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Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890

Buprenorphine

aCrystallics B.V., Meibergdreef 31, 1105 AZ Amsterdam, The Netherlands, bNoramco Inc., 503 Carr Rd, Suite 200, Wilmington, DE 19809, USA, and cNoramco Inc., 1440 Olympic Drive, Athens, GA 30601, USA
*Correspondence e-mail: jaroslaw.mazurek@crystallics.com

Edited by M. Gdaniec, Adam Mickiewicz University, Poland (Received 25 March 2014; accepted 29 April 2014; online 3 May 2014)

In the crystal structure of a semi-synthetic opioid drug buprenorphine, C29H41NO4 {systematic name: (2S)-2-[(5R,6R,7R,14S)-9α-cyclo­propyl­methyl-3-hy­droxy-6-meth­oxy-4,5-ep­oxy-6,14-ethano­morphinan-7-yl]-3,3-di­methyl­butan-2-ol}, the cyclo­propyl­methyl group is disordered over two sites with an occupancy factor of 0.611 (3) for the major component. One of the hy­droxy groups is involved in intra­molecular O—H⋯O hydrogen bond. The other hy­droxy group acts as a proton donor in an inter­molecular O—H⋯O inter­action that connects mol­ecules into a zigzag chain along the b axis.

Related literature

For the crystal structure of buprenorphine hydro­chloride, see: Flippen-Anderson et al. (1994[Flippen-Anderson, J. L., George, C., Bertha, C. M. & Rice, K. C. (1994). Heterocycles, 39, 751-766.]); Kratochvil et al. (1994[Kratochvil, B., Husak, M., Bulej, P. & Jegorov, A. (1994). Collect. Czech. Chem. Commun. 59, 2472-2480.]). For pharmacological information on buprenorphine, see: Weinberg et al. (1988[Weinberg, D. S., Inturrisi, C. E., Reidenberg, B., Moulin, D. E., Nip, T. J., Wallenstein, S., Houde, R. W. & Foley, K. M. (1988). Clin. Pharmacol. Ther. 44, 335-342.]); Huang et al. (2001[Huang, P., Kehner, G. B., Cowan, A. & Liu-Chen, L. Y. (2001). J. Pharmacol. Exp. Ther. 297, 688-695.]). For the Kitaigorodskii packing coefficient, see: Kitajgorodskij (1973[Kitajgorodskij, A. I. (1973). In Molecular Crystals and Molecules. New York: Academic Press.]).

[Scheme 1]

Experimental

Crystal data
  • C29H41NO4

  • Mr = 467.63

  • Monoclinic, P 21

  • a = 9.8154 (6) Å

  • b = 10.4283 (9) Å

  • c = 13.4508 (9) Å

  • β = 108.796 (5)°

  • V = 1303.37 (16) Å3

  • Z = 2

  • Mo Kα radiation

  • μ = 0.08 mm−1

  • T = 296 K

  • 0.45 × 0.45 × 0.25 mm

Data collection
  • Bruker KappaCCD diffractometer

  • 14483 measured reflections

  • 4886 independent reflections

  • 4312 reflections with I > 2σ(I)

  • Rint = 0.026

Refinement
  • R[F2 > 2σ(F2)] = 0.052

  • wR(F2) = 0.146

  • S = 1.04

  • 4886 reflections

  • 352 parameters

  • 112 restraints

  • H atoms treated by a mixture of independent and constrained refinement

  • Δρmax = 0.32 e Å−3

  • Δρmin = −0.31 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
O1—H1A⋯O11i 0.88 (4) 1.93 (4) 2.798 (3) 166 (3)
O11—H11A⋯O7 0.92 (3) 1.81 (3) 2.574 (2) 139 (3)
Symmetry code: (i) [-x+1, y+{\script{1\over 2}}, -z].

Data collection: COLLECT (Hooft, 1998[Hooft, R. W. W. (1998). COLLECT. Nonius BV, Delft, The Netherlands.]); cell refinement: SCALEPACK (Otwinowski & Minor, 1997[Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307-326. New York: Academic Press.]); data reduction: DENZO (Otwinowski & Minor, 1997[Otwinowski, Z. & Minor, W. (1997). Methods in Enzymology, Vol. 276, Macromolecular Crystallography, Part A, edited by C. W. Carter Jr & R. M. Sweet, pp. 307-326. New York: Academic Press.]) and SCALEPACK; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: Mercury (Macrae et al., 2008[Macrae, C. F., Bruno, I. J., Chisholm, J. A., Edgington, P. R., McCabe, P., Pidcock, E., Rodriguez-Monge, L., Taylor, R., van de Streek, J. & Wood, P. A. (2008). J. Appl. Cryst. 41, 466-470.]); software used to prepare material for publication: enCIFer (Allen et al., 2004[Allen, F. H., Johnson, O., Shields, G. P., Smith, B. R. & Towler, M. (2004). J. Appl. Cryst. 37, 335-338.]).

Supporting information


Comment top

Buprenorphine is a semisynthetic opioid (Weinberg et al., 1988) that is used as a pain killer. The molecule has clearly defined hydrophilic and hydrophobic parts. In the latter part, static disorder for cyclopropylmethyl group is observed with the occupation of 0.612 (8) and 0.388 (8) for the two disordered sites. The minor component of the disordered part adopts a conformation that is similar to the one observed for buprenorphine hydrochloride salt (Flippen-Anderson et al., 1994; Kratochvil et al., 1994). In the major component the C29-N24-C25-C26 torsion angle equals to -155.4 (4)° whereas in the minor component the corresponding C29-N24-C25A-C26A angle is -72.2 (7)°. This disorder may result from a relatively loose packing of the crystal (Kitaigorodskii packing cooeficient of 0.65 (Kitajgorodskij, 1973)) that allows for some flexibility in the hydrophobic parts of the molecule.

Related literature top

For the crystal structure of buprenorphine hydrochloride, see: Flippen-Anderson et al. (1994); Kratochvil et al. (1994). For pharmacological information on buprenorphine, see: Weinberg et al. (1988); Huang et al.( 2001). For the Kitaigorodskii packing coefficient, see: Kitajgorodskij (1973).

Experimental top

Suspension of 29.6 mg of buprenorphine in 200 ml of ethyl acetate was stirred at 25 °C for 14 days. After that time the liquid was separated from the solid and left for evaporation at room temperature. After several days colorless crystals (m.p. 492.5 K) appeared that were used for diffraction studies.

Refinement top

All C-bound H-atoms were included in the geometrically determined positions with Uiso=1.2 Ueq(C). H atoms from the OH groups were located on a Fourier difference map and refined isotropically. In the absence of significant anomalous scattering effects, Friedel pairs were merged. The absolute configuration is known from the synthetic route. The cyclopropylmethyl group is disordered over two positions. To properly model the disordered fragment restrains were imposed on some bond lengths and anisotropic thermal parameters [DFIX, SADI and SIMU commands in SHELXL-97 (Sheldrick, 2008)].

Computing details top

Data collection: COLLECT (Hooft, 1998); cell refinement: SCALEPACK (Otwinowski & Minor, 1997); data reduction: DENZO and SCALEPACK (Otwinowski & Minor, 1997); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: Mercury (Macrae et al., 2008); software used to prepare material for publication: enCIFer (Allen et al., 2004).

Figures top
[Figure 1] Fig. 1. Molecular structure and atom numbering scheme for buprenorphine. Displacement ellipsoids are shown at the 50% probability level. The minor position of the disordered part has been omitted for clarity.
[Figure 2] Fig. 2. Crystal packing diagram - view along the a axis. Hydrogen bonds are shown as blue lines.
(2S)-2-[(5R,6R,7R,14S)-9α-Cyclopropylmethyl-3-hydroxy-6-methoxy-4,5-epoxy-6,14-ethanomorphinan-7-yl]-3,3-dimethylbutan-2-ol top
Crystal data top
C29H41NO4F(000) = 508
Mr = 467.63Dx = 1.192 Mg m3
Monoclinic, P21Melting point: 492.15 K
Hall symbol: P 2ybMo Kα radiation, λ = 0.71073 Å
a = 9.8154 (6) ÅCell parameters from 6648 reflections
b = 10.4283 (9) Åθ = 1.0–32.6°
c = 13.4508 (9) ŵ = 0.08 mm1
β = 108.796 (5)°T = 296 K
V = 1303.37 (16) Å3Block, colourless
Z = 20.45 × 0.45 × 0.25 mm
Data collection top
Bruker KappaCCD
diffractometer
4312 reflections with I > 2σ(I)
Radiation source: fine-focus sealed tubeRint = 0.026
Horizonally mounted graphite crystal monochromatorθmax = 32.6°, θmin = 3.8°
Detector resolution: 9 pixels mm-1h = 1414
CCD scansk = 1515
14483 measured reflectionsl = 2020
4886 independent reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.052Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.146H atoms treated by a mixture of independent and constrained refinement
S = 1.04 w = 1/[σ2(Fo2) + (0.0762P)2 + 0.1599P]
where P = (Fo2 + 2Fc2)/3
4886 reflections(Δ/σ)max = 0.007
352 parametersΔρmax = 0.32 e Å3
112 restraintsΔρmin = 0.31 e Å3
Crystal data top
C29H41NO4V = 1303.37 (16) Å3
Mr = 467.63Z = 2
Monoclinic, P21Mo Kα radiation
a = 9.8154 (6) ŵ = 0.08 mm1
b = 10.4283 (9) ÅT = 296 K
c = 13.4508 (9) Å0.45 × 0.45 × 0.25 mm
β = 108.796 (5)°
Data collection top
Bruker KappaCCD
diffractometer
4312 reflections with I > 2σ(I)
14483 measured reflectionsRint = 0.026
4886 independent reflections
Refinement top
R[F2 > 2σ(F2)] = 0.052112 restraints
wR(F2) = 0.146H atoms treated by a mixture of independent and constrained refinement
S = 1.04Δρmax = 0.32 e Å3
4886 reflectionsΔρmin = 0.31 e Å3
352 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*/UeqOcc. (<1)
O10.79854 (19)0.6680 (2)0.14153 (17)0.0696 (5)
H1A0.754 (4)0.621 (4)0.086 (3)0.078 (10)*
C20.7100 (2)0.6599 (2)0.20083 (17)0.0492 (4)
C30.59432 (19)0.57569 (18)0.18247 (14)0.0408 (3)
O40.55939 (15)0.48055 (14)0.10755 (10)0.0442 (3)
C50.44475 (17)0.40252 (17)0.12545 (12)0.0352 (3)
H5A0.36180.40150.06090.042*
C60.48701 (18)0.26326 (17)0.15977 (13)0.0378 (3)
O70.51953 (16)0.19164 (15)0.07950 (13)0.0520 (4)
C80.6421 (3)0.2234 (3)0.0510 (3)0.0751 (9)
H8A0.64890.16640.00320.113*
H8B0.72700.21530.11120.113*
H8C0.63380.31010.02580.113*
C90.34273 (18)0.20874 (16)0.17199 (13)0.0355 (3)
H9A0.26570.25080.11630.043*
C100.3121 (2)0.06174 (16)0.15353 (14)0.0410 (3)
O110.30844 (16)0.03344 (14)0.04772 (11)0.0463 (3)
H11A0.401 (3)0.054 (3)0.050 (2)0.056 (7)*
C120.4294 (3)0.0206 (2)0.2276 (2)0.0634 (6)
H12A0.52170.00710.22560.095*
H12B0.41450.10870.20600.095*
H12C0.42590.01230.29780.095*
C130.1567 (3)0.0210 (2)0.15323 (18)0.0512 (4)
C140.0423 (3)0.1179 (3)0.0930 (3)0.0660 (7)
H14A0.05060.09060.09410.099*
H14B0.04180.12330.02160.099*
H14C0.06410.20060.12560.099*
C150.1171 (4)0.1091 (3)0.0959 (3)0.0722 (7)
H15A0.02270.13440.09510.108*
H15B0.18580.17290.13190.108*
H15C0.11810.10060.02510.108*
C160.1457 (4)0.0033 (3)0.2641 (2)0.0775 (9)
H16A0.04920.02110.25870.116*
H16B0.16960.08250.30230.116*
H16C0.21140.06240.30050.116*
C170.3285 (3)0.26244 (19)0.27611 (15)0.0467 (4)
H17A0.22870.28350.26610.056*
H17B0.35880.19780.33070.056*
C180.4216 (2)0.38261 (19)0.30967 (13)0.0449 (4)
C190.5770 (3)0.3344 (2)0.35075 (16)0.0557 (5)
H19A0.58860.27740.40990.067*
H19B0.64200.40630.37450.067*
C200.6138 (2)0.2624 (2)0.26239 (17)0.0531 (5)
H20A0.69650.30240.25070.064*
H20B0.63920.17440.28400.064*
C210.40045 (19)0.46967 (16)0.21299 (12)0.0366 (3)
C220.2464 (2)0.5222 (2)0.17321 (18)0.0498 (4)
H22A0.23900.58420.11800.060*
H22B0.18050.45240.14330.060*
C230.2020 (3)0.5858 (3)0.2599 (3)0.0722 (8)
H23A0.25420.66560.28030.087*
H23B0.10000.60530.23420.087*
N240.2327 (3)0.5006 (2)0.3518 (2)0.0752 (7)
C250.1960 (6)0.5433 (5)0.4459 (4)0.0546 (11)0.612 (8)
H25A0.21980.63320.46010.065*0.612 (8)
H25B0.24950.49370.50700.065*0.612 (8)
C25A0.1310 (9)0.5706 (7)0.3988 (7)0.0579 (17)0.388 (8)
H25C0.17420.64930.43310.069*0.388 (8)
H25D0.04070.59080.34500.069*0.388 (8)
C260.0370 (5)0.5228 (7)0.4219 (4)0.0817 (19)0.612 (8)
H260.02800.56330.35860.098*0.612 (8)
C270.0006 (12)0.3835 (9)0.4492 (6)0.101 (3)0.612 (8)
H27A0.08640.34320.40240.122*0.612 (8)
H27B0.07840.32550.48200.122*0.612 (8)
C280.0193 (12)0.4978 (15)0.5104 (10)0.111 (4)0.612 (8)
H28A0.11690.52510.50180.133*0.612 (8)
H28B0.04730.50750.58110.133*0.612 (8)
C26A0.1090 (8)0.4783 (8)0.4756 (5)0.068 (2)0.388 (8)
H26A0.19010.43310.52530.082*0.388 (8)
C27A0.0235 (18)0.407 (2)0.4081 (16)0.143 (6)0.388 (8)
H27C0.06870.43590.33660.171*0.388 (8)
H27D0.02750.31480.41820.171*0.388 (8)
C28A0.031 (2)0.492 (3)0.495 (2)0.129 (7)0.388 (8)
H28C0.04100.45160.55700.155*0.388 (8)
H28D0.08220.57250.47550.155*0.388 (8)
C290.3847 (3)0.4674 (2)0.39174 (18)0.0652 (7)
H29A0.39890.41470.45460.078*
C300.4872 (4)0.5871 (3)0.4255 (2)0.0727 (8)
H30A0.43370.65660.44340.087*
H30B0.56560.56510.48840.087*
C310.5502 (3)0.6346 (2)0.34350 (17)0.0512 (4)
C320.51126 (19)0.57300 (18)0.24722 (14)0.0407 (3)
C330.6662 (3)0.7197 (2)0.36339 (19)0.0595 (5)
H33A0.69440.76680.42540.071*
C340.7396 (2)0.7347 (2)0.2915 (2)0.0567 (5)
H34A0.81120.79680.30420.068*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.0602 (9)0.0785 (13)0.0795 (12)0.0284 (9)0.0357 (9)0.0159 (10)
C20.0464 (9)0.0461 (10)0.0558 (10)0.0073 (8)0.0174 (8)0.0025 (8)
C30.0458 (8)0.0371 (8)0.0408 (7)0.0032 (7)0.0158 (6)0.0005 (6)
O40.0529 (7)0.0451 (7)0.0428 (6)0.0126 (6)0.0267 (5)0.0058 (5)
C50.0413 (7)0.0379 (7)0.0308 (6)0.0052 (6)0.0177 (5)0.0017 (6)
C60.0422 (7)0.0368 (7)0.0390 (7)0.0003 (6)0.0197 (6)0.0058 (6)
O70.0526 (7)0.0521 (8)0.0643 (8)0.0096 (6)0.0368 (6)0.0220 (7)
C80.0686 (13)0.0789 (17)0.103 (2)0.0219 (14)0.0626 (14)0.0399 (16)
C90.0454 (8)0.0309 (6)0.0366 (7)0.0013 (6)0.0219 (6)0.0002 (6)
C100.0550 (9)0.0303 (7)0.0450 (8)0.0014 (6)0.0264 (7)0.0003 (6)
O110.0568 (7)0.0429 (7)0.0489 (6)0.0055 (6)0.0304 (6)0.0113 (5)
C120.0773 (15)0.0390 (10)0.0713 (14)0.0109 (10)0.0204 (12)0.0095 (10)
C130.0661 (11)0.0370 (8)0.0646 (11)0.0087 (8)0.0406 (10)0.0049 (8)
C140.0492 (11)0.0595 (14)0.0966 (18)0.0044 (10)0.0339 (12)0.0078 (13)
C150.0888 (18)0.0478 (12)0.097 (2)0.0240 (12)0.0537 (16)0.0190 (13)
C160.117 (2)0.0613 (15)0.0815 (16)0.0256 (16)0.0692 (17)0.0056 (13)
C170.0724 (12)0.0366 (8)0.0426 (8)0.0043 (8)0.0348 (8)0.0019 (7)
C180.0703 (11)0.0386 (8)0.0337 (7)0.0049 (8)0.0277 (7)0.0026 (6)
C190.0773 (14)0.0489 (10)0.0340 (8)0.0003 (10)0.0082 (9)0.0052 (8)
C200.0517 (10)0.0477 (10)0.0543 (10)0.0058 (8)0.0093 (8)0.0023 (9)
C210.0461 (8)0.0340 (7)0.0359 (7)0.0009 (6)0.0216 (6)0.0008 (6)
C220.0485 (9)0.0411 (9)0.0671 (12)0.0013 (8)0.0289 (9)0.0010 (8)
C230.0728 (14)0.0496 (12)0.117 (2)0.0031 (11)0.0626 (15)0.0192 (14)
N240.1076 (17)0.0555 (11)0.0982 (16)0.0207 (12)0.0827 (15)0.0271 (11)
C250.072 (3)0.0528 (19)0.052 (2)0.0074 (19)0.038 (2)0.0066 (17)
C25A0.068 (4)0.056 (3)0.060 (4)0.022 (3)0.034 (3)0.003 (3)
C260.065 (3)0.127 (5)0.064 (2)0.040 (3)0.035 (2)0.012 (3)
C270.074 (4)0.132 (7)0.089 (5)0.023 (4)0.014 (3)0.043 (5)
C280.094 (5)0.174 (9)0.095 (5)0.058 (6)0.074 (5)0.054 (5)
C26A0.074 (4)0.085 (5)0.063 (4)0.029 (4)0.047 (3)0.020 (4)
C27A0.082 (8)0.177 (14)0.174 (14)0.044 (9)0.048 (10)0.034 (12)
C28A0.099 (10)0.180 (15)0.119 (12)0.023 (11)0.051 (8)0.036 (12)
C290.114 (2)0.0501 (12)0.0533 (10)0.0199 (13)0.0572 (13)0.0161 (10)
C300.115 (2)0.0607 (14)0.0589 (12)0.0255 (15)0.0515 (13)0.0260 (12)
C310.0679 (12)0.0413 (9)0.0486 (10)0.0064 (9)0.0245 (9)0.0119 (8)
C320.0480 (8)0.0356 (8)0.0402 (7)0.0018 (7)0.0166 (6)0.0023 (6)
C330.0744 (14)0.0455 (10)0.0571 (11)0.0099 (10)0.0190 (10)0.0178 (9)
C340.0542 (10)0.0452 (10)0.0675 (13)0.0122 (9)0.0154 (9)0.0108 (10)
Geometric parameters (Å, º) top
O1—C21.358 (3)C17—H17B0.9700
O1—H1A0.88 (4)C18—C191.530 (3)
C2—C31.393 (3)C18—C211.544 (2)
C2—C341.397 (3)C18—C291.545 (3)
C3—C321.372 (2)C19—C201.544 (3)
C3—O41.377 (2)C19—H19A0.9700
O4—C51.470 (2)C19—H19B0.9700
C5—C61.540 (2)C20—H20A0.9700
C5—C211.548 (2)C20—H20B0.9700
C5—H5A0.9800C21—C321.494 (2)
C6—O71.431 (2)C21—C221.533 (3)
C6—C201.532 (3)C22—C231.522 (3)
C6—C91.583 (2)C22—H22A0.9700
O7—C81.415 (3)C22—H22B0.9700
C8—H8A0.9600C23—N241.472 (4)
C8—H8B0.9600C23—H23A0.9700
C8—H8C0.9600C23—H23B0.9700
C9—C171.556 (2)N24—C291.456 (4)
C9—C101.567 (2)N24—C251.492 (4)
C9—H9A0.9800C25—C261.504 (7)
C10—O111.443 (2)C25—H25A0.9700
C10—C121.522 (3)C25—H25B0.9700
C10—C131.582 (3)C26—C281.487 (9)
O11—H11A0.92 (3)C26—C271.572 (9)
C12—H12A0.9600C26—H260.9800
C12—H12B0.9600C27—C281.493 (10)
C12—H12C0.9600C27—H27A0.9700
C13—C141.534 (4)C27—H27B0.9700
C13—C161.541 (3)C28—H28A0.9700
C13—C151.546 (3)C28—H28B0.9700
C14—H14A0.9600C29—C301.576 (4)
C14—H14B0.9600C29—H29A0.9800
C14—H14C0.9600C30—C311.511 (3)
C15—H15A0.9600C30—H30A0.9700
C15—H15B0.9600C30—H30B0.9700
C15—H15C0.9600C31—C321.384 (3)
C16—H16A0.9600C31—C331.400 (3)
C16—H16B0.9600C33—C341.388 (4)
C16—H16C0.9600C33—H33A0.9300
C17—C181.531 (3)C34—H34A0.9300
C17—H17A0.9700
C2—O1—H1A103 (2)C18—C19—H19A109.8
O1—C2—C3125.0 (2)C20—C19—H19A109.8
O1—C2—C34119.08 (19)C18—C19—H19B109.8
C3—C2—C34115.77 (19)C20—C19—H19B109.8
C32—C3—O4113.03 (15)H19A—C19—H19B108.2
C32—C3—C2121.17 (17)C6—C20—C19111.52 (17)
O4—C3—C2125.50 (17)C6—C20—H20A109.3
C3—O4—C5107.60 (12)C19—C20—H20A109.3
O4—C5—C6115.14 (14)C6—C20—H20B109.3
O4—C5—C21106.95 (13)C19—C20—H20B109.3
C6—C5—C21108.25 (12)H20A—C20—H20B108.0
O4—C5—H5A108.8C32—C21—C22112.84 (15)
C6—C5—H5A108.8C32—C21—C18106.10 (14)
C21—C5—H5A108.8C22—C21—C18110.72 (15)
O7—C6—C20111.26 (15)C32—C21—C5101.87 (13)
O7—C6—C5111.72 (14)C22—C21—C5112.53 (15)
C20—C6—C5109.76 (15)C18—C21—C5112.33 (14)
O7—C6—C9108.39 (13)C23—C22—C21112.4 (2)
C20—C6—C9113.49 (15)C23—C22—H22A109.1
C5—C6—C9101.90 (13)C21—C22—H22A109.1
C8—O7—C6119.87 (16)C23—C22—H22B109.1
O7—C8—H8A109.5C21—C22—H22B109.1
O7—C8—H8B109.5H22A—C22—H22B107.8
H8A—C8—H8B109.5N24—C23—C22110.4 (2)
O7—C8—H8C109.5N24—C23—H23A109.6
H8A—C8—H8C109.5C22—C23—H23A109.6
H8B—C8—H8C109.5N24—C23—H23B109.6
C17—C9—C10115.25 (14)C22—C23—H23B109.6
C17—C9—C6107.89 (14)H23A—C23—H23B108.1
C10—C9—C6117.87 (13)C29—N24—C23111.19 (18)
C17—C9—H9A104.8C29—N24—C25104.9 (3)
C10—C9—H9A104.8C23—N24—C25119.5 (3)
C6—C9—H9A104.8C29—N24—C25A133.6 (4)
O11—C10—C12107.66 (16)C23—N24—C25A94.3 (4)
O11—C10—C9107.40 (14)N24—C25—C26107.0 (4)
C12—C10—C9112.49 (17)N24—C25—H25A110.3
O11—C10—C13103.00 (16)C26—C25—H25A110.3
C12—C10—C13112.04 (18)N24—C25—H25B110.3
C9—C10—C13113.52 (14)C26—C25—H25B110.3
C10—O11—H11A101.6 (16)H25A—C25—H25B108.6
C10—C12—H12A109.5C28—C26—C25118.7 (7)
C10—C12—H12B109.5C28—C26—C2758.4 (5)
H12A—C12—H12B109.5C25—C26—C27112.8 (6)
C10—C12—H12C109.5C28—C26—H26117.7
H12A—C12—H12C109.5C25—C26—H26117.7
H12B—C12—H12C109.5C27—C26—H26117.7
C14—C13—C16108.8 (2)C28—C27—C2658.0 (5)
C14—C13—C15106.9 (2)C28—C27—H27A118.0
C16—C13—C15107.1 (2)C26—C27—H27A118.0
C14—C13—C10111.42 (17)C28—C27—H27B118.0
C16—C13—C10113.5 (2)C26—C27—H27B118.0
C15—C13—C10108.93 (18)H27A—C27—H27B115.1
C13—C14—H14A109.5C26—C28—C2763.6 (5)
C13—C14—H14B109.5C26—C28—H28A117.4
H14A—C14—H14B109.5C27—C28—H28A117.4
C13—C14—H14C109.5C26—C28—H28B117.4
H14A—C14—H14C109.5C27—C28—H28B117.4
H14B—C14—H14C109.5H28A—C28—H28B114.5
C13—C15—H15A109.5N24—C29—C18108.7 (2)
C13—C15—H15B109.5N24—C29—C30113.6 (2)
H15A—C15—H15B109.5C18—C29—C30112.59 (18)
C13—C15—H15C109.5N24—C29—H29A107.2
H15A—C15—H15C109.5C18—C29—H29A107.2
H15B—C15—H15C109.5C30—C29—H29A107.2
C13—C16—H16A109.5C31—C30—C29115.01 (17)
C13—C16—H16B109.5C31—C30—H30A108.5
H16A—C16—H16B109.5C29—C30—H30A108.5
C13—C16—H16C109.5C31—C30—H30B108.5
H16A—C16—H16C109.5C29—C30—H30B108.5
H16B—C16—H16C109.5H30A—C30—H30B107.5
C18—C17—C9109.96 (14)C32—C31—C33115.8 (2)
C18—C17—H17A109.7C32—C31—C30118.4 (2)
C9—C17—H17A109.7C33—C31—C30124.6 (2)
C18—C17—H17B109.7C3—C32—C31122.89 (18)
C9—C17—H17B109.7C3—C32—C21109.98 (15)
H17A—C17—H17B108.2C31—C32—C21125.23 (17)
C19—C18—C17105.59 (17)C34—C33—C31120.7 (2)
C19—C18—C21110.22 (16)C34—C33—H33A119.6
C17—C18—C21109.11 (14)C31—C33—H33A119.6
C19—C18—C29111.45 (18)C33—C34—C2122.5 (2)
C17—C18—C29115.04 (16)C33—C34—H34A118.8
C21—C18—C29105.44 (16)C2—C34—H34A118.8
C18—C19—C20109.58 (16)
C29—N24—C25—C26155.4 (4)C29—N24—C25A—C26A72.2 (7)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1A···O11i0.88 (4)1.93 (4)2.798 (3)166 (3)
O11—H11A···O70.92 (3)1.81 (3)2.574 (2)139 (3)
Symmetry code: (i) x+1, y+1/2, z.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O1—H1A···O11i0.88 (4)1.93 (4)2.798 (3)166 (3)
O11—H11A···O70.92 (3)1.81 (3)2.574 (2)139 (3)
Symmetry code: (i) x+1, y+1/2, z.
 

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