Crystal structure of 5,11-di­hydro­pyrido[2,3-b][1,4]benzodiazepin-6-one

Riad, N.M.; Zlotos, D.P.; Holzgrabe, U.

doi:10.1107/S2056989015006817

organic compounds

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Volume 71| Part 5| May 2015| Pages o304-o305

https://doi.org/10.1107/S2056989015006817

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Crystal structure of 5,11-dihydropyrido[2,3-b][1,4]benzodiazepin-6-one

Noura M. Riad,^a Darius P. Zlotos ^a ^* and Ulrike Holzgrabe ^b

^aThe German University in Cairo, Department of Pharmaceutical Chemistry, New Cairo City, 11835 Cairo, Egypt, and ^bInstitute of Pharmacy and Food Chemistry, Wuerzburg University, 97074 Wuerzburg, Germany
^*Correspondence e-mail: darius.zlotos@guc.edu.eg

Edited by W. T. A. Harrison, University of Aberdeen, Scotland (Received 2 April 2015; accepted 4 April 2015; online 11 April 2015)

The title compound, C₁₂H₉N₃O, is an intermediate in the synthesis of the muscarinic M2 receptor antagonist AFDX-384. The seven-membered ring adopts a boat conformation and the dihedral angle between the planes of the aromatic rings is 41.51 (9)°. In the crystal, molecules are linked into [001] chains of alternating inversion dimers formed by pairs of N—H⋯O hydrogen bonds and pairs of N—H⋯N hydrogen bonds. In both cases, R₂²(8) loops are generated.

Keywords: crystal structure; pyridobenzodiazepine; boat conformation; hydrogen bonding.

CCDC reference: 1024195

1. Related literature

For the synthesis of the title compound, see: Holzgrabe & Heller (2003 ). For the biological activity of substituted 5,11-dihydropyrido[2,3-b][1,4]benzodiazepin-6-ones, see: Mohr et al. (2004 ); Tahtaoui et al. (2004 ).

2. Experimental

2.1. Crystal data

C₁₂H₉N₃O
M_r = 211.22
Triclinic, $[P \overline 1]$
a = 3.7598 (5) Å
b = 10.2467 (14) Å
c = 12.8768 (17) Å
α = 104.628 (6)°
β = 96.616 (5)°
γ = 98.009 (4)°
V = 469.43 (11) Å³
Z = 2
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 100 K
0.35 × 0.26 × 0.06 mm

2.2. Data collection

Bruker APEXII CCD diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2013 ) T_min = 0.898, T_max = 0.959
6425 measured reflections
2000 independent reflections
1467 reflections with I > 2σ(I)
R_int = 0.035

2.3. Refinement

R[F² > 2σ(F²)] = 0.041
wR(F²) = 0.110
S = 1.06
2000 reflections
153 parameters
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.23 e Å⁻³
Δρ_min = −0.22 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N2—H2⋯O1ⁱ	0.87 (2)	1.98 (2)	2.840 (2)	175 (2)
N3—H3⋯N1ⁱⁱ	0.93 (2)	2.28 (2)	3.200 (2)	168.7 (19)
Symmetry codes: (i) -x+1, -y+1, -z+1; (ii) -x+1, -y+1, -z+2.

Data collection: APEX2 (Bruker, 2013); cell refinement: SAINT (Bruker, 2013); data reduction: SAINT; program(s) used to solve structure: OLEX2.solve (Bourhis et al., 2015 ); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ); molecular graphics: OLEX2 (Dolomanov et al., 2009 ); software used to prepare material for publication: OLEX2, Mercury (Macrae et al., 2006 ) and enCIFer (Allen et al., 2004 ).

Supporting information

CCDC reference: 1024195

Crystal structure: contains datablock I. DOI: https://doi.org/10.1107/S2056989015006817/hb7396sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2056989015006817/hb7396Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2056989015006817/hb7396Isup3.cml

checkCIF report

Related literature top

For the synthesis of the title compound, see: Holzgrabe & Heller (2003). For the biological activity of substituted 5,11-dihydropyrido[2,3-b][1,4]benzodiazepin-6-ones, see: Mohr et al. (2004); Tahtaoui et al. (2004).

Experimental top

The title compound was synthesized as previously reported (Holzgrabe & Heller, 2003) and recrystallized from methanol–toluene.

Structure description top

For the synthesis of the title compound, see: Holzgrabe & Heller (2003). For the biological activity of substituted 5,11-dihydropyrido[2,3-b][1,4]benzodiazepin-6-ones, see: Mohr et al. (2004); Tahtaoui et al. (2004).

Computing details top

Data collection: APEX2 (Bruker, 2013); cell refinement: SAINT (Bruker, 2013); data reduction: SAINT (Bruker, 2013); program(s) used to solve structure: olex2.solve (Bourhis et al., 2015); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009), Mercury (Macrae et al., 2006) and enCIFer (Allen et al., 2004).

Figures top

	Fig. 1. ORTEP drawing of the title compound showing atom labeling and 50% probability displacement ellipsoids.
	Fig. 2. Unit-cell packing of the title compound showing two inverted molecules linked by hydrogen bonds indicated as dotted lines.

5,11-Dihydropyrido[2,3-b][1,4]benzodiazepin-6-one top

Crystal data top

C₁₂H₉N₃O	Z = 2
M_r = 211.22	F(000) = 220
Triclinic, P1	D_x = 1.494 Mg m⁻³
a = 3.7598 (5) Å	Mo Kα radiation, λ = 0.71073 Å
b = 10.2467 (14) Å	Cell parameters from 1512 reflections
c = 12.8768 (17) Å	θ = 2.3–26.2°
α = 104.628 (6)°	µ = 0.10 mm⁻¹
β = 96.616 (5)°	T = 100 K
γ = 98.009 (4)°	Plate, colourless
V = 469.43 (11) Å³	0.35 × 0.26 × 0.06 mm

Data collection top

Bruker APEXII CCD diffractometer	1467 reflections with I > 2σ(I)
φ and ω scans	R_int = 0.035
Absorption correction: multi-scan (SADABS; Bruker, 2013)	θ_max = 26.8°, θ_min = 1.7°
T_min = 0.898, T_max = 0.959	h = −4→4
6425 measured reflections	k = −12→12
2000 independent reflections	l = −16→16

Refinement top

Refinement on F²	Primary atom site location: iterative
Least-squares matrix: full	Hydrogen site location: mixed
R[F² > 2σ(F²)] = 0.041	H atoms treated by a mixture of independent and constrained refinement
wR(F²) = 0.110	w = 1/[σ²(F_o²) + (0.0437P)² + 0.2092P] where P = (F_o² + 2F_c²)/3
S = 1.06	(Δ/σ)_max < 0.001
2000 reflections	Δρ_max = 0.23 e Å⁻³
153 parameters	Δρ_min = −0.22 e Å⁻³
0 restraints

Crystal data top

C₁₂H₉N₃O	γ = 98.009 (4)°
M_r = 211.22	V = 469.43 (11) Å³
Triclinic, P1	Z = 2
a = 3.7598 (5) Å	Mo Kα radiation
b = 10.2467 (14) Å	µ = 0.10 mm⁻¹
c = 12.8768 (17) Å	T = 100 K
α = 104.628 (6)°	0.35 × 0.26 × 0.06 mm
β = 96.616 (5)°

Data collection top

Bruker APEXII CCD diffractometer	2000 independent reflections
Absorption correction: multi-scan (SADABS; Bruker, 2013)	1467 reflections with I > 2σ(I)
T_min = 0.898, T_max = 0.959	R_int = 0.035
6425 measured reflections

Refinement top

R[F² > 2σ(F²)] = 0.041	0 restraints
wR(F²) = 0.110	H atoms treated by a mixture of independent and constrained refinement
S = 1.06	Δρ_max = 0.23 e Å⁻³
2000 reflections	Δρ_min = −0.22 e Å⁻³
153 parameters

Special details top

Experimental. Absorption correctiuon: SADABS-2012/1 (Bruker,2012) was used for absorption correction. wR2(int) was 0.0475 before and 0.0419 after correction. The Ratio of minimum to maximum transmission is 0.9367. The λ/2 correction factor is 0.0015.

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.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
O1	0.3371 (4)	0.33046 (14)	0.49729 (10)	0.0196 (3)
N3	0.4460 (4)	0.42582 (15)	0.83790 (13)	0.0152 (4)
N1	0.3852 (4)	0.64248 (15)	0.93418 (12)	0.0157 (4)
N2	0.3945 (4)	0.51349 (17)	0.63963 (13)	0.0163 (4)
C4	0.3379 (5)	0.59565 (19)	0.74023 (14)	0.0143 (4)
C12	0.3836 (5)	0.55643 (19)	0.83732 (14)	0.0133 (4)
C1	0.3340 (5)	0.7706 (2)	0.93750 (16)	0.0174 (4)
H1	0.3431	0.8320	1.0051	0.021*
C10	0.0818 (5)	0.20571 (19)	0.81375 (15)	0.0148 (4)
H10	0.1291	0.2203	0.8887	0.018*
C3	0.2728 (5)	0.72576 (19)	0.74596 (15)	0.0168 (4)
H3A	0.2314	0.7535	0.6829	0.020*
C6	0.1477 (5)	0.28402 (18)	0.65494 (14)	0.0137 (4)
C7	−0.0602 (5)	0.15952 (19)	0.59213 (15)	0.0162 (4)
H7	−0.1071	0.1434	0.5171	0.019*
C11	0.2231 (5)	0.30746 (18)	0.76774 (14)	0.0130 (4)
C5	0.2998 (5)	0.37759 (19)	0.59331 (14)	0.0150 (4)
C2	0.2691 (5)	0.81567 (19)	0.84655 (15)	0.0170 (4)
H2A	0.2239	0.9039	0.8521	0.020*
C8	−0.1979 (5)	0.0597 (2)	0.63858 (16)	0.0177 (4)
H8	−0.3366	−0.0226	0.5956	0.021*
C9	−0.1254 (5)	0.08462 (19)	0.75055 (15)	0.0168 (4)
H9	−0.2180	0.0187	0.7831	0.020*
H3	0.497 (6)	0.419 (2)	0.9087 (19)	0.027 (6)*
H2	0.467 (6)	0.557 (2)	0.5943 (19)	0.031 (7)*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
O1	0.0270 (8)	0.0201 (7)	0.0118 (7)	0.0026 (6)	0.0058 (6)	0.0042 (6)
N3	0.0192 (9)	0.0143 (8)	0.0113 (8)	0.0023 (7)	−0.0008 (7)	0.0036 (7)
N1	0.0174 (8)	0.0157 (8)	0.0137 (8)	0.0016 (7)	0.0032 (6)	0.0039 (7)
N2	0.0212 (9)	0.0165 (9)	0.0122 (8)	0.0010 (7)	0.0043 (7)	0.0062 (7)
C4	0.0119 (9)	0.0174 (10)	0.0125 (9)	−0.0007 (8)	0.0012 (7)	0.0041 (8)
C12	0.0101 (9)	0.0155 (10)	0.0143 (9)	−0.0002 (7)	0.0015 (7)	0.0053 (8)
C1	0.0159 (10)	0.0178 (10)	0.0173 (10)	0.0024 (8)	0.0046 (8)	0.0018 (8)
C10	0.0158 (9)	0.0184 (10)	0.0128 (9)	0.0052 (8)	0.0031 (7)	0.0072 (8)
C3	0.0153 (10)	0.0203 (10)	0.0166 (10)	0.0021 (8)	0.0011 (8)	0.0097 (8)
C6	0.0117 (9)	0.0151 (10)	0.0154 (9)	0.0038 (8)	0.0046 (7)	0.0043 (8)
C7	0.0150 (10)	0.0192 (10)	0.0145 (9)	0.0047 (8)	0.0005 (7)	0.0044 (8)
C11	0.0105 (9)	0.0148 (9)	0.0139 (9)	0.0040 (7)	0.0027 (7)	0.0032 (8)
C5	0.0135 (9)	0.0193 (10)	0.0127 (9)	0.0029 (8)	0.0013 (7)	0.0056 (8)
C2	0.0160 (10)	0.0163 (10)	0.0209 (10)	0.0047 (8)	0.0045 (8)	0.0071 (9)
C8	0.0139 (10)	0.0151 (10)	0.0215 (10)	0.0012 (8)	0.0004 (8)	0.0024 (8)
C9	0.0135 (9)	0.0175 (10)	0.0229 (11)	0.0039 (8)	0.0054 (8)	0.0102 (9)

Geometric parameters (Å, º) top

O1—C5	1.240 (2)	C10—C11	1.396 (3)
N3—C12	1.392 (2)	C10—C9	1.372 (3)
N3—C11	1.406 (2)	C3—H3A	0.9300
N3—H3	0.93 (2)	C3—C2	1.390 (3)
N1—C12	1.332 (2)	C6—C7	1.396 (3)
N1—C1	1.344 (2)	C6—C11	1.399 (2)
N2—C4	1.412 (2)	C6—C5	1.487 (3)
N2—C5	1.347 (2)	C7—H7	0.9300
N2—H2	0.87 (3)	C7—C8	1.380 (3)
C4—C12	1.406 (3)	C2—H2A	0.9300
C4—C3	1.374 (3)	C8—H8	0.9300
C1—H1	0.9300	C8—C9	1.387 (3)
C1—C2	1.372 (3)	C9—H9	0.9300
C10—H10	0.9300

C12—N3—C11	121.58 (15)	C7—C6—C11	119.17 (17)
C12—N3—H3	110.9 (13)	C7—C6—C5	115.70 (16)
C11—N3—H3	112.7 (13)	C11—C6—C5	124.91 (17)
C12—N1—C1	117.87 (16)	C6—C7—H7	119.2
C4—N2—H2	115.9 (15)	C8—C7—C6	121.68 (18)
C5—N2—C4	130.98 (17)	C8—C7—H7	119.2
C5—N2—H2	112.2 (15)	C10—C11—N3	117.55 (16)
C12—C4—N2	123.05 (17)	C10—C11—C6	118.58 (17)
C3—C4—N2	118.46 (17)	C6—C11—N3	123.83 (17)
C3—C4—C12	118.12 (17)	O1—C5—N2	119.17 (17)
N3—C12—C4	121.47 (16)	O1—C5—C6	119.73 (17)
N1—C12—N3	115.93 (16)	N2—C5—C6	121.09 (16)
N1—C12—C4	122.55 (17)	C1—C2—C3	118.16 (18)
N1—C1—H1	118.2	C1—C2—H2A	120.9
N1—C1—C2	123.52 (18)	C3—C2—H2A	120.9
C2—C1—H1	118.2	C7—C8—H8	120.7
C11—C10—H10	119.4	C7—C8—C9	118.69 (18)
C9—C10—H10	119.4	C9—C8—H8	120.7
C9—C10—C11	121.27 (17)	C10—C9—C8	120.60 (18)
C4—C3—H3A	120.2	C10—C9—H9	119.7
C4—C3—C2	119.64 (17)	C8—C9—H9	119.7
C2—C3—H3A	120.2

N1—C1—C2—C3	−3.0 (3)	C7—C6—C11—C10	−1.0 (3)
N2—C4—C12—N3	−7.9 (3)	C7—C6—C5—O1	−22.0 (3)
N2—C4—C12—N1	169.29 (18)	C7—C6—C5—N2	157.23 (17)
N2—C4—C3—C2	−170.60 (17)	C7—C8—C9—C10	−0.5 (3)
C4—N2—C5—O1	170.53 (18)	C11—N3—C12—N1	132.19 (18)
C4—N2—C5—C6	−8.7 (3)	C11—N3—C12—C4	−50.5 (2)
C4—C3—C2—C1	0.4 (3)	C11—C10—C9—C8	0.5 (3)
C12—N3—C11—C10	−129.09 (19)	C11—C6—C7—C8	1.0 (3)
C12—N3—C11—C6	53.5 (2)	C11—C6—C5—O1	152.47 (18)
C12—N1—C1—C2	2.1 (3)	C11—C6—C5—N2	−28.3 (3)
C12—C4—C3—C2	2.7 (3)	C5—N2—C4—C12	42.4 (3)
C1—N1—C12—N3	178.56 (16)	C5—N2—C4—C3	−144.7 (2)
C1—N1—C12—C4	1.3 (3)	C5—C6—C7—C8	175.82 (17)
C3—C4—C12—N3	179.21 (17)	C5—C6—C11—N3	2.0 (3)
C3—C4—C12—N1	−3.6 (3)	C5—C6—C11—C10	−175.34 (17)
C6—C7—C8—C9	−0.2 (3)	C9—C10—C11—N3	−177.23 (16)
C7—C6—C11—N3	176.35 (17)	C9—C10—C11—C6	0.3 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···O1ⁱ	0.87 (2)	1.98 (2)	2.840 (2)	175 (2)
N3—H3···N1ⁱⁱ	0.93 (2)	2.28 (2)	3.200 (2)	168.7 (19)

Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) −x+1, −y+1, −z+2.

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N2—H2···O1ⁱ	0.87 (2)	1.98 (2)	2.840 (2)	175 (2)
N3—H3···N1ⁱⁱ	0.93 (2)	2.28 (2)	3.200 (2)	168.7 (19)

Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) −x+1, −y+1, −z+2.

Acknowledgements

The authors thank Andreas Lorbach and Todd B. Marder (Institute of Inorganic Chemistry, Wuerzburg University) for the data collection and structure solution. We appreciate the financial support provided to NMR by the Deutscher Akademischer Austauschdienst (DAAD). Thanks are also due to the Deutsche Forschungsgemeinschaft for financial support (SFB 630, Recognition, Preparation and Functional Analysis of Agents against Infectious Diseases, project A1).

References

Allen, F. H., Johnson, O., Shields, G. P., Smith, B. R. & Towler, M. (2004). J. Appl. Cryst. 37, 335–338. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Bourhis, L. J., Dolomanov, O. V., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2015). Acta Cryst. A71, 59–75. Web of Science CrossRef IUCr Journals Google Scholar
Bruker (2013). APEX2, SAINT and SADABS. Bruker AXS Inc., Madison, Wisconsin, USA. Google Scholar
Dolomanov, O. V., Bourhis, L. J., Gildea, R. J., Howard, J. A. K. & Puschmann, H. (2009). J. Appl. Cryst. 42, 339–341. Web of Science CrossRef CAS IUCr Journals Google Scholar
Holzgrabe, U. & Heller, E. (2003). Tetrahedron, 59, 781–787. Web of Science CrossRef CAS Google Scholar
Macrae, C. F., Edgington, P. R., McCabe, P., Pidcock, E., Shields, G. P., Taylor, R., Towler, M. & van de Streek, J. (2006). J. Appl. Cryst. 39, 453–457. Web of Science CSD CrossRef CAS IUCr Journals Google Scholar
Mohr, M., Heller, E., Ataie, A., Mohr, K. & Holzgrabe, U. (2004). J. Med. Chem. 47, 3324–3327. Web of Science CrossRef PubMed CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Tahtaoui, C., Parrot, I., Klotz, P., Guillier, F., Galzi, J.-C., Hibert, M. & Ilien, B. (2004). J. Med. Chem. 47, 4300–4315. Web of Science CrossRef PubMed CAS Google Scholar