4-(4-Fluoro-phen-yl)-2-methyl-3-(1-oxy-4-pyridyl)isoxazol-5(2H)-one.

The crystal structure of the title compound, C(15)H(11)FN(2)O(3), was determined as part of a study on the biological activity of isoxazolone derivatives as p38 mitogen-activated protein kinase (MAPK) inhibitors. The dihedral angles between rings are isoxazole/benzene = 55.0 (3)°, isoxazole/pyridine = 33.8 (2)° and benzene/pyridine = 58.1 (2)°.

Related literature

Isoxazolones as potent inhibitors of p38 MAP kinases were first described by Laughlin et al. (2005 ▶). For related literature, see: Adams et al. (1998 ▶); Clark et al. (2002 ▶); De Laszlo et al. (1998 ▶); Foster et al. (2000 ▶); Laufer & Wagner (2002 ▶); Laufer et al. (2006 ▶); Ohkawa et al. (2001 ▶); Revesz et al. (2000 ▶); Wang et al. (1998 ▶).

Experimental

Crystal data

C15H11FN2O3

M = 286.26

Tetragonal,

a = 10.0828 (6) Å

c = 25.257 (5) Å

V = 2567.6 (6) Å3

Z = 8

Cu Kα radiation

μ = 0.97 mm−1

T = 193 (2) K

0.40 × 0.20 × 0.10 mm

Data collection

Enraf–Nonius CAD-4 diffractometer

Absorption correction: multi-scan (MULABS; Blessing, 1995 ▶) T min = 0.60, T max = 0.88

5114 measured reflections

1488 independent reflections

1129 reflections with I > 2σ(I)

R int = 0.081

3 standard reflections frequency: 60 min intensity decay: 5%

Refinement

R[F 2 > 2σ(F 2)] = 0.068

wR(F 2) = 0.192

S = 1.00

1488 reflections

191 parameters

H-atom parameters constrained

Δρmax = 0.45 e Å−3

Δρmin = −0.34 e Å−3

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.

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536807066500/cf2171sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536807066500/cf2171Isup2.hkl

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C15H11FN2O3	Z = 8
Mr = 286.26	F000 = 1184
Tetragonal, P43212	Dx = 1.481 Mg m−3
Hall symbol: P 4nw 2abw	Cu Kα radiation λ = 1.54178 Å
a = 10.0828 (6) Å	Cell parameters from 25 reflections
b = 10.0828 (6) Å	θ = 20–32º
c = 25.257 (5) Å	µ = 0.97 mm−1
α = 90º	T = 193 (2) K
β = 90º	Block, yellow
γ = 90º	0.40 × 0.20 × 0.10 mm
V = 2567.6 (6) Å3

Enraf–Nonius CAD-4 diffractometer	Rint = 0.081
Monochromator: graphite	θmax = 69.8º
T = 193(2) K	θmin = 4.7º
θ/2ω scans	h = −12→12
Absorption correction: multi-scan(MULABS; Blessing, 1995)	k = −12→12
Tmin = 0.60, Tmax = 0.88	l = −23→30
5114 measured reflections	3 standard reflections
1488 independent reflections	every 60 min
1129 reflections with I > 2σ(I)	intensity decay: 5%

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)] = 0.068	H-atom parameters constrained
wR(F2) = 0.192	w = 1/[σ2(Fo2) + (0.149P)2] where P = (Fo2 + 2Fc2)/3
S = 1.00	(Δ/σ)max < 0.001
1488 reflections	Δρmax = 0.45 e Å−3
191 parameters	Δρmin = −0.34 e Å−3
Primary atom site location: structure-invariant direct methods	Extinction correction: none

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. Friedel Pairs merged (MERG 3 instruction). 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.

	x	y	z	Uiso*/Ueq
C1	0.4167 (4)	0.0719 (4)	0.3006 (2)	0.0248 (11)
C2	0.3537 (4)	0.1885 (4)	0.2905 (2)	0.0231 (10)
N3	0.2782 (4)	0.1781 (4)	0.24613 (17)	0.0272 (10)
O4	0.2804 (4)	0.0427 (3)	0.23076 (16)	0.0346 (9)
C5	0.3701 (5)	−0.0233 (5)	0.2641 (2)	0.0302 (11)
C6	0.1515 (5)	0.2379 (6)	0.2342 (2)	0.0366 (13)
H6A	0.0806	0.1855	0.2505	0.055*
H6B	0.1387	0.2403	0.1958	0.055*
H6C	0.1493	0.3284	0.2483	0.055*
O7	0.3926 (4)	−0.1402 (4)	0.25595 (18)	0.0409 (10)
C8	0.5231 (4)	0.0446 (4)	0.3400 (2)	0.0262 (11)
C9	0.6393 (5)	0.1185 (5)	0.3410 (2)	0.0290 (11)
H9	0.6499	0.1896	0.3167	0.035*
C10	0.7405 (5)	0.0908 (5)	0.3767 (3)	0.0348 (13)
H10	0.8198	0.1415	0.3774	0.042*
C11	0.7207 (5)	−0.0138 (5)	0.4112 (2)	0.0300 (12)
C12	0.6096 (5)	−0.0891 (5)	0.4118 (2)	0.0315 (12)
H12	0.6000	−0.1598	0.4364	0.038*
C13	0.5100 (5)	−0.0603 (5)	0.3757 (3)	0.0313 (12)
H13	0.4318	−0.1128	0.3752	0.038*
F14	0.8198 (3)	−0.0417 (3)	0.44649 (16)	0.0477 (10)
C15	0.3631 (4)	0.3142 (4)	0.31988 (19)	0.0198 (10)
C16	0.3580 (4)	0.4384 (4)	0.2958 (2)	0.0253 (11)
H16	0.3448	0.4438	0.2586	0.030*
C17	0.3714 (5)	0.5514 (5)	0.3240 (2)	0.0265 (11)
H17	0.3655	0.6347	0.3066	0.032*
N18	0.3934 (4)	0.5467 (4)	0.37729 (18)	0.0253 (9)
C19	0.3954 (5)	0.4264 (5)	0.4021 (2)	0.0270 (11)
H19	0.4076	0.4228	0.4394	0.032*
C20	0.3804 (4)	0.3122 (4)	0.3746 (2)	0.0254 (10)
H20	0.3817	0.2298	0.3929	0.030*
O21	0.4120 (4)	0.6544 (3)	0.40417 (17)	0.0395 (10)

	U11	U22	U33	U12	U13	U23
C1	0.0148 (19)	0.020 (2)	0.039 (3)	0.0011 (17)	0.0004 (19)	0.000 (2)
C2	0.022 (2)	0.021 (2)	0.027 (3)	0.0009 (17)	0.0007 (19)	−0.0004 (19)
N3	0.033 (2)	0.0243 (18)	0.025 (2)	0.0040 (17)	−0.0053 (18)	−0.0087 (17)
O4	0.0338 (19)	0.0286 (17)	0.041 (2)	0.0032 (15)	−0.0063 (17)	−0.0105 (16)
C5	0.025 (2)	0.022 (2)	0.043 (3)	0.0028 (19)	0.004 (2)	−0.004 (2)
C6	0.036 (3)	0.041 (3)	0.033 (3)	0.010 (2)	−0.011 (2)	0.002 (2)
O7	0.040 (2)	0.0289 (18)	0.053 (3)	0.0000 (15)	−0.002 (2)	−0.0161 (18)
C8	0.019 (2)	0.017 (2)	0.042 (3)	0.0062 (17)	−0.002 (2)	−0.005 (2)
C9	0.026 (2)	0.018 (2)	0.042 (3)	0.0040 (17)	−0.002 (2)	−0.002 (2)
C10	0.024 (2)	0.028 (2)	0.053 (4)	0.002 (2)	−0.004 (2)	−0.013 (2)
C11	0.025 (2)	0.024 (2)	0.041 (3)	0.0109 (19)	−0.010 (2)	−0.012 (2)
C12	0.035 (3)	0.023 (2)	0.037 (3)	0.007 (2)	−0.002 (2)	0.001 (2)
C13	0.022 (2)	0.023 (2)	0.048 (3)	0.001 (2)	−0.001 (2)	0.000 (2)
F14	0.0400 (17)	0.0448 (18)	0.058 (2)	0.0099 (15)	−0.0234 (17)	−0.0034 (17)
C15	0.0172 (19)	0.0174 (19)	0.025 (3)	0.0021 (15)	−0.0003 (18)	−0.0017 (18)
C16	0.025 (2)	0.022 (2)	0.028 (3)	0.0062 (18)	0.000 (2)	0.003 (2)
C17	0.029 (2)	0.020 (2)	0.030 (3)	0.0014 (18)	0.003 (2)	0.006 (2)
N18	0.0232 (19)	0.0212 (19)	0.031 (3)	0.0019 (15)	0.0016 (17)	−0.0046 (18)
C19	0.030 (2)	0.025 (2)	0.026 (3)	0.0051 (19)	−0.002 (2)	0.000 (2)
C20	0.025 (2)	0.018 (2)	0.033 (3)	0.0015 (18)	−0.002 (2)	0.0027 (19)
O21	0.049 (2)	0.0213 (17)	0.048 (3)	−0.0046 (15)	−0.0001 (19)	−0.0107 (17)

C1—C2	1.360 (6)	C10—H10	0.950
C1—C5	1.412 (7)	C11—C12	1.354 (7)
C1—C8	1.489 (7)	C11—F14	1.368 (6)
C2—N3	1.359 (6)	C12—C13	1.388 (7)
C2—C15	1.472 (6)	C12—H12	0.950
N3—O4	1.419 (5)	C13—H13	0.950
N3—C6	1.444 (6)	C15—C16	1.393 (6)
O4—C5	1.403 (6)	C15—C20	1.394 (7)
C5—O7	1.218 (6)	C16—C17	1.350 (7)
C6—H6A	0.980	C16—H16	0.950
C6—H6B	0.980	C17—N18	1.364 (7)
C6—H6C	0.980	C17—H17	0.950
C8—C9	1.389 (6)	N18—O21	1.293 (5)
C8—C13	1.395 (7)	N18—C19	1.366 (6)
C9—C10	1.391 (8)	C19—C20	1.352 (7)
C9—H9	0.950	C19—H19	0.950
C10—C11	1.382 (8)	C20—H20	0.950
C2—C1—C5	108.0 (4)	C12—C11—F14	118.8 (5)
C2—C1—C8	128.4 (4)	C12—C11—C10	123.7 (5)
C5—C1—C8	123.5 (4)	F14—C11—C10	117.5 (5)
N3—C2—C1	110.5 (4)	C11—C12—C13	118.3 (5)
N3—C2—C15	121.2 (4)	C11—C12—H12	120.9
C1—C2—C15	128.3 (5)	C13—C12—H12	120.9
C2—N3—O4	106.9 (4)	C12—C13—C8	121.0 (5)
C2—N3—C6	129.5 (4)	C12—C13—H13	119.5
O4—N3—C6	111.0 (4)	C8—C13—H13	119.5
C5—O4—N3	107.6 (4)	C16—C15—C20	116.8 (4)
O7—C5—O4	118.6 (5)	C16—C15—C2	123.5 (4)
O7—C5—C1	134.9 (5)	C20—C15—C2	119.7 (4)
O4—C5—C1	106.5 (4)	C17—C16—C15	121.6 (5)
N3—C6—H6A	109.5	C17—C16—H16	119.2
N3—C6—H6B	109.5	C15—C16—H16	119.2
H6A—C6—H6B	109.5	C16—C17—N18	120.5 (4)
N3—C6—H6C	109.5	C16—C17—H17	119.7
H6A—C6—H6C	109.5	N18—C17—H17	119.7
H6B—C6—H6C	109.5	O21—N18—C17	120.8 (4)
C9—C8—C13	118.4 (5)	O21—N18—C19	120.2 (4)
C9—C8—C1	121.4 (5)	C17—N18—C19	119.0 (4)
C13—C8—C1	120.2 (4)	C20—C19—N18	121.3 (5)
C8—C9—C10	121.5 (5)	C20—C19—H19	119.4
C8—C9—H9	119.2	N18—C19—H19	119.4
C10—C9—H9	119.2	C19—C20—C15	120.7 (4)
C11—C10—C9	117.2 (5)	C19—C20—H20	119.6
C11—C10—H10	121.4	C15—C20—H20	119.6
C9—C10—H10	121.4
C5—C1—C2—N3	−5.8 (6)	C8—C9—C10—C11	0.2 (8)
C8—C1—C2—N3	170.2 (5)	C9—C10—C11—C12	0.0 (8)
C5—C1—C2—C15	176.1 (4)	C9—C10—C11—F14	180.0 (4)
C8—C1—C2—C15	−7.9 (8)	F14—C11—C12—C13	−179.7 (5)
C1—C2—N3—O4	7.4 (5)	C10—C11—C12—C13	0.3 (8)
C15—C2—N3—O4	−174.4 (4)	C11—C12—C13—C8	−0.9 (8)
C1—C2—N3—C6	144.7 (5)	C9—C8—C13—C12	1.1 (8)
C15—C2—N3—C6	−37.1 (7)	C1—C8—C13—C12	178.5 (5)
C2—N3—O4—C5	−6.0 (5)	N3—C2—C15—C16	−33.2 (7)
C6—N3—O4—C5	−151.9 (4)	C1—C2—C15—C16	144.7 (5)
N3—O4—C5—O7	−176.3 (5)	N3—C2—C15—C20	148.1 (5)
N3—O4—C5—C1	2.5 (5)	C1—C2—C15—C20	−34.1 (7)
C2—C1—C5—O7	−179.6 (6)	C20—C15—C16—C17	1.0 (6)
C8—C1—C5—O7	4.1 (10)	C2—C15—C16—C17	−177.8 (5)
C2—C1—C5—O4	1.9 (6)	C15—C16—C17—N18	1.5 (7)
C8—C1—C5—O4	−174.4 (4)	C16—C17—N18—O21	177.0 (4)
C2—C1—C8—C9	−54.3 (8)	C16—C17—N18—C19	−3.1 (7)
C5—C1—C8—C9	121.2 (5)	O21—N18—C19—C20	−177.9 (4)
C2—C1—C8—C13	128.4 (6)	C17—N18—C19—C20	2.2 (7)
C5—C1—C8—C13	−56.1 (7)	N18—C19—C20—C15	0.3 (7)
C13—C8—C9—C10	−0.7 (8)	C16—C15—C20—C19	−1.9 (7)
C1—C8—C9—C10	−178.1 (5)	C2—C15—C20—C19	176.9 (4)