supplementary materials


rz5093 scheme

Acta Cryst. (2013). E69, o1835-o1836    [ doi:10.1107/S1600536813031735 ]

(S)-(+)-cis-4'-Benzyl­oxypraziquantel

A. Cedillo-Cruz, M. I. Aguilar and H. Jung-Cook

Abstract top

The asymmetric unit of the title compound, C26H30N2O3 {systematic name (S)-(+)-2-[cis-4-(benz­yloxy)cyclo­hexa­ne­carb­on­yl]-1,2,3,6,7,11b-hexa­hydro-4H-pyrazino­[2,1-a]isoquin­olin-4-one}, consists of two independent mol­ecules in which the O= Camide group is syn to the N-C(C=Olactam) moiety, making dihedral angles of 2.0 (8) and 3.7 (8)°. The conformation of the 1,4-disubstituted cyclo­hexane ring is cis in each independent mol­ecule, with the carbonyl group occupying an equatorial position and the benz­yloxy group an axial position. In one mol­ecule, two C and one O atom of the benz­yloxy group are disordered over two sets of sites, with a refined occupancy ratio of 0.772 (8):0.228 (8). In the crystal, mol­ecules are linked by C-H...O inter­actions, forming ribbons parallel to the b-axis direction.

Comment top

The importance of pyrazinoisoquinolone derivatives as anthelmintics is well established (Jung et al., 2008; Thétiot-Laurent et al., 2013). Extensive number of derivatives has been synthesized, nevertheless at the date there are none with an activity comparable to that of praziquantel (Duan et al., 2012; Patra et al., 2013; Wang et al., 2013). Such compounds usually have an asymmetric carbon atom and only one of the enantiomers presents anthelmintic activity, often the enantiomer with (R)-(-)-configuration (Staudt et al., 1992). Herein, we report the synthesis and crystal structure of the title compound, (S)-(+)-cis-4 -benzyloxypraziquantel (Fig. 1), as a key intermediate for the synthesis of (S)-(+)-cis-4 -hydroxypraziquantel, one of the main metabolites of praziquantel (Meier & Blaschke, 2001).

The most stable conformation for (S)-(+)-cis-4'-benzyloxypraziquantel is observed where the O Camide group is syn to the N–C(COlactam) moiety with a dihedral angle of 2.0 (8) and 3.7 (8)° for the two independent molecules per asymmetric unit. Furthermore, the conformation of the 1,4-disubstituted cyclohexane is cis, where the carbonyl moiety occupies an equatorial position and the benzyloxy moiety occupies an axial position. In the crystal (Fig. 2), molecules are linked by intermolecular C—H···O hydrogen interactions (Table 1) to form ribbons parallel to the b axis.

Related literature top

For derivatives with anthelmintic activity, see: Staudt et al. (1992); Jung et al. (2008); Thétiot-Laurent et al. (2013); Duan et al. (2012); Patra et al. (2013); Wang et al. (2013); Meier & Blaschke (2001).

Experimental top

To a solution of (S)-(+)-praziquanamine (505.5 mg, 2.50 mmol) and 4-methylmorpholine (1.4 ml, 12.73) in dichloromethane (35 ml) under nitrogen atmosphere, a solution of cis-4-(benzyloxy)cyclohexanecarbonyl chloride (586 mg, 2.50 mmol) in dichloromethane (15 ml) was added dropwise at 0°C. After stirring at room temperature for 2 h, dichloromethane (50 ml) was added. The organic layer was successively washed with 1 M HCl (3 · 50 ml), saturated solution of NaHCO3 (3 · 50 ml), water (3 · 50 ml) and dried over Na2SO4, filtered and concentrated. The residue was purified by column chromatography (SiO2, ethyl acetate 100%). A white powder was obtained (935.7 mg, 89% yield). m.p. 405–408 K. Single-crystals suitable for X-ray diffraction were prepared by evaporation of a solution of the title compound in methanol at room temperature.

Refinement top

All H atoms were geometrically positioned and refined using a riding model, with C–H = 0.95 Å for aromatic CH, 0.99 Å for secondary CH2, 1.00 Å for tertiary CH, respectively, and with Uiso(H) = 1.2Ueq(C). The absolute configuration was not established by anomalous dispersion effects, nevertheless the absolute configuration could be assigned from the known configuration of the chiral centers. In one molecule the C20A, C21A and O3A atoms of the benzyloxy group are disordered over two sets of sites with refined site occupancies of 0.772 (8):0.228 (8). During the refinement, the C21B–C26A, C21B–C22A and C21B–C20B bond lengths were constrained to be 1.38 (1), 1.38 (2) and 1.50 (1) Å, respectively. In the last cycles of refinement, 14 outliers were omitted.

Computing details top

Data collection: CrysAlis PRO (Agilent, 2011); cell refinement: CrysAlis PRO (Agilent, 2011); data reduction: CrysAlis PRO (Agilent, 2011); program(s) used to solve structure: SHELXS2013 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2013 (Sheldrick, 2008); molecular graphics: Mercury (Macrae et al., 2006) and ORTEP-3 for Windows (Farrugia, 2012); software used to prepare material for publication: WinGX (Farrugia, 2012) and publCIF (Westrip, 2010).

Figures top
[Figure 1] Fig. 1. The asymmetric unit of the title compound with displacement ellipsoids drawn at the 50% probability level. Hydrogen atoms are omitted for clarity. Only the major component of the disordered atoms is shown.
[Figure 2] Fig. 2. Intermolecular C—H···O interactions (dotted lines) forming ribbons parallel to the b axis in the title compound. Only the major components of the disordered atoms are shown.
(S)-(+)-2-[cis-4-(Benzyloxy)cyclohexanecarbonyl]-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinolin-4-one top
Crystal data top
C26H30N2O3Dx = 1.261 Mg m3
Mr = 418.52Melting point = 405–408 K
Monoclinic, P21Cu Kα radiation, λ = 1.54184 Å
a = 15.007 (2) ÅCell parameters from 1613 reflections
b = 10.3322 (8) Åθ = 3.3–73.3°
c = 16.019 (2) ŵ = 0.66 mm1
β = 117.399 (13)°T = 130 K
V = 2205.2 (5) Å3Needle, colourless
Z = 40.59 × 0.31 × 0.13 mm
F(000) = 896
Data collection top
Oxford Diffraction Xcalibur (Atlas, Gemini)
diffractometer
5852 independent reflections
Radiation source: Enhance (Cu) X-ray Source3845 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.057
Detector resolution: 10.4685 pixels mm-1θmax = 68.3°, θmin = 5.5°
ω scansh = 1718
Absorption correction: analytical
[CrysAlis PRO (Agilent, 2011), based on expressions derived by Clark & Reid (1995)]
k = 127
Tmin = 0.937, Tmax = 0.979l = 1918
8420 measured reflections
Refinement top
Refinement on F2Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: fullH-atom parameters constrained
R[F2 > 2σ(F2)] = 0.052 w = 1/[σ2(Fo2) + (0.0462P)2 + 0.6847P]
where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.137(Δ/σ)max < 0.001
S = 1.03Δρmax = 0.25 e Å3
5852 reflectionsΔρmin = 0.23 e Å3
558 parametersExtinction correction: SHELXL2013 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
4 restraintsExtinction coefficient: 0.00115 (17)
Primary atom site location: structure-invariant direct methodsAbsolute structure: Flack parameter determined using 868 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
Secondary atom site location: difference Fourier mapAbsolute structure parameter: 0.382 (265)
Crystal data top
C26H30N2O3V = 2205.2 (5) Å3
Mr = 418.52Z = 4
Monoclinic, P21Cu Kα radiation
a = 15.007 (2) ŵ = 0.66 mm1
b = 10.3322 (8) ÅT = 130 K
c = 16.019 (2) Å0.59 × 0.31 × 0.13 mm
β = 117.399 (13)°
Data collection top
Oxford Diffraction Xcalibur (Atlas, Gemini)
diffractometer
5852 independent reflections
Absorption correction: analytical
[CrysAlis PRO (Agilent, 2011), based on expressions derived by Clark & Reid (1995)]
3845 reflections with I > 2σ(I)
Tmin = 0.937, Tmax = 0.979Rint = 0.057
8420 measured reflectionsθmax = 68.3°
Refinement top
R[F2 > 2σ(F2)] = 0.052H-atom parameters constrained
wR(F2) = 0.137Δρmax = 0.25 e Å3
S = 1.03Δρmin = 0.23 e Å3
5852 reflectionsAbsolute structure: Flack parameter determined using 868 quotients [(I+)-(I-)]/[(I+)+(I-)] (Parsons et al., 2013)
558 parametersAbsolute structure parameter: 0.382 (265)
4 restraints
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 > 2σ(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)
O10.6375 (3)0.2009 (4)0.7391 (3)0.0452 (10)
O20.2778 (3)0.1973 (4)0.5624 (3)0.0489 (11)
N10.5909 (3)0.4128 (4)0.7198 (3)0.0346 (11)
N20.3976 (3)0.3440 (4)0.5860 (3)0.0350 (11)
C120.5135 (3)0.5133 (5)0.6799 (3)0.0289 (12)
H120.47920.52240.72030.035*
C130.3000 (4)0.3110 (5)0.5562 (4)0.0341 (13)
C160.0377 (4)0.4631 (6)0.4195 (4)0.0423 (15)
H16C0.02940.42260.38630.051*
H16D0.04920.51390.37290.051*
C20.4924 (4)0.7477 (5)0.6361 (3)0.0331 (13)
H20.42260.73560.61540.040*
C190.2203 (4)0.4976 (5)0.5981 (4)0.0351 (13)
H19A0.20280.44240.63890.042*
H19B0.28800.53410.63690.042*
C90.5738 (4)0.2851 (6)0.6990 (4)0.0349 (13)
O30.0086 (3)0.4888 (4)0.5570 (3)0.0477 (11)
C10.5582 (4)0.6432 (5)0.6747 (3)0.0286 (12)
C110.4367 (4)0.4709 (5)0.5816 (4)0.0330 (12)
H11A0.38110.53430.55540.040*
H11B0.46870.46780.53960.040*
C100.4747 (4)0.2445 (5)0.6220 (4)0.0386 (14)
H10A0.48520.21160.56920.046*
H10B0.44940.17150.64520.046*
C140.2207 (4)0.4154 (5)0.5181 (4)0.0350 (13)
H140.23620.47340.47650.042*
C70.7334 (4)0.5547 (6)0.7575 (4)0.0434 (15)
H7A0.79460.59110.80990.052*
H7B0.75330.51230.71320.052*
C150.1172 (4)0.3573 (6)0.4602 (4)0.0396 (14)
H15C0.10080.29910.50030.048*
H15D0.11720.30510.40830.048*
C170.0396 (4)0.5545 (6)0.4957 (4)0.0409 (14)
H170.00720.62830.46480.049*
C60.6612 (4)0.6616 (5)0.7082 (3)0.0324 (13)
C220.2257 (4)0.3782 (7)0.5544 (4)0.0466 (16)
H220.27420.42680.50340.056*
C180.1439 (4)0.6076 (6)0.5572 (4)0.0421 (15)
H18A0.14320.65890.60910.051*
H18B0.16380.66560.51950.051*
C80.6880 (4)0.4558 (6)0.7955 (4)0.0444 (16)
H8A0.73380.38090.82080.053*
H8B0.67810.49410.84730.053*
C50.6944 (4)0.7833 (6)0.6972 (4)0.0432 (15)
H50.76380.79600.71650.052*
C210.1238 (4)0.3933 (6)0.5797 (4)0.0406 (14)
C30.5275 (4)0.8674 (5)0.6280 (3)0.0372 (14)
H30.48200.93720.60100.045*
C230.2566 (5)0.2938 (7)0.6023 (4)0.0524 (18)
H230.32620.28390.58380.063*
C200.0961 (4)0.4757 (7)0.5179 (5)0.0506 (16)
H20A0.12240.43560.45490.061*
H20B0.12710.56230.51040.061*
C260.0555 (4)0.3261 (6)0.6553 (4)0.0446 (15)
H260.01420.33720.67470.054*
C250.0867 (4)0.2407 (7)0.7045 (4)0.0514 (17)
H250.03800.19460.75690.062*
C40.6288 (4)0.8862 (6)0.6590 (4)0.0433 (15)
H40.65350.96910.65420.052*
C240.1862 (4)0.2229 (7)0.6780 (4)0.0547 (18)
H240.20720.16320.71060.066*
C15A0.0948 (4)0.3602 (6)0.0635 (4)0.0425 (14)
H15A0.09770.32120.11870.051*
H15B0.07900.29050.03000.051*
C16A0.0117 (4)0.4614 (6)0.0971 (4)0.0434 (15)
H16A0.02280.52510.13750.052*
H16B0.05370.41870.13530.052*
N1A0.5699 (3)0.4053 (4)0.2033 (3)0.0333 (10)
O1A0.6124 (3)0.1921 (4)0.2158 (3)0.0442 (10)
N2A0.3746 (3)0.3446 (4)0.0686 (3)0.0354 (11)
C13A0.2762 (4)0.3121 (6)0.0364 (4)0.0389 (14)
C1A0.5421 (4)0.6375 (5)0.1644 (3)0.0313 (12)
O2A0.2541 (3)0.1984 (4)0.0393 (3)0.0564 (12)
C10A0.4491 (4)0.2433 (5)0.0997 (4)0.0392 (14)
H10C0.45830.21420.04530.047*
H10D0.42280.16880.12050.047*
C11A0.4143 (4)0.4725 (5)0.0676 (4)0.0350 (13)
H11C0.35940.53690.04570.042*
H11D0.44370.47350.02350.042*
C9A0.5500 (4)0.2787 (5)0.1779 (4)0.0357 (13)
C12A0.4943 (4)0.5080 (5)0.1658 (4)0.0316 (12)
H12A0.46150.51620.20750.038*
C14A0.1972 (4)0.4180 (6)0.0019 (4)0.0387 (13)
H14A0.21530.48260.03430.046*
C19A0.1934 (4)0.4876 (6)0.0849 (4)0.0428 (14)
H19C0.18090.42390.12440.051*
H19D0.25870.53000.12410.051*
C6A0.6451 (4)0.6533 (6)0.1976 (4)0.0359 (13)
C2A0.4790 (4)0.7449 (5)0.1282 (3)0.0356 (13)
H2A0.40870.73500.10580.043*
C5A0.6826 (4)0.7736 (6)0.1926 (4)0.0435 (15)
H5A0.75280.78370.21430.052*
C4A0.6206 (5)0.8790 (6)0.1570 (4)0.0500 (17)
H4A0.64780.96100.15440.060*
C8A0.6671 (4)0.4424 (6)0.2795 (4)0.0460 (16)
H8D0.71090.36530.30250.055*
H8C0.65810.47830.33250.055*
C7A0.7157 (4)0.5424 (6)0.2450 (4)0.0443 (15)
H7C0.77720.57570.29880.053*
H7D0.73550.50170.20010.053*
C18A0.1100 (5)0.5890 (6)0.0485 (4)0.0485 (16)
H18C0.10710.63130.10260.058*
H18D0.12610.65630.01350.058*
C21A0.1020 (7)0.3739 (16)0.1231 (8)0.0531 (12)0.772 (8)
C17A0.0086 (5)0.5313 (6)0.0152 (5)0.0531 (12)
H17A0.04130.60330.04080.064*
C3A0.5177 (4)0.8653 (6)0.1249 (3)0.0398 (14)
H3A0.47440.93790.10080.048*
C26A0.0429 (5)0.2988 (7)0.1947 (5)0.0605 (19)
H26A0.02690.31680.22720.073*
C23A0.2459 (5)0.2612 (8)0.1121 (5)0.064 (2)
H23A0.31630.24730.08290.077*
C24A0.1851 (5)0.1881 (8)0.1876 (5)0.0590 (19)
H24A0.21360.12480.21130.071*
C25A0.0821 (5)0.2051 (7)0.2303 (5)0.0610 (19)
H25A0.03940.15370.28270.073*
C22A0.2069 (5)0.3544 (8)0.0777 (5)0.064 (2)
H22A0.25110.41070.02960.076*
O3A0.0272 (4)0.4294 (5)0.0256 (4)0.0387 (13)0.772 (8)
C20A0.0532 (7)0.4814 (9)0.0929 (7)0.0531 (12)0.772 (8)
H20C0.10060.55440.06540.064*0.772 (8)
H20D0.00750.51390.14790.064*0.772 (8)
O3B0.0059 (15)0.481 (2)0.0661 (14)0.0387 (13)0.228 (8)
C20B0.106 (2)0.457 (3)0.0344 (19)0.0531 (12)0.228 (8)
H20E0.13840.41290.02760.064*0.228 (8)
H20F0.14220.53810.03090.064*0.228 (8)
C21B0.1030 (16)0.369 (5)0.112 (3)0.0531 (12)0.228 (8)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
O10.049 (2)0.033 (2)0.063 (3)0.014 (2)0.034 (2)0.006 (2)
O20.043 (2)0.028 (2)0.069 (3)0.0077 (19)0.020 (2)0.003 (2)
N10.041 (2)0.028 (3)0.032 (2)0.007 (2)0.0143 (19)0.001 (2)
N20.036 (2)0.025 (3)0.046 (3)0.002 (2)0.021 (2)0.003 (2)
C120.032 (3)0.027 (3)0.032 (3)0.008 (2)0.018 (2)0.006 (2)
C130.038 (3)0.032 (3)0.034 (3)0.004 (3)0.018 (2)0.003 (3)
C160.038 (3)0.047 (4)0.037 (3)0.001 (3)0.014 (2)0.003 (3)
C20.036 (3)0.031 (3)0.033 (3)0.002 (3)0.016 (2)0.001 (3)
C190.035 (3)0.032 (3)0.037 (3)0.001 (3)0.016 (2)0.000 (3)
C90.041 (3)0.032 (3)0.045 (3)0.008 (3)0.030 (3)0.009 (3)
O30.0348 (19)0.057 (3)0.049 (2)0.006 (2)0.0168 (18)0.010 (2)
C10.038 (3)0.024 (3)0.026 (3)0.005 (2)0.018 (2)0.003 (2)
C110.033 (3)0.030 (3)0.039 (3)0.004 (2)0.018 (2)0.004 (3)
C100.048 (3)0.023 (3)0.052 (4)0.005 (3)0.030 (3)0.001 (3)
C140.035 (3)0.031 (3)0.040 (3)0.005 (3)0.018 (2)0.000 (3)
C70.036 (3)0.041 (4)0.044 (3)0.000 (3)0.011 (3)0.008 (3)
C150.040 (3)0.035 (4)0.041 (3)0.003 (3)0.016 (3)0.001 (3)
C170.042 (3)0.039 (4)0.044 (3)0.009 (3)0.022 (3)0.014 (3)
C60.035 (3)0.032 (3)0.029 (3)0.002 (3)0.013 (2)0.007 (2)
C220.036 (3)0.065 (5)0.044 (3)0.007 (3)0.022 (3)0.006 (3)
C180.048 (3)0.035 (4)0.042 (3)0.002 (3)0.020 (3)0.006 (3)
C80.039 (3)0.045 (4)0.035 (3)0.013 (3)0.005 (2)0.001 (3)
C50.041 (3)0.043 (4)0.048 (3)0.011 (3)0.022 (3)0.009 (3)
C210.034 (3)0.043 (4)0.045 (3)0.002 (3)0.018 (3)0.006 (3)
C30.047 (3)0.029 (3)0.032 (3)0.004 (3)0.016 (2)0.001 (3)
C230.047 (4)0.077 (5)0.041 (3)0.012 (3)0.027 (3)0.011 (4)
C200.036 (3)0.048 (4)0.065 (4)0.004 (3)0.020 (3)0.012 (4)
C260.038 (3)0.043 (4)0.047 (3)0.005 (3)0.015 (3)0.004 (3)
C250.054 (4)0.049 (4)0.041 (3)0.004 (3)0.013 (3)0.008 (3)
C40.052 (4)0.037 (4)0.041 (3)0.013 (3)0.022 (3)0.008 (3)
C240.056 (4)0.067 (5)0.051 (4)0.017 (4)0.033 (3)0.012 (4)
C15A0.037 (3)0.040 (4)0.047 (3)0.006 (3)0.017 (3)0.002 (3)
C16A0.041 (3)0.040 (4)0.046 (3)0.000 (3)0.018 (3)0.012 (3)
N1A0.039 (2)0.024 (3)0.038 (2)0.004 (2)0.019 (2)0.005 (2)
O1A0.048 (2)0.028 (2)0.065 (3)0.008 (2)0.032 (2)0.008 (2)
N2A0.041 (3)0.021 (2)0.047 (3)0.002 (2)0.022 (2)0.003 (2)
C13A0.042 (3)0.033 (4)0.038 (3)0.008 (3)0.016 (3)0.002 (3)
C1A0.038 (3)0.033 (3)0.024 (3)0.003 (3)0.016 (2)0.001 (2)
O2A0.047 (2)0.031 (3)0.085 (3)0.007 (2)0.025 (2)0.007 (2)
C10A0.050 (3)0.021 (3)0.050 (3)0.000 (3)0.025 (3)0.001 (3)
C11A0.044 (3)0.027 (3)0.036 (3)0.004 (3)0.020 (3)0.000 (3)
C9A0.047 (3)0.028 (3)0.044 (3)0.003 (3)0.031 (3)0.009 (3)
C12A0.043 (3)0.023 (3)0.036 (3)0.003 (3)0.025 (2)0.004 (2)
C14A0.042 (3)0.030 (3)0.042 (3)0.003 (3)0.017 (3)0.001 (3)
C19A0.050 (3)0.038 (4)0.038 (3)0.000 (3)0.019 (3)0.000 (3)
C6A0.045 (3)0.032 (3)0.036 (3)0.006 (3)0.023 (3)0.004 (3)
C2A0.048 (3)0.030 (3)0.032 (3)0.001 (3)0.021 (3)0.000 (3)
C5A0.048 (3)0.047 (4)0.034 (3)0.016 (3)0.018 (3)0.005 (3)
C4A0.070 (4)0.040 (4)0.039 (3)0.024 (4)0.024 (3)0.009 (3)
C8A0.047 (3)0.041 (4)0.044 (3)0.006 (3)0.016 (3)0.002 (3)
C7A0.038 (3)0.043 (4)0.052 (4)0.004 (3)0.021 (3)0.007 (3)
C18A0.072 (4)0.035 (4)0.039 (3)0.009 (3)0.026 (3)0.003 (3)
C21A0.063 (3)0.045 (3)0.066 (3)0.005 (2)0.042 (2)0.002 (2)
C17A0.063 (3)0.045 (3)0.066 (3)0.005 (2)0.042 (2)0.002 (2)
C3A0.063 (4)0.025 (3)0.034 (3)0.004 (3)0.025 (3)0.002 (3)
C26A0.051 (4)0.050 (5)0.080 (5)0.010 (3)0.029 (4)0.021 (4)
C23A0.049 (4)0.099 (6)0.048 (4)0.012 (4)0.025 (3)0.022 (4)
C24A0.062 (4)0.072 (5)0.055 (4)0.027 (4)0.037 (4)0.021 (4)
C25A0.063 (4)0.064 (5)0.052 (4)0.004 (4)0.022 (3)0.008 (4)
C22A0.066 (4)0.075 (6)0.065 (4)0.020 (4)0.043 (4)0.006 (4)
O3A0.051 (3)0.030 (3)0.040 (3)0.004 (3)0.025 (3)0.009 (2)
C20A0.063 (3)0.045 (3)0.066 (3)0.005 (2)0.042 (2)0.002 (2)
O3B0.051 (3)0.030 (3)0.040 (3)0.004 (3)0.025 (3)0.009 (2)
C20B0.063 (3)0.045 (3)0.066 (3)0.005 (2)0.042 (2)0.002 (2)
C21B0.063 (3)0.045 (3)0.066 (3)0.005 (2)0.042 (2)0.002 (2)
Geometric parameters (Å, º) top
O1—C91.232 (6)C16A—C17A1.517 (8)
O2—C131.238 (6)C16A—H16A0.9900
N1—C91.356 (7)C16A—H16B0.9900
N1—C121.467 (6)N1A—C9A1.362 (7)
N1—C81.471 (6)N1A—C8A1.458 (7)
N2—C131.358 (6)N1A—C12A1.465 (6)
N2—C111.452 (7)O1A—C9A1.234 (6)
N2—C101.455 (6)N2A—C13A1.364 (7)
C12—C11.519 (7)N2A—C10A1.443 (7)
C12—C111.526 (7)N2A—C11A1.452 (6)
C12—H121.0000C13A—O2A1.227 (6)
C13—C141.512 (7)C13A—C14A1.518 (8)
C16—C151.526 (8)C1A—C6A1.394 (7)
C16—C171.533 (8)C1A—C2A1.400 (7)
C16—H16C0.9900C1A—C12A1.523 (7)
C16—H16D0.9900C10A—C9A1.499 (7)
C2—C31.374 (7)C10A—H10C0.9900
C2—C11.401 (7)C10A—H10D0.9900
C2—H20.9500C11A—C12A1.521 (7)
C19—C181.531 (7)C11A—H11C0.9900
C19—C141.540 (7)C11A—H11D0.9900
C19—H19A0.9900C12A—H12A1.0000
C19—H19B0.9900C14A—C19A1.535 (8)
C9—C101.489 (7)C14A—H14A1.0000
O3—C201.405 (6)C19A—C18A1.527 (8)
O3—C171.436 (6)C19A—H19C0.9900
C1—C61.396 (7)C19A—H19D0.9900
C11—H11A0.9900C6A—C5A1.382 (8)
C11—H11B0.9900C6A—C7A1.507 (8)
C10—H10A0.9900C2A—C3A1.385 (7)
C10—H10B0.9900C2A—H2A0.9500
C14—C151.519 (7)C5A—C4A1.375 (9)
C14—H141.0000C5A—H5A0.9500
C7—C61.494 (7)C4A—C3A1.392 (8)
C7—C81.504 (8)C4A—H4A0.9500
C7—H7A0.9900C8A—C7A1.509 (8)
C7—H7B0.9900C8A—H8D0.9900
C15—H15C0.9900C8A—H8C0.9900
C15—H15D0.9900C7A—H7C0.9900
C17—C181.517 (8)C7A—H7D0.9900
C17—H171.0000C18A—C17A1.511 (9)
C6—C51.392 (8)C18A—H18C0.9900
C22—C231.376 (8)C18A—H18D0.9900
C22—C211.398 (7)C21A—C26A1.330 (12)
C22—H220.9500C21A—C22A1.412 (12)
C18—H18A0.9900C21A—C20A1.526 (14)
C18—H18B0.9900C17A—O3B1.418 (19)
C8—H8A0.9900C17A—O3A1.466 (8)
C8—H8B0.9900C17A—H17A1.0000
C5—C41.386 (8)C3A—H3A0.9500
C5—H50.9500C26A—C25A1.384 (9)
C21—C261.363 (8)C26A—C21B1.410 (12)
C21—C201.502 (8)C26A—H26A0.9500
C3—C41.379 (7)C23A—C24A1.360 (10)
C3—H30.9500C23A—C22A1.367 (10)
C23—C241.394 (9)C23A—H23A0.9500
C23—H230.9500C24A—C25A1.383 (8)
C20—H20A0.9900C24A—H24A0.9500
C20—H20B0.9900C25A—H25A0.9500
C26—C251.400 (8)C22A—C21B1.40 (2)
C26—H260.9500C22A—H22A0.9500
C25—C241.364 (8)O3A—C20A1.411 (10)
C25—H250.9500C20A—H20C0.9900
C4—H40.9500C20A—H20D0.9900
C24—H240.9500O3B—C20B1.54 (3)
C15A—C16A1.523 (7)C20B—C21B1.523 (12)
C15A—C14A1.528 (7)C20B—H20E0.9900
C15A—H15A0.9900C20B—H20F0.9900
C15A—H15B0.9900
C9—N1—C12124.0 (4)C17A—C16A—H16A109.3
C9—N1—C8120.1 (4)C15A—C16A—H16A109.3
C12—N1—C8115.5 (4)C17A—C16A—H16B109.3
C13—N2—C11127.2 (4)C15A—C16A—H16B109.3
C13—N2—C10119.6 (5)H16A—C16A—H16B108.0
C11—N2—C10113.1 (4)C9A—N1A—C8A120.0 (5)
N1—C12—C1111.6 (4)C9A—N1A—C12A123.4 (4)
N1—C12—C11108.5 (4)C8A—N1A—C12A116.2 (4)
C1—C12—C11109.9 (4)C13A—N2A—C10A118.9 (5)
N1—C12—H12108.9C13A—N2A—C11A126.8 (5)
C1—C12—H12108.9C10A—N2A—C11A114.0 (4)
C11—C12—H12108.9O2A—C13A—N2A119.1 (5)
O2—C13—N2119.8 (5)O2A—C13A—C14A121.6 (5)
O2—C13—C14121.3 (5)N2A—C13A—C14A119.2 (5)
N2—C13—C14118.9 (5)C6A—C1A—C2A119.0 (5)
C15—C16—C17112.1 (4)C6A—C1A—C12A123.0 (5)
C15—C16—H16C109.2C2A—C1A—C12A118.0 (4)
C17—C16—H16C109.2N2A—C10A—C9A115.8 (5)
C15—C16—H16D109.2N2A—C10A—H10C108.3
C17—C16—H16D109.2C9A—C10A—H10C108.3
H16C—C16—H16D107.9N2A—C10A—H10D108.3
C3—C2—C1120.8 (5)C9A—C10A—H10D108.3
C3—C2—H2119.6H10C—C10A—H10D107.4
C1—C2—H2119.6N2A—C11A—C12A109.9 (4)
C18—C19—C14110.0 (4)N2A—C11A—H11C109.7
C18—C19—H19A109.7C12A—C11A—H11C109.7
C14—C19—H19A109.7N2A—C11A—H11D109.7
C18—C19—H19B109.7C12A—C11A—H11D109.7
C14—C19—H19B109.7H11C—C11A—H11D108.2
H19A—C19—H19B108.2O1A—C9A—N1A122.5 (5)
O1—C9—N1123.0 (5)O1A—C9A—C10A118.7 (5)
O1—C9—C10118.2 (5)N1A—C9A—C10A118.9 (5)
N1—C9—C10118.8 (5)N1A—C12A—C11A110.1 (4)
C20—O3—C17112.8 (4)N1A—C12A—C1A111.2 (4)
C6—C1—C2119.7 (5)C11A—C12A—C1A110.4 (4)
C6—C1—C12122.5 (5)N1A—C12A—H12A108.4
C2—C1—C12117.7 (4)C11A—C12A—H12A108.4
N2—C11—C12109.8 (4)C1A—C12A—H12A108.4
N2—C11—H11A109.7C13A—C14A—C15A109.8 (5)
C12—C11—H11A109.7C13A—C14A—C19A110.9 (5)
N2—C11—H11B109.7C15A—C14A—C19A110.5 (5)
C12—C11—H11B109.7C13A—C14A—H14A108.5
H11A—C11—H11B108.2C15A—C14A—H14A108.5
N2—C10—C9116.0 (5)C19A—C14A—H14A108.5
N2—C10—H10A108.3C18A—C19A—C14A110.0 (4)
C9—C10—H10A108.3C18A—C19A—H19C109.7
N2—C10—H10B108.3C14A—C19A—H19C109.7
C9—C10—H10B108.3C18A—C19A—H19D109.7
H10A—C10—H10B107.4C14A—C19A—H19D109.7
C13—C14—C15111.0 (5)H19C—C19A—H19D108.2
C13—C14—C19111.2 (4)C5A—C6A—C1A119.6 (6)
C15—C14—C19109.4 (4)C5A—C6A—C7A120.1 (5)
C13—C14—H14108.4C1A—C6A—C7A120.2 (5)
C15—C14—H14108.4C3A—C2A—C1A120.8 (5)
C19—C14—H14108.4C3A—C2A—H2A119.6
C6—C7—C8111.3 (5)C1A—C2A—H2A119.6
C6—C7—H7A109.4C4A—C5A—C6A121.3 (6)
C8—C7—H7A109.4C4A—C5A—H5A119.3
C6—C7—H7B109.4C6A—C5A—H5A119.3
C8—C7—H7B109.4C5A—C4A—C3A119.8 (6)
H7A—C7—H7B108.0C5A—C4A—H4A120.1
C14—C15—C16110.8 (5)C3A—C4A—H4A120.1
C14—C15—H15C109.5N1A—C8A—C7A109.8 (5)
C16—C15—H15C109.5N1A—C8A—H8D109.7
C14—C15—H15D109.5C7A—C8A—H8D109.7
C16—C15—H15D109.5N1A—C8A—H8C109.7
H15C—C15—H15D108.1C7A—C8A—H8C109.7
O3—C17—C18106.8 (4)H8D—C8A—H8C108.2
O3—C17—C16111.1 (5)C6A—C7A—C8A111.0 (5)
C18—C17—C16112.1 (5)C6A—C7A—H7C109.4
O3—C17—H17108.9C8A—C7A—H7C109.4
C18—C17—H17108.9C6A—C7A—H7D109.4
C16—C17—H17108.9C8A—C7A—H7D109.4
C5—C6—C1118.1 (5)H7C—C7A—H7D108.0
C5—C6—C7121.3 (5)C17A—C18A—C19A112.4 (5)
C1—C6—C7120.5 (5)C17A—C18A—H18C109.1
C23—C22—C21120.9 (6)C19A—C18A—H18C109.1
C23—C22—H22119.6C17A—C18A—H18D109.1
C21—C22—H22119.6C19A—C18A—H18D109.1
C17—C18—C19110.8 (5)H18C—C18A—H18D107.9
C17—C18—H18A109.5C26A—C21A—C22A120.2 (10)
C19—C18—H18A109.5C26A—C21A—C20A118.1 (9)
C17—C18—H18B109.5C22A—C21A—C20A121.7 (8)
C19—C18—H18B109.5O3B—C17A—C18A88.3 (9)
H18A—C18—H18B108.1O3A—C17A—C18A116.4 (5)
N1—C8—C7109.4 (5)O3B—C17A—C16A130.2 (10)
N1—C8—H8A109.8O3A—C17A—C16A101.9 (5)
C7—C8—H8A109.8C18A—C17A—C16A110.4 (5)
N1—C8—H8B109.8O3B—C17A—H17A108.4
C7—C8—H8B109.8C18A—C17A—H17A108.4
H8A—C8—H8B108.2C16A—C17A—H17A108.4
C4—C5—C6121.7 (5)C2A—C3A—C4A119.4 (6)
C4—C5—H5119.1C2A—C3A—H3A120.3
C6—C5—H5119.1C4A—C3A—H3A120.3
C26—C21—C22118.5 (6)C21A—C26A—C25A121.5 (8)
C26—C21—C20123.4 (5)C25A—C26A—C21B122.4 (13)
C22—C21—C20118.0 (5)C25A—C26A—H26A118.8
C2—C3—C4120.0 (5)C21B—C26A—H26A118.8
C2—C3—H3120.0C24A—C23A—C22A120.9 (6)
C4—C3—H3120.0C24A—C23A—H23A119.6
C22—C23—C24120.2 (6)C22A—C23A—H23A119.6
C22—C23—H23119.9C23A—C24A—C25A120.5 (7)
C24—C23—H23119.9C23A—C24A—H24A119.7
O3—C20—C21110.6 (5)C25A—C24A—H24A119.7
O3—C20—H20A109.5C24A—C25A—C26A118.4 (7)
C21—C20—H20A109.5C24A—C25A—H25A120.8
O3—C20—H20B109.5C26A—C25A—H25A120.8
C21—C20—H20B109.5C23A—C22A—C21B121.4 (11)
H20A—C20—H20B108.1C23A—C22A—C21A118.4 (7)
C21—C26—C25120.7 (6)C23A—C22A—H22A119.3
C21—C26—H26119.6C21B—C22A—H22A119.3
C25—C26—H26119.6C20A—O3A—C17A110.8 (6)
C24—C25—C26120.8 (6)O3A—C20A—C21A107.9 (9)
C24—C25—H25119.6O3A—C20A—H20C110.1
C26—C25—H25119.6C21A—C20A—H20C110.1
C3—C4—C5119.5 (5)O3A—C20A—H20D110.1
C3—C4—H4120.3C21A—C20A—H20D110.1
C5—C4—H4120.3H20C—C20A—H20D108.4
C25—C24—C23118.9 (6)C17A—O3B—C20B104.2 (15)
C25—C24—H24120.6O3B—C20B—C21B102 (2)
C23—C24—H24120.6O3B—C20B—H20E111.3
C16A—C15A—C14A112.1 (5)C21B—C20B—H20E111.3
C16A—C15A—H15A109.2O3B—C20B—H20F111.3
C14A—C15A—H15A109.2C21B—C20B—H20F111.3
C16A—C15A—H15B109.2H20E—C20B—H20F109.2
C14A—C15A—H15B109.2C22A—C21B—C26A115.4 (16)
H15A—C15A—H15B107.9C22A—C21B—C20B97.6 (14)
C17A—C16A—C15A111.6 (5)C26A—C21B—C20B147 (2)
C9—N1—C12—C1151.7 (5)C12A—N1A—C9A—C10A7.3 (8)
C8—N1—C12—C136.5 (6)N2A—C10A—C9A—O1A170.6 (5)
C9—N1—C12—C1130.5 (7)N2A—C10A—C9A—N1A10.6 (8)
C8—N1—C12—C11157.7 (4)C9A—N1A—C12A—C11A28.3 (7)
C11—N2—C13—O2178.1 (5)C8A—N1A—C12A—C11A159.1 (5)
C10—N2—C13—O22.0 (8)C9A—N1A—C12A—C1A151.0 (5)
C11—N2—C13—C143.3 (8)C8A—N1A—C12A—C1A36.4 (6)
C10—N2—C13—C14179.4 (5)N2A—C11A—C12A—N1A52.6 (5)
C12—N1—C9—O1173.6 (5)N2A—C11A—C12A—C1A175.8 (4)
C8—N1—C9—O12.2 (9)C6A—C1A—C12A—N1A1.7 (7)
C12—N1—C9—C108.5 (8)C2A—C1A—C12A—N1A178.5 (4)
C8—N1—C9—C10179.9 (5)C6A—C1A—C12A—C11A124.2 (5)
C3—C2—C1—C62.1 (8)C2A—C1A—C12A—C11A56.0 (6)
C3—C2—C1—C12179.0 (5)O2A—C13A—C14A—C15A24.5 (8)
N1—C12—C1—C62.5 (7)N2A—C13A—C14A—C15A158.3 (5)
C11—C12—C1—C6122.8 (5)O2A—C13A—C14A—C19A97.9 (7)
N1—C12—C1—C2178.7 (4)N2A—C13A—C14A—C19A79.2 (7)
C11—C12—C1—C258.4 (6)C16A—C15A—C14A—C13A177.6 (5)
C13—N2—C11—C12123.1 (5)C16A—C15A—C14A—C19A55.0 (7)
C10—N2—C11—C1260.6 (6)C13A—C14A—C19A—C18A177.2 (5)
N1—C12—C11—N255.0 (5)C15A—C14A—C19A—C18A55.2 (7)
C1—C12—C11—N2177.3 (4)C2A—C1A—C6A—C5A1.2 (8)
C13—N2—C10—C9146.1 (5)C12A—C1A—C6A—C5A179.0 (5)
C11—N2—C10—C937.3 (7)C2A—C1A—C6A—C7A174.3 (5)
O1—C9—C10—N2171.7 (5)C12A—C1A—C6A—C7A5.5 (8)
N1—C9—C10—N210.4 (7)C6A—C1A—C2A—C3A0.3 (8)
O2—C13—C14—C1520.1 (7)C12A—C1A—C2A—C3A179.9 (5)
N2—C13—C14—C15161.4 (5)C1A—C6A—C5A—C4A1.1 (9)
O2—C13—C14—C19101.9 (6)C7A—C6A—C5A—C4A174.4 (5)
N2—C13—C14—C1976.7 (6)C6A—C5A—C4A—C3A0.2 (9)
C18—C19—C14—C13176.5 (4)C9A—N1A—C8A—C7A124.0 (5)
C18—C19—C14—C1560.6 (6)C12A—N1A—C8A—C7A63.2 (6)
C13—C14—C15—C16178.4 (4)C5A—C6A—C7A—C8A155.6 (5)
C19—C14—C15—C1658.6 (6)C1A—C6A—C7A—C8A19.8 (7)
C17—C16—C15—C1454.5 (6)N1A—C8A—C7A—C6A51.7 (6)
C20—O3—C17—C18158.3 (5)C14A—C19A—C18A—C17A57.1 (7)
C20—O3—C17—C1679.2 (6)C19A—C18A—C17A—O3B76.0 (9)
C15—C16—C17—O367.5 (6)C19A—C18A—C17A—O3A58.9 (7)
C15—C16—C17—C1851.9 (7)C19A—C18A—C17A—C16A56.7 (7)
C2—C1—C6—C53.4 (8)C15A—C16A—C17A—O3B51.0 (13)
C12—C1—C6—C5177.8 (5)C15A—C16A—C17A—O3A69.6 (6)
C2—C1—C6—C7174.3 (5)C15A—C16A—C17A—C18A54.8 (7)
C12—C1—C6—C74.5 (8)C1A—C2A—C3A—C4A0.6 (8)
C8—C7—C6—C5156.6 (5)C5A—C4A—C3A—C2A0.7 (8)
C8—C7—C6—C121.0 (7)C22A—C21A—C26A—C25A3.8 (19)
O3—C17—C18—C1968.3 (6)C20A—C21A—C26A—C25A175.5 (9)
C16—C17—C18—C1953.6 (6)C22A—C21A—C26A—C21B96 (15)
C14—C19—C18—C1758.2 (6)C20A—C21A—C26A—C21B85 (14)
C9—N1—C8—C7124.8 (5)C22A—C23A—C24A—C25A1.1 (11)
C12—N1—C8—C763.1 (6)C23A—C24A—C25A—C26A0.6 (10)
C6—C7—C8—N152.4 (6)C21A—C26A—C25A—C24A1.9 (13)
C1—C6—C5—C43.5 (8)C21B—C26A—C25A—C24A6 (3)
C7—C6—C5—C4174.2 (5)C24A—C23A—C22A—C21B7 (3)
C23—C22—C21—C262.3 (9)C24A—C23A—C22A—C21A0.6 (13)
C23—C22—C21—C20173.4 (6)C26A—C21A—C22A—C23A3.1 (19)
C1—C2—C3—C40.8 (8)C20A—C21A—C22A—C23A176.2 (10)
C21—C22—C23—C240.7 (10)C26A—C21A—C22A—C21B113 (17)
C17—O3—C20—C21173.5 (5)C20A—C21A—C22A—C21B68 (15)
C26—C21—C20—O39.0 (9)O3B—C17A—O3A—C20A37.7 (15)
C22—C21—C20—O3175.5 (5)C18A—C17A—O3A—C20A70.7 (8)
C22—C21—C26—C252.0 (9)C16A—C17A—O3A—C20A169.1 (6)
C20—C21—C26—C25173.4 (6)C17A—O3A—C20A—C21A172.9 (6)
C21—C26—C25—C240.0 (9)C26A—C21A—C20A—O3A88.9 (14)
C2—C3—C4—C50.8 (8)C22A—C21A—C20A—O3A91.8 (14)
C6—C5—C4—C32.2 (9)O3A—C17A—O3B—C20B50.1 (17)
C26—C25—C24—C231.6 (10)C18A—C17A—O3B—C20B159.1 (16)
C22—C23—C24—C251.3 (10)C16A—C17A—O3B—C20B85.4 (18)
C14A—C15A—C16A—C17A54.9 (7)C17A—O3B—C20B—C21B164 (3)
C10A—N2A—C13A—O2A3.7 (8)C23A—C22A—C21B—C26A12 (6)
C11A—N2A—C13A—O2A177.6 (5)C21A—C22A—C21B—C26A56 (12)
C10A—N2A—C13A—C14A179.0 (5)C23A—C22A—C21B—C20B166.3 (18)
C11A—N2A—C13A—C14A5.1 (8)C21A—C22A—C21B—C20B126 (19)
C13A—N2A—C10A—C9A147.8 (5)C21A—C26A—C21B—C22A73 (12)
C11A—N2A—C10A—C9A37.5 (7)C25A—C26A—C21B—C22A11 (6)
C13A—N2A—C11A—C12A126.6 (5)C21A—C26A—C21B—C20B110 (21)
C10A—N2A—C11A—C12A59.2 (6)C25A—C26A—C21B—C20B165 (7)
C8A—N1A—C9A—O1A1.6 (8)O3B—C20B—C21B—C22A179 (3)
C12A—N1A—C9A—O1A173.9 (5)O3B—C20B—C21B—C26A4 (10)
C8A—N1A—C9A—C10A179.6 (5)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C20—H20B···O2i0.992.453.332 (7)149
C20A—H20C···O2Aii0.992.603.567 (10)165
C20B—H20F···O2Aii0.992.263.19 (3)156
Symmetry codes: (i) x, y+1/2, z+1; (ii) x, y+1/2, z.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C20—H20B···O2i0.992.453.332 (7)148.5
C20A—H20C···O2Aii0.992.603.567 (10)164.5
C20B—H20F···O2Aii0.992.263.19 (3)156.3
Symmetry codes: (i) x, y+1/2, z+1; (ii) x, y+1/2, z.
Acknowledgements top

AC-C is grateful to CONACyT for a graduate student scholarship. The authors acknowledge M. Flores-Alamo for the data collection.

references
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