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

Koch, P.; Schollmeyer, D.; Laufer, S.

doi:10.1107/S2414314625009873

organic compounds

IUCrDATA

ISSN: 2414-3146

Volume 10| Part 11| November 2025| x250987

https://doi.org/10.1107/S2414314625009873

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

Pierre Koch,^a ^* Dieter Schollmeyer ^b and Stefan Laufer ^c

^aUniversität Regensburg, Universitätsstrasse 31, 93053 Regensburg, Germany, ^bUniversity Mainz, Department of Chemistry, Duesbergweg 10-14, 55099 Mainz, Germany, and ^cEberhard Karls Universität Tübingen, Department of Pharmaceutical/Medicinal Chemistry, Auf der Morgenstelle 8, 72076 Tübingen, Germany
^*Correspondence e-mail: [email protected]

Edited by M. Bolte, Goethe-Universität Frankfurt, Germany (Received 4 November 2025; accepted 6 November 2025; online 21 November 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 32.64 (5) and 32.70 (7)°, respectively.

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

CCDC reference: 2500863

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 pyridinyl-substituted five-membered heterocyclic ring inhibitors and the p38α mitogen-activated protein (MAP) kinase (Abu Thaher et al., 2009 ). The isoxazole ring (O1,C2–C4,N5) makes dihedral angles of 32.64 (5) and 32.70 (7)° with the 4-fluorophenyl ring (C6–C11) and the pyridine ring (C12–C14, N15, C16, C17), respectively. The 4-fluorophenyl ring makes a dihedral angle of 46.37 (6)° with the pyridine ring. In the extended structure, C—H⋯N bonds link the molecules into C(6) chains running along the c-axis direction (Table 1, Fig. 2).

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
C7—H7⋯N5ⁱ	0.95	2.44	3.2772 (19)	148
Symmetry code: (i) $[x, -y+{\script{1\over 2}}, z-{\script{1\over 2}}]$ .

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

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

Synthesis and crystallization

The title compound was synthesized according to the protocol reported by Laufer et al. (2006 ). 500 mg of 3-(dimethylamino)-1-(4-fluorophenyl)-2-(pyridin-4-yl)prop-2-en-1-one were dissolved in methanol (8 ml) and water (4 ml). 106 mg of sodium carbonate and 123 mg hydroxylamine hydrochloride 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 ammonia. Ice was added to the mixture and the title compound slowly crystallized as a colorless solid (290 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)	11.0938 (9), 8.6289 (3), 13.1513 (12)
β (°)	116.342 (4)
V (Å³)	1128.21 (15)
Z	4
Radiation type	Cu Kα
μ (mm⁻¹)	0.86
Crystal size (mm)	0.25 × 0.25 × 0.20

Data collection
Diffractometer	Enraf–Nonius CAD-4
Absorption correction	–
No. of measured, independent and observed [I > 2σ(I)] reflections	2139, 2139, 1997
R_int	0
(sin θ/λ)_max (Å⁻¹)	0.610

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.042, 0.124, 1.07
No. of reflections	2139
No. of parameters	164
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.28, −0.28
Computer programs: Enraf–Nonius Software (Enraf–Nonius, 1989 ), CORINC (Dräger & Gattow 1971 ), SHELXT2014 (Sheldrick, 2015a ), SHELXL2019/3 (Sheldrick, 2015b ) and PLATON (Spek, 2009 ).

Structural data

CCDC reference: 2500863

Crystal structure: contains datablocks I, global. DOI: https://doi.org/10.1107/S2414314625009873/bt4187sup1.cif

Structure factors: contains datablock I. DOI: https://doi.org/10.1107/S2414314625009873/bt4187Isup2.hkl

Supporting information file. DOI: https://doi.org/10.1107/S2414314625009873/bt4187Isup3.cml

checkCIF report

Computing details top

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

Crystal data top

C₁₄H₉FN₂O	F(000) = 496
M_r = 240.23	D_x = 1.414 Mg m⁻³
Monoclinic, P2₁/c	Cu Kα radiation, λ = 1.54178 Å
a = 11.0938 (9) Å	Cell parameters from 25 reflections
b = 8.6289 (3) Å	θ = 65–69°
c = 13.1513 (12) Å	µ = 0.86 mm⁻¹
β = 116.342 (4)°	T = 193 K
V = 1128.21 (15) Å³	Block, colourless
Z = 4	0.25 × 0.25 × 0.20 mm

Data collection top

Enraf–Nonius CAD-4 diffractometer	R_int = 0
Radiation source: rotating anode	θ_max = 70.1°, θ_min = 4.5°
Graphite monochromator	h = −13→12
ω/2θ scans	k = 0→10
2139 measured reflections	l = 0→16
2139 independent reflections	3 standard reflections every 60 min
1997 reflections with I > 2σ(I)	intensity decay: 1%

Refinement top

Refinement on F²	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F² > 2σ(F²)] = 0.042	w = 1/[σ²(F_o²) + (0.0738P)² + 0.3458P] where P = (F_o² + 2F_c²)/3
wR(F²) = 0.124	(Δ/σ)_max < 0.001
S = 1.07	Δρ_max = 0.28 e Å⁻³
2139 reflections	Δρ_min = −0.28 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: 0.0086 (11)
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	0.13611 (9)	0.46819 (11)	0.00038 (8)	0.0473 (3)
O1	0.55369 (11)	0.27510 (14)	0.48748 (9)	0.0424 (3)
C2	0.58461 (15)	0.33567 (17)	0.40706 (12)	0.0335 (3)
C3	0.72080 (14)	0.33966 (16)	0.44657 (12)	0.0310 (3)
C4	0.76924 (16)	0.27421 (18)	0.55716 (13)	0.0372 (4)
H4	0.862023	0.259844	0.606378	0.045*
N5	0.67381 (14)	0.23630 (18)	0.58372 (11)	0.0452 (4)
C6	0.46742 (14)	0.37489 (17)	0.29991 (12)	0.0332 (3)
C7	0.47353 (14)	0.35792 (18)	0.19678 (13)	0.0372 (4)
H7	0.554463	0.323746	0.195893	0.045*
C8	0.36212 (15)	0.39071 (19)	0.09582 (13)	0.0396 (4)
H8	0.365560	0.380371	0.025244	0.047*
C9	0.24600 (14)	0.43875 (17)	0.10017 (14)	0.0373 (4)
C10	0.23548 (15)	0.45675 (18)	0.19966 (15)	0.0401 (4)
H10	0.153807	0.490165	0.199504	0.048*
C11	0.34809 (15)	0.42451 (18)	0.30042 (13)	0.0376 (4)
H11	0.343831	0.436385	0.370570	0.045*
C12	0.80557 (14)	0.39405 (16)	0.39348 (11)	0.0294 (3)
C13	0.92774 (14)	0.32139 (17)	0.41942 (13)	0.0344 (3)
H13	0.956804	0.237041	0.471192	0.041*
C14	1.00631 (15)	0.37309 (19)	0.36917 (14)	0.0400 (4)
H14	1.089593	0.322108	0.388691	0.048*
N15	0.97329 (13)	0.48966 (17)	0.29514 (11)	0.0420 (4)
C16	0.85625 (17)	0.55986 (19)	0.27201 (13)	0.0407 (4)
H16	0.829864	0.643649	0.219731	0.049*
C17	0.77120 (15)	0.51901 (17)	0.31884 (12)	0.0339 (3)
H17	0.690549	0.575274	0.300406	0.041*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1	0.0339 (5)	0.0487 (6)	0.0518 (6)	−0.0011 (4)	0.0122 (4)	0.0010 (4)
O1	0.0423 (6)	0.0510 (7)	0.0450 (6)	−0.0004 (5)	0.0296 (5)	0.0066 (5)
C2	0.0396 (8)	0.0324 (7)	0.0380 (8)	0.0001 (6)	0.0258 (7)	−0.0007 (6)
C3	0.0367 (7)	0.0277 (7)	0.0339 (7)	0.0019 (5)	0.0205 (6)	0.0004 (5)
C4	0.0433 (8)	0.0372 (8)	0.0369 (8)	0.0021 (6)	0.0230 (7)	0.0033 (6)
N5	0.0493 (8)	0.0521 (8)	0.0418 (8)	0.0038 (6)	0.0271 (7)	0.0093 (6)
C6	0.0327 (7)	0.0324 (7)	0.0400 (8)	−0.0020 (5)	0.0210 (6)	−0.0021 (6)
C7	0.0304 (7)	0.0441 (8)	0.0426 (8)	−0.0011 (6)	0.0212 (7)	−0.0054 (7)
C8	0.0371 (8)	0.0459 (9)	0.0402 (8)	−0.0047 (7)	0.0212 (7)	−0.0049 (7)
C9	0.0296 (7)	0.0339 (8)	0.0451 (8)	−0.0030 (6)	0.0135 (6)	−0.0008 (6)
C10	0.0339 (8)	0.0362 (8)	0.0574 (10)	0.0032 (6)	0.0266 (7)	−0.0001 (7)
C11	0.0395 (8)	0.0375 (8)	0.0454 (9)	0.0010 (6)	0.0276 (7)	−0.0014 (6)
C12	0.0327 (7)	0.0294 (7)	0.0298 (7)	−0.0036 (5)	0.0171 (6)	−0.0045 (5)
C13	0.0360 (7)	0.0322 (7)	0.0386 (8)	0.0018 (6)	0.0197 (6)	0.0000 (6)
C14	0.0346 (8)	0.0439 (9)	0.0472 (9)	−0.0005 (6)	0.0233 (7)	−0.0063 (7)
N15	0.0429 (7)	0.0493 (8)	0.0433 (7)	−0.0090 (6)	0.0278 (6)	−0.0052 (6)
C16	0.0461 (9)	0.0422 (8)	0.0376 (8)	−0.0048 (7)	0.0221 (7)	0.0038 (6)
C17	0.0341 (7)	0.0341 (7)	0.0354 (7)	0.0015 (6)	0.0173 (6)	0.0015 (6)

Geometric parameters (Å, º) top

F1—C9	1.3614 (17)	C9—C10	1.373 (2)
O1—C2	1.3533 (17)	C10—C11	1.387 (2)
O1—N5	1.4118 (17)	C10—H10	0.9500
C2—C3	1.363 (2)	C11—H11	0.9500
C2—C6	1.471 (2)	C12—C13	1.391 (2)
C3—C4	1.425 (2)	C12—C17	1.393 (2)
C3—C12	1.4748 (18)	C13—C14	1.381 (2)
C4—N5	1.295 (2)	C13—H13	0.9500
C4—H4	0.9500	C14—N15	1.333 (2)
C6—C11	1.394 (2)	C14—H14	0.9500
C6—C7	1.395 (2)	N15—C16	1.340 (2)
C7—C8	1.384 (2)	C16—C17	1.382 (2)
C7—H7	0.9500	C16—H16	0.9500
C8—C9	1.378 (2)	C17—H17	0.9500
C8—H8	0.9500

C2—O1—N5	109.06 (11)	C9—C10—C11	117.79 (14)
O1—C2—C3	109.53 (13)	C9—C10—H10	121.1
O1—C2—C6	114.50 (12)	C11—C10—H10	121.1
C3—C2—C6	135.92 (13)	C10—C11—C6	120.76 (14)
C2—C3—C4	103.39 (12)	C10—C11—H11	119.6
C2—C3—C12	131.26 (13)	C6—C11—H11	119.6
C4—C3—C12	125.35 (13)	C13—C12—C17	117.00 (13)
N5—C4—C3	113.09 (14)	C13—C12—C3	119.80 (13)
N5—C4—H4	123.5	C17—C12—C3	123.19 (13)
C3—C4—H4	123.5	C14—C13—C12	119.35 (14)
C4—N5—O1	104.93 (12)	C14—C13—H13	120.3
C11—C6—C7	119.52 (14)	C12—C13—H13	120.3
C11—C6—C2	120.23 (13)	N15—C14—C13	124.47 (14)
C7—C6—C2	120.22 (13)	N15—C14—H14	117.8
C8—C7—C6	120.21 (14)	C13—C14—H14	117.8
C8—C7—H7	119.9	C14—N15—C16	115.57 (13)
C6—C7—H7	119.9	N15—C16—C17	124.62 (15)
C9—C8—C7	118.36 (14)	N15—C16—H16	117.7
C9—C8—H8	120.8	C17—C16—H16	117.7
C7—C8—H8	120.8	C16—C17—C12	118.96 (14)
F1—C9—C10	118.64 (13)	C16—C17—H17	120.5
F1—C9—C8	118.01 (14)	C12—C17—H17	120.5
C10—C9—C8	123.35 (15)

N5—O1—C2—C3	−0.45 (17)	C7—C8—C9—C10	0.5 (2)
N5—O1—C2—C6	177.46 (12)	F1—C9—C10—C11	179.28 (13)
O1—C2—C3—C4	0.79 (16)	C8—C9—C10—C11	0.0 (2)
C6—C2—C3—C4	−176.47 (16)	C9—C10—C11—C6	−0.3 (2)
O1—C2—C3—C12	−179.98 (14)	C7—C6—C11—C10	0.2 (2)
C6—C2—C3—C12	2.8 (3)	C2—C6—C11—C10	−177.78 (14)
C2—C3—C4—N5	−0.93 (18)	C2—C3—C12—C13	−147.29 (16)
C12—C3—C4—N5	179.79 (14)	C4—C3—C12—C13	31.8 (2)
C3—C4—N5—O1	0.66 (18)	C2—C3—C12—C17	34.1 (2)
C2—O1—N5—C4	−0.13 (17)	C4—C3—C12—C17	−146.80 (15)
O1—C2—C6—C11	32.3 (2)	C17—C12—C13—C14	−1.4 (2)
C3—C2—C6—C11	−150.50 (17)	C3—C12—C13—C14	179.94 (13)
O1—C2—C6—C7	−145.61 (14)	C12—C13—C14—N15	−0.5 (2)
C3—C2—C6—C7	31.6 (3)	C13—C14—N15—C16	1.3 (2)
C11—C6—C7—C8	0.3 (2)	C14—N15—C16—C17	−0.2 (2)
C2—C6—C7—C8	178.20 (14)	N15—C16—C17—C12	−1.7 (2)
C6—C7—C8—C9	−0.6 (2)	C13—C12—C17—C16	2.4 (2)
C7—C8—C9—F1	−178.88 (13)	C3—C12—C17—C16	−179.02 (13)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
C7—H7···N5ⁱ	0.95	2.44	3.2772 (19)	148

Symmetry code: (i) x, −y+1/2, z−1/2.

References

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