4-(4-Fluoro­phen­yl)-3-(pyridin-4-yl)-1-(2,4,6-trichloro­phen­yl)-1H-pyrazol-5-amine

Bassam Abu Thaher; Pierre Koch; Dieter Schollmeyer; Stefan Laufer

doi:10.1107/S1600536812033569

. 2012 Aug 1;68(Pt 9):o2603. doi: 10.1107/S1600536812033569

4-(4-Fluorophenyl)-3-(pyridin-4-yl)-1-(2,4,6-trichlorophenyl)-1H-pyrazol-5-amine

Bassam Abu Thaher ^a, Pierre Koch ^b, Dieter Schollmeyer ^c, Stefan Laufer ^b,^*

PMCID: PMC3435635 PMID: 22969508

Abstract

In the title compound, C₂₀H₁₂Cl₃FN₄, the pyrazole ring forms dihedral angles of 47.51 (9), 47.37 (9) and 74.37 (9)° with the directly attached 4-fluorophenyl, pyridine and 2,4,6-trichlorophenyl rings, respectively. Only one of the two amino H atoms is involved in hydrogen bonding. The crystal packing is characterized by N—H⋯N hydrogen bonds, which result in infinite chains parallel to the c axis.

Related literature

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 ▶,d ▶,e ▶).

Experimental

Crystal data

C₂₀H₁₂Cl₃FN₄
M _r = 433.69
Triclinic,
a = 10.2487 (5) Å
b = 10.4643 (5) Å
c = 10.5489 (5) Å
α = 109.2377 (10)°
β = 111.4008 (10)°
γ = 98.0304 (11)°
V = 950.03 (8) Å³
Z = 2
Mo Kα radiation
μ = 0.51 mm⁻¹
T = 173 K
0.33 × 0.28 × 0.07 mm

Data collection

Bruker SMART APEXII diffractometer
Absorption correction: multi-scan (SADABS; Bruker, 2006 ▶) T _min = 0.687, T _max = 0.746
21201 measured reflections
4517 independent reflections
3864 reflections with I > 2σ(I)
R _int = 0.029

Refinement

R[F ² > 2σ(F ²)] = 0.031
wR(F ²) = 0.079
S = 1.03
4517 reflections
253 parameters
H-atom parameters constrained
Δρ_max = 0.33 e Å⁻³
Δρ_min = −0.33 e Å⁻³

Data collection: APEX2 (Bruker, 2006 ▶); cell refinement: SAINT (Bruker, 2006 ▶); data reduction: SAINT; 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.

Supplementary Material

Crystal structure: contains datablock(s) I, global. DOI: 10.1107/S1600536812033569/bt5984sup1.cif

e-68-o2603-sup1.cif^{(28.1KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S1600536812033569/bt5984Isup2.hkl

e-68-o2603-Isup2.hkl^{(221.3KB, hkl)}

Supplementary material file. DOI: 10.1107/S1600536812033569/bt5984Isup3.cml

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

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N6—H6A⋯N22ⁱ	0.90	2.17	3.0275 (17)	157

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Symmetry code: (i) Inline graphic .

Acknowledgments

BAT thanks the Alexander von Humboldt-Foundation for funding.

supplementary crystallographic information

Comment

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 changes 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,d,e). In the crystal structure of the title compound (Fig. 1), the pyrazole ring forms dihedral angels of 47.51 (9)°, 47.37 (9)°, 74.37 (9)° with the 4-fluorophenyl, pyridine and 2,4,6-trichlorophenyl rings, respectively. The 4-fluorophenyl ring encloses dihedral angels of 64.25 (8)° and 66.11 (8)° toward the pyridine and 2,4,6-trichlorophenyl rings, respectively. The pyridine ring is orientated at a dihedral angle of 78.99 (8)° toward the 2,4,6-trichlorophenyl ring. The crystal packing shows that the amino function acts as a hydrogen bond donor of an intermolecular hydrogen bond to the nitrogen atom (N22) of the pyridine ring. The length of the hydrogen bond is 2.17 Å (Table 1) and forms an infinite chain parallel to the c-axis.

Experimental

LDA (20 mmol) was added to dry THF (30 ml) in a three neck flask and cooled to 195 K. 4-Fluorophenylacetonitrile (14 mmol) in THF (10 ml) was added dropwise and the reaction was left stirring for 45 min. N-(2,4,6-trichlorophenyl)pyridine-4-carbohydrazonoyl chloride (5 mmol) was added slowly portionwise to the reaction. After about 1.0 h, the reaction was finished and left stirring to reach room temperature. Water (50 ml) was added to the reaction mixture and extracted with ethyl acetate (2x 50 mL). The organic layer was dried over Na₂SO₄. The organic layer was concentrated to about 5 ml and left overnight. The title compound was precipitated as a pale brown solid, filtered out, washed with petroleum ether. Yield 35%. The crystals for structure determination were obtained from recrystallization of the product from hot ethyl acetate.