The crystal structure determination of the title compound, C
17H
20ClN
5, has been undertaken as part of studies on antipsychotic drugs. Its structure is compared with that of clozapine (C
18H
19ClN
4), a well known atypical antipsychotic drug. The side chain is more flexible than in the
N-methylpiperazine analogues, but its folding is influenced by an intramolecular N—H
N hydrogen bond. The distances between the
N-distal atom, a possible pharmacophore, and the centres of the two aromatic rings are significantly shorter than in clozapine. The crystal packing involves one N—H
N intermolecular hydrogen bond. The title compound showed no affinity for the receptors tested.
Supporting information
CCDC reference: 180551
Key indicators
- Single-crystal X-ray study
- T = 293 K
- Mean (C-C) = 0.003 Å
- R factor = 0.044
- wR factor = 0.122
- Data-to-parameter ratio = 16.2
checkCIF results
No syntax errors found
ADDSYM reports no extra symmetry
The title compound was prepared according to previously described methods
(Liégeois et al., 1993) using a one-pot synthesis. A mixture of the
lactame derivative, the corresponding amine, titanium tetrachloride in
toluene–anisole was refluxed for several hours. The product was extracted
from basic solution with chloroform and recrystallized from methylene
chloride/hexane mixture (Liégeois et al., 2002).
All H atoms (with the exception of the nitrogen-bound atoms H5 and H16) were
included in the refinement in the riding-model approximation, with isotropic
displacement parameters fixed at 1.2Ueq of the parent atom
(1.5Ueq for methyl H-atoms). Atoms H5 and H16 were refined
isotropically, their displacement parameters being fixed at 1.2Ueq of
the nitrogen-bound atom. The two methyl groups were allowed to rotate about
their local threefold axis.
Data collection: CAD-4 EXPRESS (Enraf-Nonius, 1992); cell refinement: CAD-4 EXPRESS; data reduction: HELENA (Spek, 1997); program(s) used to solve structure: SIR92 (Altomare et al., 1993); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: ORTEPIII (Burnett & Johnson, 1996); software used to prepare material for publication: SHELXL97.
8-Chloro-6-(3-dimethylaminopropylamino)-11
H-pyrido[2,3-
b][1,4]benzodiazepine
top
Crystal data top
C17H20ClN5 | F(000) = 696 |
Mr = 329.83 | Dx = 1.273 Mg m−3 |
Monoclinic, P21/n | Mo Kα radiation, λ = 0.71069 Å |
a = 9.001 (1) Å | Cell parameters from 25 reflections |
b = 20.421 (3) Å | θ = 20–23° |
c = 9.935 (1) Å | µ = 0.23 mm−1 |
β = 109.545 (6)° | T = 293 K |
V = 1720.9 (4) Å3 | Prism, yellow |
Z = 4 | 0.50 × 0.50 × 0.50 mm |
Data collection top
Enraf-Nonius CAD-4 diffractometer | Rint = 0.022 |
Radiation source: fine-focus sealed tube | θmax = 26.3°, θmin = 2.0° |
Graphite monochromator | h = 0→11 |
θ/2θ scans | k = −25→25 |
7197 measured reflections | l = −12→11 |
3511 independent reflections | 3 standard reflections every 200 reflections |
3036 reflections with I > 2σ(I) | intensity decay: 4% |
Refinement top
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: H atoms were placed at standard calculated positions, except atoms H(N5)
and H(N16), which were obtained from difference map. |
R[F2 > 2σ(F2)] = 0.044 | H atoms treated by a mixture of independent and constrained refinement |
wR(F2) = 0.122 | w = 1/[σ2(Fo2) + (0.0528P)2 + 0.2131P] where P = (Fo2 + 2Fc2)/3 |
S = 1.11 | (Δ/σ)max < 0.001 |
3511 reflections | Δρmax = 0.34 e Å−3 |
217 parameters | Δρmin = −0.16 e Å−3 |
0 restraints | Extinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction coefficient: 0.078 (4) |
Crystal data top
C17H20ClN5 | V = 1720.9 (4) Å3 |
Mr = 329.83 | Z = 4 |
Monoclinic, P21/n | Mo Kα radiation |
a = 9.001 (1) Å | µ = 0.23 mm−1 |
b = 20.421 (3) Å | T = 293 K |
c = 9.935 (1) Å | 0.50 × 0.50 × 0.50 mm |
β = 109.545 (6)° | |
Data collection top
Enraf-Nonius CAD-4 diffractometer | Rint = 0.022 |
7197 measured reflections | 3 standard reflections every 200 reflections |
3511 independent reflections | intensity decay: 4% |
3036 reflections with I > 2σ(I) | |
Refinement top
R[F2 > 2σ(F2)] = 0.044 | 0 restraints |
wR(F2) = 0.122 | H atoms treated by a mixture of independent and constrained refinement |
S = 1.11 | Δρmax = 0.34 e Å−3 |
3511 reflections | Δρmin = −0.16 e Å−3 |
217 parameters | |
Special details top
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. |
Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2) top | x | y | z | Uiso*/Ueq | |
C1 | 0.1994 (2) | 0.07844 (9) | 0.63588 (19) | 0.0541 (4) | |
C2 | 0.0909 (2) | 0.12621 (10) | 0.57305 (18) | 0.0558 (5) | |
H2 | 0.0271 | 0.1224 | 0.4780 | 0.067* | |
C3 | 0.0776 (2) | 0.17979 (9) | 0.65227 (17) | 0.0491 (4) | |
H3 | 0.0031 | 0.2119 | 0.6103 | 0.059* | |
C4 | 0.17410 (19) | 0.18683 (8) | 0.79491 (16) | 0.0402 (3) | |
N5 | 0.15959 (18) | 0.24356 (7) | 0.86991 (14) | 0.0464 (3) | |
H5 | 0.094 (2) | 0.2720 (10) | 0.817 (2) | 0.056* | |
C6 | 0.1401 (2) | 0.23693 (8) | 1.00457 (16) | 0.0416 (4) | |
N7 | 0.02017 (18) | 0.27092 (8) | 1.01874 (15) | 0.0513 (4) | |
C8 | −0.0044 (2) | 0.26769 (10) | 1.1445 (2) | 0.0591 (5) | |
H8 | −0.0867 | 0.2919 | 1.1561 | 0.071* | |
C9 | 0.0854 (2) | 0.23063 (10) | 1.25634 (19) | 0.0574 (5) | |
H9 | 0.0621 | 0.2282 | 1.3406 | 0.069* | |
C10 | 0.2120 (2) | 0.19673 (9) | 1.24123 (17) | 0.0504 (4) | |
H10 | 0.2756 | 0.1716 | 1.3166 | 0.061* | |
C11 | 0.24474 (18) | 0.19994 (8) | 1.11439 (16) | 0.0407 (3) | |
N12 | 0.38923 (16) | 0.17396 (7) | 1.11346 (14) | 0.0436 (3) | |
C13 | 0.40794 (18) | 0.14789 (8) | 1.00144 (16) | 0.0414 (3) | |
C14 | 0.28679 (18) | 0.13908 (8) | 0.85719 (16) | 0.0402 (3) | |
C15 | 0.2966 (2) | 0.08439 (8) | 0.77592 (18) | 0.0481 (4) | |
H15 | 0.3696 | 0.0516 | 0.8168 | 0.058* | |
N16 | 0.54988 (17) | 0.12354 (8) | 1.01059 (16) | 0.0524 (4) | |
H16 | 0.567 (2) | 0.1146 (10) | 0.937 (2) | 0.063* | |
C17 | 0.6895 (2) | 0.12695 (11) | 1.1369 (2) | 0.0594 (5) | |
H171 | 0.6638 | 0.1130 | 1.2197 | 0.071* | |
H172 | 0.7267 | 0.1718 | 1.1524 | 0.071* | |
C18 | 0.8176 (2) | 0.08352 (12) | 1.1188 (2) | 0.0708 (6) | |
H181 | 0.9130 | 0.0905 | 1.1997 | 0.085* | |
H182 | 0.7864 | 0.0382 | 1.1218 | 0.085* | |
C19 | 0.8555 (2) | 0.09373 (12) | 0.9846 (3) | 0.0715 (6) | |
H191 | 0.8782 | 0.1398 | 0.9770 | 0.086* | |
H192 | 0.9501 | 0.0692 | 0.9916 | 0.086* | |
N20 | 0.72907 (19) | 0.07374 (8) | 0.85317 (17) | 0.0573 (4) | |
C21 | 0.7089 (3) | 0.00392 (12) | 0.8365 (3) | 0.0850 (7) | |
H211 | 0.6264 | −0.0055 | 0.7483 | 0.128* | |
H212 | 0.6813 | −0.0136 | 0.9147 | 0.128* | |
H213 | 0.8055 | −0.0156 | 0.8355 | 0.128* | |
C22 | 0.7641 (4) | 0.10054 (13) | 0.7309 (3) | 0.0897 (8) | |
H221 | 0.8576 | 0.0802 | 0.7244 | 0.135* | |
H222 | 0.7804 | 0.1469 | 0.7429 | 0.135* | |
H223 | 0.6773 | 0.0921 | 0.6451 | 0.135* | |
Cl1 | 0.21868 (8) | 0.01038 (3) | 0.53802 (6) | 0.0864 (2) | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
C1 | 0.0612 (11) | 0.0547 (10) | 0.0499 (9) | −0.0064 (8) | 0.0231 (8) | −0.0148 (8) |
C2 | 0.0648 (11) | 0.0632 (11) | 0.0383 (8) | −0.0051 (9) | 0.0156 (8) | −0.0055 (8) |
C3 | 0.0549 (10) | 0.0533 (9) | 0.0398 (8) | 0.0016 (8) | 0.0166 (7) | 0.0039 (7) |
C4 | 0.0466 (8) | 0.0418 (8) | 0.0379 (7) | −0.0032 (6) | 0.0218 (6) | 0.0013 (6) |
N5 | 0.0616 (9) | 0.0421 (7) | 0.0409 (7) | 0.0071 (6) | 0.0244 (7) | 0.0038 (5) |
C6 | 0.0486 (9) | 0.0412 (8) | 0.0393 (7) | −0.0044 (6) | 0.0202 (7) | −0.0046 (6) |
N7 | 0.0536 (9) | 0.0570 (8) | 0.0468 (8) | 0.0084 (7) | 0.0215 (7) | −0.0040 (6) |
C8 | 0.0581 (11) | 0.0700 (12) | 0.0573 (10) | 0.0058 (9) | 0.0300 (9) | −0.0101 (9) |
C9 | 0.0603 (11) | 0.0756 (12) | 0.0452 (9) | −0.0028 (9) | 0.0295 (8) | −0.0068 (8) |
C10 | 0.0549 (10) | 0.0608 (10) | 0.0379 (8) | −0.0037 (8) | 0.0186 (7) | −0.0009 (7) |
C11 | 0.0414 (8) | 0.0444 (8) | 0.0389 (7) | −0.0059 (6) | 0.0169 (6) | −0.0058 (6) |
N12 | 0.0420 (7) | 0.0498 (8) | 0.0398 (6) | −0.0022 (6) | 0.0147 (5) | −0.0036 (6) |
C13 | 0.0418 (8) | 0.0416 (8) | 0.0437 (8) | −0.0028 (6) | 0.0184 (6) | −0.0013 (6) |
C14 | 0.0433 (8) | 0.0416 (8) | 0.0396 (7) | −0.0056 (6) | 0.0192 (6) | −0.0025 (6) |
C15 | 0.0505 (9) | 0.0469 (9) | 0.0495 (9) | −0.0025 (7) | 0.0204 (7) | −0.0066 (7) |
N16 | 0.0440 (8) | 0.0687 (10) | 0.0451 (8) | 0.0057 (7) | 0.0159 (6) | −0.0072 (7) |
C17 | 0.0499 (10) | 0.0700 (12) | 0.0540 (10) | 0.0053 (9) | 0.0117 (8) | −0.0081 (9) |
C18 | 0.0539 (11) | 0.0812 (14) | 0.0674 (12) | 0.0137 (10) | 0.0072 (9) | −0.0108 (11) |
C19 | 0.0508 (11) | 0.0738 (14) | 0.0917 (16) | 0.0047 (10) | 0.0263 (11) | −0.0112 (12) |
N20 | 0.0578 (9) | 0.0575 (9) | 0.0621 (9) | 0.0071 (7) | 0.0272 (8) | −0.0035 (7) |
C21 | 0.0978 (19) | 0.0627 (13) | 0.0983 (18) | −0.0005 (13) | 0.0377 (15) | −0.0068 (12) |
C22 | 0.119 (2) | 0.0746 (15) | 0.1017 (19) | 0.0139 (15) | 0.0724 (17) | 0.0053 (13) |
Cl1 | 0.1033 (5) | 0.0785 (4) | 0.0739 (4) | 0.0039 (3) | 0.0250 (3) | −0.0389 (3) |
Geometric parameters (Å, º) top
C1—C2 | 1.374 (3) | C13—C14 | 1.493 (2) |
C1—C15 | 1.379 (2) | C14—C15 | 1.398 (2) |
C1—Cl1 | 1.7379 (18) | C15—H15 | 0.9300 |
C2—C3 | 1.376 (2) | N16—C17 | 1.450 (2) |
C2—H2 | 0.9300 | N16—H16 | 0.82 (2) |
C3—C4 | 1.400 (2) | C17—C18 | 1.512 (3) |
C3—H3 | 0.9300 | C17—H171 | 0.9700 |
C4—C14 | 1.394 (2) | C17—H172 | 0.9700 |
C4—N5 | 1.407 (2) | C18—C19 | 1.498 (3) |
N5—C6 | 1.4127 (19) | C18—H181 | 0.9700 |
N5—H5 | 0.87 (2) | C18—H182 | 0.9700 |
C6—N7 | 1.330 (2) | C19—N20 | 1.474 (3) |
C6—C11 | 1.400 (2) | C19—H191 | 0.9700 |
N7—C8 | 1.342 (2) | C19—H192 | 0.9700 |
C8—C9 | 1.363 (3) | N20—C21 | 1.440 (3) |
C8—H8 | 0.9300 | N20—C22 | 1.459 (3) |
C9—C10 | 1.384 (3) | C21—H211 | 0.9600 |
C9—H9 | 0.9300 | C21—H212 | 0.9600 |
C10—C11 | 1.388 (2) | C21—H213 | 0.9600 |
C10—H10 | 0.9300 | C22—H221 | 0.9600 |
C11—N12 | 1.407 (2) | C22—H222 | 0.9600 |
N12—C13 | 1.2945 (19) | C22—H223 | 0.9600 |
C13—N16 | 1.345 (2) | | |
| | | |
C2—C1—C15 | 120.71 (16) | C1—C15—H15 | 119.6 |
C2—C1—Cl1 | 120.17 (14) | C14—C15—H15 | 119.6 |
C15—C1—Cl1 | 119.10 (15) | C13—N16—C17 | 124.69 (15) |
C1—C2—C3 | 119.30 (16) | C13—N16—H16 | 119.0 (15) |
C1—C2—H2 | 120.3 | C17—N16—H16 | 114.4 (15) |
C3—C2—H2 | 120.3 | N16—C17—C18 | 110.11 (16) |
C2—C3—C4 | 121.15 (17) | N16—C17—H171 | 109.6 |
C2—C3—H3 | 119.4 | C18—C17—H171 | 109.6 |
C4—C3—H3 | 119.4 | N16—C17—H172 | 109.6 |
C14—C4—C3 | 119.37 (14) | C18—C17—H172 | 109.6 |
C14—C4—N5 | 121.58 (14) | H171—C17—H172 | 108.2 |
C3—C4—N5 | 118.99 (15) | C19—C18—C17 | 115.69 (19) |
C4—N5—C6 | 119.04 (13) | C19—C18—H181 | 108.4 |
C4—N5—H5 | 113.3 (13) | C17—C18—H181 | 108.4 |
C6—N5—H5 | 111.1 (13) | C19—C18—H182 | 108.4 |
N7—C6—C11 | 123.86 (14) | C17—C18—H182 | 108.4 |
N7—C6—N5 | 114.36 (14) | H181—C18—H182 | 107.4 |
C11—C6—N5 | 121.70 (14) | N20—C19—C18 | 114.33 (18) |
C6—N7—C8 | 117.74 (15) | N20—C19—H191 | 108.7 |
N7—C8—C9 | 123.29 (18) | C18—C19—H191 | 108.7 |
N7—C8—H8 | 118.4 | N20—C19—H192 | 108.7 |
C9—C8—H8 | 118.4 | C18—C19—H192 | 108.7 |
C8—C9—C10 | 118.32 (16) | H191—C19—H192 | 107.6 |
C8—C9—H9 | 120.8 | C21—N20—C22 | 109.25 (19) |
C10—C9—H9 | 120.8 | C21—N20—C19 | 113.98 (19) |
C9—C10—C11 | 120.50 (17) | C22—N20—C19 | 108.4 (2) |
C9—C10—H10 | 119.8 | N20—C21—H211 | 109.5 |
C11—C10—H10 | 119.8 | N20—C21—H212 | 109.5 |
C10—C11—C6 | 116.17 (15) | H211—C21—H212 | 109.5 |
C10—C11—N12 | 117.74 (15) | N20—C21—H213 | 109.5 |
C6—C11—N12 | 125.48 (14) | H211—C21—H213 | 109.5 |
C13—N12—C11 | 123.16 (13) | H212—C21—H213 | 109.5 |
N12—C13—N16 | 119.18 (15) | N20—C22—H221 | 109.5 |
N12—C13—C14 | 127.69 (14) | N20—C22—H222 | 109.5 |
N16—C13—C14 | 113.11 (14) | H221—C22—H222 | 109.5 |
C4—C14—C15 | 118.67 (15) | N20—C22—H223 | 109.5 |
C4—C14—C13 | 122.09 (14) | H221—C22—H223 | 109.5 |
C15—C14—C13 | 118.90 (15) | H222—C22—H223 | 109.5 |
C1—C15—C14 | 120.76 (17) | | |
| | | |
C15—C1—C2—C3 | −1.3 (3) | C11—N12—C13—N16 | −179.23 (15) |
Cl1—C1—C2—C3 | −179.89 (15) | C11—N12—C13—C14 | −1.0 (3) |
C1—C2—C3—C4 | 0.9 (3) | C3—C4—C14—C15 | −1.9 (2) |
C2—C3—C4—C14 | 0.7 (2) | N5—C4—C14—C15 | −178.96 (14) |
C2—C3—C4—N5 | 177.87 (16) | C3—C4—C14—C13 | 171.37 (14) |
C14—C4—N5—C6 | −53.9 (2) | N5—C4—C14—C13 | −5.7 (2) |
C3—C4—N5—C6 | 129.06 (17) | N12—C13—C14—C4 | 39.8 (2) |
C4—N5—C6—N7 | −129.63 (16) | N16—C13—C14—C4 | −141.95 (16) |
C4—N5—C6—C11 | 53.3 (2) | N12—C13—C14—C15 | −147.01 (17) |
C11—C6—N7—C8 | −2.2 (3) | N16—C13—C14—C15 | 31.3 (2) |
N5—C6—N7—C8 | −179.15 (16) | C2—C1—C15—C14 | 0.1 (3) |
C6—N7—C8—C9 | −1.2 (3) | Cl1—C1—C15—C14 | 178.71 (13) |
N7—C8—C9—C10 | 2.7 (3) | C4—C14—C15—C1 | 1.5 (2) |
C8—C9—C10—C11 | −0.8 (3) | C13—C14—C15—C1 | −171.99 (16) |
C9—C10—C11—C6 | −2.2 (2) | N12—C13—N16—C17 | −3.2 (3) |
C9—C10—C11—N12 | 169.30 (16) | C14—C13—N16—C17 | 178.33 (17) |
N7—C6—C11—C10 | 3.8 (2) | C13—N16—C17—C18 | 168.89 (18) |
N5—C6—C11—C10 | −179.43 (15) | N16—C17—C18—C19 | 51.8 (3) |
N7—C6—C11—N12 | −166.90 (15) | C17—C18—C19—N20 | −68.2 (3) |
N5—C6—C11—N12 | 9.8 (2) | C18—C19—N20—C21 | −71.8 (2) |
C10—C11—N12—C13 | 148.91 (16) | C18—C19—N20—C22 | 166.35 (19) |
C6—C11—N12—C13 | −40.5 (2) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N5—H5···N12i | 0.87 (2) | 2.49 (2) | 3.332 (2) | 162.9 (17) |
N16—H16···N20 | 0.82 (2) | 2.08 (2) | 2.787 (2) | 145 (2) |
Symmetry code: (i) x−1/2, −y+1/2, z−1/2. |
Experimental details
Crystal data |
Chemical formula | C17H20ClN5 |
Mr | 329.83 |
Crystal system, space group | Monoclinic, P21/n |
Temperature (K) | 293 |
a, b, c (Å) | 9.001 (1), 20.421 (3), 9.935 (1) |
β (°) | 109.545 (6) |
V (Å3) | 1720.9 (4) |
Z | 4 |
Radiation type | Mo Kα |
µ (mm−1) | 0.23 |
Crystal size (mm) | 0.50 × 0.50 × 0.50 |
|
Data collection |
Diffractometer | Enraf-Nonius CAD-4 diffractometer |
Absorption correction | – |
No. of measured, independent and observed [I > 2σ(I)] reflections | 7197, 3511, 3036 |
Rint | 0.022 |
(sin θ/λ)max (Å−1) | 0.624 |
|
Refinement |
R[F2 > 2σ(F2)], wR(F2), S | 0.044, 0.122, 1.11 |
No. of reflections | 3511 |
No. of parameters | 217 |
H-atom treatment | H atoms treated by a mixture of independent and constrained refinement |
Δρmax, Δρmin (e Å−3) | 0.34, −0.16 |
Selected geometric parameters (Å, º) topC4—N5 | 1.407 (2) | C13—N16 | 1.345 (2) |
N5—C6 | 1.4127 (19) | N16—C17 | 1.450 (2) |
C6—N7 | 1.330 (2) | C19—N20 | 1.474 (3) |
N7—C8 | 1.342 (2) | N20—C21 | 1.440 (3) |
C11—N12 | 1.407 (2) | N20—C22 | 1.459 (3) |
N12—C13 | 1.2945 (19) | | |
| | | |
C4—N5—C6 | 119.04 (13) | C13—N16—C17 | 124.69 (15) |
C6—N7—C8 | 117.74 (15) | C21—N20—C22 | 109.25 (19) |
C13—N12—C11 | 123.16 (13) | C21—N20—C19 | 113.98 (19) |
N12—C13—N16 | 119.18 (15) | C22—N20—C19 | 108.4 (2) |
| | | |
C14—C4—N5—C6 | −53.9 (2) | C13—N16—C17—C18 | 168.89 (18) |
C4—N5—C6—C11 | 53.3 (2) | N16—C17—C18—C19 | 51.8 (3) |
N5—C6—C11—N12 | 9.8 (2) | C17—C18—C19—N20 | −68.2 (3) |
C6—C11—N12—C13 | −40.5 (2) | C18—C19—N20—C21 | −71.8 (2) |
C11—N12—C13—N16 | −179.23 (15) | C18—C19—N20—C22 | 166.35 (19) |
N12—C13—N16—C17 | −3.2 (3) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N5—H5···N12i | 0.87 (2) | 2.49 (2) | 3.332 (2) | 162.9 (17) |
N16—H16···N20 | 0.82 (2) | 2.08 (2) | 2.787 (2) | 145 (2) |
Symmetry code: (i) x−1/2, −y+1/2, z−1/2. |
In the first part of our program, biosteric analogues of dibenzoazepines were synthesized by modulating the tricyclic nucleus (Liégeois et al., 1993, 1994). Later, new entities were further developed by modulating the N-methylpiperazine side chain either by varying the N-substituent or by replacing the piperazine ring by other nitrogen-containing rings or even by aliphatic diamines. The new compounds were used to explore the impact of such modifications on the binding affinities of these molecules for D4.2, 5-HT2 A and D2 L receptors. The title compound, (I), showed no affinity for the receptors tested. The flexibility of the side chain in the molecule is increased compared to the N-methylpiperazine analogues like, for example, 8-chloro-6-(4-methylpiperazin-1-yl)-11H-pyrido[2,3-b][1,4]benzodiazepine [clozapine drug (II); Petcher & Weber, 1976]. Nevertheless, the folding of the side chain is dominated by the existence of the intramolecular N16—H···N20(distal) hydrogen bond. In (I), the spatial position of the distal N atom, a possible pharmacophore, is modified and thus the interaction with the receptor sites could be compromised. Some geometrical features may be compared between (I) and (II). The dihedral angle between the two aromatic rings are 134.6 (2) in (I) and 115.0 (4)° in (II). The distances D1 and D2 between the N-distal atom and the the centres of the two aromatic rings are 4.754 (2) and 7.669 (2) Å in (I), and 5.972 (5) and 7.716 (5) Å in (II). In the crystal structure of (I), the side chain is more folded: D1 mainly is shorter than in (II) and in other dibenzo- or pyridobenzoazepine derivatives. In amidine moieties, the N═C double bond and C—N single bond are 1.295 (2) and 1.345 (2) Å in (I), and 1.293 (5) and 1.371 (5) in (II). The crystal packing is dominated by one hydrogen bond, viz. N5—H···N12.