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

Journal logoCRYSTALLOGRAPHIC
COMMUNICATIONS
ISSN: 2056-9890
Volume 68| Part 4| April 2012| Page o935
doi:10.1107/S160053681200877X

4-[5-Amino-4-(4-fluoro­phen­yl)-3-(pyridin-4-yl)-1H-pyrazol-1-yl]benzo­nitrile

Bassam Abu Thaher,a Pierre Koch,b Dieter Schollmeyerc and Stefan Lauferb*

aFaculty of Science, Chemistry Department, Islamic University of Gaza, Gaza Strip, Palestinian Territories, bInstitute of Pharmacy, Department of Pharmaceutical and Medicinal Chemistry, Eberhard Karls University Tübingen, Auf der Morgenstelle 8, 72076 Tübingen, Germany, and cDepartment of Organic Chemistry, Johannes Gutenberg-University Mainz, Duesbergweg 10-14, D-55099 Mainz, Germany
*Correspondence e-mail: stefan.laufer@uni-tuebingen.de

(Received 13 February 2012; accepted 27 February 2012; online 3 March 2012)

In the crystal structure of the title compound, C21H14FN5, the pyrazole ring forms dihedral angles of 38.0 (1), 40.0 (1) and 28.5 (1)° with the directly attached 4-fluoro­phenyl, 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[Abu Thaher, B., Koch, P., Schattel, V. & Laufer, S. (2009). J. Med. Chem. 52, 2613-2617.]); Peifer et al. (2006[Peifer, C., Wagner, G. & Laufer, S. (2006). Curr. Top. Med. Chem. 6, 113-149.]). For the inhibitory activity and preparation of the title compound, see: Abu Thaher et al. (2012a[Abu Thaher, B., Arnsmann, M., Totzke, F., Ehlert, J. E., Kubbutat, M. H. G., Schächtele, C., Zimmermann, M. O., Koch, P., Boeckler, F. M. & Laufer, S. A. (2012a). J. Med. Chem. 55, 961-965.]). For related structures, see: Abu Thaher et al. (2012b[Abu Thaher, B., Koch, P., Schollmeyer, D. & Laufer, S. (2012b). Acta Cryst. E68, o632.],c[Abu Thaher, B., Koch, P., Schollmeyer, D. & Laufer, S. (2012c). Acta Cryst. E68, o633.]).

[Scheme 1]

Experimental

Crystal data

  • C21H14FN5

  • Mr = 355.37

  • Orthorhombic, P c a 21

  • 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)

  • Rint = 0.026

  • 3 standard reflections every 60 min intensity decay: 3%
Refinement

  • R[F2 > 2σ(F2)] = 0.038

  • wR(F2) = 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[Flack, H. D. (1983). Acta Cryst. A39, 876-881.]), 1381 Friedel pairs

  • Flack parameter: −0.17 (18)

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) x+1, y, z; (ii) [-x+{\script{3\over 2}}, y, z-{\script{1\over 2}}].

Data collection: CAD-4 Software (Enraf–Nonius, 1989[Enraf-Nonius (1989). CAD-4 Software. Enraf-Nonius, Delft, The Netherlands.]); cell refinement: CAD-4 Software; data reduction: CORINC (Dräger & Gattow, 1971[Dräger, M. & Gattow, G. (1971). Acta Chem. Scand. 25, 761-762.]); program(s) used to solve structure: SIR97 (Altomare et al., 1999[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.]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008[Sheldrick, G. M. (2008). Acta Cryst. A64, 112-122.]); molecular graphics: PLATON (Spek, 2009[Spek, A. L. (2009). Acta Cryst. D65, 148-155.]); software used to prepare material for publication: PLATON.

Supporting information

Crystal structure: contains datablocks I, global. DOI: 10.1107/S160053681200877X/im2359sup1.cif

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

Supporting information file. DOI: 10.1107/S160053681200877X/im2359Isup3.cml

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). We showed that the regioisomeric switch from 3-(4-fluorophenyl)-4-(pyridin-4-yl)-1-(aryl)-1H-pyrazol-5-amine to 4-(4-fluorophenyl)-3-(pyridin-4-yl)-1-(aryl)-1H-pyrazol-5-amine completely changed the inhibitory profile from p38α MAP kinase to kinases relevant in cancer (Abu Thaher et al. 2012a). Recently, we reported similar crystal structures (Abu Thaher et al. 2012b,c).

In the crystal structure of the title compound (Fig. 1) the pyrazole ring forms dihedral angels of 38.0 (1)°, 40.0 (1)°, 28.5 (1)° with the directly attached 4-fluorophenyl, pyridine and benzonitrile rings, respectively. The 4-fluorophenyl ring encloses dihedral angels of 57.7 (1)° and 22.1 (9)° toward the pyridine and benzonitrile rings, respectively. The pyridine ring is oriented at a dihedral angle of 35.6 (1)° toward the benzonitrile ring.

The crystal packing (Fig. 2) shows that the amino function acts as a hydrogen bond donor of two intermolecular hydrogen bonds formed to two different molecules - one to the nitrogen atom (N26) of the pyridine ring and one to the nitrogen atom (N14) of the nitrile group. The length of the hydrogen bonds is 2.14Å and 2.58 Å, respectively (Table 1). The two hydrogen bonds result in a two dimensional network parallel to the ac-plane.

Related literature top

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 top

20 mmol of LDA were added to 30 ml of dry THF in a three neck flask and cooled to 194 K. 14 mmol of 4-fluorophenylacetonitril in 10 ml THF were added dropwise and the reaction mixture was stirred for 45 min. 5 mmol of N-(4-cyanophenyl)-4-pyridinecarbohydrazonoyl chloride were added slowly and stirring of the reaction mixture was continued for 1 h. After warming to 293 K, 50 ml of water were added to the reaction mixture which then was extracted with ethyl acetate (2x 50 mL). The combined organic layers were dried over Na2SO4. The organic solution was concentrated to about 5 ml and the product precipitated as pure pale brown crystalls which were washed with diethyl ether. Yield 62%.

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). 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).

Structure description 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). We showed that the regioisomeric switch from 3-(4-fluorophenyl)-4-(pyridin-4-yl)-1-(aryl)-1H-pyrazol-5-amine to 4-(4-fluorophenyl)-3-(pyridin-4-yl)-1-(aryl)-1H-pyrazol-5-amine completely changed the inhibitory profile from p38α MAP kinase to kinases relevant in cancer (Abu Thaher et al. 2012a). Recently, we reported similar crystal structures (Abu Thaher et al. 2012b,c).

In the crystal structure of the title compound (Fig. 1) the pyrazole ring forms dihedral angels of 38.0 (1)°, 40.0 (1)°, 28.5 (1)° with the directly attached 4-fluorophenyl, pyridine and benzonitrile rings, respectively. The 4-fluorophenyl ring encloses dihedral angels of 57.7 (1)° and 22.1 (9)° toward the pyridine and benzonitrile rings, respectively. The pyridine ring is oriented at a dihedral angle of 35.6 (1)° toward the benzonitrile ring.

The crystal packing (Fig. 2) shows that the amino function acts as a hydrogen bond donor of two intermolecular hydrogen bonds formed to two different molecules - one to the nitrogen atom (N26) of the pyridine ring and one to the nitrogen atom (N14) of the nitrile group. The length of the hydrogen bonds is 2.14Å and 2.58 Å, respectively (Table 1). The two hydrogen bonds result in a two dimensional network parallel to the ac-plane.

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).

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. View of the title compound. Displacement ellipsoids are drawn at the 50% probability level. H atoms are depicted as circles of arbitrary size.
[Figure 2] Fig. 2. A packing section of the crystal viewed down the b axis. Hydrogen bonds are shown as dashed lines. Separated layers are indicated by different colours.
4-[5-Amino-4-(4-fluorophenyl)-3-(pyridin-4-yl)-1H- pyrazol-1-yl]benzonitrile top
Crystal data top
C21H14FN5F(000) = 736
Mr = 355.37Dx = 1.379 Mg m−3
Orthorhombic, Pca21Cu Kα radiation, λ = 1.54178 Å
Hall symbol: P 2c -2acCell parameters from 25 reflections
a = 10.5189 (5) Åθ = 65–70°
b = 8.1339 (3) ŵ = 0.76 mm−1
c = 20.0009 (13) ÅT = 193 K
V = 1711.27 (15) Å3Block, brown
Z = 40.50 × 0.30 × 0.30 mm
Data collection top
Enraf–Nonius CAD-4
diffractometer		Rint = 0.026
Radiation source: rotating anodeθmax = 69.9°, θmin = 4.4°
Graphite monochromatorh = −12→12
ω/2θ scansk = −9→9
3163 measured reflectionsl = −24→24
3059 independent reflections3 standard reflections every 60 min
3005 reflections with I > 2σ(I) intensity decay: 3%
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)] = 0.038H-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 reflectionsΔρmax = 0.17 e Å−3
244 parametersΔρmin = −0.23 e Å−3
1 restraintAbsolute structure: Flack (1983), 1381 Friedel pairs
Primary atom site location: structure-invariant direct methodsAbsolute structure parameter: −0.17 (18)
Crystal data top
C21H14FN5V = 1711.27 (15) Å3
Mr = 355.37Z = 4
Orthorhombic, Pca21Cu Kα radiation
a = 10.5189 (5) ŵ = 0.76 mm−1
b = 8.1339 (3) ÅT = 193 K
c = 20.0009 (13) Å0.50 × 0.30 × 0.30 mm
Data collection top
Enraf–Nonius CAD-4
diffractometer		Rint = 0.026
3163 measured reflections3 standard reflections every 60 min
3059 independent reflections intensity decay: 3%
3005 reflections with I > 2σ(I)
Refinement top
R[F2 > 2σ(F2)] = 0.038H-atom parameters constrained
wR(F2) = 0.103Δρmax = 0.17 e Å−3
S = 1.04Δρmin = −0.23 e Å−3
3059 reflectionsAbsolute structure: Flack (1983), 1381 Friedel pairs
244 parametersAbsolute structure parameter: −0.17 (18)
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
xyzUiso*/Ueq
N10.43666 (14)0.21998 (19)0.52903 (8)0.0245 (3)
C20.46323 (15)0.2397 (2)0.46188 (10)0.0233 (4)
C30.34814 (17)0.2656 (2)0.43004 (10)0.0234 (4)
C40.25715 (16)0.2607 (2)0.48226 (9)0.0236 (4)
N50.30861 (14)0.23527 (19)0.54156 (8)0.0253 (3)
N60.58360 (15)0.2377 (2)0.43736 (9)0.0322 (4)
H6A0.64920.25470.46390.048*
H6B0.59750.24250.39490.048*
C70.51679 (16)0.1880 (2)0.58436 (10)0.0240 (4)
C80.47853 (17)0.2416 (3)0.64701 (11)0.0307 (4)
H80.40140.30130.65160.037*
C90.55154 (18)0.2090 (3)0.70281 (10)0.0319 (4)
H90.52450.24460.74570.038*
C100.66595 (17)0.1229 (2)0.69545 (9)0.0269 (4)
C110.70398 (19)0.0686 (2)0.63280 (10)0.0309 (4)
H110.78160.01020.62810.037*
C120.62949 (18)0.0992 (2)0.57720 (10)0.0287 (4)
H120.65480.06000.53450.034*
C130.74546 (19)0.0933 (2)0.75280 (11)0.0306 (4)
N140.81025 (18)0.0714 (3)0.79805 (10)0.0402 (4)
C160.33007 (16)0.3156 (2)0.35985 (9)0.0235 (4)
C170.24094 (18)0.4368 (2)0.34404 (10)0.0279 (4)
H170.19150.48430.37880.033*
C180.22306 (19)0.4892 (2)0.27863 (11)0.0315 (4)
H180.16050.56930.26810.038*
C190.29837 (19)0.4220 (3)0.22958 (9)0.0303 (4)
C200.38681 (19)0.3029 (3)0.24196 (10)0.0329 (4)
H200.43690.25850.20680.039*
C210.40156 (19)0.2480 (3)0.30763 (10)0.0294 (4)
H210.46110.16340.31700.035*
F220.28240 (13)0.47710 (18)0.16555 (6)0.0439 (3)
C230.11619 (16)0.2723 (2)0.47901 (10)0.0247 (4)
C240.04902 (17)0.3515 (3)0.52898 (10)0.0301 (4)
H240.09270.40430.56460.036*
C25−0.08274 (18)0.3532 (3)0.52667 (11)0.0357 (5)
H25−0.12730.40930.56110.043*
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)
H27−0.13060.15110.39590.043*
C280.04695 (18)0.1972 (3)0.42836 (11)0.0301 (4)
H280.08910.14220.39280.036*
Atomic displacement parameters (Å2) top
U11U22U33U12U13U23
N10.0145 (6)0.0350 (8)0.0241 (8)−0.0011 (6)0.0004 (6)0.0023 (7)
C20.0160 (8)0.0292 (9)0.0246 (10)−0.0018 (6)0.0001 (7)−0.0011 (7)
C30.0177 (8)0.0267 (8)0.0259 (9)−0.0007 (6)0.0000 (7)−0.0014 (8)
C40.0149 (8)0.0299 (8)0.0259 (9)−0.0019 (6)−0.0023 (7)0.0007 (7)
N50.0128 (7)0.0366 (8)0.0265 (9)0.0008 (5)−0.0004 (6)0.0013 (7)
N60.0119 (7)0.0586 (11)0.0260 (8)−0.0022 (7)0.0012 (6)−0.0019 (8)
C70.0164 (8)0.0288 (9)0.0268 (9)−0.0026 (7)−0.0035 (7)0.0019 (8)
C80.0175 (8)0.0447 (11)0.0298 (10)0.0032 (7)0.0008 (8)−0.0026 (9)
C90.0228 (9)0.0469 (11)0.0261 (10)−0.0006 (8)−0.0003 (7)−0.0042 (9)
C100.0224 (8)0.0318 (9)0.0265 (10)−0.0038 (7)−0.0041 (7)0.0022 (8)
C110.0252 (9)0.0357 (10)0.0320 (10)0.0068 (8)−0.0031 (8)−0.0003 (9)
C120.0254 (9)0.0363 (9)0.0244 (9)0.0042 (8)0.0003 (7)−0.0028 (8)
C130.0260 (8)0.0365 (10)0.0291 (9)−0.0040 (8)−0.0014 (8)0.0014 (8)
N140.0332 (9)0.0541 (11)0.0333 (9)−0.0074 (8)−0.0090 (8)0.0054 (9)
C160.0172 (7)0.0292 (9)0.0241 (9)−0.0039 (7)−0.0008 (6)−0.0019 (7)
C170.0248 (9)0.0328 (9)0.0261 (10)−0.0002 (7)0.0017 (7)−0.0024 (8)
C180.0297 (10)0.0336 (10)0.0314 (10)−0.0008 (8)−0.0043 (8)0.0041 (8)
C190.0300 (9)0.0406 (10)0.0202 (9)−0.0136 (8)−0.0034 (7)0.0013 (8)
C200.0277 (9)0.0456 (11)0.0254 (10)−0.0079 (8)0.0058 (8)−0.0078 (9)
C210.0202 (9)0.0367 (10)0.0313 (10)−0.0014 (7)0.0004 (8)−0.0033 (8)
F220.0503 (8)0.0578 (8)0.0236 (6)−0.0142 (6)−0.0051 (5)0.0065 (6)
C230.0156 (8)0.0316 (9)0.0268 (9)0.0008 (6)0.0006 (7)0.0040 (7)
C240.0205 (8)0.0449 (11)0.0250 (9)0.0002 (7)−0.0024 (7)−0.0022 (9)
C250.0213 (9)0.0538 (12)0.0318 (10)0.0055 (8)0.0055 (8)−0.0036 (9)
N260.0160 (7)0.0569 (11)0.0382 (10)−0.0002 (7)0.0001 (7)0.0016 (9)
C270.0206 (9)0.0542 (12)0.0337 (11)−0.0049 (8)−0.0040 (8)−0.0026 (10)
C280.0210 (8)0.0428 (11)0.0265 (9)−0.0017 (7)−0.0020 (8)−0.0022 (9)
Geometric parameters (Å, º) top
N1—N51.376 (2)C13—N141.147 (3)
N1—C21.381 (3)C16—C171.397 (3)
N1—C71.415 (2)C16—C211.399 (3)
C2—N61.358 (2)C17—C181.389 (3)
C2—C31.384 (2)C17—H170.9500
C3—C41.417 (3)C18—C191.374 (3)
C3—C161.474 (3)C18—H180.9500
C4—N51.320 (2)C19—C201.366 (3)
C4—C231.487 (2)C19—F221.367 (2)
N6—H6A0.8816C20—C211.396 (3)
N6—H6B0.8621C20—H200.9500
C7—C81.386 (3)C21—H210.9500
C7—C121.395 (3)C23—C241.383 (3)
C8—C91.380 (3)C23—C281.389 (3)
C8—H80.9500C24—C251.387 (3)
C9—C101.400 (3)C24—H240.9500
C9—H90.9500C25—N261.336 (3)
C10—C111.388 (3)C25—H250.9500
C10—C131.440 (3)N26—C271.336 (3)
C11—C121.383 (3)C27—C281.383 (3)
C11—H110.9500C27—H270.9500
C12—H120.9500C28—H280.9500
N5—N1—C2111.40 (14)C17—C16—C21117.97 (18)
N5—N1—C7117.21 (15)C17—C16—C3119.80 (17)
C2—N1—C7131.39 (15)C21—C16—C3122.22 (17)
N6—C2—N1122.58 (16)C18—C17—C16121.39 (18)
N6—C2—C3130.64 (18)C18—C17—H17119.3
N1—C2—C3106.74 (15)C16—C17—H17119.3
C2—C3—C4104.33 (17)C19—C18—C17118.20 (18)
C2—C3—C16126.37 (16)C19—C18—H18120.9
C4—C3—C16128.50 (17)C17—C18—H18120.9
N5—C4—C3112.93 (16)C20—C19—F22119.08 (19)
N5—C4—C23117.26 (16)C20—C19—C18123.03 (18)
C3—C4—C23129.75 (18)F22—C19—C18117.90 (18)
C4—N5—N1104.59 (15)C19—C20—C21118.24 (19)
C2—N6—H6A120.7C19—C20—H20120.9
C2—N6—H6B120.9C21—C20—H20120.9
H6A—N6—H6B117.0C20—C21—C16121.13 (19)
C8—C7—C12120.14 (18)C20—C21—H21119.4
C8—C7—N1118.43 (16)C16—C21—H21119.4
C12—C7—N1121.39 (18)C24—C23—C28117.64 (16)
C9—C8—C7120.58 (17)C24—C23—C4120.48 (17)
C9—C8—H8119.7C28—C23—C4121.79 (17)
C7—C8—H8119.7C23—C24—C25119.40 (18)
C8—C9—C10119.30 (19)C23—C24—H24120.3
C8—C9—H9120.4C25—C24—H24120.3
C10—C9—H9120.4N26—C25—C24123.45 (19)
C11—C10—C9120.12 (18)N26—C25—H25118.3
C11—C10—C13119.92 (17)C24—C25—H25118.3
C9—C10—C13119.95 (18)C27—N26—C25116.60 (16)
C12—C11—C10120.38 (18)N26—C27—C28124.0 (2)
C12—C11—H11119.8N26—C27—H27118.0
C10—C11—H11119.8C28—C27—H27118.0
C11—C12—C7119.46 (19)C27—C28—C23118.87 (19)
C11—C12—H12120.3C27—C28—H28120.6
C7—C12—H12120.3C23—C28—H28120.6
N14—C13—C10178.9 (2)
N5—N1—C2—N6176.84 (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—C3178.89 (17)C4—C3—C16—C1732.0 (3)
N6—C2—C3—C4−177.24 (19)C2—C3—C16—C2142.5 (3)
N1—C2—C3—C40.45 (19)C4—C3—C16—C21−149.42 (18)
N6—C2—C3—C16−6.8 (3)C21—C16—C17—C180.1 (3)
N1—C2—C3—C16170.87 (17)C3—C16—C17—C18178.76 (17)
C2—C3—C4—N50.3 (2)C16—C17—C18—C19−1.9 (3)
C16—C3—C4—N5−169.81 (17)C17—C18—C19—C202.1 (3)
C2—C3—C4—C23−176.61 (17)C17—C18—C19—F22−178.44 (16)
C16—C3—C4—C2313.2 (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—N1176.39 (15)C19—C20—C21—C16−1.5 (3)
C2—N1—N5—C41.26 (19)C17—C16—C21—C201.7 (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—C2438.6 (3)
C2—N1—C7—C8152.71 (19)C3—C4—C23—C24−144.6 (2)
N5—N1—C7—C12150.24 (17)N5—C4—C23—C28−137.84 (19)
C2—N1—C7—C12−29.7 (3)C3—C4—C23—C2839.0 (3)
C12—C7—C8—C90.5 (3)C28—C23—C24—C250.0 (3)
N1—C7—C8—C9178.05 (18)C4—C23—C24—C25−176.60 (18)
C7—C8—C9—C100.9 (3)C23—C24—C25—N260.8 (3)
C8—C9—C10—C11−1.1 (3)C24—C25—N26—C27−0.8 (3)
C8—C9—C10—C13177.70 (19)C25—N26—C27—C280.1 (3)
C9—C10—C11—C120.1 (3)N26—C27—C28—C230.6 (4)
C13—C10—C11—C12−178.77 (19)C24—C23—C28—C27−0.6 (3)
C10—C11—C12—C71.3 (3)C4—C23—C28—C27175.92 (19)
Hydrogen-bond geometry (Å, º) top
D—H···AD—HH···AD···AD—H···A
N6—H6A···N26i0.882.142.938 (2)150
N6—H6B···N14ii0.862.583.292 (3)141
Symmetry codes: (i) x+1, y, z; (ii) −x+3/2, y, z−1/2.

Experimental details

Crystal data
Chemical formulaC21H14FN5
Mr355.37
Crystal system, space groupOrthorhombic, Pca21
Temperature (K)193
a, b, c (Å)10.5189 (5), 8.1339 (3), 20.0009 (13)
V (Å3)1711.27 (15)
Z4
Radiation typeCu Kα
µ (mm−1)0.76
Crystal size (mm)0.50 × 0.30 × 0.30
Data collection
DiffractometerEnraf–Nonius CAD-4
Absorption correction–
No. of measured, independent and
observed [I > 2σ(I)] reflections		3163, 3059, 3005
Rint0.026
(sin θ/λ)max (Å−1)0.609
Refinement
R[F2 > 2σ(F2)], wR(F2), S 0.038, 0.103, 1.04
No. of reflections3059
No. of parameters244
No. of restraints1
H-atom treatmentH-atom parameters constrained
Δρmax, Δρmin (e Å−3)0.17, −0.23
Absolute structureFlack (1983), 1381 Friedel pairs
Absolute structure parameter−0.17 (18)

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···AD—HH···AD···AD—H···A
N6—H6A···N26i0.882.142.938 (2)150
N6—H6B···N14ii0.862.583.292 (3)141
Symmetry codes: (i) x+1, y, z; (ii) −x+3/2, y, z−1/2.
 

Acknowledgements

BAT thanks the Alexander von Humboldt-Foundation (AvH) for funding.

References

First citationAbu Thaher, B., Arnsmann, M., Totzke, F., Ehlert, J. E., Kubbutat, M. H. G., Schächtele, C., Zimmermann, M. O., Koch, P., Boeckler, F. M. & Laufer, S. A. (2012a). J. Med. Chem. 55, 961–965.  Web of Science CAS PubMed Google Scholar
 First citationAbu Thaher, B., Koch, P., Schattel, V. & Laufer, S. (2009). J. Med. Chem. 52, 2613–2617.  Web of Science PubMed CAS Google Scholar
 First citationAbu Thaher, B., Koch, P., Schollmeyer, D. & Laufer, S. (2012b). Acta Cryst. E68, o632.  CSD CrossRef IUCr Journals Google Scholar
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 First citationDräger, M. & Gattow, G. (1971). Acta Chem. Scand. 25, 761–762.  Google Scholar
 First citationEnraf–Nonius (1989). CAD-4 Software. Enraf–Nonius, Delft, The Netherlands.  Google Scholar
 First citationFlack, H. D. (1983). Acta Cryst. A39, 876–881.  CrossRef CAS Web of Science IUCr Journals Google Scholar
 First citationPeifer, C., Wagner, G. & Laufer, S. (2006). Curr. Top. Med. Chem. 6, 113–149.  Web of Science CrossRef PubMed CAS Google Scholar
 First citationSheldrick, G. M. (2008). Acta Cryst. A64, 112–122.  Web of Science CrossRef CAS IUCr Journals Google Scholar
 First citationSpek, A. L. (2009). Acta Cryst. D65, 148–155.  Web of Science CrossRef CAS IUCr Journals Google Scholar

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ISSN: 2056-9890
Volume 68| Part 4| April 2012| Page o935
doi:10.1107/S160053681200877X
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