Methyl 4-[5-(4-fluoro­phen­yl)-4-(pyridin-4-yl)-1H-imidazol-2-ylsulfan­yl]butanoate

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

doi:10.1107/S1600536808016000

organic compounds

CRYSTALLOGRAPHIC
COMMUNICATIONS

ISSN: 2056-9890

Volume 64| Part 7| July 2008| Pages o1183-o1184

doi:10.1107/S1600536808016000

Open

access

Methyl 4-[5-(4-fluorophenyl)-4-(pyridin-4-yl)-1H-imidazol-2-ylsulfanyl]butanoate

Pierre Koch,^a Christiane Bäuerlein,^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 17 April 2008; accepted 27 May 2008; online 7 June 2008)

The title compound, C₁₉H₁₈FN₃O₂S, was synthesized in the course of studies on 2-alkylsufanylimidazoles as p38 mitogen-activated protein kinase inhibitors. The synthesis was achieved by nucleophilic substitution of 4-(4-fluorophenyl)-5-(pyridin-4-yl)-1,3-dihydroimidazole-2-thione with methyl 4-bromobutanoate. The five-membered heterocycle makes dihedral angles of 32.4 (2) and 18.3 (2)° with the fluorophenyl and pyridinyl rings, respectively, indicating a low degree of conjugation between these rings. Intramolecular C—H⋯N and intermolecular N—H⋯N hydrogen bonds as well as C—H⋯π interactions seem to be effective in stabilization of the crystal structure.

Related literature

Substituted imidazoles as small-molecule inhibitors of p38 MAP kinase have been reviewed by Peifer et al. (2006 ) and Wagner & Laufer (2006 ). For the preparation of 4-(4-fluorophenyl)-5-(pyridin-4-yl)-1,3-dihydroimidazole-2-thione, see: Lantos et al. (1988 ). For related literature, see: Laufer, Striegel & Wagner (2002 ); Laufer, Wagner & Kotschenreuther (2002 ); Laufer & Koch (2008 ); Wang et al. (1998 ); Peifer et al. (2007 ).

Experimental

Crystal data

C₁₉H₁₈FN₃O₂S
M_r = 371.42
Orthorhombic, P c a 2₁
a = 18.494 (4) Å
b = 12.4367 (10) Å
c = 7.5255 (5) Å
V = 1730.9 (4) Å³
Z = 4
Cu Kα radiation
μ = 1.92 mm⁻¹
T = 193 (2) K
0.55 × 0.12 × 0.09 mm

Data collection

Enraf–Nonius CAD-4 diffractometer
Absorption correction: Gaussian (PLATON; Spek, 2003 ) T_min = 0.61, T_max = 0.85
3363 measured reflections
3086 independent reflections
2869 reflections with I > 2σ(I)
R_int = 0.051
3 standard reflections frequency: 60 min intensity decay: 5%

Refinement

R[F² > 2σ(F²)] = 0.076
wR(F²) = 0.188
S = 1.14
3086 reflections
236 parameters
1 restraint
H-atom parameters constrained
Δρ_max = 1.14 e Å⁻³
Δρ_min = −0.60 e Å⁻³
Absolute structure: Flack (1983 ), 1307 Friedel pairs
Flack parameter: −0.02 (3)

Table 1
Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N5—H5⋯N17ⁱ	0.90	1.95	2.849 (4)	174
Symmetry code: (i) $[x+{\script{1\over 2}}, -y+1, z]$ .

Table 2
Nonconventional C—H⋯X contacts (Å, °)

C–H⋯A	C–H	H⋯A	C–H⋯A	C⋯A
C13–H13B⋯Cg1ⁱⁱ	0.98	2.65	156	3.566 (6)
C7–H7A⋯N2	0.99	2.57	100	2.910 (5)
Symmetry code: (ii) x, y-1, z. Cg1 is the centroid of the C20–C25 ring.

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, 2003); software used to prepare material for publication: PLATON.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808016000/bx2140sup1.cif

Structure factors: contains datablock I. DOI: 10.1107/S1600536808016000/bx2140Isup2.hkl

checkCIF report

Comment top

The title compound was prepared in the course of our studies on 2-alkylsulfanyl-4-(4-fluorophenyl)-5-pyridinyl imidazoles as p38 mitogen-activated protein (MAP) kinase inhibitors. The p38 MAP kinase plays a central role for the biosynthesis and release of pro-inflammatory cytokines like TNF-α and IL-1β. Inhibition of p38 MAP kinase is therefore a promising therapeutic strategy for the treatment of inflammatory disorders like psoriasis, inflammatory bowel disease and rheumatoid arthritis. The fundamental SAR for the class of pyridinyl imidazole derivative as p38 MAP kinase inhibitors can be exemplified by the way SB203580 binds to the protein (Wang et al., 1998). There is a crucial hydrogen bond between the pyridin-4-yl moiety and Met109 of the enzyme. The 4-fluorophenyl ring binds to the hydrophobic region I, mainly gaining selectivity. Another possible ligand-protein interaction is a hydrogen bond between Lys53 and N3 of the imidazole core (Peifer et al., 2007).

The analysis of the crystal structure of methyl 4-(5-(4-fluorophenyl)-4-(pyridin-4-yl)-1H-imidazol-2-ylthio)butanoate (I) is shown in Figure 1. The crystal packing (Figure 2) shows that N5—H5 of the imidazole ring forms an intermolecular N–H···N hydrogen bond to pyridine (N17). The length of the hydrogen bond is 1.95Å (Table 1). Non-conventional C—H···X H-bonds are also present in addition to intermolecular N—H···N hydrogen interactions (Table 2).

Related literature top

Substituted imidazoles as small-molecule inhibitors of p38 MAP kinase have been reviewed by Peifer et al. (2006) and Wagner & Laufer (2006). For the preparation of 4-(4-fluorophenyl)-5-(pyridin-4-yl)-1,3-dihydroimidazole-2-thione, see: Lantos et al. (1988). For related literature, see: Laufer, Striegel & Wagner (2002); Laufer, Wagner & Kotschenreuther (2002); Laufer & Koch (2008); Wang et al. (1998); Peifer et al. (2007).

Experimental top

To a stirred solution of 4-(4-fluorophenyl)-5-(pyridin-4-yl)-1,3-dihydroimidazole-2-thione (0.74 mmol) and potassium tert-butoxide (0.77 mmol) in dry methanol (15 ml) was added under argon atmosphere after 15 min metyl 4-bromobutanoate (0.77 mmol). The solution was heated for 1 h to reflux temperature. After extraction with water and ethyl acetate the organic layer was washed twice with water, dried over sodium sulfate and evaporated under reduced pressure. The crude product was purified by flash chromatography (silica gel, dichloromethane - ethyl acetate 1:1 to 2:3) to yield methyl 4-(5-(4-fluorophenyl)-4-(pyridin-4-yl)-1H-imidazol-2-ylthio)butanoate (I) (49%) as a colorless solid. Compound I was crystallized from 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, 2003); software used to prepare material for publication: PLATON (Spek, 2003).

Figures top

	Fig. 1. View of compound I. Displacement ellipsoids are drawn at the 50% probability level. H atoms are depicted as circles of arbitrary size.
	Fig. 2. Part of the crystal packing of compound I. The hydrogen bond is shown with dashed lines. View along c axis. N17_b:x + 1/2, 1 - y, z

Methyl 4-[5-(4-fluorophenyl)-4-(pyridin-4-yl)-1H-imidazol-2-ylsulfanyl]butanoate top

Crystal data top

C₁₉H₁₈FN₃O₂S	F(000) = 776
M_r = 371.42	D_x = 1.425 Mg m⁻³
Orthorhombic, Pca2₁	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: P 2c -2ac	Cell parameters from 25 reflections
a = 18.494 (4) Å	θ = 31–44°
b = 12.4367 (10) Å	µ = 1.92 mm⁻¹
c = 7.5255 (5) Å	T = 193 K
V = 1730.9 (4) Å³	Needle, colourless
Z = 4	0.55 × 0.12 × 0.09 mm

Data collection top

Enraf–Nonius CAD-4 diffractometer	2869 reflections with I > 2σ(I)
Radiation source: rotating anode	R_int = 0.051
Graphite monochromator	θ_max = 70.0°, θ_min = 3.6°
ω/2θ scans	h = −22→22
Absorption correction: gaussian (PLATON; Spek, 2003)	k = −15→15
T_min = 0.61, T_max = 0.85	l = −7→9
3363 measured reflections	3 standard reflections every 60 min
3086 independent reflections	intensity decay: 5%

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)] = 0.076	H-atom parameters constrained
wR(F²) = 0.188	w = 1/[σ²(F_o²) + (0.1374P)²] where P = (F_o² + 2F_c²)/3
S = 1.14	(Δ/σ)_max < 0.001
3086 reflections	Δρ_max = 1.14 e Å⁻³
236 parameters	Δρ_min = −0.60 e Å⁻³
1 restraint	Absolute structure: Flack (1983), 1307 Friedel pairs
Primary atom site location: structure-invariant direct methods	Absolute structure parameter: −0.02 (3)

Crystal data top

C₁₉H₁₈FN₃O₂S	V = 1730.9 (4) Å³
M_r = 371.42	Z = 4
Orthorhombic, Pca2₁	Cu Kα radiation
a = 18.494 (4) Å	µ = 1.92 mm⁻¹
b = 12.4367 (10) Å	T = 193 K
c = 7.5255 (5) Å	0.55 × 0.12 × 0.09 mm

Data collection top

Enraf–Nonius CAD-4 diffractometer	2869 reflections with I > 2σ(I)
Absorption correction: gaussian (PLATON; Spek, 2003)	R_int = 0.051
T_min = 0.61, T_max = 0.85	3 standard reflections every 60 min
3363 measured reflections	intensity decay: 5%
3086 independent reflections

Refinement top

R[F² > 2σ(F²)] = 0.076	H-atom parameters constrained
wR(F²) = 0.188	Δρ_max = 1.14 e Å⁻³
S = 1.14	Δρ_min = −0.60 e Å⁻³
3086 reflections	Absolute structure: Flack (1983), 1307 Friedel pairs
236 parameters	Absolute structure parameter: −0.02 (3)
1 restraint

Special details top

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. 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
C1	0.3643 (2)	0.3750 (3)	0.3172 (5)	0.0204 (8)
N2	0.29502 (16)	0.3630 (3)	0.3227 (4)	0.0203 (7)
C3	0.26668 (19)	0.4629 (3)	0.2819 (5)	0.0179 (7)
C4	0.32215 (19)	0.5351 (3)	0.2524 (5)	0.0183 (8)
N5	0.38455 (15)	0.4764 (2)	0.2738 (4)	0.0173 (6)
H5	0.4314	0.4967	0.2711	0.021*
S6	0.42920 (5)	0.27420 (8)	0.35250 (18)	0.0298 (3)
C7	0.3694 (2)	0.1589 (3)	0.3710 (7)	0.0300 (9)
H7A	0.3312	0.1650	0.2796	0.036*
H7B	0.3975	0.0929	0.3456	0.036*
C8	0.3338 (2)	0.1474 (4)	0.5527 (8)	0.0371 (12)
H8A	0.2967	0.0901	0.5463	0.044*
H8B	0.3089	0.2155	0.5825	0.044*
C9	0.3870 (3)	0.1202 (4)	0.7011 (8)	0.0451 (13)
H9A	0.4239	0.1778	0.7061	0.054*
H9B	0.3604	0.1214	0.8153	0.054*
C10	0.4252 (2)	0.0150 (4)	0.6867 (7)	0.0360 (11)
O11	0.4808 (2)	−0.0057 (4)	0.7602 (7)	0.0621 (12)
O12	0.38975 (17)	−0.0571 (2)	0.5875 (5)	0.0368 (8)
C13	0.4252 (3)	−0.1576 (4)	0.5589 (7)	0.0413 (12)
H13A	0.4738	−0.1447	0.5115	0.062*
H13B	0.3973	−0.2004	0.4737	0.062*
H13C	0.4288	−0.1965	0.6717	0.062*
C14	0.1875 (2)	0.4721 (3)	0.2746 (5)	0.0189 (7)
C15	0.14573 (19)	0.3934 (3)	0.3609 (6)	0.0225 (7)
H15	0.1684	0.3374	0.4260	0.027*
C16	0.07186 (19)	0.3987 (3)	0.3501 (7)	0.0267 (8)
H16	0.0447	0.3439	0.4076	0.032*
N17	0.03515 (16)	0.4759 (3)	0.2637 (6)	0.0270 (8)
C18	0.0753 (2)	0.5502 (3)	0.1816 (6)	0.0244 (9)
H18	0.0509	0.6056	0.1186	0.029*
C19	0.14979 (19)	0.5514 (3)	0.1825 (5)	0.0201 (7)
H19	0.1753	0.6061	0.1207	0.024*
C20	0.32620 (18)	0.6506 (3)	0.2109 (5)	0.0185 (8)
C21	0.2750 (2)	0.7236 (3)	0.2741 (6)	0.0217 (8)
H21	0.2373	0.6988	0.3493	0.026*
C22	0.2782 (2)	0.8313 (3)	0.2294 (6)	0.0261 (9)
H22	0.2423	0.8801	0.2704	0.031*
C23	0.3342 (2)	0.8664 (3)	0.1244 (6)	0.0274 (9)
C24	0.3875 (2)	0.7984 (4)	0.0657 (6)	0.0267 (9)
H24	0.4265	0.8252	−0.0032	0.032*
C25	0.38349 (19)	0.6910 (3)	0.1081 (6)	0.0220 (8)
H25	0.4201	0.6434	0.0672	0.026*
F26	0.33578 (16)	0.9714 (2)	0.0773 (4)	0.0405 (7)

Atomic displacement parameters (Å²) top

	U¹¹	U²²	U³³	U¹²	U¹³	U²³
C1	0.0269 (17)	0.0264 (18)	0.008 (2)	0.0036 (14)	−0.0006 (13)	0.0032 (14)
N2	0.0239 (14)	0.0260 (15)	0.0110 (19)	0.0029 (11)	0.0001 (12)	−0.0007 (12)
C3	0.0263 (18)	0.0242 (17)	0.0031 (17)	0.0023 (13)	0.0009 (14)	−0.0015 (14)
C4	0.0211 (16)	0.032 (2)	0.0019 (18)	0.0020 (14)	0.0004 (13)	−0.0021 (14)
N5	0.0177 (13)	0.0271 (16)	0.0072 (15)	0.0012 (11)	−0.0002 (12)	−0.0022 (12)
S6	0.0229 (5)	0.0303 (5)	0.0362 (7)	0.0068 (3)	0.0024 (4)	0.0086 (4)
C7	0.037 (2)	0.0238 (18)	0.029 (3)	0.0044 (15)	−0.005 (2)	0.0005 (17)
C8	0.039 (2)	0.033 (2)	0.039 (3)	0.0064 (18)	0.011 (2)	0.013 (2)
C9	0.078 (4)	0.033 (2)	0.024 (3)	0.004 (2)	0.005 (3)	0.002 (2)
C10	0.045 (3)	0.037 (2)	0.026 (3)	−0.0026 (18)	0.002 (2)	0.004 (2)
O11	0.059 (2)	0.061 (2)	0.067 (3)	0.009 (2)	−0.027 (2)	−0.019 (2)
O12	0.0440 (17)	0.0313 (16)	0.035 (2)	0.0030 (12)	−0.0122 (15)	0.0029 (15)
C13	0.060 (3)	0.035 (2)	0.029 (3)	0.008 (2)	−0.014 (2)	0.002 (2)
C14	0.0255 (17)	0.0277 (17)	0.0036 (17)	−0.0002 (14)	0.0021 (14)	−0.0047 (14)
C15	0.0294 (17)	0.0239 (16)	0.014 (2)	0.0004 (14)	0.0036 (18)	−0.0007 (15)
C16	0.0281 (18)	0.0265 (18)	0.025 (2)	−0.0021 (14)	0.0060 (18)	−0.0044 (19)
N17	0.0193 (14)	0.0349 (18)	0.027 (2)	−0.0003 (13)	−0.0008 (13)	−0.0080 (15)
C18	0.033 (2)	0.031 (2)	0.010 (2)	0.0058 (15)	−0.0052 (16)	−0.0029 (17)
C19	0.0266 (18)	0.0275 (17)	0.006 (2)	−0.0008 (14)	0.0003 (14)	−0.0004 (15)
C20	0.0224 (17)	0.0276 (18)	0.0055 (18)	−0.0017 (13)	−0.0034 (13)	−0.0007 (14)
C21	0.0266 (18)	0.031 (2)	0.0076 (18)	0.0008 (14)	−0.0018 (15)	0.0005 (15)
C22	0.034 (2)	0.0285 (19)	0.016 (2)	0.0043 (16)	−0.0011 (16)	−0.0031 (16)
C23	0.037 (2)	0.0259 (19)	0.020 (2)	−0.0043 (15)	−0.0059 (17)	0.0033 (16)
C24	0.031 (2)	0.036 (2)	0.013 (2)	−0.0078 (16)	−0.0001 (15)	0.0056 (17)
C25	0.0221 (17)	0.0320 (19)	0.012 (2)	−0.0004 (14)	0.0006 (15)	−0.0026 (16)
F26	0.0596 (17)	0.0272 (12)	0.0346 (18)	−0.0027 (11)	0.0013 (13)	0.0072 (11)

Geometric parameters (Å, º) top

C1—N2	1.290 (5)	C13—H13B	0.9800
C1—N5	1.356 (5)	C13—H13C	0.9800
C1—S6	1.756 (4)	C14—C19	1.392 (5)
N2—C3	1.384 (5)	C14—C15	1.405 (5)
C3—C4	1.381 (5)	C15—C16	1.370 (5)
C3—C14	1.470 (5)	C15—H15	0.9500
C4—N5	1.375 (5)	C16—N17	1.344 (6)
C4—C20	1.471 (5)	C16—H16	0.9500
N5—H5	0.9032	N17—C18	1.336 (6)
S6—C7	1.816 (4)	C18—C19	1.378 (5)
C7—C8	1.525 (7)	C18—H18	0.9500
C7—H7A	0.9900	C19—H19	0.9500
C7—H7B	0.9900	C20—C21	1.395 (5)
C8—C9	1.527 (8)	C20—C25	1.405 (5)
C8—H8A	0.9900	C21—C22	1.383 (5)
C8—H8B	0.9900	C21—H21	0.9500
C9—C10	1.491 (6)	C22—C23	1.374 (6)
C9—H9A	0.9900	C22—H22	0.9500
C9—H9B	0.9900	C23—F26	1.354 (5)
C10—O11	1.196 (6)	C23—C24	1.371 (6)
C10—O12	1.339 (6)	C24—C25	1.375 (6)
O12—C13	1.427 (6)	C24—H24	0.9500
C13—H13A	0.9800	C25—H25	0.9500

N2—C1—N5	113.0 (3)	H13A—C13—H13B	109.5
N2—C1—S6	126.2 (3)	O12—C13—H13C	109.5
N5—C1—S6	120.7 (3)	H13A—C13—H13C	109.5
C1—N2—C3	105.3 (3)	H13B—C13—H13C	109.5
C4—C3—N2	109.8 (3)	C19—C14—C15	116.6 (3)
C4—C3—C14	133.1 (3)	C19—C14—C3	124.9 (3)
N2—C3—C14	117.1 (3)	C15—C14—C3	118.4 (3)
N5—C4—C3	105.0 (3)	C16—C15—C14	119.2 (4)
N5—C4—C20	120.0 (3)	C16—C15—H15	120.4
C3—C4—C20	134.9 (3)	C14—C15—H15	120.4
C1—N5—C4	106.9 (3)	N17—C16—C15	124.5 (4)
C1—N5—H5	122.1	N17—C16—H16	117.8
C4—N5—H5	130.9	C15—C16—H16	117.8
C1—S6—C7	99.14 (18)	C18—N17—C16	115.9 (3)
C8—C7—S6	114.0 (3)	N17—C18—C19	124.1 (4)
C8—C7—H7A	108.8	N17—C18—H18	117.9
S6—C7—H7A	108.8	C19—C18—H18	117.9
C8—C7—H7B	108.8	C18—C19—C14	119.7 (4)
S6—C7—H7B	108.8	C18—C19—H19	120.2
H7A—C7—H7B	107.7	C14—C19—H19	120.2
C7—C8—C9	113.4 (4)	C21—C20—C25	117.8 (4)
C7—C8—H8A	108.9	C21—C20—C4	121.9 (3)
C9—C8—H8A	108.9	C25—C20—C4	120.3 (3)
C7—C8—H8B	108.9	C22—C21—C20	121.3 (4)
C9—C8—H8B	108.9	C22—C21—H21	119.4
H8A—C8—H8B	107.7	C20—C21—H21	119.4
C10—C9—C8	116.6 (4)	C23—C22—C21	118.7 (4)
C10—C9—H9A	108.2	C23—C22—H22	120.7
C8—C9—H9A	108.2	C21—C22—H22	120.7
C10—C9—H9B	108.2	F26—C23—C24	119.7 (4)
C8—C9—H9B	108.2	F26—C23—C22	118.3 (4)
H9A—C9—H9B	107.3	C24—C23—C22	122.1 (4)
O11—C10—O12	122.4 (5)	C23—C24—C25	119.1 (4)
O11—C10—C9	124.3 (5)	C23—C24—H24	120.5
O12—C10—C9	113.3 (4)	C25—C24—H24	120.5
C10—O12—C13	116.5 (4)	C24—C25—C20	121.0 (4)
O12—C13—H13A	109.5	C24—C25—H25	119.5
O12—C13—H13B	109.5	C20—C25—H25	119.5

N5—C1—N2—C3	−0.5 (4)	N2—C3—C14—C15	19.8 (5)
S6—C1—N2—C3	−178.3 (3)	C19—C14—C15—C16	0.1 (6)
C1—N2—C3—C4	−0.2 (4)	C3—C14—C15—C16	−177.7 (4)
C1—N2—C3—C14	178.7 (3)	C14—C15—C16—N17	−1.2 (7)
N2—C3—C4—N5	0.8 (4)	C15—C16—N17—C18	1.3 (7)
C14—C3—C4—N5	−177.8 (4)	C16—N17—C18—C19	−0.4 (6)
N2—C3—C4—C20	−177.7 (4)	N17—C18—C19—C14	−0.5 (6)
C14—C3—C4—C20	3.6 (7)	C15—C14—C19—C18	0.7 (6)
N2—C1—N5—C4	1.0 (4)	C3—C14—C19—C18	178.3 (3)
S6—C1—N5—C4	179.0 (3)	N5—C4—C20—C21	−146.2 (4)
C3—C4—N5—C1	−1.1 (4)	C3—C4—C20—C21	32.2 (7)
C20—C4—N5—C1	177.7 (4)	N5—C4—C20—C25	32.5 (5)
N2—C1—S6—C7	5.7 (4)	C3—C4—C20—C25	−149.2 (4)
N5—C1—S6—C7	−172.0 (3)	C25—C20—C21—C22	3.4 (6)
C1—S6—C7—C8	−80.0 (3)	C4—C20—C21—C22	−177.9 (4)
S6—C7—C8—C9	−67.3 (4)	C20—C21—C22—C23	−1.7 (6)
C7—C8—C9—C10	−63.6 (6)	C21—C22—C23—F26	178.2 (4)
C8—C9—C10—O11	158.8 (6)	C21—C22—C23—C24	−1.2 (7)
C8—C9—C10—O12	−23.6 (6)	F26—C23—C24—C25	−177.2 (4)
O11—C10—O12—C13	−6.0 (8)	C22—C23—C24—C25	2.2 (7)
C9—C10—O12—C13	176.3 (4)	C23—C24—C25—C20	−0.4 (6)
C4—C3—C14—C19	20.7 (7)	C21—C20—C25—C24	−2.4 (6)
N2—C3—C14—C19	−157.8 (4)	C4—C20—C25—C24	178.9 (4)
C4—C3—C14—C15	−161.6 (4)

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N5—H5···N17ⁱ	0.90	1.95	2.849 (4)	174

Symmetry code: (i) x+1/2, −y+1, z.

Experimental details

Crystal data
Chemical formula	C₁₉H₁₈FN₃O₂S
M_r	371.42
Crystal system, space group	Orthorhombic, Pca2₁
Temperature (K)	193
a, b, c (Å)	18.494 (4), 12.4367 (10), 7.5255 (5)
V (Å³)	1730.9 (4)
Z	4
Radiation type	Cu Kα
µ (mm⁻¹)	1.92
Crystal size (mm)	0.55 × 0.12 × 0.09

Data collection
Diffractometer	Enraf–Nonius CAD-4 diffractometer
Absorption correction	Gaussian (PLATON; Spek, 2003)
T_min, T_max	0.61, 0.85
No. of measured, independent and observed [I > 2σ(I)] reflections	3363, 3086, 2869
R_int	0.051
(sin θ/λ)_max (Å⁻¹)	0.610

Refinement
R[F² > 2σ(F²)], wR(F²), S	0.076, 0.188, 1.14
No. of reflections	3086
No. of parameters	236
No. of restraints	1
H-atom treatment	H-atom parameters constrained
Δρ_max, Δρ_min (e Å⁻³)	1.14, −0.60
Absolute structure	Flack (1983), 1307 Friedel pairs
Absolute structure parameter	−0.02 (3)

Computer programs: CAD-4 Software (Enraf–Nonius, 1989), CORINC (Dräger & Gattow, 1971), SIR97 (Altomare et al., 1999), SHELXL97 (Sheldrick, 2008), PLATON (Spek, 2003).

Hydrogen-bond geometry (Å, º) top

D—H···A	D—H	H···A	D···A	D—H···A
N5—H5···N17ⁱ	0.90	1.95	2.849 (4)	173.8

Symmetry code: (i) x+1/2, −y+1, z.

Nonconventional C–H···X contacts (Å, °). top

C–H···A	C–H	H···A	C–H···A	C···A
C13–H13B···Cg1ⁱⁱ	0.98	2.65	156	3.566 (6)
C7–H7A···N2	0.99	2.57	100	2.910 (5)

Symmetry code: (ii) x, y-1, z. Cg1 is the centroid of the C20–C25 ring.

Acknowledgements

The authors acknowledge financial support from the EU, part of the EU-Craft Programme, Framework Project 6 `MACROCEPT'.

References

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
Flack, H. D. (1983). Acta Cryst. A39, 876–881. CrossRef CAS Web of Science IUCr Journals Google Scholar
Lantos, I., Gombatz, K., McGuire, M., Pridgen, L., Remich, J. & Shilcrat, S. (1988). J. Org. Chem. 53, 4223–4227. CrossRef CAS Web of Science Google Scholar
Laufer, S. & Koch, P. (2008). Org. Biomol. Chem. 6, 437–439. Web of Science CrossRef PubMed CAS Google Scholar
Laufer, S. A., Striegel, H.-G. & Wagner, G. K. (2002). J. Med. Chem. 45, 4695–4705. Web of Science CrossRef PubMed CAS Google Scholar
Laufer, S., Wagner, G. & Kotschenreuther, D. (2002). Angew. Chem. Int. Ed. 41, 2290–2293. CrossRef CAS Google Scholar
Peifer, C., Kinkel, K., Abadleh, M., Schollmeyer, D. & Laufer, S. (2007). J. Med. Chem. 50, 1213–1221. Web of Science CrossRef PubMed CAS 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. (2003). J. Appl. Cryst. 36, 7–13. Web of Science CrossRef CAS IUCr Journals Google Scholar
Wagner, G. & Laufer, S. (2006). Med. Res. Rev. 26, 1–62. Web of Science CrossRef PubMed CAS Google Scholar
Wang, Z., Canagarajah, B. J., Boehm, J. C., Kassisa, S., Cobb, M. H., Young, P. R., Abdel-Meguid, S., Adams, J. L. & Goldsmith, E. J. (1998). Structure, 6, 1117–1128. Web of Science CrossRef CAS PubMed 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 64| Part 7| July 2008| Pages o1183-o1184

doi:10.1107/S1600536808016000

Open

access

Format		BIBTeX
		EndNote
		RefMan
		Refer
		Medline
		CIF
		SGML
		Plain Text

Format		BIBTeX
		EndNote
		RefMan
		Refer
		Medline
		CIF
		SGML
		Plain Text

Search IUCr Journals		doi		Advanced search
Author		volume	page

organic compounds\(\def\hfill{\hskip 5em}\def\hfil{\hskip 3em}\def\eqno#1{\hfil {#1}}\)

Methyl 4-[5-(4-fluoro­phen­yl)-4-(pyridin-4-yl)-1H-imidazol-2-ylsulfan­yl]butanoate

Related literature

Experimental

Crystal data

Data collection

Refinement

Supporting information

Acknowledgements

References

organic compounds

Methyl 4-[5-(4-fluorophenyl)-4-(pyridin-4-yl)-1H-imidazol-2-ylsulfanyl]butanoate