Methyl 4-[5-(4-fluoro-phen-yl)-4-(pyridin-4-yl)-1H-imidazol-2-ylsulfan-yl]butanoate.

The title compound, C(19)H(18)FN(3)O(2)S, was synthesized in the course of studies on 2-alkyl-sufanylimidazoles as p38 mitogen-activated protein kinase inhibitors. The synthesis was achieved by nucleophilic substitution of 4-(4-fluoro-phen-yl)-5-(pyridin-4-yl)-1,3-dihydro-imidazole-2-thione with methyl 4-bromo-butanoate. The five-membered heterocycle makes dihedral angles of 32.4 (2) and 18.3 (2)° with the fluoro-phenyl and pyridinyl rings, respectively, indicating a low degree of conjugation between these rings. Intra-molecular C-H⋯N and inter-molecular N-H⋯N hydrogen bonds as well as C-H⋯π inter-actions 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 = 371.42

Orthorhombic,

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[F 2 > 2σ(F 2)] = 0.076

wR(F 2) = 0.188

S = 1.14

3086 reflections

236 parameters

1 restraint

H-atom parameters constrained

Δρmax = 1.14 e Å−3

Δρmin = −0.60 e Å−3

Absolute structure: Flack (1983 ▶), 1307 Friedel pairs

Flack parameter: −0.02 (3)

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.

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

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

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

C19H18FN3O2S	F000 = 776
Mr = 371.42	Dx = 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 = 31–44º
b = 12.4367 (10) Å	µ = 1.92 mm−1
c = 7.5255 (5) Å	T = 193 (2) K
V = 1730.9 (4) Å3	Needle, colourless
Z = 4	0.55 × 0.12 × 0.09 mm

Enraf–Nonius CAD-4 diffractometer	Rint = 0.051
Monochromator: graphite	θmax = 70.0º
T = 193(2) K	θmin = 3.6º
ω/2θ scans	h = −22→22
Absorption correction: gaussian(PLATON; Spek, 2003)	k = −15→15
Tmin = 0.61, Tmax = 0.85	l = −7→9
3363 measured reflections	3 standard reflections
3086 independent reflections	every 60 min
2869 reflections with I > 2σ(I)	intensity decay: 5%

Refinement on F2	Hydrogen site location: inferred from neighbouring sites
Least-squares matrix: full	H-atom parameters constrained
R[F2 > 2σ(F2)] = 0.076	w = 1/[σ2(Fo2) + (0.1374P)2] where P = (Fo2 + 2Fc2)/3
wR(F2) = 0.188	(Δ/σ)max < 0.001
S = 1.14	Δρmax = 1.14 e Å−3
3086 reflections	Δρmin = −0.60 e Å−3
236 parameters	Extinction correction: none
1 restraint	Absolute structure: Flack (1983), 1307 Friedel pairs
Primary atom site location: structure-invariant direct methods	Flack parameter: −0.02 (3)
Secondary atom site location: difference Fourier map

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.

	x	y	z	Uiso*/Ueq
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)

	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)

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)

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

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)

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) .

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) . Cg1 is the centroid of the C20–C25 ring.