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Regorafenib {systematic name: 4-[4-({[4-chloro-3-(trifluoromethy)phenyl]carbamoyl}amino)-3-fluorophenoxy]-1-methylpyridine-2-carboxamide}, C
21H
15ClF
4N
4O
3, 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, C
21H
15ClF
4N
4O
3·H
2O. 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
CCDC references: 1045583; 1045581
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
C21H15ClF4N4O3 | F(000) = 984 |
Mr = 482.82 | Dx = 1.508 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2ybc | Cell parameters from 10707 reflections |
a = 7.6972 (4) Å | θ = 3.0–27.5° |
b = 24.3703 (12) Å | µ = 0.25 mm−1 |
c = 11.3580 (7) Å | T = 296 K |
β = 93.545 (2)° | Platelet, colorless |
V = 2126.5 (2) Å3 | 0.49 × 0.39 × 0.13 mm |
Z = 4 | |
Data collection top
Rigaku R-AXIS RAPID/ZJUG diffractometer | 3738 independent reflections |
Radiation source: rotating anode | 2311 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.051 |
Detector resolution: 10.00 pixels mm-1 | θmax = 25.0°, θmin = 3.1° |
ω scans | h = −9→9 |
Absorption correction: multi-scan (ABSCOR; Higashi, 1995) | k = −28→28 |
Tmin = 0.879, Tmax = 0.969 | l = −13→13 |
16556 measured reflections | |
Refinement top
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.048 | H-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 reflections | Δρmax = 0.29 e Å−3 |
300 parameters | Δρmin = −0.35 e Å−3 |
0 restraints | Extinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction 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 | x | y | z | Uiso*/Ueq | |
C1 | 0.1725 (4) | 0.72715 (13) | 0.5281 (3) | 0.0464 (8) | |
C2 | 0.1757 (4) | 0.77854 (12) | 0.5813 (3) | 0.0478 (8) | |
H2 | 0.2250 | 0.7821 | 0.6577 | 0.057* | |
C3 | 0.1076 (4) | 0.82442 (13) | 0.5236 (3) | 0.0479 (8) | |
C4 | 0.0367 (4) | 0.81959 (13) | 0.4082 (3) | 0.0500 (8) | |
C5 | 0.0327 (5) | 0.76842 (14) | 0.3559 (3) | 0.0559 (9) | |
H5 | −0.0146 | 0.7650 | 0.2789 | 0.067* | |
C6 | 0.0965 (4) | 0.72215 (13) | 0.4142 (3) | 0.0526 (9) | |
H6 | 0.0888 | 0.6880 | 0.3776 | 0.063* | |
C7 | 0.1012 (5) | 0.87705 (15) | 0.5909 (4) | 0.0621 (10) | |
C8 | 0.2354 (4) | 0.62834 (13) | 0.5659 (3) | 0.0502 (8) | |
C9 | 0.3390 (4) | 0.53934 (12) | 0.6434 (3) | 0.0480 (8) | |
C10 | 0.4959 (4) | 0.51292 (13) | 0.6646 (3) | 0.0535 (9) | |
C11 | 0.5121 (5) | 0.45734 (14) | 0.6781 (3) | 0.0568 (9) | |
H11 | 0.6205 | 0.4409 | 0.6917 | 0.068* | |
C12 | 0.3624 (5) | 0.42683 (13) | 0.6707 (3) | 0.0557 (10) | |
C13 | 0.2018 (5) | 0.45053 (14) | 0.6465 (3) | 0.0626 (10) | |
H13 | 0.1019 | 0.4290 | 0.6394 | 0.075* | |
C14 | 0.1916 (5) | 0.50704 (13) | 0.6328 (3) | 0.0583 (9) | |
H14 | 0.0837 | 0.5234 | 0.6163 | 0.070* | |
C15 | 0.3663 (5) | 0.33260 (12) | 0.6101 (3) | 0.0494 (8) | |
C16 | 0.3099 (5) | 0.34309 (13) | 0.4950 (3) | 0.0532 (9) | |
H16 | 0.2773 | 0.3783 | 0.4707 | 0.064* | |
C17 | 0.3033 (5) | 0.29997 (14) | 0.4174 (3) | 0.0577 (9) | |
H17 | 0.2639 | 0.3072 | 0.3399 | 0.069* | |
C18 | 0.4042 (4) | 0.23938 (12) | 0.5568 (3) | 0.0437 (8) | |
C19 | 0.4145 (4) | 0.27964 (13) | 0.6419 (3) | 0.0478 (8) | |
H19 | 0.4530 | 0.2715 | 0.7191 | 0.057* | |
C20 | 0.4530 (4) | 0.18162 (13) | 0.5882 (3) | 0.0488 (8) | |
C21 | 0.4420 (6) | 0.08557 (14) | 0.5253 (4) | 0.0761 (12) | |
H21A | 0.5504 | 0.0791 | 0.5697 | 0.114* | |
H21B | 0.4430 | 0.0672 | 0.4506 | 0.114* | |
H21C | 0.3480 | 0.0717 | 0.5684 | 0.114* | |
Cl1 | −0.04400 (14) | 0.87514 (4) | 0.32732 (9) | 0.0708 (4) | |
F1 | 0.1663 (4) | 0.91993 (9) | 0.5372 (3) | 0.1068 (10) | |
F2 | 0.1880 (4) | 0.87469 (9) | 0.6945 (2) | 0.1096 (11) | |
F3 | −0.0588 (4) | 0.89191 (12) | 0.6106 (3) | 0.1110 (11) | |
F4 | 0.6431 (3) | 0.54431 (9) | 0.6759 (2) | 0.0844 (8) | |
N1 | 0.2461 (4) | 0.68325 (10) | 0.5930 (2) | 0.0534 (8) | |
H1 | 0.3048 | 0.6916 | 0.6574 | 0.064* | |
N2 | 0.3362 (4) | 0.59694 (10) | 0.6409 (3) | 0.0569 (8) | |
H2A | 0.4046 | 0.6138 | 0.6915 | 0.068* | |
N3 | 0.3490 (4) | 0.24839 (11) | 0.4441 (2) | 0.0535 (7) | |
N4 | 0.4190 (4) | 0.14425 (11) | 0.5061 (3) | 0.0573 (8) | |
H4 | 0.3811 | 0.1552 | 0.4372 | 0.069* | |
O1 | 0.1457 (4) | 0.60980 (9) | 0.4827 (2) | 0.0730 (8) | |
O2 | 0.3784 (4) | 0.37076 (9) | 0.6987 (2) | 0.0700 (8) | |
O3 | 0.5190 (4) | 0.17076 (9) | 0.6882 (2) | 0.0654 (7) | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
C1 | 0.0463 (18) | 0.0434 (18) | 0.048 (2) | −0.0009 (14) | −0.0054 (15) | 0.0005 (15) |
C2 | 0.0523 (19) | 0.0450 (18) | 0.045 (2) | −0.0004 (15) | −0.0089 (15) | 0.0016 (15) |
C3 | 0.0467 (18) | 0.0421 (17) | 0.054 (2) | −0.0015 (15) | −0.0018 (16) | −0.0048 (15) |
C4 | 0.0525 (19) | 0.0489 (19) | 0.048 (2) | 0.0047 (16) | −0.0021 (16) | 0.0044 (15) |
C5 | 0.065 (2) | 0.059 (2) | 0.042 (2) | 0.0091 (18) | −0.0067 (17) | 0.0008 (16) |
C6 | 0.062 (2) | 0.0441 (18) | 0.050 (2) | 0.0019 (16) | −0.0061 (17) | −0.0060 (15) |
C7 | 0.064 (2) | 0.051 (2) | 0.070 (3) | −0.0005 (19) | −0.013 (2) | −0.0019 (19) |
C8 | 0.057 (2) | 0.0422 (18) | 0.050 (2) | −0.0022 (16) | −0.0080 (17) | −0.0020 (15) |
C9 | 0.058 (2) | 0.0349 (16) | 0.050 (2) | −0.0021 (15) | −0.0058 (16) | −0.0022 (14) |
C10 | 0.056 (2) | 0.0426 (18) | 0.061 (2) | −0.0097 (16) | −0.0058 (17) | 0.0040 (16) |
C11 | 0.067 (2) | 0.0442 (19) | 0.058 (2) | 0.0053 (18) | −0.0082 (18) | 0.0027 (16) |
C12 | 0.089 (3) | 0.0343 (17) | 0.042 (2) | −0.0062 (18) | −0.0103 (19) | −0.0006 (14) |
C13 | 0.072 (2) | 0.047 (2) | 0.067 (3) | −0.0154 (18) | −0.012 (2) | 0.0034 (18) |
C14 | 0.060 (2) | 0.0459 (19) | 0.067 (2) | −0.0056 (17) | −0.0086 (18) | −0.0002 (17) |
C15 | 0.065 (2) | 0.0387 (17) | 0.043 (2) | −0.0048 (15) | −0.0068 (16) | 0.0010 (14) |
C16 | 0.071 (2) | 0.0412 (18) | 0.047 (2) | −0.0009 (16) | −0.0062 (17) | 0.0096 (15) |
C17 | 0.077 (2) | 0.055 (2) | 0.039 (2) | 0.0018 (19) | −0.0080 (17) | 0.0047 (16) |
C18 | 0.0469 (18) | 0.0447 (17) | 0.0389 (19) | −0.0029 (14) | −0.0035 (14) | 0.0050 (14) |
C19 | 0.060 (2) | 0.0451 (18) | 0.0373 (18) | −0.0079 (16) | −0.0063 (15) | 0.0041 (14) |
C20 | 0.0516 (19) | 0.0445 (18) | 0.049 (2) | 0.0039 (15) | −0.0046 (16) | 0.0033 (16) |
C21 | 0.092 (3) | 0.046 (2) | 0.090 (3) | 0.011 (2) | 0.005 (2) | −0.007 (2) |
Cl1 | 0.0917 (8) | 0.0579 (6) | 0.0616 (6) | 0.0171 (5) | −0.0061 (5) | 0.0108 (5) |
F1 | 0.149 (3) | 0.0457 (13) | 0.126 (2) | −0.0188 (15) | 0.0107 (19) | 0.0017 (14) |
F2 | 0.167 (3) | 0.0591 (14) | 0.094 (2) | 0.0092 (15) | −0.0652 (19) | −0.0231 (13) |
F3 | 0.0850 (19) | 0.112 (2) | 0.136 (3) | 0.0117 (16) | 0.0082 (17) | −0.0691 (19) |
F4 | 0.0649 (14) | 0.0612 (13) | 0.124 (2) | −0.0101 (11) | −0.0187 (13) | 0.0195 (13) |
N1 | 0.0669 (19) | 0.0383 (15) | 0.0521 (18) | 0.0016 (13) | −0.0197 (14) | −0.0006 (12) |
N2 | 0.0671 (19) | 0.0347 (14) | 0.065 (2) | −0.0002 (13) | −0.0241 (16) | −0.0005 (13) |
N3 | 0.0684 (19) | 0.0492 (16) | 0.0417 (17) | 0.0026 (14) | −0.0081 (14) | 0.0012 (13) |
N4 | 0.077 (2) | 0.0413 (15) | 0.0520 (19) | 0.0021 (14) | −0.0058 (15) | −0.0033 (13) |
O1 | 0.093 (2) | 0.0476 (14) | 0.0733 (19) | −0.0051 (13) | −0.0369 (16) | −0.0029 (13) |
O2 | 0.126 (2) | 0.0345 (12) | 0.0469 (15) | −0.0066 (13) | −0.0187 (15) | 0.0024 (10) |
O3 | 0.0899 (19) | 0.0463 (13) | 0.0568 (17) | 0.0035 (13) | −0.0216 (14) | 0.0036 (12) |
Geometric parameters (Å, º) top
C1—C2 | 1.390 (4) | C12—C13 | 1.377 (5) |
C1—C6 | 1.391 (4) | C12—O2 | 1.407 (4) |
C1—N1 | 1.399 (4) | C13—C14 | 1.387 (5) |
C2—C3 | 1.383 (4) | C13—H13 | 0.9300 |
C2—H2 | 0.9300 | C14—H14 | 0.9300 |
C3—C4 | 1.393 (5) | C15—O2 | 1.370 (4) |
C3—C7 | 1.496 (5) | C15—C16 | 1.376 (4) |
C4—C5 | 1.381 (5) | C15—C19 | 1.384 (4) |
C4—Cl1 | 1.730 (3) | C16—C17 | 1.371 (5) |
C5—C6 | 1.382 (5) | C16—H16 | 0.9300 |
C5—H5 | 0.9300 | C17—N3 | 1.335 (4) |
C6—H6 | 0.9300 | C17—H17 | 0.9300 |
C7—F3 | 1.316 (4) | C18—N3 | 1.341 (4) |
C7—F2 | 1.317 (4) | C18—C19 | 1.376 (4) |
C7—F1 | 1.324 (4) | C18—C20 | 1.495 (4) |
C8—O1 | 1.222 (4) | C19—H19 | 0.9300 |
C8—N2 | 1.353 (4) | C20—O3 | 1.244 (4) |
C8—N1 | 1.375 (4) | C20—N4 | 1.318 (4) |
C9—C10 | 1.377 (5) | C21—N4 | 1.456 (4) |
C9—C14 | 1.380 (5) | C21—H21A | 0.9600 |
C9—N2 | 1.404 (4) | C21—H21B | 0.9600 |
C10—F4 | 1.366 (4) | C21—H21C | 0.9600 |
C10—C11 | 1.368 (5) | N1—H1 | 0.8600 |
C11—C12 | 1.370 (5) | N2—H2A | 0.8600 |
C11—H11 | 0.9300 | N4—H4 | 0.8600 |
| | | |
C2—C1—C6 | 118.6 (3) | C12—C13—H13 | 120.6 |
C2—C1—N1 | 117.6 (3) | C14—C13—H13 | 120.6 |
C6—C1—N1 | 123.8 (3) | C9—C14—C13 | 121.0 (3) |
C3—C2—C1 | 121.8 (3) | C9—C14—H14 | 119.5 |
C3—C2—H2 | 119.1 | C13—C14—H14 | 119.5 |
C1—C2—H2 | 119.1 | O2—C15—C16 | 125.1 (3) |
C2—C3—C4 | 119.5 (3) | O2—C15—C19 | 115.9 (3) |
C2—C3—C7 | 118.3 (3) | C16—C15—C19 | 119.0 (3) |
C4—C3—C7 | 122.0 (3) | C17—C16—C15 | 117.7 (3) |
C5—C4—C3 | 118.6 (3) | C17—C16—H16 | 121.1 |
C5—C4—Cl1 | 118.7 (3) | C15—C16—H16 | 121.1 |
C3—C4—Cl1 | 122.7 (3) | N3—C17—C16 | 125.2 (3) |
C4—C5—C6 | 122.2 (3) | N3—C17—H17 | 117.4 |
C4—C5—H5 | 118.9 | C16—C17—H17 | 117.4 |
C6—C5—H5 | 118.9 | N3—C18—C19 | 123.7 (3) |
C5—C6—C1 | 119.4 (3) | N3—C18—C20 | 116.2 (3) |
C5—C6—H6 | 120.3 | C19—C18—C20 | 120.1 (3) |
C1—C6—H6 | 120.3 | C18—C19—C15 | 118.6 (3) |
F3—C7—F2 | 106.8 (4) | C18—C19—H19 | 120.7 |
F3—C7—F1 | 104.2 (3) | C15—C19—H19 | 120.7 |
F2—C7—F1 | 105.1 (3) | O3—C20—N4 | 123.5 (3) |
F3—C7—C3 | 112.5 (3) | O3—C20—C18 | 120.1 (3) |
F2—C7—C3 | 112.9 (3) | N4—C20—C18 | 116.5 (3) |
F1—C7—C3 | 114.6 (3) | N4—C21—H21A | 109.5 |
O1—C8—N2 | 123.5 (3) | N4—C21—H21B | 109.5 |
O1—C8—N1 | 123.8 (3) | H21A—C21—H21B | 109.5 |
N2—C8—N1 | 112.7 (3) | N4—C21—H21C | 109.5 |
C10—C9—C14 | 117.1 (3) | H21A—C21—H21C | 109.5 |
C10—C9—N2 | 118.9 (3) | H21B—C21—H21C | 109.5 |
C14—C9—N2 | 123.8 (3) | C8—N1—C1 | 127.6 (3) |
F4—C10—C11 | 118.3 (3) | C8—N1—H1 | 116.2 |
F4—C10—C9 | 117.9 (3) | C1—N1—H1 | 116.2 |
C11—C10—C9 | 123.7 (3) | C8—N2—C9 | 125.9 (3) |
C10—C11—C12 | 117.4 (3) | C8—N2—H2A | 117.1 |
C10—C11—H11 | 121.3 | C9—N2—H2A | 117.1 |
C12—C11—H11 | 121.3 | C17—N3—C18 | 115.8 (3) |
C11—C12—C13 | 121.7 (3) | C20—N4—C21 | 123.7 (3) |
C11—C12—O2 | 116.9 (3) | C20—N4—H4 | 118.1 |
C13—C12—O2 | 121.2 (3) | C21—N4—H4 | 118.1 |
C12—C13—C14 | 118.9 (3) | C15—O2—C12 | 119.5 (3) |
| | | |
C6—C1—C2—C3 | −0.8 (5) | N2—C9—C14—C13 | −174.2 (3) |
N1—C1—C2—C3 | 179.4 (3) | C12—C13—C14—C9 | −0.2 (6) |
C1—C2—C3—C4 | −1.3 (5) | O2—C15—C16—C17 | −179.1 (4) |
C1—C2—C3—C7 | 174.4 (3) | C19—C15—C16—C17 | 0.4 (5) |
C2—C3—C4—C5 | 1.7 (5) | C15—C16—C17—N3 | −0.7 (6) |
C7—C3—C4—C5 | −173.8 (3) | N3—C18—C19—C15 | −0.4 (5) |
C2—C3—C4—Cl1 | −177.6 (3) | C20—C18—C19—C15 | −179.2 (3) |
C7—C3—C4—Cl1 | 6.9 (5) | O2—C15—C19—C18 | 179.6 (3) |
C3—C4—C5—C6 | −0.1 (5) | C16—C15—C19—C18 | 0.1 (5) |
Cl1—C4—C5—C6 | 179.2 (3) | N3—C18—C20—O3 | 174.0 (3) |
C4—C5—C6—C1 | −2.0 (6) | C19—C18—C20—O3 | −7.0 (5) |
C2—C1—C6—C5 | 2.4 (5) | N3—C18—C20—N4 | −7.3 (4) |
N1—C1—C6—C5 | −177.8 (3) | C19—C18—C20—N4 | 171.7 (3) |
C2—C3—C7—F3 | −111.0 (4) | O1—C8—N1—C1 | −6.0 (6) |
C4—C3—C7—F3 | 64.6 (5) | N2—C8—N1—C1 | 173.6 (3) |
C2—C3—C7—F2 | 9.9 (5) | C2—C1—N1—C8 | 169.7 (3) |
C4—C3—C7—F2 | −174.5 (3) | C6—C1—N1—C8 | −10.1 (6) |
C2—C3—C7—F1 | 130.2 (4) | O1—C8—N2—C9 | −7.5 (6) |
C4—C3—C7—F1 | −54.3 (5) | N1—C8—N2—C9 | 173.0 (3) |
C14—C9—C10—F4 | −179.7 (3) | C10—C9—N2—C8 | 141.3 (4) |
N2—C9—C10—F4 | −3.4 (5) | C14—C9—N2—C8 | −42.7 (6) |
C14—C9—C10—C11 | −1.6 (6) | C16—C17—N3—C18 | 0.4 (5) |
N2—C9—C10—C11 | 174.7 (3) | C19—C18—N3—C17 | 0.1 (5) |
F4—C10—C11—C12 | 177.6 (3) | C20—C18—N3—C17 | 179.1 (3) |
C9—C10—C11—C12 | −0.5 (6) | O3—C20—N4—C21 | 4.9 (6) |
C10—C11—C12—C13 | 2.3 (5) | C18—C20—N4—C21 | −173.8 (3) |
C10—C11—C12—O2 | −172.5 (3) | C16—C15—O2—C12 | −11.8 (5) |
C11—C12—C13—C14 | −2.0 (6) | C19—C15—O2—C12 | 168.7 (3) |
O2—C12—C13—C14 | 172.6 (3) | C11—C12—O2—C15 | −105.6 (4) |
C10—C9—C14—C13 | 1.9 (6) | C13—C12—O2—C15 | 79.5 (5) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N1—H1···O3i | 0.86 | 2.21 | 2.997 (4) | 152 |
N2—H2A···O3i | 0.86 | 2.01 | 2.825 (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·H2O | F(000) = 1024 |
Mr = 500.84 | Dx = 1.544 Mg m−3 |
Monoclinic, P21/c | Mo Kα radiation, λ = 0.71073 Å |
Hall symbol: -P 2ybc | Cell parameters from 13751 reflections |
a = 4.7783 (2) Å | θ = 3.1–27.4° |
b = 21.9538 (9) Å | µ = 0.25 mm−1 |
c = 20.5581 (8) Å | T = 296 K |
β = 92.341 (1)° | Platelet, colorless |
V = 2154.78 (15) Å3 | 0.48 × 0.38 × 0.16 mm |
Z = 4 | |
Data collection top
Rigaku R-AXIS RAPID/ZJUG diffractometer | 4903 independent reflections |
Radiation source: rotating anode | 3197 reflections with I > 2σ(I) |
Graphite monochromator | Rint = 0.045 |
Detector resolution: 10.00 pixels mm-1 | θmax = 27.5°, θmin = 3.1° |
ω scans | h = −5→6 |
Absorption correction: multi-scan (ABSCOR; Higashi, 1995) | k = −28→28 |
Tmin = 0.890, Tmax = 0.961 | l = −26→26 |
20501 measured reflections | |
Refinement top
Refinement on F2 | Secondary atom site location: difference Fourier map |
Least-squares matrix: full | Hydrogen site location: inferred from neighbouring sites |
R[F2 > 2σ(F2)] = 0.042 | H-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 reflections | Δρmax = 0.23 e Å−3 |
309 parameters | Δρmin = −0.31 e Å−3 |
0 restraints | Extinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4 |
Primary atom site location: structure-invariant direct methods | Extinction 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 | x | y | z | Uiso*/Ueq | |
C1 | 0.3084 (4) | 0.50642 (9) | 0.78416 (9) | 0.0365 (4) | |
C2 | 0.2383 (4) | 0.56444 (9) | 0.80461 (9) | 0.0396 (4) | |
H2 | 0.3179 | 0.5980 | 0.7849 | 0.048* | |
C3 | 0.0523 (4) | 0.57359 (9) | 0.85373 (9) | 0.0399 (5) | |
C4 | −0.0680 (4) | 0.52315 (10) | 0.88298 (9) | 0.0431 (5) | |
C5 | −0.0057 (4) | 0.46555 (10) | 0.86138 (10) | 0.0467 (5) | |
H5 | −0.0906 | 0.4321 | 0.8800 | 0.056* | |
C6 | 0.1811 (4) | 0.45644 (10) | 0.81244 (10) | 0.0449 (5) | |
H6 | 0.2211 | 0.4172 | 0.7986 | 0.054* | |
C7 | −0.0075 (5) | 0.63711 (11) | 0.87514 (12) | 0.0528 (6) | |
C8 | 0.6276 (4) | 0.45096 (9) | 0.71187 (9) | 0.0384 (4) | |
C9 | 0.9572 (4) | 0.42249 (9) | 0.62695 (9) | 0.0380 (4) | |
C10 | 1.1447 (5) | 0.44482 (10) | 0.58269 (10) | 0.0464 (5) | |
C11 | 1.3031 (5) | 0.40850 (11) | 0.54408 (10) | 0.0497 (5) | |
H11 | 1.4264 | 0.4253 | 0.5151 | 0.060* | |
C12 | 1.2726 (4) | 0.34615 (10) | 0.54983 (9) | 0.0428 (5) | |
C13 | 1.0902 (5) | 0.32204 (10) | 0.59238 (11) | 0.0490 (5) | |
H13 | 1.0718 | 0.2800 | 0.5957 | 0.059* | |
C14 | 0.9328 (5) | 0.35968 (10) | 0.63054 (10) | 0.0480 (5) | |
H14 | 0.8086 | 0.3426 | 0.6590 | 0.058* | |
C15 | 1.3094 (4) | 0.26889 (9) | 0.47089 (9) | 0.0384 (4) | |
C16 | 1.4089 (4) | 0.21037 (10) | 0.46580 (10) | 0.0451 (5) | |
H16 | 1.5580 | 0.1968 | 0.4924 | 0.054* | |
C17 | 1.2815 (5) | 0.17248 (10) | 0.42016 (10) | 0.0494 (5) | |
H17 | 1.3448 | 0.1325 | 0.4180 | 0.059* | |
C18 | 0.9847 (4) | 0.24709 (9) | 0.38363 (9) | 0.0356 (4) | |
C19 | 1.0900 (4) | 0.28804 (9) | 0.42978 (9) | 0.0384 (4) | |
H19 | 1.0158 | 0.3270 | 0.4330 | 0.046* | |
C20 | 0.7640 (4) | 0.26877 (9) | 0.33469 (9) | 0.0379 (4) | |
C21 | 0.4359 (5) | 0.24031 (11) | 0.24568 (10) | 0.0506 (5) | |
H21A | 0.3351 | 0.2762 | 0.2576 | 0.076* | |
H21B | 0.3088 | 0.2065 | 0.2415 | 0.076* | |
H21C | 0.5218 | 0.2471 | 0.2049 | 0.076* | |
Cl1 | −0.29708 (13) | 0.53054 (3) | 0.94589 (3) | 0.0634 (2) | |
F1 | −0.2793 (3) | 0.65122 (7) | 0.87287 (8) | 0.0683 (4) | |
F2 | 0.1154 (4) | 0.67905 (7) | 0.83876 (9) | 0.0874 (6) | |
F3 | 0.0824 (3) | 0.64786 (8) | 0.93637 (8) | 0.0883 (6) | |
F4 | 1.1708 (3) | 0.50629 (6) | 0.57779 (7) | 0.0740 (5) | |
N1 | 0.5009 (4) | 0.50228 (8) | 0.73467 (8) | 0.0429 (4) | |
H1 | 0.5447 | 0.5360 | 0.7164 | 0.051* | |
N2 | 0.8044 (4) | 0.46440 (8) | 0.66270 (8) | 0.0422 (4) | |
H2A | 0.8229 | 0.5022 | 0.6529 | 0.051* | |
N3 | 1.0727 (4) | 0.18938 (8) | 0.37872 (8) | 0.0435 (4) | |
N4 | 0.6509 (3) | 0.22688 (8) | 0.29560 (8) | 0.0426 (4) | |
H4 | 0.7074 | 0.1899 | 0.3000 | 0.051* | |
O1 | 0.5883 (3) | 0.39990 (7) | 0.73256 (7) | 0.0514 (4) | |
O2 | 1.4446 (3) | 0.30739 (7) | 0.51463 (7) | 0.0533 (4) | |
O3 | 0.7020 (3) | 0.32373 (6) | 0.33169 (7) | 0.0501 (4) | |
O4 | 0.7761 (4) | 0.60161 (7) | 0.67180 (9) | 0.0682 (5) | |
H41 | 0.9210 | 0.6212 | 0.6771 | 0.102* | |
H42 | 0.6563 | 0.6250 | 0.6570 | 0.102* | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
C1 | 0.0385 (10) | 0.0353 (10) | 0.0355 (9) | 0.0003 (8) | −0.0005 (8) | −0.0002 (8) |
C2 | 0.0391 (10) | 0.0357 (10) | 0.0440 (10) | −0.0038 (9) | 0.0013 (9) | 0.0018 (8) |
C3 | 0.0347 (10) | 0.0429 (11) | 0.0419 (10) | 0.0011 (9) | −0.0023 (8) | −0.0041 (9) |
C4 | 0.0356 (10) | 0.0556 (13) | 0.0382 (10) | 0.0042 (10) | 0.0021 (8) | 0.0074 (9) |
C5 | 0.0474 (12) | 0.0410 (12) | 0.0522 (12) | −0.0008 (10) | 0.0074 (10) | 0.0100 (9) |
C6 | 0.0499 (12) | 0.0354 (11) | 0.0495 (11) | 0.0011 (9) | 0.0044 (10) | 0.0035 (9) |
C7 | 0.0392 (11) | 0.0526 (14) | 0.0667 (14) | −0.0015 (10) | 0.0048 (11) | −0.0134 (12) |
C8 | 0.0434 (11) | 0.0340 (10) | 0.0375 (10) | −0.0003 (9) | −0.0008 (8) | −0.0032 (8) |
C9 | 0.0410 (10) | 0.0376 (11) | 0.0351 (9) | 0.0009 (9) | −0.0017 (8) | −0.0030 (8) |
C10 | 0.0539 (12) | 0.0394 (12) | 0.0462 (11) | −0.0014 (10) | 0.0055 (10) | 0.0012 (9) |
C11 | 0.0497 (13) | 0.0540 (14) | 0.0459 (11) | −0.0023 (11) | 0.0098 (10) | −0.0019 (10) |
C12 | 0.0385 (10) | 0.0503 (13) | 0.0390 (10) | 0.0062 (9) | −0.0046 (9) | −0.0120 (9) |
C13 | 0.0581 (13) | 0.0369 (11) | 0.0523 (12) | 0.0003 (10) | 0.0040 (11) | −0.0077 (9) |
C14 | 0.0562 (13) | 0.0395 (12) | 0.0492 (12) | −0.0031 (10) | 0.0115 (10) | −0.0033 (9) |
C15 | 0.0340 (10) | 0.0460 (12) | 0.0355 (9) | −0.0024 (9) | 0.0047 (8) | −0.0054 (8) |
C16 | 0.0436 (11) | 0.0482 (12) | 0.0435 (11) | 0.0085 (10) | −0.0001 (9) | 0.0025 (9) |
C17 | 0.0558 (13) | 0.0375 (11) | 0.0545 (12) | 0.0083 (10) | −0.0019 (11) | 0.0004 (10) |
C18 | 0.0371 (10) | 0.0329 (10) | 0.0372 (9) | −0.0008 (8) | 0.0061 (8) | 0.0013 (8) |
C19 | 0.0383 (10) | 0.0361 (10) | 0.0412 (10) | 0.0020 (8) | 0.0064 (8) | −0.0033 (8) |
C20 | 0.0361 (10) | 0.0371 (11) | 0.0409 (10) | −0.0014 (9) | 0.0047 (8) | −0.0002 (8) |
C21 | 0.0482 (12) | 0.0573 (14) | 0.0456 (11) | −0.0010 (11) | −0.0077 (10) | −0.0001 (10) |
Cl1 | 0.0567 (4) | 0.0824 (5) | 0.0525 (3) | 0.0105 (3) | 0.0181 (3) | 0.0094 (3) |
F1 | 0.0450 (7) | 0.0585 (9) | 0.1017 (11) | 0.0110 (6) | 0.0062 (7) | −0.0105 (8) |
F2 | 0.0861 (11) | 0.0408 (8) | 0.1391 (15) | −0.0050 (8) | 0.0526 (11) | −0.0124 (9) |
F3 | 0.0791 (11) | 0.0966 (13) | 0.0876 (11) | 0.0064 (9) | −0.0146 (9) | −0.0525 (10) |
F4 | 0.0999 (12) | 0.0393 (8) | 0.0856 (10) | −0.0040 (7) | 0.0408 (9) | 0.0048 (7) |
N1 | 0.0529 (10) | 0.0309 (9) | 0.0456 (9) | 0.0005 (8) | 0.0126 (8) | 0.0010 (7) |
N2 | 0.0516 (10) | 0.0329 (9) | 0.0427 (9) | 0.0002 (8) | 0.0080 (8) | −0.0004 (7) |
N3 | 0.0495 (10) | 0.0340 (9) | 0.0468 (9) | 0.0029 (8) | −0.0001 (8) | −0.0014 (7) |
N4 | 0.0449 (9) | 0.0378 (9) | 0.0445 (9) | 0.0007 (8) | −0.0047 (8) | −0.0006 (7) |
O1 | 0.0670 (10) | 0.0330 (8) | 0.0553 (9) | −0.0003 (7) | 0.0170 (8) | 0.0012 (7) |
O2 | 0.0392 (8) | 0.0650 (10) | 0.0553 (9) | 0.0063 (7) | −0.0037 (7) | −0.0239 (8) |
O3 | 0.0497 (8) | 0.0360 (8) | 0.0637 (9) | 0.0048 (7) | −0.0087 (7) | −0.0023 (7) |
O4 | 0.0555 (10) | 0.0393 (9) | 0.1097 (14) | 0.0004 (8) | 0.0043 (10) | 0.0222 (9) |
Geometric parameters (Å, º) top
C1—C2 | 1.387 (3) | C12—O2 | 1.404 (2) |
C1—C6 | 1.393 (3) | C13—C14 | 1.383 (3) |
C1—N1 | 1.402 (3) | C13—H13 | 0.9300 |
C2—C3 | 1.387 (3) | C14—H14 | 0.9300 |
C2—H2 | 0.9300 | C15—C16 | 1.375 (3) |
C3—C4 | 1.395 (3) | C15—O2 | 1.376 (2) |
C3—C7 | 1.494 (3) | C15—C19 | 1.385 (3) |
C4—C5 | 1.377 (3) | C16—C17 | 1.377 (3) |
C4—Cl1 | 1.736 (2) | C16—H16 | 0.9300 |
C5—C6 | 1.386 (3) | C17—N3 | 1.338 (3) |
C5—H5 | 0.9300 | C17—H17 | 0.9300 |
C6—H6 | 0.9300 | C18—N3 | 1.340 (2) |
C7—F1 | 1.334 (2) | C18—C19 | 1.386 (3) |
C7—F3 | 1.334 (3) | C18—C20 | 1.505 (3) |
C7—F2 | 1.337 (3) | C19—H19 | 0.9300 |
C8—O1 | 1.216 (2) | C20—O3 | 1.243 (2) |
C8—N1 | 1.371 (2) | C20—N4 | 1.322 (2) |
C8—N2 | 1.375 (3) | C21—N4 | 1.452 (3) |
C9—C14 | 1.386 (3) | C21—H21A | 0.9600 |
C9—C10 | 1.392 (3) | C21—H21B | 0.9600 |
C9—N2 | 1.401 (3) | C21—H21C | 0.9600 |
C10—F4 | 1.359 (2) | N1—H1 | 0.8600 |
C10—C11 | 1.374 (3) | N2—H2A | 0.8600 |
C11—C12 | 1.382 (3) | N4—H4 | 0.8600 |
C11—H11 | 0.9300 | O4—H41 | 0.8191 |
C12—C13 | 1.366 (3) | O4—H42 | 0.8189 |
| | | |
C2—C1—C6 | 118.80 (19) | C14—C13—H13 | 119.7 |
C2—C1—N1 | 116.96 (17) | C13—C14—C9 | 121.0 (2) |
C6—C1—N1 | 124.23 (18) | C13—C14—H14 | 119.5 |
C3—C2—C1 | 121.58 (19) | C9—C14—H14 | 119.5 |
C3—C2—H2 | 119.2 | C16—C15—O2 | 117.97 (17) |
C1—C2—H2 | 119.2 | C16—C15—C19 | 119.51 (18) |
C2—C3—C4 | 119.11 (19) | O2—C15—C19 | 122.42 (18) |
C2—C3—C7 | 119.06 (19) | C15—C16—C17 | 118.13 (19) |
C4—C3—C7 | 121.81 (19) | C15—C16—H16 | 120.9 |
C5—C4—C3 | 119.45 (19) | C17—C16—H16 | 120.9 |
C5—C4—Cl1 | 118.51 (17) | N3—C17—C16 | 124.3 (2) |
C3—C4—Cl1 | 122.03 (17) | N3—C17—H17 | 117.8 |
C4—C5—C6 | 121.4 (2) | C16—C17—H17 | 117.8 |
C4—C5—H5 | 119.3 | N3—C18—C19 | 123.94 (18) |
C6—C5—H5 | 119.3 | N3—C18—C20 | 117.53 (16) |
C5—C6—C1 | 119.6 (2) | C19—C18—C20 | 118.51 (17) |
C5—C6—H6 | 120.2 | C15—C19—C18 | 117.74 (18) |
C1—C6—H6 | 120.2 | C15—C19—H19 | 121.1 |
F1—C7—F3 | 105.52 (19) | C18—C19—H19 | 121.1 |
F1—C7—F2 | 105.6 (2) | O3—C20—N4 | 123.65 (18) |
F3—C7—F2 | 105.91 (19) | O3—C20—C18 | 119.95 (17) |
F1—C7—C3 | 113.84 (18) | N4—C20—C18 | 116.38 (17) |
F3—C7—C3 | 112.6 (2) | N4—C21—H21A | 109.5 |
F2—C7—C3 | 112.60 (19) | N4—C21—H21B | 109.5 |
O1—C8—N1 | 124.14 (19) | H21A—C21—H21B | 109.5 |
O1—C8—N2 | 124.27 (18) | N4—C21—H21C | 109.5 |
N1—C8—N2 | 111.60 (17) | H21A—C21—H21C | 109.5 |
C14—C9—C10 | 116.30 (19) | H21B—C21—H21C | 109.5 |
C14—C9—N2 | 125.33 (19) | C8—N1—C1 | 127.84 (17) |
C10—C9—N2 | 118.35 (18) | C8—N1—H1 | 116.1 |
F4—C10—C11 | 118.6 (2) | C1—N1—H1 | 116.1 |
F4—C10—C9 | 117.50 (19) | C8—N2—C9 | 126.40 (17) |
C11—C10—C9 | 123.9 (2) | C8—N2—H2A | 116.8 |
C10—C11—C12 | 117.6 (2) | C9—N2—H2A | 116.8 |
C10—C11—H11 | 121.2 | C17—N3—C18 | 116.26 (17) |
C12—C11—H11 | 121.2 | C20—N4—C21 | 123.23 (18) |
C13—C12—C11 | 120.7 (2) | C20—N4—H4 | 118.4 |
C13—C12—O2 | 119.8 (2) | C21—N4—H4 | 118.4 |
C11—C12—O2 | 119.3 (2) | C15—O2—C12 | 116.10 (15) |
C12—C13—C14 | 120.5 (2) | H41—O4—H42 | 107.0 |
C12—C13—H13 | 119.7 | | |
| | | |
C6—C1—C2—C3 | 2.1 (3) | C10—C9—C14—C13 | 0.7 (3) |
N1—C1—C2—C3 | −179.30 (17) | N2—C9—C14—C13 | 178.94 (19) |
C1—C2—C3—C4 | −0.3 (3) | O2—C15—C16—C17 | −177.33 (19) |
C1—C2—C3—C7 | 177.96 (18) | C19—C15—C16—C17 | −1.1 (3) |
C2—C3—C4—C5 | −1.7 (3) | C15—C16—C17—N3 | 2.4 (3) |
C7—C3—C4—C5 | −179.96 (19) | C16—C15—C19—C18 | −1.7 (3) |
C2—C3—C4—Cl1 | 178.65 (14) | O2—C15—C19—C18 | 174.42 (17) |
C7—C3—C4—Cl1 | 0.4 (3) | N3—C18—C19—C15 | 3.6 (3) |
C3—C4—C5—C6 | 2.0 (3) | C20—C18—C19—C15 | −174.64 (17) |
Cl1—C4—C5—C6 | −178.36 (16) | N3—C18—C20—O3 | −170.53 (18) |
C4—C5—C6—C1 | −0.2 (3) | C19—C18—C20—O3 | 7.8 (3) |
C2—C1—C6—C5 | −1.8 (3) | N3—C18—C20—N4 | 7.8 (3) |
N1—C1—C6—C5 | 179.68 (18) | C19—C18—C20—N4 | −173.84 (17) |
C2—C3—C7—F1 | 125.5 (2) | O1—C8—N1—C1 | −0.1 (3) |
C4—C3—C7—F1 | −56.3 (3) | N2—C8—N1—C1 | 179.85 (17) |
C2—C3—C7—F3 | −114.5 (2) | C2—C1—N1—C8 | 171.48 (19) |
C4—C3—C7—F3 | 63.8 (3) | C6—C1—N1—C8 | −10.0 (3) |
C2—C3—C7—F2 | 5.2 (3) | O1—C8—N2—C9 | 2.7 (3) |
C4—C3—C7—F2 | −176.54 (19) | N1—C8—N2—C9 | −177.20 (17) |
C14—C9—C10—F4 | 179.43 (19) | C14—C9—N2—C8 | 7.3 (3) |
N2—C9—C10—F4 | 1.1 (3) | C10—C9—N2—C8 | −174.52 (18) |
C14—C9—C10—C11 | −0.6 (3) | C16—C17—N3—C18 | −0.7 (3) |
N2—C9—C10—C11 | −178.92 (19) | C19—C18—N3—C17 | −2.4 (3) |
F4—C10—C11—C12 | −179.89 (19) | C20—C18—N3—C17 | 175.85 (18) |
C9—C10—C11—C12 | 0.1 (3) | O3—C20—N4—C21 | −1.5 (3) |
C10—C11—C12—C13 | 0.2 (3) | C18—C20—N4—C21 | −179.85 (18) |
C10—C11—C12—O2 | −175.58 (18) | C16—C15—O2—C12 | −140.3 (2) |
C11—C12—C13—C14 | 0.0 (3) | C19—C15—O2—C12 | 43.5 (3) |
O2—C12—C13—C14 | 175.73 (18) | C13—C12—O2—C15 | 64.7 (2) |
C12—C13—C14—C9 | −0.5 (3) | C11—C12—O2—C15 | −119.5 (2) |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
O4—H42···O3i | 0.82 | 2.07 | 2.810 (2) | 150 |
O4—H41···O3ii | 0.82 | 2.18 | 2.988 (2) | 168 |
N4—H4···O1iii | 0.86 | 2.46 | 3.080 (2) | 129 |
N1—H1···O4 | 0.86 | 2.05 | 2.880 (2) | 161 |
N2—H2A···O4 | 0.86 | 2.23 | 3.021 (2) | 153 |
Symmetry codes: (i) −x+1, −y+1, −z+1; (ii) −x+2, −y+1, −z+1; (iii) x, −y+1/2, z−1/2. |
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