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Acta Crystallogr Sect E Struct Rep Online. 2009 May 1; 65(Pt 5): o1077.
Published online 2009 April 18. doi:  10.1107/S1600536809013609
PMCID: PMC2977756

5-(4-Chloro­phen­yl)-1-(2,4-dichloro­phen­yl)-4-methyl-N-(3-pyridylmeth­yl)-1H-pyrazole-3-carboxamide

Abstract

In the title compound, C23H17Cl3N4O, the benzene rings are oriented with respect to the pyrazole ring at dihedral angles of 39.9 (2) and 72.90 (13)° for the chloro­phenyl and di­chloro­phenyl rings, respectively. Inter­molecular C—H(...)N and C—H(...)Cl inter­actions are observed in the crystal packing.

Related literature

For general background to pyrazole derivatives and their biological activity, see: Srivastava et al. (2008 [triangle]); LoVerme et al. (2009 [triangle]); Rinaldi-Carmona et al. (1994 [triangle]). For the synthesis, see: Li et al. (2007 [triangle]).

An external file that holds a picture, illustration, etc.
Object name is e-65-o1077-scheme1.jpg

Experimental

Crystal data

  • C23H17Cl3N4O
  • M r = 471.76
  • Monoclinic, An external file that holds a picture, illustration, etc.
Object name is e-65-o1077-efi1.jpg
  • a = 9.0032 (4) Å
  • b = 20.1001 (8) Å
  • c = 11.4664 (5) Å
  • β = 92.003 (2)°
  • V = 2073.75 (15) Å3
  • Z = 4
  • Mo Kα radiation
  • μ = 0.47 mm−1
  • T = 113 K
  • 0.26 × 0.20 × 0.18 mm

Data collection

  • Rigaku Saturn CCD area-detector diffractometer
  • Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005 [triangle]) T min = 0.888, T max = 0.921
  • 19184 measured reflections
  • 4914 independent reflections
  • 4152 reflections with I > 2σ(I)
  • R int = 0.034

Refinement

  • R[F 2 > 2σ(F 2)] = 0.032
  • wR(F 2) = 0.085
  • S = 1.06
  • 4914 reflections
  • 285 parameters
  • H atoms treated by a mixture of independent and constrained refinement
  • Δρmax = 0.75 e Å−3
  • Δρmin = −0.38 e Å−3

Data collection: CrystalClear (Rigaku/MSC, 2005 [triangle]); cell refinement: CrystalClear; data reduction: CrystalClear; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 [triangle]); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 [triangle]); molecular graphics: SHELXTL (Sheldrick, 2008 [triangle]); software used to prepare material for publication: CrystalStructure (Rigaku/MSC, 2004 [triangle]) and publCIF (Westrip, 2009 [triangle]).

Table 1
Hydrogen-bond geometry (Å, °)

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809013609/ez2158sup1.cif

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809013609/ez2158Isup2.hkl

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

Acknowledgments

We thank T. L. Liang for her fruitful help.

supplementary crystallographic information

Comment

Pyrazole derivatives have been found to be a novel class of cannabinoid CB1 receptor antagonists (Srivastava et al., 2008; LoVerme et al., 2009; Rinaldi-Carmona M. et al., 1994). The crystal structure of the title compound (IC50 =0.139nM at CB1) was analyzed by X-ray diffraction, for the purpose of studying its quantitative structure-activity relationship (QSAR).

In the molecule of the title compound (Fig. 1) the bond lengths and angles are generally within normal ranges. The benzene rings (C6—C11) and (C12—C17) are oriented at dihedral angles of 39.9 (2)° and 72.90 (13)°, respectively, with respect to the pyrazole ring.

In the crystal structure, the molecules are linked by intermolecular C17—H17···N4 and C7—H7···Cl2 interactions (Fig. 2).

Experimental

The title compound was synthesized according to the procedure of Li et al.(2007). Colorless single crystals were obtained by slow evaporation of a solution in ehtyl acetate.

Refinement

The H atoms linked to the C atoms were fixed geometrically and treated as riding with C—H = 0.95 Å (aromatic), 0.98Å (methyl), 0.99 Å (methylene) with Uiso(H) =1.2–1.5Ueq(C). H atoms of the amino group were located in a difference Fourier map and refined freely.

Figures

Fig. 1.
The molecular structure of the title compound, with the atom-numbering scheme and ellipsoids at the 30 % probability level.
Fig. 2.
The crystal packing of the title compound. Hydrogen bonds are indicated by dashed lines.

Crystal data

C23H17Cl3N4OF(000) = 968
Mr = 471.76Dx = 1.511 Mg m3
Monoclinic, P21/cMo Kα radiation, λ = 0.71070 Å
a = 9.0032 (4) ÅCell parameters from 4274 reflections
b = 20.1001 (8) Åθ = 1.8–27.9°
c = 11.4664 (5) ŵ = 0.47 mm1
β = 92.003 (2)°T = 113 K
V = 2073.75 (15) Å3Block, colorless
Z = 40.26 × 0.20 × 0.18 mm

Data collection

Rigaku Saturn CCD area-detector diffractometer4914 independent reflections
Radiation source: rotating anode4152 reflections with I > 2σ(I)
confocalRint = 0.034
Detector resolution: 7.31 pixels mm-1θmax = 27.9°, θmin = 2.0°
ω and [var phi] scansh = −11→11
Absorption correction: multi-scan (CrystalClear; Rigaku/MSC, 2005)k = −26→26
Tmin = 0.888, Tmax = 0.921l = −15→15
19184 measured reflections

Refinement

Refinement on F2Primary atom site location: structure-invariant direct methods
Least-squares matrix: fullSecondary atom site location: difference Fourier map
R[F2 > 2σ(F2)] = 0.032Hydrogen site location: inferred from neighbouring sites
wR(F2) = 0.085H atoms treated by a mixture of independent and constrained refinement
S = 1.06w = 1/[σ2(Fo2) + (0.0441P)2 + 0.5347P] where P = (Fo2 + 2Fc2)/3
4914 reflections(Δ/σ)max = 0.002
285 parametersΔρmax = 0.75 e Å3
0 restraintsΔρmin = −0.38 e Å3

Special details

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)

xyzUiso*/Ueq
Cl10.01811 (4)0.643967 (18)0.56112 (3)0.02233 (10)
Cl20.52709 (4)0.554267 (18)0.22278 (3)0.02014 (10)
Cl30.15192 (4)0.596113 (19)−0.14473 (3)0.02088 (10)
O10.60926 (12)0.24050 (6)0.40372 (10)0.0235 (3)
N10.65174 (14)0.25624 (6)0.21143 (12)0.0177 (3)
H10.633 (2)0.2770 (10)0.1553 (17)0.023 (5)*
N20.47501 (14)0.36428 (6)0.20324 (11)0.0158 (3)
N30.38825 (14)0.41730 (6)0.22738 (11)0.0149 (3)
N41.09010 (16)0.18709 (7)0.40063 (13)0.0255 (3)
C10.59001 (16)0.27258 (7)0.31272 (14)0.0160 (3)
C20.49452 (15)0.33347 (7)0.30626 (13)0.0145 (3)
C30.41906 (16)0.36537 (7)0.39652 (13)0.0142 (3)
C40.35219 (16)0.42006 (7)0.34305 (13)0.0138 (3)
C50.40835 (18)0.34400 (8)0.52139 (13)0.0203 (3)
H5A0.49380.36140.56720.030*
H5B0.40800.29530.52560.030*
H5C0.31630.36140.55290.030*
C60.26488 (16)0.47476 (7)0.39330 (12)0.0135 (3)
C70.30933 (16)0.49932 (8)0.50303 (13)0.0159 (3)
H70.39270.48000.54320.019*
C80.23420 (17)0.55137 (7)0.55469 (13)0.0169 (3)
H80.26620.56790.62900.020*
C90.11196 (16)0.57867 (7)0.49587 (13)0.0155 (3)
C100.06310 (16)0.55496 (7)0.38774 (13)0.0155 (3)
H10−0.02150.57400.34880.019*
C110.13936 (16)0.50292 (7)0.33683 (13)0.0144 (3)
H110.10600.48630.26290.017*
C120.33945 (16)0.45989 (7)0.13373 (12)0.0143 (3)
C130.39214 (16)0.52489 (7)0.12519 (13)0.0144 (3)
C140.33693 (16)0.56739 (7)0.03826 (13)0.0154 (3)
H140.37210.61180.03250.019*
C150.22900 (16)0.54305 (7)−0.03979 (12)0.0155 (3)
C160.17985 (17)0.47747 (7)−0.03588 (13)0.0181 (3)
H160.10900.4613−0.09230.022*
C170.23618 (17)0.43610 (8)0.05187 (13)0.0172 (3)
H170.20370.39120.05570.021*
C180.74791 (16)0.19856 (7)0.19942 (14)0.0185 (3)
H18A0.75110.18670.11580.022*
H18B0.70400.16050.24080.022*
C190.95085 (18)0.18300 (8)0.35444 (15)0.0213 (3)
H190.87860.16070.39850.026*
C200.90543 (16)0.20918 (7)0.24668 (13)0.0158 (3)
C211.01070 (18)0.24347 (8)0.18393 (14)0.0200 (3)
H210.98440.26300.11060.024*
C221.15446 (18)0.24873 (8)0.23013 (15)0.0237 (3)
H221.22810.27210.18920.028*
C231.18931 (18)0.21935 (8)0.33690 (16)0.0254 (4)
H231.28890.22220.36660.031*

Atomic displacement parameters (Å2)

U11U22U33U12U13U23
Cl10.0286 (2)0.01416 (17)0.0247 (2)0.00408 (14)0.00882 (16)−0.00229 (14)
Cl20.01844 (19)0.02230 (19)0.01936 (19)−0.00254 (14)−0.00415 (14)−0.00143 (14)
Cl30.0230 (2)0.02238 (19)0.01701 (19)0.00224 (15)−0.00231 (14)0.00519 (14)
O10.0245 (6)0.0209 (6)0.0252 (6)0.0074 (5)0.0007 (5)0.0043 (5)
N10.0171 (6)0.0151 (6)0.0208 (7)0.0055 (5)−0.0006 (5)0.0016 (5)
N20.0145 (6)0.0130 (6)0.0199 (7)0.0034 (5)0.0021 (5)−0.0005 (5)
N30.0163 (6)0.0135 (6)0.0151 (6)0.0048 (5)0.0021 (5)0.0009 (5)
N40.0232 (7)0.0239 (7)0.0290 (8)0.0020 (6)−0.0049 (6)0.0042 (6)
C10.0110 (7)0.0131 (7)0.0239 (8)−0.0007 (5)−0.0010 (6)−0.0006 (6)
C20.0108 (7)0.0132 (6)0.0194 (7)−0.0009 (5)−0.0002 (5)0.0004 (6)
C30.0113 (7)0.0139 (7)0.0172 (7)−0.0002 (5)−0.0016 (5)0.0003 (5)
C40.0127 (7)0.0150 (7)0.0136 (7)−0.0003 (5)0.0001 (5)−0.0006 (5)
C50.0229 (8)0.0208 (8)0.0170 (8)0.0047 (6)−0.0015 (6)0.0028 (6)
C60.0126 (7)0.0136 (7)0.0144 (7)−0.0001 (5)0.0024 (5)0.0010 (5)
C70.0124 (7)0.0202 (7)0.0151 (7)−0.0006 (6)0.0000 (5)0.0007 (6)
C80.0166 (7)0.0186 (7)0.0154 (7)−0.0036 (6)0.0016 (6)−0.0025 (6)
C90.0165 (7)0.0103 (6)0.0201 (8)−0.0010 (5)0.0075 (6)−0.0006 (5)
C100.0137 (7)0.0139 (7)0.0190 (7)0.0010 (5)0.0020 (6)0.0033 (6)
C110.0148 (7)0.0146 (7)0.0139 (7)−0.0006 (5)0.0004 (5)0.0004 (5)
C120.0156 (7)0.0149 (7)0.0128 (7)0.0050 (5)0.0037 (6)0.0011 (5)
C130.0123 (7)0.0173 (7)0.0138 (7)0.0017 (5)0.0017 (5)−0.0028 (5)
C140.0170 (7)0.0142 (7)0.0153 (7)0.0006 (5)0.0034 (6)0.0002 (6)
C150.0168 (7)0.0171 (7)0.0127 (7)0.0039 (6)0.0024 (6)0.0017 (6)
C160.0188 (7)0.0198 (7)0.0157 (7)−0.0001 (6)−0.0011 (6)−0.0019 (6)
C170.0188 (7)0.0142 (7)0.0188 (8)0.0004 (6)0.0023 (6)−0.0020 (6)
C180.0152 (7)0.0142 (7)0.0262 (8)0.0031 (6)−0.0004 (6)−0.0041 (6)
C190.0194 (8)0.0181 (7)0.0265 (8)−0.0005 (6)0.0015 (6)0.0041 (6)
C200.0154 (7)0.0110 (6)0.0212 (8)0.0033 (5)0.0012 (6)−0.0037 (6)
C210.0238 (8)0.0174 (7)0.0190 (8)0.0003 (6)0.0029 (6)−0.0015 (6)
C220.0198 (8)0.0235 (8)0.0284 (9)−0.0049 (6)0.0073 (7)−0.0030 (7)
C230.0168 (8)0.0247 (8)0.0344 (10)0.0002 (6)−0.0033 (7)−0.0044 (7)

Geometric parameters (Å, °)

Cl1—C91.7437 (15)C8—H80.9500
Cl2—C131.7268 (15)C9—C101.386 (2)
Cl3—C151.7346 (15)C10—C111.391 (2)
O1—C11.2336 (19)C10—H100.9500
N1—C11.346 (2)C11—H110.9500
N1—C181.4565 (18)C12—C171.383 (2)
N1—H10.78 (2)C12—C131.395 (2)
N2—C21.3399 (19)C13—C141.391 (2)
N2—N31.3556 (16)C14—C151.387 (2)
N3—C41.3776 (19)C14—H140.9500
N3—C121.4303 (18)C15—C161.392 (2)
N4—C231.341 (2)C16—C171.388 (2)
N4—C191.346 (2)C16—H160.9500
C1—C21.496 (2)C17—H170.9500
C2—C31.412 (2)C18—C201.515 (2)
C3—C41.386 (2)C18—H18A0.9900
C3—C51.501 (2)C18—H18B0.9900
C4—C61.480 (2)C19—C201.391 (2)
C5—H5A0.9800C19—H190.9500
C5—H5B0.9800C20—C211.392 (2)
C5—H5C0.9800C21—C221.385 (2)
C6—C71.397 (2)C21—H210.9500
C6—C111.4019 (19)C22—C231.385 (2)
C7—C81.390 (2)C22—H220.9500
C7—H70.9500C23—H230.9500
C8—C91.384 (2)
C1—N1—C18122.73 (14)C10—C11—H11119.6
C1—N1—H1119.9 (14)C6—C11—H11119.6
C18—N1—H1117.3 (14)C17—C12—C13119.89 (13)
C2—N2—N3104.00 (12)C17—C12—N3118.96 (13)
N2—N3—C4112.65 (12)C13—C12—N3121.14 (13)
N2—N3—C12118.77 (12)C14—C13—C12120.77 (13)
C4—N3—C12128.47 (12)C14—C13—Cl2118.68 (11)
C23—N4—C19116.36 (15)C12—C13—Cl2120.55 (11)
O1—C1—N1123.54 (14)C15—C14—C13118.06 (13)
O1—C1—C2122.20 (14)C15—C14—H14121.0
N1—C1—C2114.26 (13)C13—C14—H14121.0
N2—C2—C3112.63 (13)C14—C15—C16121.99 (13)
N2—C2—C1118.63 (13)C14—C15—Cl3119.01 (11)
C3—C2—C1128.74 (13)C16—C15—Cl3119.00 (12)
C4—C3—C2104.40 (13)C17—C16—C15118.84 (14)
C4—C3—C5127.40 (13)C17—C16—H16120.6
C2—C3—C5128.16 (13)C15—C16—H16120.6
N3—C4—C3106.29 (13)C12—C17—C16120.33 (14)
N3—C4—C6123.44 (13)C12—C17—H17119.8
C3—C4—C6130.20 (13)C16—C17—H17119.8
C3—C5—H5A109.5N1—C18—C20113.96 (12)
C3—C5—H5B109.5N1—C18—H18A108.8
H5A—C5—H5B109.5C20—C18—H18A108.8
C3—C5—H5C109.5N1—C18—H18B108.8
H5A—C5—H5C109.5C20—C18—H18B108.8
H5B—C5—H5C109.5H18A—C18—H18B107.7
C7—C6—C11118.31 (13)N4—C19—C20124.54 (15)
C7—C6—C4118.28 (13)N4—C19—H19117.7
C11—C6—C4123.41 (13)C20—C19—H19117.7
C8—C7—C6121.43 (14)C19—C20—C21117.51 (14)
C8—C7—H7119.3C19—C20—C18120.44 (14)
C6—C7—H7119.3C21—C20—C18122.03 (14)
C9—C8—C7118.78 (14)C22—C21—C20118.94 (15)
C9—C8—H8120.6C22—C21—H21120.5
C7—C8—H8120.6C20—C21—H21120.5
C8—C9—C10121.46 (13)C21—C22—C23119.02 (15)
C8—C9—Cl1118.58 (12)C21—C22—H22120.5
C10—C9—Cl1119.96 (11)C23—C22—H22120.5
C9—C10—C11119.23 (13)N4—C23—C22123.58 (15)
C9—C10—H10120.4N4—C23—H23118.2
C11—C10—H10120.4C22—C23—H23118.2
C10—C11—C6120.77 (13)
C2—N2—N3—C4−0.44 (16)Cl1—C9—C10—C11179.90 (11)
C2—N2—N3—C12−177.01 (12)C9—C10—C11—C6−0.4 (2)
C18—N1—C1—O10.1 (2)C7—C6—C11—C101.4 (2)
C18—N1—C1—C2−179.79 (13)C4—C6—C11—C10−179.03 (14)
N3—N2—C2—C31.05 (16)N2—N3—C12—C1769.79 (18)
N3—N2—C2—C1−178.45 (12)C4—N3—C12—C17−106.16 (17)
O1—C1—C2—N2−177.73 (14)N2—N3—C12—C13−111.38 (15)
N1—C1—C2—N22.13 (19)C4—N3—C12—C1372.7 (2)
O1—C1—C2—C32.9 (2)C17—C12—C13—C143.0 (2)
N1—C1—C2—C3−177.28 (14)N3—C12—C13—C14−175.77 (13)
N2—C2—C3—C4−1.25 (16)C17—C12—C13—Cl2−177.12 (11)
C1—C2—C3—C4178.18 (14)N3—C12—C13—Cl24.06 (19)
N2—C2—C3—C5176.76 (14)C12—C13—C14—C15−0.4 (2)
C1—C2—C3—C5−3.8 (2)Cl2—C13—C14—C15179.75 (11)
N2—N3—C4—C3−0.31 (16)C13—C14—C15—C16−2.5 (2)
C12—N3—C4—C3175.84 (14)C13—C14—C15—Cl3176.98 (11)
N2—N3—C4—C6176.89 (13)C14—C15—C16—C172.8 (2)
C12—N3—C4—C6−7.0 (2)Cl3—C15—C16—C17−176.73 (11)
C2—C3—C4—N30.89 (15)C13—C12—C17—C16−2.8 (2)
C5—C3—C4—N3−177.14 (14)N3—C12—C17—C16176.05 (13)
C2—C3—C4—C6−176.05 (14)C15—C16—C17—C12−0.1 (2)
C5—C3—C4—C65.9 (3)C1—N1—C18—C20−78.52 (18)
N3—C4—C6—C7−138.52 (15)C23—N4—C19—C200.6 (2)
C3—C4—C6—C738.0 (2)N4—C19—C20—C21−1.8 (2)
N3—C4—C6—C1141.9 (2)N4—C19—C20—C18176.56 (15)
C3—C4—C6—C11−141.62 (16)N1—C18—C20—C19102.36 (17)
C11—C6—C7—C8−1.5 (2)N1—C18—C20—C21−79.37 (18)
C4—C6—C7—C8178.89 (13)C19—C20—C21—C221.2 (2)
C6—C7—C8—C90.6 (2)C18—C20—C21—C22−177.11 (14)
C7—C8—C9—C100.4 (2)C20—C21—C22—C230.4 (2)
C7—C8—C9—Cl1180.00 (11)C19—N4—C23—C221.3 (3)
C8—C9—C10—C11−0.5 (2)C21—C22—C23—N4−1.8 (3)

Hydrogen-bond geometry (Å, °)

D—H···AD—HH···AD···AD—H···A
C17—H17···N4i0.952.563.272 (2)132
C7—H7···Cl2ii0.952.843.5903 (15)137

Symmetry codes: (i) x−1, −y+1/2, z−1/2; (ii) −x+1, −y+1, −z+1.

Footnotes

Supplementary data and figures for this paper are available from the IUCr electronic archives (Reference: EZ2158).

References

  • Li, S., Liu, M. J. & Zheng, Z. B. (2007). WO Patent WO2007079681.
  • LoVerme, J., Duranti, A., Tontini, A., Spadoni, G., Mor, M., Rivara, S., Stella, N., Xu, C., Tarzia, G. & Piomelli, D. (2009). Bioorg. Med. Chem. Lett.19, 639–643. [PubMed]
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