4-[5-Amino-4-(4-fluoro-phen-yl)-3-(pyridin-4-yl)-1H-pyrazol-1-yl]benzo-nitrile.

In the crystal structure of the title compound, C(21)H(14)FN(5), the pyrazole ring forms dihedral angles of 38.0 (1), 40.0 (1) and 28.5 (1)° with the directly attached 4-fluoro-phenyl, pyridine and benzonitrile rings, respectively. The crystal packing is characterized by N-H⋯N hydrogen bonds, which result in a two-dimensional network parallel to the ac-plane.

Related literature

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 ▶); Peifer et al. (2006 ▶). For the inhibitory activity and preparation of the title compound, see: Abu Thaher et al. (2012a ▶). For related structures, see: Abu Thaher et al. (2012b ▶,c ▶).

Experimental

Crystal data

C21H14FN5

M = 355.37

Orthorhombic,

a = 10.5189 (5) Å

b = 8.1339 (3) Å

c = 20.0009 (13) Å

V = 1711.27 (15) Å3

Z = 4

Cu Kα radiation

μ = 0.76 mm−1

T = 193 K

0.50 × 0.30 × 0.30 mm

Data collection

Enraf–Nonius CAD-4 diffractometer

3163 measured reflections

3059 independent reflections

3005 reflections with I > 2σ(I)

R int = 0.026

3 standard reflections every 60 min intensity decay: 3%

Refinement

R[F 2 > 2σ(F 2)] = 0.038

wR(F 2) = 0.103

S = 1.04

3059 reflections

244 parameters

1 restraint

H-atom parameters constrained

Δρmax = 0.17 e Å−3

Δρmin = −0.23 e Å−3

Absolute structure: Flack (1983 ▶), 1381 Friedel pairs

Flack parameter: −0.17 (18)

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.

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S160053681200877X/im2359sup1.cif

Structure factors: contains datablock(s) I. DOI: 10.1107/S160053681200877X/im2359Isup2.hkl

Supplementary material file. DOI: 10.1107/S160053681200877X/im2359Isup3.cml

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

C21H14FN5	F(000) = 736
Mr = 355.37	Dx = 1.379 Mg m−3
Orthorhombic, Pca21	Cu Kα radiation, λ = 1.54178 Å
Hall symbol: P 2c -2ac	Cell parameters from 25 reflections
a = 10.5189 (5) Å	θ = 65–70°
b = 8.1339 (3) Å	µ = 0.76 mm−1
c = 20.0009 (13) Å	T = 193 K
V = 1711.27 (15) Å3	Block, brown
Z = 4	0.50 × 0.30 × 0.30 mm

Enraf–Nonius CAD-4 diffractometer	Rint = 0.026
Radiation source: rotating anode	θmax = 69.9°, θmin = 4.4°
Graphite monochromator	h = −12→12
ω/2θ scans	k = −9→9
3163 measured reflections	l = −24→24
3059 independent reflections	3 standard reflections every 60 min
3005 reflections with I > 2σ(I)	intensity decay: 3%

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)] = 0.038	H-atom parameters constrained
wR(F2) = 0.103	w = 1/[σ2(Fo2) + (0.0752P)2 + 0.2913P] where P = (Fo2 + 2Fc2)/3
S = 1.04	(Δ/σ)max < 0.001
3059 reflections	Δρmax = 0.17 e Å−3
244 parameters	Δρmin = −0.23 e Å−3
1 restraint	Absolute structure: Flack (1983), 1381 Friedel pairs
Primary atom site location: structure-invariant direct methods	Flack parameter: −0.17 (18)

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
N1	0.43666 (14)	0.21998 (19)	0.52903 (8)	0.0245 (3)
C2	0.46323 (15)	0.2397 (2)	0.46188 (10)	0.0233 (4)
C3	0.34814 (17)	0.2656 (2)	0.43004 (10)	0.0234 (4)
C4	0.25715 (16)	0.2607 (2)	0.48226 (9)	0.0236 (4)
N5	0.30861 (14)	0.23527 (19)	0.54156 (8)	0.0253 (3)
N6	0.58360 (15)	0.2377 (2)	0.43736 (9)	0.0322 (4)
H6A	0.6492	0.2547	0.4639	0.048*
H6B	0.5975	0.2425	0.3949	0.048*
C7	0.51679 (16)	0.1880 (2)	0.58436 (10)	0.0240 (4)
C8	0.47853 (17)	0.2416 (3)	0.64701 (11)	0.0307 (4)
H8	0.4014	0.3013	0.6516	0.037*
C9	0.55154 (18)	0.2090 (3)	0.70281 (10)	0.0319 (4)
H9	0.5245	0.2446	0.7457	0.038*
C10	0.66595 (17)	0.1229 (2)	0.69545 (9)	0.0269 (4)
C11	0.70398 (19)	0.0686 (2)	0.63280 (10)	0.0309 (4)
H11	0.7816	0.0102	0.6281	0.037*
C12	0.62949 (18)	0.0992 (2)	0.57720 (10)	0.0287 (4)
H12	0.6548	0.0600	0.5345	0.034*
C13	0.74546 (19)	0.0933 (2)	0.75280 (11)	0.0306 (4)
N14	0.81025 (18)	0.0714 (3)	0.79805 (10)	0.0402 (4)
C16	0.33007 (16)	0.3156 (2)	0.35985 (9)	0.0235 (4)
C17	0.24094 (18)	0.4368 (2)	0.34404 (10)	0.0279 (4)
H17	0.1915	0.4843	0.3788	0.033*
C18	0.22306 (19)	0.4892 (2)	0.27863 (11)	0.0315 (4)
H18	0.1605	0.5693	0.2681	0.038*
C19	0.29837 (19)	0.4220 (3)	0.22958 (9)	0.0303 (4)
C20	0.38681 (19)	0.3029 (3)	0.24196 (10)	0.0329 (4)
H20	0.4369	0.2585	0.2068	0.039*
C21	0.40156 (19)	0.2480 (3)	0.30763 (10)	0.0294 (4)
H21	0.4611	0.1634	0.3170	0.035*
F22	0.28240 (13)	0.47710 (18)	0.16555 (6)	0.0439 (3)
C23	0.11619 (16)	0.2723 (2)	0.47901 (10)	0.0247 (4)
C24	0.04902 (17)	0.3515 (3)	0.52898 (10)	0.0301 (4)
H24	0.0927	0.4043	0.5646	0.036*
C25	−0.08274 (18)	0.3532 (3)	0.52667 (11)	0.0357 (5)
H25	−0.1273	0.4093	0.5611	0.043*
N26	−0.15029 (15)	0.2799 (2)	0.47859 (10)	0.0370 (4)
C27	−0.08439 (19)	0.2038 (3)	0.43060 (12)	0.0362 (5)
H27	−0.1306	0.1511	0.3959	0.043*
C28	0.04695 (18)	0.1972 (3)	0.42836 (11)	0.0301 (4)
H28	0.0891	0.1422	0.3928	0.036*

	U11	U22	U33	U12	U13	U23
N1	0.0145 (6)	0.0350 (8)	0.0241 (8)	−0.0011 (6)	0.0004 (6)	0.0023 (7)
C2	0.0160 (8)	0.0292 (9)	0.0246 (10)	−0.0018 (6)	0.0001 (7)	−0.0011 (7)
C3	0.0177 (8)	0.0267 (8)	0.0259 (9)	−0.0007 (6)	0.0000 (7)	−0.0014 (8)
C4	0.0149 (8)	0.0299 (8)	0.0259 (9)	−0.0019 (6)	−0.0023 (7)	0.0007 (7)
N5	0.0128 (7)	0.0366 (8)	0.0265 (9)	0.0008 (5)	−0.0004 (6)	0.0013 (7)
N6	0.0119 (7)	0.0586 (11)	0.0260 (8)	−0.0022 (7)	0.0012 (6)	−0.0019 (8)
C7	0.0164 (8)	0.0288 (9)	0.0268 (9)	−0.0026 (7)	−0.0035 (7)	0.0019 (8)
C8	0.0175 (8)	0.0447 (11)	0.0298 (10)	0.0032 (7)	0.0008 (8)	−0.0026 (9)
C9	0.0228 (9)	0.0469 (11)	0.0261 (10)	−0.0006 (8)	−0.0003 (7)	−0.0042 (9)
C10	0.0224 (8)	0.0318 (9)	0.0265 (10)	−0.0038 (7)	−0.0041 (7)	0.0022 (8)
C11	0.0252 (9)	0.0357 (10)	0.0320 (10)	0.0068 (8)	−0.0031 (8)	−0.0003 (9)
C12	0.0254 (9)	0.0363 (9)	0.0244 (9)	0.0042 (8)	0.0003 (7)	−0.0028 (8)
C13	0.0260 (8)	0.0365 (10)	0.0291 (9)	−0.0040 (8)	−0.0014 (8)	0.0014 (8)
N14	0.0332 (9)	0.0541 (11)	0.0333 (9)	−0.0074 (8)	−0.0090 (8)	0.0054 (9)
C16	0.0172 (7)	0.0292 (9)	0.0241 (9)	−0.0039 (7)	−0.0008 (6)	−0.0019 (7)
C17	0.0248 (9)	0.0328 (9)	0.0261 (10)	−0.0002 (7)	0.0017 (7)	−0.0024 (8)
C18	0.0297 (10)	0.0336 (10)	0.0314 (10)	−0.0008 (8)	−0.0043 (8)	0.0041 (8)
C19	0.0300 (9)	0.0406 (10)	0.0202 (9)	−0.0136 (8)	−0.0034 (7)	0.0013 (8)
C20	0.0277 (9)	0.0456 (11)	0.0254 (10)	−0.0079 (8)	0.0058 (8)	−0.0078 (9)
C21	0.0202 (9)	0.0367 (10)	0.0313 (10)	−0.0014 (7)	0.0004 (8)	−0.0033 (8)
F22	0.0503 (8)	0.0578 (8)	0.0236 (6)	−0.0142 (6)	−0.0051 (5)	0.0065 (6)
C23	0.0156 (8)	0.0316 (9)	0.0268 (9)	0.0008 (6)	0.0006 (7)	0.0040 (7)
C24	0.0205 (8)	0.0449 (11)	0.0250 (9)	0.0002 (7)	−0.0024 (7)	−0.0022 (9)
C25	0.0213 (9)	0.0538 (12)	0.0318 (10)	0.0055 (8)	0.0055 (8)	−0.0036 (9)
N26	0.0160 (7)	0.0569 (11)	0.0382 (10)	−0.0002 (7)	0.0001 (7)	0.0016 (9)
C27	0.0206 (9)	0.0542 (12)	0.0337 (11)	−0.0049 (8)	−0.0040 (8)	−0.0026 (10)
C28	0.0210 (8)	0.0428 (11)	0.0265 (9)	−0.0017 (7)	−0.0020 (8)	−0.0022 (9)

N1—N5	1.376 (2)	C13—N14	1.147 (3)
N1—C2	1.381 (3)	C16—C17	1.397 (3)
N1—C7	1.415 (2)	C16—C21	1.399 (3)
C2—N6	1.358 (2)	C17—C18	1.389 (3)
C2—C3	1.384 (2)	C17—H17	0.9500
C3—C4	1.417 (3)	C18—C19	1.374 (3)
C3—C16	1.474 (3)	C18—H18	0.9500
C4—N5	1.320 (2)	C19—C20	1.366 (3)
C4—C23	1.487 (2)	C19—F22	1.367 (2)
N6—H6A	0.8816	C20—C21	1.396 (3)
N6—H6B	0.8621	C20—H20	0.9500
C7—C8	1.386 (3)	C21—H21	0.9500
C7—C12	1.395 (3)	C23—C24	1.383 (3)
C8—C9	1.380 (3)	C23—C28	1.389 (3)
C8—H8	0.9500	C24—C25	1.387 (3)
C9—C10	1.400 (3)	C24—H24	0.9500
C9—H9	0.9500	C25—N26	1.336 (3)
C10—C11	1.388 (3)	C25—H25	0.9500
C10—C13	1.440 (3)	N26—C27	1.336 (3)
C11—C12	1.383 (3)	C27—C28	1.383 (3)
C11—H11	0.9500	C27—H27	0.9500
C12—H12	0.9500	C28—H28	0.9500
N5—N1—C2	111.40 (14)	C17—C16—C21	117.97 (18)
N5—N1—C7	117.21 (15)	C17—C16—C3	119.80 (17)
C2—N1—C7	131.39 (15)	C21—C16—C3	122.22 (17)
N6—C2—N1	122.58 (16)	C18—C17—C16	121.39 (18)
N6—C2—C3	130.64 (18)	C18—C17—H17	119.3
N1—C2—C3	106.74 (15)	C16—C17—H17	119.3
C2—C3—C4	104.33 (17)	C19—C18—C17	118.20 (18)
C2—C3—C16	126.37 (16)	C19—C18—H18	120.9
C4—C3—C16	128.50 (17)	C17—C18—H18	120.9
N5—C4—C3	112.93 (16)	C20—C19—F22	119.08 (19)
N5—C4—C23	117.26 (16)	C20—C19—C18	123.03 (18)
C3—C4—C23	129.75 (18)	F22—C19—C18	117.90 (18)
C4—N5—N1	104.59 (15)	C19—C20—C21	118.24 (19)
C2—N6—H6A	120.7	C19—C20—H20	120.9
C2—N6—H6B	120.9	C21—C20—H20	120.9
H6A—N6—H6B	117.0	C20—C21—C16	121.13 (19)
C8—C7—C12	120.14 (18)	C20—C21—H21	119.4
C8—C7—N1	118.43 (16)	C16—C21—H21	119.4
C12—C7—N1	121.39 (18)	C24—C23—C28	117.64 (16)
C9—C8—C7	120.58 (17)	C24—C23—C4	120.48 (17)
C9—C8—H8	119.7	C28—C23—C4	121.79 (17)
C7—C8—H8	119.7	C23—C24—C25	119.40 (18)
C8—C9—C10	119.30 (19)	C23—C24—H24	120.3
C8—C9—H9	120.4	C25—C24—H24	120.3
C10—C9—H9	120.4	N26—C25—C24	123.45 (19)
C11—C10—C9	120.12 (18)	N26—C25—H25	118.3
C11—C10—C13	119.92 (17)	C24—C25—H25	118.3
C9—C10—C13	119.95 (18)	C27—N26—C25	116.60 (16)
C12—C11—C10	120.38 (18)	N26—C27—C28	124.0 (2)
C12—C11—H11	119.8	N26—C27—H27	118.0
C10—C11—H11	119.8	C28—C27—H27	118.0
C11—C12—C7	119.46 (19)	C27—C28—C23	118.87 (19)
C11—C12—H12	120.3	C27—C28—H28	120.6
C7—C12—H12	120.3	C23—C28—H28	120.6
N14—C13—C10	178.9 (2)
N5—N1—C2—N6	176.84 (17)	C8—C7—C12—C11	−1.5 (3)
C7—N1—C2—N6	−3.2 (3)	N1—C7—C12—C11	−179.04 (17)
N5—N1—C2—C3	−1.1 (2)	C2—C3—C16—C17	−136.16 (19)
C7—N1—C2—C3	178.89 (17)	C4—C3—C16—C17	32.0 (3)
N6—C2—C3—C4	−177.24 (19)	C2—C3—C16—C21	42.5 (3)
N1—C2—C3—C4	0.45 (19)	C4—C3—C16—C21	−149.42 (18)
N6—C2—C3—C16	−6.8 (3)	C21—C16—C17—C18	0.1 (3)
N1—C2—C3—C16	170.87 (17)	C3—C16—C17—C18	178.76 (17)
C2—C3—C4—N5	0.3 (2)	C16—C17—C18—C19	−1.9 (3)
C16—C3—C4—N5	−169.81 (17)	C17—C18—C19—C20	2.1 (3)
C2—C3—C4—C23	−176.61 (17)	C17—C18—C19—F22	−178.44 (16)
C16—C3—C4—C23	13.2 (3)	F22—C19—C20—C21	−179.87 (17)
C3—C4—N5—N1	−0.97 (19)	C18—C19—C20—C21	−0.4 (3)
C23—C4—N5—N1	176.39 (15)	C19—C20—C21—C16	−1.5 (3)
C2—N1—N5—C4	1.26 (19)	C17—C16—C21—C20	1.7 (3)
C7—N1—N5—C4	−178.71 (15)	C3—C16—C21—C20	−176.99 (18)
N5—N1—C7—C8	−27.3 (2)	N5—C4—C23—C24	38.6 (3)
C2—N1—C7—C8	152.71 (19)	C3—C4—C23—C24	−144.6 (2)
N5—N1—C7—C12	150.24 (17)	N5—C4—C23—C28	−137.84 (19)
C2—N1—C7—C12	−29.7 (3)	C3—C4—C23—C28	39.0 (3)
C12—C7—C8—C9	0.5 (3)	C28—C23—C24—C25	0.0 (3)
N1—C7—C8—C9	178.05 (18)	C4—C23—C24—C25	−176.60 (18)
C7—C8—C9—C10	0.9 (3)	C23—C24—C25—N26	0.8 (3)
C8—C9—C10—C11	−1.1 (3)	C24—C25—N26—C27	−0.8 (3)
C8—C9—C10—C13	177.70 (19)	C25—N26—C27—C28	0.1 (3)
C9—C10—C11—C12	0.1 (3)	N26—C27—C28—C23	0.6 (4)
C13—C10—C11—C12	−178.77 (19)	C24—C23—C28—C27	−0.6 (3)
C10—C11—C12—C7	1.3 (3)	C4—C23—C28—C27	175.92 (19)

D—H···A	D—H	H···A	D···A	D—H···A
N6—H6A···N26i	0.88	2.14	2.938 (2)	150
N6—H6B···N14ii	0.86	2.58	3.292 (3)	141

Table 1

Hydrogen-bond geometry (Å, °)

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N6—H6A⋯N26i	0.88	2.14	2.938 (2)	150
N6—H6B⋯N14ii	0.86	2.58	3.292 (3)	141

Symmetry codes: (i) ; (ii) .