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The crystal structure determination of the title compound, C17H20ClN5, has been undertaken as part of studies on antipsychotic drugs. Its structure is compared with that of clozapine (C18H19ClN4), 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

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536801021286/bt6097sup1.cif
Contains datablocks I, sm0301

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S1600536801021286/bt6097Isup2.hkl
Contains datablock I

CCDC reference: 180551

Key indicators

  • Single-crystal X-ray study
  • T = 293 K
  • Mean [sigma](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








Comment top

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 NC 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.

Experimental top

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).

Refinement top

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.

Computing details top

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.

Figures top
[Figure 1] Fig. 1. The molecular structure of (I) with the atom-labelling scheme. Displacement ellipsoids are shown at the 50% probability level.
8-Chloro-6-(3-dimethylaminopropylamino)-11H-pyrido[2,3-b][1,4]benzodiazepine top
Crystal data top
C17H20ClN5F(000) = 696
Mr = 329.83Dx = 1.273 Mg m3
Monoclinic, P21/nMo Kα radiation, λ = 0.71069 Å
a = 9.001 (1) ÅCell parameters from 25 reflections
b = 20.421 (3) Åθ = 20–23°
c = 9.935 (1) ŵ = 0.23 mm1
β = 109.545 (6)°T = 293 K
V = 1720.9 (4) Å3Prism, yellow
Z = 40.50 × 0.50 × 0.50 mm
Data collection top
Enraf-Nonius CAD-4
diffractometer
Rint = 0.022
Radiation source: fine-focus sealed tubeθmax = 26.3°, θmin = 2.0°
Graphite monochromatorh = 011
θ/2θ scansk = 2525
7197 measured reflectionsl = 1211
3511 independent reflections3 standard reflections every 200 reflections
3036 reflections with I > 2σ(I) intensity decay: 4%
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen 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)] = 0.044H 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 reflectionsΔρmax = 0.34 e Å3
217 parametersΔρmin = 0.16 e Å3
0 restraintsExtinction correction: SHELXL97, Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.078 (4)
Crystal data top
C17H20ClN5V = 1720.9 (4) Å3
Mr = 329.83Z = 4
Monoclinic, P21/nMo Kα radiation
a = 9.001 (1) ŵ = 0.23 mm1
b = 20.421 (3) ÅT = 293 K
c = 9.935 (1) Å0.50 × 0.50 × 0.50 mm
β = 109.545 (6)°
Data collection top
Enraf-Nonius CAD-4
diffractometer
Rint = 0.022
7197 measured reflections3 standard reflections every 200 reflections
3511 independent reflections intensity decay: 4%
3036 reflections with I > 2σ(I)
Refinement top
R[F2 > 2σ(F2)] = 0.0440 restraints
wR(F2) = 0.122H atoms treated by a mixture of independent and constrained refinement
S = 1.11Δρmax = 0.34 e Å3
3511 reflectionsΔρmin = 0.16 e Å3
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
xyzUiso*/Ueq
C10.1994 (2)0.07844 (9)0.63588 (19)0.0541 (4)
C20.0909 (2)0.12621 (10)0.57305 (18)0.0558 (5)
H20.02710.12240.47800.067*
C30.0776 (2)0.17979 (9)0.65227 (17)0.0491 (4)
H30.00310.21190.61030.059*
C40.17410 (19)0.18683 (8)0.79491 (16)0.0402 (3)
N50.15959 (18)0.24356 (7)0.86991 (14)0.0464 (3)
H50.094 (2)0.2720 (10)0.817 (2)0.056*
C60.1401 (2)0.23693 (8)1.00457 (16)0.0416 (4)
N70.02017 (18)0.27092 (8)1.01874 (15)0.0513 (4)
C80.0044 (2)0.26769 (10)1.1445 (2)0.0591 (5)
H80.08670.29191.15610.071*
C90.0854 (2)0.23063 (10)1.25634 (19)0.0574 (5)
H90.06210.22821.34060.069*
C100.2120 (2)0.19673 (9)1.24123 (17)0.0504 (4)
H100.27560.17161.31660.061*
C110.24474 (18)0.19994 (8)1.11439 (16)0.0407 (3)
N120.38923 (16)0.17396 (7)1.11346 (14)0.0436 (3)
C130.40794 (18)0.14789 (8)1.00144 (16)0.0414 (3)
C140.28679 (18)0.13908 (8)0.85719 (16)0.0402 (3)
C150.2966 (2)0.08439 (8)0.77592 (18)0.0481 (4)
H150.36960.05160.81680.058*
N160.54988 (17)0.12354 (8)1.01059 (16)0.0524 (4)
H160.567 (2)0.1146 (10)0.937 (2)0.063*
C170.6895 (2)0.12695 (11)1.1369 (2)0.0594 (5)
H1710.66380.11301.21970.071*
H1720.72670.17181.15240.071*
C180.8176 (2)0.08352 (12)1.1188 (2)0.0708 (6)
H1810.91300.09051.19970.085*
H1820.78640.03821.12180.085*
C190.8555 (2)0.09373 (12)0.9846 (3)0.0715 (6)
H1910.87820.13980.97700.086*
H1920.95010.06920.99160.086*
N200.72907 (19)0.07374 (8)0.85317 (17)0.0573 (4)
C210.7089 (3)0.00392 (12)0.8365 (3)0.0850 (7)
H2110.62640.00550.74830.128*
H2120.68130.01360.91470.128*
H2130.80550.01560.83550.128*
C220.7641 (4)0.10054 (13)0.7309 (3)0.0897 (8)
H2210.85760.08020.72440.135*
H2220.78040.14690.74290.135*
H2230.67730.09210.64510.135*
Cl10.21868 (8)0.01038 (3)0.53802 (6)0.0864 (2)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0612 (11)0.0547 (10)0.0499 (9)0.0064 (8)0.0231 (8)0.0148 (8)
C20.0648 (11)0.0632 (11)0.0383 (8)0.0051 (9)0.0156 (8)0.0055 (8)
C30.0549 (10)0.0533 (9)0.0398 (8)0.0016 (8)0.0166 (7)0.0039 (7)
C40.0466 (8)0.0418 (8)0.0379 (7)0.0032 (6)0.0218 (6)0.0013 (6)
N50.0616 (9)0.0421 (7)0.0409 (7)0.0071 (6)0.0244 (7)0.0038 (5)
C60.0486 (9)0.0412 (8)0.0393 (7)0.0044 (6)0.0202 (7)0.0046 (6)
N70.0536 (9)0.0570 (8)0.0468 (8)0.0084 (7)0.0215 (7)0.0040 (6)
C80.0581 (11)0.0700 (12)0.0573 (10)0.0058 (9)0.0300 (9)0.0101 (9)
C90.0603 (11)0.0756 (12)0.0452 (9)0.0028 (9)0.0295 (8)0.0068 (8)
C100.0549 (10)0.0608 (10)0.0379 (8)0.0037 (8)0.0186 (7)0.0009 (7)
C110.0414 (8)0.0444 (8)0.0389 (7)0.0059 (6)0.0169 (6)0.0058 (6)
N120.0420 (7)0.0498 (8)0.0398 (6)0.0022 (6)0.0147 (5)0.0036 (6)
C130.0418 (8)0.0416 (8)0.0437 (8)0.0028 (6)0.0184 (6)0.0013 (6)
C140.0433 (8)0.0416 (8)0.0396 (7)0.0056 (6)0.0192 (6)0.0025 (6)
C150.0505 (9)0.0469 (9)0.0495 (9)0.0025 (7)0.0204 (7)0.0066 (7)
N160.0440 (8)0.0687 (10)0.0451 (8)0.0057 (7)0.0159 (6)0.0072 (7)
C170.0499 (10)0.0700 (12)0.0540 (10)0.0053 (9)0.0117 (8)0.0081 (9)
C180.0539 (11)0.0812 (14)0.0674 (12)0.0137 (10)0.0072 (9)0.0108 (11)
C190.0508 (11)0.0738 (14)0.0917 (16)0.0047 (10)0.0263 (11)0.0112 (12)
N200.0578 (9)0.0575 (9)0.0621 (9)0.0071 (7)0.0272 (8)0.0035 (7)
C210.0978 (19)0.0627 (13)0.0983 (18)0.0005 (13)0.0377 (15)0.0068 (12)
C220.119 (2)0.0746 (15)0.1017 (19)0.0139 (15)0.0724 (17)0.0053 (13)
Cl10.1033 (5)0.0785 (4)0.0739 (4)0.0039 (3)0.0250 (3)0.0389 (3)
Geometric parameters (Å, º) top
C1—C21.374 (3)C13—C141.493 (2)
C1—C151.379 (2)C14—C151.398 (2)
C1—Cl11.7379 (18)C15—H150.9300
C2—C31.376 (2)N16—C171.450 (2)
C2—H20.9300N16—H160.82 (2)
C3—C41.400 (2)C17—C181.512 (3)
C3—H30.9300C17—H1710.9700
C4—C141.394 (2)C17—H1720.9700
C4—N51.407 (2)C18—C191.498 (3)
N5—C61.4127 (19)C18—H1810.9700
N5—H50.87 (2)C18—H1820.9700
C6—N71.330 (2)C19—N201.474 (3)
C6—C111.400 (2)C19—H1910.9700
N7—C81.342 (2)C19—H1920.9700
C8—C91.363 (3)N20—C211.440 (3)
C8—H80.9300N20—C221.459 (3)
C9—C101.384 (3)C21—H2110.9600
C9—H90.9300C21—H2120.9600
C10—C111.388 (2)C21—H2130.9600
C10—H100.9300C22—H2210.9600
C11—N121.407 (2)C22—H2220.9600
N12—C131.2945 (19)C22—H2230.9600
C13—N161.345 (2)
C2—C1—C15120.71 (16)C1—C15—H15119.6
C2—C1—Cl1120.17 (14)C14—C15—H15119.6
C15—C1—Cl1119.10 (15)C13—N16—C17124.69 (15)
C1—C2—C3119.30 (16)C13—N16—H16119.0 (15)
C1—C2—H2120.3C17—N16—H16114.4 (15)
C3—C2—H2120.3N16—C17—C18110.11 (16)
C2—C3—C4121.15 (17)N16—C17—H171109.6
C2—C3—H3119.4C18—C17—H171109.6
C4—C3—H3119.4N16—C17—H172109.6
C14—C4—C3119.37 (14)C18—C17—H172109.6
C14—C4—N5121.58 (14)H171—C17—H172108.2
C3—C4—N5118.99 (15)C19—C18—C17115.69 (19)
C4—N5—C6119.04 (13)C19—C18—H181108.4
C4—N5—H5113.3 (13)C17—C18—H181108.4
C6—N5—H5111.1 (13)C19—C18—H182108.4
N7—C6—C11123.86 (14)C17—C18—H182108.4
N7—C6—N5114.36 (14)H181—C18—H182107.4
C11—C6—N5121.70 (14)N20—C19—C18114.33 (18)
C6—N7—C8117.74 (15)N20—C19—H191108.7
N7—C8—C9123.29 (18)C18—C19—H191108.7
N7—C8—H8118.4N20—C19—H192108.7
C9—C8—H8118.4C18—C19—H192108.7
C8—C9—C10118.32 (16)H191—C19—H192107.6
C8—C9—H9120.8C21—N20—C22109.25 (19)
C10—C9—H9120.8C21—N20—C19113.98 (19)
C9—C10—C11120.50 (17)C22—N20—C19108.4 (2)
C9—C10—H10119.8N20—C21—H211109.5
C11—C10—H10119.8N20—C21—H212109.5
C10—C11—C6116.17 (15)H211—C21—H212109.5
C10—C11—N12117.74 (15)N20—C21—H213109.5
C6—C11—N12125.48 (14)H211—C21—H213109.5
C13—N12—C11123.16 (13)H212—C21—H213109.5
N12—C13—N16119.18 (15)N20—C22—H221109.5
N12—C13—C14127.69 (14)N20—C22—H222109.5
N16—C13—C14113.11 (14)H221—C22—H222109.5
C4—C14—C15118.67 (15)N20—C22—H223109.5
C4—C14—C13122.09 (14)H221—C22—H223109.5
C15—C14—C13118.90 (15)H222—C22—H223109.5
C1—C15—C14120.76 (17)
C15—C1—C2—C31.3 (3)C11—N12—C13—N16179.23 (15)
Cl1—C1—C2—C3179.89 (15)C11—N12—C13—C141.0 (3)
C1—C2—C3—C40.9 (3)C3—C4—C14—C151.9 (2)
C2—C3—C4—C140.7 (2)N5—C4—C14—C15178.96 (14)
C2—C3—C4—N5177.87 (16)C3—C4—C14—C13171.37 (14)
C14—C4—N5—C653.9 (2)N5—C4—C14—C135.7 (2)
C3—C4—N5—C6129.06 (17)N12—C13—C14—C439.8 (2)
C4—N5—C6—N7129.63 (16)N16—C13—C14—C4141.95 (16)
C4—N5—C6—C1153.3 (2)N12—C13—C14—C15147.01 (17)
C11—C6—N7—C82.2 (3)N16—C13—C14—C1531.3 (2)
N5—C6—N7—C8179.15 (16)C2—C1—C15—C140.1 (3)
C6—N7—C8—C91.2 (3)Cl1—C1—C15—C14178.71 (13)
N7—C8—C9—C102.7 (3)C4—C14—C15—C11.5 (2)
C8—C9—C10—C110.8 (3)C13—C14—C15—C1171.99 (16)
C9—C10—C11—C62.2 (2)N12—C13—N16—C173.2 (3)
C9—C10—C11—N12169.30 (16)C14—C13—N16—C17178.33 (17)
N7—C6—C11—C103.8 (2)C13—N16—C17—C18168.89 (18)
N5—C6—C11—C10179.43 (15)N16—C17—C18—C1951.8 (3)
N7—C6—C11—N12166.90 (15)C17—C18—C19—N2068.2 (3)
N5—C6—C11—N129.8 (2)C18—C19—N20—C2171.8 (2)
C10—C11—N12—C13148.91 (16)C18—C19—N20—C22166.35 (19)
C6—C11—N12—C1340.5 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N5—H5···N12i0.87 (2)2.49 (2)3.332 (2)162.9 (17)
N16—H16···N200.82 (2)2.08 (2)2.787 (2)145 (2)
Symmetry code: (i) x1/2, y+1/2, z1/2.

Experimental details

Crystal data
Chemical formulaC17H20ClN5
Mr329.83
Crystal system, space groupMonoclinic, P21/n
Temperature (K)293
a, b, c (Å)9.001 (1), 20.421 (3), 9.935 (1)
β (°) 109.545 (6)
V3)1720.9 (4)
Z4
Radiation typeMo Kα
µ (mm1)0.23
Crystal size (mm)0.50 × 0.50 × 0.50
Data collection
DiffractometerEnraf-Nonius CAD-4
diffractometer
Absorption correction
No. of measured, independent and
observed [I > 2σ(I)] reflections
7197, 3511, 3036
Rint0.022
(sin θ/λ)max1)0.624
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.044, 0.122, 1.11
No. of reflections3511
No. of parameters217
H-atom treatmentH atoms treated by a mixture of independent and constrained refinement
Δρmax, Δρmin (e Å3)0.34, 0.16

Computer programs: CAD-4 EXPRESS (Enraf-Nonius, 1992), CAD-4 EXPRESS, HELENA (Spek, 1997), SIR92 (Altomare et al., 1993), SHELXL97 (Sheldrick, 1997), ORTEPIII (Burnett & Johnson, 1996), SHELXL97.

Selected geometric parameters (Å, º) top
C4—N51.407 (2)C13—N161.345 (2)
N5—C61.4127 (19)N16—C171.450 (2)
C6—N71.330 (2)C19—N201.474 (3)
N7—C81.342 (2)N20—C211.440 (3)
C11—N121.407 (2)N20—C221.459 (3)
N12—C131.2945 (19)
C4—N5—C6119.04 (13)C13—N16—C17124.69 (15)
C6—N7—C8117.74 (15)C21—N20—C22109.25 (19)
C13—N12—C11123.16 (13)C21—N20—C19113.98 (19)
N12—C13—N16119.18 (15)C22—N20—C19108.4 (2)
C14—C4—N5—C653.9 (2)C13—N16—C17—C18168.89 (18)
C4—N5—C6—C1153.3 (2)N16—C17—C18—C1951.8 (3)
N5—C6—C11—N129.8 (2)C17—C18—C19—N2068.2 (3)
C6—C11—N12—C1340.5 (2)C18—C19—N20—C2171.8 (2)
C11—N12—C13—N16179.23 (15)C18—C19—N20—C22166.35 (19)
N12—C13—N16—C173.2 (3)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N5—H5···N12i0.87 (2)2.49 (2)3.332 (2)162.9 (17)
N16—H16···N200.82 (2)2.08 (2)2.787 (2)145 (2)
Symmetry code: (i) x1/2, y+1/2, z1/2.
 

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