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

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

doi:10.1107/S1600536810009189

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 66| Part 4| April 2010| Page o917

doi:10.1107/S1600536810009189

Open

access

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

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

^aInstitute of Pharmacy, Department of Pharmaceutical and Medicinal Chemistry, Eberhard-Karls-University Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany, and ^bDepartment of Organic Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14, 55099 Mainz, Germany
^*Correspondence e-mail: stefan.laufer@uni-tuebingen.de

(Received 9 March 2010; accepted 10 March 2010; online 24 March 2010)

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.

Related literature

For the 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

Crystal data

C₁₄H₁₀FN₃O
M_r = 255.25
Orthorhombic, P b c a
a = 10.1017 (4) Å
b = 8.3889 (8) Å
c = 29.127 (2) Å
V = 2468.3 (3) Å³
Z = 8
Cu Kα radiation
μ = 0.84 mm⁻¹
T = 193 K
0.40 × 0.30 × 0.10 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
Absorption correction: ψ scan (CORINC; Dräger & Gattow, 1971 ) T_min = 0.899, T_max = 0.997
2331 measured reflections
2331 independent reflections
1859 reflections with I > 2σ(I)
3 standard reflections every 60 min intensity decay: 2%

Refinement

R[F² > 2σ(F²)] = 0.043
wR(F²) = 0.119
S = 1.05
2331 reflections
173 parameters
H-atom parameters constrained
Δρ_max = 0.20 e Å⁻³
Δρ_min = −0.17 e Å⁻³

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N1—H1A⋯N4ⁱ	1.00	1.99	2.983 (2)	175
N1—H1B⋯N15ⁱⁱ	0.91	2.03	2.929 (2)	165
Symmetry codes: (i) -x, -y+1, -z+1; (ii) x-1, y, z.

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: 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.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536810009189/nc2179sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536810009189/nc2179Isup2.hkl

checkCIF report

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.

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

	Fig. 1. Molecular structure of the title compound with labelling and displacement ellipsoids are drawn at the 50% propability level.
	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

C₁₄H₁₀FN₃O	F(000) = 1056
M_r = 255.25	D_x = 1.374 Mg m⁻³
Orthorhombic, Pbca	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: -P 2ac 2ab	Cell parameters from 25 reflections
a = 10.1017 (4) Å	θ = 30–46°
b = 8.3889 (8) Å	µ = 0.84 mm⁻¹
c = 29.127 (2) Å	T = 193 K
V = 2468.3 (3) Å³	Plate, yellow
Z = 8	0.40 × 0.30 × 0.10 mm

Data collection top

Enraf–Nonius CAD-4 diffractometer	1859 reflections with I > 2σ(I)
Radiation source: rotating anode	R_int = 0.000
Graphite monochromator	θ_max = 69.9°, θ_min = 3.0°
ω/2θ scans	h = 0→12
Absorption correction: ψ scan (CORINC; Dräger & Gattow, 1971)	k = 0→10
T_min = 0.899, T_max = 0.997	l = −35→0
2331 measured reflections	3 standard reflections every 60 min
2331 independent reflections	intensity decay: 2%

Refinement top

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)] = 0.043	H-atom parameters constrained
wR(F²) = 0.119	w = 1/[σ²(F_o²) + (0.0607P)² + 0.5691P] where P = (F_o² + 2F_c²)/3
S = 1.05	(Δ/σ)_max = 0.001
2331 reflections	Δρ_max = 0.20 e Å⁻³
173 parameters	Δρ_min = −0.17 e Å⁻³
0 restraints	Extinction correction: SHELXL97 (Sheldrick, 2008), Fc^*=kFc[1+0.001xFc²λ³/sin(2θ)]^-1/4
Primary atom site location: structure-invariant direct methods	Extinction coefficient: 0.00056 (12)

Crystal data top

C₁₄H₁₀FN₃O	V = 2468.3 (3) Å³
M_r = 255.25	Z = 8
Orthorhombic, Pbca	Cu Kα radiation
a = 10.1017 (4) Å	µ = 0.84 mm⁻¹
b = 8.3889 (8) Å	T = 193 K
c = 29.127 (2) Å	0.40 × 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)	R_int = 0.000
T_min = 0.899, T_max = 0.997	3 standard reflections every 60 min
2331 measured reflections	intensity decay: 2%
2331 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.043	0 restraints
wR(F²) = 0.119	H-atom parameters constrained
S = 1.05	Δρ_max = 0.20 e Å⁻³
2331 reflections	Δρ_min = −0.17 e Å⁻³
173 parameters

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

	x	y	z	U_iso*/U_eq
F1	0.14358 (14)	0.10350 (16)	0.19761 (4)	0.0644 (4)
N1	−0.13607 (15)	0.4430 (3)	0.45720 (6)	0.0541 (5)
H1A	−0.1264	0.4860	0.4890	0.081*
H1B	−0.2133	0.4266	0.4415	0.081*
O1	−0.03766 (11)	0.36315 (17)	0.39018 (4)	0.0382 (3)
C2	0.09228 (16)	0.3491 (2)	0.37416 (6)	0.0329 (4)
C3	0.17254 (16)	0.3972 (2)	0.40860 (6)	0.0321 (4)
N4	0.09727 (14)	0.44405 (19)	0.44663 (5)	0.0362 (4)
C5	−0.02508 (16)	0.4204 (2)	0.43365 (6)	0.0378 (4)
C6	0.10541 (15)	0.2869 (2)	0.32790 (6)	0.0325 (4)
C7	0.20470 (17)	0.3409 (2)	0.29845 (6)	0.0371 (4)
H7	0.2644	0.4208	0.3087	0.044*
C8	0.21765 (18)	0.2803 (2)	0.25471 (6)	0.0423 (5)
H8	0.2856	0.3175	0.2348	0.051*
C9	0.1303 (2)	0.1652 (2)	0.24045 (6)	0.0435 (5)
C10	0.0300 (2)	0.1098 (2)	0.26787 (7)	0.0463 (5)
H10	−0.0300	0.0314	0.2569	0.056*
C11	0.01776 (17)	0.1703 (2)	0.31191 (6)	0.0394 (4)
H11	−0.0507	0.1324	0.3314	0.047*
C12	0.31809 (16)	0.4044 (2)	0.41163 (6)	0.0316 (4)
C13	0.37771 (16)	0.5163 (2)	0.43992 (6)	0.0348 (4)
H13	0.3254	0.5891	0.4571	0.042*
C14	0.51470 (17)	0.5205 (2)	0.44293 (6)	0.0395 (4)
H14	0.5539	0.5991	0.4621	0.047*
N15	0.59471 (15)	0.4203 (2)	0.42047 (5)	0.0439 (4)
C16	0.53651 (17)	0.3118 (3)	0.39376 (7)	0.0434 (5)
H16	0.5915	0.2388	0.3777	0.052*
C17	0.40105 (17)	0.2992 (2)	0.38802 (6)	0.0371 (4)
H17	0.3649	0.2201	0.3683	0.045*

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
F1	0.0878 (10)	0.0654 (8)	0.0399 (6)	0.0139 (7)	−0.0042 (6)	−0.0098 (6)
N1	0.0211 (7)	0.0942 (14)	0.0470 (9)	0.0003 (8)	0.0007 (7)	−0.0199 (9)
O1	0.0204 (6)	0.0547 (8)	0.0394 (7)	0.0007 (5)	−0.0015 (5)	−0.0051 (6)
C2	0.0199 (8)	0.0389 (9)	0.0400 (9)	0.0008 (7)	0.0013 (7)	0.0024 (7)
C3	0.0233 (8)	0.0345 (8)	0.0383 (9)	−0.0002 (7)	0.0002 (7)	0.0010 (7)
N4	0.0236 (7)	0.0476 (9)	0.0375 (8)	−0.0002 (6)	−0.0009 (6)	−0.0051 (7)
C5	0.0237 (8)	0.0513 (11)	0.0384 (10)	0.0011 (8)	−0.0010 (7)	−0.0059 (8)
C6	0.0229 (7)	0.0369 (9)	0.0378 (9)	0.0032 (7)	−0.0047 (7)	0.0036 (7)
C7	0.0294 (8)	0.0396 (9)	0.0422 (10)	0.0006 (7)	−0.0020 (7)	0.0017 (8)
C8	0.0394 (10)	0.0465 (11)	0.0410 (10)	0.0096 (8)	0.0044 (8)	0.0064 (9)
C9	0.0513 (11)	0.0455 (11)	0.0339 (9)	0.0147 (9)	−0.0062 (8)	−0.0038 (8)
C10	0.0401 (10)	0.0481 (12)	0.0507 (11)	0.0015 (9)	−0.0138 (9)	−0.0063 (9)
C11	0.0258 (8)	0.0480 (11)	0.0444 (10)	−0.0017 (8)	−0.0047 (7)	−0.0005 (9)
C12	0.0222 (8)	0.0362 (9)	0.0364 (9)	0.0005 (7)	−0.0014 (7)	0.0050 (7)
C13	0.0269 (8)	0.0406 (10)	0.0368 (9)	−0.0008 (7)	0.0002 (7)	−0.0003 (8)
C14	0.0279 (8)	0.0510 (11)	0.0396 (10)	−0.0071 (8)	−0.0049 (7)	0.0010 (9)
N15	0.0245 (7)	0.0632 (11)	0.0441 (9)	−0.0009 (7)	−0.0029 (6)	0.0010 (8)
C16	0.0274 (9)	0.0548 (12)	0.0480 (11)	0.0074 (8)	−0.0006 (8)	−0.0032 (9)
C17	0.0281 (9)	0.0391 (10)	0.0442 (10)	0.0020 (7)	−0.0034 (7)	−0.0023 (8)

Geometric parameters (Å, º) top

F1—C9	1.358 (2)	C8—H8	0.9500
N1—C5	1.328 (2)	C9—C10	1.372 (3)
N1—H1A	0.9994	C10—C11	1.385 (3)
N1—H1B	0.9144	C10—H10	0.9500
O1—C5	1.360 (2)	C11—H11	0.9500
O1—C2	1.3981 (19)	C12—C13	1.386 (2)
C2—C3	1.351 (2)	C12—C17	1.398 (2)
C2—C6	1.451 (2)	C13—C14	1.387 (2)
C3—N4	1.400 (2)	C13—H13	0.9500
C3—C12	1.474 (2)	C14—N15	1.337 (3)
N4—C5	1.308 (2)	C14—H14	0.9500
C6—C7	1.395 (2)	N15—C16	1.334 (3)
C6—C11	1.399 (2)	C16—C17	1.383 (2)
C7—C8	1.378 (3)	C16—H16	0.9500
C7—H7	0.9500	C17—H17	0.9500
C8—C9	1.372 (3)

C5—N1—H1A	116.6	F1—C9—C8	118.89 (18)
C5—N1—H1B	116.2	C10—C9—C8	122.51 (17)
H1A—N1—H1B	126.9	C9—C10—C11	118.74 (18)
C5—O1—C2	104.64 (13)	C9—C10—H10	120.6
C3—C2—O1	106.88 (15)	C11—C10—H10	120.6
C3—C2—C6	137.89 (15)	C10—C11—C6	120.54 (18)
O1—C2—C6	115.22 (14)	C10—C11—H11	119.7
C2—C3—N4	110.20 (14)	C6—C11—H11	119.7
C2—C3—C12	130.92 (17)	C13—C12—C17	117.35 (15)
N4—C3—C12	118.87 (15)	C13—C12—C3	119.78 (16)
C5—N4—C3	104.01 (14)	C17—C12—C3	122.85 (16)
N4—C5—N1	128.84 (17)	C12—C13—C14	119.23 (17)
N4—C5—O1	114.27 (15)	C12—C13—H13	120.4
N1—C5—O1	116.89 (15)	C14—C13—H13	120.4
C7—C6—C11	118.51 (17)	N15—C14—C13	123.78 (18)
C7—C6—C2	121.31 (15)	N15—C14—H14	118.1
C11—C6—C2	120.18 (16)	C13—C14—H14	118.1
C8—C7—C6	121.12 (17)	C16—N15—C14	116.61 (16)
C8—C7—H7	119.4	N15—C16—C17	123.99 (18)
C6—C7—H7	119.4	N15—C16—H16	118.0
C9—C8—C7	118.57 (18)	C17—C16—H16	118.0
C9—C8—H8	120.7	C16—C17—C12	119.03 (17)
C7—C8—H8	120.7	C16—C17—H17	120.5
F1—C9—C10	118.59 (19)	C12—C17—H17	120.5

C5—O1—C2—C3	0.36 (19)	C7—C8—C9—F1	−179.13 (16)
C5—O1—C2—C6	179.09 (15)	C7—C8—C9—C10	0.8 (3)
O1—C2—C3—N4	−0.7 (2)	F1—C9—C10—C11	178.78 (17)
C6—C2—C3—N4	−179.0 (2)	C8—C9—C10—C11	−1.1 (3)
O1—C2—C3—C12	178.41 (17)	C9—C10—C11—C6	0.6 (3)
C6—C2—C3—C12	0.1 (4)	C7—C6—C11—C10	0.3 (3)
C2—C3—N4—C5	0.7 (2)	C2—C6—C11—C10	−179.70 (16)
C12—C3—N4—C5	−178.50 (16)	C2—C3—C12—C13	151.88 (19)
C3—N4—C5—N1	178.7 (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—N4	0.1 (2)	N4—C3—C12—C17	148.94 (17)
C2—O1—C5—N1	−179.15 (18)	C17—C12—C13—C14	1.0 (3)
C3—C2—C6—C7	−37.0 (3)	C3—C12—C13—C14	179.18 (17)
O1—C2—C6—C7	144.77 (16)	C12—C13—C14—N15	−1.1 (3)
C3—C2—C6—C11	142.9 (2)	C13—C14—N15—C16	0.3 (3)
O1—C2—C6—C11	−35.3 (2)	C14—N15—C16—C17	0.5 (3)
C11—C6—C7—C8	−0.6 (3)	N15—C16—C17—C12	−0.6 (3)
C2—C6—C7—C8	179.34 (16)	C13—C12—C17—C16	−0.3 (3)
C6—C7—C8—C9	0.1 (3)	C3—C12—C17—C16	−178.35 (18)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···N4ⁱ	1.00	1.99	2.983 (2)	175
N1—H1B···N15ⁱⁱ	0.91	2.03	2.929 (2)	165

Symmetry codes: (i) −x, −y+1, −z+1; (ii) x−1, y, z.

Experimental details

Crystal data
Chemical formula	C₁₄H₁₀FN₃O
M_r	255.25
Crystal system, space group	Orthorhombic, Pbca
Temperature (K)	193
a, b, c (Å)	10.1017 (4), 8.3889 (8), 29.127 (2)
V (Å³)	2468.3 (3)
Z	8
Radiation type	Cu Kα
µ (mm⁻¹)	0.84
Crystal size (mm)	0.40 × 0.30 × 0.10

Data collection
Diffractometer	Enraf–Nonius CAD-4 diffractometer
Absorption correction	ψ scan (CORINC; Dräger & Gattow, 1971)
T_min, T_max	0.899, 0.997
No. of measured, independent and observed [I > 2σ(I)] reflections	2331, 2331, 1859
R_int	0.000
(sin θ/λ)_max (Å⁻¹)	0.609

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.043, 0.119, 1.05
No. of reflections	2331
No. of parameters	173
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	0.20, −0.17

Computer programs: CAD-4 Software (Enraf–Nonius, 1989), CORINC (Dräger & Gattow, 1971), SIR97 (Altomare et al., 1999), SHELXL97 (Sheldrick, 2008), PLATON (Spek, 2009).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N1—H1A···N4ⁱ	1.00	1.99	2.983 (2)	175
N1—H1B···N15ⁱⁱ	0.91	2.03	2.929 (2)	165

Symmetry codes: (i) −x, −y+1, −z+1; (ii) x−1, y, z.

References

Abu Thaher, B., Koch, P., Schattel, V. & Laufer, S. (2009). J. Med. Chem. 52, 2613–2617. Web of Science PubMed CAS Google Scholar
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. Web of Science CrossRef CAS IUCr Journals Google Scholar
Dräger, M. & Gattow, G. (1971). Acta Chem. Scand. 25, 761–762. Google Scholar
Enraf–Nonius (1989). CAD-4 Software. Enraf–Nonius, Delft, The Netherlands. Google Scholar
Peifer, C., Wagner, G. & Laufer, S. (2006). Curr. Top. Med. Chem. 6, 113–149. Web of Science CrossRef PubMed CAS Google Scholar
Sheldrick, G. M. (2008). Acta Cryst. A64, 112–122. Web of Science CrossRef CAS IUCr Journals Google Scholar
Spek, A. L. (2009). Acta Cryst. D65, 148–155. Web of Science CrossRef CAS IUCr Journals Google Scholar

This is an open-access article distributed under the terms of the Creative Commons Attribution (CC-BY) Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original authors and source are cited.

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 66| Part 4| April 2010| Page o917

doi:10.1107/S1600536810009189

Open

access