, z-1/2. Values were calculated using PLATON (Version 200905; Spek, 2003). Cg1 and Cg2 are the centroids of the phenyl and 3-methylphenyl rings C35/C36/C39/C38/C37/C40 and C41/C42/C43/C44/C45/C46, respectively. |
Several benzodiazepine derivatives containing additional rings have proven to be of pharmacological interest (Sternbach, 1978; Bellantuono et al., 1980). For years, our research team is interested in the synthesis of such compounds by cyclization reactions onto 1,4-benzodiazepines (Benelbaghdadi et al., 1997) and 1,5-benzodiazepines (Baouid et al., 1994; Boudina et al., 2006). Within this context, we have studied the 1,3-dipolar cycloadditions of diarylnitrilimines with ethyl 3a-methyl-3-(4-nitrophenyl)-5-phenyl-3a,4-dihydro[1,2,4] triazolo[4,3-a][1,5]benzodiazepine-1-carboxylate (1) (Baouid et al., 1994).
From the spectral data (mass; 1H– 13C– NMR) possible diastereoisomers 3X or 3Y of the cycloadduct were established. In particular, the chemical shifts of 86 and 90 p.p.m. observed for the quaternary carbon atoms C8a and C9a have ruled out the formation of the alternative regioisomer that would be formed by a reverse addition of the dipolar compound (2) on C=N of the ethyl 3a-methyl-3-(4-nitrophenyl)-5-phenyl-3a,4-dihydro[1,2,4]triazolo[4,3-a] [1,5]benzodiazepine-1-carboxylate, (1). For the alternative regioisomer chemical shifts of about 50 p.p.m. would be expected (Begtrup et al. 1988). However, the NMR spectroscopic data (1H and 13C) did not allow to distinguish between the two diastereoisomers 3X (RS/SR) and 3Y (RR/SS).
On the other hand, the present crystallographic study has confirmed the formation of the (3X) trans diastereoisomer with its two asymmetric carbon atoms C8a and C9a displaying respective (RS,SR) absolute configurations. The 1,3-dipolar cycloaddition of diarylnitrilimine on ethyl 3a-methyl-3-(4-nitrophenyl)-5-phenyl-3a,4-dihydro[1,2,4]triazolo[4,3-a] [1,5]benzodiazepine-1-carboxylate, (1), is completely regio- and diastereoselective.
The molecule of the title compound (Scheme 1; Fig. 1) is composed of a tetracylic core formed by a benzodiazepine bicycle and two 5-membered rings (triazoles) that are differently substituted.
The 7-membered diazepine ring displays a boat conformation; the atoms N5, N13, C8a and C9a form the "bottom" of the boat. The atoms (C8a, C9, C9a) form the "prow" while (N5, N13, C13a, C4a) form the "stern". The angles between the best planes of the "bottom" and the "prow" and between the "bottom" and the "stern" equal to 47.5 (3) and 53.2 (2)°, respectively.
The bonds within the triazole rings are comparable with those reported in the literature for related compounds, as for example in 1-(2-Bromo-5-methoxyphenyl)-8-chloro-6-(2-fluorophenyl)- 4H-1,2,4-triazolo[4,3-a][1,4]benzodiazepine (Harrison et al., 2005).