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Acta Cryst. (2010). E66, o917    [ doi:10.1107/S1600536810009189 ]

5-(4-Fluorophenyl)-4-(4-pyridyl)-1,3-oxazol-2-amine

P. Koch, D. Schollmeyer and S. Laufer

Abstract top

In the crystal structure of the title compound, C14H10FN3O, the plane of the isoxazole ring makes dihedral angles of 35.72 (9) and 30.00 (9)°, respectively, with those of the 4-fluorophenyl and pyridine rings. The plane of the 4-fluorophenyl ring makes a dihedral angle of 45.85 (8)° with that of the pyridine ring. The crystal structure is stabilized by intermolecular N-H...N hydrogen bonding. The two types of hydrogen bonds result in two chains, extending along the a axis, which are related by centres of symmetry.

Comment top

Compounds having a vicinal 4-fluorophenyl/pyridin-4-yl system connected to a five-membered heterocyclic core have been considered to be potential p38α MAP kinase inhibitors (Abu Thaher et al. 2009, Peifer et al. 2006).

The microwave-assisted reaction of 2-bromo-2-(4-fluorophenyl)-1-(pyridin-4-yl)ethanone hydrobromide and urea could gave two products, namely 5-(4-flouorophenyl)-4-(pyridin-4-yl)oxazol-2-amine and 4-(4-fluorophenyl)-5-(pyridin-4-yl)-1,3-dihydroimidazol-2-one. The structure determination was undertaken to identify the obtained product and showed that only 5-(4-flouorophenyl)-4-(pyridin-4-yl)oxazol-2-amine was formed in the reaction above-mentioned.

In the crystal structure of the title compound, the isoxazole ring makes dihedral angles of 35.72 (9)° and 30.00 (9)° to the 4-fluorophenyl ring and the pyridine ring, respectively (Figure 1). The 4-fluorophenyl ring makes dihedral angles of 45.85 (8)° to the pyridine ring.

The crystal packing (Figure 2) shows that the amino function acts an a hydrogen bond donor forming hydrogen bonds to the nitrogen atom of the pyridine ring and to the nitrogen atom of the oxale ring of two different molecules. The lenght of the hydrogen bonds is 1.99 Å and 2.03 Å, respectively (Table 1). The two types of hydrogen bonds result in two chains that elongate along the a-axis which are related by centres of symmetry.

Related literature top

For biological activity of pyridinyloxazoles, see: Peifer et al. (2006). For p38α MAP kinase inhibitors having a vicinal 4-fluorophenyl/pyridin-4-yl system connected to a five-membered heterocyclic core, see: Abu Thaher et al. (2009).

Experimental top

2-Bromo-2-(4-fluorophenyl)-1-(pyridin-4-yl)ethanone hydrobromide (150 mg, 0.40 mmol), urea (24 mg, 0.40 mmol) and DMF (1 ml) were combined in a reaction vial. The reaction vessel was heated in a CEM microwave reactor for 10 min at 433 K (initial power 250 W) and afterwards the vessel was cooled down to room temperature by a stream of compressed air. Water and ethyl acetate were added and the organic layer was separated. This layer was washed with water (3x), dried over Na2SO4 and concentrated in vacuo. The yellow residue was suspended twice with DCM/EtOH 95-5, filtered and finally dried. Yield 83 mg (81 %). Suitable crystals of the title compound for X-ray were obtained by slow evaporation at 298 K of a solution of methanol.

Refinement top

Hydrogen atoms attached to carbons were placed at calculated positions with C—H = 0.95 Å (aromatic) or 0.98–0.99 Å (sp3 C-atom). The H atoms attached to N1 were located in diff. Fourier maps. All H atoms were refined in the riding-model approximation with isotropic displacement parameters (set at 1.2–1.5 times of the Ueq of the parent atom).

Computing details top

Data collection: CAD-4 Software (Enraf–Nonius, 1989); cell refinement: CAD-4 Software (Enraf–Nonius, 1989); data reduction: CORINC (Dräger & Gattow, 1971); program(s) used to solve structure: SIR97 (Altomare et al., 1999); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008); molecular graphics: PLATON (Spek, 2009); software used to prepare material for publication: PLATON (Spek, 2009).

Figures top
[Figure 1] Fig. 1. Molecular structure of the title compound with labelling and displacement ellipsoids are drawn at the 50% propability level.
[Figure 2] Fig. 2. Crystal structure of the title compound with view along the b-axis (hydrogen bonding is shown with dashed lines).
5-(4-Fluorophenyl)-4-(4-pyridyl)-1,3-oxazol-2-amine top
Crystal data top
C14H10FN3OF(000) = 1056
Mr = 255.25Dx = 1.374 Mg m−3
Orthorhombic, PbcaCu Kα radiation, λ = 1.54178 Å
Hall symbol: -P 2ac 2abCell parameters from 25 reflections
a = 10.1017 (4) Åθ = 30–46°
b = 8.3889 (8) ŵ = 0.84 mm−1
c = 29.127 (2) ÅT = 193 K
V = 2468.3 (3) Å3Plate, yellow
Z = 80.40 × 0.30 × 0.10 mm
Data collection top
Enraf–Nonius CAD-4
diffractometer		1859 reflections with I > 2σ(I)
Radiation source: rotating anodeRint = 0.0000
graphiteθmax = 69.9°, θmin = 3.0°
ω/2θ scansh = 0→12
Absorption correction: ψ scan
(CORINC; Dräger & Gattow, 1971)		k = 0→10
Tmin = 0.899, Tmax = 0.997l = −35→0
2331 measured reflections3 standard reflections every 60 min
2331 independent reflections intensity decay: 2%
Refinement top
Refinement on F2Secondary atom site location: difference Fourier map
Least-squares matrix: fullHydrogen site location: inferred from neighbouring sites
R[F2 > 2σ(F2)] = 0.043H-atom parameters constrained
wR(F2) = 0.119 w = 1/[σ2(Fo2) + (0.0607P)2 + 0.5691P]
where P = (Fo2 + 2Fc2)/3
S = 1.05(Δ/σ)max = 0.001
2331 reflectionsΔρmax = 0.20 e Å−3
173 parametersΔρmin = −0.17 e Å−3
0 restraintsExtinction correction: SHELXL97 (Sheldrick, 2008), Fc*=kFc[1+0.001xFc2λ3/sin(2θ)]-1/4
Primary atom site location: structure-invariant direct methodsExtinction coefficient: 0.00056 (12)
Crystal data top
C14H10FN3OV = 2468.3 (3) Å3
Mr = 255.25Z = 8
Orthorhombic, PbcaCu Kα radiation
a = 10.1017 (4) ŵ = 0.84 mm−1
b = 8.3889 (8) ÅT = 193 K
c = 29.127 (2) Å0.40 × 0.30 × 0.10 mm
Data collection top
Enraf–Nonius CAD-4
diffractometer		1859 reflections with I > 2σ(I)
Absorption correction: ψ scan
(CORINC; Dräger & Gattow, 1971)		Rint = 0.0000
Tmin = 0.899, Tmax = 0.997θmax = 69.9°
2331 measured reflections3 standard reflections every 60 min
2331 independent reflections intensity decay: 2%
Refinement top
R[F2 > 2σ(F2)] = 0.043H-atom parameters constrained
wR(F2) = 0.119Δρmax = 0.20 e Å−3
S = 1.05Δρmin = −0.17 e Å−3
2331 reflectionsAbsolute structure: ?
173 parametersFlack parameter: ?
0 restraintsRogers parameter: ?
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 > 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
xyzUiso*/Ueq
F10.14358 (14)0.10350 (16)0.19761 (4)0.0644 (4)
N1−0.13607 (15)0.4430 (3)0.45720 (6)0.0541 (5)
H1A−0.12640.48600.48900.081*
H1B−0.21330.42660.44150.081*
O1−0.03766 (11)0.36315 (17)0.39018 (4)0.0382 (3)
C20.09228 (16)0.3491 (2)0.37416 (6)0.0329 (4)
C30.17254 (16)0.3972 (2)0.40860 (6)0.0321 (4)
N40.09727 (14)0.44405 (19)0.44663 (5)0.0362 (4)
C5−0.02508 (16)0.4204 (2)0.43365 (6)0.0378 (4)
C60.10541 (15)0.2869 (2)0.32790 (6)0.0325 (4)
C70.20470 (17)0.3409 (2)0.29845 (6)0.0371 (4)
H70.26440.42080.30870.044*
C80.21765 (18)0.2803 (2)0.25471 (6)0.0423 (5)
H80.28560.31750.23480.051*
C90.1303 (2)0.1652 (2)0.24045 (6)0.0435 (5)
C100.0300 (2)0.1098 (2)0.26787 (7)0.0463 (5)
H10−0.03000.03140.25690.056*
C110.01776 (17)0.1703 (2)0.31191 (6)0.0394 (4)
H11−0.05070.13240.33140.047*
C120.31809 (16)0.4044 (2)0.41163 (6)0.0316 (4)
C130.37771 (16)0.5163 (2)0.43992 (6)0.0348 (4)
H130.32540.58910.45710.042*
C140.51470 (17)0.5205 (2)0.44293 (6)0.0395 (4)
H140.55390.59910.46210.047*
N150.59471 (15)0.4203 (2)0.42047 (5)0.0439 (4)
C160.53651 (17)0.3118 (3)0.39376 (7)0.0434 (5)
H160.59150.23880.37770.052*
C170.40105 (17)0.2992 (2)0.38802 (6)0.0371 (4)
H170.36490.22010.36830.045*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
F10.0878 (10)0.0654 (8)0.0399 (6)0.0139 (7)−0.0042 (6)−0.0098 (6)
N10.0211 (7)0.0942 (14)0.0470 (9)0.0003 (8)0.0007 (7)−0.0199 (9)
O10.0204 (6)0.0547 (8)0.0394 (7)0.0007 (5)−0.0015 (5)−0.0051 (6)
C20.0199 (8)0.0389 (9)0.0400 (9)0.0008 (7)0.0013 (7)0.0024 (7)
C30.0233 (8)0.0345 (8)0.0383 (9)−0.0002 (7)0.0002 (7)0.0010 (7)
N40.0236 (7)0.0476 (9)0.0375 (8)−0.0002 (6)−0.0009 (6)−0.0051 (7)
C50.0237 (8)0.0513 (11)0.0384 (10)0.0011 (8)−0.0010 (7)−0.0059 (8)
C60.0229 (7)0.0369 (9)0.0378 (9)0.0032 (7)−0.0047 (7)0.0036 (7)
C70.0294 (8)0.0396 (9)0.0422 (10)0.0006 (7)−0.0020 (7)0.0017 (8)
C80.0394 (10)0.0465 (11)0.0410 (10)0.0096 (8)0.0044 (8)0.0064 (9)
C90.0513 (11)0.0455 (11)0.0339 (9)0.0147 (9)−0.0062 (8)−0.0038 (8)
C100.0401 (10)0.0481 (12)0.0507 (11)0.0015 (9)−0.0138 (9)−0.0063 (9)
C110.0258 (8)0.0480 (11)0.0444 (10)−0.0017 (8)−0.0047 (7)−0.0005 (9)
C120.0222 (8)0.0362 (9)0.0364 (9)0.0005 (7)−0.0014 (7)0.0050 (7)
C130.0269 (8)0.0406 (10)0.0368 (9)−0.0008 (7)0.0002 (7)−0.0003 (8)
C140.0279 (8)0.0510 (11)0.0396 (10)−0.0071 (8)−0.0049 (7)0.0010 (9)
N150.0245 (7)0.0632 (11)0.0441 (9)−0.0009 (7)−0.0029 (6)0.0010 (8)
C160.0274 (9)0.0548 (12)0.0480 (11)0.0074 (8)−0.0006 (8)−0.0032 (9)
C170.0281 (9)0.0391 (10)0.0442 (10)0.0020 (7)−0.0034 (7)−0.0023 (8)
Geometric parameters (Å, °) top
F1—C91.358 (2)C8—H80.9500
N1—C51.328 (2)C9—C101.372 (3)
N1—H1A0.9994C10—C111.385 (3)
N1—H1B0.9144C10—H100.9500
O1—C51.360 (2)C11—H110.9500
O1—C21.3981 (19)C12—C131.386 (2)
C2—C31.351 (2)C12—C171.398 (2)
C2—C61.451 (2)C13—C141.387 (2)
C3—N41.400 (2)C13—H130.9500
C3—C121.474 (2)C14—N151.337 (3)
N4—C51.308 (2)C14—H140.9500
C6—C71.395 (2)N15—C161.334 (3)
C6—C111.399 (2)C16—C171.383 (2)
C7—C81.378 (3)C16—H160.9500
C7—H70.9500C17—H170.9500
C8—C91.372 (3)
C5—N1—H1A116.6F1—C9—C8118.89 (18)
C5—N1—H1B116.2C10—C9—C8122.51 (17)
H1A—N1—H1B126.9C9—C10—C11118.74 (18)
C5—O1—C2104.64 (13)C9—C10—H10120.6
C3—C2—O1106.88 (15)C11—C10—H10120.6
C3—C2—C6137.89 (15)C10—C11—C6120.54 (18)
O1—C2—C6115.22 (14)C10—C11—H11119.7
C2—C3—N4110.20 (14)C6—C11—H11119.7
C2—C3—C12130.92 (17)C13—C12—C17117.35 (15)
N4—C3—C12118.87 (15)C13—C12—C3119.78 (16)
C5—N4—C3104.01 (14)C17—C12—C3122.85 (16)
N4—C5—N1128.84 (17)C12—C13—C14119.23 (17)
N4—C5—O1114.27 (15)C12—C13—H13120.4
N1—C5—O1116.89 (15)C14—C13—H13120.4
C7—C6—C11118.51 (17)N15—C14—C13123.78 (18)
C7—C6—C2121.31 (15)N15—C14—H14118.1
C11—C6—C2120.18 (16)C13—C14—H14118.1
C8—C7—C6121.12 (17)C16—N15—C14116.61 (16)
C8—C7—H7119.4N15—C16—C17123.99 (18)
C6—C7—H7119.4N15—C16—H16118.0
C9—C8—C7118.57 (18)C17—C16—H16118.0
C9—C8—H8120.7C16—C17—C12119.03 (17)
C7—C8—H8120.7C16—C17—H17120.5
F1—C9—C10118.59 (19)C12—C17—H17120.5
C5—O1—C2—C30.36 (19)C7—C8—C9—F1−179.13 (16)
C5—O1—C2—C6179.09 (15)C7—C8—C9—C100.8 (3)
O1—C2—C3—N4−0.7 (2)F1—C9—C10—C11178.78 (17)
C6—C2—C3—N4−179.0 (2)C8—C9—C10—C11−1.1 (3)
O1—C2—C3—C12178.41 (17)C9—C10—C11—C60.6 (3)
C6—C2—C3—C120.1 (4)C7—C6—C11—C100.3 (3)
C2—C3—N4—C50.7 (2)C2—C6—C11—C10−179.70 (16)
C12—C3—N4—C5−178.50 (16)C2—C3—C12—C13151.88 (19)
C3—N4—C5—N1178.7 (2)N4—C3—C12—C13−29.1 (2)
C3—N4—C5—O1−0.5 (2)C2—C3—C12—C17−30.1 (3)
C2—O1—C5—N40.1 (2)N4—C3—C12—C17148.94 (17)
C2—O1—C5—N1−179.15 (18)C17—C12—C13—C141.0 (3)
C3—C2—C6—C7−37.0 (3)C3—C12—C13—C14179.18 (17)
O1—C2—C6—C7144.77 (16)C12—C13—C14—N15−1.1 (3)
C3—C2—C6—C11142.9 (2)C13—C14—N15—C160.3 (3)
O1—C2—C6—C11−35.3 (2)C14—N15—C16—C170.5 (3)
C11—C6—C7—C8−0.6 (3)N15—C16—C17—C12−0.6 (3)
C2—C6—C7—C8179.34 (16)C13—C12—C17—C16−0.3 (3)
C6—C7—C8—C90.1 (3)C3—C12—C17—C16−178.35 (18)
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1A···N4i1.001.992.983 (2)175
N1—H1B···N15ii0.912.032.929 (2)165
Symmetry codes: (i) −x, −y+1, −z+1; (ii) x−1, y, z.
Table 1
Hydrogen-bond geometry (Å, °) top
D—H···AD—HH···AD···AD—H···A
N1—H1A···N4i1.001.992.983 (2)175
N1—H1B···N15ii0.912.032.929 (2)165
Symmetry codes: (i) −x, −y+1, −z+1; (ii) x−1, y, z.
references
References top

Abu Thaher, B., Koch, P., Schattel, V. & Laufer, S. (2009). J. Med. Chem. 52, 2613–2617.

Altomare, A., Burla, M. C., Camalli, M., Cascarano, G. L., Giacovazzo, C., Guagliardi, A., Moliterni, A. G. G., Polidori, G. & Spagna, R. (1999). J. Appl. Cryst. 32, 115–119.

Dräger, M. & Gattow, G. (1971). Acta Chem. Scand. 25, 761–762.

Enraf–Nonius (1989). CAD-4 Software. Enraf–Nonius, Delft, The Netherlands.

Peifer, C., Wagner, G. & Laufer, S. (2006). Curr. Top. Med. Chem. 6, 113–149.

Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122.

Spek, A. L. (2009). Acta Cryst. D65, 148–155.