supplementary materials


cv5433 scheme

Acta Cryst. (2013). E69, o1804-o1805    [ doi:10.1107/S1600536813031395 ]

Ethyl 3-(10-bromo­anthracen-9-yl)-5-methyl-1,2-oxazole-4-carboxyl­ate

C. Li, M. J. Campbell, M. J. Weaver, N. S. Duncan, J. L. Hunting and N. R. Natale

Abstract top

In the title compound, C21H16BrNO3, the mean planes of the anthracene tricycle and isoxazole ring are inclined to each other at a dihedral angle of 72.12 (7)°. The carb­oxy group is slightly out of the isoxazole mean plane, with a maximum deviation of 0.070 (5) Å for the carbonyl O atom. In the crystal, pairs of weak C-H...O hydrogen bonds link the mol­ecules into dimers, and weak C-H...N inter­actions further link these dimers into corrugated layers parallel to the bc plane.

Introduction top

The aryl isoxazole amides (AIMs) (Han et al., 2009; Gajewski et al., 2009) have significant activity in the National Cancer Institutes 60 cell line screen (Kohn et al., 2012; Shoemaker et al., 2006) comparable to several agents in general medical practice, such as fluoro­uridine and bleomycin. Our working hypothesis for developing the structure activity relationship (SAR) of AIMs to improve their anti-tumor efficacy is focused on the quadruplex DNA conformations (Balasubramanian et al., 2011; Neidle, 2012). To more accurately inform our G-4 - small molecule docking studies, we rely on crystallographic determinations of AIMs.

Experimental top

Synthesis and crystallization top

To a suspension of anthracene-9-carbaldehyde (10.0 g, 48.49 mmol; Sigma-Aldrich, 97%) in THF:Ethanol:H2O (135 mL:67.5 mL:67.5 mL) was dissolved sodium acetate (3.5 eq., 13.92 g, 169.7 mmol) and hydroxyl­amine hydro­chloride (2 eq, 6.7387 g, 96.974 mmol). The reaction was covered and let stir at room temperature until TLC showed no starting material remained (ca. 96 hours). The solution was then transferred to a separatory funnel and washed 4 x 350 mL Brine and the combined aqueous layers washed 2x100 mL CHCl3, dried over sodium sulfate, filtered, and the solvent removed under vacuum to yield anthracene-9-carbaldehyde oxime (99%). 1H NMR(CDCl3) δ 9.22 (s, 1H), 8.51 (s, 1H), 8.42 (d, J=8.66 Hz, 2H), 8.03 (d, J=8.16 Hz, 2H), 7.55 (m, 4H).

The anthracene-9-carbaldehyde oxime (10.516 g, 47.53 mmol) was taken up in 200 mL of chloro­form at room temperature, to which solution was added pyridine (10 mol%, 0.38 mL) and recrystallized NCS (1.1 eq., 7.197 g, 52.28 mmol). The solution brought to 40°C for three hours then cooled to room temperature. The organic layer was washed with 4x450 mL Brine and 4x300 mL H2O, then the aqueous layer washed with 2x300 mL CHCl3, dried with sodium sulfate, filtered, and the solvent removed under reduced pressure to yield the nitrile oxide. The inter­mediate was purified only through extractive isolation using brine and CHCl3 and taken on to the next reaction as is. To a solution of the nitrile oxide in absolute ethanol (230 mL) was added 1.4 equivalents of ethyl­aceto­acetate. In a separate flask was added 115 mL absolute ethanol and 2.341 g Na(s). Once the sodium dissociation had completed, the warm solution was added to the nitrile oxide and the mixture was allowed to stir at room temperature under argon for 20 hours until TLC in 4:1 Hex/EtOAc revealed all nitrile oxide had been consumed. Finally, the ethanol was removed via rotary evaporation and the solid chromatographed using 4:1 Hex/EtOAc (Rf=0.56). Ethyl 3-(anthracen-9-yl)-5-methyl­isoxazole-4-carboxyl­ate. Yield 97%. 1H NMR(400 MHz, CDCl3) δ 8.59 (s, 1H), 8.06 (d, J=7.91 Hz, 2H), 7.66 (d, J=8.16 Hz, 2H), 7.41-7.50 (m, 4H), 3.70 (q, J=7.15, 14.31 Hz, 2H), 2.93 (s, 3H), 0.33 (t, J=7.15 Hz, 3H). Spectral data are in accord with those reported previously (Mirzaei et al., 2012).

Ethyl 3-(anthracen-9-yl)-5-methyl­isoxazole-4-carboxyl­ate (4.88 g, 14.73 mmol) was taken up in 80 mL DMF to which was added a solution of recrystallized N-Bromo­succinamide (NBS) (1.1 eq, 2.884 g, 16.203 mmol) dissolved in 80 mL DMF. The solution was brought to 40°C and let stir for 5 hours where upon the solution was poured into 1200mL ice/water which was allowed to stir for 2 hours, in which the product precipitated out. Product was filtered, dissolved in CH2Cl2, dried over anhydrous sodium sulfate, filtered and concentrated under vacuum. Yield 88%, 1H NMR(CDCl3) δ 8.62 (d, J=8.91 Hz, 2H), 7.60-7.67 (m, 4H), 7.61 (m, 2H), 3.72 (q, J=7.03, 14.18 Hz, 2H), 2.94 (s, 3H), 0.39 (t, J=7.15, 14.31 Hz, 3H); 13C NMR(CDCl3) δ 176.28, 161.23, 160.21, 131.31, 130.01, 128.03, 127.04, 126.50, 125.87, 125.18, 123.62, 111.40, 60.14, 13.41, 12.89. Spectral data are in accord with those reported previously (Han et al., 2003), the crystals were obtained by slow evapotation from a methyl­ene chloride and heptane solution.

Refinement top

All H atoms were placed at geometrically calculated positions and included in the refinement in the riding model approximation, with C—H lengths of 0.95 (aromatic CH), 0.98 (CH3) and 0.99 (CH2) Å. Idealized methyl groups were refined as rotating groups. Uiso of the H atoms was set at 1.5Ueq of the parent C atom for the methyl group and at 1.2Ueq for the remaining H atoms.

Results and discussion top

The aryl isoxazole amides (AIMs) (Han et al., 2009; Gajewski et al., 2009) have significant activity in the National Cancer Institutes 60 cell line screen, (Kohn et al., 2012; Shoemaker, 2006) comparable to several agents in general medical practice, such as fluoro­uridine and bleomycin. Our working hypothesis for developing the structure activity relationship (SAR) of AIMs to improve their anti-tumor efficacy is focused on the quadruplex DNA conformations (Balasubramanian et al., 2011; Neidle et al., 2012). To more accurately inform our G-4 - small molecule docking studies, we rely on crystallographic determinations of AIMs. In previous studies we have determined that the dihedral angle between the isoxazole and the C-3 aryl is approximately orthogonal (Mosher et al., 1996; Li et al., 2008), and we have postulated that this is a critical feature in the biological activity of the AIMs. The anthracenyl group is almost perpendicular to the isoxazole plane in ethyl 3-(10'-chloro­anthracenyl)-5-(1''-phenyl-2''-hydroxyl­ethyl­enyl)isoxazole-4-carboxyl­ate [85.51 (4)°] (Li et al., 2006), which is similar to analogous anthracenyl isoxazole structures in the Cambridge Structural Database, i.e. ethyl 3-(10'-chloro-9'-anthracenyl)-5-methyl-4-isoxazolcarboxyl­ate [74.3°] (Han et al., 2003; CSD refcode EZENEC), ethyl 3-(10'-chloro-9'-anthracenyl)-5-(2-phenyl­ethyl)-4-isoxazole­carboxyl­ate [78.5°] (Han et al., 2002; CSD refcode MUQMOA). This AIM analog represents a key inter­mediate in future synthesis and SAR studies, and our progress will be reported in due course.

Related literature top

For the synthesis of anthryl isoxazoles, see: Mosher & Natale (1995); Zhou et al. (1997); Han & Natale (2001); Rider et al. (2010); Mirzaei et al. (2012). For related structures, see: Mosher et al. (1996); Han et al. (2002, 2003); Li et al. (2006, 2008). For the antitumor activity of aryl isoxazole amides (AIMs), see: Han et al. (2009); Gajewski et al. (2009); Balasubramanian et al. (2011); Neidle (2012); Kohn et al. (2012); Shoemaker (2006).

Computing details top

Data collection: APEX2 (Bruker, 2008); cell refinement: SAINT (Bruker, 2008); data reduction: SAINT (Bruker, 2008); program(s) used to solve structure: SHELXL97 (Sheldrick, 2008); program(s) used to refine structure: SHELXS97 (Sheldrick, 2008); molecular graphics: OLEX2 (Dolomanov et al., 2009); software used to prepare material for publication: OLEX2 (Dolomanov et al., 2009) and publCIF (Westrip, 2010).

Figures top
[Figure 1] Fig. 1. The molecular structure of titled compound, with atom labels and 50% probability displacement ellipsoids for non-H atoms.
[Figure 2] Fig. 2. A portion of the packing diagram viewed in [100]. Weak intermolecular C—H···O and C—H···N hydrogen bond interactions are shown as dashed lines.
Ethyl 3-(10-bromoanthracen-9-yl)-5-methyl-1,2-oxazole-4-carboxylate top
Crystal data top
C21H16BrNO3F(000) = 832
Mr = 410.26Dx = 1.575 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
a = 8.8437 (1) ÅCell parameters from 330 reflections
b = 16.7099 (2) Åθ = 0.3–27.5°
c = 11.7157 (2) ŵ = 2.40 mm1
β = 92.419 (1)°T = 100 K
V = 1729.77 (4) Å3Prism, translucent yellow
Z = 40.49 × 0.47 × 0.38 mm
Data collection top
Bruker SMART BREEZE CCD
diffractometer
4128 reflections with I > 2σ(I)
Radiation source: 2 kW sealed X-ray tubeRint = 0.020
π and ω scansθmax = 28.3°, θmin = 2.1°
Absorption correction: multi-scan
(SADABS; Bruker, 2008)
h = 1111
Tmin = 0.39, Tmax = 0.47k = 2222
34958 measured reflectionsl = 1514
4290 independent reflections
Refinement top
Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.025H-atom parameters constrained
wR(F2) = 0.074 w = 1/[σ2(Fo2) + (0.0448P)2 + 1.2294P]
where P = (Fo2 + 2Fc2)/3
S = 1.05(Δ/σ)max = 0.002
4290 reflectionsΔρmax = 0.51 e Å3
237 parametersΔρmin = 0.39 e Å3
0 restraints
Crystal data top
C21H16BrNO3V = 1729.77 (4) Å3
Mr = 410.26Z = 4
Monoclinic, P21/cMo Kα radiation
a = 8.8437 (1) ŵ = 2.40 mm1
b = 16.7099 (2) ÅT = 100 K
c = 11.7157 (2) Å0.49 × 0.47 × 0.38 mm
β = 92.419 (1)°
Data collection top
Bruker SMART BREEZE CCD
diffractometer
4290 independent reflections
Absorption correction: multi-scan
(SADABS; Bruker, 2008)
4128 reflections with I > 2σ(I)
Tmin = 0.39, Tmax = 0.47Rint = 0.020
34958 measured reflectionsθmax = 28.3°
Refinement top
R[F2 > 2σ(F2)] = 0.025H-atom parameters constrained
wR(F2) = 0.074Δρmax = 0.51 e Å3
S = 1.05Δρmin = 0.39 e Å3
4290 reflectionsAbsolute structure: ?
237 parametersAbsolute structure parameter: ?
0 restraintsRogers parameter: ?
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*/Ueq
Br10.65922 (2)0.19002 (2)0.12783 (2)0.02178 (7)
O10.29601 (12)0.46676 (6)0.02087 (8)0.0145 (2)
O20.14962 (15)0.57548 (8)0.00887 (10)0.0261 (3)
O30.06569 (12)0.53843 (6)0.34089 (9)0.0145 (2)
N10.15853 (14)0.46963 (7)0.35626 (10)0.0142 (2)
C10.31314 (18)0.19895 (9)0.06508 (13)0.0166 (3)
H10.38000.15800.04240.020*
C20.16567 (19)0.19731 (9)0.02681 (13)0.0187 (3)
H20.13100.15540.02240.022*
C30.06357 (17)0.25744 (9)0.05964 (12)0.0167 (3)
H30.03900.25550.03230.020*
C40.11134 (17)0.31807 (8)0.13019 (12)0.0135 (3)
H40.04120.35770.15200.016*
C50.52484 (16)0.45590 (8)0.35132 (12)0.0141 (3)
H50.45710.49690.37250.017*
C60.67305 (17)0.45991 (9)0.38810 (12)0.0171 (3)
H60.70750.50340.43450.020*
C70.77617 (17)0.39918 (10)0.35718 (13)0.0191 (3)
H70.87910.40220.38340.023*
C80.72856 (16)0.33668 (9)0.29027 (13)0.0175 (3)
H80.79930.29690.27010.021*
C90.52055 (16)0.26791 (8)0.17830 (12)0.0133 (2)
C100.31823 (15)0.38718 (8)0.23963 (11)0.0111 (2)
C110.46912 (15)0.39100 (8)0.28134 (11)0.0116 (2)
C120.57441 (16)0.32977 (8)0.24980 (12)0.0132 (3)
C130.36915 (16)0.26146 (8)0.13894 (11)0.0126 (2)
C140.26560 (16)0.32284 (8)0.17184 (11)0.0114 (2)
C150.21490 (15)0.45584 (8)0.25655 (11)0.0111 (2)
C160.16273 (15)0.51365 (8)0.17353 (11)0.0118 (2)
C170.06993 (15)0.56274 (8)0.23177 (12)0.0128 (2)
C180.02091 (17)0.63431 (9)0.19866 (13)0.0184 (3)
H18A0.10800.63840.24740.028*
H18B0.05670.62950.11860.028*
H18C0.04190.68240.20810.028*
C190.19946 (16)0.52302 (8)0.05278 (12)0.0139 (3)
C200.34574 (17)0.47134 (9)0.09567 (12)0.0162 (3)
H20A0.41470.51740.10440.019*
H20B0.25780.47780.15000.019*
C210.42720 (19)0.39376 (10)0.11786 (13)0.0211 (3)
H21A0.46470.39440.19540.032*
H21B0.35710.34880.11020.032*
H21C0.51260.38780.06240.032*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
Br10.01713 (9)0.01729 (9)0.03139 (10)0.00372 (5)0.00673 (6)0.00296 (5)
O10.0174 (5)0.0153 (5)0.0111 (4)0.0030 (4)0.0040 (4)0.0021 (4)
O20.0333 (7)0.0279 (6)0.0175 (5)0.0158 (5)0.0050 (5)0.0084 (4)
O30.0153 (5)0.0136 (5)0.0146 (5)0.0031 (4)0.0024 (4)0.0010 (4)
N10.0152 (6)0.0125 (5)0.0150 (5)0.0029 (4)0.0015 (4)0.0002 (4)
C10.0210 (7)0.0129 (6)0.0162 (6)0.0005 (5)0.0036 (5)0.0019 (5)
C20.0237 (8)0.0157 (7)0.0167 (7)0.0045 (5)0.0010 (6)0.0026 (5)
C30.0169 (7)0.0167 (6)0.0162 (6)0.0039 (5)0.0020 (5)0.0016 (5)
C40.0143 (7)0.0125 (6)0.0135 (6)0.0005 (5)0.0004 (5)0.0020 (5)
C50.0157 (6)0.0142 (6)0.0124 (6)0.0002 (5)0.0003 (5)0.0002 (5)
C60.0177 (7)0.0183 (7)0.0150 (6)0.0038 (5)0.0016 (5)0.0002 (5)
C70.0128 (6)0.0222 (7)0.0219 (7)0.0011 (5)0.0023 (5)0.0041 (6)
C80.0121 (6)0.0175 (7)0.0227 (7)0.0020 (5)0.0006 (5)0.0028 (5)
C90.0131 (6)0.0108 (6)0.0162 (6)0.0029 (5)0.0042 (5)0.0010 (5)
C100.0123 (6)0.0110 (6)0.0101 (5)0.0013 (5)0.0013 (4)0.0018 (4)
C110.0126 (6)0.0115 (6)0.0106 (6)0.0000 (5)0.0012 (4)0.0019 (4)
C120.0124 (6)0.0128 (6)0.0143 (6)0.0008 (5)0.0015 (5)0.0033 (5)
C130.0147 (6)0.0107 (6)0.0126 (6)0.0001 (5)0.0024 (5)0.0014 (5)
C140.0125 (6)0.0111 (5)0.0107 (6)0.0004 (5)0.0013 (5)0.0021 (5)
C150.0108 (6)0.0104 (6)0.0122 (6)0.0010 (5)0.0003 (4)0.0007 (4)
C160.0114 (6)0.0111 (6)0.0129 (6)0.0004 (5)0.0005 (4)0.0004 (5)
C170.0121 (6)0.0120 (6)0.0144 (6)0.0012 (5)0.0008 (5)0.0009 (5)
C180.0179 (7)0.0135 (6)0.0235 (7)0.0043 (5)0.0016 (5)0.0019 (5)
C190.0132 (6)0.0145 (6)0.0139 (6)0.0001 (5)0.0006 (5)0.0001 (5)
C200.0207 (7)0.0175 (7)0.0106 (6)0.0008 (5)0.0049 (5)0.0010 (5)
C210.0246 (8)0.0213 (7)0.0180 (7)0.0028 (6)0.0063 (6)0.0027 (6)
Geometric parameters (Å, º) top
Br1—C91.8996 (13)C8—H80.9500
O1—C191.3340 (17)C8—C121.4290 (19)
O1—C201.4539 (16)C9—C121.4013 (19)
O2—C191.2073 (18)C9—C131.4017 (19)
O3—N11.4197 (15)C10—C111.4031 (18)
O3—C171.3435 (17)C10—C141.4043 (19)
N1—C151.3097 (18)C10—C151.4853 (18)
C1—H10.9500C11—C121.4420 (19)
C1—C21.361 (2)C13—C141.4384 (19)
C1—C131.4314 (19)C15—C161.4332 (18)
C2—H20.9500C16—C171.3636 (19)
C2—C31.415 (2)C16—C191.4731 (18)
C3—H30.9500C17—C181.4832 (19)
C3—C41.363 (2)C18—H18A0.9800
C4—H40.9500C18—H18B0.9800
C4—C141.4316 (19)C18—H18C0.9800
C5—H50.9500C20—H20A0.9900
C5—C61.364 (2)C20—H20B0.9900
C5—C111.4342 (19)C20—C211.511 (2)
C6—H60.9500C21—H21A0.9800
C6—C71.422 (2)C21—H21B0.9800
C7—H70.9500C21—H21C0.9800
C7—C81.362 (2)
C19—O1—C20116.66 (11)C9—C12—C11118.01 (12)
C17—O3—N1109.05 (10)C1—C13—C14118.32 (13)
C15—N1—O3105.62 (11)C9—C13—C1123.80 (13)
C2—C1—H1119.5C9—C13—C14117.85 (12)
C2—C1—C13121.07 (14)C4—C14—C13118.50 (12)
C13—C1—H1119.5C10—C14—C4121.59 (13)
C1—C2—H2119.7C10—C14—C13119.86 (13)
C1—C2—C3120.64 (13)N1—C15—C10120.96 (12)
C3—C2—H2119.7N1—C15—C16111.28 (12)
C2—C3—H3119.8C16—C15—C10127.76 (12)
C4—C3—C2120.50 (14)C15—C16—C19130.21 (12)
C4—C3—H3119.8C17—C16—C15104.43 (12)
C3—C4—H4119.5C17—C16—C19125.33 (12)
C3—C4—C14120.97 (13)O3—C17—C16109.62 (12)
C14—C4—H4119.5O3—C17—C18117.14 (12)
C6—C5—H5119.3C16—C17—C18133.24 (13)
C6—C5—C11121.34 (13)C17—C18—H18A109.5
C11—C5—H5119.3C17—C18—H18B109.5
C5—C6—H6119.9C17—C18—H18C109.5
C5—C6—C7120.18 (14)H18A—C18—H18B109.5
C7—C6—H6119.9H18A—C18—H18C109.5
C6—C7—H7119.7H18B—C18—H18C109.5
C8—C7—C6120.54 (13)O1—C19—C16111.34 (12)
C8—C7—H7119.7O2—C19—O1124.46 (13)
C7—C8—H8119.3O2—C19—C16124.19 (13)
C7—C8—C12121.36 (14)O1—C20—H20A110.5
C12—C8—H8119.3O1—C20—H20B110.5
C12—C9—Br1118.94 (10)O1—C20—C21106.36 (11)
C12—C9—C13123.32 (12)H20A—C20—H20B108.6
C13—C9—Br1117.72 (10)C21—C20—H20A110.5
C11—C10—C14121.29 (12)C21—C20—H20B110.5
C11—C10—C15120.00 (12)C20—C21—H21A109.5
C14—C10—C15118.41 (12)C20—C21—H21B109.5
C5—C11—C12118.23 (12)C20—C21—H21C109.5
C10—C11—C5122.15 (12)H21A—C21—H21B109.5
C10—C11—C12119.57 (12)H21A—C21—H21C109.5
C8—C12—C11118.36 (13)H21B—C21—H21C109.5
C9—C12—C8123.60 (13)
Br1—C9—C12—C81.87 (19)C10—C15—C16—C192.4 (2)
Br1—C9—C12—C11176.22 (10)C11—C5—C6—C70.1 (2)
Br1—C9—C13—C11.24 (19)C11—C10—C14—C4179.20 (12)
Br1—C9—C13—C14176.59 (9)C11—C10—C14—C133.33 (19)
O3—N1—C15—C10179.64 (11)C11—C10—C15—N175.68 (17)
O3—N1—C15—C160.03 (15)C11—C10—C15—C16104.71 (16)
N1—O3—C17—C160.55 (15)C12—C9—C13—C1179.42 (13)
N1—O3—C17—C18179.89 (11)C12—C9—C13—C141.6 (2)
N1—C15—C16—C170.35 (16)C13—C1—C2—C30.3 (2)
N1—C15—C16—C19178.00 (13)C13—C9—C12—C8179.97 (13)
C1—C2—C3—C40.0 (2)C13—C9—C12—C111.9 (2)
C1—C13—C14—C40.65 (19)C14—C10—C11—C5179.58 (12)
C1—C13—C14—C10176.89 (12)C14—C10—C11—C122.97 (19)
C2—C1—C13—C9177.91 (14)C14—C10—C15—N1110.56 (15)
C2—C1—C13—C140.1 (2)C14—C10—C15—C1669.05 (18)
C2—C3—C4—C140.6 (2)C15—C10—C11—C56.85 (19)
C3—C4—C14—C10176.60 (13)C15—C10—C11—C12170.60 (12)
C3—C4—C14—C130.9 (2)C15—C10—C14—C47.13 (19)
C5—C6—C7—C80.3 (2)C15—C10—C14—C13170.34 (12)
C5—C11—C12—C80.29 (19)C15—C16—C17—O30.54 (15)
C5—C11—C12—C9177.91 (12)C15—C16—C17—C18179.99 (15)
C6—C5—C11—C10177.89 (13)C15—C16—C19—O10.5 (2)
C6—C5—C11—C120.4 (2)C15—C16—C19—O2178.75 (15)
C6—C7—C8—C120.4 (2)C17—O3—N1—C150.32 (14)
C7—C8—C12—C9178.20 (14)C17—C16—C19—O1178.55 (13)
C7—C8—C12—C110.1 (2)C17—C16—C19—O20.7 (2)
C9—C13—C14—C4178.60 (12)C19—O1—C20—C21169.06 (12)
C9—C13—C14—C101.06 (19)C19—C16—C17—O3177.91 (12)
C10—C11—C12—C8177.84 (12)C19—C16—C17—C181.6 (2)
C10—C11—C12—C90.36 (19)C20—O1—C19—O21.5 (2)
C10—C15—C16—C17179.29 (13)C20—O1—C19—C16177.73 (11)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C2—H2···N1i0.952.543.4305 (19)155
C4—H4···O2ii0.952.583.1990 (18)123
Symmetry codes: (i) x, y+1/2, z1/2; (ii) x, y+1, z.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
C2—H2···N1i0.952.543.4305 (19)155
C4—H4···O2ii0.952.583.1990 (18)123
Symmetry codes: (i) x, y+1/2, z1/2; (ii) x, y+1, z.
Acknowledgements top

The Bruker single-crystal X-ray diffraction facility was established at Ithaca College in 2012. NRN, MJC, MJW and ND thank the National Institutes of Health for grants NINDS P20RR015583 Center for Structural and Functional Neuroscience (CSFN) and P20 RR017670 Center for Environmental Health Sciences (CEHS), and the University of Montana Grant Program.

references
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