organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 70| Part 3| March 2014| Pages o297-o298

4-Hy­dr­oxy-5-meth­­oxy-N,1-di­methyl-2-oxo-N-[4-(tri­fluoro­meth­yl)phen­yl]-1,2-di­hydro­quinoline-3-carboxamide

aThe Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University, 1650 Orleans Street, Baltimore, MD 21287, USA, bDepartment of Chemistry, Howard University, 525 College Street NW, Washington DC 20059, USA, and cDepartment of Physics, Faculty of Sciences, Erciyes University, 38039 Kayseri, Turkey
*Correspondence e-mail: rbutcher99@yahoo.com

(Received 25 January 2014; accepted 10 February 2014; online 15 February 2014)

The title compound, C20H17F3N2O4, named tasquinimod, is a second-generation oral quinoline-3-carboxamide analogue, which is currently in phase III clinical trials for the treatment of metastatic prostate cancer. The quinoline unit is almost planar (r.m.s. deviation of fitted atoms = 0.0075 Å). The carboxamide side chain, substituted at position 3, is tilted by 88.07 (7)° to the quinoline plane. Both the methyl and carbonyl groups of this carboxamide side chain are in a syn conformation. The 4-(tri­fluoro­meth­yl)phenyl plane is inclined at 50.62 (17)° to the plane of the carboxamide side chain, and at 87.14 (4)° to the plane of the quinoline ring system. The 4-hy­droxy H atom acts as a double proton donor in an intra­molecular hydrogen bond to the 5-position meth­oxy O atom and in an inter­molecular contact to the 2-oxo group, generating a chain along [010] in the crystal structure.

Related literature

For background to the activity of the second generation quinolone-3-carboxamide analogues roquinimex (also known as linomide, systematic name: 4-hy­droxy-N,1-dimethyl-2-oxo-N-phenyl-1,2-di­hydro­quinoline-3-carboxamide) and tasquin­imod (systematic name: 4-hy­droxy-5-meth­oxy-N,1-dimethyl-2-oxo-N-[(4-tri­fluoro­meth­yl)phen­yl]-1,2-di­hydro­quinoline-3-carboxamide), see: Isaacs (2010[Isaacs, J. T. (2010). Expert Opin. Investig. Drugs, 19, 1235-1243.]). For similar structures, see: Dasari & Srikrishnan (2002[Dasari, K. B. & Srikrishnan, T. (2002). J. Chem. Crystallogr. 32, 499-504.]); Jönsson et al. (2004[Jönsson, S., Andersson, G., Fex, T., Fristedt, T., Hedlund, G., Jansson, K., Abramo, L., Fritzson, I., Pekarski, O., Runström, A., Sandin, H., Thuvesson, I. & Björk, A. (2004). J. Med. Chem. 47, 2075-2088.]); Jansson et al. (2006[Jansson, K., Fristedt, T., Olsson, A., Svensson, B. & Jönsson, S. (2006). J. Org. Chem. 71, 1658-1667.]).

[Scheme 1]

Experimental

Crystal data
  • C20H17F3N2O4

  • Mr = 406.36

  • Monoclinic, P 21 /c

  • a = 10.8643 (9) Å

  • b = 10.6705 (9) Å

  • c = 15.8062 (13) Å

  • β = 105.696 (9)°

  • V = 1764.1 (3) Å3

  • Z = 4

  • Cu Kα radiation

  • μ = 1.10 mm−1

  • T = 298 K

  • 0.35 × 0.24 × 0.12 mm

Data collection
  • Agilent Xcalibur (Ruby, Gemini) diffractometer

  • Absorption correction: multi-scan (CrysAlis PRO; Agilent, 2012[Agilent (2012). CrysAlis PRO. Agilent Technologies, Yarnton, England.]) Tmin = 0.741, Tmax = 1.000

  • 6559 measured reflections

  • 3539 independent reflections

  • 3010 reflections with I > 2σ(I)

  • Rint = 0.019

Refinement
  • R[F2 > 2σ(F2)] = 0.044

  • wR(F2) = 0.132

  • S = 1.06

  • 3539 reflections

  • 269 parameters

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

  • Δρmax = 0.35 e Å−3

  • Δρmin = −0.27 e Å−3

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A D—H H⋯A DA D—H⋯A
O2—H2O⋯O4 0.89 (3) 1.82 (3) 2.5538 (16) 138 (2)
O2—H2O⋯O3i 0.89 (3) 2.28 (3) 2.8591 (17) 123 (2)
Symmetry code: (i) [-x+1, y+{\script{1\over 2}}, -z+{\script{1\over 2}}].

Data collection: CrysAlis PRO (Agilent, 2012[Agilent (2012). CrysAlis PRO. Agilent Technologies, Yarnton, England.]); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; 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: SHELXTL (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); software used to prepare material for publication: SHELXTL.

Supporting information


Comment top

Roquinimex (also known as linomide: 4-hydroxy-N, 1-dimethyl-2-oxo-N phenyl-1,2-dihydroquinoline-3-carboxamide) is an orally active molecule that is therapeutic against solid malignancies via tumor selective anti-angiogenic abilities (Isaacs, 2010). In clinical trials, however, it had dose-limiting unacceptable side effects. From a library of second generation quinolone-3-carboxamide analogues, an analogue termed tasquinimod (i.e., 4-hydroxy-5-methoxy-N,1-dimethyl-2-oxo-N-[(4-trifluoromethyl) phenyl]-1,2-dihydroquinoline-3-carboxamide) was identified being more than 30 times more potent than an anti-angiogenic agent without the toxic effects of roquinimex (Isaacs, 2010). Presently, tasquinimod is undergoing phase III clinical trials as monotherapy for castration resistant metastatic prostate cancer. Ultimately, tasquinimod will be optimally used in combination with other therapeutic agents. To identify the optimal combinational regime, the identification of the molecular target(s) involved in its mechanism of action is critical. Similar structures have been previously reported (Dasari et al., 2002; Jönsson et al., 2004; Jansson et al., 2006).

As a lead for defining pharmacophoric features of tasquinimod, its three-dimensional structure was determined by X-ray structure analysis. The molecular structure shows that quinoline ring is almost planar (rms deviation of fitted atoms = 0.0075 Å). The carboxamide side chain at position 3, is tilted by 88.07 (7)° to the quinoline plane. Both, the methyl and carbonyl groups of this carboxamide side chain are in a syn conformation. The N-[4-trifluoromethyl)phenyl] plane is inclined at 50.62 (17)° to the plane of the carboxamide side chain, and 87.14 (4)° to the plane of the quinoline ring. The 4-hydroxy proton forms intramolecular hydrogen bond with the 5-position methoxy oxygen being planar to the quinoline ring (Fig. 1, Table 1). In the crystal packing molecules are linked by an intermolecular hydrogen bond between 4-hydroxy and 2-oxo groups generating a chain in the direction [010] (Fig. 2, Table 1).

Related literature top

For background to the activity of the second generation quinolone-3-carboxamide analogues roquinimex (also known as linomide, systematic name: 4-hydroxy-N,1-dimethyl-2-oxo-N-phenyl-1,2-dihydroquinoline-3-carboxamide) and tasquinimod (systematic name: 4-hydroxy-5-methoxy-N,1-dimethyl-2-oxo-N-[(4-trifluoromethyl)phenyl]-1,2-dihydroquinoline-3-carboxamide), see: Isaacs (2010). For similar structures, see: Dasari & Srikrishnan (2002); Jönsson et al. (2004); Jansson et al. (2006).

Experimental top

The preparation of the titled compound was reported by Jönsson et al. (2004).

To obtain crystal of this compound, a saturated solution of a pure sample of the title compound was made in 5 mL of acetonitrile (HPLC grade) at room temperature. The solution was filtered, and 2.5 mL of this saturated solution was transferred into a transparent 2 dram glass vial. Crystallization of this sample was by vapor diffusion in diethyl ether at room temperature over a period of 48 h. Crystal growth was observed within 24 h, but the experiment was left to stand for 48 h. A gentle vacuum filtration of the sample followed by air drying afforded white crystals of the compound for X-ray diffraction studies.

Refinement top

H atoms were positioned geometrically and refined using the riding model, with C–H distance of 0.93–0.96 Å, with Uiso (H) = 1.20 Ueq (C) or 1.50 Ueq (C) for methyl H atoms. Hydrogen atoms involved in hydrogen bonding were refined isotropically.

Computing details top

Data collection: CrysAlis PRO (Agilent, 2012); cell refinement: CrysAlis PRO (Agilent, 2012); data reduction: CrysAlis PRO (Agilent, 2012); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: SHELXTL (Sheldrick, 2008); software used to prepare material for publication: SHELXTL (Sheldrick, 2008).

Figures top
[Figure 1] Fig. 1. ORTEP diagram of the title compound showing the atom numbering and the atomic displacement parameters drawn at the 30% probability level. Intramolecular hydrogen bonding is shown by dashed lines.
[Figure 2] Fig. 2. Crystal packing of the title compound viewed along the a axis. Hydrogen bonding is shown by dashed lines.
4-Hydroxy-5-methoxy-N,1-dimethyl-2-oxo-N-[4-(trifluoromethyl)phenyl]-1,2-dihydroquinoline-3-carboxamide top
Crystal data top
C20H17F3N2O4F(000) = 840
Mr = 406.36Dx = 1.530 Mg m3
Monoclinic, P21/cCu Kα radiation, λ = 1.54184 Å
a = 10.8643 (9) ÅCell parameters from 2882 reflections
b = 10.6705 (9) Åθ = 2.9–75.7°
c = 15.8062 (13) ŵ = 1.10 mm1
β = 105.696 (9)°T = 298 K
V = 1764.1 (3) Å3Prism, colourless
Z = 40.35 × 0.24 × 0.12 mm
Data collection top
Agilent Xcalibur (Ruby, Gemini)
diffractometer
3539 independent reflections
Radiation source: Enhance (Cu) X-ray Source3010 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.019
Detector resolution: 10.5081 pixels mm-1θmax = 75.9°, θmin = 4.2°
ω scansh = 813
Absorption correction: multi-scan
(CrysAlis PRO; Agilent, 2012)
k = 1213
Tmin = 0.741, Tmax = 1.000l = 1919
6559 measured 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)] = 0.044Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.132H atoms treated by a mixture of independent and constrained refinement
S = 1.06 w = 1/[σ2(Fo2) + (0.079P)2 + 0.3326P]
where P = (Fo2 + 2Fc2)/3
3539 reflections(Δ/σ)max < 0.001
269 parametersΔρmax = 0.35 e Å3
0 restraintsΔρmin = 0.27 e Å3
Crystal data top
C20H17F3N2O4V = 1764.1 (3) Å3
Mr = 406.36Z = 4
Monoclinic, P21/cCu Kα radiation
a = 10.8643 (9) ŵ = 1.10 mm1
b = 10.6705 (9) ÅT = 298 K
c = 15.8062 (13) Å0.35 × 0.24 × 0.12 mm
β = 105.696 (9)°
Data collection top
Agilent Xcalibur (Ruby, Gemini)
diffractometer
3539 independent reflections
Absorption correction: multi-scan
(CrysAlis PRO; Agilent, 2012)
3010 reflections with I > 2σ(I)
Tmin = 0.741, Tmax = 1.000Rint = 0.019
6559 measured reflections
Refinement top
R[F2 > 2σ(F2)] = 0.0440 restraints
wR(F2) = 0.132H atoms treated by a mixture of independent and constrained refinement
S = 1.06Δρmax = 0.35 e Å3
3539 reflectionsΔρmin = 0.27 e Å3
269 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*/Ueq
F10.01967 (12)0.99424 (13)0.21797 (7)0.0584 (4)
F20.02599 (11)0.89869 (12)0.34160 (8)0.0513 (3)
F30.15877 (10)1.02840 (11)0.31447 (8)0.0480 (3)
O10.42263 (14)0.38668 (14)0.11242 (8)0.0479 (3)
O20.59427 (11)0.58973 (11)0.24904 (7)0.0341 (3)
H2O0.665 (2)0.627 (3)0.2800 (17)0.056 (7)*
O30.26656 (11)0.31456 (11)0.25976 (7)0.0374 (3)
O40.77617 (11)0.61692 (12)0.38907 (7)0.0404 (3)
N10.29733 (14)0.55256 (14)0.11795 (8)0.0358 (3)
N20.43399 (12)0.33345 (13)0.38337 (8)0.0305 (3)
C10.24402 (16)0.64495 (15)0.16254 (10)0.0339 (3)
C20.11175 (16)0.66235 (17)0.13832 (11)0.0405 (4)
H2A0.05980.61000.09660.049*
C30.05753 (16)0.75701 (17)0.17604 (11)0.0404 (4)
H3A0.03060.76820.15970.049*
C40.13541 (15)0.83560 (15)0.23863 (10)0.0338 (3)
C50.26668 (15)0.81696 (15)0.26418 (10)0.0334 (3)
H5A0.31840.86780.30720.040*
C60.32089 (14)0.72269 (15)0.22568 (10)0.0329 (3)
H6A0.40910.71150.24220.039*
C70.07592 (15)0.93888 (17)0.27743 (10)0.0365 (4)
C80.25048 (19)0.54745 (18)0.02153 (10)0.0442 (4)
H8A0.32070.53080.00290.066*
H8B0.21220.62630.00020.066*
H8C0.18800.48200.00480.066*
C90.38280 (16)0.46314 (16)0.15651 (10)0.0350 (3)
C100.43151 (15)0.45503 (15)0.25502 (9)0.0313 (3)
C110.54421 (15)0.50991 (15)0.29655 (9)0.0303 (3)
C120.60720 (14)0.47863 (15)0.38701 (9)0.0291 (3)
C130.72526 (15)0.53184 (16)0.43456 (10)0.0322 (3)
C140.78219 (15)0.49785 (16)0.52027 (10)0.0346 (3)
H14A0.85940.53360.55100.042*
C150.72218 (16)0.40882 (16)0.56024 (10)0.0362 (3)
H15A0.76020.38620.61830.043*
C160.60834 (15)0.35357 (15)0.51625 (10)0.0331 (3)
H16A0.57080.29380.54410.040*
C170.54900 (14)0.38831 (14)0.42858 (9)0.0297 (3)
C180.36910 (14)0.36439 (15)0.29723 (10)0.0313 (3)
C190.37877 (16)0.23443 (16)0.42576 (10)0.0361 (3)
H19A0.36560.26560.47960.054*
H19B0.43610.16420.43820.054*
H19C0.29840.20850.38730.054*
C200.88302 (17)0.6906 (2)0.43465 (12)0.0461 (4)
H20A0.90080.75260.39560.069*
H20B0.95630.63750.45540.069*
H20C0.86390.73140.48370.069*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
F10.0625 (7)0.0633 (8)0.0377 (5)0.0276 (6)0.0067 (5)0.0050 (5)
F20.0575 (6)0.0533 (7)0.0479 (6)0.0070 (5)0.0224 (5)0.0005 (5)
F30.0453 (5)0.0401 (6)0.0594 (6)0.0072 (5)0.0155 (5)0.0122 (5)
O10.0600 (8)0.0492 (8)0.0284 (5)0.0130 (6)0.0014 (5)0.0064 (5)
O20.0374 (6)0.0372 (6)0.0250 (5)0.0019 (5)0.0036 (4)0.0034 (4)
O30.0362 (6)0.0355 (6)0.0356 (6)0.0014 (5)0.0012 (4)0.0019 (5)
O40.0403 (6)0.0441 (7)0.0314 (5)0.0102 (5)0.0005 (5)0.0059 (5)
N10.0438 (7)0.0350 (7)0.0228 (6)0.0013 (6)0.0009 (5)0.0007 (5)
N20.0337 (6)0.0302 (6)0.0261 (6)0.0003 (5)0.0056 (5)0.0003 (5)
C10.0404 (8)0.0312 (7)0.0255 (7)0.0025 (6)0.0010 (6)0.0050 (6)
C20.0399 (8)0.0364 (8)0.0361 (8)0.0045 (7)0.0056 (6)0.0006 (6)
C30.0342 (7)0.0389 (9)0.0403 (8)0.0032 (7)0.0034 (6)0.0011 (7)
C40.0369 (8)0.0323 (8)0.0285 (7)0.0033 (6)0.0028 (6)0.0038 (6)
C50.0368 (7)0.0328 (8)0.0261 (7)0.0057 (6)0.0011 (6)0.0029 (6)
C60.0330 (7)0.0339 (8)0.0273 (7)0.0029 (6)0.0005 (5)0.0041 (6)
C70.0340 (7)0.0415 (9)0.0298 (7)0.0032 (6)0.0013 (6)0.0030 (6)
C80.0584 (10)0.0421 (9)0.0245 (7)0.0007 (8)0.0020 (7)0.0010 (6)
C90.0402 (8)0.0346 (8)0.0260 (7)0.0023 (6)0.0017 (6)0.0022 (6)
C100.0363 (7)0.0301 (7)0.0240 (7)0.0034 (6)0.0020 (5)0.0003 (5)
C110.0353 (7)0.0303 (7)0.0237 (6)0.0037 (6)0.0054 (5)0.0008 (5)
C120.0325 (7)0.0297 (7)0.0226 (6)0.0040 (6)0.0030 (5)0.0015 (5)
C130.0341 (7)0.0320 (8)0.0284 (7)0.0019 (6)0.0050 (6)0.0004 (6)
C140.0326 (7)0.0373 (8)0.0286 (7)0.0001 (6)0.0010 (6)0.0008 (6)
C150.0421 (8)0.0380 (8)0.0243 (7)0.0035 (7)0.0018 (6)0.0026 (6)
C160.0397 (8)0.0322 (7)0.0260 (7)0.0027 (6)0.0068 (6)0.0021 (6)
C170.0331 (7)0.0302 (7)0.0243 (6)0.0035 (6)0.0053 (5)0.0022 (5)
C180.0337 (7)0.0299 (7)0.0274 (7)0.0030 (6)0.0034 (6)0.0034 (6)
C190.0399 (8)0.0349 (8)0.0324 (7)0.0041 (6)0.0080 (6)0.0011 (6)
C200.0399 (8)0.0497 (11)0.0430 (9)0.0116 (8)0.0013 (7)0.0059 (8)
Geometric parameters (Å, º) top
F1—C71.3351 (19)C5—H5A0.9300
F2—C71.343 (2)C6—H6A0.9300
F3—C71.334 (2)C8—H8A0.9600
O1—C91.225 (2)C8—H8B0.9600
O2—C111.3440 (19)C8—H8C0.9600
O2—H2O0.89 (3)C9—C101.505 (2)
O3—C181.232 (2)C10—C111.356 (2)
O4—C131.365 (2)C10—C181.444 (2)
O4—C201.426 (2)C11—C121.447 (2)
N1—C91.356 (2)C12—C171.409 (2)
N1—C11.423 (2)C12—C131.418 (2)
N1—C81.4713 (19)C13—C141.377 (2)
N2—C171.390 (2)C14—C151.396 (2)
N2—C181.3930 (19)C14—H14A0.9300
N2—C191.464 (2)C15—C161.377 (2)
C1—C61.390 (2)C15—H15A0.9300
C1—C21.396 (2)C16—C171.411 (2)
C2—C31.383 (3)C16—H16A0.9300
C2—H2A0.9300C19—H19A0.9600
C3—C41.395 (2)C19—H19B0.9600
C3—H3A0.9300C19—H19C0.9600
C4—C51.387 (2)C20—H20A0.9600
C4—C71.491 (2)C20—H20B0.9600
C5—C61.387 (2)C20—H20C0.9600
C11—O2—H2O113.5 (17)N1—C9—C10120.79 (14)
C13—O4—C20119.44 (13)C11—C10—C18122.75 (13)
C9—N1—C1125.87 (12)C11—C10—C9119.65 (14)
C9—N1—C8116.27 (14)C18—C10—C9116.03 (13)
C1—N1—C8117.75 (14)O2—C11—C10116.88 (13)
C17—N2—C18123.35 (13)O2—C11—C12122.92 (14)
C17—N2—C19119.43 (12)C10—C11—C12120.16 (14)
C18—N2—C19117.18 (13)C17—C12—C13118.84 (13)
C6—C1—C2119.45 (16)C17—C12—C11117.81 (14)
C6—C1—N1121.55 (15)C13—C12—C11123.33 (15)
C2—C1—N1118.89 (14)O4—C13—C14123.74 (14)
C3—C2—C1120.39 (15)O4—C13—C12115.12 (13)
C3—C2—H2A119.8C14—C13—C12121.14 (15)
C1—C2—H2A119.8C13—C14—C15118.94 (14)
C2—C3—C4119.84 (15)C13—C14—H14A120.5
C2—C3—H3A120.1C15—C14—H14A120.5
C4—C3—H3A120.1C16—C15—C14121.90 (14)
C5—C4—C3119.93 (16)C16—C15—H15A119.1
C5—C4—C7120.80 (14)C14—C15—H15A119.1
C3—C4—C7119.27 (15)C15—C16—C17119.54 (15)
C6—C5—C4120.09 (14)C15—C16—H16A120.2
C6—C5—H5A120.0C17—C16—H16A120.2
C4—C5—H5A120.0N2—C17—C12120.19 (13)
C5—C6—C1120.28 (15)N2—C17—C16120.19 (14)
C5—C6—H6A119.9C12—C17—C16119.63 (14)
C1—C6—H6A119.9O3—C18—N2121.36 (15)
F3—C7—F1107.22 (15)O3—C18—C10122.93 (14)
F3—C7—F2105.04 (13)N2—C18—C10115.69 (13)
F1—C7—F2106.06 (14)N2—C19—H19A109.5
F3—C7—C4113.18 (14)N2—C19—H19B109.5
F1—C7—C4112.25 (13)H19A—C19—H19B109.5
F2—C7—C4112.52 (15)N2—C19—H19C109.5
N1—C8—H8A109.5H19A—C19—H19C109.5
N1—C8—H8B109.5H19B—C19—H19C109.5
H8A—C8—H8B109.5O4—C20—H20A109.5
N1—C8—H8C109.5O4—C20—H20B109.5
H8A—C8—H8C109.5H20A—C20—H20B109.5
H8B—C8—H8C109.5O4—C20—H20C109.5
O1—C9—N1121.14 (14)H20A—C20—H20C109.5
O1—C9—C10118.07 (15)H20B—C20—H20C109.5
C9—N1—C1—C653.1 (2)O2—C11—C12—C17176.45 (13)
C8—N1—C1—C6131.00 (17)C10—C11—C12—C171.4 (2)
C9—N1—C1—C2130.73 (18)O2—C11—C12—C131.9 (2)
C8—N1—C1—C245.2 (2)C10—C11—C12—C13179.78 (14)
C6—C1—C2—C30.7 (3)C20—O4—C13—C1410.4 (2)
N1—C1—C2—C3175.56 (15)C20—O4—C13—C12169.82 (15)
C1—C2—C3—C40.0 (3)C17—C12—C13—O4178.95 (13)
C2—C3—C4—C51.3 (3)C11—C12—C13—O40.6 (2)
C2—C3—C4—C7178.77 (15)C17—C12—C13—C140.9 (2)
C3—C4—C5—C61.9 (2)C11—C12—C13—C14179.19 (15)
C7—C4—C5—C6178.19 (14)O4—C13—C14—C15179.40 (15)
C4—C5—C6—C11.2 (2)C12—C13—C14—C150.4 (2)
C2—C1—C6—C50.1 (2)C13—C14—C15—C160.4 (3)
N1—C1—C6—C5176.04 (14)C14—C15—C16—C170.8 (3)
C5—C4—C7—F319.4 (2)C18—N2—C17—C121.2 (2)
C3—C4—C7—F3160.76 (15)C19—N2—C17—C12176.37 (13)
C5—C4—C7—F1140.90 (16)C18—N2—C17—C16179.06 (14)
C3—C4—C7—F139.2 (2)C19—N2—C17—C163.4 (2)
C5—C4—C7—F299.54 (18)C13—C12—C17—N2179.28 (13)
C3—C4—C7—F280.34 (18)C11—C12—C17—N20.8 (2)
C1—N1—C9—O1179.39 (16)C13—C12—C17—C160.5 (2)
C8—N1—C9—O13.4 (2)C11—C12—C17—C16178.94 (14)
C1—N1—C9—C100.6 (2)C15—C16—C17—N2179.92 (14)
C8—N1—C9—C10176.58 (15)C15—C16—C17—C120.3 (2)
O1—C9—C10—C1183.9 (2)C17—N2—C18—O3179.18 (14)
N1—C9—C10—C1196.11 (19)C19—N2—C18—O33.2 (2)
O1—C9—C10—C1882.2 (2)C17—N2—C18—C102.4 (2)
N1—C9—C10—C1897.77 (18)C19—N2—C18—C10175.13 (13)
C18—C10—C11—O2177.94 (13)C11—C10—C18—O3179.83 (15)
C9—C10—C11—O212.8 (2)C9—C10—C18—O314.5 (2)
C18—C10—C11—C120.1 (2)C11—C10—C18—N21.8 (2)
C9—C10—C11—C12165.21 (14)C9—C10—C18—N2163.83 (13)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O2—H2O···O40.89 (3)1.82 (3)2.5538 (16)138 (2)
O2—H2O···O3i0.89 (3)2.28 (3)2.8591 (17)123 (2)
Symmetry code: (i) x+1, y+1/2, z+1/2.
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O2—H2O···O40.89 (3)1.82 (3)2.5538 (16)138 (2)
O2—H2O···O3i0.89 (3)2.28 (3)2.8591 (17)123 (2)
Symmetry code: (i) x+1, y+1/2, z+1/2.
 

Acknowledgements

This study was partially supported by a sponsored research agreement between The Johns Hopkins University School of Medicine (J. Isaacs, PI) and Active Biotech Research AB. RJB acknowledges the NSF–MRI program (grant No. CHE0619278) for funds to purchase the X-ray diffractometer as well as the Howard University Nanoscience Facility for access to liquid nitro­gen.

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Volume 70| Part 3| March 2014| Pages o297-o298
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