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Regorafenib {systematic name: 4-[4-({[4-chloro-3-(tri­fluoro­methy)phen­yl]car­bam­o­yl}amino)-3-fluoro­phen­oxy]-1-methyl­pyridine-2-carboxamide}, C21H15ClF4N4O3, is a potent anti­cancer and anti-angiogenic agent that possesses various activities on the VEGFR, PDGFR, raf and/or flt-3 kinase signaling mol­ecules. The compound has been crystallized as polymorphic form I and as the mono­hydrate, C21H15ClF4N4O3·H2O. The regorafenib mol­ecule consists of bi­aryl­urea and pyridine-2-carboxamide units linked by an ether group. A comparison of both forms shows that they differ in the relative orientation of the bi­aryl­urea and pyridine-2-carboxamide units, due to different rotations around the ether group, as measured by the C—O—C bond angles [119.5 (3)° in regorafenib and 116.10 (15)° in the monohydrate]. Meanwhile, the conformational differences are reflected in different hydrogen-bond networks. Polymorphic form I contains two inter­molecular N—H...O hydrogen bonds, which link the regorafenib mol­ecules into an infinite mol­ecular chain along the b axis. In the monohydrate, the presence of the solvent water mol­ecule results in more abundant hydrogen bonds. The water mol­ecules act as donors and acceptors, forming N—H...O and O—H...O hydrogen-bond inter­actions. Thus, R42(28) ring motifs are formed, which are fused to form continuous spiral ring motifs along the a axis. The (tri­fluoro­meth­yl)phenyl rings protrude on the outside of these motifs and inter­digitate with those of adjacent ring motifs, thereby forming columns populated by halogen atoms.

Supporting information

cif

Crystallographic Information File (CIF) https://doi.org/10.1107/S2053229616003727/ku3173sup1.cif
Contains datablocks I, II, global

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S2053229616003727/ku3173Isup2.hkl
Contains datablock I

hkl

Structure factor file (CIF format) https://doi.org/10.1107/S2053229616003727/ku3173IIsup4.hkl
Contains datablock II

CCDC references: 1045583; 1045581

Computing details top

For both compounds, data collection: PROCESS-AUTO (Rigaku, 2006); cell refinement: PROCESS-AUTO (Rigaku, 2006); data reduction: CrystalStructure (Rigaku, 2007); program(s) used to solve structure: SHELXS97 (Sheldrick, 2008); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: ORTEP-3 for Windows (Farrugia, 2012) and DIAMOND (Brandenburg & Putz, 2005); software used to prepare material for publication: WinGX (Farrugia, 2012).

(I) 4-[4-({[4-Chloro-3-(trifluoromethy)phenyl]carbamoyl}amino)-3-fluorophenoxy]-1-methylpyridine-2-carboxamide top
Crystal data top
C21H15ClF4N4O3F(000) = 984
Mr = 482.82Dx = 1.508 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 10707 reflections
a = 7.6972 (4) Åθ = 3.0–27.5°
b = 24.3703 (12) ŵ = 0.25 mm1
c = 11.3580 (7) ÅT = 296 K
β = 93.545 (2)°Platelet, colorless
V = 2126.5 (2) Å30.49 × 0.39 × 0.13 mm
Z = 4
Data collection top
Rigaku R-AXIS RAPID/ZJUG
diffractometer
3738 independent reflections
Radiation source: rotating anode2311 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.051
Detector resolution: 10.00 pixels mm-1θmax = 25.0°, θmin = 3.1°
ω scansh = 99
Absorption correction: multi-scan
(ABSCOR; Higashi, 1995)
k = 2828
Tmin = 0.879, Tmax = 0.969l = 1313
16556 measured reflections
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.048H-atom parameters constrained
wR(F2) = 0.148 w = 1/[σ2(Fo2) + (0.0537P)2 + 2.3081P]
where P = (Fo2 + 2Fc2)/3
S = 1.00(Δ/σ)max < 0.001
3738 reflectionsΔρmax = 0.29 e Å3
300 parametersΔρmin = 0.35 e Å3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0149 (12)
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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
C10.1725 (4)0.72715 (13)0.5281 (3)0.0464 (8)
C20.1757 (4)0.77854 (12)0.5813 (3)0.0478 (8)
H20.22500.78210.65770.057*
C30.1076 (4)0.82442 (13)0.5236 (3)0.0479 (8)
C40.0367 (4)0.81959 (13)0.4082 (3)0.0500 (8)
C50.0327 (5)0.76842 (14)0.3559 (3)0.0559 (9)
H50.01460.76500.27890.067*
C60.0965 (4)0.72215 (13)0.4142 (3)0.0526 (9)
H60.08880.68800.37760.063*
C70.1012 (5)0.87705 (15)0.5909 (4)0.0621 (10)
C80.2354 (4)0.62834 (13)0.5659 (3)0.0502 (8)
C90.3390 (4)0.53934 (12)0.6434 (3)0.0480 (8)
C100.4959 (4)0.51292 (13)0.6646 (3)0.0535 (9)
C110.5121 (5)0.45734 (14)0.6781 (3)0.0568 (9)
H110.62050.44090.69170.068*
C120.3624 (5)0.42683 (13)0.6707 (3)0.0557 (10)
C130.2018 (5)0.45053 (14)0.6465 (3)0.0626 (10)
H130.10190.42900.63940.075*
C140.1916 (5)0.50704 (13)0.6328 (3)0.0583 (9)
H140.08370.52340.61630.070*
C150.3663 (5)0.33260 (12)0.6101 (3)0.0494 (8)
C160.3099 (5)0.34309 (13)0.4950 (3)0.0532 (9)
H160.27730.37830.47070.064*
C170.3033 (5)0.29997 (14)0.4174 (3)0.0577 (9)
H170.26390.30720.33990.069*
C180.4042 (4)0.23938 (12)0.5568 (3)0.0437 (8)
C190.4145 (4)0.27964 (13)0.6419 (3)0.0478 (8)
H190.45300.27150.71910.057*
C200.4530 (4)0.18162 (13)0.5882 (3)0.0488 (8)
C210.4420 (6)0.08557 (14)0.5253 (4)0.0761 (12)
H21A0.55040.07910.56970.114*
H21B0.44300.06720.45060.114*
H21C0.34800.07170.56840.114*
Cl10.04400 (14)0.87514 (4)0.32732 (9)0.0708 (4)
F10.1663 (4)0.91993 (9)0.5372 (3)0.1068 (10)
F20.1880 (4)0.87469 (9)0.6945 (2)0.1096 (11)
F30.0588 (4)0.89191 (12)0.6106 (3)0.1110 (11)
F40.6431 (3)0.54431 (9)0.6759 (2)0.0844 (8)
N10.2461 (4)0.68325 (10)0.5930 (2)0.0534 (8)
H10.30480.69160.65740.064*
N20.3362 (4)0.59694 (10)0.6409 (3)0.0569 (8)
H2A0.40460.61380.69150.068*
N30.3490 (4)0.24839 (11)0.4441 (2)0.0535 (7)
N40.4190 (4)0.14425 (11)0.5061 (3)0.0573 (8)
H40.38110.15520.43720.069*
O10.1457 (4)0.60980 (9)0.4827 (2)0.0730 (8)
O20.3784 (4)0.37076 (9)0.6987 (2)0.0700 (8)
O30.5190 (4)0.17076 (9)0.6882 (2)0.0654 (7)
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0463 (18)0.0434 (18)0.048 (2)0.0009 (14)0.0054 (15)0.0005 (15)
C20.0523 (19)0.0450 (18)0.045 (2)0.0004 (15)0.0089 (15)0.0016 (15)
C30.0467 (18)0.0421 (17)0.054 (2)0.0015 (15)0.0018 (16)0.0048 (15)
C40.0525 (19)0.0489 (19)0.048 (2)0.0047 (16)0.0021 (16)0.0044 (15)
C50.065 (2)0.059 (2)0.042 (2)0.0091 (18)0.0067 (17)0.0008 (16)
C60.062 (2)0.0441 (18)0.050 (2)0.0019 (16)0.0061 (17)0.0060 (15)
C70.064 (2)0.051 (2)0.070 (3)0.0005 (19)0.013 (2)0.0019 (19)
C80.057 (2)0.0422 (18)0.050 (2)0.0022 (16)0.0080 (17)0.0020 (15)
C90.058 (2)0.0349 (16)0.050 (2)0.0021 (15)0.0058 (16)0.0022 (14)
C100.056 (2)0.0426 (18)0.061 (2)0.0097 (16)0.0058 (17)0.0040 (16)
C110.067 (2)0.0442 (19)0.058 (2)0.0053 (18)0.0082 (18)0.0027 (16)
C120.089 (3)0.0343 (17)0.042 (2)0.0062 (18)0.0103 (19)0.0006 (14)
C130.072 (2)0.047 (2)0.067 (3)0.0154 (18)0.012 (2)0.0034 (18)
C140.060 (2)0.0459 (19)0.067 (2)0.0056 (17)0.0086 (18)0.0002 (17)
C150.065 (2)0.0387 (17)0.043 (2)0.0048 (15)0.0068 (16)0.0010 (14)
C160.071 (2)0.0412 (18)0.047 (2)0.0009 (16)0.0062 (17)0.0096 (15)
C170.077 (2)0.055 (2)0.039 (2)0.0018 (19)0.0080 (17)0.0047 (16)
C180.0469 (18)0.0447 (17)0.0389 (19)0.0029 (14)0.0035 (14)0.0050 (14)
C190.060 (2)0.0451 (18)0.0373 (18)0.0079 (16)0.0063 (15)0.0041 (14)
C200.0516 (19)0.0445 (18)0.049 (2)0.0039 (15)0.0046 (16)0.0033 (16)
C210.092 (3)0.046 (2)0.090 (3)0.011 (2)0.005 (2)0.007 (2)
Cl10.0917 (8)0.0579 (6)0.0616 (6)0.0171 (5)0.0061 (5)0.0108 (5)
F10.149 (3)0.0457 (13)0.126 (2)0.0188 (15)0.0107 (19)0.0017 (14)
F20.167 (3)0.0591 (14)0.094 (2)0.0092 (15)0.0652 (19)0.0231 (13)
F30.0850 (19)0.112 (2)0.136 (3)0.0117 (16)0.0082 (17)0.0691 (19)
F40.0649 (14)0.0612 (13)0.124 (2)0.0101 (11)0.0187 (13)0.0195 (13)
N10.0669 (19)0.0383 (15)0.0521 (18)0.0016 (13)0.0197 (14)0.0006 (12)
N20.0671 (19)0.0347 (14)0.065 (2)0.0002 (13)0.0241 (16)0.0005 (13)
N30.0684 (19)0.0492 (16)0.0417 (17)0.0026 (14)0.0081 (14)0.0012 (13)
N40.077 (2)0.0413 (15)0.0520 (19)0.0021 (14)0.0058 (15)0.0033 (13)
O10.093 (2)0.0476 (14)0.0733 (19)0.0051 (13)0.0369 (16)0.0029 (13)
O20.126 (2)0.0345 (12)0.0469 (15)0.0066 (13)0.0187 (15)0.0024 (10)
O30.0899 (19)0.0463 (13)0.0568 (17)0.0035 (13)0.0216 (14)0.0036 (12)
Geometric parameters (Å, º) top
C1—C21.390 (4)C12—C131.377 (5)
C1—C61.391 (4)C12—O21.407 (4)
C1—N11.399 (4)C13—C141.387 (5)
C2—C31.383 (4)C13—H130.9300
C2—H20.9300C14—H140.9300
C3—C41.393 (5)C15—O21.370 (4)
C3—C71.496 (5)C15—C161.376 (4)
C4—C51.381 (5)C15—C191.384 (4)
C4—Cl11.730 (3)C16—C171.371 (5)
C5—C61.382 (5)C16—H160.9300
C5—H50.9300C17—N31.335 (4)
C6—H60.9300C17—H170.9300
C7—F31.316 (4)C18—N31.341 (4)
C7—F21.317 (4)C18—C191.376 (4)
C7—F11.324 (4)C18—C201.495 (4)
C8—O11.222 (4)C19—H190.9300
C8—N21.353 (4)C20—O31.244 (4)
C8—N11.375 (4)C20—N41.318 (4)
C9—C101.377 (5)C21—N41.456 (4)
C9—C141.380 (5)C21—H21A0.9600
C9—N21.404 (4)C21—H21B0.9600
C10—F41.366 (4)C21—H21C0.9600
C10—C111.368 (5)N1—H10.8600
C11—C121.370 (5)N2—H2A0.8600
C11—H110.9300N4—H40.8600
C2—C1—C6118.6 (3)C12—C13—H13120.6
C2—C1—N1117.6 (3)C14—C13—H13120.6
C6—C1—N1123.8 (3)C9—C14—C13121.0 (3)
C3—C2—C1121.8 (3)C9—C14—H14119.5
C3—C2—H2119.1C13—C14—H14119.5
C1—C2—H2119.1O2—C15—C16125.1 (3)
C2—C3—C4119.5 (3)O2—C15—C19115.9 (3)
C2—C3—C7118.3 (3)C16—C15—C19119.0 (3)
C4—C3—C7122.0 (3)C17—C16—C15117.7 (3)
C5—C4—C3118.6 (3)C17—C16—H16121.1
C5—C4—Cl1118.7 (3)C15—C16—H16121.1
C3—C4—Cl1122.7 (3)N3—C17—C16125.2 (3)
C4—C5—C6122.2 (3)N3—C17—H17117.4
C4—C5—H5118.9C16—C17—H17117.4
C6—C5—H5118.9N3—C18—C19123.7 (3)
C5—C6—C1119.4 (3)N3—C18—C20116.2 (3)
C5—C6—H6120.3C19—C18—C20120.1 (3)
C1—C6—H6120.3C18—C19—C15118.6 (3)
F3—C7—F2106.8 (4)C18—C19—H19120.7
F3—C7—F1104.2 (3)C15—C19—H19120.7
F2—C7—F1105.1 (3)O3—C20—N4123.5 (3)
F3—C7—C3112.5 (3)O3—C20—C18120.1 (3)
F2—C7—C3112.9 (3)N4—C20—C18116.5 (3)
F1—C7—C3114.6 (3)N4—C21—H21A109.5
O1—C8—N2123.5 (3)N4—C21—H21B109.5
O1—C8—N1123.8 (3)H21A—C21—H21B109.5
N2—C8—N1112.7 (3)N4—C21—H21C109.5
C10—C9—C14117.1 (3)H21A—C21—H21C109.5
C10—C9—N2118.9 (3)H21B—C21—H21C109.5
C14—C9—N2123.8 (3)C8—N1—C1127.6 (3)
F4—C10—C11118.3 (3)C8—N1—H1116.2
F4—C10—C9117.9 (3)C1—N1—H1116.2
C11—C10—C9123.7 (3)C8—N2—C9125.9 (3)
C10—C11—C12117.4 (3)C8—N2—H2A117.1
C10—C11—H11121.3C9—N2—H2A117.1
C12—C11—H11121.3C17—N3—C18115.8 (3)
C11—C12—C13121.7 (3)C20—N4—C21123.7 (3)
C11—C12—O2116.9 (3)C20—N4—H4118.1
C13—C12—O2121.2 (3)C21—N4—H4118.1
C12—C13—C14118.9 (3)C15—O2—C12119.5 (3)
C6—C1—C2—C30.8 (5)N2—C9—C14—C13174.2 (3)
N1—C1—C2—C3179.4 (3)C12—C13—C14—C90.2 (6)
C1—C2—C3—C41.3 (5)O2—C15—C16—C17179.1 (4)
C1—C2—C3—C7174.4 (3)C19—C15—C16—C170.4 (5)
C2—C3—C4—C51.7 (5)C15—C16—C17—N30.7 (6)
C7—C3—C4—C5173.8 (3)N3—C18—C19—C150.4 (5)
C2—C3—C4—Cl1177.6 (3)C20—C18—C19—C15179.2 (3)
C7—C3—C4—Cl16.9 (5)O2—C15—C19—C18179.6 (3)
C3—C4—C5—C60.1 (5)C16—C15—C19—C180.1 (5)
Cl1—C4—C5—C6179.2 (3)N3—C18—C20—O3174.0 (3)
C4—C5—C6—C12.0 (6)C19—C18—C20—O37.0 (5)
C2—C1—C6—C52.4 (5)N3—C18—C20—N47.3 (4)
N1—C1—C6—C5177.8 (3)C19—C18—C20—N4171.7 (3)
C2—C3—C7—F3111.0 (4)O1—C8—N1—C16.0 (6)
C4—C3—C7—F364.6 (5)N2—C8—N1—C1173.6 (3)
C2—C3—C7—F29.9 (5)C2—C1—N1—C8169.7 (3)
C4—C3—C7—F2174.5 (3)C6—C1—N1—C810.1 (6)
C2—C3—C7—F1130.2 (4)O1—C8—N2—C97.5 (6)
C4—C3—C7—F154.3 (5)N1—C8—N2—C9173.0 (3)
C14—C9—C10—F4179.7 (3)C10—C9—N2—C8141.3 (4)
N2—C9—C10—F43.4 (5)C14—C9—N2—C842.7 (6)
C14—C9—C10—C111.6 (6)C16—C17—N3—C180.4 (5)
N2—C9—C10—C11174.7 (3)C19—C18—N3—C170.1 (5)
F4—C10—C11—C12177.6 (3)C20—C18—N3—C17179.1 (3)
C9—C10—C11—C120.5 (6)O3—C20—N4—C214.9 (6)
C10—C11—C12—C132.3 (5)C18—C20—N4—C21173.8 (3)
C10—C11—C12—O2172.5 (3)C16—C15—O2—C1211.8 (5)
C11—C12—C13—C142.0 (6)C19—C15—O2—C12168.7 (3)
O2—C12—C13—C14172.6 (3)C11—C12—O2—C15105.6 (4)
C10—C9—C14—C131.9 (6)C13—C12—O2—C1579.5 (5)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N1—H1···O3i0.862.212.997 (4)152
N2—H2A···O3i0.862.012.825 (4)158
Symmetry code: (i) x+1, y+1/2, z+3/2.
(II) 4-[4-({[4-Chloro-3-(trifluoromethy)phenyl]carbamoyl}amino)-3-fluorophenoxy]-1-methylpyridine-2-carboxamide monohydrate top
Crystal data top
C21H15ClF4N4O3·H2OF(000) = 1024
Mr = 500.84Dx = 1.544 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71073 Å
Hall symbol: -P 2ybcCell parameters from 13751 reflections
a = 4.7783 (2) Åθ = 3.1–27.4°
b = 21.9538 (9) ŵ = 0.25 mm1
c = 20.5581 (8) ÅT = 296 K
β = 92.341 (1)°Platelet, colorless
V = 2154.78 (15) Å30.48 × 0.38 × 0.16 mm
Z = 4
Data collection top
Rigaku R-AXIS RAPID/ZJUG
diffractometer
4903 independent reflections
Radiation source: rotating anode3197 reflections with I > 2σ(I)
Graphite monochromatorRint = 0.045
Detector resolution: 10.00 pixels mm-1θmax = 27.5°, θmin = 3.1°
ω scansh = 56
Absorption correction: multi-scan
(ABSCOR; Higashi, 1995)
k = 2828
Tmin = 0.890, Tmax = 0.961l = 2626
20501 measured reflections
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.042H-atom parameters constrained
wR(F2) = 0.120 w = 1/[σ2(Fo2) + (0.0538P)2 + 0.7939P]
where P = (Fo2 + 2Fc2)/3
S = 1.00(Δ/σ)max < 0.001
4903 reflectionsΔρmax = 0.23 e Å3
309 parametersΔρmin = 0.31 e Å3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.0203 (14)
Special details top

Geometry. All esds (except the esd in the dihedral angle between two l.s. planes) are estimated using the full covariance matrix. The cell esds are taken into account individually in the estimation of esds in distances, angles and torsion angles; correlations between esds in cell parameters are only used when they are defined by crystal symmetry. An approximate (isotropic) treatment of cell esds is used for estimating esds 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 > 2sigma(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
C10.3084 (4)0.50642 (9)0.78416 (9)0.0365 (4)
C20.2383 (4)0.56444 (9)0.80461 (9)0.0396 (4)
H20.31790.59800.78490.048*
C30.0523 (4)0.57359 (9)0.85373 (9)0.0399 (5)
C40.0680 (4)0.52315 (10)0.88298 (9)0.0431 (5)
C50.0057 (4)0.46555 (10)0.86138 (10)0.0467 (5)
H50.09060.43210.88000.056*
C60.1811 (4)0.45644 (10)0.81244 (10)0.0449 (5)
H60.22110.41720.79860.054*
C70.0075 (5)0.63711 (11)0.87514 (12)0.0528 (6)
C80.6276 (4)0.45096 (9)0.71187 (9)0.0384 (4)
C90.9572 (4)0.42249 (9)0.62695 (9)0.0380 (4)
C101.1447 (5)0.44482 (10)0.58269 (10)0.0464 (5)
C111.3031 (5)0.40850 (11)0.54408 (10)0.0497 (5)
H111.42640.42530.51510.060*
C121.2726 (4)0.34615 (10)0.54983 (9)0.0428 (5)
C131.0902 (5)0.32204 (10)0.59238 (11)0.0490 (5)
H131.07180.28000.59570.059*
C140.9328 (5)0.35968 (10)0.63054 (10)0.0480 (5)
H140.80860.34260.65900.058*
C151.3094 (4)0.26889 (9)0.47089 (9)0.0384 (4)
C161.4089 (4)0.21037 (10)0.46580 (10)0.0451 (5)
H161.55800.19680.49240.054*
C171.2815 (5)0.17248 (10)0.42016 (10)0.0494 (5)
H171.34480.13250.41800.059*
C180.9847 (4)0.24709 (9)0.38363 (9)0.0356 (4)
C191.0900 (4)0.28804 (9)0.42978 (9)0.0384 (4)
H191.01580.32700.43300.046*
C200.7640 (4)0.26877 (9)0.33469 (9)0.0379 (4)
C210.4359 (5)0.24031 (11)0.24568 (10)0.0506 (5)
H21A0.33510.27620.25760.076*
H21B0.30880.20650.24150.076*
H21C0.52180.24710.20490.076*
Cl10.29708 (13)0.53054 (3)0.94589 (3)0.0634 (2)
F10.2793 (3)0.65122 (7)0.87287 (8)0.0683 (4)
F20.1154 (4)0.67905 (7)0.83876 (9)0.0874 (6)
F30.0824 (3)0.64786 (8)0.93637 (8)0.0883 (6)
F41.1708 (3)0.50629 (6)0.57779 (7)0.0740 (5)
N10.5009 (4)0.50228 (8)0.73467 (8)0.0429 (4)
H10.54470.53600.71640.051*
N20.8044 (4)0.46440 (8)0.66270 (8)0.0422 (4)
H2A0.82290.50220.65290.051*
N31.0727 (4)0.18938 (8)0.37872 (8)0.0435 (4)
N40.6509 (3)0.22688 (8)0.29560 (8)0.0426 (4)
H40.70740.18990.30000.051*
O10.5883 (3)0.39990 (7)0.73256 (7)0.0514 (4)
O21.4446 (3)0.30739 (7)0.51463 (7)0.0533 (4)
O30.7020 (3)0.32373 (6)0.33169 (7)0.0501 (4)
O40.7761 (4)0.60161 (7)0.67180 (9)0.0682 (5)
H410.92100.62120.67710.102*
H420.65630.62500.65700.102*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
C10.0385 (10)0.0353 (10)0.0355 (9)0.0003 (8)0.0005 (8)0.0002 (8)
C20.0391 (10)0.0357 (10)0.0440 (10)0.0038 (9)0.0013 (9)0.0018 (8)
C30.0347 (10)0.0429 (11)0.0419 (10)0.0011 (9)0.0023 (8)0.0041 (9)
C40.0356 (10)0.0556 (13)0.0382 (10)0.0042 (10)0.0021 (8)0.0074 (9)
C50.0474 (12)0.0410 (12)0.0522 (12)0.0008 (10)0.0074 (10)0.0100 (9)
C60.0499 (12)0.0354 (11)0.0495 (11)0.0011 (9)0.0044 (10)0.0035 (9)
C70.0392 (11)0.0526 (14)0.0667 (14)0.0015 (10)0.0048 (11)0.0134 (12)
C80.0434 (11)0.0340 (10)0.0375 (10)0.0003 (9)0.0008 (8)0.0032 (8)
C90.0410 (10)0.0376 (11)0.0351 (9)0.0009 (9)0.0017 (8)0.0030 (8)
C100.0539 (12)0.0394 (12)0.0462 (11)0.0014 (10)0.0055 (10)0.0012 (9)
C110.0497 (13)0.0540 (14)0.0459 (11)0.0023 (11)0.0098 (10)0.0019 (10)
C120.0385 (10)0.0503 (13)0.0390 (10)0.0062 (9)0.0046 (9)0.0120 (9)
C130.0581 (13)0.0369 (11)0.0523 (12)0.0003 (10)0.0040 (11)0.0077 (9)
C140.0562 (13)0.0395 (12)0.0492 (12)0.0031 (10)0.0115 (10)0.0033 (9)
C150.0340 (10)0.0460 (12)0.0355 (9)0.0024 (9)0.0047 (8)0.0054 (8)
C160.0436 (11)0.0482 (12)0.0435 (11)0.0085 (10)0.0001 (9)0.0025 (9)
C170.0558 (13)0.0375 (11)0.0545 (12)0.0083 (10)0.0019 (11)0.0004 (10)
C180.0371 (10)0.0329 (10)0.0372 (9)0.0008 (8)0.0061 (8)0.0013 (8)
C190.0383 (10)0.0361 (10)0.0412 (10)0.0020 (8)0.0064 (8)0.0033 (8)
C200.0361 (10)0.0371 (11)0.0409 (10)0.0014 (9)0.0047 (8)0.0002 (8)
C210.0482 (12)0.0573 (14)0.0456 (11)0.0010 (11)0.0077 (10)0.0001 (10)
Cl10.0567 (4)0.0824 (5)0.0525 (3)0.0105 (3)0.0181 (3)0.0094 (3)
F10.0450 (7)0.0585 (9)0.1017 (11)0.0110 (6)0.0062 (7)0.0105 (8)
F20.0861 (11)0.0408 (8)0.1391 (15)0.0050 (8)0.0526 (11)0.0124 (9)
F30.0791 (11)0.0966 (13)0.0876 (11)0.0064 (9)0.0146 (9)0.0525 (10)
F40.0999 (12)0.0393 (8)0.0856 (10)0.0040 (7)0.0408 (9)0.0048 (7)
N10.0529 (10)0.0309 (9)0.0456 (9)0.0005 (8)0.0126 (8)0.0010 (7)
N20.0516 (10)0.0329 (9)0.0427 (9)0.0002 (8)0.0080 (8)0.0004 (7)
N30.0495 (10)0.0340 (9)0.0468 (9)0.0029 (8)0.0001 (8)0.0014 (7)
N40.0449 (9)0.0378 (9)0.0445 (9)0.0007 (8)0.0047 (8)0.0006 (7)
O10.0670 (10)0.0330 (8)0.0553 (9)0.0003 (7)0.0170 (8)0.0012 (7)
O20.0392 (8)0.0650 (10)0.0553 (9)0.0063 (7)0.0037 (7)0.0239 (8)
O30.0497 (8)0.0360 (8)0.0637 (9)0.0048 (7)0.0087 (7)0.0023 (7)
O40.0555 (10)0.0393 (9)0.1097 (14)0.0004 (8)0.0043 (10)0.0222 (9)
Geometric parameters (Å, º) top
C1—C21.387 (3)C12—O21.404 (2)
C1—C61.393 (3)C13—C141.383 (3)
C1—N11.402 (3)C13—H130.9300
C2—C31.387 (3)C14—H140.9300
C2—H20.9300C15—C161.375 (3)
C3—C41.395 (3)C15—O21.376 (2)
C3—C71.494 (3)C15—C191.385 (3)
C4—C51.377 (3)C16—C171.377 (3)
C4—Cl11.736 (2)C16—H160.9300
C5—C61.386 (3)C17—N31.338 (3)
C5—H50.9300C17—H170.9300
C6—H60.9300C18—N31.340 (2)
C7—F11.334 (2)C18—C191.386 (3)
C7—F31.334 (3)C18—C201.505 (3)
C7—F21.337 (3)C19—H190.9300
C8—O11.216 (2)C20—O31.243 (2)
C8—N11.371 (2)C20—N41.322 (2)
C8—N21.375 (3)C21—N41.452 (3)
C9—C141.386 (3)C21—H21A0.9600
C9—C101.392 (3)C21—H21B0.9600
C9—N21.401 (3)C21—H21C0.9600
C10—F41.359 (2)N1—H10.8600
C10—C111.374 (3)N2—H2A0.8600
C11—C121.382 (3)N4—H40.8600
C11—H110.9300O4—H410.8191
C12—C131.366 (3)O4—H420.8189
C2—C1—C6118.80 (19)C14—C13—H13119.7
C2—C1—N1116.96 (17)C13—C14—C9121.0 (2)
C6—C1—N1124.23 (18)C13—C14—H14119.5
C3—C2—C1121.58 (19)C9—C14—H14119.5
C3—C2—H2119.2C16—C15—O2117.97 (17)
C1—C2—H2119.2C16—C15—C19119.51 (18)
C2—C3—C4119.11 (19)O2—C15—C19122.42 (18)
C2—C3—C7119.06 (19)C15—C16—C17118.13 (19)
C4—C3—C7121.81 (19)C15—C16—H16120.9
C5—C4—C3119.45 (19)C17—C16—H16120.9
C5—C4—Cl1118.51 (17)N3—C17—C16124.3 (2)
C3—C4—Cl1122.03 (17)N3—C17—H17117.8
C4—C5—C6121.4 (2)C16—C17—H17117.8
C4—C5—H5119.3N3—C18—C19123.94 (18)
C6—C5—H5119.3N3—C18—C20117.53 (16)
C5—C6—C1119.6 (2)C19—C18—C20118.51 (17)
C5—C6—H6120.2C15—C19—C18117.74 (18)
C1—C6—H6120.2C15—C19—H19121.1
F1—C7—F3105.52 (19)C18—C19—H19121.1
F1—C7—F2105.6 (2)O3—C20—N4123.65 (18)
F3—C7—F2105.91 (19)O3—C20—C18119.95 (17)
F1—C7—C3113.84 (18)N4—C20—C18116.38 (17)
F3—C7—C3112.6 (2)N4—C21—H21A109.5
F2—C7—C3112.60 (19)N4—C21—H21B109.5
O1—C8—N1124.14 (19)H21A—C21—H21B109.5
O1—C8—N2124.27 (18)N4—C21—H21C109.5
N1—C8—N2111.60 (17)H21A—C21—H21C109.5
C14—C9—C10116.30 (19)H21B—C21—H21C109.5
C14—C9—N2125.33 (19)C8—N1—C1127.84 (17)
C10—C9—N2118.35 (18)C8—N1—H1116.1
F4—C10—C11118.6 (2)C1—N1—H1116.1
F4—C10—C9117.50 (19)C8—N2—C9126.40 (17)
C11—C10—C9123.9 (2)C8—N2—H2A116.8
C10—C11—C12117.6 (2)C9—N2—H2A116.8
C10—C11—H11121.2C17—N3—C18116.26 (17)
C12—C11—H11121.2C20—N4—C21123.23 (18)
C13—C12—C11120.7 (2)C20—N4—H4118.4
C13—C12—O2119.8 (2)C21—N4—H4118.4
C11—C12—O2119.3 (2)C15—O2—C12116.10 (15)
C12—C13—C14120.5 (2)H41—O4—H42107.0
C12—C13—H13119.7
C6—C1—C2—C32.1 (3)C10—C9—C14—C130.7 (3)
N1—C1—C2—C3179.30 (17)N2—C9—C14—C13178.94 (19)
C1—C2—C3—C40.3 (3)O2—C15—C16—C17177.33 (19)
C1—C2—C3—C7177.96 (18)C19—C15—C16—C171.1 (3)
C2—C3—C4—C51.7 (3)C15—C16—C17—N32.4 (3)
C7—C3—C4—C5179.96 (19)C16—C15—C19—C181.7 (3)
C2—C3—C4—Cl1178.65 (14)O2—C15—C19—C18174.42 (17)
C7—C3—C4—Cl10.4 (3)N3—C18—C19—C153.6 (3)
C3—C4—C5—C62.0 (3)C20—C18—C19—C15174.64 (17)
Cl1—C4—C5—C6178.36 (16)N3—C18—C20—O3170.53 (18)
C4—C5—C6—C10.2 (3)C19—C18—C20—O37.8 (3)
C2—C1—C6—C51.8 (3)N3—C18—C20—N47.8 (3)
N1—C1—C6—C5179.68 (18)C19—C18—C20—N4173.84 (17)
C2—C3—C7—F1125.5 (2)O1—C8—N1—C10.1 (3)
C4—C3—C7—F156.3 (3)N2—C8—N1—C1179.85 (17)
C2—C3—C7—F3114.5 (2)C2—C1—N1—C8171.48 (19)
C4—C3—C7—F363.8 (3)C6—C1—N1—C810.0 (3)
C2—C3—C7—F25.2 (3)O1—C8—N2—C92.7 (3)
C4—C3—C7—F2176.54 (19)N1—C8—N2—C9177.20 (17)
C14—C9—C10—F4179.43 (19)C14—C9—N2—C87.3 (3)
N2—C9—C10—F41.1 (3)C10—C9—N2—C8174.52 (18)
C14—C9—C10—C110.6 (3)C16—C17—N3—C180.7 (3)
N2—C9—C10—C11178.92 (19)C19—C18—N3—C172.4 (3)
F4—C10—C11—C12179.89 (19)C20—C18—N3—C17175.85 (18)
C9—C10—C11—C120.1 (3)O3—C20—N4—C211.5 (3)
C10—C11—C12—C130.2 (3)C18—C20—N4—C21179.85 (18)
C10—C11—C12—O2175.58 (18)C16—C15—O2—C12140.3 (2)
C11—C12—C13—C140.0 (3)C19—C15—O2—C1243.5 (3)
O2—C12—C13—C14175.73 (18)C13—C12—O2—C1564.7 (2)
C12—C13—C14—C90.5 (3)C11—C12—O2—C15119.5 (2)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
O4—H42···O3i0.822.072.810 (2)150
O4—H41···O3ii0.822.182.988 (2)168
N4—H4···O1iii0.862.463.080 (2)129
N1—H1···O40.862.052.880 (2)161
N2—H2A···O40.862.233.021 (2)153
Symmetry codes: (i) x+1, y+1, z+1; (ii) x+2, y+1, z+1; (iii) x, y+1/2, z1/2.
 

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