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

Abstract

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, R ₂ ²(8) loops are generated.

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 ▸).

Experimental  

Crystal data  

• C₁₂H₉N₃O

• M _r = 211.22

• Triclinic,

• 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) ų

• Z = 2

• Mo Kα radiation

• μ = 0.10 mm⁻¹

• T = 100 K

• 0.35 × 0.26 × 0.06 mm

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

Refinement  

• R[F ² > 2σ(F ²)] = 0.041

• wR(F ²) = 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

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 ▸).

Supplementary Material

CCDC reference: 1024195

Additional supporting information: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (, ).

DHA	DH	HA	D A	DHA
N2H2O1i	0.87(2)	1.98(2)	2.840(2)	175(2)
N3H3N1ii	0.93(2)	2.28(2)	3.200(2)	168.7(19)

Symmetry codes: (i) ; (ii) .

supplementary crystallographic information

S1. Experimental

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

S2. Refinement

The N- and C-bound H atoms were included in calculated positions and refined as riding: N2—H = 0.86 Å, C—H and N3—H = 0.93 Å with U_iso(H) = 1.2U_eq(C).

Figures

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.

Crystal data

C12H9N3O	Z = 2
Mr = 211.22	F(000) = 220
Triclinic, P1	Dx = 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

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

Refinement

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(Fo2) + (0.0437P)2 + 0.2092P] where P = (Fo2 + 2Fc2)/3
S = 1.06	(Δ/σ)max < 0.001
2000 reflections	Δρmax = 0.23 e Å−3
153 parameters	Δρmin = −0.22 e Å−3
0 restraints

Special details

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 (Ų)

	x	y	z	Uiso*/Ueq
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 (Ų)

	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)

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)

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.