rac-Ethyl (8aR,9aS)-8a-methyl-8-(4-nitro­phen­yl)-9a,10-diphenyl-12-(p-tol­yl)-9,9a-dihydro-8aH-di-1,2,4-triazolo[4,3-a:3′,4′-d][1,5]benzodiazepine-6-carboxyl­ate

Boudina, A.; Baouid, A.; Hasnaoui, A.; Eddike, D.; Tillard, M.

doi:10.1107/S1600536807030103

rac-Ethyl (8aR,9aS)-8a-methyl-8-(4-nitrophenyl)-9a,10-diphenyl-12-(p-tolyl)-9,9a-dihydro-8aH-di-1,2,4-triazolo[4,3-a:3′,4′-d][1,5]benzodiazepine-6-carboxylate

A. Boudina, A. Baouid, A. Hasnaoui, D. Eddike and M. Tillard

The structure of the title compound, C₄₀H₃₅N₇O₄, is stabilized by weak C—H

N and C—H

O hydrogen bonds. There are also π–π interactions between triazole and 9a-phenyl rings [the distance between the pertinent centroids is 3.708 (2) Å], as well as C—H

π interactions. In the title molecule, the C8a-methyl and C9a-phenyl groups are present in trans positions. The structure analysis established the presence of the enantiomeric pair of the diastereoisomer RS/SR and excluded the presence of the enantiomers of the diastereoisomer RR/SS.

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Supporting information

	Crystallographic Information File (CIF) https://doi.org/10.1107/S1600536807030103/fb2049sup1.cif Contains datablocks global, I
	Structure factor file (CIF format) https://doi.org/10.1107/S1600536807030103/fb2049Isup2.hkl Contains datablock I

CCDC reference: 655024

checkCIF report

Key indicators

Single-crystal X-ray study
T = 293 K
Mean (C-C) = 0.005 Å
R factor = 0.077
wR factor = 0.213
Data-to-parameter ratio = 13.1

checkCIF/PLATON results

No syntax errors found



Alert level B
PLAT222_ALERT_3_B Large Non-Solvent    H     Ueq(max)/Ueq(min) ...       4.06 Ratio

Alert level C
PLAT220_ALERT_2_C Large Non-Solvent    C     Ueq(max)/Ueq(min) ...       3.34 Ratio
PLAT340_ALERT_3_C Low Bond Precision on C-C Bonds (x 1000) Ang ...          5
PLAT360_ALERT_2_C Short  C(sp3)-C(sp3) Bond  C16    -   C17    ...       1.42 Ang.

Alert level G
REFLT03_ALERT_1_G ALERT: Expected hkl max differ from CIF values
           From the CIF: _diffrn_reflns_theta_max           32.40
           From the CIF: _reflns_number_total               6080
           From the CIF: _diffrn_reflns_limit_ max hkl   13.   31.   25.
           From the CIF: _diffrn_reflns_limit_ min hkl  -14.  -31.  -25.
           TEST1: Expected hkl limits for theta max
           Calculated maximum hkl   14.   32.   28.
           Calculated minimum hkl  -14.  -32.  -28.
PLAT199_ALERT_1_G Check the Reported _cell_measurement_temperature        293 K
PLAT200_ALERT_1_G Check the Reported _diffrn_ambient_temperature .        293 K
PLAT793_ALERT_1_G Check the Absolute Configuration of C8A    = ...          R
PLAT793_ALERT_1_G Check the Absolute Configuration of C9A    = ...          S

   0 ALERT level A = In general: serious problem
   1 ALERT level B = Potentially serious problem
   3 ALERT level C = Check and explain
   5 ALERT level G = General alerts; check

   5 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
   2 ALERT type 2 Indicator that the structure model may be wrong or deficient
   2 ALERT type 3 Indicator that the structure quality may be low
   0 ALERT type 4 Improvement, methodology, query or suggestion
   0 ALERT type 5 Informative message, check

Comment top

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).

Related literature top

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).

Experimental top

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%.

Structure description top

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.

Computing details top

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).

Figures top

	Fig. 1. Molecular view of the title molecule. The displacement ellipsoids are drawn at the 30% probability level (hydrogen atoms have been omitted for clarity).
	Fig. 2. Reaction scheme of the preparation of the title compound 3X and the scheme of the hypothetic diastereoisomer 3Y that was not found.

rac-Ethyl (8aR,9aS)-8a-methyl-8-(4-nitrophenyl)-9a,10- diphenyl-12-(p-tolyl)-9,9a-dihydro-8aH-di-1,2,4- triazolo[4,3 - a:3',4'-d][1,5]benzodiazepine-6-carboxylate top

Crystal data top

C₄₀H₃₅N₇O₄	F(000) = 1424
M_r = 677.75	D_x = 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

Data collection top

Oxford Diffraction Xcalibur CCD diffractometer	4822 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	R_int = 0.058
Graphite monochromator	θ_max = 32.4°, θ_min = 3.1°
ω scans	h = −14→13
59538 measured reflections	k = −31→31
6080 independent reflections	l = −25→25

Refinement top

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(F_o²) + (0.098P)² + 1.8217P] where P = (F_o² + 2F_c²)/3
6080 reflections	(Δ/σ)_max = 0.001
463 parameters	Δρ_max = 0.36 e Å⁻³
0 restraints	Δρ_min = −0.27 e Å⁻³
136 constraints

Crystal data top

C₄₀H₃₅N₇O₄	V = 3511.2 (4) Å³
M_r = 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)°

Data collection top

Oxford Diffraction Xcalibur CCD diffractometer	4822 reflections with I > 2σ(I)
59538 measured reflections	R_int = 0.058
6080 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.077	0 restraints
wR(F²) = 0.213	H-atom parameters constrained
S = 1.14	Δρ_max = 0.36 e Å⁻³
6080 reflections	Δρ_min = −0.27 e Å⁻³
463 parameters

Special details top

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 U_iso(H) = 1.5U_eq(C) for methyl groups and U_iso(H) = 1.2U_eq for others hydrogen atoms.

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

	x	y	z	U_iso*/U_eq
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*

Atomic displacement parameters (Å²) top

	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)

Geometric parameters (Å, º) top

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)

Hydrogen-bond geometry (Å, º) top

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
M_r	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
R_int	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
Δρ_max, Δρ_min (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).