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The crystal structure of the title compound, C17H15FN2O2, was determined as part of a study of the biological activity of pyridine-substituted isoxazole derivatives as mitogen-activated protein kinase (MAPK) inhibitors. In the crystal structure of the title compound, the compound exists in the lactam and not in the tautomeric pyridin-2-ol form. As the aromatic pyridine nitrogen is considered to be important for accepting a hydrogen bond from p38MAPK, the structure of the lactam unit is correlated with the loss of biological activity of the title compound in the p38MAPK assay. In the crystal structure, the lactam is involved in hydrogen bonds, forming chains along the b axis.
Supporting information
CCDC reference: 640244
Key indicators
- Single-crystal X-ray study
- T = 193 K
- Mean (C-C) = 0.002 Å
- R factor = 0.042
- wR factor = 0.114
- Data-to-parameter ratio = 11.2
checkCIF/PLATON results
No syntax errors found
Alert level C
PLAT220_ALERT_2_C Large Non-Solvent C Ueq(max)/Ueq(min) ... 3.02 Ratio
PLAT222_ALERT_3_C Large Non-Solvent H Ueq(max)/Ueq(min) ... 3.11 Ratio
0 ALERT level A = In general: serious problem
0 ALERT level B = Potentially serious problem
2 ALERT level C = Check and explain
0 ALERT level G = General alerts; check
0 ALERT type 1 CIF construction/syntax error, inconsistent or missing data
1 ALERT type 2 Indicator that the structure model may be wrong or deficient
1 ALERT type 3 Indicator that the structure quality may be low
0 ALERT type 4 Improvement, methodology, query or suggestion
0 ALERT type 5 Informative message, check
Data collection: CAD-4 Software (Enraf–Nonius, 1989); cell refinement: CAD-4 Software; data reduction: CORINC (Dräger & Gattow, 1971); program(s) used to solve structure: SIR92 (Altomare et al., 1994); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics: PLATON (Spek, 2003); software used to prepare material for publication: SHELXL97 (Sheldrick, 1997) and ORTEPII (Johnson, 1976).
Crystal data top
C17H15FN2O2 | F(000) = 624 |
Mr = 298.31 | Dx = 1.310 Mg m−3 |
Monoclinic, P21/c | Melting point: 210 K |
Hall symbol: -P 2ybc | Cu Kα radiation, λ = 1.54178 Å |
a = 14.6895 (7) Å | Cell parameters from 25 reflections |
b = 7.3663 (2) Å | θ = 60–69° |
c = 14.2056 (6) Å | µ = 0.79 mm−1 |
β = 100.266 (5)° | T = 193 K |
V = 1512.54 (10) Å3 | Block, colourless |
Z = 4 | 0.26 × 0.26 × 0.19 mm |
Data collection top
Enraf–Nonius CAD-4 diffractometer | Rint = 0.045 |
Radiation source: rotating anode | θmax = 69.9°, θmin = 3.1° |
Graphite monochromator | h = −17→17 |
ω/2θ scans | k = −8→0 |
2980 measured reflections | l = −17→0 |
2853 independent reflections | 3 standard reflections every 60 min |
2644 reflections with I > 2σ(I) | intensity decay: 5% |
Refinement top
Refinement on F2 | Primary atom site location: structure-invariant direct methods |
Least-squares matrix: full | Secondary atom site location: difference Fourier map |
R[F2 > 2σ(F2)] = 0.042 | Hydrogen site location: difference Fourier map |
wR(F2) = 0.114 | All H-atom parameters refined |
S = 1.07 | w = 1/[σ2(Fo2) + (0.0613P)2 + 0.5807P] where P = (Fo2 + 2Fc2)/3 |
2853 reflections | (Δ/σ)max < 0.001 |
255 parameters | Δρmax = 0.22 e Å−3 |
0 restraints | Δρmin = −0.30 e Å−3 |
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 | x | y | z | Uiso*/Ueq | |
F1 | 0.64605 (7) | 0.02486 (16) | 0.23995 (8) | 0.0543 (3) | |
N2 | 0.31295 (9) | 0.44516 (19) | 0.52676 (10) | 0.0382 (3) | |
O3 | 0.39003 (7) | 0.38647 (15) | 0.48846 (7) | 0.0359 (3) | |
C1 | 0.24428 (10) | 0.3405 (2) | 0.48876 (10) | 0.0311 (3) | |
C4 | 0.36422 (9) | 0.24555 (19) | 0.42853 (9) | 0.0275 (3) | |
H4 | 0.3535 (12) | 0.107 (2) | 0.2533 (12) | 0.032 (4)* | |
C5 | 0.27276 (9) | 0.20878 (19) | 0.42549 (9) | 0.0264 (3) | |
C6 | 0.15133 (12) | 0.3637 (3) | 0.51868 (12) | 0.0448 (4) | |
H6 | 0.1045 (14) | 0.368 (3) | 0.4602 (15) | 0.049 (5)* | |
C7 | 0.14373 (16) | 0.5443 (3) | 0.56895 (15) | 0.0558 (5) | |
H7A | 0.1907 (18) | 0.549 (3) | 0.6281 (19) | 0.074 (4)* | |
H7B | 0.0801 (18) | 0.554 (3) | 0.5853 (18) | 0.074 (4)* | |
H7C | 0.1565 (17) | 0.650 (4) | 0.5279 (19) | 0.074 (4)* | |
C8 | 0.1332 (2) | 0.2048 (4) | 0.5807 (2) | 0.0750 (8) | |
H8A | 0.1338 (19) | 0.085 (4) | 0.547 (2) | 0.087 (5)* | |
H8B | 0.179 (2) | 0.206 (4) | 0.642 (2) | 0.087 (5)* | |
H8C | 0.075 (2) | 0.223 (4) | 0.600 (2) | 0.087 (5)* | |
C9 | 0.43702 (9) | 0.17557 (19) | 0.38017 (10) | 0.0278 (3) | |
H9 | 0.6642 (13) | 0.144 (3) | 0.4073 (13) | 0.042 (5)* | |
C10 | 0.52927 (10) | 0.1855 (2) | 0.42614 (11) | 0.0339 (3) | |
H10 | 0.5436 (13) | 0.237 (3) | 0.4911 (14) | 0.042 (5)* | |
C11 | 0.59993 (10) | 0.1327 (2) | 0.37927 (12) | 0.0387 (4) | |
C12 | 0.57674 (11) | 0.0726 (2) | 0.28668 (12) | 0.0370 (4) | |
C13 | 0.48685 (11) | 0.0602 (2) | 0.23860 (12) | 0.0368 (4) | |
H13 | 0.4719 (13) | 0.017 (3) | 0.1747 (15) | 0.043 (5)* | |
C14 | 0.41666 (10) | 0.1122 (2) | 0.28629 (11) | 0.0316 (3) | |
C15 | 0.21636 (9) | 0.06009 (18) | 0.37490 (9) | 0.0248 (3) | |
C16 | 0.12750 (9) | 0.09107 (19) | 0.32920 (10) | 0.0258 (3) | |
H16 | 0.1006 (11) | 0.210 (2) | 0.3234 (11) | 0.029 (4)* | |
C17 | 0.06938 (9) | −0.05383 (18) | 0.28727 (9) | 0.0254 (3) | |
N18 | 0.10801 (8) | −0.22320 (16) | 0.29544 (8) | 0.0262 (3) | |
H18 | 0.0718 (14) | −0.320 (3) | 0.2749 (14) | 0.047 (5)* | |
C19 | 0.19709 (10) | −0.25521 (19) | 0.33714 (10) | 0.0293 (3) | |
H19 | 0.2183 (11) | −0.380 (2) | 0.3352 (11) | 0.028 (4)* | |
C20 | 0.25278 (9) | −0.1186 (2) | 0.37679 (10) | 0.0298 (3) | |
H20 | 0.3182 (12) | −0.147 (2) | 0.4047 (12) | 0.035 (4)* | |
O21 | −0.01270 (7) | −0.03583 (13) | 0.24475 (8) | 0.0336 (3) | |
Atomic displacement parameters (Å2) top | U11 | U22 | U33 | U12 | U13 | U23 |
F1 | 0.0390 (6) | 0.0582 (7) | 0.0718 (7) | −0.0059 (5) | 0.0264 (5) | −0.0186 (5) |
N2 | 0.0336 (7) | 0.0441 (8) | 0.0369 (7) | −0.0031 (6) | 0.0062 (5) | −0.0126 (6) |
O3 | 0.0288 (5) | 0.0399 (6) | 0.0380 (6) | −0.0072 (4) | 0.0037 (4) | −0.0124 (5) |
C1 | 0.0305 (7) | 0.0361 (8) | 0.0263 (7) | −0.0015 (6) | 0.0037 (5) | −0.0021 (6) |
C4 | 0.0269 (7) | 0.0279 (7) | 0.0256 (6) | −0.0033 (5) | −0.0011 (5) | −0.0006 (5) |
C5 | 0.0249 (6) | 0.0288 (7) | 0.0243 (6) | −0.0019 (5) | 0.0011 (5) | 0.0021 (5) |
C6 | 0.0346 (8) | 0.0641 (12) | 0.0378 (8) | −0.0030 (8) | 0.0122 (7) | −0.0136 (8) |
C7 | 0.0536 (11) | 0.0697 (14) | 0.0480 (11) | 0.0084 (10) | 0.0194 (9) | −0.0154 (10) |
C8 | 0.0867 (18) | 0.0764 (17) | 0.0763 (16) | −0.0269 (14) | 0.0533 (14) | −0.0133 (13) |
C9 | 0.0247 (7) | 0.0260 (7) | 0.0317 (7) | −0.0032 (5) | 0.0026 (5) | 0.0018 (5) |
C10 | 0.0277 (7) | 0.0382 (8) | 0.0341 (8) | −0.0030 (6) | 0.0008 (6) | −0.0009 (6) |
C11 | 0.0239 (7) | 0.0415 (9) | 0.0493 (9) | −0.0024 (6) | 0.0032 (6) | −0.0007 (7) |
C12 | 0.0317 (8) | 0.0314 (8) | 0.0511 (9) | −0.0024 (6) | 0.0160 (7) | −0.0041 (7) |
C13 | 0.0389 (8) | 0.0342 (8) | 0.0376 (8) | −0.0044 (6) | 0.0081 (6) | −0.0077 (6) |
C14 | 0.0271 (7) | 0.0308 (7) | 0.0354 (7) | −0.0036 (6) | 0.0014 (6) | −0.0030 (6) |
C15 | 0.0237 (6) | 0.0272 (7) | 0.0233 (6) | −0.0032 (5) | 0.0038 (5) | 0.0017 (5) |
C16 | 0.0239 (6) | 0.0236 (7) | 0.0293 (7) | 0.0005 (5) | 0.0031 (5) | 0.0023 (5) |
C17 | 0.0232 (6) | 0.0245 (7) | 0.0281 (6) | −0.0002 (5) | 0.0034 (5) | 0.0025 (5) |
N18 | 0.0231 (6) | 0.0223 (6) | 0.0322 (6) | −0.0021 (4) | 0.0020 (4) | 0.0013 (5) |
C19 | 0.0256 (7) | 0.0256 (7) | 0.0358 (7) | 0.0033 (5) | 0.0034 (5) | 0.0035 (6) |
C20 | 0.0220 (6) | 0.0311 (7) | 0.0341 (7) | 0.0014 (5) | −0.0009 (5) | 0.0033 (6) |
O21 | 0.0224 (5) | 0.0255 (5) | 0.0486 (6) | 0.0000 (4) | −0.0052 (4) | −0.0001 (4) |
Geometric parameters (Å, º) top
F1—C12 | 1.3570 (18) | C10—C11 | 1.385 (2) |
N2—C1 | 1.307 (2) | C10—H10 | 0.984 (19) |
N2—O3 | 1.4087 (16) | C11—C12 | 1.372 (2) |
O3—C4 | 1.3532 (17) | C11—H9 | 0.960 (19) |
C1—C5 | 1.435 (2) | C12—C13 | 1.377 (2) |
C1—C6 | 1.510 (2) | C13—C14 | 1.385 (2) |
C4—C5 | 1.3637 (19) | C13—H13 | 0.95 (2) |
C4—C9 | 1.464 (2) | C14—H4 | 0.963 (17) |
C5—C15 | 1.4799 (18) | C15—C16 | 1.3695 (18) |
C6—C8 | 1.517 (3) | C15—C20 | 1.419 (2) |
C6—C7 | 1.523 (3) | C16—C17 | 1.4288 (19) |
C6—H6 | 0.98 (2) | C16—H16 | 0.959 (18) |
C7—H7A | 0.99 (3) | C17—O21 | 1.2556 (17) |
C7—H7B | 1.00 (3) | C17—N18 | 1.3670 (18) |
C7—H7C | 1.01 (3) | N18—C19 | 1.3573 (18) |
C8—H8A | 1.00 (3) | N18—H18 | 0.91 (2) |
C8—H8B | 1.01 (3) | C19—C20 | 1.355 (2) |
C8—H8C | 0.96 (3) | C19—H19 | 0.976 (18) |
C9—C14 | 1.394 (2) | C20—H20 | 0.995 (17) |
C9—C10 | 1.3974 (19) | | |
| | | |
C1—N2—O3 | 105.88 (12) | C11—C10—H10 | 120.3 (11) |
C4—O3—N2 | 108.90 (10) | C9—C10—H10 | 119.1 (11) |
N2—C1—C5 | 111.59 (13) | C12—C11—C10 | 118.18 (14) |
N2—C1—C6 | 119.12 (13) | C12—C11—H9 | 119.0 (11) |
C5—C1—C6 | 129.21 (13) | C10—C11—H9 | 122.7 (11) |
O3—C4—C5 | 109.65 (12) | F1—C12—C11 | 118.22 (14) |
O3—C4—C9 | 114.78 (12) | F1—C12—C13 | 118.49 (14) |
C5—C4—C9 | 135.50 (13) | C11—C12—C13 | 123.29 (14) |
C4—C5—C1 | 103.97 (12) | C12—C13—C14 | 118.09 (14) |
C4—C5—C15 | 128.71 (13) | C12—C13—H13 | 122.3 (12) |
C1—C5—C15 | 127.18 (12) | C14—C13—H13 | 119.6 (12) |
C1—C6—C8 | 109.70 (17) | C13—C14—C9 | 120.60 (13) |
C1—C6—C7 | 112.11 (15) | C13—C14—H4 | 119.2 (10) |
C8—C6—C7 | 111.50 (17) | C9—C14—H4 | 120.2 (10) |
C1—C6—H6 | 107.3 (12) | C16—C15—C20 | 119.19 (12) |
C8—C6—H6 | 110.4 (12) | C16—C15—C5 | 120.71 (12) |
C7—C6—H6 | 105.6 (12) | C20—C15—C5 | 120.04 (12) |
C6—C7—H7A | 109.5 (15) | C15—C16—C17 | 121.43 (12) |
C6—C7—H7B | 108.6 (15) | C15—C16—H16 | 122.5 (10) |
H7A—C7—H7B | 110 (2) | C17—C16—H16 | 116.1 (10) |
C6—C7—H7C | 111.5 (15) | O21—C17—N18 | 119.06 (12) |
H7A—C7—H7C | 107 (2) | O21—C17—C16 | 124.95 (12) |
H7B—C7—H7C | 111 (2) | N18—C17—C16 | 115.99 (12) |
C6—C8—H8A | 112.5 (17) | C19—N18—C17 | 123.29 (12) |
C6—C8—H8B | 109.8 (17) | C19—N18—H18 | 118.0 (13) |
H8A—C8—H8B | 111 (2) | C17—N18—H18 | 118.6 (13) |
C6—C8—H8C | 108.7 (18) | C20—C19—N18 | 121.07 (13) |
H8A—C8—H8C | 110 (2) | C20—C19—H19 | 122.8 (9) |
H8B—C8—H8C | 104 (2) | N18—C19—H19 | 116.1 (9) |
C14—C9—C10 | 119.30 (13) | C19—C20—C15 | 118.92 (12) |
C14—C9—C4 | 121.11 (12) | C19—C20—H20 | 118.4 (10) |
C10—C9—C4 | 119.40 (12) | C15—C20—H20 | 122.7 (11) |
C11—C10—C9 | 120.53 (14) | | |
| | | |
C1—N2—O3—C4 | −0.48 (16) | C9—C10—C11—C12 | 0.6 (2) |
O3—N2—C1—C5 | 0.64 (17) | C10—C11—C12—F1 | 178.48 (14) |
O3—N2—C1—C6 | 177.50 (13) | C10—C11—C12—C13 | −0.7 (3) |
N2—O3—C4—C5 | 0.13 (16) | F1—C12—C13—C14 | −178.88 (14) |
N2—O3—C4—C9 | 177.50 (11) | C11—C12—C13—C14 | 0.3 (2) |
O3—C4—C5—C1 | 0.24 (15) | C12—C13—C14—C9 | 0.2 (2) |
C9—C4—C5—C1 | −176.36 (15) | C10—C9—C14—C13 | −0.2 (2) |
O3—C4—C5—C15 | −175.71 (13) | C4—C9—C14—C13 | 174.69 (14) |
C9—C4—C5—C15 | 7.7 (3) | C4—C5—C15—C16 | −139.88 (15) |
N2—C1—C5—C4 | −0.57 (17) | C1—C5—C15—C16 | 45.0 (2) |
C6—C1—C5—C4 | −177.03 (16) | C4—C5—C15—C20 | 42.8 (2) |
N2—C1—C5—C15 | 175.47 (13) | C1—C5—C15—C20 | −132.26 (15) |
C6—C1—C5—C15 | −1.0 (2) | C20—C15—C16—C17 | 2.9 (2) |
N2—C1—C6—C8 | −108.0 (2) | C5—C15—C16—C17 | −174.42 (12) |
C5—C1—C6—C8 | 68.3 (2) | C15—C16—C17—O21 | 179.66 (13) |
N2—C1—C6—C7 | 16.5 (2) | C15—C16—C17—N18 | −0.20 (19) |
C5—C1—C6—C7 | −167.28 (16) | O21—C17—N18—C19 | 177.63 (13) |
O3—C4—C9—C14 | −144.17 (14) | C16—C17—N18—C19 | −2.50 (19) |
C5—C4—C9—C14 | 32.3 (2) | C17—N18—C19—C20 | 2.4 (2) |
O3—C4—C9—C10 | 30.76 (19) | N18—C19—C20—C15 | 0.5 (2) |
C5—C4—C9—C10 | −152.77 (16) | C16—C15—C20—C19 | −3.1 (2) |
C14—C9—C10—C11 | −0.2 (2) | C5—C15—C20—C19 | 174.28 (13) |
C4—C9—C10—C11 | −175.19 (14) | | |
Hydrogen-bond geometry (Å, º) top
D—H···A | D—H | H···A | D···A | D—H···A |
N18—H18···O21i | 0.91 (2) | 1.81 (2) | 2.7027 (15) | 168.2 (19) |
Symmetry code: (i) −x, y−1/2, −z+1/2. |
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