2-(3-tert-Butyldimethylsiloxy-4-methoxyphenyl)-6-methoxy-3-(3,4,5-trimethoxybenzoyl)indole

In the crystal structure of the title compound, C₃₂H₃₉NO₇Si, all geometric parameters fall within experimental error of expected values. The analysis of molecular-packing plots reveals an infinite two-dimensional linear array running parallel to the b axis, formed by one N—H...O intermolecular hydrogen-bonding interaction. Several potential C—H...O interactions are also present.

S1. Comment

The protein tubulin plays a vital role during mitosis through the process of polymerization and depolymerization. Inhibitors of tubulin polymerization are known to arrest the assembly of tubulin into microtubules, resulting in the disruption of cell division (Hamel, 1996). Recently, it has been established that some of these agents rapidly shut down tumor vasculature, which results in necrosis of the tumor cells (Galbraith et al., 2001; Tozer et al., 1999). Combretastatin A-4(CA-4), (I) (Pettit et al., 1982, 1987, 2000), interacts with the colchicine binding site with a high binding affinity and inhibits the assembly of tubulin into microtubules (Hamel & Lin, 1983), while its corresponding water soluble prodrug, disodium phosphate CA-4P, (II) (Pettit et al., 1998), is inactive with tubulin. It is suggested that the phosphate moiety navigates the molecule in selectively targeting the sites of increased vascularization, as it undergoes dephosphorylation at these sites by the action of endothelial alkaline phosphatases, which release the active form of the drug, CA-4.

Two benzo[b]thiophene analogs, i.e. (III) and (IV), which bear structural features similar to CA-4, demonstrate excellent cytotoxicity and inhibition of tubulin polymerization (Mullica et al., 1998; Pinney et al., 1998, 1999; Flynn et al., 2001). Encouraged by these promising research results, we synthesized an indole variant as both the free phenol (V) (Pinney et al., 2001; Flynn, 2001; during the preparation of this manuscript, we learned that this compound had also been prepared independently by an alternate synthetic route), and its corresponding tert-butyldimethylsilyl ether, (VI), which will be eventually converted to its water-soluble phosphate prodrug form.

In order to unequivocally confirm the molecular structure, as well as gather information paramount for our molecular recognition studies, we have determined the crystal structure of (VI).

Fig. 1 shows the molecular structure of (VI), while selected geometric parameters are presented in Table 1. A l l internuclear distances and angles fall within the range of expected values and are comparable with those found in the related benzo[b]thiophene (III) structure determined by Mullica et al. (1998).

The indole ring is planar within 0.028 Å and forms respective dihedral angles of 49.50 (9) and 46.97 (7)° with the methoxyphenyl and trimethoxybenzoyl moieties. The latter two ring systems are also planar within 0.005 and 0.009 Å, respectively, and exhibit a dihedral angle of 48.93 (10)°, with a centroid-to-centroid separation of 4.36 Å.

The methoxy substituents on the several ring systems are rotated by various intervals to accommodate steric and crystal-packing requirements. Appropriate torsion angles are given in Table 1. Most notably, the methoxy group in position 4 of the 3,4,5-trimethoxybenzoyl component is rotated approximately 92.5° from the least-squares plane of the ring, with the terminal C24 atom extending 1.332 Å from the ring. The remaining substituents on the same group are twisted by 13.3 and 3.8°, respectively, with C23 and C25 protruding by 0.275 and 0.040 Å, respectively, above and below the ring. Elsewhere, the methoxy groups on the TBS–methoxyphenyl (TBS is tert-butyldimethylsiloxy) and methoxyindole moieties are turned 12.9 and 25.1° from their respective ring planes; atoms C26 and C22 project from their corresponding rings by 0.207 and 0.632 Å, respectively.

The supramolecular structure of (VI) consist of corrugated ribbons formed by an infinite linear array of molecules linked by an intermolecular N—H···O hydrogen-bonding interaction. According to Etter's graph-set analysis, this hydrogen-bond system is designated C(6) (Etter et al., 1990; Bernstein et al., 1995) and runs parallel to the b axis of the crystal lattice. Additionally, several other O atoms are involved in multiple close contacts with surrounding H atoms of the various adjacent groups. According to the somewhat liberal definition ascribed by Desiraju & Steiner (1999), these contacts may be classified as weak C—H···O hydrogen bonds; details are included in Table 2.

S2. Experimental

To a well stirred solution of 2-(3-tert-butyldimethylsiloxy-4-methoxyphenyl)-6-methoxyindole (0.511 g, 1.33 mmol) in o-dichlorobenzene (10 ml) was added 3,4,5-trimethoxybenzoylchloride (0.464 g, 2.01 mmol, 1.51 equivalents). The reaction mixture was refluxed for 12 h, after which the excess of o-dichlorobenzene was removed in vacuo and the resulting dark solid was subjected to flash chromatography (silica gel, 25% EtOAc in hexanes) to afford the title compound as a yellow powder. Recrystallization from hexanes–EtOAc afforded indole (VI) as prismatic pale-yellow crystals (0.355 g, 0.614 mmol, 46% yield, m.p. 438–440 K). ¹H NMR (300 MHz, CDCl₃): δ 0.035 (3H, s), 0.93 (9H, s), 3.69 (6H, s), 3.75 (3H, s), 3.79 (3H, s), 3.87 (3H, s), 6.71 (1H, d, J = 8.8 Hz), 6.77 (1H, d, J = 2.3 Hz) 6.87–6.94 (3H, m), 6.99 (2H, s), 7.95 (1H, d, J = 9.9 Hz), 8.39 (1H, s, broad).

S3. Refinement

The indolic H atom was located in a difference Fourier synthesis and was allowed to refine with a fixed isotropic displacement parameter of U_iso(H) = 1.2U_ew(N). All other H atoms were constrained to idealized geometries and were assigned isotropic displacement parameters U_iso(H) = 1.2U_eq(C), or U_iso(H) = 1.5U_eq(C) for methyl H atoms. The final electron-density difference synthesis indicated a randomly fluctuating background with no significant residual peaks.

Computing details

Data collection: CAD-4 Software (Enraf-Nonius, 1989); cell refinement: CAD-4 Software; data reduction: XCAD4 (Harms, 1993); program(s) used to solve structure: SHELXTL/PC (Sheldrick, 1995); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: XP in SHELXTL/PC; software used to prepare material for publication: SHELXL97.

Figures

Fig. 1. Displacement ellipsoid plot (40% probability) of (VI) with the atom labels. All H atoms, except for the indole NH atom, have been omitted for clarity.

(VI)

Crystal data

C32H39NO7Si	Dx = 1.249 Mg m^−3
Mr = 577.73	Melting point = 165–167 K
Orthorhombic, Pbca	Mo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ac 2ab	Cell parameters from 25 reflections
a = 14.596 (1) Å	θ = 10.1–16.2°
b = 14.753 (1) Å	µ = 0.12 mm^−1
c = 28.531 (4) Å	T = 173 K
V = 6143.8 (10) Å^3	Prism, pale yellow
Z = 8	0.55 × 0.49 × 0.49 mm
F(000) = 2464

Data collection

Enraf-Nonius CAD-4 diffractometer	3841 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tube	Rint = 0.017
Graphite monochromator	θmax = 25.0°, θmin = 2.0°
ω–2θ scans	h = 0→17
Absorption correction: ψ scan (SHELXTL/PC; Sheldrick, 1995)	k = 0→17
Tmin = 0.926, Tmax = 0.945	l = −2→33
5570 measured reflections	3 standard reflections every 120 min
5335 independent reflections	intensity decay: 10.1%

Refinement

Refinement on F^2	Secondary atom site location: difference Fourier map
Least-squares matrix: full	Hydrogen site location: inferred from neighbouring sites
R[F^2 > 2σ(F^2)] = 0.048	H atoms treated by a mixture of independent and constrained refinement
wR(F^2) = 0.127	w = 1/[σ^2(Fo^2) + (0.0242P)^2 + 12.4107P] where P = (Fo^2 + 2Fc^2)/3
S = 1.08	(Δ/σ)max < 0.001
5335 reflections	Δρmax = 0.37 e Å^−3
374 parameters	Δρmin = −0.41 e Å^−3
0 restraints	Extinction correction: SHELXL97, Fc^*=kFc[1+0.001xFc^2λ^3/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.00155 (13)

Special details

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 (Ų)

	x	y	z	Uiso*/Ueq
N	−0.26520 (16)	0.69893 (16)	0.08777 (9)	0.0216 (6)
H	−0.265 (2)	0.754 (2)	0.0939 (11)	0.026*
C1	−0.19566 (19)	0.64124 (18)	0.09920 (10)	0.0206 (6)
C2	−0.22425 (19)	0.55248 (18)	0.09141 (10)	0.0198 (6)
C3	−0.31885 (19)	0.55737 (18)	0.07709 (10)	0.0205 (6)
C4	−0.3875 (2)	0.49437 (19)	0.06624 (10)	0.0245 (7)
H4	−0.3741	0.4314	0.0664	0.029*
C5	−0.4740 (2)	0.5237 (2)	0.05541 (11)	0.0273 (7)
H5	−0.5208	0.4805	0.0493	0.033*
C6	−0.49468 (19)	0.6165 (2)	0.05321 (11)	0.0260 (7)
C7	−0.42859 (19)	0.68083 (19)	0.06209 (11)	0.0243 (7)
H7	−0.4419	0.7437	0.0600	0.029*
C8	−0.34182 (19)	0.65030 (18)	0.07422 (10)	0.0203 (6)
C9	−0.1747 (2)	0.46659 (18)	0.09576 (10)	0.0215 (6)
C10	−0.0720 (2)	0.46222 (18)	0.09404 (10)	0.0217 (6)
C11	−0.02167 (19)	0.52018 (18)	0.06576 (11)	0.0226 (7)
H11	−0.0509	0.5693	0.0503	0.027*
C12	0.0719 (2)	0.50587 (19)	0.06023 (10)	0.0226 (6)
C13	0.11448 (19)	0.43387 (19)	0.08323 (11)	0.0244 (7)
C14	0.0642 (2)	0.37725 (19)	0.11293 (10)	0.0243 (7)
C15	−0.0296 (2)	0.39121 (19)	0.11797 (11)	0.0244 (7)
H15	−0.0646	0.3525	0.1376	0.029*
C16	−0.11208 (19)	0.68028 (18)	0.12034 (11)	0.0213 (6)
C17	−0.0698 (2)	0.75465 (19)	0.09989 (11)	0.0240 (7)
H17	−0.0929	0.7784	0.0713	0.029*
C18	0.0061 (2)	0.79479 (19)	0.12074 (11)	0.0266 (7)
H18	0.0346	0.8454	0.1063	0.032*
C19	0.04000 (19)	0.76124 (19)	0.16246 (11)	0.0257 (7)
C20	−0.00169 (19)	0.68562 (19)	0.18311 (11)	0.0227 (6)
C21	−0.07642 (19)	0.64579 (19)	0.16210 (11)	0.0226 (6)
H21	−0.1041	0.5942	0.1762	0.027*
C22	−0.6570 (2)	0.5927 (3)	0.05076 (16)	0.0493 (10)
H22A	−0.7133	0.6240	0.0412	0.074*
H22B	−0.6600	0.5787	0.0843	0.074*
H22C	−0.6507	0.5364	0.0329	0.074*
C23	0.0932 (2)	0.6410 (2)	0.01586 (12)	0.0299 (7)
H23A	0.1394	0.6707	−0.0037	0.045*
H23B	0.0784	0.6800	0.0426	0.045*
H23C	0.0377	0.6303	−0.0027	0.045*
C24	0.2281 (2)	0.3636 (3)	0.03850 (13)	0.0472 (10)
H24A	0.2947	0.3569	0.0357	0.071*
H24B	0.2037	0.3912	0.0099	0.071*
H24C	0.2002	0.3038	0.0430	0.071*
C25	0.0646 (2)	0.2471 (2)	0.16264 (13)	0.0360 (8)
H25A	0.1071	0.2007	0.1742	0.054*
H25B	0.0167	0.2182	0.1438	0.054*
H25C	0.0366	0.2785	0.1893	0.054*
C26	0.1678 (2)	0.8616 (3)	0.16355 (15)	0.0499 (10)
H26A	0.2164	0.8821	0.1848	0.075*
H26B	0.1303	0.9136	0.1541	0.075*
H26C	0.1952	0.8337	0.1357	0.075*
C27	0.1895 (3)	0.7006 (3)	0.27905 (14)	0.0493 (10)
H27A	0.2031	0.7560	0.2614	0.074*
H27B	0.2466	0.6751	0.2914	0.074*
H27C	0.1482	0.7149	0.3051	0.074*
C28	0.2023 (2)	0.5955 (3)	0.18550 (14)	0.0475 (10)
H28A	0.2129	0.6531	0.1692	0.071*
H28B	0.1688	0.5541	0.1648	0.071*
H28C	0.2613	0.5684	0.1941	0.071*
C29	0.1113 (3)	0.5080 (2)	0.27182 (12)	0.0396 (9)
C30	0.0450 (3)	0.5260 (3)	0.31268 (13)	0.0506 (10)
H30A	−0.0128	0.5501	0.3004	0.076*
H30B	0.0724	0.5701	0.3342	0.076*
H30C	0.0333	0.4692	0.3294	0.076*
C31	0.2012 (3)	0.4687 (3)	0.29134 (15)	0.0615 (12)
H31A	0.2443	0.4585	0.2655	0.092*
H31B	0.1885	0.4110	0.3071	0.092*
H31C	0.2279	0.5114	0.3138	0.092*
C32	0.0674 (3)	0.4383 (2)	0.23914 (14)	0.0555 (11)
H32A	0.1078	0.4275	0.2123	0.083*
H32B	0.0083	0.4613	0.2280	0.083*
H32C	0.0579	0.3814	0.2562	0.083*
O6	−0.57989 (14)	0.64981 (15)	0.04186 (10)	0.0421 (6)
O9	−0.21806 (14)	0.39510 (13)	0.09896 (8)	0.0310 (5)
O12	0.12816 (14)	0.55628 (14)	0.03247 (8)	0.0307 (5)
O13	0.20723 (13)	0.42008 (14)	0.07782 (8)	0.0310 (5)
O14	0.11336 (14)	0.31087 (14)	0.13442 (8)	0.0336 (6)
O19	0.11156 (14)	0.79672 (14)	0.18701 (8)	0.0339 (6)
O20	0.02891 (14)	0.65289 (15)	0.22516 (8)	0.0312 (5)
Si	0.13378 (6)	0.61646 (6)	0.23950 (3)	0.0320 (2)

Atomic displacement parameters (Ų)

	U^11	U^22	U^33	U^12	U^13	U^23
N	0.0205 (13)	0.0109 (11)	0.0335 (15)	−0.0003 (10)	−0.0035 (11)	−0.0011 (11)
C1	0.0186 (14)	0.0141 (13)	0.0291 (17)	0.0006 (11)	−0.0005 (12)	0.0006 (12)
C2	0.0181 (15)	0.0156 (14)	0.0257 (16)	−0.0008 (12)	0.0001 (12)	0.0013 (12)
C3	0.0199 (15)	0.0132 (13)	0.0283 (16)	−0.0011 (12)	0.0019 (13)	0.0005 (12)
C4	0.0265 (16)	0.0163 (14)	0.0305 (17)	−0.0029 (12)	−0.0001 (13)	−0.0006 (13)
C5	0.0225 (16)	0.0248 (16)	0.0348 (19)	−0.0085 (13)	−0.0013 (14)	−0.0005 (14)
C6	0.0176 (15)	0.0280 (16)	0.0325 (17)	0.0013 (13)	−0.0051 (13)	0.0034 (14)
C7	0.0228 (15)	0.0174 (14)	0.0327 (18)	0.0014 (12)	0.0005 (13)	0.0021 (13)
C8	0.0183 (14)	0.0159 (13)	0.0268 (16)	−0.0005 (12)	−0.0005 (12)	0.0020 (12)
C9	0.0230 (15)	0.0166 (14)	0.0250 (16)	−0.0013 (12)	0.0006 (13)	−0.0015 (12)
C10	0.0229 (15)	0.0146 (14)	0.0275 (16)	0.0022 (12)	−0.0018 (13)	−0.0044 (12)
C11	0.0207 (15)	0.0151 (14)	0.0319 (17)	0.0032 (12)	−0.0041 (13)	−0.0004 (13)
C12	0.0245 (15)	0.0193 (14)	0.0240 (16)	−0.0039 (12)	−0.0017 (13)	−0.0003 (12)
C13	0.0190 (15)	0.0231 (15)	0.0312 (17)	0.0023 (13)	−0.0035 (13)	−0.0016 (13)
C14	0.0260 (16)	0.0186 (15)	0.0282 (16)	0.0043 (13)	−0.0052 (13)	0.0000 (13)
C15	0.0253 (16)	0.0174 (14)	0.0304 (17)	0.0001 (13)	0.0012 (13)	0.0005 (13)
C16	0.0188 (14)	0.0133 (13)	0.0319 (17)	0.0007 (11)	0.0006 (13)	−0.0016 (12)
C17	0.0248 (16)	0.0169 (14)	0.0304 (17)	−0.0001 (12)	−0.0032 (13)	0.0027 (13)
C18	0.0243 (16)	0.0176 (15)	0.0380 (19)	−0.0054 (13)	0.0013 (14)	0.0041 (14)
C19	0.0188 (15)	0.0201 (15)	0.0382 (19)	−0.0028 (12)	−0.0008 (14)	−0.0056 (14)
C20	0.0190 (15)	0.0233 (15)	0.0258 (16)	0.0014 (12)	0.0012 (12)	0.0018 (13)
C21	0.0180 (14)	0.0164 (14)	0.0335 (17)	−0.0002 (12)	0.0024 (13)	0.0021 (13)
C22	0.0189 (17)	0.048 (2)	0.081 (3)	−0.0053 (16)	0.0019 (18)	−0.001 (2)
C23	0.0315 (17)	0.0231 (16)	0.0351 (18)	−0.0024 (14)	0.0016 (15)	0.0066 (14)
C24	0.035 (2)	0.049 (2)	0.057 (2)	0.0111 (18)	0.0121 (18)	−0.0057 (19)
C25	0.0391 (19)	0.0236 (16)	0.045 (2)	0.0031 (15)	−0.0068 (17)	0.0126 (15)
C26	0.0295 (19)	0.053 (2)	0.067 (3)	−0.0248 (18)	−0.0098 (18)	0.014 (2)
C27	0.045 (2)	0.045 (2)	0.058 (3)	−0.0024 (18)	−0.0234 (19)	−0.0098 (19)
C28	0.039 (2)	0.045 (2)	0.059 (3)	0.0053 (18)	0.0051 (19)	−0.0011 (19)
C29	0.054 (2)	0.0319 (18)	0.0331 (19)	0.0051 (17)	−0.0076 (17)	−0.0033 (15)
C30	0.074 (3)	0.041 (2)	0.037 (2)	0.003 (2)	0.001 (2)	0.0055 (17)
C31	0.080 (3)	0.050 (2)	0.055 (3)	0.025 (2)	−0.019 (2)	0.002 (2)
C32	0.084 (3)	0.033 (2)	0.049 (3)	−0.010 (2)	−0.002 (2)	0.0003 (18)
O6	0.0171 (11)	0.0344 (13)	0.0746 (19)	−0.0019 (10)	−0.0098 (12)	0.0069 (12)
O9	0.0255 (11)	0.0141 (10)	0.0535 (15)	−0.0020 (9)	0.0032 (10)	0.0003 (10)
O12	0.0216 (11)	0.0256 (11)	0.0449 (14)	0.0002 (9)	0.0028 (10)	0.0101 (10)
O13	0.0187 (11)	0.0336 (12)	0.0408 (13)	0.0063 (9)	0.0008 (10)	0.0010 (10)
O14	0.0279 (12)	0.0273 (12)	0.0456 (14)	0.0073 (10)	−0.0034 (10)	0.0122 (10)
O19	0.0231 (11)	0.0331 (12)	0.0454 (14)	−0.0137 (10)	−0.0064 (10)	−0.0003 (11)
O20	0.0241 (11)	0.0352 (12)	0.0345 (13)	−0.0046 (10)	−0.0053 (10)	0.0069 (10)
Si	0.0273 (5)	0.0311 (5)	0.0375 (5)	0.0005 (4)	−0.0087 (4)	−0.0031 (4)

Geometric parameters (Å, º)

N—H	0.83 (3)	C29—C31	1.539 (5)
N—C1	1.364 (4)	C29—Si	1.875 (4)
N—C8	1.384 (4)	O20—Si	1.673 (2)
N—O9^i	2.922 (3)	N—H	0.83 (3)
C1—C2	1.392 (4)	N—H	0.83 (3)
C1—C16	1.478 (4)	C4—H4A	0.95
C2—C3	1.442 (4)	C5—H5A	0.95
C2—C9	1.464 (4)	C7—H7A	0.95
C3—C4	1.401 (4)	C11—H11A	0.95
C3—C8	1.414 (4)	C15—H15A	0.95
C4—C5	1.370 (4)	C17—H17A	0.95
C5—C6	1.403 (4)	C18—H18A	0.95
C6—O6	1.376 (3)	C21—H21A	0.95
C6—C7	1.377 (4)	C22—H22A	0.98
C7—C8	1.388 (4)	C22—H22B	0.98
C9—O9	1.233 (3)	C22—H22C	0.98
C9—C10	1.502 (4)	C23—H23A	0.98
C10—C11	1.386 (4)	C23—H23B	0.98
C10—C15	1.395 (4)	C23—H23C	0.98
C11—C12	1.391 (4)	C24—H24A	0.98
C12—O12	1.362 (3)	C24—H24B	0.98
C12—C13	1.395 (4)	C24—H24C	0.98
C13—O13	1.378 (3)	C25—H25A	0.98
C13—C14	1.398 (4)	C25—H25B	0.98
C14—O14	1.360 (3)	C25—H25C	0.98
C14—C15	1.391 (4)	C26—H26A	0.98
C16—C17	1.388 (4)	C26—H26B	0.98
C16—C21	1.396 (4)	C26—H26C	0.98
C17—C18	1.389 (4)	C27—H27A	0.98
C18—C19	1.381 (4)	C27—H27B	0.98
C19—O19	1.362 (3)	C27—H27C	0.98
C19—C20	1.401 (4)	C28—H28A	0.98
C20—O20	1.368 (4)	C28—H28B	0.98
C20—C21	1.376 (4)	C28—H28C	0.98
C22—O6	1.429 (4)	C30—H30A	0.98
C23—O12	1.430 (3)	C30—H30B	0.98
C24—O13	1.430 (4)	C30—H30C	0.98
C25—O14	1.429 (4)	C31—H31A	0.98
C26—O19	1.427 (4)	C31—H31B	0.98
C27—Si	1.864 (3)	C31—H31C	0.98
C28—Si	1.863 (4)	C32—H32A	0.98
C29—C32	1.530 (5)	C32—H32B	0.98
C29—C30	1.538 (5)	C32—H32C	0.98
H—N—C1	124 (2)	C4—C5—H5A	119.5
H—N—C8	124 (2)	C6—C5—H5A	119.5
C1—N—C8	110.2 (2)	C6—C7—H7A	121.3
N—C1—C2	109.0 (2)	C8—C7—H7A	121.3
N—C1—C16	117.9 (2)	C10—C11—H11A	120.2
C2—C1—C16	132.8 (2)	C12—C11—H11A	120.2
C1—C2—C3	106.6 (2)	C14—C15—H15A	120.1
C1—C2—C9	130.7 (3)	C10—C15—H15A	120.1
C3—C2—C9	122.7 (2)	C16—C17—H17A	119.6
C4—C3—C8	117.4 (3)	C18—C17—H17A	119.6
C4—C3—C2	135.6 (3)	C19—C18—H18A	119.9
C8—C3—C2	107.0 (2)	C17—C18—H18A	119.9
C5—C4—C3	120.0 (3)	C20—C21—H21A	119.6
C4—C5—C6	121.1 (3)	C16—C21—H21A	119.6
O6—C6—C7	115.5 (3)	O6—C22—H22A	109.5
O6—C6—C5	123.6 (3)	O6—C22—H22B	109.5
C7—C6—C5	120.9 (3)	H22A—C22—H22B	109.5
C6—C7—C8	117.5 (3)	O6—C22—H22C	109.5
N—C8—C7	129.7 (2)	H22A—C22—H22C	109.5
N—C8—C3	107.2 (2)	H22B—C22—H22C	109.5
C7—C8—C3	123.1 (3)	O12—C23—H23A	109.5
O9—C9—C2	119.5 (3)	O12—C23—H23B	109.5
O9—C9—C10	118.5 (3)	H23A—C23—H23B	109.5
C2—C9—C10	121.8 (2)	O12—C23—H23C	109.5
C11—C10—C15	120.9 (3)	H23A—C23—H23C	109.5
C11—C10—C9	121.4 (3)	H23B—C23—H23C	109.5
C15—C10—C9	117.3 (3)	O13—C24—H24A	109.5
C10—C11—C12	119.5 (3)	O13—C24—H24B	109.5
O12—C12—C11	125.1 (3)	H24A—C24—H24B	109.5
O12—C12—C13	114.9 (3)	O13—C24—H24C	109.5
C11—C12—C13	120.0 (3)	H24A—C24—H24C	109.5
O13—C13—C12	119.9 (3)	H24B—C24—H24C	109.5
O13—C13—C14	119.7 (3)	O14—C25—H25A	109.5
C12—C13—C14	120.4 (3)	O14—C25—H25B	109.5
O14—C14—C15	125.4 (3)	H25A—C25—H25B	109.5
O14—C14—C13	115.2 (3)	O14—C25—H25C	109.5
C15—C14—C13	119.4 (3)	H25A—C25—H25C	109.5
C14—C15—C10	119.8 (3)	H25B—C25—H25C	109.5
C17—C16—C21	118.8 (3)	O19—C26—H26A	109.5
C17—C16—C1	120.3 (3)	O19—C26—H26B	109.5
C21—C16—C1	120.9 (3)	H26A—C26—H26B	109.5
C16—C17—C18	120.8 (3)	O19—C26—H26C	109.5
C19—C18—C17	120.1 (3)	H26A—C26—H26C	109.5
O19—C19—C18	125.5 (3)	H26B—C26—H26C	109.5
O19—C19—C20	115.0 (3)	Si—C27—H27A	109.5
C18—C19—C20	119.5 (3)	Si—C27—H27B	109.5
O20—C20—C21	119.3 (3)	H27A—C27—H27B	109.5
O20—C20—C19	120.5 (3)	Si—C27—H27C	109.5
C21—C20—C19	120.1 (3)	H27A—C27—H27C	109.5
C20—C21—C16	120.8 (3)	H27B—C27—H27C	109.5
C32—C29—C30	108.3 (3)	Si—C28—H28A	109.5
C32—C29—C31	108.9 (3)	Si—C28—H28B	109.5
C30—C29—C31	109.1 (3)	H28A—C28—H28B	109.5
C32—C29—Si	110.3 (2)	Si—C28—H28C	109.5
C30—C29—Si	109.6 (2)	H28A—C28—H28C	109.5
C31—C29—Si	110.5 (3)	H28B—C28—H28C	109.5
C6—O6—C22	117.4 (2)	C29—C30—H30A	109.5
C12—O12—C23	117.0 (2)	C29—C30—H30B	109.5
C13—O13—C24	112.5 (2)	H30A—C30—H30B	109.5
C14—O14—C25	117.7 (2)	C29—C30—H30C	109.5
C19—O19—C26	117.2 (3)	H30A—C30—H30C	109.5
C20—O20—Si	128.80 (19)	H30B—C30—H30C	109.5
O20—Si—C28	110.01 (15)	C29—C31—H31A	109.5
O20—Si—C27	109.48 (15)	C29—C31—H31B	109.5
C28—Si—C27	112.12 (18)	H31A—C31—H31B	109.5
O20—Si—C29	103.55 (14)	C29—C31—H31C	109.5
C28—Si—C29	111.06 (17)	H31A—C31—H31C	109.5
C27—Si—C29	110.29 (17)	H31B—C31—H31C	109.5
H—N—C1	124 (2)	C29—C32—H32A	109.5
H—N—C8	124 (2)	C29—C32—H32B	109.5
C1—N—H	124 (2)	H32A—C32—H32B	109.5
C8—N—H	124 (2)	C29—C32—H32C	109.5
C5—C4—H4A	120.0	H32A—C32—H32C	109.5
C3—C4—H4A	120.0	H32B—C32—H32C	109.5
H—N—C1—C2	170 (3)	O13—C13—C14—C15	−179.5 (3)
C8—N—C1—C2	2.5 (3)	C12—C13—C14—C15	2.5 (4)
H—N—C1—C16	−5 (3)	O14—C14—C15—C10	179.7 (3)
C8—N—C1—C16	−172.3 (3)	C13—C14—C15—C10	−1.1 (4)
N—C1—C2—C3	−3.6 (3)	C11—C10—C15—C14	−1.0 (4)
C16—C1—C2—C3	170.1 (3)	C9—C10—C15—C14	172.2 (3)
N—C1—C2—C9	176.5 (3)	N—C1—C16—C17	−49.2 (4)
C16—C1—C2—C9	−9.8 (6)	C2—C1—C16—C17	137.5 (3)
C1—C2—C3—C4	−176.7 (3)	N—C1—C16—C21	128.1 (3)
C9—C2—C3—C4	3.3 (5)	C2—C1—C16—C21	−45.2 (5)
C1—C2—C3—C8	3.4 (3)	C21—C16—C17—C18	−0.7 (4)
C9—C2—C3—C8	−176.7 (3)	C1—C16—C17—C18	176.7 (3)
C8—C3—C4—C5	−2.8 (4)	C16—C17—C18—C19	−0.4 (4)
C2—C3—C4—C5	177.2 (3)	C17—C18—C19—O19	−177.5 (3)
C3—C4—C5—C6	2.4 (5)	C17—C18—C19—C20	1.0 (4)
C4—C5—C6—O6	179.0 (3)	O19—C19—C20—O20	0.7 (4)
C4—C5—C6—C7	−0.3 (5)	C18—C19—C20—O20	−178.0 (3)
O6—C6—C7—C8	179.3 (3)	O19—C19—C20—C21	178.1 (3)
C5—C6—C7—C8	−1.4 (5)	C18—C19—C20—C21	−0.6 (4)
H—N—C8—C7	9 (3)	O20—C20—C21—C16	176.9 (3)
C1—N—C8—C7	176.4 (3)	C19—C20—C21—C16	−0.5 (4)
H—N—C8—C3	−167 (3)	C17—C16—C21—C20	1.1 (4)
C1—N—C8—C3	−0.3 (3)	C1—C16—C21—C20	−176.2 (3)
C6—C7—C8—N	−175.3 (3)	C7—C6—O6—C22	−155.2 (3)
C6—C7—C8—C3	0.9 (5)	C5—C6—O6—C22	25.4 (5)
C4—C3—C8—N	178.1 (3)	C11—C12—O12—C23	14.1 (4)
C2—C3—C8—N	−1.9 (3)	C13—C12—O12—C23	−167.5 (3)
C4—C3—C8—C7	1.1 (5)	C12—C13—O13—C24	−88.5 (3)
C2—C3—C8—C7	−178.9 (3)	C14—C13—O13—C24	93.5 (3)
C1—C2—C9—O9	161.3 (3)	C15—C14—O14—C25	3.4 (4)
C3—C2—C9—O9	−18.6 (4)	C13—C14—O14—C25	−175.8 (3)
C1—C2—C9—C10	−21.8 (5)	C18—C19—O19—C26	−13.6 (4)
C3—C2—C9—C10	158.3 (3)	C20—C19—O19—C26	167.8 (3)
O9—C9—C10—C11	142.3 (3)	C21—C20—O20—Si	124.8 (3)
C2—C9—C10—C11	−34.6 (4)	C19—C20—O20—Si	−57.9 (4)
O9—C9—C10—C15	−30.8 (4)	C20—O20—Si—C28	−15.4 (3)
C2—C9—C10—C15	152.3 (3)	C20—O20—Si—C27	108.2 (3)
C15—C10—C11—C12	1.7 (4)	C20—O20—Si—C29	−134.2 (3)
C9—C10—C11—C12	−171.2 (3)	C32—C29—Si—O20	64.1 (3)
C10—C11—C12—O12	178.0 (3)	C30—C29—Si—O20	−55.1 (3)
C10—C11—C12—C13	−0.3 (4)	C31—C29—Si—O20	−175.4 (2)
O12—C12—C13—O13	1.7 (4)	C32—C29—Si—C28	−53.9 (3)
C11—C12—C13—O13	−179.8 (3)	C30—C29—Si—C28	−173.1 (3)
O12—C12—C13—C14	179.7 (3)	C31—C29—Si—C28	66.6 (3)
C11—C12—C13—C14	−1.8 (4)	C32—C29—Si—C27	−178.8 (3)
O13—C13—C14—O14	−0.3 (4)	C30—C29—Si—C27	61.9 (3)
C12—C13—C14—O14	−178.3 (3)	C31—C29—Si—C27	−58.3 (3)

Symmetry code: (i) −x−1/2, y+1/2, z.

Hydrogen-bond geometry (Å, º)

D—H···A	D—H	H···A	D···A	D—H···A
N—H···O9^i	0.83 (3)	2.10 (3)	2.922 (4)	170 (3)
C4—H4···O9	0.95	2.52	3.022 (4)	113
C22—H22a···O12^ii	0.98	2.53	3.224 (4)	127
C26—H26c···O13^iii	0.98	2.53	3.171 (4)	123
C27—H27a···O19	0.98	2.58	3.194 (4)	121

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