4-[4-(4-Fluoro­phen­yl)-1,2-oxazol-5-yl]pyridine

Koch, P.; Schollmeyer, D.

doi:10.1107/S2414314625011071

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 10| Part 12| December 2025| x251107

https://doi.org/10.1107/S2414314625011071

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4-[4-(4-Fluorophenyl)-1,2-oxazol-5-yl]pyridine

Pierre Koch ^a ^* and Dieter Schollmeyer ^b

^aUniversität Regensburg, Universitätsstrasse 31, 93053 Regensburg, Germany, and ^bUniversity Mainz, Duesbergweg 10-14, 55099 Mainz, Germany
^*Correspondence e-mail: [email protected]

Edited by M. Bolte, Goethe-Universität Frankfurt, Germany (Received 2 December 2025; accepted 9 December 2025; online 24 December 2025)

The title compound, C₁₄H₉FN₂O, crystallizes in the monoclinic space group P2₁/c. The dihedral angles between the central isoxazole ring and the 4-fluorophenyl and pyridine rings are 37.51 (10) and 12.11 (15)°, respectively.

Keywords: crystal structure; pyridine; isoxazole; MAP kinase inhibitor.

CCDC reference: 2514389

Structure description

The title compound, C₁₄H₉FN₂O, (Fig. 1), was synthesized to extend our study on the role of the hydrogen-bonding heteroatom-Lys53 interaction between pyridin-4-yl-substituted five-membered heterocyclic ring inhibitors and the p38α mitogen-activated protein (MAP) kinase (Abu Thaher et al., 2009 ). For the structure of a regioisomer of the title compound, see Koch et al. (2025 ).

Figure 1
View of the title compound. Displacement ellipsoids are drawn at the 50% probability level.

The isoxazole ring (C1–C3,O4,N5) makes dihedral angles of 37.51 (10) and 12.11 (15)° with 4-fluorophenyl (C6–C11) and pyridine (C12–C14,N15,C16,C17) rings, respectively. The 4-fluorophenyl ring makes a dihedral angle of 41.82 (9)° with the pyridine ring. In the crystal, the π-hydrogen–nitrogen bond (C1—H1⋯N15, Table 1) leads to the formation of chains along the c-axis direction. The packing is shown in Fig. 2.

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C1—H1⋯N15ⁱ	0.95	2.54	3.459 (4)	164
Symmetry code: (i) .

Figure 2
Part of the packing diagram. View along the a-axis direction. Hydrogen bonds are shown as dashed lines.

Synthesis and crystallization

3-(Dimethylamino)-2-(4-fluorophenyl)-1-(pyridin-4-yl)prop-2-en-1-one (500 mg) was dissolved in methanol (8 ml) and water (4 ml). Sodium carbonate (106 mg) and hydroxylamine hydrochloride (123 mg) were added. The pH was adjusted to 5 by dropwise addition of acetic acid. The reaction mixture was heated to reflux temperature for 2.5 h. After cooling to room temperature, the pH was set to 7 by addition of ammonium hydroxide solution. Ice was added to the mixture and the title compound crystallized slowly as colorless needles (180 mg).

Refinement

Crystal data, data collection and structure refinement details are summarized in Table 2.

Table 2
Experimental details

Crystal data
Chemical formula	C₁₄H₉FN₂O
M_r	240.23
Crystal system, space group	Monoclinic, P2₁/c
Temperature (K)	193
a, b, c (Å)	3.9252 (18), 29.539 (4), 9.642 (4)
β (°)	102.06 (2)
V (Å³)	1093.3 (7)
Z	4
Radiation type	Cu Kα
μ (mm⁻¹)	0.88
Crystal size (mm)	0.30 × 0.05 × 0.05

Data collection
Diffractometer	Enraf–Nonius CAD-4
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	2383, 2077, 1387
R_int	0.048
(sin θ/λ)_max (Å⁻¹)	0.609

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.055, 0.157, 1.06
No. of reflections	2077
No. of parameters	164
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.28, −0.27
Computer programs: CAD-4 Software (Enraf–Nonius, 1989 ), CORINC (Dräger & Gattow, 1971 ), SHELXT2014 (Sheldrick, 2015a ), SHELXL2019/3 (Sheldrick, 2015b ) and PLATON (Spek, 2009 ).

Structural data

CCDC reference: 2514389

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S2414314625011071/bt4194sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314625011071/bt4194Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314625011071/bt4194Isup3.cml

checkCIF report

Computing details top

4-[4-(4-Fluorophenyl)-1,2-oxazol-5-yl]pyridine top

Crystal data top

C₁₄H₉FN₂O	F(000) = 496
M_r = 240.23	D_x = 1.459 Mg m⁻³
Monoclinic, P2₁/c	Cu Kα radiation, λ = 1.54178 Å
a = 3.9252 (18) Å	Cell parameters from 25 reflections
b = 29.539 (4) Å	θ = 21–29°
c = 9.642 (4) Å	µ = 0.88 mm⁻¹
β = 102.06 (2)°	T = 193 K
V = 1093.3 (7) Å³	Needles, colourless
Z = 4	0.30 × 0.05 × 0.05 mm

Data collection top

Enraf–Nonius CAD-4 diffractometer	R_int = 0.048
Radiation source: rotating anode	θ_max = 70.0°, θ_min = 3.0°
Graphite monochromator	h = −4→0
ω/2θ scans	k = 0→36
2383 measured reflections	l = −11→11
2077 independent reflections	3 standard reflections every 60 min
1387 reflections with I > 2σ(I)	intensity decay: 2%

Refinement top

Refinement on F²	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F² > 2σ(F²)] = 0.055	w = 1/[σ²(F_o²) + (0.078P)²] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.157	(Δ/σ)_max < 0.001
S = 1.06	Δρ_max = 0.28 e Å⁻³
2077 reflections	Δρ_min = −0.27 e Å⁻³
164 parameters	Extinction correction: SHELXL-2019/3 (Sheldrick, 2015b), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
0 restraints	Extinction coefficient: 0.0051 (10)
Primary atom site location: structure-invariant direct methods

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. Hydrogen atoms were placed at calculated positions and were refined in the riding-model approximation with C–H = 0.95 Å, and with U_iso(H) = 1.2 U_eq(C).

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å²) top

	x	y	z	U_iso*/U_eq
F1	0.9320 (6)	0.22890 (6)	0.9777 (2)	0.0623 (7)
C1	0.4161 (9)	0.43647 (9)	0.8975 (3)	0.0366 (7)
H1	0.448981	0.431370	0.996651	0.044*
C2	0.4831 (7)	0.40304 (9)	0.7999 (3)	0.0285 (6)
C3	0.4057 (7)	0.42489 (8)	0.6731 (3)	0.0295 (6)
O4	0.2967 (6)	0.46779 (6)	0.69270 (19)	0.0385 (6)
N5	0.3058 (8)	0.47453 (8)	0.8374 (2)	0.0439 (7)
C6	0.6013 (7)	0.35668 (8)	0.8417 (3)	0.0275 (6)
C7	0.4785 (8)	0.31866 (9)	0.7610 (3)	0.0311 (6)
H7	0.316577	0.322411	0.673623	0.037*
C8	0.5878 (8)	0.27570 (9)	0.8056 (3)	0.0377 (7)
H8	0.505879	0.249920	0.749620	0.045*
C9	0.8192 (9)	0.27122 (9)	0.9338 (3)	0.0398 (7)
C10	0.9413 (8)	0.30723 (10)	1.0186 (3)	0.0376 (7)
H10	1.096255	0.302943	1.107434	0.045*
C11	0.8325 (8)	0.35024 (9)	0.9712 (3)	0.0324 (7)
H11	0.916967	0.375771	1.027989	0.039*
C12	0.4195 (7)	0.41517 (8)	0.5250 (3)	0.0278 (6)
C13	0.2652 (8)	0.44483 (9)	0.4176 (3)	0.0329 (7)
H13	0.153322	0.471542	0.440137	0.040*
C14	0.2755 (8)	0.43522 (9)	0.2785 (3)	0.0358 (7)
H14	0.166021	0.455787	0.207181	0.043*
N15	0.4307 (7)	0.39864 (8)	0.2382 (2)	0.0366 (6)
C16	0.5827 (8)	0.37062 (9)	0.3421 (3)	0.0355 (7)
H16	0.695501	0.344424	0.316372	0.043*
C17	0.5861 (8)	0.37730 (9)	0.4841 (3)	0.0318 (6)
H17	0.700583	0.356340	0.553090	0.038*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1	0.0842 (17)	0.0341 (10)	0.0623 (13)	0.0099 (10)	0.0010 (11)	0.0143 (8)
C1	0.0539 (19)	0.0356 (15)	0.0222 (13)	−0.0003 (14)	0.0121 (12)	0.0010 (11)
C2	0.0333 (15)	0.0302 (14)	0.0229 (12)	−0.0042 (12)	0.0076 (11)	−0.0009 (10)
C3	0.0337 (16)	0.0244 (13)	0.0299 (14)	−0.0010 (11)	0.0058 (11)	−0.0018 (10)
O4	0.0618 (15)	0.0301 (10)	0.0245 (9)	0.0069 (10)	0.0113 (9)	0.0013 (8)
N5	0.072 (2)	0.0360 (13)	0.0254 (12)	0.0057 (13)	0.0152 (12)	−0.0034 (10)
C6	0.0312 (15)	0.0297 (14)	0.0229 (13)	−0.0016 (11)	0.0084 (11)	0.0027 (10)
C7	0.0356 (16)	0.0327 (14)	0.0234 (13)	−0.0035 (12)	0.0024 (11)	0.0004 (11)
C8	0.0460 (19)	0.0280 (14)	0.0373 (15)	−0.0045 (13)	0.0047 (14)	−0.0016 (11)
C9	0.047 (2)	0.0298 (15)	0.0414 (17)	0.0023 (13)	0.0067 (14)	0.0100 (12)
C10	0.0429 (18)	0.0402 (16)	0.0268 (13)	0.0023 (14)	0.0009 (12)	0.0060 (11)
C11	0.0392 (17)	0.0329 (15)	0.0244 (13)	−0.0029 (12)	0.0049 (11)	−0.0008 (11)
C12	0.0321 (15)	0.0286 (13)	0.0223 (12)	−0.0046 (11)	0.0047 (10)	0.0000 (10)
C13	0.0402 (17)	0.0306 (14)	0.0273 (13)	0.0020 (12)	0.0055 (12)	0.0013 (10)
C14	0.0468 (18)	0.0345 (14)	0.0239 (13)	−0.0003 (13)	0.0024 (12)	0.0032 (11)
N15	0.0481 (16)	0.0386 (13)	0.0232 (11)	−0.0012 (12)	0.0075 (10)	−0.0018 (10)
C16	0.0426 (18)	0.0350 (15)	0.0298 (14)	0.0018 (13)	0.0100 (12)	−0.0016 (11)
C17	0.0382 (17)	0.0313 (14)	0.0254 (12)	0.0014 (12)	0.0054 (11)	0.0008 (11)

Geometric parameters (Å, º) top

F1—C9	1.364 (3)	C9—C10	1.366 (4)
C1—N5	1.297 (3)	C10—C11	1.387 (4)
C1—C2	1.426 (4)	C10—H10	0.9500
C1—H1	0.9500	C11—H11	0.9500
C2—C3	1.359 (3)	C12—C17	1.394 (4)
C2—C6	1.475 (3)	C12—C13	1.394 (4)
C3—O4	1.363 (3)	C13—C14	1.380 (4)
C3—C12	1.469 (3)	C13—H13	0.9500
O4—N5	1.403 (3)	C14—N15	1.337 (4)
C6—C7	1.394 (3)	C14—H14	0.9500
C6—C11	1.395 (4)	N15—C16	1.340 (3)
C7—C8	1.379 (4)	C16—C17	1.381 (4)
C7—H7	0.9500	C16—H16	0.9500
C8—C9	1.379 (4)	C17—H17	0.9500
C8—H8	0.9500

N5—C1—C2	113.3 (2)	C9—C10—C11	118.1 (3)
N5—C1—H1	123.3	C9—C10—H10	120.9
C2—C1—H1	123.3	C11—C10—H10	120.9
C3—C2—C1	103.1 (2)	C10—C11—C6	121.2 (3)
C3—C2—C6	133.3 (2)	C10—C11—H11	119.4
C1—C2—C6	123.6 (2)	C6—C11—H11	119.4
C2—C3—O4	109.5 (2)	C17—C12—C13	116.8 (2)
C2—C3—C12	137.3 (2)	C17—C12—C3	123.1 (2)
O4—C3—C12	113.1 (2)	C13—C12—C3	120.0 (2)
C3—O4—N5	109.05 (19)	C14—C13—C12	119.8 (3)
C1—N5—O4	104.9 (2)	C14—C13—H13	120.1
C7—C6—C11	118.3 (2)	C12—C13—H13	120.1
C7—C6—C2	122.9 (2)	N15—C14—C13	123.8 (3)
C11—C6—C2	118.7 (2)	N15—C14—H14	118.1
C8—C7—C6	121.2 (2)	C13—C14—H14	118.1
C8—C7—H7	119.4	C14—N15—C16	116.1 (2)
C6—C7—H7	119.4	N15—C16—C17	124.3 (3)
C9—C8—C7	118.1 (3)	N15—C16—H16	117.8
C9—C8—H8	120.9	C17—C16—H16	117.8
C7—C8—H8	120.9	C16—C17—C12	119.2 (2)
F1—C9—C10	118.5 (3)	C16—C17—H17	120.4
F1—C9—C8	118.5 (3)	C12—C17—H17	120.4
C10—C9—C8	123.0 (3)

N5—C1—C2—C3	0.7 (4)	C7—C8—C9—C10	0.7 (5)
N5—C1—C2—C6	−178.3 (3)	F1—C9—C10—C11	178.3 (3)
C1—C2—C3—O4	−0.7 (3)	C8—C9—C10—C11	−1.6 (5)
C6—C2—C3—O4	178.1 (3)	C9—C10—C11—C6	0.9 (5)
C1—C2—C3—C12	176.7 (3)	C7—C6—C11—C10	0.6 (4)
C6—C2—C3—C12	−4.5 (6)	C2—C6—C11—C10	177.4 (3)
C2—C3—O4—N5	0.6 (3)	C2—C3—C12—C17	−10.5 (5)
C12—C3—O4—N5	−177.6 (2)	O4—C3—C12—C17	166.9 (3)
C2—C1—N5—O4	−0.4 (4)	C2—C3—C12—C13	170.4 (3)
C3—O4—N5—C1	−0.1 (3)	O4—C3—C12—C13	−12.2 (4)
C3—C2—C6—C7	−38.6 (5)	C17—C12—C13—C14	1.6 (4)
C1—C2—C6—C7	140.1 (3)	C3—C12—C13—C14	−179.2 (3)
C3—C2—C6—C11	144.8 (3)	C12—C13—C14—N15	−0.7 (5)
C1—C2—C6—C11	−36.6 (4)	C13—C14—N15—C16	−0.2 (4)
C11—C6—C7—C8	−1.5 (4)	C14—N15—C16—C17	0.2 (5)
C2—C6—C7—C8	−178.1 (3)	N15—C16—C17—C12	0.7 (5)
C6—C7—C8—C9	0.9 (5)	C13—C12—C17—C16	−1.5 (4)
C7—C8—C9—F1	−179.1 (3)	C3—C12—C17—C16	179.3 (3)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C1—H1···N15ⁱ	0.95	2.54	3.459 (4)	164

Symmetry code: (i) x, y, z+1.

References

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